New Drug Law in Canada

With a tip of the cap to our old friend, Peter Pliszka, north of border: Earlier this month, the so-called Protecting Canadians from Unsafe Drugs Act (Vanessa's Law) received royal assent and became law in Canada. This new legislation on paper was intended to protect Canadians from the potential risks related to drugs and medical devices by substantially increasing Health Canada's pre- and post-market powers over industry stakeholders, and changing the consequences for violating the Food and Drugs Act and its regulations.

Peter suggests that Vanessa's Law introduces the most significant amendments to the Food and Drugs Act in 50 years, and represents in some ways a new chapter in Canadian drug and medical device regulatory enforcement.

Peter notes that the new powers granted to Health Canada include:

• The power to order any person to provide information related to a drug or medical device where Health Canada believes that the product may present a serious risk of injury to human health;
• The power to order a manufacturer to conduct an assessment of a drug or medical device and to provide Health Canada with the results;
• The power to order a manufacturer to conduct additional tests or studies, or monitor experience, in relation to a drug or medical device for the purpose of obtaining additional information about the product's effects on health or safety, and to provide Health Canada with the results;
• The power to order a manufacturer to modify the label of a drug or medical device or to replace its packaging, where Health Canada believes that doing so is necessary to prevent injury to health; and
• The power to order any person who sells a drug or medical device to recall the product where Health Canada believes that a drug presents a serious risk of injury to health.

It appears that new regulations may be coming down the pike as well, on issues such as clinical trials information and product label issues outside of Canada.

PhRMA Submits Amicus Brief on First Amendment Issues

The Pharmaceutical Research and Manufacturers of America recently submitted an amicus brief urging a federal court to dismiss a whistleblower's False Claims Act suit because the off-label claims in the case violate the defendants' free speech rights. See U.S. ex rel. Solis v. Millennium Pharmaceuticals Inc. et al., No. 2:09-cv-03010 (E.D. Cal. Brief August 15, 2014). The Pharmaceutical Research and Manufacturers of America (“PhRMA”) is a voluntary, nonprofit association representing the nation’s leading research-based pharmaceutical and biotechnology companies.

Readers know that physicians may lawfully prescribe FDA-approved drugs to treat any condition or disease, including unapproved uses, based on their independent medical judgment. See Buckman Co. v. Plaintiffs’ Legal Comm., 531 U.S. 341, 350 (2001). Indeed, many unapproved uses are integral to the practice of medicine, and reflect the standard of patient care. E.g., Joseph W. Cranston et al., Report of the Council on Scientific Affairs: Unlabeled Indications of Food and Drug Administration-Approved Drugs, 32 Drug Info. J. 1049, 1050 (1998). The case here involved a qui tam False Claims Act (FCA) suit against defendants. This case raises serious First Amendment concerns, said amicus, because relator’s and the United States’ construction of the FCA would impose liability on manufacturers for engaging in truthful speech about “off-label” uses of their drugs, i.e., particular uses of an FDA-approved medication that the FDA has not yet approved. The First Amendment unquestionably protects such truthful and non-misleading speech. E.g., Sorrell v. IMS Health Inc., 131 S. Ct. 2653, 2659 (2011).  The prevalence of unapproved—but fully legal—uses of many FDA-approved prescription medicines to treat patients makes it critical that healthcare professionals have access to accurate, comprehensive, and current information about such uses. 

Notably, pointed out amicus, neither relator nor the government alleged that the speech at issue here—relaying reprinted articles about unapproved uses of the drug Integrilin from peer-reviewed journals, and summarizing the results of clinical trials—was false or misleading. Relator and the United States did not even agree on why the FCA proscribes this speech, or how this speech somehow causes others to submit false claims. But their interpretations of the FCA shared a critical flaw according to the Brief: both threaten core First Amendment rights and should be rejected under principles of constitutional avoidance. See Edward J. DeBartolo Corp. v. Fla. Gulf Coast Bldg. & Const. Trades Council, 485 U.S. 568, 575 (1988).

These constitutional concerns seem well-founded: “Speech in aid of pharmaceutical marketing . . . is a form of expression protected by the Free Speech Clause of the First Amendment.” Sorrell, 131 S. Ct. at 2659. Interpreting the FDCA to punish manufacturers for truthfully speaking about unapproved uses impermissibly restricts speech based on its content and the identity of the speaker, and thus triggers heightened scrutiny. These First Amendment concerns apply with particular force to the speech that relator targeted here. The Complaint alleged that the manufacturer merely distributed reprints of medical studies published in reputable independent journals like Cardiology, the American Heart Journal, and the American Journal of Cardiology, and sent letters accurately relaying summaries of clinical trials.  There was no question that the authors of the reprints, the studies’ investigators, physicians, or anyone other than manufacturers can speak about the reprints and trial results as much as they wish. Indeed, everyone but manufacturers apparently can talk to physicians about prescribing Integrilin for unapproved uses without penalty. Relator even conceded that the manufacturer can distribute reprints promoting unapproved uses so long as physicians request such information.

Physicians who received the reprints or other information from the manufacturer in this case received precisely the type of educational information that a trained physician would wish to receive about his patients. Physicians were not only free to disregard these reprints; their Hippocratic Oath obligated them to use their own, independent medical judgment as to whether a given prescription was warranted. And after those physicians prescribed the FDA-approved drug for an unapproved use, hospitals then made additional, independent determinations whether the prescriptions were reimbursable. Only after that did hospitals submit claims to the government.

A good summary of the issues from defense perspective.

 

Industry Comments on Draft FDA Guidance

Several leading drug manufacturers have worked to shed light on serious issues with the social media guidance issued earlier this year by the U.S. Food and Drug Administration.

Readers may recall the draft guidance was intended to describe FDA’s current thinking about how manufacturers and distributors can fulfill regulatory requirements for postmarketing submissions
of interactive promotional media for their FDA-approved products.  A number of industry members have submitted formal comments

PhRMA and its member companies highlighted two fundamental concerns with the Draft Guidance. First, the Draft Guidance assumes that a biopharmaceutical manufacturer can be held accountable for content written by third-parties on third-party web sites if the company merely somehow "influences" the third-party. This premise is overbroad and is inconsistent with the FDCA. Put simply, third-party statements not caused or controlled by a manufacturer do not fall within the statutory or regulatory scope of FDA‘s authority to regulate promotional labeling or advertising. Second, the Draft Guidance erroneously assumes that all manufacturer statements about prescription medicines on social media constitute promotional labeling or advertising. This expansive interpretation of labeling and advertising adopted in the Draft Guidance could chill truthful and non-misleading communication protected by the First Amendment. Thus, it is critical that FDA address these fundamental issues in the Final Guidance.

WLF echoed the latter concern. noting serious problems with the Draft Guidance at Section IV (entitled, "Factors Considered in Determining Postmarket Submission Requirements for Interactive Promotional Media"). The Draft Guidance's basic premise seems to be that everything a manufacturer posts on-line: (1) qualifies as "promotional" material; (2) falls within FDA's statutory purview; and (3) is not protected from FDA regulation by the First Amendment. Those premises are 
demonstrably incorrect. Accordingly, agency policy in this area ought to begin with guidance
regarding where FDA draws the line between speech that it is and is not permitted to regulate.
The Draft Guidance brushes aside such concerns and seems to indicate that FDA intends to regulate everything that a manufacturer says regarding its products on social media sites.

It will be interesting to see how the FDA reacts to these valid comments.

 

FDA Seeks Comments on DTC Study

The Food and Drug Administration is seeking public comment on its investigation of the impact of communicating risks in direct-to-consumer prescription drug television advertisements.  Readers know of the importance of the DTC context in drug litigation.

The notice announcing the comment period notes that prescription drug advertising regulations (21 CFR 202.1) require that broadcast (TV or radio) advertisements present the product's major risks in either audio or audio and visual parts of the advertisement; this is often called the "major statement." There is concern that as currently implemented in DTC ads, the major statement is often too long, which may result in reduced consumer comprehension, minimization of important risk information and, potentially, therapeutic noncompliance due to fear of side effects. Not all agree; one possible resolution is to limit the risks in the major statement to those that are serious and actionable, and include a disclosure to alert consumers that there are other product risks not included in the ad. For example, the disclosure could be, "This is not a full list of risks and side effects. Talk to your doctor and read the patient labeling for [drug name] before starting it."

The Office of Prescription Drug Promotion  plans to investigate the effectiveness of this "limited risks plus disclosure" strategy through empirical research, with the hypothesis that, relative to inclusion of the full major statement, providing limited risk information along with the disclosure about additional risks will promote improved consumer perception and understanding of serious and actionable drug risks. 

 

The FDA invites comments by 4/21 on: 

• whether the proposed collection of information is necessary for the proper performance of the FDA's functions;
•the validity of the methodology and assumptions used;
• ways to enhance the quality, utility and clarity of the information to be collected.

.

FDA Issues Draft Guidance on Social Media

The U.S. Food and Drug Administration recently took a small step towards providing industry with the long-awaited guidance on how pharmaceutical makers may communicate about their products on social media like Twitter. 

In July, 2012, Congress gave the FDA two years to come up with comprehensive policies on Internet promotion, and FDA has now released for comment the draft guidance document entitled, "Fulfilling Regulatory Requirements for Postmarketing Submissions of Interactive Promotional Media for Prescription Human and Animal Drugs and Biologics." It is the first of what is certain to be a series of guidance documents on this subject. 

This draft guidance is intended to describe FDA’s current thinking about how manufacturers, packers, and distributors (firms), that may either be the applicant or acting on behalf of the applicant, of prescription human and animal drug and biological products (drugs) can fulfill regulatory requirements for postmarketing submissions of interactive promotional media for their FDA-approved products. 

FDA states that a company will be responsible for product promotional communications on sites that are owned, controlled, created, influenced, or operated by, or on behalf of, the firm. Such product promotional communications may include firm-sponsored microblogs (e.g., Twitter), social networking sites (e.g., Facebook), firm blogs, and other sites that are under the control or influence of the firm. In determining whether a firm must submit promotional material about its product to FDA, the Agency considers whether the firm, or anyone acting on its behalf, is influencing or controlling the promotional activity or communication in whole or part. Thus, a firm is responsible if it exerts influence over a site in any particular, even if the influence is limited in scope. For example, if the firm collaborates on or has editorial, preview, or review privilege over the content provided, then it is going to be responsible for that content, says the document. A firm is responsible for promotion on a third-party site if the firm has any control or influence on the third-party site, even if that influence is limited in scope. For example, if a firm collaborates, or has editorial, preview, or review privilege, then it is responsible for its promotion on the site and, as such, that  the site is subject to submission to FDA to meet postmarketing submission requirements. 

FDA said it recognizes the challenges of submitting promotional materials that display real-time information and thus in the draft makes recommendations for submitting interactive promotional media. The main point of this part of the draft guidance is that marketers don’t always need to obtain FDA pre-clearance on planned tweets or an online posting before it is sent out.  If a firm submits interactive promotional media in the manner described in this draft guidance, FDA intends to exercise enforcement discretion regarding the regulatory requirements for postmarketing submissions related to promotional labeling and advertising.

The draft does not address such things as how risks can be communicated within the character-limits of media like Twitter, and  what constitutes acceptable use of hyperlinks. Clearly, more to come.

 

Summary Judgment Granted on Product Identification

Sometimes simpler is better.  In product liability litigation nothing is more basic, perhaps, than proof the plaintiff used defendant's product.  Last week, a federal judge granted summary judgment against two plaintiffs' making claims in multi-district litigation over injuries allegedly related to the painkillers Darvocet and Darvon. See In Re: Darvocet, Darvon and Propoxyphene Products Liability Litigation, No. 2:11-md-02226 (E.D. Ky.). The issue was this basic cause in fact element.

Summary judgment is appropriate when “the movant shows that there is no genuine dispute as to any material fact and the movant is entitled to judgment as a matter of law.” Fed. R. Civ. P. 56(a); see Celotex Corp. v. Catrett, 477 U.S. 317, 322-23 (1986).

Defendant argued that it was entitled to summary judgment because neither plaintiff demonstrated the ingestion of a propoxyphene product manufactured, sold, or distributed by the defendant. In their Amended Complaint, both plaintiffs allege that they ingested propoxyphene products manufactured by Lilly. It is indeed a general principle of products liability law in Texas and Georgia (the applicable rules under choice of law in an MDL) that a plaintiff must allege sufficient facts to allow the reasonable inference that the injury-causing product was sold, manufactured, or distributed by the defendant. Plaintiffs could not dispute that they failed to establish the ingestion of a Lilly  product.

Instead, Lilly presented evidence demonstrating that plaintiffs represented that they intended to pursue only claims that relate to generic drugs; that is, they would seek to hold Lilly liable for
the injuries allegedly arising out of their taking of generic drugs made by someone else.

Such arguments were already rejected by the Court in this MDL.  The Court had previously found unpersuasive the plaintiffs’ argument that a brand-name manufacturer may be held liable under a misrepresentation theory of liability to a plaintiff who ingested generic propoxyphene. The prevailing rule regarding misrepresentation claims against brand-name manufacturers has its origins, noted the Court, in Foster v. American Home Products Corp., 29 F.3d 165 (4th Cir. 1994), which rejected “the contention that a name brand manufacturer’s statements regarding its drug can serve as the basis for liability for injuries caused by another manufacturer’s drug.” Id. at 170.

The majority of courts that have addressed similar claims have followed the Fourth Circuit’s lead. Notably, federal district courts in Texas have repeatedly found that “the Texas Supreme Court would conclude that a brand-name manufacturer does not owe a duty to warn users of the risks related to another manufacturer’s product.” Finnicum v. Wyeth, Inc., 708 F. Supp. 2d 616, 621 (E.D. Tex. 2010); see also Burke v. Wyeth, Inc., No. G-09-82, 2009 WL 3698480, at *2-3 (S.D. Tex. Oct. 29,
2009).  And, similarly, there can be no recovery under Georgia law, “[u]nless the manufacturer’s defective product can be shown to be the proximate cause of the injuries . . .” Hoffman v. AC&S, Inc., 548 S.E.2d 379, 382 (Ga. Ct. App. 2001) (“To survive summary judgment, [the plaintiff] clearly
needed to present evidence that she was exposed to defendants’ products.”).

Defendant thus sufficiently established that there was no genuine dispute concerning the only
material fact that determined the viability of these plaintiffs’ misrepresentation claims: the identity
of the propoxyphene product ingested.  Therefore, the plaintiffs’ claims failed as a matter of law.

 

 

 

Summary Judgment for Defendant in Drug Case

A federal court recently granted summary judgment against Illinois plaintiffs who alleged that the blood clotting drug Trasylol caused the husband's kidney failure. See Miller v. Bayer Corp., No. 09-81262 (S.D. Fla., 7/3/13). (One of the remaining cases in the MDL.)

Plaintiff underwent double coronary artery bypass graft and aortic valve replacement surgery. At the time of his surgery, he was a former smoker with a lengthy medical history which included hypertension, hyper-lipidemia, chronic renal insufficiency, and coronary artery disease. The surgeon used Trasylol during the surgery to help control the bleeding. Plaintiff had signed an informed consent which enumerated the potential risks and benefits of cardiac surgery including infection, bleeding, heart damage, stroke, kidney damage, or even death.

After his surgery, Mr. Miller experienced a small acute left hemispheric stroke;  he also experienced a transient rise in his serum creatinine which peaked at 2.4 on postoperative day eight. (Creatinine is a waste product formed by the breakdown of a substance important for converting food into energy; if the kidneys are damaged and cannot function normally, the amount creatinine in the blood can increase.)

Plaintiffs sued for personal injuries allegedly caused by the use of the drug during surgery. Defendant moved for summary judgment as to each of Plaintiffs’ claims, asserting (1) under Illinois law, causation is an element of each of Plaintiff’s claims, and Plaintiffs’ expert’s causation testimony was inadmissible; (2) even if Plaintiffs’ expert’s testimony were admissible, their apparent claims failed because they were seeking damages for Mr. Miller’s stroke, and their
expert was not qualified to render an opinion as to the cause of the stroke. Plaintiffs responded that despite some confusion, ultimately they were not seeking damages due to Mr. Miller’s stroke, but for his “acute renal failure”; that the expert was qualified to testify; and “the temporal connection" between Mr. Miller’s acute renal failure and the injection of Trasylol, together with the alleged absence of renal issues prior to the surgery and the fact that Trasylol is supposedly a nephrotoxic agent, were sufficient to support an opinion that Trasylol was a substantial contributing factor in causing Mr. Miller’s injuries. 

The court noted that expert medical opinion evidence is usually required to show the cause of an injury or disease because the medical effect on the human system of the infliction of injuries is generally not within the sphere of the “common knowledge of the lay person.” See Fuesting v. Zimmer, Inc., 421 F.3d 528, 536 (7th Cir. 2005), rev’d on other grounds by Fuesting v. Zimmer, Inc., 448 F.3d 936 (7th Cir. 2006); Ancho v. Pentek Corp., 157 F.3d 512, 519 (7th Cir. 1998); Goffman v. Gross, 59 F.3d 668, 672 (7th Cir. 1995); Wallace v. McGlothan, 606 F.3d 410, 420 (7th Cir. 2010). Claims for negligence, strict liability, breach of express warranty, breach of implied warranty, fraudulent misrepresentation, fraudulent concealment, violation of consumer protection statutes, wrongful death, and loss of companionship, as well as a survival claim  all will fail where a plaintiff has no evidence of specific causation. See Schrott v. Bristol-Myers Squibb Co., 403 F.3d 940 (7th Cir. 2005). To avoid summary judgment, the Plaintiffs therefore must come forward with evidence that would allow a reasonable jury to find causation. Causation must be established by provable facts; it cannot be based on guess, conjecture, surmise, possibility, speculation, or mere allegation. 

In summary, plaintiffs' expert opined that in all medical certainty causation of Mr. Miller’s
alleged renal failure was likely multifactorial, with significant contributing factors including
cardiopulmonary bypass surgery, associated blood pressure fluctuations, and the use of the medication.  The drug, he said, "in all medical certainty, was a significant contributing factor.”
Additionally  he opined that the physicians caring for Mr. Miller “would not have used” this drug
had they been aware of the association of mortality and acute kidney injury.  Plaintiffs argued the expert had conducted a legally sufficient differential diagnosis which emphasized the  "temporal connection between Mr. Miller’s acute renal failure and the injection of Trasylol, together with the absence of renal disease or issues prior to the surgery.

This court falls in the camp of those who conclude that a differential diagnosis, properly performed, constitutes a reliable methodology for determining medical causation under Daubert. See Guinn v. Astrazeneca Pharms. LP, 602 F.3d 145, 153 (11th Cir. 2010); Ervin v. Johnson & Johnson, Inc., 492 F.3d 901, 904 (7th Cir. 2007).  Readers will recall that we have explained how plaintiffs have mis-used the notion of differential diagnosis, jumping from a medical method to figure out what disease a patient has to a legal method to figure out why the patient has the disease.  In any event, the court noted that an expert does not establish the reliability of his techniques or the validity of his conclusions simply by claiming that he performed a differential diagnosis on a patient.  Instead, a court must examine whether the expert correctly applied the differential diagnosis methodology. 

As applied in several courts, the method requires an expert to rule in all the potential causes of a patient’s ailment and then by systematically ruling out causes that would not apply to the patient, the physician arrives at what is the likely cause of the ailment. Westberry v. Gislaved Gummi AB, 178 F.3d 257, 262 (4th Cir. 1999)).  Plaintiff experts routinely make a couple mistakes:  Expert testimony that rules in a potential cause of a patient’s symptoms that is not so capable is unreliable.  At the rule out step, the expert must at least consider the other causes that could have given rise to Plaintiffs’ injury.  Courts vary on whether the expert must rule out all possible alternative causes, or the most likely ones, or at least consider other factors that could have been the sole cause of the plaintiff's injury.  A differential diagnosis that fails to take serious account of other potential causes may be so lacking that it cannot provide a reliable basis for an opinion on causation.  And an expert must provide a reasonable explanation as to why he or she has concluded that any alternative cause suggested by the defense was not the sole cause of the plaintiff’s injury.

The court then noted that  a temporal connection between exposure to chemicals and an onset of
symptoms, standing alone, is entitled to little weight in determining causation. See McClain v.
Metabolife Int’l, Inc., 401 F.3d 1233, 1254 (11th Cir. 2005); Happel v. Walmart Stores, Inc., 602 F.3d 820 (7th Cir. 2010).  Temporal proximity is especially unreliable where conditions independent of
exposure to the drug could have been the sole cause of the plaintiff’s injury, and the expert fails to
explain the relative contribution of the drug to the injury.  Here, one flaw in the expert's methodology was his failure to account for or appropriately address numerous risk factors at both the rule in and rule out stage., factors which either alone or in combination could explain Mr. Miller’s alleged renal injury. These factors include, but were not limited to: pressure stabilizing medications; extended pre-surgical and post-operative hypertension; and pre-surgical chronic renal failure. Even to those factors which the expert did rule in, he either gave them short shrift at the rule-out stage, or dismissed them without discussion.  In neither his report nor deposition did the expert provide any explanation for why he concluded that Mr. Miller’s various risk factors other than exposure to Trasylol were not the sole cause of his injuries. In fact, during his deposition, he conceded several additional risk factors for Mr. Miller that he had failed to consider in rendering his opinion, and further testified that many of those risk factors, either alone or in concert, could have caused Mr. Miller’s transient creatinine rise. He was forced to admit that Mr. Miller, without Trasylol, “could have had the same postoperative course.”


Thus there was no way to determine that one factor had more of an effect than the others. That led plaintiff to argue that Trasylol somehow tipped the scales causing his renal injury (the so-called straw that broke the camel's back).  But after sorting through these opinions and the Plaintiffs’ response to Defendants’ Motion, the court found that exclusion of the expert was warranted because of the absence of a reliable methodology, the failure to provide a plausible explanation for why he concluded that Mr. Miller’s various risk factors other than exposure to Trasylol were not the sole cause of his renal injury. Under Illinois law, a party cannot create a genuine issue of fact merely by presenting an expert witness who is willing to express an unsupported opinion that favors the party’s position. See Lewis v. CITGO Petroleum Corp, 561 F.3d 698, 705 (7th Cir. 2009).

 

 

 


 

Second Circuit Rejects Claims Over Scientific Literature

The Second Circuit recently held that scientific opinions voiced during debate of unsettled questions generally cannot support false advertising or deceptive business practices claims. See ONY Inc. v. Cornerstone Therapeutics Inc., No.12-2414 (2d Cir. June 26, 2013).

Defendants in this case were various corporate sponsors, authors, and publishers of a scientific journal article comparing the effectiveness of several types of medical surfactants -- biological substances that line the surface of human lungs. Surfactants are critical to lung function: they facilitate the transfer of oxygen from inhaled air into the blood stream.  Plaintiff ONY and defendant Chiesi Farmaceutici are two of the biggest producers of surfactants for medical treatment.  These parties vigorously contested the relative effectiveness of their products – in the marketplace, in the scientific literature, and in this lawsuit. The parties agreed that two variables are particularly relevant to this comparison: mortality rate and length of stay. Mortality rate means the percentage of patients (typically infants) treated with a particular surfactant who do not survive. Length of stay refers to the amount of time a patient infant remains in the hospital for treatment.

The dispute stemmed from a study funded by Chiesi, carried out by a private research firm, and then promoted and ultimately published by three doctors, which concluded that Chiesi's surfactant product allegedly led to lower infant mortality rates than ONY's product. The doctors submitted their article to the Journal of Perinatology, a leading journal in the field of neonatology. .After the article’s publication, Chiesi issued a press release touting its conclusions and distributed promotional materials that cited the article’s findings.  Plaintiff complained that the article – and the distribution of selections from it – violated the Lanham Act and New York General Business Law § 349, and also constituted tortious injurious falsehood and interference with prospective economic advantage.

The district court concluded that plaintiff failed to state a claim based on publication of the article because the challenged statements were protected scientific opinion. The Second Circuit agreed, concluding that, as a matter of law, statements of scientific conclusions about unsettled matters of scientific debate cannot give rise to liability for damages sounding in defamation.

Plaintiff claimed that the article made statements about scientific findings that were intentionally deceptive and misleading, and that it therefore constituted false advertising. Plaintiff’s theory was that scientific claims made in print purport to be statements of fact that are falsifiable, and such statements can be defamatory or represent false advertising if known to be false when made. Plaintiff argued on appeal that the district court based its conclusion that the article’s statements were non-actionable solely on its determination that the assertions were statements of opinion, without conducting a more vigorous inquiry. 

The court of appeals noted that scientific academic discourse poses several problems for the fact-opinion paradigm of traditional First Amendment jurisprudence. Many conclusions contained in a scientific journal article are, in principle, “capable of verification or refutation by means of objective proof,” Phantom Touring, Inc. v. Affiliated Publ’ns, 953 F.2d 724, 728 n.7 (1st Cir. 1992). Indeed, it is the very premise of the scientific enterprise that it engages with empirically verifiable facts about the universe. At the same time, however, it is the essence of the scientific method that the conclusions of empirical research are tentative and subject to revision, because they represent inferences about the nature of reality based on the results of experimentation and observation. Importantly, those conclusions are presented in publications directed to the relevant scientific community, ideally in peer reviewed academic journals that warrant that research approved for publication demonstrates at least some degree of basic scientific competence. These conclusions are then available to other scientists who may respond by attempting to replicate the described experiments, conducting their own experiments, or analyzing or refuting the soundness of the experimental design or the validity of the inferences drawn from the results.

In a sufficiently novel area of research, propositions of empirical “fact” advanced in the literature may be highly controversial and subject to rigorous debate by qualified experts. Needless to say, courts are ill-equipped to undertake to referee such controversies. Instead, the trial of ideas plays out in the pages of peer-reviewed journals, and the scientific public sits as the jury.

Where, as here, a statement is made as part of an ongoing scientific discourse about which there is considerable disagreement, the traditional dividing line between fact and opinion is not entirely helpful. While statements about contested and contestable scientific hypotheses constitute assertions about the world that are in principle matters of verifiable “fact,” for purposes of the First Amendment and the
laws relating to fair competition and defamation, they are more closely akin to matters of opinion, and are so understood by the relevant scientific communities.

In that regard, said the court, it was relevant that plaintiff did not allege that the data presented in the article were fabricated or fraudulently created. If the data were falsified, the fraud might not be easily detectable by even the most informed members of the relevant scientific community. Rather, plaintiff here alleged that the inferences drawn from those data were the wrong ones, and that competent scientists would have included other data that were available to the defendant authors but that were not sufficiently taken into account in their analysis.

But when the conclusions reached by experiments are presented alongside an accurate description of the data taken into account and the methods used, the validity of the authors’ conclusions may be
assessed on their face by other members of the relevant discipline or specialty.The appeals panel therefore concluded that, to the extent a speaker or author draws conclusions from non-fraudulent data, based on accurate descriptions of the data and methodology underlying those conclusions, on subjects about which there is legitimate ongoing scientific disagreement, those statements are not grounds for a claim of false advertising. Even if the conclusions that the authors drew from the results of their data could be actionable, such claims would be suspect when, as here, the authors readily disclosed the potential shortcomings of their methodology and their potential conflicts of interest

This analysis properly reflected a worry about the chilling impact on crucial and valuable research, including comparative effectiveness research, of lawsuits by competitors who are unhappy with or disagree with the results of such studies. Such a debate belongs in the marketplace of scientific ideas, not in the court room. 

Supreme Court Issues Important Preemption Ruling

The Supreme Court last week reversed the First Circuit decision in Mutual Pharmaceutical Co. v. Bartlett, No. 12-142 (U.S., 6/24/13).

Readers will recall that in PLIVA, Inc. v. Mensing, 131 S. Ct. 2567 (2011), the Supreme Court held that state tort law claims against generic drug manufacturers based on the alleged inadequacy of the drug labeling are preempted; under the Hatch-Waxman Amendments to the Food, Drug and Cosmetic Act, generic drug labeling must be the same as the labeling of the reference-listed drug. Because generic drug manufacturers cannot independently change the labeling, state law failure to warn claims are preempted.

Plaintiffs proceeded to hunt for exceptions, ways around the ruling.  One of the strategies was to resurrect design defect theories, which traditionally were not a major aspect of most drug plaintiff claims. This case was tried on a design defect theory of liability after the plaintiff’s failure to warn claims were dismissed prior to trial and the district court rejected the generic manufacturer’s preemption defense on the design claim.  The jury found for plaintiff, and defendant appealed, arguing that just as the manufacturer cannot alter the label, once a drug—whether generic or brand-name—is approved, the manufacturer is prohibited from making any major changes to the qualitative or quantitative formulation of the drug product, including active ingredients, or in the specifications provided in the approved new drug application.  In Bartlett, the First Circuit held that the plaintiff’s state law theory of liability could nevertheless be reconciled with federal law because, although the generic manufacturer could change neither the design nor the labeling, it could avoid liability if it stopped selling the drug entirely within the state.

The Supreme Court reversed.

New Hampshire imposes design defect liability where the design of the product created a defective condition unreasonably dangerous to the user. To determine whether a product is “unreasonably dangerous,” the New Hampshire Supreme Court employs a risk/utility approach under which a product is defective as designed if the magnitude of the danger outweighs the utility of the product. The New Hampshire Supreme Court has repeatedly identified three factors as germane to the risk-utility inquiry: the usefulness and desirability of the product to the public as a whole, whether the risk of danger could have been reduced without significantly affecting either the product’s effectiveness or manufacturing cost, and the presence and efficacy of a warning to avoid an unreasonable risk of harm from hidden dangers or from foreseeable uses.  

In the drug context, either increasing the “usefulness” of a product or reducing its “risk of danger” would require redesigning the drug: a drug’s usefulness and its risk of danger are both direct results of its chemical design and, most saliently, its active ingredients. Here, said the Supreme Court, redesign was not possible, as the FDCA requires a generic drug to have the same active ingredients, route of administration, dosage form, strength, as the brand-name drug on which it is based. Given the impossibility of redesigning the drug, the only way for the defendant to ameliorate the drug’s “risk-utility” profile—and thus to escape liability—was to strengthen the presence and efficacy of the warning in such a way that the warning avoided an unreasonable risk of harm from hidden dangers or from foreseeable uses.

That was, of course, preempted.  When federal law forbids an action that state law requires, the state law is “without effect.” Because it is impossible for generic manufacturers to comply with both state and federal law, New Hampshire’s warning-infused design defect cause of action was pre-empted with respect to FDA-approved drugs sold in interstate commerce.

The Supreme Court rejected the argument that a defendant could satisfy both laws by paying tort judgments or refraining from selling its product in that particular state. And rejected the “stop-selling” rationale as incompatible with its pre-emption jurisprudence. The Court's pre-emption cases presume that an actor seeking to satisfy both his federal and state law obligations is not required to cease acting altogether in order to avoid liability. Indeed, if the option of ceasing to act defeated a claim of impossibility, impossibility pre-emption would be all but meaningless. The incoherence of the stop-selling theory becomes plain when viewed through the lens of the previous cases. In every instance in which the Court has found impossibility pre-emption, the direct conflict between federal and state law duties could easily have been avoided if the regulated actor had simply ceased acting.

Interestingly, there is nothing in the Court's rejection of “stop-selling” limiting it to generic drugs; the rejection seems applicable to all federally regulated products because it's not based on the FDCA but is an argument “incompatible with our pre-emption jurisprudence.”

 

Supreme Court Declines to Review Defense Win in Drug Case

The Supreme Court declined earlier this month to review a decision by the Second Circuit affirming a defense verdict in the Fosamax litigation.  See Secrest v. Merck, Sharp & Dohme Corp., U.S., No. 12-1318, cert. petition denied 6/3/13).  The case explicates an interesting and somewhat rare evidentiary issue.

Readers may recall that a jury in the Southern District of New York handed down a defense verdict for Merck in October, 2011. One of the key evidentiary issues was the trial court's decision to exclude one of the expert witnesses for plaintiff under the so-called “sham issue of fact” doctrine. Dr. Epstein initially was designated a fact witness, and deposed as such.  After Merck moved for summary judgment, Dr. Epstein was designated as an expert, and he was re-deposed, and changed his testimony.  The second time around the witness testified that plaintiff took Fosamax in 2004 and 2005, but earlier had said he did not know about her alleged usage.

Because the physician’s expert testimony contained contradictions that were unequivocal and inescapable, unexplained, arose after the motion for summary judgment was filed, and were central to Secrest’s failure-to-warn claim, the Second Circuit held that the District Court did not err in determining that there was no genuine dispute of material fact raised by the later testimony.  The Supreme Court refused to entertain plaintiff's appeal.

Specifically, the District Court was entitled to disregard Dr. Epstein’s new testimony relating to his knowledge based on the “sham issue of fact” doctrine, which prohibits a party from defeating summary judgment simply by submitting an affidavit that contradicts the party’s previous sworn testimony. See Perma Research & Dev. Co. v. Singer Co., 410 F.2d 572, 578 (2d Cir. 1969). Although courts more typically apply the sham issue of fact doctrine where a party submits an affidavit that contradicts the party’s own prior statements, it may also apply when a party attempts to use evidence from an expert witness to defeat summary judgment.


Here, said the Second Circuit, the doctrine applied to stop Secrest from manufacturing a factual dispute by submitting testimony from an expert whom she tendered, where the relevant contradictions between the first and second depositions were unequivocal and inescapable, unexplained, arose after the motion for summary judgment was filed, and were central to the claim at issue.  See Rivera v. Rochester Genesee Reg’l Transp. Auth., No. 11-762-cv, 2012 WL 6633938, at *7 (2d Cir. Dec. 21, 2012) (concluding that summary judgment was inappropriate because the inconsistencies in the plaintiff’s testimony were not “real, unequivocal, and inescapable contradiction[s]”).  Here, Dr. Epstein’s February 2011 expert deposition testimony inescapably and unequivocally contradicted the testimony he gave in August, 2008.

Also, the relevant contradiction was not only unequivocal but was left unexplained – indeed, was inexplicable – so the trial court could properly determine that plaintiff had manufactured a sham issue of fact. See Rojas, 660 F.3d at 105-06; AEP Energy, 626 F.3d at 735-36. Finally, the sham issue of fact doctrine applied here, continued the Second Circuit, because the relevant contradictions in Dr. Epstein’s testimony were central to Secrest’s failure-to-warn claim. Applicable Florida law required Secrest to show that her treating physician would have recommended that she cease taking the drug if a different, adequate warning had been provided. Here, no reasonable juror could find that Dr. Epstein would have recommended that Secrest cease taking Fosamax if he did not even know she was taking it at the relevant time. 

The Supreme Court then denied plaintiff's cert petition. 

 

 

Drug and Device Seminar Approaches

It is spring time -- although you might not know it from the weather -- and it is time for one of the premier educational and networking conferences for the pharmaceutical and medical device defense bar – the DRI Drug and Medical Device Seminar.  Your hosts this year include my partner and Drug and Medical Device Committee Chair Scott Sayler, and my old pal Jeffrey A. Holmstrand, Flaherty Sensabaugh Bonasso PLLC, Wheeling, West Virginia.

The 2013 DRI Drug and Medical Device Seminar  will be held May 16-17 in New York City at the Sheraton Hotel in Midtown. Most of my readers are familiar with the Seminar and many routinely attend. Here are just a few highlights of the program this year.


• Judge Arnold New of the Philadelphia Court of Common Pleas will present on recent changes in that busy Court.
•  Judge Raymond Lohier of the Second Circuit will speak at the Diversity Luncheon.
• A presentation on how to get the most from Comment K in a medical device case.
• A discussion of  the conflict between free speech and off-label promotion.

  • Observations from the American Tort Reform Association on tough venues.
     

Other benefits-  I am told in-house counsel can attend for FREE, either as a member of DRI or via sponsorship by an outside counsel. FREE wi-fi in the conference room (so, yes, you can multi-task and read this blog.)  All of the usual networking events will be in full swing. 

For more information or to register, go to http://www.dri.org/Event/20130070.

DES Plaintiff's Reach for Market Share Liability Rejected Again

If asbestos is the grandfather of mass torts, the DES litigation may be the grandmother, with claims continuing today for harm allegedly caused by in utero exposure to diethylstilbestrol decades ago. DES is a drug once prescribed during pregnancy to prevent miscarriages or premature deliveries. In the U.S. an estimated 5 to 10 million persons were exposed to DES from 1938 to 1971, including pregnant women prescribed DES and their children. So we are 40 years out now, with some litigation remaining.

Recently, a federal court in New York held that a DES plaintiff could not meet the product identification requirement under applicable Texas law.  See Bezuidenhout v. Abbott Laboratories,  No. 10-CV-1011(E.D.N.Y., 1/17/13).

Readers may recall that what is often termed "product identification" is part of the cause in fact requirement of every tort claim.  A plaintiff must show that he or she has been injured not just by a type of product but by a product actually made or sold by the defendant.  In the context of DES, product identification may be especially challenging because the plaintiff's exposure may be in utero and the manifestation of the injury may not come for many years after the exposure.  A tiny minority of jurisdictions have flirted with weakening the traditional cause in fact requirement by adopting some form of the "market share" doctrine, under which defendants may be held proportionately liable to a plaintiff who cannot show which manufacturer sold the product that caused the injury, based on that defendant's sales of the product in the "relevant market."  Flawed and unfair, the concept did not gain wide acceptance.

Bezuidenhout was born in 1957 in Texas. While pregnant, her mother allegedly took DES, which was prescribed to her in Texas, according to the amended complaint. Decades later, plaintiff alleged various personal injury and increased risk of future injuries.  Defendants moved for summary judgment, asserting that plaintiff could not identify which manufacturer made the DES her mother took, as required under Texas law.

Plaintiff argued that Texas law was unsettled, that Texas courts had not clearly rejected the market share theory.  The court said it  need not wade too deeply into Bezuidenhout's "pool of hypotheticals", since it rested upon a false premise—that Texas law, as to proof of causation, is unsettled..."It is not.”  Indeed, the court opined that one of the goals of this case was to unsettle it. Texas does not permit recovery under a collective liability or market share theory. The courts in In re Fibreboard Corp., 893 F.2d 706 (5th Cir. 1990), and Cimino v. Raymark Indust., Inc., 151 F.3d 297, 312 (5th Cir. 1998), held that in Texas, it is a fundamental principle of traditional products liability law that the plaintiff must prove that the defendants supplied the product which caused the injury. Plaintiff tried to bootstrap to an "alternate reality," said the court. The Texas Supreme Court has never chosen to adopt market share liability.  

With the market share approach rejected, plaintiff had not proffered sufficient evidence to identify the defendant as a manufacturer of her mother's DES. Her mother's affidavit contradicted her prior sworn deposition testimony about whose product she might have used.  And, at best, a log from the pharmacist indicated that defendant's DES was among the many medications available at the pharmacy, but did not show which DES her mother took. The court thus found plaintiff failed to raise a genuine issue of material fact regarding the identity of the DES manufacturer.

Solomon Court Issues Wise Decision in Drug Case

The federal court in New Jersey recently granted summary judgment to a drug manufacturer in a failure to warn claim under Texas law.  See Solomon v. Bristol-Myers Squibb Co., No. 07-1102 (D.N.J., 1/3/12).  The opinion offers a number of useful observations.

The case involved Plavix, a drug that inhibits blood platelets from forming clots. The drug is often used in patients with recent heart attack, stroke, or diagnosed peripheral vascular disease, to prevent dangerous clots.Taking Plavix, like any medicine, is not without risk. Because it functions by inhibiting the formation of blood clots, Plavix increases the risk of bleeding. The manufacturer warned of this risk extensively on the label. 

In November 2002, Plaintiff suffered a heart attack, and his doctors placed two metal stents in his arteries to maintain blood flow to his heart. At that time, one of his doctors prescribed Plavix with aspirin in order “to prevent clots.” Subsequently, Plaintiff’s treating cardiologist continued this prescription. In July 2005, Plaintiff began suffering gastrointestinal bleeding, which led him to sue Defendants asserting product liability related causes of action, under Texas state law, for defective design, manufacturing defect, failure to warn, and negligence.  All these  claims essentially turned on whether Defendants adequately warned that Plavix carried a risk of bleeding complications.

Defendants moved for summary judgment, relying in large measure on the learned intermediary doctrine. Readers will recall that within the prescription drug context, where a plaintiff sues the manufacturer of a prescription drug for failing to adequately warn of the drug’s effects, Texas courts employ the learned intermediary doctrine. As the Texas Supreme Court has explained, the underlying premise for the learned intermediary doctrine is that prescription drugs are complex and vary in effect, depending on the unique circumstances of an individual user, and for this reason, patients can obtain them only through a prescribing physician. Indeed, a patient’s doctor, who stands between the patient and the drug manufacturer, is in the best position to professionally evaluate the patient's needs, assess the risks and benefits of available drugs, prescribe one, and supervise its use. Hence, if the doctor is properly warned of the possibility of a side effect and is advised of the symptoms normally accompanying the side effect, it is anticipated that injury to the patient will often be avoided. Recognizing the doctor-patient relationship, the doctrine excuses a drug manufacturer from warning each patient who receives the product when the manufacturer properly warns the prescribing physician of the product’s dangers.

In arguing the warning claim, Plaintiff contended that he was entitled to a heeding presumption that proper warnings would have a made a difference and that this presumption excused him from proving causation. However, Texas law creates no such presumption. The Fifth Circuit has noted that neither Texas nor federal courts applying Texas law have applied the read-and-heed
presumption to pharmaceutical cases involving learned intermediaries. Indeed, Texas has explicitly rejected the Restatement (SECOND) Of Torts § 402A, Comment j's read-and-heed presumption for policy reasons and, said the court, because it has been superseded by Restatement (THIRD) Of Torts::Products Liability § 2.

On the factual assertions of failure to warn, the court found that although Plaintiff presented various studies and articles challenging the efficacy of Plavix in certain types of patients, none of those studies were  relevant to Plaintiff’s medical situation. For example, the studies upon which Plaintiff tried to rely regarding Plavix’s alleged ineffectiveness for patients 75 years or older had no relevance since Plaintiff was well under 75 years old when he stopped taking the drug. More fundamentally, many of Plaintiff's arguments seemed to center on an alleged lack of efficacy; Plaintiff’s efficacy arguments were not relevant in the context of a failure-to-warn analysis. Plaintiff’s claim was essentially premised on the fact that he suffered substantial bleeding, while his response to the motion argued Plavix did not work. A proper warning should adequately alert any danger or harm that may result from ingesting the drug; efficacyis a separate issue. Permitting Plaintiff to pursue his failure-to-warn claim on an efficacy theory would, as has been found in other jurisdictions with similar laws, impermissibly expand liability under Texas law on the adequacy of pharmaceutical warning labels.

Focusing on the alleged inadequacy of the warning, Texas law is clear that when a warning appropriately and specifically mentions the circumstances complained of, the warning is adequate as a matter of law. First and foremost, said the court, the warning label here clearly cautioned users that PLAVIX use with aspirin was associated with an increase in bleeding. Plaintiff failed to provide any evidence to show that the risk levels published on the Plavix warning label were inaccurate, insofar as the warnings concerned the risk of bleeding.

Another ground for summary judgment. In addition to proving inaccuracy, Plaintiff had to show that
the allegedly defective warning label was the producing cause of Plaintiff’s injury. Thus, it was Plaintiff’s burden to demonstrate that the treating physician would not have used or prescribed the product but for the inadequate warning. However, the cardiologist insisted that despite the risks, it was important that these drugs were prescribed to Plaintiff to prevent a life-threatening problem.  The doctor acknowledged that the therapy could cause serious risk of bleeding in patients.   Nevertheless, the cardiologist insisted that despite the risks, it was important to prescribe the drug.  Furthermore, throughout the prescribing doctor's deposition, he  consistently testified that he did not rely on Plavix warning labels.  Texas law is clear on causation: when the prescribing physician is aware of the product’s risks and decides to use it anyway, any inadequacy of the product’s warning, as a matter of law, is not the producing cause of the patient’s injuries.  It was clear that  the doctors were aware of the serious risks of bleeding when placing Plaintiff on the medicine. 

Plaintiff’s failure-to-warn claim failed for the additional  reason that, under Texas law, Defendants are presumed not liable because the Plavix warning labels were approved by the FDA. In Texas, where prescription drug manufacturers comply with the FDA regulations, Texas law creates a rebuttable presumption of non-liability in prescription drug suits. See Tex. Civ. Prac. & Rem.
Code. Ann. § 82.007.

Summary judgment granted.

Drug Maker Defeats AG Motion to Dismiss Action Challenging Private Contingency Counsel

We have warned readers before about the dangerous and growing practice of governmental agencies delegating state police powers to private (plaintiff) attorneys on a contingency fee basis.  The latest round in this nationwide battle comes from Kentucky, where the court recently ruled that Merck can continue its suit alleging violation of its due process rights after the state hired such outside counsel.  See Merck Sharp & Dohme Corp. v. Conway, No. 3:11-cv-51 (E.D. Ky., 12/19/12).

The matter underlying this action arose from Merck’s marketing and distribution of the prescription medication Vioxx. The AG filed suit against Merck in the Franklin County Circuit Court in 2009, alleging a violation of the Kentucky Consumer Protection Act (“KCPA”). Merck removed the case to federal court, and the action was then transferred to the Eastern District of Louisiana on April 15, 2010, as part of the multidistrict litigation, In re Vioxx Product Liability Litigation, MDL No. 1657.  But on January 3, 2012, the District Court for the Eastern District of Louisiana granted the AG’s motion to remand, concluding that the case was improperly removed from state court. In re Vioxx Prods. Liab. Litig., MDL No. 1657, 2012 WL 10552, at *14 (E.D. La. Jan. 3, 2012).

Now, approximately one year into the proceeding, the AG had retained outside counsel to take over the Vioxx KCPA litigation.  Under the contract executed, private counsel agreed to be compensated by a contingency fee “to be withheld from any settlement award resulting from the litigation.” Merck filed suit against the AG in federal court in August, 2011, seeking a declaratory judgment and injunctive relief. In its complaint,  Merck alleged that the AG had “delegated his coercive powers to private lawyers having a clear, direct and substantial financial stake in the outcome...."  The case was "a punitive enforcement action that must be prosecuted in the public interest or not at all.”  As a result, Merck asserted, its “right to due process under the Fourteenth Amendment had been infringed.” 

The AG moved to dismiss, and the issue in this decision focused on the abstention doctrine announced in Younger v. Harris, 401 U.S. 37 (1971); it provides that when a state proceeding is pending, principles of federalism dictate that any federal constitutional claims should be raised and decided in state court without interference by the federal courts. See Pennzoil Co. v. Texaco, Inc., 481 U.S. 1, 17 (1987).  If a federal district court concludes that its resolution of the case before it would directly interfere with ongoing state proceedings, then it must determine whether to abstain from hearing the case altogether, under the following: (1) there must be an ongoing state
judicial proceeding; (2) the proceeding must implicate important state interests; and (3) there
must be an adequate opportunity in the state proceeding to raise constitutional challenges.

Merck argued that the AG’s active litigation in federal court — through the filing of answers, motions to dismiss, and motions for summary judgment — was sufficient to establish that proceedings of substance had taken place before the remand, i.e., before an action had been pending in state court.  The court agreed that the abstention doctrine did not require a strict view of the federal action timeline nor a formalistic approach to the abstention analysis. Using a "common sense approach," several factors weighed in favor of a conclusion that proceedings of substance had taken place: (1) the federal action had been pending for over seven months when the state court proceeding was remanded on March 20, 2012; (2) on the date of the remand, there were two important motions that were fully briefed and ripe for adjudication; and (3) the court had held a scheduling conference during which the parties advised the court about their positions on those two motions. Based on these facts, the court concluded that the federal action was well beyond an “embryonic stage.” Because the state proceeding was not “ongoing” in a meaningful sense, abstention was not appropriate under the principles of Younger.

Your humble blogger notes that the legal policy of many states strongly favors open, competitive bidding for contracts involving state funds. Such requirements, included in some state Constitutions and various statutes, are designed to prevent fraud, eliminate bias and favoritism, and thus protect vital public interests. Those same goals of open and good government reside in the requirement that state officials give their undivided loyalty to the people of a state. Many of the contingent fee contracts used by state officials to bring mass tort actions violate the core principle that attorneys pursuing actions on behalf of the state represent a sovereign whose obligation to govern impartially is essential to its right to govern. Government attorneys must exercise independent judgment as a ministers of justice and not act simply as advocates. The impartiality required of government lawyers cannot be met where the private pecuniary interest inherent in the contingent fee is the primary motive force behind the bringing of the action. By turning over sovereign prosecutorial-like power to contingency counsel, a state effectively creates a new branch of government – motivated by the prospect of private gain rather than the pursuit of justice or the public welfare. This subversion of neutrality does more than implicate the due process rights of those confronting such tainted prosecutions. Direction of state prosecutions by financially interested surrogates also damages the very public interest that such litigation is supposed to advance. 
 

Defense Verdict Upheld on Post-trial Motion in Levaquin MDL

About 1700 federal cases sit in the MDL for the product Levaquin makers.  Levaquin is an antibiotic used to treat a variety of bacterial infections, including upper respiratory infections. Plaintiffs in the MDL allege they have been prescribed Levaquin, and allege that it causes tendons to rupture. They claim that defendants' warnings about this alleged side effect were inadequate.  Defendants deny these allegations.

In this mass tort, the MDL court has begun to try bellwether cases. Recently the MDL court rejected a plaintiff's post-trial motion after he lost the third such trial. See Straka v. Johnson & Johnson, No. 08-5742 (D. Minn., 9/28/12).  A jury found that the alleged failure to warn Straka's prescribing physician about the risk of tendon rupture did not cause the plaintiff's injuries. After trial, one issue was the ubiquitous and almost never prevailing "verdict against the weight of the evidence" argument.  The court disposed of this by noting the sufficient evidence at trial supporting the jury's finding in that Straka's injuries were caused by something other than Levaquin, and that a different warning would not have changed his physician's decision to prescribe Levaquin. Defendants presented evidence about Straka’s steroid use and testimony that steroid use can contribute to tendon injury without the use of Levaquin.  And defendants did a good job presenting evidence that the prescriber could not remember reading the Levaquin label and did not learn of the tendon-associated risks of Levaquin until well after the black box warning was added and a Dear Doctor letter was distributed.

Perhaps more interesting for the trial lawyers among our readers is the argument for a new trial because one juror worked for a company that had a business connection to one of the defendants. Specifically the juror disclosed after trial began that her employer provided services to one of the defendants' (J&J) disability insurance carrier. Straka contended the doctrine of “implied bias” required the court to strike this juror. But the juror could not recall having ever worked on a Johnson & Johnson issue, and she indicated that she was unaware what proportion of her work came indirectly from Johnson & Johnson. When asked if her company’s connection with Johnson & Johnson would affect her ability to be fair and impartial, she said no. 

The doctrine of implied bias (also referred to in some cases as “implicit bias”) requires a court to strike a juror in extreme situations where the relationship between a prospective juror and some aspect of the litigation is such that it is highly unlikely that the average person could remain impartial in his deliberations under the circumstances. See Sanders v. Norris, 529 F.3d 787, 792 (8th Cir. 2008).  The juror here did not have the type of financial relationship that would require the Court to presume implied bias: she was not employed by defendants, or even employed by a company that worked directly for Johnson & Johnson.  Nor was it unlikely that the average person could remain impartial in deliberations in this situation. She was sufficiently removed from Johnson & Johnson that she did not realize that her company did any work relating to the defendants until a co-worker recognized it. So no error in proceeding.

[FYI, according to the court, some MDL parties discussed have discussed a tentative settlement agreement reached on September 25, 2012, in a conference held in front of Chief Magistrate Judge Boylan. This tentative settlement agreement is being drafted, and involves the case inventories of 6 law firms. The effect of this settlement would reduce the MDL case count by 845 cases and plaintiffs. At the time of the status conference several other plaintiffs' firms have expressed an interest in exploring settlement, but there remain firms that are interested in going forward with the litigation, according to the court.]


 

Another Federal Court Applies Mensing

A federal court in Ohio recently ruled that a plaintiff who used only the generic form of the drug  metoclopramide has no cause of action under the Ohio Product Liability Act against makers of the brand-name drug. Hogue v. Pfizer Inc., No. 10-805 (S.D. Ohio, 9/27/12).

In late 2000, Ms. Hogue's physician prescribed Reglan® to treat plaintiff''s abdominal pain and digestive problems. Ms. Hogue then began to take generic metoclopramide and continued to do so until about August 2009. The parties stipulate she ingested only the generic version of metoclopramide, which the Brand Defendants did not manufacture. She later allegedly suffered side effects and sued both the branded and the generic manufacturers for an alleged failure to warn. And so  we have two rulings to reflect the status of each kind of defendant.

The generic defendants filed a motion to dismiss, arguing that the United States Supreme Court held in PLIVA, Inc. v. Mensing that such state law tort claims against generic drug manufacturers are preempted by federal law. Generic defendants pointed out that the Mensing case involved the same generic medication at issue in this case, the same alleged injuries, some of the same generic drug manufacturer defendants, the same claims, etc.  Plaintiff argued that nonetheless the Mensing holding was somehow more limited.  The court agreed with the defendants: First, the Supreme Court rejected the theories that generic drug manufacturers could use the "changes-being-effected" ("CBE") process to change their labels to satisfy the state law. The FDA interprets the CBE process to allow generic manufacturers to change generic drug labels only to match an updated brand-name label or to follow the FDA's instructions. Any unilateral change to labels by generic drug manufacturers would violate the federal requirement that generic drugs be identical to brand name drugs in both substance and labeling.

Second, the court noted that  the Supreme Court has considered and rejected the plaintiff's argument that the generic drug manufacturers could have sent "Dear Doctor" letters as additional
warnings. Dear Doctor letters qualify as "labeling" and therefore must be consistent with, and not
contrary to, the rest of the drug's approved labeling.  Any Dear Doctor letter containing substantially new warnings would not conform to the approved labeling. Moreover, if generic drug
manufacturers, but not the brand-name manufacturer, sent such letters, that would inaccurately imply a therapeutic difference between the branded and generic drugs and thus could be impermissibly misleading.

Third, the Supreme Court already considered whether the generic drug  manufacturers could have complied with the state laws by proposing stronger warning labels to the FDA. Even assuming such a duty exists on the part of generics, which is not clear, fulfillment of that duty would not have satisfied the state law requirements. Because it was impossible to comply with both federal law and state law, the plaintiff's state law claims were preempted.

Plaintiff further argued that Mensing didn't apply when the FDA has designated a defendant's drug as a reference listed drug ("RLD"). But the designation of a drug as an RLD does not change the manufacturer's status as an Amended New Drug Application ("ANDA'') holder,  the RLD designation does nothing to alter an ANDA holder's duties concerning labeling changes.

On the legal side, even if a failure to warn was preempted, plaintiff argued that several of her legal claims were not based on a theory of failure to warn. For example, plaintiff stated her breach of warranty claims did not conflict with any federal requirement regarding labeling and thus were not preempted. But the required analysis here is to focus not on the label or caption of the count, but the substance of the claim; and the other claims such as breach of warranty were in fact predicated on the failure to provide adequate warnings and were preempted. See also Smith v. Wyeth, 657 F.3d 420, 423 (6th Cir. 2011 ), cert. denied 132 S. Ct. 2103.

Brand defendants moved for summary judgment, arguing that Ohio law requires a plaintiff to prove the defendant manufactured the product that caused her injuries. Because they did not manufacture the metoclopramide Ms. Hogue ingested, her claims against them should fail as a matter of law.

The court noted that under Ohio law the defendant must have sold the actual product that was the cause of harm for which the claimant seeks to recover compensatory damages, and proof that a manufacturer designed or sold the type of product in question is not proof that the manufacturer did so for the actual defective product in the product liability claim. The Ohio Product Liability Act displaced plaintiff's common law claims, and required plaintiff to prove the defendant manufactured the product that caused her injuries.  They did not, so summary judgment was warranted.

(Note SHB works for the defense in part of this litigation.)
 

 

 

Federal Court Offers Cogent Analysis of Warning Causation in Drug Case

A New Jersey federal court granted summary judgment last week to a pharmaceutical defendant in a failure to warn case. See Baker et al. v. APP Pharmaceuticals LLP et al., No. 3:09-cv-05725 (D.N.J.).  The case should be interesting to our readers in part because there really isn't a huge amount of law on warning causation in the busy jurisdiction of New Jersey.

During a hospital stay, plaintiff Baker was administered the commonly prescribed drug heparin. Heparin is an anticoagulant: it prevents blood clots. The opinion noted that the drug is associated  with heparin induced thrombocytopenia (“HIT”), or low blood platelet count. HIT may in a few patients progress to a more serious adverse reaction called heparin induced thrombocytopenia  and thrombosis (“HITT”). Plaintiff received heparin during and after her surgery, and a few days later her  platelet count was down; but according to the opinion it was not known at what point her platelet count reached serious levels because no one measured her platelet level for several days, despite the hospital’s stated protocol to monitor a patient’s platelet count periodically in order to detect possible HIT.

Plaintiff suffered injury to her left foot and leg, and thereafter sued several manufacturers of heparin, asserting they failed to adequately warn of the serious side-effects associated with heparin use. The parties agreed that defendant’s heparin has always contained FDA-approved labeling, including risk disclosures and warnings. In 2001, the heparin label specifically disclosed the risk of HIT and HITT in the “Precautions” section.  In 2005, defendant submitted a supplemental NDA via the “changes being effected” process to include additional HIT and HITT information the “Warnings” section of its heparin labeling. See 21 C.F.R. 314.70. The FDA suggested several alterations, all of which defendant incorporated into the labeling, and the FDA found the updated labeling “acceptable” in June 2007. 

In New Jersey, product liability actions are governed by the New Jersey Products Liability Act (“PLA”). N.J. Stat. Ann. §2A:58C-1, et seq. Under the PLA, in failure to warn cases involving prescription drugs, if the warning or instruction given in connection with a drug has been approved or prescribed by the FDA, there is a rebuttable presumption that the warning is adequate. This is no ordinary rebuttable presumption, remarked the court. Compliance with FDA regulations gives rise to “what can be denominated as a super-presumption.” Kendall v. Hoffman-La Roche, Inc., 36 A.3d 541, 544 (N.J. 2012).  Indeed, the PLA’s presumption that an FDA-approved prescription drug label is adequate “is stronger and of greater evidentiary weight than the customary presumption referenced" in the rules of evidence. Bailey v. Wyeth, Inc., 37 A.3d 549, 571 (N.J. Super. Ct. Law Div. 2008), aff’d sub nom. Deboard v. Wyeth, 28 A.3d 1245 (N.J. Super Ct. App. Div. 2011).

In this case, there is no dispute that the heparin labeling was approved by the FDA. Therefore, defendant was entitled to the statutory presumption that its heparin labeling satisfied its duty to warn. Plaintiff tried to rebut the presumption, first, with allegations of deliberate concealment or nondisclosure of after-acquired knowledge of harmful effects by the pharmaceutical company, and second with allegations of an economically-driven manipulation of the post-market regulatory process. See McDarby v. Merck & Co., Inc., 949 A.2d 223, 256 (N.J. Super. Ct. App. Div. 2008).

However, significantly, all of the information plaintiff accused defendant of withholding was publicly available in published scientific and medical literature.  And defendant did in fact disclose much
of what plaintiff claimed was deliberately concealed or withheld. For example, when submitting its proposed updated label to the FDA in 2005, Baxter included several scientific articles and a number of adverse event reports relating to HIT and HITT.  As to the second rebuttal effort, plaintiff offered no real evidence that Baxter rejected the FDA’s proposed changes to heparin labeling, or asked pharmaceutical representatives to avoid discussing HIT and HITT when speaking to physicians, or manipulated the conclusions of heparin clinical trials, or did anything sufficient to "manipulate" the regulatory process.

The more interesting part of the opinion arises from the fact that even if a plaintiff is able to demonstrate that a prescription drug’s warning is inadequate, that plaintiff still must prove that the inadequate warning proximately caused her injury. See Campos v. Firestone Tire & Rubber Co., 485 A.2d 305, 311 (N.J. 1984). “To satisfy this burden, a plaintiff must show that adequate warnings would have altered her doctors’ decision to prescribe.” Strumph v. Schering Corp., 606 A.2d 1140 (N.J. Super. Ct. App. Div. 1992) (Skillman, J., dissenting), rev’d 626 A.2d 1090 (1993) (adopting Judge Skillman’s dissent).

The court noted that “a heeding presumption may be applicable to claims of failure to warn of the dangers of pharmaceuticals.” McDarby, 949 A.2d at 267. A heeding presumption allows one to presume that the plaintiff’s physician would not have prescribed the drug to the plaintiff if there had been an adequate warning; in other words, the plaintiff’s physician would have heeded the adequate warning. The heeding presumption is rebuttable and can be rebutted if the plaintiff’s physician was aware of the risks of the drug that he prescribed, and having conducted a risk-benefit analysis, nonetheless determined its use to be warranted. Also. a manufacturer who allegedly fails to warn the medical community of a particular risk may nonetheless be relieved of liability under the learned intermediary doctrine if the prescribing physician either did not read the warning at all, or if the physician was aware of the risk from other sources and already considered the risk in prescribing the product. In that context, the physician’s conduct is the superseding, intervening cause that breaks the chain of liability between the manufacturer and the patient.

Here, the doctor stood by his decision to administer heparin to Mrs. Baker. She required heparin by standard medical procedure, and well documented clinical knowledge, at several different  points during her operation and for several different reasons, he opined.  Since he was aware of the risks of the drug that he prescribed and, having conducted a risk-benefit analysis, nonetheless determined its use to be warranted, the presumption was rebutted as a matter of law.

Moreover, the prescriber testified in his deposition that he does not read the label of drugs he frequently prescribes, which includes heparin. Therefore, a different warning would not have made a difference in plaintiff's treatment or outcome because there was no evidence he would have reviewed it.

Finally, there was a third causation problem; the opinion notes that it was undisputed that, despite doctors orders, the Hospital failed to follow its own heparin treatment protocol. Had that monitoring occurred, Mrs. Baker’s physicians would have discovered the onset of HIT sooner. Plaintiff's own expert admitted that her injuries “would have been substantially mitigated” with a “good chance of avoiding" them.   Therefore, plaintiff failed to raise a genuine issue of material fact that it was the heparin labeling, as opposed to the conduct of the hospital, that caused her injury.

 Summary judgment on the warning claim.

Busy Mass Tort Court Revises Punitive Damages Rule

The Philadelphia Court of Common Pleas, a busy mass tort jurisdiction, to say the least, has continued to tinker with its mass tort general rules, last week issuing General Court Regulation No. 2012-03, amending the protocols for cases in the mass tort program.

The biggest change was to allow punitive damages in some pharmaceutical cases subject to the approval of the Complex Litigation Center coordinating judges, Judge Sandra Mazer Moss and Judge Arnold L. New. The Court said it continues to review recommendations concerning
punitive damages and will likely further amend this rule. But until a final version is established, the following procedure was adopted: Punitive damage claims may be litigated in pharmaceutical mass tort cases provided that the Coordinating Judges, following appropriate motion practice by defense counsel at least 60 days in advance of trial, rule that there are sufficient requisite proofs to support the claim going to trial.

Philadelphia is of course the home base of MassTortDefense, and we have posted on the evolving rules before.  Other than a few outliers, the defense bar had generally supported the continuation of the deferral of punitive damages because this practice furthered the Court’s stated goal of meeting the American Bar Association’s suggested standards for the disposition of cases. Deferral of punitive damages claims in these cases can remove a major obstacle to settlement of mass tort litigation and open the way for the prompt resolution of the damage claims of many thousands of injured plaintiffs. 

Furthermore, when mass tort claims involve pharmaceutical and medical device defendants that market life-saving or life-enhancing products, additional policy considerations support deferral. Drugs and devices are subject to comprehensive regulation by the FDA. Absent extraordinary circumstances, a defendant that has complied with the FDA requirements should not be deemed to have engaged in punishable conduct with the potential for repeat sanctions.

We will keep an eye on this one for you.
 

Defense Victory in Bellwether Drug Trial Affirmed

A state appeals court recently upheld a judgment for defendant in the first bellwether trial in consolidated litigation in New Jersey over claims concerning the cancer drugs Aredia and Zometa. See Bessemer et al. v. Novartis Pharmaceuticals Corp., No. A-2069-10T1 (Sup. Ct. NJ, App. Div.)


Plaintiff allegedly developed osteonecrosis of the jaw (ONJ), and had sued alleging that defendant knew or should have known that Aredia and Zometa could cause ONJ and should have issued warnings to plaintiff and her treating dentists and oral surgeons, as well as to her prescribing oncologist.  The jury returned a verdict in defendant's favor; plaintiff appealed claiming that the pre-trial grant of partial summary judgment to defendant constituted reversible error. The trial judge had decided that defendant had no duty to warn non-prescribing dentists or oral surgeons under the NY Product Liability Act. The trial judge applied the learned intermediary doctrine, rejecting plaintiff's allegation that the so-called DTC exception applied pursuant to Perez v. Wyeth Laboratories Inc., 161 N.J. 1, 14-15 (1999).

The court of appeals affirmed the "well-considered and thorough opinions" of the trial court. The two relevant opinions are: Bessemer v. Novartis Pharmaceuticals Corp., 2010 WL 6052544 (N.J. Super. L.D. Nov. 12, 2010) (denying post trial motion), and Bessemer v. Novartis Pharmaceuticals Corp., 2010 WL 6257855 (N.J. Super. L.D. April 30, 2010) (partial summary judgment).

Thus, the direct-to-consumer advertising exception to the learned intermediary doctrine did not apply to plaintiff; even if the drug was advertised to consumers, and even if plaintiff had seen a magazine advertisement for Zometa while taking the drug, it was not a substantial factor in her use of the medication.  The appeals court ruling also confirms that the defendant did not have a duty to warn dentists and oral surgeons (that is, doctors in a different field) of the drugs' possible risks, in addition to actual prescribing physicians. 

    

Learned Intermediary Adopted in Texas

We cannot comment, but commend to your study the recent decision by the Texas Supreme Court on the applicability of the learned intermediary doctrine under state law. See Centocor Inc. v. Hamilton et al., No. 10-0223 (6/8/12, Texas).

In the context of prescription medication, the learned intermediary doctrine holds that a drug manufacturer satisfies its duty to warn when it informs a prescribing physician about the drug's potential risks. Most but not all jurisdictions have adopted the doctrine. 

Congratulations to my colleagues at Shook, Hardy & Bacon, including Gene Williams. and Manuel Lopez

House Passes FDA Reauthorization Bill

The House of Representatives last week passed a bill (387 to 5 vote) that would reauthorize the Food and Drug Administration's user fee programs and amend the rules regarding marketing exclusivity, medical device safety, drug importation, and other FDA programs. The "FDA Reform Act of 2012," H.R. 5651, reauthorizes and amends various user fee statutes, creates new and additional user fees, reauthorizes the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, changes the rules for public comment on draft guidance documents, and contains new provisions dealing with drug shortages.  The fees are supposed to reflect agreements negotiated between the FDA and industry regarding about $2.8 billion in user fees over five years.

The vote came shortly after the Senate approved its own version of FDA legislation, S. 3187 (the FDA Safety and Innovation Act). The Senate bill was also passed with bipartisan support.

The differences between the House and Senate bills now must be worked out in conference. The bills differ in a variety of ways, such as which antibiotics will be eligible for incentives, which include a five-year extension of market exclusivity. The bills also differ on the details of a national  track-and-trace system for drugs. The Senate bill also included language about Risk Evaluation and Mitigation Strategies (REMS) which is not in the House version. See a comparison of the bills here.  Various observers report that House and Senate leaders expect to have a compromise bill for the President to sign in early July.

 

Court of Appeals Rejects RICO Claim in Drug Case

One of the things we like to do here at MassTortDefense is keep an eye on the non-traditional claims plaintiffs concoct -- to evade the requirements of traditional torts, or to expand the group of "injured" plaintiffs.  Earlier this month the Third Circuit knocked down just such an attempt. See In Re: Schering Plough Corp. Intron/Temodar Consumer Class Action, Nos. 10-3046 and 10-3047 (3d Cir. May 16, 2012).

The issue here was an attempt by two groups of plaintiffs to hold a drug manufacturer liable for violating the federal Racketeer Influenced and Corrupt Organizations Act (RICO) by allegedly marketing drugs for off-label uses. The court of appeals affirmed that neither had standing to maintain this cause of action, primarily for failure to allege a plausible nexus between the assailed marketing campaign and the physicians‘ decisions to prescribe certain drugs for off-label use.

While off-label marketing is prohibited, prescription drugs frequently have therapeutic uses other than their FDA-approved indications. The FDCAct does not regulate the practice of medicine, and so physicians may lawfully prescribe drugs for off-label uses. See Buckman Co. v. Plaintiffs’ Legal Comm., 531 U.S. 341, 350 (2001) (recognizing off-label usage as an accepted and necessary corollary of the FDA‘s mission to regulate in this area without directly interfering with the practice of medicine); Wash. Legal Found. v. Henney, 202 F.3d 331, 333 (D.C. Cir. 2000) (physician may prescribe a legal drug to serve any purpose that he or she deems appropriate, regardless of whether the drug has been approved for that use by the FDA).

Plaintiffs' claims, as is so common, attempted to piggy-back off of prior government investigations. They alleged that Schering‘s marketing practices caused physicians to prescribe the drugs for off-label uses instead of equally effective alternative treatments that were approved for the prescribed uses or no medication at all. They assert that these marketing techniques led to a significant increase in prescriptions of the drugs for off-label uses, and contend that this caused the plaintiffs an "ascertainable loss" (key concept) because they supposedly paid millions of dollars for the drugs that they otherwise would not have paid.

The district court granted a motion to dismiss, and the plaintiffs appealed.

A motion to dismiss for lack of standing implicates Rule 12(b)(1) because standing is a jurisdictional matter, and 12(b)(6) with the Twombly/Iqbal guidance.  While the plausibility standard of those cases does not impose a probability requirement, it does demand more than a sheer possibility that a defendant has acted unlawfully. The plausibility determination is a context-specific task that requires the reviewing court to draw on its judicial experience and common sense; and some claims require more factual explication than others to state a plausible claim for relief.

The Constitution imposes a requirement that there be an actual case or controversy. Federal courts have developed several justiceability doctrines to enforce the case-or-controversy requirement, and perhaps the most important of these doctrines is the requirement that a litigant have standing to invoke the power of a federal court. The standing question is whether the plaintiff has alleged such a personal stake in the outcome of the controversy as to warrant his invocation of federal-court jurisdiction and to justify exercise of the court's remedial powers on his behalf. The plaintiff bears the burden of meeting the irreducible constitutional minimum of Article III standing by establishing three elements: First, the plaintiff must have suffered an injury in fact—an invasion of a legally protected interest which is (a) concrete and particularized and (b) actual or imminent, not conjectural or hypothetical. Second, there must be a causal connection between the injury and the conduct complained of—the injury has to be fairly traceable to the challenged action of the defendant, and not the result of the independent action of some third party not before the court. Third, it must be likely, as opposed to merely speculative, that the injury will be redressed by a favorable decision.

In addition to meeting the constitutional standing requirements, plaintiffs seeking recovery under RICO must satisfy additional standing criterion set forth in section 1964(c) of the statute: that the plaintiff suffered an injury to business or property; and that the plaintiff‘s injury was proximately caused by the defendant‘s violation.

The Union plaintiff on behalf of a proposed class of third-party payors alleged economic loss based on paying for ineffective drugs. Accordingly, to establish standing, it must allege facts showing a causal relationship between the alleged injury—payments for a specific drug that was ineffective or unsafe for the use for which it was prescribed—and Schering‘s alleged wrongful conduct. However, there were no averments that came close to satisfying this standard. It was pure conjecture to conclude that because Schering‘s misconduct supposedly caused other doctors to write prescriptions for ineffective off-label uses for other products, the Union ended up paying for prescriptions for a different drug due to the same kind of alleged misconduct. (Again, attempted piggy-backing on government allegations.)

The court of appeals spent considerable effort reviewing claims of a proposed class of plaintiff consumers, who tried to prove standing by incorporating materials from the government investigation and concocting a series of purported links between drug trials, marketing activities and prescribing doctors' behavior.  The district court rejected this, and plaintiffs' focus on appeal on the pleading standards for each of these claims was secondary to the threshold issue that the consumers did not adequately allege an injury fairly traceable to Schering‘s alleged misconduct. Although the complaint was replete with factual allegations and indeed asserted them with somewhat greater specificity than the third-party payor complaint, they do not present a plausible allegation actually linking the injuries to any type of miscommunication or false claim about the drugs that were actually prescribed.

No standing. Dismissal affirmed. 

Consumer Fraud Class Action Decertified in Drug Case

A state appeals court last week de-certified a class action by consumers over alleged misrepresentations in marketing a drug.  See Merck & Co. v. Ratliff, No. 2011-000234 (Ky. Ct. App.,  2/10/12).

The case involved the drug Vioxx, which was a highly effective medication formerly in widespread use for patients with arthritis and other conditions causing chronic or acute pain.  Plaintiff was a former user of Vioxx for his chronic osteoarthritis.  Although Ratliff’s insurance paid for most of the cost of the drug, which was at the time approximately $66 per month, Ratliff contributed about $5 each month out of pocket.  Ratliff discontinued using Vioxx in early 2004.

Plaintiff brought a putative class action on behalf of product users who had not suffered cardio-vascular side effects, alleging that the defendant deceived the members of the proposed class in violation of the state Consumer Protection Act by promoting and/or allowing the sale of Vioxx with the use of unfair, false, misleading or deceptive acts or practices.  As a result, the class purchased the drug when it wouldn't have otherwise.

The case followed a twisting path, to federal court, to the MDL, back to state court, up to the state supreme court on mandamus, and back.  Long story short, the class was certified by the trial court, and that decision eventually became ripe for review by the court of appeals.

The Kentucky rules are similar to the federal class action rules. The trial court certified the class under the prong (like b3) requiring that the questions of law or fact common to members of the class predominate over any questions affecting only individual members, and that a class action
is superior to other available methods for the fair and efficient adjudication of the controversy. The trial court found that common questions of law and fact did predominate, stating that there was a common nucleus of facts from which the potential plaintiffs’ claims arose. All of the potential
plaintiffs were prescribed Vioxx by doctors who supposedly relied on Merck’s assertions that it was safe and effective.

On appeal, Merck contended that plaintiff’s claims would require individualized proof such that common questions would not predominate. Merck argued that individual proof would be necessary to show that Merck made fraudulent or negligent misrepresentations toward each putative class member or his or her physician through the marketing and sale of Vioxx, that the alleged
misrepresentations were received by each putative member’s physician, that each putative member’s physician relied on such representations in his or her decision to prescribe Vioxx over another drug, and the amount of any damages suffered by each putative member.

The court of appeals noted that the common law misrepresentation claims would require proof of causation in the nature of reliance, and while "there are fewer obstacles to a class claim proceeding under the" state consumer protection act, that law still requires loss as a result of the wrongful act. Plaintiffs alleged that there was supposedly a consistent pattern of deception lasting essentially the entire time that Vioxx was on the market, and thus that generalized proof could be used to show the elements of fraud and misrepresentation in this case. This theory concerning generalized proof regarding Merck’s alleged conduct was similar to the rebuttable presumption of reliance and causation known in securities litigation as "fraud-on-the-market." The court of appeals noted that the “fraud-on-the-market” approach had never been recognized in the state for a fraud or misrepresentation case. Indeed, pretty much every other jurisdiction which has been confronted with the theory has rejected it outside of the securities litigation context. See, e.g., Kaufman v. i-Stat Corp, 754 A.2d 1188, 1191 (N.J. 2000); International Union of Operating Engineers Local No. 68 Welfare Fund v. Merck & Co., Inc, 929 A.2d 1076, 1088 (N.J. 2007); Mirkin v. Wasserman, 858 P.2d 568, 584-95 (CA. 1993); Southeast Laborers Health and Welfare Fund v. Bayer Corp., 2011 WL 5061645 (11th Cir. 2011); Buckman Co. v. Plaintiffs’ Legal Committee, 531 U.S. 341 (2001).

Accordingly, causation, reliance, and damages must be shown on an individual basis. Thus, if the action were tried as a class, even after the alleged common questions of Merck’s representations were decided, the case would essentially fragment into a series of amalgamated “mini-trials” on each of these individualized questions. Because these individualized questions would substantially overtake the litigation, and would override any common questions of law or fact concerning defendant’s alleged conduct, the court found that a class action was not the superior mechanism by which to try these cases. See, e.g., Zinser v. Accufix Research Institute, Inc., 253 F.3d 1180, 1192 (9th Cir. 2001).

 

 

Study Examines Impact of FDA Drug Risk Communications

A recurring topic here at MassTortDefense is the role of hazard communications in product safety, and the related issues of a consumer reading, heeding, or relying on such warnings.  This is particularly true in the area of prescription drug litigation, focused on over at Drug and Device Law.

So, that makes a recent study in Medical Care interesting reading: Dusetzina, et al.,  Impact of FDA Drug Risk Communications on Health Care Utilization and Health Behaviors: A Systematic Review.

The paper reviews the literature of the past 20 years on the impact of FDA drug risk communications on medication utilization, health care services use, and health outcomes.  These 50 or so studies covered roughly 16 therapeutic classes; most used medical or pharmacy claims and a few examined patient-provider communication, decision making, or risk perceptions.

The authors concluded that although some FDA drug risk communications had immediate and strong impacts, many had either delayed or no impact on health care utilization or health behaviors. These data demonstrate the complexity of using risk communication to improve the quality and safety of prescription drug use, and suggest the importance of continued assessments of the effect of future advisories and label changes, according to the authors.

Although not the focus of the article, the findings are relevant to those of us who need to think about the learned intermediary doctrine, preemption, and other legal warning doctrines.

Dismissal of Actimmune Proposed Class Action Affirmed

The Ninth Circuit late last month upheld the dismissal of a proposed class action concerning alleged off-label marketing of the drug Actimmune.  In re: Actimmune Marketing Litigation, Nos. 10-17237 and 10-17239 (9th Cir. 12/30/11).

The panel, in an unpublished opinion, affirmed the judgment of the district court “for the reasons set forth in the district court's orders.”  See In re Actimmune Marketing Litig., 614 F.Supp.2d 1037
(N.D. Cal. 2009) (Actimmune I); In re Actimmune Marketing Litig., 2009 WL 3740648 (N.D. Cal. Nov. 6, 2009)(Actimmune II ); In re Actimmune Marketing Litig., 2010 WL 3463491 (N.D. Cal. Sept. 1, 2010) (Actimmune III).

In September 2010, the trial court had issued a ruling dismissing the amended complaints filed by consumers and an insurer, who alleged that defendants had improperly marketed Actimmune as a treatment for idiopathic pulmonary fibrosis.  Despite the additional allegations included in plaintiffs' latest amended pleadings, plaintiffs still failed to properly allege that defendants' conduct caused plaintiffs' injuries. Therefore, plaintiffs lacked standing to pursue their off-label marketing claims under the asserted consumer fraud claims.  Establishing that a defendant violated a law only accomplishes part of a plaintiff's burden; plaintiffs were also required to prove that they were injured “as a result of” defendants' alleged law-violating conduct.

In the context of the instant case, the “as a result of” language placed the burden on plaintiffs to establish that they actually relied upon the representations delivered through defendants' off-label marketing. Plaintiffs failed to allege a plausible causal chain of injury as required by Iqbal/Twombly.

The shortcoming in the consumer plaintiffs' pleadings was simple: all of the consumer plaintiffs failed to allege that their doctors believed that Actimmune was an effective treatment for IPF “as a result of” defendants' off-label promotion of Actimmune. With respect to each plaintiff, the complaint alleged only that their doctors were “exposed to at least some of InterMune's unfair and unlawful off-label marketing.”  That was not enough;  claims dismissed.

Strict Liability Does Not Apply to Medical Devices

Another court has recognized that strict liability or breach of implied warranty claims do not lie against medical device makers. Horsmon v. Zimmer Holdings Inc., No. 11-1050 (W.D. Pa., 11/10/11).

Plaintiff had a total hip replacement whereby her right hip joint was replaced with implant components designed, manufactured, and sold by defendants. Ms. Horsmon alleeged she later began to experience pain in her right hip, which eventually required further surgery. She alleged this was due to a defect in the original liner that was used during the hip replacement.  She sued, and defendants moved to dismiss.

Defendants asserted that plaintiff‟s claim for strict liability was barred by Pennsylvania law. The Supreme Court of Pennsylvania in Hahn v. Richter, 673 A.2d 888 (Pa. 1996), held that strict liability claims cannot be brought against prescription drug manufacturers. The court relied on Comment k to the Restatement (Second) of Torts § 402A, regarding unavoidably unsafe products. The Superior Court of Pennsylvania and several United States District Courts applying Pennsylvania law have extended Hahn to bar strict liability claims against medical device manufacturers. E.g., Creazzo v. Medtronic, Inc., 903 A.2d 24, 31 (Pa. Super. Ct. 2006).  This court agreed that the reasoning of Hahn extends to medical devices.

Defendants further asserted that plaintiff's breach of implied warranties claim was also barred by Pennsylvania law. In a claim for breach of implied warranty of merchantability, the essence of the warranty of merchantability is that the item sold is fit for the ordinary purposes for which such goods are used. Under Pennsylvania law, the very nature of prescription drugs precludes the imposition of a warranty of fitness for ordinary purposes, as each individual for whom they are prescribed is a unique organism who must be examined by a physician who is aware of the nature of the patient's condition as well as the medical history of the patient. Breach of implied warranty of merchantability claims, therefore, are precluded for prescription drugs. Again, several courts have extended this reasoning to preclude claims against medical device manufacturers for breach of implied warranties of merchantability and fitness for a particular purpose.  And the district court here agreed; there was no compelling reason to distinguish between prescription drugs and medical devices.

The court then turned to the express warranty claim. Under Pennsylvania law, any affirmation of fact or promise made by the seller to the buyer which relates to the goods and becomes part of the basis of the bargain creates an express warranty that the goods shall conform to the affirmation or promise.  Here, plaintiff alleged that defendants expressly warranted in written literature, advertisements and representations of representatives and agents that the systems, bone screws, liners and other related components were safe, effective, fit, and proper for the use for which they were intended. But plaintiff did not allege any particular affirmation of fact or promise, as required under federal pleading rules, that would give rise to a reasonable inference that defendants expressly warranted that its products were safe, effective, fit, and proper for the use for which they were intended. Plaintiff failed to allege that any particular affirmation of fact or promise was made in any of those sources.  Plaintiff's allegations also did not support a reasonable inference that any affirmation of fact or promise by defendants became part of the basis of the bargain in plaintiff's purchase. (Of course, plaintiff could not allege that any particular affirmation of fact or promise became “part of the basis of the bargain” without alleging any particular affirmation of fact or promise.)  Thus, plaintiff failed to state a plausible claim for breach of express warranties under Pennsylvania law. (However, the court gave Horsmon another chance to amend and replead her breach of express warranty claim.)

 

Defect Allegations Insufficient in Drug Case

We may be accustomed to talking about whether a product was "defective" and, as counsel for defendant sellers, working hard to show that the product contained no "defect."  Earlier this month came a decision reminding us that, in some contexts, a defect, even one that caused the injury, may not be all plaintiffs need to allege and prove. Mills v. Bristol-Myers Squibb Co., No. 11-00968 (D. Ariz., 10/7/11).

Plaintiff was prescribed Clopidogrel (branded as "Plavix") for the treatment of peripheral vascular disease.  Two years later, plaintiff initiated this action alleging that the drug caused excessive rectal bleeding. The court dismissed, and plaintiff eventually sought leave to file a Second Amended Complaint. Defendants argued that leave to amend should be denied as futile.  And the court agreed.

The interesting part of the opinion for our readers is the discussion of strict products  liability, premised on two theories: design defect and failure to warn. (Plaintiff also premised her negligence claim on these theories.)  For plaintiff to prevail under both theories she had to show that the product left the defendants' hands in a defective condition, the defect rendered the product unreasonably dangerous, and the defect was a proximate cause of plaintiff's injuries. Sw Pet Prods., Inc. v. Koch Indus., Inc., 273 F. Supp. 2d. 1041, 1051 (D. Ariz. 2003).

Plaintiff alleged that Plavix was allegedly defective when ingested along with aspirin by people who have peripheral vascular disease, and that the defect caused her injury.  So there you have it.   But wait... simply pleading a defect is not enough. To prevail on a design defect claim in Arizona, a plaintiff must also show that the defective product is unreasonably dangerous.  Although plaintiff's design defect claim was apparently pled pursuant to the Restatement (Second) of Torts § 402(a), the federal court concluded that Arizona would now use the Restatement (Third) of Torts, particularly its definition of an unreasonably safe prescription drug or medical device in a design defect claim.  Section 6(c) of the Third Restatement, noted the court, declares that a prescription drug or medical device is unreasonably unsafe due to defective design only if the foreseeable risks of harm posed by the drug or medical device are sufficiently great in relation to its foreseeable therapeutic benefits that reasonable health-care providers, knowing of such foreseeable risks and therapeutic benefits, would not prescribe the drug or medical device for any class of patients.

Here, although plaintiff alleged that no reasonable health-care provider would prescribe Plavix
for plaintiff knowing of the alleged risks to Caucasian patients who genetically are poor metabolizers of Plavix, and who are diagnosed with peripheral vascular disease and concomitantly ingest aspirin, nowhere did the plaintiff allege that Plavix would not be prescribed for any class of patients. (We leave for a later post the interesting and scary theory that the drug was defective because it had greater adverse effects among a narrow group with a genetic pre-disposition.)

And arguably even under a traditional risk/benefit analysis used to determine whether a product is unreasonably dangerous based on the Restatement (Second) of Torts, plaintiff's pleading did not state a plausible claim.  Although detailed factual allegations are not necessary in pleadings, "labels and conclusions" are insufficient. Bell Atlantic Corp v. Twombly, 550 U.S. 544, 555 (2007).  And that's what she offered on risk benefit elements.

As to the warning claim, plaintiff needed to allege, then show, that had a proper warning been given, the injury would not have happened. See Gosewisch v. Am. Honda Motor Co., Inc., 153 Ariz. 400, 403, 737 P.2d 376, 379 (1987) (superseded by statute on other grounds).  Here, plaintiff averred only on information and belief that her doctor would not have prescribed Plavix had he known of its true risks for patients like plaintiff.   But the court noted that plaintiff could simply have contacted her physician to determine the facts, which were not solely in the control of defendants. She did not do so, and her allegations thus fell short. This may be an important use of the clarified pleading standard, particularly in those jurisdictions in which defendants are precluded from informally contacting the plaintiff’s prescriber.  


 

FDA Releases New Strategic Plan for Regulatory Science

This week the FDA released a plan for fostering innovative science. It is entitled the “Strategic Plan for Regulatory Science,” and it focuses on the agency’s goal to enhance the processes for developing and evaluating new medical products and materials.

The strategic plan describes the agency’s intent to collaboratively enhance the process for developing and evaluating promising new products and novel materials from fields such as cell therapy, tissue engineering, genomics, personalized medicine, advanced computing, and information technology. It reportedly also underscores the agency’s emphasis on food safety.

The plan also emphasizes the agency’s intention to study and improve how it communicates health information to consumers, particularly as communication technologies rapidly evolve and change the way people receive that information.

The priority areas listed in the report are:

  • Modernize Toxicology to Enhance Product Safety
  • Stimulate Innovation in Clinical Evaluations and Personalized Medicine to Improve Product Development and Patient Outcomes
  • Support New Approaches to Improve Product Manufacturing and Quality
  • Ensure FDA Readiness to Evaluate Innovative Emerging Technologies
  • Harness Diverse Data through Information Sciences to Improve Health Outcomes
  • Implement a New Prevention-Focused Food Safety System to Protect Public Health
  • Facilitate Development of Medical Countermeasures to Protect Against Threats to U.S. and Global Health and Security
  • Strengthen Social and Behavioral Science to Help Consumers and Professionals Make Informed Decisions about Regulated Products
     

 

Yaz Court in NJ Issues Bellwether Trial CMO

The court overseeing the coordinated litigation in New Jersey state court over the birth control pills Yaz, Yasmin, and Ocella recently issued a case management order.  See CMO No. 25 - Bellwether Trial Selection Plan.

Here at MassTortDefense we are always interested in the nuts and bolts of how mass tort litigation is managed, and have posted about bellwether trials before. The NJ court order calls for creation of a pool of 18 cases from which the first trials will come. Nine will be selected by plaintiffs and nine by defendant. Of the nine on each side, 3 must allege each of the three main alleged injuries in this litigation.

Case specific discovery for the cases in the pool will begin in August, 2011, and must be completed in November, 2011. The order establishes a schedule for expert discovery and challenges to experts.

The bellwether trials will be selected from the group of 18.  If the parties cannot agree on a sequence, the Court will decide. The first trial is set for September, 2012.

There are about 1,000 cases pending in the New Jersey proceedings. The Court stated it had not yet decided whether there will be individual trials or consolidations. See In re Yaz, Yasmin, and Ocella Litigation, N.J. Super. Ct., No. 287 (7/8/11). 
 

FDA Releases Draft Guidance on Nanotechnology

The U.S. Food and Drug Administration last week released draft guidance designed to move the process forward of providing its regulated industries with greater certainty about the use of nanotechnology (which generally involves materials made up of particles that are one billionth of a meter in size). The guidance outlines the agency’s current view on certain issues about regulated products that contain nanomaterials or involve the application of nanotechnology.

FDA has not to date established regulatory definitions of “nanotechnology,” “nanoscale” or related terms. The term is perhaps most commonly used to refer to the engineering (i.e., deliberate manipulation, manufacture or selection) of materials that have at least one dimension in the size range of approximately 1 to 100 nanometers. For example, theNational Nanotechnology Initiative Program defines nanotechnology as the understanding and control of matter at dimensions between approximately 1 and 100 nanometers, where unique phenomena enable novel applications. Other factors such as function, shape, charge, the ratio of surface area to volume, or other physical or chemical properties have also been mentioned in various published definitions.

Our readers know that nanotechnology, the science involving manipulation of materials on an atomic or molecular scale, is an emerging technology with a broad range of potential applications, such as increasing bio-availability of a drug, improving food packaging, and in cosmetics.

The draft guidance document, “Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology,” represents a first step toward providing some regulatory clarity on the FDA’s approach to nanotechnology. Specifically, the agency named certain characteristics – such as the size of nanomaterials used and the exhibited properties of those materials – that may be considered when attempting to identify applications of nanotechnology in regulated products.

For products subject to premarket review, the FDA intends to apply the points contained in the draft guidance, when finalized, to better understand the properties and behavior of engineered nanomaterials. For products not subject to premarket review, the FDA will urge manufacturers to consult with the agency early in the product development process so questions related to the regulatory status, safety, effectiveness, or public health impact of these products can be adequately addressed.

In 2006, the FDA formed the Nanotechnology Task Force, charged with identifying and addressing ways to better enable the agency to evaluate possible adverse health effects from FDA-regulated nanotechnology products.  The agency issued a report by the task force in 2007 that recommended that the FDA issue additional guidance and take steps to address the potential risks and benefits of drugs, medical devices and other FDA-regulated products using nanotechnology.

 

Supreme Court Declines to Clarify Tolling Effect of Mass Tort Class Actions

Earlier this week, the Supreme Court declined to take a case raising the tricky issues of cross-jurisdictional class action tolling.  Novartis Pharmaceuticals Corp. v. Stevens, No. 10-1196 (U.S., certiorari denied 5/31/11).

The question presented in the cert petition was whether was whether tolling the statute  of limitations for individual claimants based on the pendency of a mass personal injury class action violates fundamental federal due process protections where the class action provides no notice to a defendant of the identity of unnamed class members, thus absolutely precluding the timely preservation of evidence and testimony critical to presenting an effective defense.

Defendant/petitioner has been involved for several years in litigation claiming that the drug Zometa is linked to osteonecrosis of the jaw or “ONJ.”  Plaintiff below obtained a jury verdict on such a claim, affirmed by the Montana Supreme Court . 358 Mont. 474, 247 P.3d 244 (2010). The sole aspect of the Montana Supreme Court’s opinion at issue here was its ruling that the pendency of a never-certified federal class action on ONJ acts to resurrect respondent’s otherwise time-barred personal injury claims. The Montana Supreme Court determined as a matter of first impression in Montana that federal class action tolling should apply to render timely respondent’s complaint against petitioner. The Montana court noted that the concept of federal class action tolling was articulated by the Supreme Court in American Pipe & Construction Co. v. Utah, 414 U.S. 538 (1974). In American Pipe, the Court held that in some contexts, the commencement of the class action suit satisfied the purpose of the limitation provision as to all those who might subsequently participate in the suit as well as for the named plaintiffs. One reason was concerns of judicial economy, as a contrary holding might invite a multiplicity of activity that the federal rules of procedure were designed to avoid, as individual plaintiffs would be forced to file preventative motions to join or intervene as parties if the class action status was still pending at the expiration of the statute of limitations.

The problem is that in the specific context of a personal injury mass tort, the application of American Pipe federal class action tolling seems to infringe on a defendant’s ability to defend itself -- in violation of due process principles. Suspending statutes of limitation indefinitely for all purported members of the kinds of  “worldwide” classes we see of personal injury plaintiffs, based on nothing more than the filing a Rule 23 federal class action, introduces systemic unfairness to defendants. 

A  pharmaceutical personal injury case may be an especially poor vehicle for federal class action tolling. Virtually no pharmaceutical personal injury class action has been certified over opposition and survived appeal in the federal system for a decade now. See, e.g., Jolly v. Eli Lilly & Co., 751 P.2d 923, 933-38 (Cal. 1988) (en banc) (rejecting tolling due to pending personal injury class action because such torts are not susceptible to class action certification). Tolling individual  actions based on a pending personal injury class action renders limitations periods impermissibly uncertain and invites unnecessary litigation by giving plaintiffs’ counsel everywhere an incentive to add putative class relief to every federal complaint just to toll statutes of limitations to the benefit of unknown future plaintiffs -- knowing there will never be a certified class.  Some lower courts have thus concluded that class action tolling should not be applied in the mass tort context unless the defendant had actual notice of the identities of unnamed class members.

Petitioner argued that tolling the limitations period for all purported members of the class during the pendency of class certification proceedings – which in a mass class action can take years – creates an unacceptable risk that by the time the claims of unnamed individuals are adjudicated, evidence critical to defending claims of that individual plaintiff will have been lost.  Issues relating to exposures, learned intermediaries, concurrent risk factors, specific (as opposed to general) causation, proximate causation regarding warnings, and assumption of the risk, all involve evidence that can be both peculiar to the individual plaintiff, and turn out to be the central evidence in the action.

Perhaps because of unique procedural issues below (involving fictitious parties), however, the Court passed on the opportunity to address these serious issues.


 

State High Court Issues Consumer Fraud Act Decision

One of the dangers for defendants of claims based on state consumer fraud acts is the reluctance of some state courts to recognize the reliance and causation elements inherent in most such statutes.  The absence of a reliance element allows plaintiffs to argue that such claims are more amenable to class treatment, removing a significant individual element.  West Virginia's high court recently confirmed, however, that plaintiffs alleging affirmative misrepresentation claims under West Virginia's consumer protection law must show actual reliance on the allegedly misleading statement. White v. Wyeth, No. 35296 (W. Va., 12/17/10).
 

The underlying consumer fraud suit was filed pursuant to the WV Consumer Protection Act by purchasers of prescription hormone replacement therapy (“HRT”) drugs.  Plaintiffs alleged that the defendants used unfair and deceptive practices in promoting HRT prescription drug products to doctors and patients for treatment of serious menopausal disorders by allegedly using misleading statements in advertising, marketing and labeling.  Following completion of class certification discovery, defendant Wyeth filed alternative motions for dismissal or summary judgment, arguing that plaintiffs could not establish that they had standing to sue because they failed to meet their burden of showing a causal connection between their individual claims of injury and any alleged unfair or deceptive conduct attributed to Wyeth.

Defendant Wyeth particularly noted the lack of evidence demonstrating that plaintiffs decided to purchase HRT drugs because of anything they learned from Wyeth, or that their treating physicians considered information from Wyeth when they issued the prescriptions for HRT drugs. Plaintiffs responded that the statutory language only requires that they prove causation by alleging that Wyeth engaged in deceptive practices and that Respondents were harmed. They maintained that reliance on deceptive statements or practices need not be demonstrated.  In essence, plaintiffs read out of the WVCCPA the requirement that they “suffered ascertainable loss”  as a "result of” various unfair and deceptive acts of Wyeth. W. Va. Code § 46A-6-106(a).  Wyeth argued that the “as a result of” language contained in the statute requires plaintiffs to allege that they relied, or their doctors relied, on Wyeth’s allegedly deceptive actions when they made the decision to purchase hormone replacement therapy -- the phrase “as of result of” has to be read to mean that a plaintiff relied on the improper act or practice alleged in order to satisfy standing requirements.  Plaintiffs, in turn, argued that if the plaintiffs received drugs that were different from or inferior to that which they were entitled to receive, they did not receive the benefit of their bargain, and they therefore suffered an ascertainable loss.

The court noted that the private cause of action provisions of twenty-eight states' consumer fraud acts contain the “as a result of” language.  Many of the decisions addressing the issue of reliance in the context of private consumer protection causes of action show courts struggling to arrive at a way to be faithful to the purposes of consumer protection statutes – promoting fair and honest business practices and protecting consumers – without inviting nuisance lawsuits which impede commerce. In determining the meaning of the phrase “as a result of” in the WVCCPA, the court agreed with those decisions requiring proof of a causal nexus between the deceptive conduct giving rise to the private cause of action and the ascertainable loss, and the conclusion that this may require proof of reliance in some but not all instances.  The court found that reliance and causation are twin concepts, "often intertwined, but not identical."

Following this reasoning, when consumers allege that a purchase was made because of an express or affirmative misrepresentation, the causal connection between the deceptive conduct and the loss would necessarily include proof of reliance on those overt representations. Where concealment or omission is alleged, and proving reliance is an impossibility, the causal connection between the deceptive act and the ascertainable loss is established by presentation of facts showing that the deceptive conduct was the proximate cause of the loss. In other words, the facts have to establish that “but for” the deceptive conduct or practice a reasonable consumer would not have purchased the product and incurred the ascertainable loss. 

The court determined that this approach best serves the WVCCPA’s dual purpose of protecting the consumer while promoting “fair and honest competition.” W. Va. Code § 46A-6-101. Thus, a private cause of action under the provisions of West Virginia Code § 46A-6-106(a) of the West Virginia Consumer Credit and Protection Act must allege: (1) unlawful conduct by a seller; (2) an ascertainable loss on the part of the consumer; and (3) proof of a causal connection between the alleged unlawful conduct and the consumer’s ascertainable loss. Where the deceptive conduct or practice alleged involves affirmative misrepresentations, reliance on such misrepresentations must be proven in order to satisfy the requisite causal connection

The court went on to address an important second issue, finding that prescription drug cases are not the type of private causes of action contemplated under the terms and purposes of the WVCCPA.  The consumer cannot and does not decide what product to purchase. The intervention by a physician in the decision-making process necessitated by his or her exercise of judgment whether or not to prescribe a particular medication protects consumers in ways respecting efficacy that are lacking in advertising campaigns for other products. Accordingly, the court found that the private cause of action afforded consumers under West Virginia Code § 46A-6-106(a) does not extend to prescription drug purchases. See also New Jersey Citizen Action v. Schering-Plough Corp., 842 A.2d 174 (N.J. Super. 2003). , in which a New Jersey appeals court emphasized the difference between the pharmaceutical industry and other companies. According to the West Virginia court, the New Jersey court noted that physician intervention in prescribing decisions protects consumers and observed that the high degree of federal regulation of prescription drug products “attenuates the effect product marketing has on a consumer's prescriptive drug purchasing decision.”
The court remanded for dismissal.
 

Proof of General Causation in Drug Case Not Automatic

A West Virginia federal court has granted summary judgment against a plaintiff alleging that the heartburn drug metoclopramide caused her tardive dyskinesia.  Meade v. Parsley, et al., 2010 WL 4909435 (S.D.W.Va.,  11/24/10).

Since its approval by the Food and Drug Administration in 1980, metoclopramide has been widely used to treat gastroesophageal reflux disease (“GRD”), nausea, and gastroparesis.  Plaintiff's treater, Dr. Deidre Parsley, prescribed metoclopramide to Mrs. Meade in order to treat her
GRD, nausea, and loss of appetite. Plaintiff  never read any written materials accompanying her metoclopramide prescriptions, which included a statement that therapy longer than 12 weeks has not been evaluated and cannot be recommended.  Dr. Parsley likewise did not read the metoclopramide package insert or any other written materials produced by PLIVA before prescribing the drug to Mrs. Meade. After the drug usage, the FDA added a black box warning about tardive dyskinesia.  But, save for the placement of the warning in a black box, the previous warning seemed not too different.

Plaintiffs contended that the warnings were inadequate in that they misleadingly invited long term use that has never been approved by the FDA, despite the fact that the warning did state that therapy longer than 12 weeks has not been evaluated and cannot be recommended. In addition,
plaintiffs claim that the warnings downplayed the seriousness and potential irreversibility of the risk of tardive dyskinesia in long term use, but the warning did state that the risk is highest among the elderly, especially elderly women (like this plaintiff), and that the likelihood of irreversibility is believed to increase with the duration of treatment and the total cumulative dose. 

Defendant moved for summary judgment, contending that there were no genuine issues of material fact inasmuch as (1) plaintiffs could not establish causation; (2) Dr. Parsley was aware of the risks of using metoclopramide when she prescribed the drug to Mrs. Meade; (3) PLIVA satisfied any alleged duty to warn by providing a package insert explaining potential side effects of
metoclopramide.  The court never had to reach the third argument.

In a pharmaceutical products liability action, a plaintiff must initially establish both general and specific causation for his injuries. Bourne ex rel. Bourne v. E.I. Dupont de Nemours & Co., 189 F. Supp. 2d 482, 485 (S.D. W. Va. 2002).  General causation is whether a substance is capable of causing a particular injury or condition in the general population, while specific causation is whether a substance caused a particular individual's injury. In re Rezulin Prods. Liab. Litig., 369 F.
Supp. 2d 398, 402 (S.D.N.Y. 2005); In re Hanford Nuclear Reservation Litig., 292 F.3d 1124, 1129 (9th Cir. 2002). General causation is established by demonstrating, often through a review of scientific and medical literature, that exposure to a substance can cause a particular disease.

In addition to general and specific causation, plaintiffs must establish proximate causation.To
show proximate causation in a failure-to-warn case based on an allegedly inadequate drug label, a plaintiff must show that a different label or warning would have avoided the plaintiff’s injuries. The court noted that the West Virginia Supreme Court has not had occasion to clarify whether a drug manufacturer must warn both the patient and the physician, or just the patient.  But it did not need to resolve this issue in evaluating proximate causation, however, because the undisputed evidence shows that an adequate warning would not have changed either Mrs. Meade’s or Dr. Parsley’s behavior in a manner which would have avoided Mrs. Meade’s injury.  Rather than merely showing that “adequate warnings would have changed behavior,”  as plaintiff argued, plaintiffs must
establish that an adequate warning would have changed behavior in a manner which would have avoided the plaintiff’s injury.  Mrs. Meade testified that she never read the package insert or any other documents accompanying her metoclopramide prescription.  Dr. Parsley likewise testified that she did not read the metoclopramide warning. And while Dr. Parsley did read the PDR for
the brand name version of the drug, it is undisputed that the defendant did not create that PDR.

The more interesting part of the opinion for our readers is the treatment of the issue of general causation.  It seems that none of plaintiffs’ retained experts offered any opinions regarding general
causation. So plaintiffs were left to argue that several of Mrs. Meade’s treating physicians (whom plaintiffs began referring to as “non-retained experts”) testified regarding the causal link between metoclopramide and tardive dyskinesia. None of these non-retained experts provided written
reports, and in deposition none of these physicians testified directly as to general causation. They assumed causation as a prelude to a specific causation opinion, but this mere assumption does not establish general causation. The law is clear that a mere possibility of causation and, more
specifically, indeterminate expert testimony on causation that is based solely on possibility is not sufficient to allow a reasonable juror to find causation. 

As an alternative basis for general causation, plaintiffs tried to rely on the fact that defendant's own package inserts and brand name warnings refer to a "causal link” between metoclopramide and tardive dyskinesia. Plaintiffs could cite no authority for the proposition that a plaintiff in a pharmaceutical products liability case can satisfy his or her burden of proving general causation by relying on the defendant manufacturer’s drug label warnings. Moreover, this contention was undermined by the general principle that causation evidence in toxic tort cases must be in the form of expert scientific testimony.  PLIVA’s drug label, which merely warns of metoclopramide’s potential side-effects without explaining the scientific basis for the warning, was no substitute for expert testimony that establishes causation in terms of reasonable probability.

Third, plaintiffs also tried to cite, as evidence of general causation, the subsequent FDA directive requiring drug manufacturers to insert a black box warning on metoclopramide labels to convey a
greater risk of tardive dyskinesia. The court, as have several other courts have, however, rejected reliance on agency determinations as a basis for general causation. Inasmuch as the cost-benefit balancing employed by the FDA differs from the threshold standard for establishing causation in tort actions, this court likewise concluded that the FDA-mandated tardive dyskinesia warning cannot establish general causation.

 Summary judgment granted.

Lone Pine Order Adopted in Avandia MDL

In the right case, we are big fans of the "Lone Pine" order as a tool of case management.  Named for Lore v. Lone Pine Corp., No. L-33606-85, 1986 WL 637507 (N.J.Super. Ct. Law Div. Nov. 18, 1986), Lone Pine orders are designed to handle the complex issues and potential burdens on the parties and the court in mass tort and toxic tort litigation. Acuna v. Brown & Root Inc., 200 F.3d 335, 340 (5th Cir.2000).   The term refers to case management orders that require the plaintiffs to make a showing regarding causation, injury, and/or damages to demonstrate, typically at an early stage, some minimal level of evidentiary support for the key components of their claims which will be in dispute.

While the 1986 New Jersey Superior Court case involved traditional toxic tort claims, the device has gotten good use in drug cases as well.  E.g., In re Vioxx Products Liab. Litig., 2010 WL 2802352 (5th Cir. July 16, 2010). After a tentative settlement was reached in the Vioxx litigation, the MDL court entered several pre-trial orders with respect to the claims of those plaintiffs who could not or chose not to participate in the Master Settlement Agreement.  The order required non-settling plaintiffs to notify their health-care providers that they must preserve evidence pertaining to the plaintiffs' use of Vioxx. Plaintiffs were also required to produce pharmacy records and medical authorizations, answers to interrogatories, and a Rule 26(a)(2) report from a medical expert attesting that the plaintiff sustained an injury caused by Vioxx and that the injury occurred within a specified time period. Failure to comply eventually resulted in dismissal of several of the plaintiffs' claims with prejudice.

And the federal judge overseeing the MDL for Celebrex and Bextra found that a “Lone Pine” order was appropriate for managing the claims of the remaining, non-settling plaintiffs. In re: Bextra and Celebrex Marketing Sales Practices and Product Liability Litigation, No. M:05-cv-01699 (N.D. Cal.) (Pretrial Order No. 29, Aug. 1, 2008).

In the drug context, a Lone Pine order might require plaintiffs to submit a case-specific expert report on the issue of medical causation; or to turn over medical records that documented an injury, prescription records that showed medication history and dosages prescribed, and/or proof of dosage in relation to the injury. The benefit to the court of requiring plaintiffs to supply this information is that the parties will not have to engage in protracted discovery in hundreds or thousands of cases just to see whether each one has some threshold evidence of medical causation. The production of such basic and threshold evidence is simply a part of a good-faith investigation that should precede the filing of a lawsuit.

Requiring plaintiffs to identify basic information about injuries and causation is not unreasonable given the costs that mass tort claims have on the legal system, and on defendants in particular. Lone Pine orders allow courts to weed out the frivolous suits where there is insufficient exposure, or no sufficient scientific connection between injury and exposure. Accordingly, Lone Pine orders can be effective when entered early in the game. Early disposal of frivolous claims allows the parties to focus their attention on the serious cases. Ideally, the order will actually phase discovery, and motions practice as well, with the Lone Pine issues pushed up front.

But the device also has a role later in mature mass torts when, as seen above, a chunk of the litigation has settled and there still remain numerous claims of questionable strength.

In the MDL involving the the diabetes medication Avandia, In re Avandia Marketing, Sales Practices, and Products Liab. Litig., MDL No. 1871 (Pretrial Order No. 121)(E.D. Pa. Nov. 15, 2010), the federal court has recently adopted a Lone Pine order.  The court found that many of the remaining claims lacked sufficient support or detail even after submission of the Plaintiff Fact Sheets.  Thus, additional detail about the plaintiffs' claims was necessary in furtherance of settlement agreements, for the selection of cases for bellwether trials, and for the timely remand of cases to the transferor courts for resolution.

The court's overriding concern was having sufficient information to objectively identify which of the many thousands of remaining plaintiffs have injuries that could credibly be linked to the drug usage.  The order calls for information that the court said the plaintiffs should have had before filing their claims.

Specifically, plaintiffs have to have a licensed physician identify the plaintiff's Avandia usage, the alleged injury, the time lag between drug usage and injury, and a certification that the drug usage caused the injury.

Failure of a plaintiff to submit these required expert certification (and supporting documents) in a timely fashion may result in the dismissal of that plaintiff's claims with prejudice.

A defendant in such litigation should not bear the burden of winnowing cases that never should have been filed, nor should the court be saddled with consideration of claims that would not have survived reasonable pre-complaint investigation.

 

Democrats Release Discussion Draft of FDA Bill

Five Democratic Congressmen released a discussion draft of possible legislation that would alter the powers of the U.S. Food and Drug Administration.  The bill would increase FDA's authority and funding to regulate the importation of foreign-manufactured drugs, and also give the FDA the authority to mandate recalls for unsafe drugs.

Rep. John D. Dingell, Chairman Emeritus of the Energy and Commerce Committee, Rep. Henry A. Waxman, Chairman of the Energy and Commerce Committee, Rep. Frank Pallone, Chairman of the Subcommittee on Health, and Rep. Bart Stupak, Chairman of the Subcommittee on Oversight and Investigations, released a discussion draft proposal, which builds on H.R. 759, the Food and Drug Globalization Act, which was introduced by Dingell, Pallone and Stupak last year.

The discussion draft calls for "parity" between foreign and domestic drug facility inspections, would increase the number of pre-approval drug inspections, and would prohibit the importation of drugs into the United States lacking appropriate documentation of safety.  The legislation would also require manufacturers to take steps to ensure the safety of their supply chain.

The sponsors noted that the byproduct of Internet communications and a rapidly-evolving international marketplace is an increase in the purchase of medications from foreign sources. Cong. Pallone claimed that, “One of the downsides is quality control and one of the dangers is the threat to the health and safety of consumers. We need to find the best ways to vest the FDA with the ability and the authority to ensure the safety of medications consumed by Americans.”

Cong. Waxman said he would work with the FDA "and all stakeholders to move this legislation forward as soon as possible." But the current Congress is heading home for the November elections, and the measure's fate is unclear if Republicans take control of the House next year.

Federal Appeals Court Vacates Third Party Payor Class Certification

A federal appeals court last week reversed an order by a district court certifying a class action of insurers, labor unions, and pension funds who alleged that they overpaid for a drug when the manufacturer allegedly didn't reveal all of the drug's adverse side effects. UFCW Local 1776, et al. v. Eli Lilly & Co., No. 09-0222 (2d Cir. 9/10/10).

Plaintiffs acted as third-party payors (TPP) who underwrite the purchase of prescription drugs by their members or insureds; they brought a putative class action against Eli Lilly, manufacturer of the drug Zyprexa, alleging that Lilly had misrepresented Zyprexa’s efficacy and side effects to physicians. The putative class alleged they paid for the many Zyprexa prescriptions. Plaintiffs argued that they were injured in two ways: first, by paying for Zyprexa prescriptions that would not have been issued but for the alleged misrepresentations; and second, by paying a higher price for Zyprexa than would have been charged, absent the alleged misrepresentations.

In a nearly 300-page opinion issued in  2008, Judge Jack Weinstein of the Eastern District of New York granted class certification to the third-party payors. Specifically, the district court certified a class of TPPs on RICO claims predicated on the overpricing theory of damages, but refused to certify a class related to state consumer protection law claims. The lower court concluded that the proposed TPP class presented common questions of law and fact because the “only difference among class third-party payors is how much of the total overcharge each shall receive in damages.” The lower court  had  addressed whether the losses suffered by the class could be established with sufficient precision, a huge issue in these kinds of cases, concluding that damages could be estimated based on the difference between what was paid for Zyprexa and the actual value of the product. The computation would supposedly require: (i) estimating the total out-of-pocket expenditures for the class members and (ii) using "well-accepted  techniques" in applied economics to determine the actual value or appropriate launch price of Zyprexa.

The district court also found that reliance could be proven for the class simply because the alleged fraud was “directed through mailings and otherwise at doctors who relied, causing damages in overpayments by plaintiffs.” This reliance, the district court concluded, could appropriately be shown by generalized proof, but without resort to the “fraud on the market” theory rejected in cases like McLaughlin v. Am. Tobacco Co., 522 F.3d 215 (2d Cir. 2008).

Defendant appealed.  The Second Circuit noted that to determine whether the proposed TPP class was properly certified, it had to consider whether substantial elements of the claim against Lilly may be established by generalized, rather than individualized, proof.  (Predominance of common or individual issues under Rule 23(b) was the focus.)  Even if the issue whether an act of marketing of the drug was in violation of RICO is considered common, Lilly disputed that the other elements required to recover damages – proof of an injury and proof that such injury was by reason of the RICO violation – were common to the proposed class.  To show injury by reason of a RICO violation, a plaintiff must demonstrate that the violation caused his injury in two senses. First, he must show that the RICO violation was the proximate cause of his injury, meaning there was a direct relationship between the plaintiff’s injury and the defendant’s injurious conduct. Second, he must show that the RICO violation was the but-for (or transactional) cause of his injury, meaning that but for the RICO violation, he would not have been injured.

Traditionally, to show causation in a fraud context, reliance needed to be shown. But in Bridge v.
Phoenix Bond & Indemnity Co
., 128 S. Ct. 2131, 2134 (2008), the Court lessened the emphasis on traditional reliance as an element of the RICO fraud claim to show causation in some cases.  But how a plaintiff can or must prove causation is bound up in what the factual claim is. The Bridge Court also said that in “most cases, the plaintiff will not be able to establish even but-for causation if no one relied on the misrepresentation.” 128 S.Ct. at 2144.  Here, while reliance may not be an element of the cause of action, there was no question that the plaintiffs alleged, and thus had to prove, third-party reliance as part of their factual chain of causation.  Plaintiffs alleged an injury that was caused by physicians relying on Lilly’s supposed misrepresentations and prescribing Zyprexa accordingly. Because reliance was a necessary part of the factual causation theory advanced by the plaintiffs, they had to show it to prevail, and show it by generalized proof if they wished to proceed in a class action.

The court of appeals concluded that plaintiffs’ excess price theory was not susceptible to generalized proof with respect to either but-for or proximate causation, and therefore class certification based on this theory was an abuse of discretion.

The evidence in the record made clear that prescribing doctors do not generally consider the price of a medication when deciding what to prescribe for an individual patient. Any reliance by doctors on alleged misrepresentations as to the efficacy and side effects of a drug, therefore, was not a but-for cause of the price that TPPs ultimately paid for each prescription.  Moreover, the TPP plaintiffs, who unlike the doctors were in a position to negotiate the prices of drugs in their formularies, were unable to show proximate causation.  The TPP plaintiffs drew an alleged chain of causation in which Lilly distributed misinformation about Zyprexa, physicians relied upon that misinformation and prescribed Zyprexa for their patients, and then the TPPs overpaid.  But this narrative skipped several crucial steps: after the doctors prescribe the drug, TPPs relying on the advice of Pharmacy Benefit Managers and their Pharmacy and Therapeutics Committees, placed Zyprexa on their formularies as approved drugs, and then TPPs failed to negotiate the price of Zyprexa below the level set by Lilly.  Thus, in this case, the conduct directly causing the harm was distinct from the conduct giving rise to the fraud. The plaintiff TPPs could not and did not allege that they themselves relied on Lilly’s alleged misrepresentations. But because only the TPPs were in a position to negotiate the price paid for Zyprexa, the only factual reliance that might show proximate causation with respect to price was reliance by the TPPs, not reliance by the doctors.

Since plaintiffs could not show the entire factual causal chain by generalized proof, individual issues would abound, and class certification was improper. The court of appeals also remanded for reconsideration of defendant's summary judgment motion in light of its ruling.

 

Appeals Court Vacates Verdict On Exclusion of Context Evidence

Comic Dimitri Martin notes, "I'm sorry" and "I apologize" mean the same thing -- unless you are speaking to the widow at a funeral.  The lesson? Context is key.

The New Jersey appeals court last week vacated a jury verdict for a woman who used the acne drug Accutane and allegedly developed inflammatory bowel disease (IBD).  See Kendall v. Hoffmann-LaRoche Inc.,No. A-2633-08T3 (N.J. Super. Ct.,  8/5/10). The court found that the trial court erred by restricting the defendant's use of evidence concerning the incidence of IBD in the general population to set a proper context.

Readers know that defendants frequently want to put evidence in a fuller context and give the jury a full picture.  Plaintiffs seem much less concerned that a jury will take evidence (a word in an email, a phrase in a memo, a point of data) out of context.

Some background- In 1982 the Food and Drug Administration approved the use of Accutane to treat recalcitrant nodular acne. Patients using Accutane have reported a number of common side effects. The alleged side effect that was centrally at issue in this case was the alleged propensity of Accutane to cause patients to suffer from inflammatory bowel disease. The exact scientific causes of IBD have not been conclusively established, said the court. IBD has been statistically associated with several factors, including family history, prior infections, frequent use of antibiotics, and possibly the use of contraceptives and nonsteroidal anti-inflammatory drugs.

Plaintiff underwent several courses of treatment. She had taken four courses of Accutane before she developed IBD, with no apparent gastrointestinal effects. Her medical records indicated that plaintiff's mother informed the treating physician that plaintiff had been diagnosed with an IBD, and that disease "has nothing to do with her Accutane use, according to her G.I. doctors."  Plaintiff took two courses of Accutane after she developed IBD, with "no evidence of exacerbation" of the
IBD.  But in early 2005, plaintiff suffered from excessive diarrhea, bowel incontinence, bloody diarrhea, fatigue, cramping, and abdominal pain. As 2005 progressed, plaintiff's symptoms
worsened, leading to surgery.

Plaintiff contends that if she had been warned that Accutane use could cause, or exacerbate, her IBD, she would not have taken the drug. She alleged that there was no specific reference to IBD, or that Accutane use could cause IBD, in any of the materials she personally received from 1997 to 2003.  However, prior to the use of Accutane by plaintiff, defendant revised the various warnings that it supplied concerning the drug. Roche amended the "WARNINGS" section of the Accutane package insert provided to physicians to include language about Inflammatory Bowel Disease.  In a "Dear Doctor" letter, dated August 1998, which was sent to board-certified dermatologists, Roche warned that patients taking Accutane should be monitored for IBD. Roche subsequently revised its product warnings for Accutane, with FDA approval, in 2000 and again in 2002. Plaintiff's expert opined, not surprisingly, that even the amended warnings contained in the later label were inadequate.

The appeal presented several issues, including statute of limitations, but for our readers we want to focus on the argument that the trial court abused its discretion in preventing Roche from adducing evidence as to the number of Accutane users and in limiting Roche's arguments to the jury concerning such data.

In opening, in her trial proofs, and in her counsel's closing arguments to the jury, plaintiff relied heavily upon the number of adverse case reports for Accutane and other quantitative evidence as
proof of at least two critical issues: (1) that a patient's use of Accutane can cause IBD and other gastrointestinal problems, and (2) that Roche allegedly acted too slowly and ineffectively in
responding to those risks with more forceful product warnings. Roche contended that the trial court unfairly curtailed its ability at trial to defend that numbers-oriented evidence and advocacy.

Prior to the trial in this case, plaintiff moved to bar defense counsel from presenting certain proofs and arguments concerning the background incident rates of IBD in the general population. That makes complete sense; how often do people get the disease when they aren't exposed? But, in
essence, plaintiff argued those general background rates are unreliable because symptoms of IBD are allegedly frequently under-reported.  The trial court agreed and precluded Roche from referring at trial to the background rates of IBD in the general population to disprove causation. The order did allow Roche only to present "factual testimony" to show that it acted reasonably based on such background rates, and only if "the numbers are not told to the jury."  The trial court did not, however, impose any restrictions upon plaintiff in her own use of numerical proofs at trial, other than a restriction against using the numbers in a specific formula.

Thus, during opening statements, plaintiff's counsel noted that she would present proof that Roche was aware of at least 104 reported cases of IBD, of which thirty-three cases were supposedly given a causality rating of possible or probable by the company. Plaintiff's counsel also cited in opening argument to an internal Roche report supposedly stating that, in 2002, there had been sixty-four reports of Crohn's disease (BTW, a form of IBD with no epidemiological link to the drug in any reputable study).  The trial court ruled that Roche could not argue that a comparison of those AERs vs. the background rate was a scientifically valid way to help evaluate the risk of a drug. Defendant was also curtailed in cross-examination of plaintiff's labeling expert,  particularly with regard to how Roche had analyzed certain data on Accutane that it had in fact presented to the FDA.

During the defense case in chief, the trial court did loosen her ruling and did permit a defense expert to explain to the jury that, in calculating the number of IBD cases in the exposed population, Roche had assessed the reported adverse events. Because it was suspected such events are under-reported, Roche already  factored in under-reporting. In calendar year 1988, when approximately one million patients took Accutane, there were only seven reports of IBD. From 1982 to 1999, when more than 32 million patients took the drug, there were only 206 case reports of IBD.

(Readers know that an adverse event report does not establish a causal relationship between the drug and a particular event. The FDA itself has warned that for any given ADE case, there is no certainty that the suspected drug caused the event. This is because physicians and consumers are encouraged to report all suspected ADEs, not just those that are known or even suspected to be caused by the drug. The adverse event may have been related to an underlying disease for which the drug was given, to other concomitant drug usage, or may have occurred by chance at the same time the suspect drug was administered. The courts have characterized ADEs as “complaints called in by product consumers without any medical controls or scientific assessment.” McClain v. Metabolife Intern., Inc., 401 F. 3d 1233, 1250 (11th Cir. 2005). Because the reporting system is not subject to scientific controls, data from it is subject to various statistical biases. It is likely that the mix of reported events does not represent an accurate sampling of those events that can occur while a person is taking any medication. Moreover, medical or media attention can stimulate reporting in a distorted manner, and known adverse reactions are more likely to be diagnosed and reported than others. See DeLuca v. Merrell Dow Pharmaceuticals, Inc., 791 F. Supp. 1042, 1050 (D. N.J. 1992), aff’d 6 F. 3d 778 (3d Cir. 1993), cert. denied, 510 U.S. 1044 (1994) (ADEs “have inherent biases as they are second-or-third hand reports, are affected by medical or mass media attention, and are subject to other distortions.”).)

However, the trial court here gave the jury a limiting instruction on this evidence that defendant on appeal argued was especially harmful, by accentuating to the jurors that Roche's internal corporate use of background numbers was supposedly, at least in some respects, "unscientific."  Defendant argued that the trial court's directive to the jurors that at least one use of the background numbers was not "scientifically accepted," placed a prejudicial and unnecessary spin on the proofs, to Roche's detriment.

The appellate court concluded it lacked confidence that this trial, when considered as a whole, provided a full and fair opportunity for Roche to contest, present, and advocate the relevant "numbers" evidence. Specifically, the trial court erred in forbidding Roche from placing into
evidence (and arguing) statistics about Accutane usage that could have made Roche's conduct and labeling decisions appear far more reasonable to the jury. The number of users evidence  could have given the jurors very relevant contextual background, and possibly led the jury to view differently Roche's pacing in upgrading the risk information on Accutane's label and package insert.  Even accepting, for the sake of argument, plaintiff's contention that adverse events are heavily under-reported, the quantity of actual users of a drug logically is a significant part of the
numerical landscape. At a minimum, the actual usage data for Accutane would go to "safety signaling" concerns, i.e., whether Roche had received sufficiently frequent adverse "signals" to take corrective action. Had Roche been allowed to fully present the statistics on users and other related counter-proofs, the jury would have had a fuller and more balanced picture of the data bearing upon the company's conduct in changing its label. See McCarrell v. Hoffman-La Roche, Inc., No. A-3280-07 (App. Div. Mar. 12, 2009), certif. denied, 199 N.J. 518 (2009).

The court recognized that the trial court's attempted conceptual boundary between using background data for purposes of evaluating "signals" and company conduct, but not for "causation," is a technical and somewhat elusive distinction. Increased reports of a medical condition occurring in a drug's users, as contrasted with the general population, may well provoke a drug maker to strengthen its labeling, even if such adverse reports may suggest only an association and not that the product is, in fact, "causing" such adverse results. In any event, the court of appeals felt there was no need here to draw the boundaries between causation and conduct with precision or with definiteness. The point remains that, even accepting, arguendo, as reasonable the trial court's prohibition upon Roche using background numbers to disprove causation (because of a concern about reporting), the trial as a whole did not provide Roche with a sufficient opportunity to make full and legitimate uses of such contextual evidence as part of its trial advocacy.  In particular, the jury instruction issued by the court went too far in characterizing to the jurors the use of background numbers to prove or disprove causation as "unscientific."

The case was remanded for a new trial.  And on remand, the defense will not be foreclosed from attempting to use the numbers evidence to show not only that the company acted reasonably in the manner in which it developed and modified the Accutane product warnings, but also to attempt (if it chooses to do so) to disprove general causation (along with the multiple epidemiological studies refuting causation).

Roche has successfully defended IBD claims in the federal cases brought to date, obtaining dismissals in each case that have been affirmed on appeal by the United States Court of Appeals for the Eleventh Circuit.

 

Failure to Warn Even When You Warn? Court Rejects Plaintiff's Theory

One of the fascinating and disturbing things about failure to warn claims is the endless supply of creative, far-fetched, fantastic, implausible, fanciful, incredible, questionable, even bizarre theories that plaintiff lawyers sometimes come up with to support this type of claim.

Last week, a Pennsylvania appeals court rejected just such a theory. Specifically, plaintiff alleged that a failure to warn caused her injury -- nothing strange there.  But the manufacturer DID warn specifically of the condition she developed.  So, what was the plaintiff's failure to warn theory?  That a drug maker may be liable for failure to warn despite warning of the condition plaintiff developed, because a warning about a different medical issue —one that she did not develop— would somehow have caused her doctor to not prescribe the drug.  Cochran v. Wyeth Inc., 2010 WL 2902717 (Pa. Super. Ct., 7/27/10).

Plaintiff ingested the prescription weight-loss drug dexfenfluramine, which was manufactured by Wyeth and sold under the brand name Redux. Wyeth informed the prescriber that Redux may cause primary pulmonary hypertension (“PPH”). The doctor, in turn, warned plaintiff of the risk of PPH prior to prescribing her Redux. At the time of his decision, however, the prescriber claimed he was unaware of the risk that Redux may cause valvular heart disease (“VHD”).  Later, plaintiff was diagnosed with PPH, which she had been warned about.  But she claimed that the doctor would not have prescribed Redux to her had he been warned that Redux could cause VHD.

Proximate cause is an essential element in a failure to warn case.  A proximate, or legal cause, is defined under Pennsylvania law as a substantial contributing factor in bringing about the harm in question. That is, a plaintiff must establish proximate causation by showing that had defendant issued a proper warning to the learned intermediary, he would have altered his behavior and the injury would have been avoided.   Wyeth argued that even if its warnings with regard to VHD were inadequate, its failure to warn of VHD was not the proximate cause of plaintiff's PPH.  To establish proximate causation, plaintiff must prove that the warnings failed to disclose the risk of her particular injury (PPH).

The trial court agreed. On appeal, the court found an absence of clear authority on the issue, but strong guidance in those cases that have addressed a plaintiff's burden of proving proximate causation in the informed consent context.  Finding the torts of informed consent and failure to warn analogous, the superior court was persuaded by those jurisdictions that have concluded a plaintiff cannot establish proximate causation where the non-disclosed risk never materialized into an injury.

Here, the risk of VHD did not develop into the actual injury of VHD. Although the prescriber testified in deposition that he would not have prescribed Redux had he known of the risk of VHD, this does not alter the fact that while Wyeth allegedly failed to disclose the risk of VHD the plaintiff suffered from PPH. In these circumstances, the relationship between the legal wrong (the alleged failure to disclose the risk of VHD) and the injury (PPH) was  "not directly correlative and is too remote" for proximate causation.

Summary judgment for defendant affirmed.

 

Supreme Court Passes On Chance to Clarify Punitive Damages Issue

We posted before about an important punitive damages issue, hoping the Supreme Court would take a look.  However, last week the Court declined to review the federal appeals court decision ordering a re-trial on punitive damages. Wyeth LLC v. Scroggin, U.S., No. 09-1123, review denied 6/21/10.

The case involves a woman who allegedly developed cancer after taking hormone therapy drugs. (The FDA continues to approve the drugs as safe and effective.) The plaintiff contended that Wyeth was negligent in failing to include a stronger warning on its label, and that she would not have taken the drug if the warning had been stronger. The district court conducted a bifurcated trial
before a single jury, with liability determined first and punitive damages determined second. In the first phase, the jury found for plaintiff and awarded $2.7 million in compensatory damages. In the second phase, the same jury determined that defendant was liable for punitive damages of $19.4 million. Wyeth LLC v. Scroggin, 554 F.Supp.2d 571 (E.D. Ark. 2008). On appeal, the U.S. Court of Appeals for the Eighth Circuit overturned the punitive damages award, ruling that the award was tainted by the admission of improper evidence during the punitive damages phase of the trial. But rather than ordering an entirely new trial, the appeals court ordered a partial new trial limited to punitive damages only. Scroggin v. Wyeth, 586 F.3d 547 (8th Cir.2009).

We would argue that the Seventh Amendment prohibits such partial retrials limited to punitive damages. The Seventh Amendment “right to trial by jury” has long been understood to constitute those jury trial rights that existed under the English common law when the Seventh Amendment was adopted in 1791. At common law there was no practice of setting aside a verdict in part. If the verdict was erroneous as to any issue, a new trial was directed as to all issues, so that all related issues could be decided by a single jury. Where the issue to be re-tried is related to issues already decided by the first jury, partial re-trials create a danger that the second jury will be confused when told that some issues have already been decided. Moreover, there is considerable empirical evidence suggesting that permitting partial re-trials regarding punitive damages exacerbates the unpredictability of punitive damages awards.

Chief Justice John G. Roberts Jr. took no part in the consideration or decision of the petition.
 

Brand Name Drug Maker Not Liable To Plaintiff Who Used Generics

A federal trial court in Texas has held that a plaintiff who admitted using only generic products cannot maintain failure to warn claims against brand-name drug manufacturers. Finnicum v. Wyeth Inc.,  2010 WL 1718204 (E.D. Tex., 4/28/10). 

Finnicum alleged that her doctor prescribed metoclopramide to treat her heartburn sometime in 2003 and that she regularly ingested a generic form of the drug until at least 2007. Finnicum stipulated, however, that she never ingested any form of metoclopramide manufactured or distributed by defendants Wyeth or Schwarz. In mid-2007, Finnicum alleged she began exhibiting symptoms of tardive dyskinesia, a neurological disorder characterized by involuntary movements, especially of the lower face. Finnicum contended that her long-term ingestion of metoclopramide caused her to develop the disease.

She brought suit, asserting causes of action against Wyeth and Schwarz for negligence, strict products liability, breach of warranty, fraud, and violations of the Texas Deceptive Trade Practices Act.

Although plaintiff never ingested any form of metoclopramide that defendants manufactured or distributed, she alleged that manufacturers of generic metoclopramide are required by federal law to use brand name warnings when selling their products. Finnicum further contended that physicians rely on brand-name warnings when prescribing generic drugs. Finnicum maintained that defendants, as manufacturers of the brand name drug (Reglan), failed to provide adequate warnings of the long-term effects of metoclopramide use. And that impacted the warnings she did get.

The court granted summary judgment to the defendants, joining the majority of courts that have considered this question. Texas law applied. The Texas Supreme Court has stated that a manufacturer generally does not have a duty to warn or instruct about another manufacturer's products, even though a third party might use those products in connection with the manufacturer's own products. Thus, Texas law does not permit a plaintiff who ingested another manufacturer's drug to maintain a failure-to-warn claim against a brand-name manufacturer.  This result is in accord with, for example, the Eighth Circuit in Mensing v. Wyeth, Inc., 588 F.3d 603 (8th Cir.2009); see also Foster v. American Home Prods. Corp., 29 F.3d 165 (4th Cir. 1994).

The court expressly rejected the California decision, Conte v. Wyeth, Inc., 85 Cal.Rptr.3d 299 (Cal.Ct.App.2008). In Conte, the court extended a brand name drug manufacturer's duty of care regarding product information to patients who were injured by generic brands. This ruling would impose a duty that would stretch the concept of foreseeability too far.

Senator Urges House to Amend FDA Powers on Drugs

Like a cross-over episode from two bad TV shows, Sen. Chuck Grassley, ranking member of the Senate Committee on Finance testified before a subcommittee of the U.S. House of Representatives Committee on Appropriations last week.  His Senate Committee staff is generally regarded as having issues presenting a balanced or complete view of the FDA and industry's efforts to monitor the safety and efficacy of approved medication.

In his testimony, the Senator urged Congress to give the U.S. Food and Drug Administration more power to monitor drugs' safety after they enter the market.

He raised questions about whether or not various post-marketing studies sanctioned by the FDA were properly performed.  He talked about his twice-introduced legislation to establish an independent office of drug safety at the FDA, a Center for Postmarket Drug Evaluation and Research.  This entity would tackle the alleged lack of equality between the Office of New Drugs (OND), which decides whether to approve a drug, and the Office of Surveillance and Epidemiology (OSE). OSE, he said, is the office that monitors a drug’s safety once it’s on the market and being sold to patients.

The supposed imbalance between OND and OSE was apparent, he argued, in various drug safety issues that developed into major mass torts. Individuals in the office responsible for post-market surveillance should be allowed to provide an “independent opinion” based on the best available evidence, he asserted. He claimed vaguely that FDA physicians and scientists committed to post-market monitoring of drugs have sometimes been suppressed or ignored.

Other speakers included a Yale School of Medicine Professor who testifies for plaintiffs in pharma cases, and the Director of the anti-industry Health Research Group of Public Citizen.  More fair balance? Maybe after November.

 

FDA Proposes Regs on Direct-to-Consumer Prescription Drug Ads

The Food and Drug Administration has proposed to amend its regulations concerning direct-to-
consumer (DTC) advertisements of prescription drugs. Specifically, the proposed rule would implement a new requirement of the Federal Food, Drug, and Cosmetic Act, added by the Food and Drug Administration Amendments Act of 2007 (FDAAA), that the major statement in DTC television or radio advertisements relating to the side effects and contraindications of an advertised prescription drug intended for use by humans be presented in a clear, conspicuous, and neutral manner. See 75 Fed. Reg. 15,376 (3/29/10). FDA is also proposing standards that the agency would consider in determining whether the major statement in these advertisements is presented in the manner required by FDAAA.

Readers of MassTortDefense know how DTC ads have impacted products litigation, from effects on the learned intermediary doctrine, to influence on the jury pool, to forming part of the basis of substantive information-based claims.

Under the current regulations the presentation of risk information in an advertisement for a prescription human or animal drug is required to be comparable in prominence and readability to the presentation of effectiveness information in the advertisement. If an advertisement presents effectiveness information in a clear and conspicuous manner, risk information is required to be presented in a comparable manner.  The new proposal would require disclosure of the major side effects and contraindications of the drug in a clear, conspicuous, and neutral manner, regardless of the manner in which effectiveness information is presented in the advertisement.

The proposed regulations would define the required clear, conspicuous, and neutral manner, as being met if:

1. Information is presented in language that is readily understandable by consumers;
2. Audio information is understandable in terms of the volume, articulation, and pacing used;
3. Textual information is placed appropriately and is presented against a contrasting background for sufficient duration and in a size and style of font that allows the information to be read easily; and
4. The advertisement does not include distracting representations (including statements, text, images, or sounds or any combination thereof) that detract from the communication of the major
statement.

FDA said it recognizes that these standards require judgment in their application. Therefore, the agency does not intend to prescribe a set formula for ‘‘clear, conspicuous, and neutral’’ major
statements because there is more than one way to achieve these standards in a television or radio ad. FDA intends to be flexible enough to consider the variety of techniques sponsors may use to appropriately convey required risk information in prescription drug ads. Sponsors have the flexibility to be creative in designing their ads as long as all of the standards listed here are complied with such that the major statement is communicated effectively to consumers and the overall message
that the advertisement conveys to consumers is accurate and non-misleading.

Comments on the proposed rule are due by June 28, 2010.

Upcoming Drug and Medical Device Seminar

DRI’s Drug and Medical Device Committee will hold its 26th annual Seminar on May 20-21, 2010, at the San Francisco Marriott, in San Francisco, California.

The Seminar is one of the best of its kind, highly useful to practitioners who represent pharmaceutical and/or medical device manufacturers. This year's Seminar will feature a number of nationally recognized attorneys, both in-house and outside counsel, who will address cutting-edge topics that are relevant to all who practice in this area, whether they are associates, lead trial counsel, or in-house counsel.

This year’s program will offer a mixture of presentations, such as trial skills demonstrations, panel discussions, and individual presentations from leaders in their practice areas. In addition to the outstanding program, there will be numerous networking opportunities, including the annual Young Lawyers Blockbuster. 

See the Seminar Brochure to register or to learn additional information. The advanced registration deadline is April 30, 2010.
 

Fifth Circuit Affirms Exclusion of Plaintiff's Causation Experts

A federal appeals court recently affirmed a judgment for the maker of a drug used to treat Parkinson's disease in litigation alleging that the drug caused plaintiff's compulsive gambling.  Wells v. SmithKline Beecham Corp., 2010 WL 1010591 (5th Cir. 2010).

Wells sued GlaxoSmithKline, the manufacturer of Requip, alleging that GSK had failed to warn patients about the alleged side effect of pathological gambling.  For Wells to win under Texas law,  he had to show that the failure to warn caused his injury.  Causation has two levels, general and specific, and a plaintiff must prove both. General causation is whether a substance is capable of causing a particular injury or condition in the general population, while specific causation is whether a substance caused a particular individual's injury. Sequence matters, said the 5th Circuit: a plaintiff must establish general causation before moving to specific causation. Without the predicate proof of general causation, the tort claim fails.

Wells engaged three expert witnesses to address general causation, that the drug supposedly could cause pathological gambling. In reaching their conclusions, the experts relied upon: (1) published articles documenting case-specific correlations between Requip and gambling; (2) a single unpublished study allegedly showing a nexus between Parkinson's medicines generally and gambling; (3)  internal data supposedly revealing case-specific associations between Requip and gambling; and (4) the fact that GSK has since changed the Requip label to warn about possible gambling side-effects. (Of course, on the last point a regulatory agency can require a warning based on a lesser level of proof than is required to recover in a tort action.) Defendant challenged the evidence under Daubert, and the district court granted summary judgment.  Plaintiff appealed.

Readers know that Daubert requires admissible expert testimony to be both reliable and relevant.  This entails a preliminary assessment of whether the reasoning or methodology underlying the testimony is scientifically valid and of whether that reasoning or methodology properly can be applied to the facts in issue.  Although there are “no certainties in science,” the expert must present conclusions grounded in the methods and procedures of science.  In short, the expert must employ in the courtroom the same level of intellectual rigor that characterizes the practice of an expert in the relevant field.

The court of appeals found that each of the three experts had, in deposition, in essence conceded that there exists no scientifically reliable evidence of a cause-and-effect relationship between Requip and gambling, that the state of the art was mere association, not cause.  That alone would doom the plaintiff's case.

But more interesting for readers is when the court went on, in the alternative, to address the methodologies and fit. 

The studies relied on were, each expert conceded, not statistically significant epidemiology. They were, in fact, case studies. Although case-control studies are not per se inadmissible evidence on general causation,  the courts have frowned on causative conclusions bereft of statistically significant epidemiological support. While the court agreed that in epidemiology hardly any single study is ever conclusive, and it did not suggest that an expert must back his or her opinion with multiple published studies that unequivocally support his or her conclusions, here there was simply too great an analytical gap between the data and the opinion proffered.  Bottom line-- the bases for the experts' conclusions passed none of the applicable Daubert factors: that Requip causes problem gambling is not generally accepted, has not been subjected to peer review and publication, and is not backed by studies meeting requisite scientific standards.

Without the expert testimony, Wells could not prove general causation.  Here's a useful quote:  "Wells urges the law to lead science -- a sequence not countenanced by Daubert."  See also Rosen v. Ciba-Geigy Corp., 78 F.3d 316, 319 (7th Cir.1996) (“Law lags science; it does not lead it.”).

 

Appeals Court Affirms Summary Judgment Based on Learned Intermediary Rule

A federal appeals court recently affirmed judgment for the maker of an anti-depressant drug, ruling that the plaintiff could not show that an allegedly inadequate warning caused the injury at issue. Dietz v. Smithkline Beecham Corp., 2010 WL 744273 (11th Cir. 2009).

The case reminds readers about the importance of the testimony of the prescriber in a pharmaceutical case. The plaintiff's physician diagnosed him with major depression and offered him hospitalization for psychiatric treatment, which Dietz declined. The doctor then prescribed him Paxil, a selective serotonin reuptake inhibitor (“SSRI”) antidepressant.  Eight days after having filled and begun his Paxil prescription, Dietz apparently committed suicide by throwing himself in front of a train.

Appellant filed a diversity suit. During discovery, the parties deposed Dietz's physician, who testified that he had considered the potential risks and benefits of prescribing Paxil to Dietz when he wrote the prescription in 2002.  He also testified that, even in retrospect, he agreed with his decision to treat Dietz with Paxil and would do so again today under the same circumstances.

Within the context of prescription drugs, Georgia employs the learned intermediary doctrine, which alters the general rule which imposes liability on a manufacturer for failing to warn an end user of the known risks or hazards of its products. According to the doctrine, the manufacturer of a prescription drug does not have a duty to warn the patient of the dangers involved with the product, but instead has a duty to warn the patient's doctor, who acts as a learned intermediary between the patient and the manufacturer. The rationale for the doctrine is that the treating physician is in a better position to warn the patient than the manufacturer, in that the decision to employ prescription medication involves professional assessment of potential medical risks in light of the physician's knowledge of a patient's particular needs.

Here the court affirmed summary judgment for the manufacturer since the appellant could not demonstrate that any alleged failure to warn the treater about increased suicide risks associated with Paxil proximately caused Dietz to commit suicide. The doctor provided explicit, uncontroverted testimony that, even when provided with the most current research and FDA mandated warnings, he still would have prescribed Paxil for Dietz's depression. Pursuant to Georgia's learned intermediary doctrine, this assertion severs any potential chain of causation through which appellant could seek relief. 

FDA Official Testifies Before Congress on REMS and Sentinel

Last week, the House Energy and Commerce Committee's Health Subcommittee held a hearing on drug safety.  A quick report: Chairman Waxman's opening comments indicated that the committee was eager to hear about FDA’s implementation of the 2007 FDA Amendments Act, giving FDA the authority to require manufacturers to implement “Risk Evaluation and Mitigation Strategies” or “REMS.”

FDA Principal Deputy Commissioner Joshua Sharfstein indicated that using this REMS authority is “a work in progress” and acknowledged a "lack of clarity" in certain provisions of the law with respect to REMS. FDA recognizes that designing and implementing the most comprehensive REMS requires a careful balancing of the need to adequately manage risks and also to maintain patient access to important medications. In the design of REMS with elements to ensure safe use (the most comprehensive REMS programs), FDA is mindful, he said, that the elements to ensure safe use must not be unduly burdensome on patient access to the drug, and be designed to be compatible with established distribution, procurement, and dispensing systems for drugs.

If FDA determines that a REMS is necessary to ensure that the benefits of a drug continue to outweigh the risks of the drug, FDA can require manufacturers to have a REMS in place when a drug comes on the market, or implement one later if FDA becomes aware of new safety data. Most of the REMS with elements to ensure safe use include educating prescribers about the risks and appropriate use of the drug as a condition of certification or enrollment in the REMS program. Some programs require the prescriber to monitor the patient immediately following drug administration and for a period of time afterwards. 

The FDA official also gave a brief update on the Sentinel Initiative. FDAAA requires the HHS Secretary to develop methods to obtain access to disparate data sources and to establish a post-market risk identification and analysis system to link and analyze health care data from multiple sources. On May 22, 2008, FDA officially launched the Sentinel Initiative with the ultimate goal of creating and implementing the Sentinel System—a national, integrated, electronic system for monitoring medical product safety. The Sentinel System, testified the Commissioner, once up and running, will enable FDA to actively gather information about the post-market safety and performance of its regulated products—a significant change from the current, primarily passive safety surveillance systems. The law sets a goal of access to data from 25 million patients by July 1, 2010, and 100 million patients by July 1, 2012.

FDA has gathered public input on issues related to the creation and development of Sentinel, held numerous meetings and a public workshop, and established a working group consisting of representatives of numerous federal agencies to share information and discuss issues related to ongoing efforts that are complementary to Sentinel. FDA has awarded key contracts for a pilot project to gather information that will be essential to fully implementing the Sentinel System. As we posted about before, there is still work to be done to address significant issues with this plan.

One risk is that plaintiffs’ attorneys will find a way to misuse the system, to “find” spurious associations between drugs and effects, to assert a causal link based on the “government approved, government sanctioned” database program, and to blame the drug companies for not having seen that same link sooner. Fundamentally, the system creates a corresponding need to improve the ability to determine as quickly as possible which findings reflect a genuine and health risk. That determination may take epidemiological investigations or clinical trials before any conclusion about whether a product actually caused an event. And the new system doesn’t change the reality that sometimes patients suffer adverse events after receiving drugs because they are sick, not because the drug has any issues. Plaintiffs have no incentive to place the new product information uncovered in a context of the continuing benefits of the product for many patients, the lack of certainty in the findings, the limitations of the data, etc.

 

Summary Judgment for Drug Company in Pain Pump Case

A federal court has granted defendant summary judgment in a case which alleged that cartilage damage sustained by the plaintiff, a former high school athlete, was caused by the post-surgery use of the drug company’s pain medication in an automated pump device. Jensen Meharg, et al. v. I-Flow Corp., et al., No. 1:08-cv-00184 (S.D. Ind. 3/1/10).

The former high school athlete underwent shoulder surgery, after which a pain pump was utilized. The pain pump in question was manufactured and sold by I-Flow Corporation; the local anesthetic–bupivacaine Hcl – was manufactured and sold by defendant AstraZeneca.  AstraZeneca did not in any way promote the use of bupivacaine with pain pumps, and that use was not mentioned in the instructions and warnings provided with the drug -- an off-label use. Several months later, plaintiff began to experience shoulder pain again. An MRI allegedly revealed that plaintiff had developed chondrolysis in her shoulder, which she alleged was caused by the post-surgery administration of the bupivacaine with the pain pump.

The strict liability claim was for alleged failure to warn; a warning defect claim requires that defendant had a duty to warn.  Duty is generally a legal issue.  In the context of a prescription drug manufacturer, the duty to warn does not arise until the manufacturer knows or should know of the risk.  In cases that involve an off-label use of a prescription drug that is not promoted by the manufacturer, the requisite knowledge of the risk, at a minimum, includes that the manufacturer must know (or be charged with knowledge of) both that the off-label use is occurring and that the off-label use carries with it the risk of the harm at issue – in this case, damage to cartilage.

The court found as a matter of law that the information allegedly possessed by defendant was insufficient to trigger AstraZeneca’s duty to warn of the risk of cartilage damage from continuous infusion of bupivacaine into a patient’s joint. Simply put, the plaintiff failed to point to sufficient evidence that demonstrated that at the time of plaintiff’s surgery AstraZeneca knew of that risk or that it should have known of the risk because experts in the relevant field had such knowledge.

More interesting was plaintiff's other theory. Plaintiff's expert also opined that prior to plaintiff’s surgery the defendant supposedly knew that bupivacaine was being used in pain pumps, and that this knowledge triggered an alleged duty to “investigate the nature of that use, determine whether the drug was being promoted in accordance with approved indications, conduct or sponsor those studies necessary to ensure that the promoted use was safe, and to warn physicians that long-term risks to the joint had not been scientifically established but that the risks should be weighed seriously, given that the anticipated use was for elective post-operative pain therapy for which multiple alternatives existed.”  The court noted that such a  “duty” does not exist under relevant (Indiana) law.  The duty to warn does not arise until the manufacturer knows or should know of the risk.  The alleged far broader duty  – a  duty, in essence, to warn physicians that there might be a risk, although we don’t know yet because neither we or the scientific community at large has studied it yet -- doesn't exist.

Such a duty would cause physicians to be inundated with such pseudo-warnings and quasi-risk information distracting them from heeding real warnings of actual risk; and it would add very little to the fact that physicians already know, i.e., that if a use is omitted from a prescription drug’s label, that use has not been tested sufficiently to demonstrate to the FDA that it is safe and effective.

House Committee to Hold Hearing on FDA

The House Energy and Commerce Committee's Subcommittee on Health will hold a hearing titled, "Drug Safety: An Update from the FDA" -- tomorrow, Wednesday, March 10, 2010.

 At the hearing, the Food and Drug Administration will detail the Agency's views on current challenges and successes in the area of drug safety. Set to testify is Joshua M. Sharfstein, M.D., Principal Deputy Commissioner, Food and Drug Administration. 

 
 

State Court Affirms Exclusion of Expert Evidence in Accutane Case

A New Jersey appellate court recently affirmed a trial court's decision that an Accutane plaintiff's expert's study must be excluded as unreliable. See Palazzolo v. Hoffmann La Roche Inc., 2010 WL 363834 (N.J. Super. Ct., 2/3/10).

Plaintiffs filed a product liability and consumer fraud complaint against defendants claiming that Accutane, a drug used to treat acne, caused their family member to develop depression which led to his suicide. They contended that at the time of his death in 1997, Accutane should have carried a warning label concerning the possibility that the drug could cause depression and suicide.

As one element of their product liability cause of action, plaintiffs needed to establish “general causation,” by showing that Accutane can cause depression and suicide. See Kemp v. State, 174 N.J. 412, 417 (2002); Coffman v. Keene Corp., 133 N.J. 581, 594 (1993). On that issue, plaintiffs retained Dr. James Bremner, as an expert.  Plaintiffs paid Bremner to undertake a study of the issue; there was no dispute that the study was commissioned specifically for use in this litigation.

In the study at issue, Bremner and a team of other scientists used positron emission tomography (PET) technology to compare changes in brain metabolism between two groups of subjects being treated for acne. One group was receiving antibiotic treatment and the other group was being treated with Accutane.  According to Bremner, the PET study demonstrated that the subjects treated with Accutane showed decreased metabolism in the orbital frontal cortex, a portion of the brain associated with depression. He published an article about the study in a scientific journal, describing his methodology and his conclusions. Based largely but not entirely on the PET study, he issued an expert report opining that Accutane can cause depression and suicide.

Defendants challenged the evidence. In deposition and at a hearing, Bremner was repeatedly confronted with potential problems in the PET study, including missing data, inaccurate data, and deviations from the methodology he claimed to have followed. As a result, in the middle of the Rule 104 hearing, the court permitted Bremner to re-work his study data and issue a supplemental expert report and allowed defendant to re-depose him. The trial court then excluded the evidence.

The court of appeals affirmed. First, Bremner did not actually use the methodology he claimed to have used. Although his PET scan article was peer-reviewed, he admitted that he did not in fact follow the steps described in the article. Significantly, contrary to representations made in the article, he did not get before-and-after questionnaires from many of the subjects.  Those questionnaires were designed to elicit the extent to which the subjects might be worried about their acne. This was relevant because some scientists were of the view that worrying, as well as depression, could affect activity in the orbital frontal cortex.

Secondly, Bremner also could not document much of the data on which his published results were based. Third, he admitted that some of the statistical analysis was inaccurate. For example, in the hearing session, Bremner admitted that, for each study participant, comparing the activity in the orbital frontal cortex with the activity in the whole brain revealed no difference between the subjects who took Accutane and those who took antibiotics.

The court noted that an expert's scientific peers cannot fairly judge the expert's written work, including whether it is worthy of publication, if his article does not accurately represent either the underlying data or what the author did to produce his results. In essence, Bremner's study was not  soundly and reliably generated.

There also was no error in precluding Bremner from providing supplemental reports or information after the Rule 104 hearing record closed. The judge allowed Bremner multiple opportunities to correct errors in his study before the record closed. The orderly conduct of litigation demands that expert opinions reach closure. See Miller v. Pfizer, Inc., 356 F.3d 1326, 1334 (10th Cir.), cert. denied, 543 U.S. 917 (2004).

The court of appeals remanded the case for consideration whether, even without the PET study, Dr. Bremner can still offer an opinion that Accutane can affect the brain and produce depression.

State Supreme Court Reverses Class Certification on Predominance Grounds

The Alabama Supreme Court has recently reversed a lower court's certification of a class of third-party payers of health care services who complained about damages allegedly flowing from the recall of a drug from the market.  Wyeth, Inc. v. Blue Cross and Blue Shield of Alabama, 2010 WL 152123 (Ala. Jan. 15, 2010).

Defendant Wyeth voluntarily withdrew Duract from the market, notifying the public of its decision to do so through a press release.  As part of the process of withdrawing Duract from the market, Wyeth voluntarily instituted a customer refund program for customers who still had Duract capsules in their possession. The third-party payers sued Wyeth solely on a theory of unjust enrichment, alleging that their payment for the drug had conferred an inappropriate benefit on Wyeth in light of the withdrawal.

After a hearing on the class certification motion, the trial court entered an order certifying a nationwide class of TPPs who paid for the prescription drug Duract that was not used as of the date of its withdrawal from the market.  On appeal, the defendant argued that predominance of common issues had not been established, a requirement of Alabama Rule 23 analogous to FRCP 23 (b)(3).

As in many states, Alabama recognizes that unjust enrichment claims are particularly unsuitable for class treatment. Funliner of Alabama, L.L.C. v. Pickard, 873 So.2d 198, 211 (Ala.2003) (unjust enrichment claims based on allegations of mistake or fraud require an individualized inquiry into the state of mind of each plaintiff).  The trial court distinguished this body of law, finding that this particular enrichment claim was not based on fraud or mistake, but on the somehow different theory that “equity and good conscience” required the defendant to disgorge money that belongs to the plaintiff.

The court observed that Wyeth probably had the better of the argument on this, meaning that the trial court had fashioned on a distinction without a difference.  But the state high court did not need to resolve the unjust enrichment issue under Alabama law, because the plaintiffs sought a nationwide class. Regardless of what Alabama law was, there had been no adequate showing, either to the trial court or to the Supreme Court, that the laws of all (or even most of) the 49 other states would allow unjust enrichment claims to proceed on such a "good conscience" basis somehow distinct from a traditional claim. 

Even a cursory examination showed that variances exist in state common laws of unjust enrichment. The actual definition of unjust enrichment varies from state to state. Some states do not specify the misconduct necessary to proceed, while others require that the misconduct include dishonesty or fraud. See Clay v. American Tobacco Co., 188 F.R.D. 483, 501 (S.D.Ill.1999).

Accordingly, common issues could not predominate.  Certification was vacated.

New Paper On Reduced Legal Oversight of FDA Warning Letters

The WLF has just published a thought piece, co-authored by your humble blogger and colleagues Jim Beck and Vincent Gallo, on how "Reduced Legal Oversight For FDA Warning Letters Amplifies Compliance And Liability Risks."
 

Last summer, the Commissioner of the Food and Drug Administration reversed existing, sound policy that required prior legal review of regulatory letters (Untitled and Warning Letters) by the Agency's Office of Chief Counsel. This reversal -- eliminating review of regulatory letters for legal integrity except in cases of "significant legal issues" -- is one of several changes instituted by the Commissioner to increase enforcement activity and purportedly to limit enforcement delays.

Our paper explores the potential problems with this policy reversal and the risks for industry.

MDL Court Rejects Consolidation of Bellwether Trials

Readers of MassTortDefense know how significant the earliest few trials in any mass tort can be, influencing later trials and shaping settlement strategies.  Accordingly, which cases go first, from among the hundreds or thousands in the mass tort, and how they are tried, can be extremely significant.  The federal court overseeing the MDL concerning the antibiotic Levaquin recently denied plaintiffs' motion to consolidate three bellwether cases for the first trial. In re Levaquin Products Liability Litigation, MDL No. 08-1943, (D. Minn.). 

In the Order, the court noted that it had initially selected fifteen cases for evaluation and initial case-specific fact discovery in the bellwether-selection process. Directed by the court to meet and confer on an ordering of these cases for the first trials, the parties narrowed the field to seven remaining bellwether cases for selection for trial. Plaintiffs then moved to consolidate three of the cases for the first trial.  They asserted that the cases share similar characteristics that are central to this litigation and that consolidation would promote judicial efficiency and the interests of justice, while testing the merits of plaintiffs’ arguments. Defendants opposed the motion, arguing that plaintiffs had not met their burden of showing that a consolidated trial’s benefits would outweigh individual
issues in the case. Specifically, defendants argued that individual issues – including each
plaintiff’s unique medical history, each prescribing physician’s knowledge of warnings in the Levaquin package insert, and each plaintiff’s alleged injuries – precluded consolidation.

Federal Rule of Civil Procedure 42(a)(2) affords a court broad discretion to consolidate for trial actions involving common questions of law or fact. The party seeking consolidation bears the burden of showing that consolidation would promote judicial convenience and economy. Consolidation is inappropriate, however, if it leads to inefficiency, inconvenience, or unfair prejudice to a party.

Plaintiffs also argued that judicial economy would be served by consolidation because common sources of evidence established the supposedly common facts. For example, the same generic
expert witnesses would testify on behalf of each individual plaintiff, and the regulatory and
corporate history of the drug is the same for each plaintiff. Because of these alleged commonalities and claimed efficiencies, plaintiffs argued that consolidation of the three cases would save the court twenty trial days, not insignificant.
 
In opposition, defendants argued that individual issues, including what dose of Levaquin each physician prescribed to treat each plaintiff’s infection, and each individual plaintiff’s medical history, including their various risk factors for the injury alleged such as age, concomitant medication use including corticosteroids, prior injury, and other factors, all made consolidation inappropriate.

Moreover, defendants argued that consolidation would be prejudicial to them because there are complicated causation issues in each case, and multiple plaintiffs would testify regarding similar injuries, which could cause jury confusion. See In re Consol. Parlodel Litig., 182 F.R.D. 441, 447 (D.N.J. 1999) (“A consolidated trial . . . would compress critical evidence of specific causation and
marketing to a level which would deprive [the defendant] of a fair opportunity to defend itself.”).

At this stage of the MDL, the court concluded, consolidation was not merited. With respect to
the consolidation of cases, the Manual for Complex Litigation notes, “If there are few prior verdicts, judgments, or settlements, additional information may be needed to determine whether aggregation is appropriate. The need for such information may lead a judge to require a number of single-plaintiff, single-defendant trials, or other small trials.” Manual for Complex Litigation § 22.314, at 359 (4th ed. 2004). In the mass tort involving breast implants, the courts noted that that “[u]ntil enough trials have occurred so that the contours of various types of claims within the . . .
litigation are known, courts should proceed with extreme caution in consolidating claims.” In re Bristol-Myers Squibb Co., 975 S.W.2d 601, 603 (Tex. 1998).

To date, there are over 240 federal court cases in this MDL and just under 100 state court cases addressing claims similar to those brought by the bellwether plaintiffs. Indeed, this is a still growing MDL, found the court, the exact factual and legal contours of which are still undefined. The parties continue to conduct critical discovery, including deposing plaintiffs’ prescribing physicians. The merits of the parties’ arguments have not been tested at trial or in dispositive motions.

The court recognized that "the stakes are high" because the initial bellwether trials in this MDL may serve as the basis for the parties’ resolution of remaining, pending cases. Thus, although plaintiffs
appear to have demonstrated some commonalities in fact and law among the three
individual plaintiffs’ cases, this motion was denied at this time. 

CAFA Mass Tort Removal in Drug Case

A federal court in Illinois recently denied remand of approximately 100 cases involving Trasylol, an anti-bleeding drug, citing the Class Action Fairness Act. Gilmore v. Bayer Corp., 2009 WL 4789406(N.D. Ill., 12/10/09). (Federal Trasylol litigation was consolidated in 2008 in the Southern District of Florida. In re Trasylol Prods. Liab. Litig., No. 08-MD-1928 (S.D. Fla.). The plaintiffs typically assert that the product causes heart and kidney complications, and that the defendants allegedly failed to warn of the risks.)

The suit was originally filed in state court. The defendants removed the case, but Judge G. Patrick Murphy remanded it for lack of federal jurisdiction. Additional plaintiffs were added in October, followed by a second removal motion. The defendants asserted diversity of citizenship under CAFA. The plaintiffs again sought remand.

The Southern District of Illinois ruled that the removing defendants asserted correctly that this case was a removable “mass action” within the meaning of CAFA. Among the actions covered by CAFA is a “mass action,” defined by the statute as “any civil action ... in which monetary relief claims of 100 or more persons are proposed to be tried jointly on the ground that the plaintiffs' claims involve common questions of law or fact,” and in which there is minimal diversity of citizenship (at least one plaintiff is not a citizen of the same state as at least one defendant) and the plaintiffs each seek a recovery exceeding $75,000, exclusive of interest and costs. 28 U.S .C. § 1332(d)(11)(B)(i).

The court concluded that an independent review “discloses plainly that the removal of this case is proper under the CAFA.”  The operative complaint asserted claims on behalf of one hundred persons, the minimum number of plaintiffs required for the exercise of jurisdiction pursuant to CAFA's “mass action” provisions.  Further, this case obviously presented questions of law and fact common to the claims of all one hundred plaintiffs, said the court. Common questions of fact and law included, for example, what information Bayer, Bayer LLC, and Bayer Healthcare possessed concerning the alleged harmful effects of Trasylol, what information they elected to disclose to physicians and patients about those harmful effects, and what information they were required by law to disclose about those effects, according to the court.

With respect to the requirement of minimal diversity of citizenship, this jurisdictional prerequisite was satisfied in this case as plaintiff Thomas Gilmore is a citizen of Washington and Bayer is incorporated under Indiana law and has its principal place of business in Pennsylvania.

Finally, with respect to the jurisdictional amount in controversy under the CAFA's “mass action” provisions, the Court noted that in other cases involving allegations of personal injuries allegedly caused by the drug similar to the allegations contained in the operative complaint in this case that the plaintiffs' claims individually exceeded $75,000.

Our readers know that Congress enacted CAFA to allow more interstate class actions to be heard in federal court, and to address class action abuse.  "Mass actions" were recognized as class actions in disguise, and included in CAFA the provision to prevent the statute's objectives from being undermined by these "close substitutes that escape the statute's application." The courts increasingly offer a common sense reading of CAFA  that thwarts any attempt by plaintiffs' counsel to avoid federal court through the class-action substitute.

Summary Judgment in Remicade Case

Defendants were granted summary judgment in a case in which the parents of a young woman alleged her death was caused by the infusion treatment Remicade.  Mack v. AmerisourceBergen Drug Corp., 2009 WL 4342513 (D. Md. 11/24/09).  The lesson here for defendants is to put plaintiffs to their proof on every element of a claim.

Crystal Ann Mack was diagnosed with a severe form of Crohn's disease, an inflammatory disease affecting the gastrointestinal tract. In the autumn of 2006, Ms. Mack was hospitalized on two occasions and ultimately diagnosed with anemia, vomiting, weight loss, and various other symptoms. Her treating physician recommended that Ms. Mack undergo Remicade treatments. She received four infusions, in accordance with the medication's dosing instructions. Later, Mack fell unconscious in her home and died. Mack's parents sued three defendants, the drug makers and the distributor, alleging that Mack died of a cardiac arrhythmia that was proximately caused by Remicade.

The defendants sought summary judgment.  Analyzing the product liability claims first, the court concluded that plaintiffs' claims cannot survive summary judgment because they did not establish an issue of fact on whether Remicade is a defective product. Plaintiffs made great efforts to prove specific and general causation, but they made no adequate showing with respect to the issue of defect. Because a showing of defect is an independent prerequisite for a products liability claim, the court didn't even feel the need not address whether plaintiffs satisfied their burden on the issue of causation.

In order to recover on a product defect claim, under the applicable state law, a plaintiff must prove that a defect which renders the product unreasonably dangerous might arise from the design of the product, a deficiency in its manufacture, or from the absence or inadequacy of any instructions or warnings as to its safe and appropriate use. The court noted that the plaintiffs did not assert a failure-to-warn theory.

Under Maryland law, courts may apply both the “risk/utility” test and the “consumer expectation” test when evaluating the efficacy of design defect claims. The “risk/utility” test involves an assessment of “whether the benefits of a product outweigh the dangers of its design.”  Alternatively, a drug could be deemed unreasonably dangerous if it is “dangerous to an extent beyond that which would be contemplated by the ordinary consumer who purchases it, with the ordinary knowledge common to the community as to its characteristics. Here, plaintiffs merely cited the legal standards for alleging and proving defect. 

Moreover, plaintiffs failed to present expert testimony on the issue of defect.  The testimony of the doctors largely focused on the issue of causation, and they failed to explain how Remicade was unreasonably dangerous. This shortcoming was especially damaging to plaintiffs' claims, because the issue of defect in this case involved technical medical questions beyond the common knowledge of laypersons.

Nor was there sufficient circumstantial evidence of defect. Plaintiffs' counsel proffered several miscellaneous documents, including internal corporate memoranda and correspondence that referred to the exhibited side effects of Remicade. However, such documents did not militate for the submission of the defect issue to a jury. The fact that a drug may exhibit certain adverse side effects does not, by itself, create an issue of material fact on whether the drug is unreasonably dangerous. The courts have recognized that all drugs involve risks of adverse side effects in those who take them.  In the face of FDA approval, plaintiffs would need to provide a much greater evidentiary showing to establish that the medication's attendant risks outweigh its benefits, the necessary showing under the “risk/utility” test.

 


 

MDL Status Denied in Pharma Case

The JPML has denied centralization of the litigation accusing a drug maker of fraudulently promoting and allegedly misrepresenting the safety of 11 prescription drugs including Viagra
and Zoloft.  In re: Pfizer Inc. Marketing and Sales Practices Litigation, MDL Number 2115.

The Panel said that these actions do, on their face, share some allegations that defendants engaged in a fraudulent scheme to promote different prescription drugs: Geodon, Zyvox, Lyrica, Aricept, Lipitor, Norvasc, Relpax, Viagra, Zithromax, Zoloft, and Zyrtec. According to
plaintiffs, the company (1) promoted the drugs to physicians by offering them inducements, (2) promoted the drugs at doses or for durations of use that were not medically safe or efficacious, (3) made false representations about the safety and efficacy of the drugs, and (4) promoted certain of the drugs for non-indicated “off-label” uses.

But, the named plaintiffs allege that they themselves each took only one of those eleven drugs, and that they did not take the same drugs.  Given that each of the eleven drugs necessarily has a different clinical, regulatory, medical, and promotional history, and that it is at least questionable whether a plaintiff can prosecute claims regarding drugs that he or she never actually took, the Panel was not convinced that centralization under Section 1407 was appropriate.

The cases thus seemed to fall in that category of litigation which the Panel may be less likely to centralize because the underlying actions raise primarily individual, not common, issues, as when they involve many different defendants, diverse plaintiffs, or different modes of exposure to the allegedly offending products.
 

 

Causation Proof Still Insufficient In Drug Case

A while back we posted about an interesting toxic tort case involving important causation issues. See Zandi v. Wyeth, 2009 WL 2151141 (Minn.App.).  A Minnesota appeals court recently refused to rehear its prior affirmance of summary judgment for defendants in a suit by a woman who alleged hormone replacement drugs caused her breast cancer.  2009 Minn. LEXIS 648. 

Plaintiff alleged that between approximately 1981 and 2001, she ingested hormone replacement therapy (HRT) drugs manufactured, designed, packaged, marketed, and distributed by defendants. In November 2001, Zandi alleges she was diagnosed with "hormone-dependent breast cancer." She contended that the HRT drugs caused her cancer. 

The trial court found that plaintiff's specific causation evidence did not satisfy Minnesota's standard for admissibility of expert testimony. Zandi offered testimony from Dr. Lester Layfield and Dr. Gail Bender to try to prove that HRT drugs caused her cancer. Minnesota courts use the Frye standard to determine the admissibility of novel scientific evidence. Zandi's claims were based on the following propositions: 1) it is supposedly generally accepted that HRT causes hormone-dependent breast cancer, and 2) there is a generally accepted method of diagnosing the cause of hormone-dependent breast cancer in an individual. The appellate issues revolved around the second.

Plaintiff's experts based their specific causation opinions in part on "differential diagnosis."  As readers of MassTortDefense know,  differential diagnosis, sometimes called “differential etiology”  is a process through which all the scientifically plausible causes of an injury are “ruled in,” and the expert then “rules out” the less plausible causes until reaching the one that theoretically cannot be ruled out.  If you've watched "House" on TV, you have seen the use of differential diagnosis to discover what disease a patient is suffering from.  Less traditional, and more questionable, is the use of the technique to discover what is the cause of the disease in the patient.  Most doctors don't care as much about the cause of the disease as getting the right disease and treating it.  As used by toxic tort plaintiffs, differential diagnosis adopts a process of elimination to identify not just the injury (which may be debated) but also the cause; in theory, it seeks to eliminate the possibility of competing causes or confounding factors. 

Again, in performing a differential diagnosis, a physician begins by ruling in all scientifically plausible causes of the patient's injury. The physician then rules out the least plausible causes of injury until the most likely cause remains. Yet, breast cancer does not lend itself to such a differential diagnosis because the scientific community has not accepted that breast cancer has a limited number of discrete and recognized possible causes such that ruling out one or a few causes would necessarily implicate another. For differential diagnosis to be sufficiently reliable to even come close to proving causation, even assuming one accepts the method in this context, the diagnostician should rule out all other hypotheses, or at least explain why the other conceivable causes are excludable. But additional risk factors that plaintiff failed to adequately account for here in this case included family history. When faced with this dilemma, as is common when a disease has many idiopathic cases, plaintiff's experts simply suggest that it is possible to conduct a reliable differential diagnosis without ruling out other hypotheses, as long as "major" or "most" explanations are ruled out.  Courts should be wary of this.

Courts generally recognize that the proffered expert must have a sufficient basis to “rule in” the drug or toxic substance at issue as a plausible cause of plaintiff’s injury. E.g., Jazairi v. Royal Oaks Apts., 217 Fed. Appx. 895 (8th Cir. 2007).  But this case is a good reminder that the plaintiff's expert testimony must also reliably “rule out” the other plausible causes of the injury--  again, especially difficult when its causes are largely unknown.  On this record, the court said, “We conclude that there is not a method of diagnosing the specific cause of a particular woman's breast cancer that is generally accepted in the relevant scientific community. This reality leaves Zandi without a legally sufficient ability to prove specific causation.”  See also Perry v. Novartis, 564 F. Supp.2d 452 (E.D. Pa. 2008).

This clear reasoning can be contrasted with the inexplicable finding of the 8th Circuit in Scroggin v. Wyeth, 2009 WL 3518245 (8th Cir. Nov. 2, 2009), which accepted plaintiff's carefully constructed circular reasoning.  Unable to prove that the breast cancer was caused by hormone therapy drugs, plaintiff's expert simply re-diagnosed the disease as hormone-induced breast cancer.  This allowed the expert to engage in a so-called differential diagnosis to determine the cause of the breast cancer simply by ruling out the two possible sources of these hormones: (1) plaintiff produced the hormones herself, or (2) they came from the hormone replacement therapy she had allegedly taken for the past eleven years.  Under this circular reasoning, any form of cancer can easily be linked to the defendant's product because it will be re-characterized as the sub-type of disease caused by the substance at issue. 
 

 

Update on Digitek Litigation

In the Digitek MDL, the parties have been wrangling over the defense motion for a Lone Pine order. See generally Lore v. Lone Pine, No. L-336006-85, 1986 WL 637507 (N.J. Super. Ct. Nov. 18, 1986).

Dozens of product liability cases alleging that defendants Actavis Totowa LLC, Actavis Inc. and Actavis Elizabeth LLC marketed Digitek tablets containing double the appropriate dosage were transferred to an MDL assigned to Chief Judge Goodwin of the Southern District of West Virginia last summer. In Re: Digitek Products Liability Litigation, MDL No. 1968 (S.D. W.Va.).
 

Defendants recently moved for a Lone Pine order under which each plaintiff must submit an "affidavit from a medical expert in each case establishing that there is medical evidence of digoxin toxicity." Readers of MassTortDefense recognize this important and logical procedural tool for management of mass toxic tort litigation.  When the major factual battles will be over injury and causation, it may make sense to focus discovery on these issues, and prior to resorting to expensive and time-consuming discovery, to require plaintiffs to come forward with some prima facie showing of injury and specific causation, or as the court put it, "some evidence of certain elements of their claims, e.g. medical causation, to support a credible claim."

The plaintiffs in the federal Digitek multidistrict litigation filed a brief opposing the motion, arguing that the discovery in the MDL is still in its "incipient stages."  As they typically do, the plaintiffs argued that such orders "effectively function as untimely and unjust summary judgment devices and violate the discovery rules for expert witness disclosures and reports." They also argued that they have provided significant case-specific discovery in the form of Plaintiffs' Fact Sheets and records authorizations.

The court entered PTO #43 (Order re Request for Lone Pine Order), saying the motion is taken under advisement pending completion of basic fact discovery of Group 1 cases. Under the latest schedule, Plaintiff shall serve their reports from liability experts no later than March 15, 2010.  The parties shall complete their depositions of Plaintiffs’ liability experts no later than May 28, 2010.  Defendants shall serve their reports from liability experts no later than June 15, 2010. The parties shall complete their depositions of Defendants’ liability experts no later than August 31, 2010. 

At the November 20, 2009, conference each party is to present to the court their choice of five cases that they believe to be representative plaintiffs for trial in accordance with PTO #38, governing the creation of a trial pool upon completion of basic fact discovery, including but not limited to the depositions of plaintiffs, plaintiffs’ physicians who prescribed Digitek® to them, physicians who treated Plaintiffs for alleged digoxin toxicity, and pharmacists who filled plaintiffs’ prescriptions for Digitek®.
 

MDL Created For Zicam Litigation

The Judicial Panel on Multidistrict Litigation has decided to consolidate multiple federal cases arising from the Zicam product line.  IN RE: ZICAM COLD REMEDY MARKETING AND SALES PRACTICES LITIGATION, MDL No. 2096.  Plaintiffs moved, pursuant to 28 U.S.C. § 1407, for coordinated or consolidated pretrial proceedings of multiple proposed class actions.  By the time the Panel issued its Order, there were 40 related actions pending in 26 federal districts.

Many of the pending cases were consumer fraud class actions against Matrixx Initiatives, Inc., and its subsidiaries Zicam, LLC, and Zicam Swab, LLC.  Plaintiffs opposed centralization of any actions alleging personal injury claims. But the Panel found that both kinds of actions involved sufficient common questions of fact, and that centralization of the actions under Section 1407 would serve the convenience of the parties and witnesses and promote the just and efficient conduct of this litigation. The actions share factual questions regarding, inter alia, the marketing and sale of three Zicam nasal cold remedy products, and alleged injuries sustained by the use and/or purchase of those products, particularly whether the products cause anosmia (the loss of sense of smell). Centralization under Section 1407, the court found, would eliminate duplicative discovery, prevent inconsistent pretrial rulings (particularly with respect to class certification), and conserve the resources of the parties, their counsel and the judiciary.

The Panel declined to separate purported consumer class actions from other actions alleging personal injury. Centralization of all actions in this docket would, said the court, allow a single judge to structure pretrial proceedings to accommodate all parties’ discovery needs while ensuring that the common parties and witnesses are not subjected to discovery demands that duplicate activity that will or has occurred in other actions.

The court chose the District of Arizona as the appropriate transferee forum. The defendants are based within the District of Arizona, and relevant documents and witnesses are likely found there, observed the Panel. In addition, centralization in the District of Arizona will allow for coordination of the federal actions with related litigation pending in Arizona state court.

 

Third-Party Payor Class Action Alleging Off-Label Marketing Dismissed by Federal Court

The federal court has dismissed a putative class action brought by a group of municipal benefit funds over a pharmaceutical company's alleged efforts to market drugs for uses that did not have regulatory approval. Central Regional Employees Benefit Fund, et al. v. Cephalon Inc., No. 09-cv-03418 (D.N.J. Oct. 15, 2009).

Plaintiffs commenced this putative class action against defendants alleging violations of the New Jersey Consumer Fraud Act (“NJCFA”), and for fraudulent concealment, and “illegal fraud.”  The plaintiffs defined their putative class as including “all governmental entities in the United States of
America who have been caused to expend monies" for certain drugs as a "result of the off label promotion by the defendants.”  They alleged that defendant Cephalon promoted drugs for uses other than those approved by the FDA, and that as part of its “off label” marketing efforts, Cephalon allegedly made false representations regarding the use and application of several in particular, Provigil, Gabitril, Actiq and Fentora.

The case, thus, falls in the growing body of cases by governmental third-party payors searching for a windfall in revenue by challenging the marketing practices of pharmaceutical companies over drugs that are effective, are safe, are prescribed by physicians, and are often affirmatively recommended by other branches of the entity bringing suit.  As many courts have held, off-label use is an accepted and necessary corollary of the FDA’s mission to regulate in this area without directly interfering with the practice of medicine. E.g., Southard v. Temple University Hospital, 566 Pa. 335, 340 781 A.2d 101, 104 (2001) (quoting Buckman Co. v. Plaintiffs’ Legal Committee, 531 U.S. 341, 350 (2001)). Such use, necessary because medical practice inevitably runs ahead of the slower pace of governmental regulation, is generally accepted, widespread in the medical community, and often is essential to giving patients optimal medical care. Buckman, 531 U.S. at 351 & n.5 (citation omitted).  Thus, a physician, using his or her best medical judgment for the benefit of his patient, generally is free to use an approved product in a manner different from that for which the FDA has approved. Cabiroy v. Scipione, 767 A.2d 1078, 1082 (Pa. Super. 2001).

The FDA has accepted off-label use for decades:

  • Accepted medical practice often includes drug use that is not reflected in approved drug labeling. . . . a physician may prescribe a drug for. . .patient populations that are not included in approved labeling. Such. . .‘unlabeled’ uses may be appropriate and rational in certain circumstances, and may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature. . . . Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations.

FDA, “Use of Approved Drugs for Unlabeled Indications,” 12 FDA Drug Bulletin 4, 5 (1982). 

It is clear that physicians may prescribe a drug off-label for an unapproved population without FDA knowledge or approval.  Blain v. Smithkline Beecham Corp., 240 F.R.D. 179, 182 (E.D. Pa. 2007). And courts are “not willing to accept that a plaintiff could somehow be injured by purchasing a drug that is as effective, or more effective, than alternative treatments simply because the drug is marketed off-label.”  In re Schering-Plough Corp. Intron/Temodar Consumer Class Action, 2009 WL 2043604, at *10 (D.N.J. July 10, 2009). Absent some “adverse effects,” a “theory under which [plaintiffs] would be entitled to reimbursement for some or all of the purchase price of [a drug] whose benefits they clearly enjoyed. . . is patently absurd.”  Heindel v. Pfizer, Inc., 381 F. Supp.2d 364, 380 (D.N.J. 2004).  

Cephalon moved to dismiss the NJCFA and common law fraud claims, contending that the plaintiffs failed to plead specific acts of fraud to support the legal conclusions contained in the Complaint. The plaintiff’s factual allegations must be enough to raise a right to relief above the speculative level. Bell Atl. Corp. v. Twombly, 550 U.S. 544, 555-56 (2007). Also, the plaintiffs’ common law fraud claims were subject to the heightened pleading standards of Rule 9(b), which requires that in all averments of fraud or mistake, the circumstances constituting fraud or mistake shall be stated with particularity. Fed.R.Civ.P. 9(b).

Cephalon argued that the plaintiffs, as third-party payors of prescription medication benefits, are not “consumers” under the NJCFA. The court said that the nature of the transaction, not the identity of the purchaser, determines whether the NJCFA is applicable. J & R Ice Cream Corp. v. Cal. Smoothie Lic. Corp., 31 F.3d 1259, 1273 (3d Cir. 1994).  For a NJCFA plaintiff to be a consumer respecting the transaction in question, the business entity must be one who uses economic goods, and so diminishes or destroys their utilities. However, third-party payors essentially serve as middlemen or insurers, paying all or part of the cost of a beneficiary’s drugs in return for a stream of payments from the beneficiary.  Because third-party payors do not use or consume prescription medications themselves, they are not “consumers” within the meaning of the NJCFA, and that statute was therefore inapplicable to the circumstances alleged in the Complaint.

Next, the court found that the plaintiffs’ common law fraud claims failed to meet the pleading requirements of Twombly, Iqbal, and Rule 9(b). Count II of the Complaint, fraudulent concealment, referred merely to an unspecified “transaction and/or providing of the prescription drugs Provigil,
Gabitril, Actiq and Fentora.” The court was at a loss to discern to what transaction the plaintiffs were
referring, as the Complaint fails to identify or explain the who,what, where, why, and how of any “transaction.”  Mere allegations that Cephalon provided prescription drugs, without saying to whom or under what circumstances, wholly failed to state a claim for fraud. 

The plaintiffs attempted to rely on a reference in the Complaint to a proceeding in the Eastern District of Pennsylvania in 2003, brought pursuant to the False Claims Act, 31 U.S.C. § 3729 et seq., wherein Cephalon was alleged to have engaged in “misbranding” of its products. However, referring to a plea agreement and civil settlement in another action does not satisfy the plaintiffs’ burden; it is well-established that off-label marketing of an approved drug is itself not inherently fraudulent. Merely alleging that Cephalon marketed the drugs at issue for off-label purposes did not state a claim for fraud.

The court thus also dismissed the claims for fraudulent concealment and illegal fraud, but without prejudice.
 

PhRMA Issues New Principles on Clinical Trials

Readers of MassTortDefense know how the conduct and results of clinical trials can reach out and affect later product liability litigation: plaintiffs frequently assert that drug makers missed or ignored safety signals present in those trials. 

In reality, developing new therapies to treat disease and to improve quality of life is a long and complex process. And a critical part of that process is clinical research -- without clinical research studies, no new medicines could be made available to patients.

Last week PhRMA issued revised Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results with a goal of helping assure that the clinical research conducted by pharmaceutical research and biotechnology companies continues to be carefully conducted and that meaningful medical research results are communicated to healthcare professionals and patients.

Among the key changes in the updated Principles: Increased transparency about clinical trials for patients and healthcare professionals; enhanced standards for medical research authorship; and improved disclosure to better manage potential conflicts of interest in medical research.

PhRMA members have indeed had a longstanding commitment to sponsoring clinical research that fully complies with all legal and regulatory requirements. And actually, many different entities and individuals contribute to the safe and appropriate conduct of clinical research, including not only sponsoring companies but also regulatory agencies; investigative site staff and medical professionals who serve as clinical investigators; hospitals and other institutions where research is conducted; and Institutional Review Boards and Ethics Committees.

The key issues addressed are:
• Protecting Research Participants
• Conduct of Clinical Trials
• Ensuring Objectivity in Research
• Providing Information About Clinical Trials

Of particular note to my readers may be the document's call for consistency with standards of the International Committee of Medical Journal Editors as journal guidelines for authorship;  under these, anyone who: (1) provides substantial contributions into the conception or design of a study, or data acquisition, or data analysis and interpretation; and/or (2) writes or revises the manuscript involving important intellectual content; and/or (3) has final approval of the version to be published, should receive appropriate recognition as an author when the manuscript is published. Conversely, individuals who do not contribute in this manner do not warrant authorship. We have posted about this issue before.

As always, the guidelines are purely voluntary, and even member companies are free to adopt their own best practices and mold general guidance to their particular situations.

 

FDA Releases Draft Guidance on Risk Evaluation and Mitigation Strategies

The FDA has released its draft guidance on Risk Evaluation and Mitigation Strategies, or REMS, laying out guidelines for how pharmaceutical companies should follow the plans, and describing the consequences for not doing so. The draft guidance for industry entitled ‘‘Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments, and Proposed REMS Modifications,’’  follows on the Food and Drug Administration Amendments Act of
2007 (FDAAA) which added new provisions to the Federal Food, Drug, and Cosmetic Act giving FDA the authority to require REMS.

For every drug approved by the FDA, the risks associated with its use are communicated through the labeling/product package insert. The manufacturer or the FDA may determine that a formal ongoing effort may be needed to monitor and manage risk issues, and thus that a Risk Evaluation and Mitigation Strategy is necessary to go beyond traditional product labeling to ensure that the benefits outweigh the risks on an ongoing basis.  FDA may now require REMS for any NDA, ANDA, or BLA, at any stage of the product life-cycle.  REMS components include medication guides; patient package inserts; a communication plan for health care providers; elements to ensure safe use including requirements for those who prescribe, dispense, or use the drug; and a timetable for REMS submission.  About 60 medicines are currently sold with such plans.

We have posted before about the opportunities and pitfalls in REMS that could have a significant effect on future litigation involving the product. The REMS process may engender “bad documents” (a paper trail that casts the company or its products in a bad light). On the other hand, one of the common claims asserted in product litigation is that a manufacturer was aware of and failed to adequately warn about its product’s risk. As the REMS process is specifically designed to increase the effectiveness of warnings to the health care and patient communities, it may bolster a defense against the assertion that the manufacturer failed to provide adequate warnings.

The new draft guidance describes the format and content of a proposed risk evaluation and mitigation strategy, including REMS supporting documentation, the content of assessments and proposed modifications of approved REMS, what identifiers to use on REMS documents, and how to communicate with FDA about a REMS. The draft guidance was issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the agency’s current thinking on the format and content of proposed REMS, REMS assessments, and proposed REMS modifications.

REMS required by the FDA are subject to regulatory inspection and are enforceable under the FDCA as amended by FDAAA.  A drug may be considered misbranded if the responsible person for that drug fails to comply with a requirement of the approved strategy.  Firms that don't follow their plans will face fines of up to $10 million for a continued violation, according to the FDA guidance.
 

State Supreme Court Decision Turns On Absence Of Causation Proof

The Indiana Supreme Court issued a decision recently, reminding us of the importance of fully developing the causation case, in addition to the response to plaintiff's defect allegations. Kovach v. Caligor Midwest, 2009 WL 2871172 (Ind. September 8, 2009).

The plaintiffs alleged their son was given a fatal overdose of pain medication by a nurse after a surgical procedure. The plaintiffs sued the manufacturers and distributors of the medicine cup used to administer the medication, alleging that defects in design of the cup made it unsuitable for the precise measurements necessary for drugs, and alleging a failure to warn that the cup was not suitable for precision measurement. The interior of the cup bore translucent markings to measure its contents, and graduations delineated both 15 and 30 mL. The nurse had used that type of cup frequently, both at this surgical center and at other hospitals, and she had no difficulty reading its markings. The nurse testified she filled the cup approximately half-way and administered 15 mL of medication to plaintiff's decedent.  According to decedent's father, however, who was present when the drug was administered, the nurse gave the son a full cup of medicine.

So, as is frequently the case, a potential malpractice claim is turned into a product liability claim against an ostensibly deeper pocket, unencumbered by med mal tort reform restrictions.

The plaintiffs presented expert evidence opining that the cup was defective in design and warnings, evidence that was challenged by the defense.  Plaintiffs also argued that if the medicine cup had been better suited as a precision measuring device or had contained a warning that it was not suitable for precision measurement, the decedent would not have received an overdose -- the alleged causal link.  The court did not have to reach the issues surrounding the alleged defects and the expert affidavit which plaintiffs had put forward to support their theory of defect, because the facts established that there was no such causal connection. The results of an autopsy revealed that the decedent had more than twice the recommended therapeutic level of codeine in his blood stream. The undisputed evidence thus demonstrated that if there was an overdose in this case, it was not caused by an imprecise measurement of medication attributable to less than readily discernible marks. (The plaintiff expert had estimated that the cup's imprecision could result in up to a 20% to 30% margin of error.) Rather, if the drug was the medical cause of the death, it was due to an erroneous, double dosage; the accident therefore cannot be attributed in a legal cause sense to any alleged defects in the cup itself.

Plaintiffs tried to then rely on the "read-and-heed" presumption -- i.e., the notion in some jurisdictions that the jury can presume that if an adequate warning had been given it would have been heeded. Such a presumption may aid a defendant when a warning was given.  Plaintiffs often try to use the presumption to attempt to clear the causation hurdle when no warning is given.  But the presumption does not completely dispose of the causation issue in a failure-to-warn case, said the court. The most the presumption does is establish that a warning would have been read and obeyed. It does not necessarily establish that the defect in fact caused the plaintiff's injury. The plaintiff invoking the presumption must still show that the danger which allegedly would have been prevented by an appropriate warning was the danger that actually materialized in the plaintiff's case.  

Plaintiffs could not show that element, given the circumstances of the drug usage. The judgment of the trial court granting summary judgment in favor of the cup defendants was affirmed. 

 

Motion To Dismiss Filed in Combination Aspirin MDL

Bayer Healthcare LLC moved last week to dismiss the master complaint in the federal MDL involving combination aspirin products. In Re: Bayer Corp. Combination Aspirin Products Marketing and Sales Practices Litigation, No. 1:09-md-02023 (E.D. N.Y.). Aspirin has been sold in the United States for more than a hundred years; a daily regimen of low-dose aspirin is widely recognized as useful in preventing heart attacks and strokes.

Plaintiffs are consumers who claim to have purchased Bayer combination aspirin and dietary supplement products. They do not claim that they were injured by these products or that the products were ineffective. Instead, plaintiffs seek damages because they say they would not have purchased these products if they had known that Bayer, instead of submitting a New Drug Application (“NDA”) for each of these combination products, relied on the preexisting separate regulatory review of aspirin and the supplements. Plaintiffs allege that Bayer misled and deceived
consumers into believing that the products had been proven to be safe and effective for their marketed purposes.
 

The Motion argues that plaintiffs’ claims fail, first, because they are, in essence, private attempts to enforce the FDCA, 21 U.S.C. §301 et seq.  MassTortDefense notes that courts have repeatedly refused to construe such private attempts to enforce the FDCA as valid state law causes of action like the plaintiffs have brought in this litigation. Under the FDCA, the United States government has the exclusive power to enforce the FDA’s regulatory requirements (which include provisions relating to the approval of new prescription and over-the-counter drugs, as well as regulation of dietary supplements and food additives). The FDCA provides that “[a]ll such proceedings for the enforcement, or to restrain violations, of this Act, shall be by and in the name of the United States.” 21 U.S.C. § 337(a) (2009).

Even if a state were to recognize it, a cause of action based on a failure to obtain FDA approval would be preempted as interfering with the FDA’s approval processes. Courts have repeatedly held that private plaintiffs fail to state a claim where they, in essence, seek redress for a violation of the FDCA. Courts have applied this doctrine to dismiss a variety of causes of action, from RICO and the Lanham Act, to state law unfair competition and consumer fraud act claims. See, e.g., Mylan Labs. v. Matkari, 7 F.3d 1130, 1139 (4th Cir. 1993) (dismissing Lanham Act claim); In re Epogen & Aranesp Off-Label Mktg. & Sales Practices Litig., 590 F. Supp. 2d 1282, 1290 (C.D. Cal. 2008) (dismissing state consumer fraud and false advertising and RICO claims); Ethex v. First
Horizon Pharm. Corp
., 228 F. Supp. 2d 1048, 1055 (E.D. Mo. 2002) (dismissing deceptive trade practices claims and Lanham Act claim).

Additionally, defendant argues that plaintiffs, who do not claim harm or that their products did not work, have not alleged a cognizable injury. Accordingly, plaintiffs have not stated a claim for any of the causes of action they have brought. Under Fed. R. Civ. P. 12(b)(6), a complaint must be dismissed if it fails to articulate grounds upon which relief can be granted. Under Rule 8(a), a plaintiff’s obligation to provide the grounds of his entitlement to relief requires more than labels and conclusions, and a formulaic recitation of the elements of a cause of action will not do. Bell Atlantic Corp. v. Twombly, 550 US 544, 555 (2007).   The Supreme Court recently reaffirmed these principles in Ashcroft v. Iqbal, 129 S. Ct. 1937 (2009).

These standards apply to injury and loss requirements as well as to other elements of a claim. As the Second Circuit recently explained, to state a claim for relief, a plaintiff must do more than simply allege an injury or loss – that theory must be “plausible.” McLaughlin v. American Tobacco Co., 522 F.3d 215, 227 (2d Cir. 2008). Legally cognizable theories of injury must also not require a court to “engage in a series of speculative calculations to ascertain whether, or in what amount, plaintiffs suffered a loss.” Id. at 230.  Like many convoluted consumer fraud actions, plaintiffs' claims here fail to allege a plausible theory that is open to private plaintiffs.
 

 


 

 

State Supreme Court To Address Government Use Of Contingency Fee Private Counsel

Next month the Supreme Court of Pennsylvania will hear argument in a pharmaceutical case that has implication for all readers of MassTortDefense, regardless of what industry they may represent. See Commonwealth of Pennsylvania, C/O Office of General Counsel v. Janssen Pharmaceutica, Inc., No. 24 Eap 2009 (S.Ct. Pa.).  This case presents not only significant constitutional and statutory issues, but also impacts policies affecting the public interest in open government, health care policy, and the regulation of the practice of law in the context of governmental litigation.

In the underlying case, the Commonwealth seeks damages for asserted financial harm allegedly caused by Janssen’s supposed deceptive marketing practices in promoting its anti-psychotic drug, Risperdal, for off-label uses. This action was originally filed in the Court of Common Pleas of Philadelphia County in February 2007. In June 2008, Janssen filed a Motion to Disqualify Plaintiff’s Counsel, the private Texas-based plaintiff personal injury firm of Bailey Perrin & Bailey, which had been hired by the state on a contingency fee basis.   Public records indicate that during the precise time period that the fee contract was negotiated and executed, one of Bailey Perrin’s founding partners made repeated and significant contributions, totaling more than $100,000, to Pennsylvania Governor Rendell’s re-election campaign and to the Democratic Governors Association, according to defendant.

The Commonwealth opposed the Motion; the trial court denied the Motion on December 8, 2008. Janssen thereafter sought extraordinary appellate relief in the state Supreme Court, which was granted.

The Commonwealth’s retention of contingent fee private counsel in this matter raises significant issues including whether and when state law authorizes the Office of General Counsel to enter into a contingent fee contract with outside counsel; whether the Commonwealth’s hiring of outside litigation counsel on a contingent fee basis violates the state constitution, including the separation-of-powers mandate of the Pennsylvania Constitution; and whether the Commonwealth’s hiring of outside litigation counsel on a contingent fee basis violates the due process rights of the defendant company.

In many contexts, the legal policy of the Commonwealth -- like many states -- strongly favors open, competitive bidding for contracts involving state funds. Such requirements, included in the state Constitution and various statutes, are designed to prevent fraud, eliminate bias and favoritism, and thus protect vital public interests.

Those same goals of open and good government reside in the requirement that state officials give their undivided loyalty to the people of the Commonwealth. The antithesis of these goals and policies is “pay-to-play,” the award of government contracts to major campaign contributors. This case threatens to expand the scope of pay-to-play in unprecedented fashion. The very sovereignty of the Commonwealth itself – its legal enforcement authority and parens patriae powers – should not be subject to sale. Public records reveal hundreds of thousands of dollars of contributions to the benefit of the state governor in close proximity to the issuance of a no-bid, contingency fee contract to one of the contributors, according to defendant.  The media has widely and correctly assailed the appearance of impropriety thus created.


Aside from its questionable origins, the contingent fee contract violates the core principle that attorneys pursuing actions on behalf of the Commonwealth represent a sovereign whose obligation to govern impartially is essential to its right to govern. Government attorneys must exercise independent judgment as a ministers of justice and not act simply as advocates. The impartiality required of government lawyers cannot be met here, where the private pecuniary interest inherent in the contingent fee is the primary motive force behind the bringing of this very action. By turning over sovereign prosecutorial power to contingency counsel, the Governor effectively created a new branch of government – motivated by the prospect of private gain rather than the pursuit of justice or the public welfare.

This subversion of neutrality does more than implicate the due process rights of those confronting such tainted prosecutions. Direction of state prosecutions by financially interested surrogates also damages the very public interest that such litigation is supposed to advance. Here, it is already clear that Pennsylvania’s in-force health care policies concerning the use of atypical anti-psychotic medications dramatically conflict with the reckless allegations of contingent fee counsel’s complaint. Those (typical plaintiff) allegations broadly equate all “off-label” use of prescription drugs with “medically unnecessary” use, and blindly assert that all such “medically unnecessary” use is “illegal.” The law, however, recognizes off-label use as generally accepted by the medical community and the FDA, and as perfectly legal, and does not consider prescription drugs unsuitable for use merely due to lack of FDA approval. The allegations of the complaint – crafted more for the pecuniary goals of counsel than for the needs of the patients served by the affected state programs – risk the public health by threatening to deprive some of our neediest citizens of a medicine that the Commonwealth’s own unbiased administrators consider “preferred” for the same off-label indications that the complaint brands “illegal.”

It will be interesting to see how the Supreme Court approaches these significant issues int he coming weeks.

[Your faithful blogger was able to contribute to the amicus brief of the Washington Legal Foundation , the public interest law and policy center, in this matter.]

Canadian Court Rejects Pharmaceutical Class Action

We have posted before about just how difficult Canada is becoming as a jurisdiction for class actions defendants, particularly companies in the pharmaceutical industry. Frequently, identical consumer products, drugs, and medical devices are marketed in Canada as well as the U.S.  When a product is recalled, or new science suggests risks in a product leading to American product liability and mass tort litigation, Canadian plaintiff attorneys have not been bashful about bringing copycat litigation, borrowing from U.S.-conducted theories and discovery.

A ray of hope to the north?  The Quebec Superior Court last week declined to certify (authorize is the term they use) a class action for Canadians claiming to have experienced side effects from the use of GlaxoSmithKline Inc.’s antidepressant Paxil.  This is the first time a Quebec court has rejected a class action involving a prescription pharmaceutical product -- ever as far as we can tell. See Goyette v. GlaxoSmithKline Inc., Quebec Superior Court, No. 500-06-000157-020 (8/17/09).

Plaintiff sought to represent a national class of Paxil users. Three issues were prominent: Did the claims of the class members raise identical, similar or related questions of law or fact?  Did the facts alleged seem to justify the relief sought? And was the plaintiff an adequate class representative?  Importantly, at the time of the complaint, the class rules required plaintiff to submit a supporting affidavit (on which she was cross-examined).  Since that time, Quebec has sought to minimize the amount of factual material presented to the court in support of class certification (making opposition a bit more difficult).

The first issues sounds like the commonality aspect of U.S. class procedure. GSK argued that the highly subjective nature of the alleged symptoms in the present case, such as headaches, nausea, vertigo, the infinite variations on the symptoms, and the intensity and duration are so subjective that they cannot be decided collectively and so cannot satisfy the common question element.  Nevertheless, the court found that while the claim for exemplary damages was not common, there were common questions concerning the warnings GSK had given.

However, even in the absence of a true predominance requirement, some Canadian courts will look at whether and what issues will require individual determination. Here, the court agreed that the underlying question is whether allowing the suit to proceed as a representative one will avoid duplication of fact-finding or legal analysis. Thus an issue will be “common” only where its resolution is necessary to the resolution of each class member’s claim. The court found that if  "a class action were permitted here, there would be no saving in judicial time since there is no real common question and each case must be litigated on its on merits."  The court noted that each year there was a different set of information in the CPS (Canadian PDR), and accordingly, there would be different sub-classes depending on changes in the relevant wording in each of the years.

Similarly, in this case, civil liability must be determined by assessing the specific risks disclosed for each individual patient which risks vary depending on multiple factors:

 a) whether the adverse effects occur during the use of the product and lead to discontinuation;

 b) whether adverse effects follow discontinuation;

c) whether the user was advised prior to use, by either their physician or pharmacist, of whether they may experience dependency or withdrawal symptoms;

d) whether the symptoms suffered were described in the C.P.S. (PDR);

e) whether the symptoms were not described in the C.P.S. but are proved to be directly related to the use of Paxil; or

f) to the extent that the symptoms arose following discontinuation, whether such symptoms were "mild and transient" and were described in the C.P.S.

Next, the court determined that the facts alleged do not support the relief requested. All of the symptoms that Ms. Goyette alleges to have experienced were mentioned by GSK in the C.P.S. and that any fault must have been through the misreading of the C.P.S. by Ms. Goyette's prescribing physician.  And she made no specific allegations about the injuries of the absent class members.  Accepting as true the well-pleaded allegations, in essence, the facts that are taken as proven do not include impressions, opinion, legal argument, inferences or hypotheses that are not verified.

Finally, adequacy of representation is evaluated on three criteria:

 1- an interest in undertaking the legal proceedings;

 2- an ability to instruct counsel; and

 3- absence of a conflict with the other group members.
 

Based on the previous analysis, the court found that Ms. Goyette could not represent a class since she herself does not have a valid cause of action.  Moreover, plaintiff had shown a singular lack of interest in that she never sought to speak with any of the other members of the proposed class, none of whom she knows; she has never sought to communicate with any of the individuals alleged to have signed up at her attorneys' website; and she could provide no explanation as to why these legal proceedings which started on May 2, 2002 remained dormant for several years.

An analysis with a little bit of teeth.
 

Federal Court Dismisses Trasylol Class Action Complaint

A federal judge in Florida has dismissed the class action claims of plaintiffs asserting economic loss from Bayer's drug Trasylol, ruling that they have failed to adequately plead that their alleged damages flowed directly from the company's alleged conduct in marketing the drug. See Southeast Laborers Health and Welfare Fund, et al. v. Bayer Corporation, et al., 2009 WL 2355747 (S.D. Fla.).

Trasylol was approved by the U.S. Food and Drug Administration to prevent excessive bleeding during coronary artery bypass graft (CABG) surgery. The plaintiffs, including a health and welfare fund responsible for paying for members' prescription drugs, allege that cheaper and safer alternatives were available but that Bayer somehow "over-promoted" the drug for CABG use.  They also allege the company promoted it for unapproved off-label uses, such as orthopedic surgery. They say, bottom line, that they would not have paid for Trasylol had they known the true story.

Such claims are typical of the consumer fraud act claims of plaintiffs in drug litigation, and equally typical is the fact that calculation of plaintiff's alleged losses would be extremely difficult, fact intensive, and absent such facts, purely speculative. Plaintiff must allege the causation element of the claim, and even the requisite short and plain statement of the claim requires more than labels and conclusions, and more than a formulaic recitation of the elements of a cause of action. (citing Twombly, 550 U.S. at 555 ).

In a causation analysis that applies to both the consumer fraud act and RICO allegations, the court noted that there are many factors that a doctor may consider in determining what medication to administer to a given patient. Doctors are presumed to, and actually do, go beyond advertising and marketing and also use their independent knowledge in making medical decisions. Loss calculation, therefore, necessarily would require an analysis of whether or not a particular physician ever received or relied on Bayer's allegedly fraudulent statements, and whether or not a physician, knowing the risks vs. benefit of Trasylol, would still have used it during an operation.

It would require a determination as to how many doses a patient received, and whether or not the number of doses was tied into any fraudulent marketing. It would also require speculation as to what alternative medications a particular physician would have ordered in a particular surgery, and how much that medication would have cost. Such a cost calculation would be problematic, as costs clearly would have fluctuated over the ten year period. Lastly, it would entail determining those patients who received Trasylol who did not suffer any adverse reactions, and who might have been helped by the use of the drug. Plaintiffs plead none of those facts.

The plaintiffs here attempted to rely on a "fraud on the market" theory to avoid this analysis, citing In re Zyprexa Prod Liab. Litig., 493 F.Supp.2d 571 (E.D. N.Y. 2007), but the court called this "simply misplaced." The fraud-on-the-market doctrine in both the Eleventh and Third Circuits has been held to be limited strictly to securities cases and is inappropriate in claims alleging deceptive advertising such as the ones presented by drug litigation.   

Further, on the RICO count, the court said that the plaintiffs' factual allegations were not sufficient to constitute a representative sample of the defendants' allegedly fraudulent acts, when they occurred and who engaged in them.

Judge Middlebrooks granted the plaintiffs leave to amend but said it was "unlikely" they would be able to cure the proximate causation deficiency in their claims.

 

 

 

Senator Writes Letter To NIH About "Ghostwriting"

Plaintiffs in pharmaceutical and other biomedical litigation have frequently resorted to allegations of “ghostwriting” to attack various aspects of scientific articles that defendants seek to rely on.  “Ghostwriting” is a somewhat pejorative term used to vilify some versions of a common practice – the use of biomedical communications companies to provide professional assistance in medical research and/or writing. Plaintiffs often imply that the named author had little or nothing to do with the direction or content of the article.

Several courts have rejected such generally overblown allegations. In the HRT litigation, In re Prempro Products Liability Litigation, 554 F. Supp.2d 871 (E.D. Ark. 2008), the court noted that while plaintiff focused heavily on the evidence that Wyeth collaborated with authors to have articles written about HRT, there was no evidence that this practice is inappropriate or that Wyeth supported articles that it knew were false or misrepresented the science. Rather, the articles supported Wyeth’s position on the state of the science. Additionally, there was evidence that ghostwriting was a common practice in the industry.  Similarly, in In re Seroquel Prods. Liab. Litig., No. 6:06-md-1769-Orl-22DAB, slip op. at 3-5 (M.D. Fla. Jan. 30, 2009), Judge Conway held that plaintiffs could not use the words "ghostwriting" or "plagiarism" to characterize the process by which articles were written.

A “ghostwriter” may:
– Analyze data
– Research issues, gather review data
– Organize/format materials
– Assist in writing by, e.g., drafting publications

Such third-parties can save busy scientists time and effort- by doing time-consuming preliminary tasks. Having medical communications specialists involved can make the articles easier to read, more informative The fact is, a great doctor does not mean a great writer; outside writers can expedite publication and eliminate artificial drag in the process.

Nevertheless, Senator Charles E. Grassley, an Iowa Republican, has written a letter to NIH asking for information about possible ghostwriting:
I1) What is the current NIH policy on ghostwriting with regards to NIH researchers?  2) What is the current NIH policy on ghostwriting with regards to NIH grantee institutions? 3) What is the current NIH policy on ghostwriting with regards to primary investigators of NIH grants? 4) Has NIH received any complaints about individual grantee institutions, primary investigators and/or NIH researchers regarding possible ghostwriting, and if so how has NIH handled these complaints? 5) What is the current NIH policy regarding primary investigators found to have violated medical ethics and/or have medical licenses that have been suspended or revoked?

The response, when it comes, may be significant because the N.I.H. underwrites much of the country’s medical research. Many doctors depend on federal grants to support their work, and attaching fresh conditions to those grants could influence new publication guidelines more broadly.

In reality, typically, the named author has access to all data. The authors can reorganize the presentation of the data and edit the article. The articles are subjected to extensive peer review before publication, often in journals the author selects.  In litigation, the plaintiff’s prescriber may not have read or relied on any such articles. And doctors who prescribe are well familiar with the industry practice and custom. Plaintiff’s “ghostwriting” claims also fail to offer proof that the articles which were, in any event, peer-reviewed and medically sound, affected the FDA’s actions.

Any debate on “ghost writing” of medical publications ought to include an understanding of the realities of supply and demand for published research, of the time pressures, needs, and priorities of leading researchers, and the evidence demonstrating the author's control over final publication.

Readers of MassTortDefense interested in these issues should look at the International Committee of Medical Journal Editors' Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication;  the American Medical Writers Association's Position Statement and Code of Ethics; and the  World Association of Medical Editors' Policy Statement on Ghost-writing Initiated by Commercial Companies.

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FDA Commissioner Outlines New Enforcement Plans

Readers of MassTortDefense know how FDA actions can instigate and affect potential mass tort litigation involving drugs and devices. Last week, in a presentation to the Food and Drug Law Institute (FDLI), new FDA Commissioner Margaret A. Hamburg revealed that the FDA will implement procedural reforms designed to allow the agency to act more quickly and aggressively on the enforcement of food, drug, and medical device regulations. The FDA commissioner told FDLI that the federal watchdog will be a leaner and meaner organization under her leadership.


In her remarks, the Commissioner noted that while impressed by the commitment to compliance that many companies have made – both in terms of their corporate culture and their investment in compliance systems -- her goal is for all companies to make and implement such a commitment in order to prevent harm to the public. A key part of the strategy to support private sector compliance is more effective enforcement against violations of the law. She suggested that such enforcement helps industry too – by maintaining a level playing field for safe products. Making sure that offenders are held legally accountable prevents companies from having to choose between doing the right thing and staying competitive.

An effective enforcement strategy depends on several key elements she said:

  • The FDA must be vigilant. Through regular inspections and follow-up on signals indicating problems, the FDA must work to identify and resolve problems early. Companies must have a realistic expectation that if they are crossing the line, they will be caught, and that if they fail to act, FDA will.
  • The FDA must be strategic, she continued. The agency must place greater emphasis on significant risks and violations, and use meaningful penalties to send a strong message to discourage future offenses.
  • The FDA must be quick. The agency must be able to respond rapidly to egregious violations or violations that jeopardize public health.

More specifically, she said the pathways for enforcement action can be too long and arduous. To address this, the FDA will set post-inspection deadlines. When the FDA finds that a firm is significantly out of compliance, it will expect a prompt response to the findings, generally no more than fifteen working days before the FDA moves ahead with a warning letter or enforcement action.

Second, the FDA will take steps to speed the issuance of warning letters. There will be a new policy to limit warning letter review to significant legal issues.

Third, the FDA will work more closely with regulatory partners to develop effective risk control and enforcement strategies. In many food safety cases, for example, local, state, and international officials have more authority to take action quickly than the FDA.

Fourth, the FDA will prioritize enforcement follow-up. After a warning letter is issued or a major product recall occurs, FDA will make it a priority to follow up promptly with appropriate action, such as an inspection or investigation to assess whether or not a company has made required changes in its practices.

Fifth, she said, the FDA will no longer issue multiple warning letters to non-compliant firms before taking enforcement action. And, in the case of significant health concerns or egregious violations, FDA will consider immediate action – even before issuing a formal warning letter.

Finally, the FDA is developing a formal warning letter “close-out” process. If the FDA can determine, usually based on a re-inspection, that a firm has fully corrected the violations raised in a warning letter, it will provide to the firm a “close-out” letter, indicating that the issues in the warning letter have been successfully addressed. One can imagine how the obtaining or failure to obtain a close-out letter may be anissue in litigation.
 

State Court Excludes Plaintiff's Causation Expert Under Frye Test

A Minnesota appeals court recently affirmed summary judgment for defendants in a suit by a woman who alleged hormone replacement drugs caused her breast cancer. Zandi v. Wyeth, 2009 WL 2151141 (Minn.App.)

Plaintiff alleged that between approximately 1981 and 2001, she ingested hormone-replacement-therapy (HRT) drugs manufactured, designed, packaged, marketed, and distributed by defendants.   In November 2001, Zandi was diagnosed with "hormone-dependent breast cancer."  She contended that the HRT drugs caused her cancer.  She brought claims for negligence, strict liability, breach of implied warranty, breach of ex-press warranty, fraud, misrepresentation, and violation of the Minnesota fraudulent advertising act, the Minnesota Prevention of Consumer Fraud Act, and the Minnesota Uniform Deceptive Trade Practices Act.


The trial court  found that plaintiff's specific causation evidence did not satisfy Minnesota's standard for admissibility of expert testimony.  Zandi offered testimony from Dr. Lester Layfield and Dr. Gail Bender to prove that HRT drugs caused her cancer. Minnesota courts use the Frye standard to determine the admissibility of novel scientific evidence. Goeb v. Tharaldson, 615 N.W.2d 800, 814 (Minn.2000). Under Minnesota's version of this standard, the proponent of scientific evidence must establish that the scientific theory is generally accepted in the relevant medical or scientific community and that the principles and methodology used are reliable.  McDonough v. Allina Health Sys., 685 N.W.2d 688, 694 (Minn.App.2004). When novel scientific evidence is offered, (1) the trial court must determine whether it is generally accepted in the relevant scientific community; (2) the particular scientific evidence in each case must be shown to have foundational reliability.

Zandi's claims were based on the following propositions: 1) it is generally accepted that HRT causes hormone-dependent breast cancer, and 2) there is a generally accepted method of diagnosing the cause of hormone-dependent breast cancer in an individual.  The appellate issues revolved around the second.  Defendants alleged that even if one assumes the relevant scientific community generally accepts that HRT causes hormone-dependent breast cancer, Zandi had failed to establish that the relevant scientific community generally agrees that there is a method of diagnosing the cause of breast cancer in a particular person.

Plaintiff's experts based their specific causation opinions on epidemiological studies and differential diagnosis. But  the science of epidemiology does not address the cause of an individual's disease. Epidemiology is concerned with the incidence of disease in populations and does not address the question of cause of an individual's disease. Epidemiology has its limits at the point where an inference is made that the relationship between an agent and a disease is causal (general causation) and where magnitude of excess risk attributed to the agent has been determined; that is, epidemiology addresses whether an agent can cause disease, not whether an agent did cause a specific plaintiff's disease. See Green et al., Reference Guide on Epidemiology, in Reference Manual on Scientific Evidence 333, 381-82 (Fed.Jud.Ctr.2d ed.2000).

Plaintiff's experts also relied on differential diagnosis. As used by plaintiffs, differential diagnosis adopts a process of elimination to identify cause; it  seeks to eliminates the possibility of competing causes or confounding factors. Goeb, 615 N.W.2d at 815.  In performing a differential diagnosis, a physician begins by ruling in all scientifically plausible causes of the patient's injury. The physician then rules out the least plausible causes of injury until the most likely cause remains.  Yet, breast cancer does not lend itself to such a differential diagnosis because the scientific community has not accepted that breast cancer has a limited number of discrete and recognized possible causes such that ruling out one cause would implicate another. For differential diagnosis to be sufficiently reliable to prove causation, the diagnostician should rule out all other hypotheses, or at least explain why the other conceivable causes are excludable.

Additional risk factors that plaintiff failed to adequately account for here included family history. Indeed, plaintiff's experts suggested that it is possible to conduct a reliable differential diagnosis without ruling out other hypotheses.

On this record, the court said, “We conclude that there is not a method of diagnosing the specific cause of a particular woman's breast cancer that is generally accepted in the relevant scientific community. This reality leaves Zandi without a legally sufficient ability to prove specific causation.”
 

Presidential Memo On Preemption Sends A Warning

Along with my partner Andy Gaddes, I taught a recent CLE seminar on products liability issues.  One of the topics the attendees -- in-house counsel from a variety of industries -- were most interested in was President Obama's May, 2009 memorandum to federal agencies reversing the Bush administration's well-reasoned preemption policy.
 
The new policy is contained in a memo, not a formal executive order, but it clearly expresses a new view of preemption. Cloaked somewhat ironically in the guise of "state's rights", the policy comes from an administration that apparently has no trouble expanding the role of the federal government in unprecedented ways, taking over the auto companies, banks, and others.
 
The memo provides that heads of departments and agencies should not include in regulatory preambles statements that the department or agency intends to preempt State law through the regulation except where preemption provisions are also included in the codified regulation.  Heads of departments and agencies should not include preemption provisions in codified regulations except where such provisions would be justified under the Administration's new interpretation of the legal principles governing preemption.  Finally, heads of departments and agencies should review regulations issued within the past 10 years that contain statements in regulatory preambles or codified provisions intended by the department or agency to preempt State law, in order to decide whether such statements or provisions are justified under the new interpretation of the applicable legal principles governing preemption.
 
The legal basis of the doctrine is not really that malleable. Federal preemption is derived from the supremacy clause of the Constitution that says federal law is the supreme law of the land and any conflicting state law or regulation is without effect.  The policy basis of the doctrine is equally clear: allowing each state to set diverse and individual safety standards can undercut needed uniformity and can subject manufacturers to expensive, unfair, and confusing requirements. It forces product sellers to potentially navigate a confusing, often contradictory patchwork quilt of up to 50 sets of laws and regulations.  Of course, the preemption issue affects more than traditional administrative regulation by the states: companies may become subject to regulation by litigation at the hands of the plaintiffs' bar. 
 
The new policy has the potential to create a real chilling effect in agencies that should be clear about the preemptive intent and reach of their regulations.  While the Obama administration claims its approach breaks no new ground, it may well fundamentally weaken the federal government's ability to address problems on a national level and thus may have untended consequences by allowing states to interfere with parts of the Obama administration's domestic agenda. Regulations for health care and climate change, for example, arguably cannot work absent preemption.
 
Preemption has been applied to drugs and medical devices, vehicular roof crush standards issued by the National Highway Traffic Safety Administration, mattress flammability standards issued by the Consumer Product Safety Commission, pesticides regulated by the EPA and a variety of other products.  A majority of the regulations containing preemptive language were issued by the FDA and NHTSA.   
 

 

State Supreme Court Issues Design Defect Ruling On Intrinsic Characteristics

The Wisconsin Supreme Court has affirmed a lower court's dismissal of strict liability and negligence claims against white lead carbonate pigment manufacturers, ruling that a product's characteristic ingredient cannot  constitute a design defect. See Ruben Baez Godoy v. E.I. du Pont Nemours and Co. et al., No. 2006AP2670 (Wisc. S.Ct.).

The court affirmed a circuit court's ruling that the complaint had failed to allege a design feature that rendered defective the design of white carbonate lead pigment, which can be found in white paint.
Plaintiff alleged lead poisoning from white lead carbonate pigment in the paint in his Milwaukee apartment, and sued DuPont, Armstrong Containers, Sherwin-Williams and American Cyanamid.
He asserted that despite alleged knowledge that lead is hazardous to human health, the manufacturers promoted the use of the pigment and marketed it as safe.

The lower court dismissed the design defect claims, finding  that lead is an inherent  characteristic of white lead carbonate, and thus the product cannot be designed without lead. The court of
appeals found that a product cannot be said to be defectively designed when that design is inherent in the nature of the product so that an alternative design would make the product something else.  This is the long-standing, but often misunderstood notion, that an alternative product is not an alternative design.  In those states in which a plaintiff must prove the existence of a feasible alternative design that would have avoided the injury, or in which the defendant may show the absence of any feasible alternative design, it is not enough for a plaintiff to point to a different product that might serve the same use. 

The state Supreme Court affirmed, noting that a claim for defective design cannot be maintained where the presence of lead is the alleged defect in design, and its very presence is a characteristic of the product itself.  Without lead, there can be no white lead carbonate pigment.  The court offered an analogy:  Foil for your kitchen use can be made using ingredients other than aluminum (gold, for example), but aluminum foil cannot be made without aluminum. The presence of aluminum is characteristic of aluminum foil. If the mere presence of aluminum posed a danger, a manufacturer might be liable based on the failure to adequately warn or other claims. However, the manufacturer
would not be liable based on the "design" of aluminum foil for including aluminum.

Interestingly, the court reaffirmed that Wisconsin strict products liability law does not require a
plaintiff to prove the feasibility of an alternative design.  However, the feasibility of an alternative design can be considered when evaluating a design defect claim. While plaintiff argued that it is inconsistent to reject a reasonable alternative design requirement and still maintain that characteristic ingredients of the product cannot support a claim for defective design, the court clarified that it was not requiring that a plaintiff affirmatively prove, through expert testimony, that an alternative design was commercially viable. The court was simply acknowledging that some ingredients cannot be eliminated from a design without eliminating the product itself. When the ingredient cannot be designed out of the product, the Restatement (Second) instructs that although other claims may be theoretically asserted, the proper claim is not design defect.  

That rationale would seem to apply to design defect claims in drug cases, where the characteristics of a chemical constituting an FDA-approved drug are challenged. The "design" of a typical drug cannot be changed without creating a different molecular structure, and hence  a different product, one which would require a second FDA approval.

JPML Declines to Consolidate Metoclopramide Litigation

Some have expressed the sentiment that the the Judicial Panel on Multidistrict Litigation always grants requests for MDL status.  In reality, that is not the case, although opposition to MDL status can be an uphill battle in burgeoning mass torts. (FYI Volume 82, Number 6 (June 2008) issue of the Tulane Law Review is devoted to "The Problem of Multidistrict Litigation." )

The JPML recently declined to consolidate federal litigation involving the heartburn medication metoclopramide, finding that the pending actions do not share sufficient factual issues concerning whether the drug causes neurological injuries. (In re Reglan/Metoclopramide Products Liability Litigation, MDL No. 2049, 6/3/09).

The Panel was not persuaded that Section 1407 centralization would serve the convenience of the parties and witnesses or further the just and efficient conduct of this litigation at the present time. The eleven actions at issue did share some factual issues as to whether the drug metoclopramide causes neurological injuries (principally, tardive dyskinesia). But there is no single common defendant, and some entities, are named in only one or two actions. Moreover, several of the actions appear to be substantially more advanced (five were commenced in either 2006 or 2007). Metoclopramide litigation thus has a somewhat lengthy history, and the record indicates that a significant amount of the common discovery has already taken place in some cases. The proponents of centralization failed to convince the Panel that any remaining common questions of fact among these actions are sufficiently complex and/or numerous to justify Section 1407 transfer at this time. Alternatives to transfer exist that may minimize whatever possibilities there might be of duplicative discovery and/or inconsistent pretrial rulings, concluded the Panel. 

FDA Issues New Draft Guidance on Presenting Risk Information

The FDA recently issued a new draft Guidance for Industry titled “Presenting Risk Information in Prescription Drug and Medical Device Promotion.”  This new guidance document represents a comprehensive and fairly detailed overview of the FDA’s approach to reviewing drug and device advertising, albeit with a somewhat surprising omission regarding Internet-specific guidance.

As readers of MassTortDefense know, promotional pieces: (1) cannot be false or misleading, (2) must reveal material facts, including facts about consequences, and (3) should present information about effectiveness and risk in a balanced manner. The guidance confirms that promotional pieces will be judged based on the “reasonable consumer” standard, essentially adopting the definition used by the Federal Trade Commission. Importantly, the FDA also adopts the FTC position that multiple interpretations of a claim are possible if they are all reasonable, and a violation will be found if any one reasonable interpretation violates regulations.

Finally, while the guidance acknowledges the different levels of expertise of consumers and healthcare professionals and notes that the FDA takes account the intended audience in determining compliance, the guidance specifically highlights the social science research finding that experts are “subject to the same cognitive biases and processing limitations as non-experts.”  As a result, it arguably gives insufficient credit to physicians’ abilities to understand important information and make appropriate prescribing decisions;  the recommendations listed in the guidance seemingly apply equally to promotional materials directed to consumers and healthcare professionals.

The general considerations the FDA will use in assessment include (1) use of language appropriate for the target audience, (2) appropriate use of signals (e.g., headlines, change of announcer), (3) appropriate framing of risk information (e.g., severity, specificity), and (4) hierarchy of risk information (i.e., most important risk information should come first).

More specifically, the FDA considers the quantity, materiality, and comprehensiveness of the risk information contained in the piece. Concerning quantity, the FDA notes that risk information should be comparable to benefit information and should include enough detail to convey an “accurate” impression of the product. Among the relevant factors are (1) the number of statements about benefits and risk, (2) the completeness and depth of detail about benefits and risks, (3) the amount of time or space devoted to benefits and risks, and (4) the use of components that enhance or distract from the presentation of risk or benefit information. In assessing materiality and comprehensiveness, the guidance notes that material risks are those that would influence a reasonable member of the target audience—often the most serious and the most frequently occurring risks.

Despite the guidance’s clear and intentional application to Internet advertisements, it makes no special mention of such advertisements and provides no specific guidance on issues unique to Internet promotion.

The comment period for this draft guidance ends August 25, 2009. Additional information, including information on how to submit comments, can be found here.

 

 

Court Refuses To Consolidate Class Action Into Lexapro MDL

A federal court last week rejected an attempt to consolidate a newly filed proposed class action over Lexapro and Celexa with the multidistrict litigation involving the drugs. In Re: Celexa and Lexapro Products Liability Litigation, MDL No. 1736 (E.D. Mo.).

Judge Rodney W. Sippel said in his ruling that plaintiffs had not demonstrated that consolidation would be appropriate. The MDL is currently comprised of 42 cases brought by individual plaintiffs who claim Lexapro or Celexa caused or induced a suicide or suicide attempt. In originally creating this MDL in 2006, the Judicial Panel on Multidistrict Litigation noted that the actions shared allegations relating to the safety of Celexa or Lexapro and the adequacy of Forest's warnings concerning the possible adverse effects of using the drugs, in particular, the potential for each product to induce its users to commit, or attempt to commit, suicide. The JPML recently declined to transfer two personal injury cases to the MDL because they involved injuries other than suicide.

The new suit, Universal Care, Inc., et al. v. Forest Laboratories, Inc., et al., on the other hand, involves allegations relating to Forest Laboratories Inc.'s marketing of the drugs, and economic damages allegedly caused from the sale of Celexa or Lexapro. Specifically, the new suit alleges violations of the Missouri Merchandising Practices Act and makes claims for unjust enrichment,  fraudulent concealment , and misrepresentation. The plaintiffs in this case claim that Forest engaged in improper promotional activities, causing third-party payors to reimburse patients and health care institutions for prescriptions of Lexapro and Celexa that were written for patients for whom the drugs were not indicated.

Moreover, the cases pending in the MDL are individual actions, not a putative class actions. The extensive discovery and motion practice relating to the alleged appropriateness of class-wide treatment and the adequacy of the class representatives are not part of the current MDL. These factors could significantly delay the progress of the MDL proceedings, prejudicing both the MDL plaintiffs and Forest. A final factor is that the MDL is already more than 2 years old, with significant pretrial proceedings already haven taken place.

Even in the MDL context, Rule 42 applies, and the court has discretion to assess the impact of allegedly common questions.  Consolidation is inappropriate if it causes confusion or leads to delay, inefficiency, inconvenience, or unfair prejudice to a party. E.g., EEOC v. HBE Corp., 135 F.3d 543, 551 (8th Cir. 1998).

Administration Releases Memorandum On Preemption

The Democratic assault on the preemption doctrine has taken its next step with the release last week by the White House of a Presidential memorandum which restricts federal agency statements on preemption and directs those agencies to review preemption pronouncements made in the past decade under the Bush Administration.


Ironically, the directive ostensibly rests on the grounds of States rights: noting State law and national law often operate concurrently to provide independent safeguards for the public, and that throughout our history, State and local governments have frequently protected health, safety, and the environment more aggressively than has the national government.  “An understanding of the important role of State governments in our Federal system is reflected in longstanding practices by executive departments and agencies, which have shown respect for the traditional prerogatives of the States,” argues the memorandum.

The memorandum comes two months after the Supreme Court’s ruling on preemption in the context of drugs in Wyeth v. Levine, and concurrently with democratic efforts in Congress to overturn Medtronic v. Riegel in the medical device context.


The memorandum sets for the general policy of the new Administration that preemption of State law by executive departments and agencies should be undertaken only with full consideration of the “legitimate prerogatives of the States and with a sufficient legal basis for preemption.” Specifically, it orders that agencies should not include in regulatory preambles statements that the department intends to preempt State law through the regulation except where preemption provisions are also included in the codified regulation. Also, agencies should not include preemption provisions in codified regulations except where such provisions would be justified under the (presumably re-assessed) legal principles governing preemption.

Finally, departments should review regulations issued within the past 10 years that contain statements in regulatory preambles or codified provisions intended by the agency to preempt State law, in order to decide whether such statements or provisions are justified under (again, re-interpreted) applicable legal principles governing preemption. Where the head of a department or agency determines that a regulatory statement of preemption or codified regulatory provision cannot be so justified, the head of that department or agency should initiate appropriate action, which may include amendment of the relevant regulation.


The memorandum is a political statement as much as a legal document, and is consistent with President’s Obama’s comments while a candidate. As it eventually evolves into specific agency statements and policy, it promises to create a hodge-podge regulatory quilt, under which business will struggle with product safety decisions which will comply with federal, national standards, be upheld in some state jurisdictions, but nevertheless be subject to review by lay juries in others.

 

Daubert Ruling In Zyprexa: A Lesson For Mature Mass Torts

Zyprexa is a mature mass tort, as the defendant has settled approximately 31,000 individual product liability lawsuits over the drug, which was widely used in the treatment of psychiatric disorders. The federal court overseeing the multidistrict litigation over Eli Lilly and Co.'s product has made an important ruling on a Daubert challenge to a plaintiff expert in 13 cases involving 20 of the remaining claimants. In re Zyprexa Products Liability Litigation, MDL No. 1596 (E.D.N.Y. May 12, 2009).

Plaintiffs proposed to call an expert to establish the specific causal relationship between the Zyprexa taken and the onset or worsening of their diabetes. After briefing and an extensive evidentiary hearing, Senior Judge Jack B. Weinstein granted Eli Lilly's motion to disqualify Dr. Stephen J. Hamburger, M.D. While the expert met the necessary educational and experiential qualifications warranting the admissibility of his expert opinions, the court found his testimony lacked sufficient scientific reliability.

The court noted that in longstanding and highly complex litigation (read mass tort), particular emphasis must be placed on the reliability and scientific validity of the expert's opinions. Particularly in a mature mass tort ("advanced stage" described the court) when the issues of the benefits and risks of the drug have been a focus of the scientific community for some time, precision with respect to the relevant scientific knowledge and its application to the facts of the individual cases is expected, said the court.

The record demonstrated to the court that this expert's opinions relied on "a subjective methodology, a fast and loose application of his scientific theories to the facts, and conclusion-driven assessments on the issues of causation in the cases on which he proposes to testify,” the order said. In particular, the court pointed to the opinion that Zyprexa supposedly has a direct adverse effect on cells essential to the body's production of insulin, even in cases in which there was no documented weight gain. This opinion was not based on sufficient facts or data, nor was it the product of a reliable method.

In applying this theory to the facts of the cases (the "fit" required by Daubert), the expert had been, in the view of the court, “shockingly careless” about the scientific facts in these cases, including whether weight gain preceded or followed the plaintiffs' use of Zyprexa, and whether there was any weight gain at all. When confronted with these issues, he merely "shrugged off" factual discrepancies in his analyses or shifted to new theories on the fly.

Significantly, the court correctly observed that other mass torts had been subject to a kind of junk science, and it it could not "permit a major pharmaceutical litigation to become the subject of the kind of 'rubber-stamp' expert opinions that have so marred mass litigations such as those involving asbestos and breast implants.”

Plaintiffs Denied Discovery In Class Certification Phase

The certification decision in a proposed class action may be the most important aspect of such litigation. Few certified class actions go to jury verdict (they settle), and, frequently, cases in which class certification is denied are dismissed without even named plaintiffs’ claims being adjudicated. Accordingly, the preparation for the class certification hearing/briefing is crucial. Both sides have important tactical decisions to make about the amount and nature of pre-certification discovery they wish to conduct. Discovery of named plaintiffs and absent class members, when available, can show important distinctions among the class members, which in turn demonstrate an absence of commonality, a predominance of individual issues, and manageability problems. Not infrequently, plaintiffs object to defendants’ attempted discovery as allegedly "going to the merits" and thus as inappropriate for the certification stage. In an interesting, recent little decision in the Ketek antibiotic litigation, the show was on the other foot.

Plaintiffs, who alleged the maker of the antibiotic Ketek fraudulently concealed the drug's dangers, were denied the right to depose various non-party witnesses at the certification stage of this litigation. Sergeants Benevolent Association Health and Welfare Fund v. Sanofi-Aventis U.S. LLP, 2009 WL 1181808 (E.D.N.Y., 4/30/09). The plaintiffs are employee benefit plans that paid for Ketek, known generically as telithromycin. The FDA approved Ketek in 2004 for treatment of three medical conditions. Plaintiffs assert that this approval was based in part on data generated in a study that allegedly “was contaminated by fraudulent activity.”

As part of class certification discovery, plaintiffs proposed to take the deposition of nine non-party witnesses, all of whom were involved with the challenged study and the FDA's approval of Ketek. The court found “unconvincing” plaintiffs' assertion that the proposed non-party depositions were necessary to establish common impact through a “loss of value” methodology; the court found that plaintiffs had misunderstood that methodology in the Zyprexa litigation, which they claimed to be mirroring. Second, the proposed non-party depositions were highly unlikely to produce or lead to evidence relevant to numerosity, typicality, or adequacy of representation. Evidence relating to the complexity of attempting to prove plaintiffs' civil RICO claim may be relevant to predominance and superiority, but plaintiffs need not actually prove their RICO claim, or conduct the discovery necessary to prove that claim, in order to make this showing. Third, defendants did not dispute that the evidence relating to the study was common to all members of the putative class. Thus, discovery postponed to merits phase.
 

White Paper Explains Detrimental Impact of Proposed Medical Device Anti-Preemption Bill

Much of the debate over the preemption doctrine, certainly in the media and even in many legal circles, has focused on the alleged inadequacy of the FDA to regulate drugs and devices, and the purported consequent  need to have state juries of lay people “police” the health industry. Comparatively little attention has been given to the other impacts of eliminating federal preemption.

A new white paper demonstrates that erasing this doctrine would decrease access to life-enhancing medical devices, increase health care costs, and reduce medical device industry employment. Congressional Democrats are seeking to do just this in the device context -- the Medical Device Safety Act of 2009 was crafted in response to the U.S. Supreme Court's 8-1 ruling in February, 2008 in Riegel v. Medtronic, upholding preemption for certain medical devices when the devices, and their warning labels, had been approved by the U.S. Food and Drug Administration.


The Economic Impact of Eliminating Federal Preemption for Medical Devices on Patients, Innovation and Jobs” was authored by Ernst Berndt, professor in applied economics at MIT's Sloan School of Management, and Mark Trusheim. They argue that among the effects of the bill would be:

 • Reduced patient access to products and the health benefits they provide

• Unreliable, variable patient access to products and the health benefits they provide as varying state regulations and tort liabilities discourage or eliminate products in some regions but not others

• Increased medical costs and lower net public health compared to what could be achieved with increased medical device innovation and product introductions

• Increased defensive medical practices by physicians to avoid possible litigation, raising health costs and exposing patients to greater risks from the added unnecessary procedures

• Reduction in the number of products being developed as manufacturers and their investors respond to greater uncertainty regarding product approval and economic sustainability

• Transfer of health regulatory decisions to untrained, non-expert juries who are exposed to only a biased fraction of the scientific fact base on which to base their decisions


The authors compare the bill to what happened with vaccines: from 1967 to 2004 the number of vaccine makers plummeted from 26 to 3, leading to reduced access, higher costs, no new products, shortages of existing products, a fragile vaccine supply chain, reduced employment and increases in preventable illness. Congress had to step in and take the vaccines out of the traditional tort system.

Under the bill, the authors note, state juries would be asked to render decisions regarding device safety and efficacy based on a limited range of information focused on individual risk versus broad benefit at a trial typically lasting at most several weeks. Allowing state tort suits to do this will place state juries in the position of replacing, by overriding, professionally trained federal regulators in evaluating and quantifying the risks of medical devices. And unlike federal regulators, state juries will not balance, perhaps not even consider, the benefits to those for whom the medical devices enhances health and quality of life -- who of course are not parties to the action.
 

FDA To Hold Meeting on Risk Communication Strategies

The Food and Drug Administration’s Risk Communication Advisory Committee will be holding a public meeting on April 30, 2009, and May 1, 2009, at the Center for Drug Evaluation and Research Advisory Committee Conference Room, in Rockville, MD. On both days the Committee will discuss the Agency’s draft risk communication strategic plan and will be asked for comment and further advice on strategic priorities for research on effective risk communication.

That draft plan describes FDA’s strategy for improving how the agency communicates about regulated products. The strategy is intended to guide program development and research planning in a dynamic environment where rapidly evolving technologies enable patients and consumers to become increasingly involved in managing their own health and well-being. FDA has been looking to improve how it produces communications about the risks and benefits of regulated products, as well as how it oversees those communications produced by regulated entities. For example, as the Internet and emerging technologies have both enabled and fed the public’s demand for greater transparency and communication frequency, the traditional waiting periods for FDA guidance have given way to communication in real time. Designing a contemporary risk communication strategy is key to FDA’s efforts to reposition itself to realize its potential for effective protection and promotion of health, enabled by 21st century knowledge and technology.

Effective communication supports both optimal use of medical products and safe consumption of foods to maximize health. The IOM report on The Future of Drug Safety: Promoting and Protecting the Health of the Public (2006) focused on drug safety, but also highlighted communication more generally, referencing FDA’s mission of helping the public get the accurate, science-based information it needs. In response to an IOM recommendation, FDA launched its Risk Communication Advisory Committee in 2007 to give advice about FDA’s risk communication approaches for all FDA-regulated products.

The FDA has begun to identify research needs in this area, including on the broad topics of:

  • When and what to communicate
  • Reaching the audience (dissemination)
  • Ensuring audience understanding
  • Motivating audiences
  • Evaluating effectiveness of communications
     

Preemption Decision in Wake of Levine

Much attention has been focused on what aspects of the preemption doctrine were restricted by the U.S. Supreme Court's recent decision in Wyeth v. Levine. A recent decision holds that claims that a drug was “unreasonably dangerous” and that no warning would have been adequate, are preempted. Longs v. Wyeth, 2009 WL 754524 (N.D. Ohio, 3/20/09). Plaintiff sued Wyeth and asserted strict liability and negligence claims concerning the diet drug Redux. Wyeth argued that plaintiff's claim that Redux was an unreasonably dangerous drug, for which no warning would have been adequate, directly conflicts with the FDA's authority to determine which drugs are sufficiently safe and effective to be marketed. The court affirmed its grant of summary judgment, finding that the strict liability and negligence claims related to pre-FDA approval were preempted by federal law, and that the claims that were not preempted failed on their merits.

The Court rejected plaintiff’s claim that Wyeth v. Levine called for reconsideration. In Wyeth, the Court considered the narrow issue of whether the FDA's drug labeling judgments preempt certain state law product liability claims premised on the theory that different labeling judgments were necessary to make drugs reasonably safe for use. The court noted that the Supreme Court emphasized that it was Congress' intent to have state law complement federal drug regulation because manufacturers may have superior access to information about their drugs, especially in the postmarketing phase as new risks emerge.

The instant case was distinguishable from Wyeth v. Levine because it did not involve a failure to warn claim, and because Levine arose out of the actions of the manufacturer post-FDA approval. A post-FDA approval duty is distinguishable from a manufacturer's duty prior to approval by the FDA, a circumstance that the Supreme Court did not explicitly address. Whatever Wyeth v. Levine may stand for regarding whether post-FDA approval claims are preempted, it does not purport to hold anything for pre-FDA approval claims, held the court.
 

State Appellate Accutane Decision Reverses Verdict

The New Jersey Superior Court issued an interesting decision in the Accutane litigation last week.  See  McCarrell v. Hoffman-La Roche, Inc., And Roche Laboratories, Inc., 2009 WL 614484 (N.J.Super.A.D.) (March 12, 2009).

Plaintiff alleged that as a result of taking Accutane for an acne condition, he developed inflammatory bowel disease ("IBD"). The IBD allegedly led to the surgical removal of his colon and other serious medical complications. A jury returned a verdict in plaintiff's favor on his product liability claim against Roche, but not on his consumer fraud claim, and awarded him compensatory damages.

By order dated May 2, 2005, the state Supreme Court had designated all pending and future statewide actions involving Accutane as a mass tort.  Thus, all Accutane cases, including plaintiff's lawsuit, were transferred to Atlantic County to be heard on a coordinated basis. Discovery in the state cases proceeded in tandem with discovery in the federal Accutane multidistrict ("MDL") litigation.

On appeal from the jury verdict, Roche specifically argued, inter alia, that the trial court erred in admitting the opinion testimony of plaintiff's causation expert Dr. Sachar because his methodology was unreliable and thus improper under  N.J.R.E. 702; and that the trial court denied Roche a fair trial in admitting the testimony about causality assessments based on Accutane ADEs, but in restricting the defense in presenting competing quantitative proofs to put the ADEs in context, including the actual number of Accutane users.

On the issue whether Dr. Sachar's causation testimony was sufficiently reliable in the field of scientific research to be admitted, the court noted that in New Jersey the standard of review of such
rulings under Rule 702 is a narrow one. "In reviewing a trial court's evidential ruling, an appellate court is limited to examining the decision for abuse of discretion."

On the merits, the defendant objected to the expert's heavy reliance on animal studies. The NJ  Supreme Court has previously recognized that animal studies can be an accepted scientific method to study the safety and efficacy of drugs.  Even though the dose administered in the animal studies was far different than the medicinal dose, "trained experts commonly extrapolate from existing data." Gen. Elec. v. Joiner, 522 U.S. 136, 146 (1997). In assessing the results of animal studies, which frequently involve high doses, experts should be careful to consider the dose-response differential between animals and humans. Magistrini v. One Hour Martinizing
Dry Cleaning
, 180 F. Supp. 2d 584, 593 (D.N.J. 2002), aff'd, 68 Fed. App'x. 356 (3d Cir. 2003). (Readers also know that the biological differences between commonly used animals such as rats and humans make the models inappropriate for many comparisons, regardless of dose.)

Defendants also challenged the use of anecdotal case reports as a basis for the causation opinion. The court recognized that "[c]ausal attribution based on case studies must be regarded with caution." Federal Judicial Center, Reference Manual on Sci. Evidence 497 (2d ed. 2000).
That is so because case reports typically reflect reported observations, and do not themselves contain scientific analyses. For instance, case reports may lack controls, may fail to screen out alternative causes, and may omit relevant facts about the patient's condition that can be pertinent to a causation assessment. Consequently, a number of courts have concluded that anecdotal case reports are not a scientifically reliable basis for an expert's opinion on causation.

Nevertheless, some other courts have allowed consideration of case reports as an acceptable basis for trying to show causation, particularly when accompanied by other reliable scientific evidence. New Jersey courts have previously upheld the admission of expert testimony that has relied, at least in part, upon case reports or comparable anecdotal evidence. The court also found significant that the case reports here included dechallenge and rechallenge reports. Dechallenge and rechallenge reports are a type of case report. Dunn v. Sandoz Pharms. Corp., 275 F. Supp. 2d 672, 682 (M.D.N.C. 2003). Such reports have limitations, but have been considered useful in some contexts in ascertaining causation because they measure a patient's reaction to a drug, said the appellate court.  (Readers will note that the dechallenge/rechallenge concept appears to make little sense when the effect of the drug is supposedly a permanent disease!)

The New Jersey court recognized it was issuing a causation decision contrary to the ruling in the Accutane MDL.  The state court declined to follow the federal court's decision because (1) the causation expert in the federal case was not Dr. Sachar, and that particular expert's methodology was not as "demonstrably sound" as that of Dr. Sachar; (2) the standards for expert admissibility under N.J.R.E. 702 are not identical to F.R.E. 702; and (3) the testimonial record in this case, having proceeded to trial, was more developed than it was in the Florida case on a pretrial motion, lending greater confidence to a conclusion to sustain the trial judge's decision to admit Dr. Sachar's testimony.

Defendant also challenged the expert's testimony about the company's alleged intent and motive and mind-set, a typical plaintiffs' tactic in mass torts.  Totally improper, highly prejudicial, and ignored by some courts because they seem overwhelmed by the plaintiff's characterization of the defendant's conduct.  Well-reasoned opinions exclude such testimony. See In re Baycol Prods. Litig., 532 F. Supp. 2d 1029, 1053 (D.Minn. 2007) (observing that "[p]ersonal views on corporate ethics and morality are not expert opinions"); In re Rezulin Prods. Liab. Litig., 309 F. Supp. 2d 531, 546 (S.D.N.Y. 2004) (holding that the objected-to opinions of expert witnesses on intent, motives, or state of mind of a corporation had no basis in any relevant body of knowledge or expertise).  Here, the court seemed not to understand the impact and purpose of this improper testimony, finding that although Dr. Sachar's testimony sharply criticized Roche, his criticisms did not rise to "such an inflammatory level" that would cause the appeals court to find an abuse of discretion by the trial court in not excluding it.  The issue is not only a Rule 403 prejudice issue; there is a fundamental relevance issue, and a serious issue about fit, foundation, and reliability.

Finally, there was what has been described as the "numbers" issue. The issue refers to the fact that the trial court allowed plaintiff's witnesses and counsel to refer, on repeated occasions, to the number of adverse incidents reported from Accutane users or from other sources while, at the same time, the court restricted Roche's attempt at trial to place those adverse numbers into any larger quantitative context. Specifically, the judge precluded Roche witnesses from more
fully informing the jury about the large number of persons who had taken Accutane before it was prescribed to plaintiff in 1995, and the comparative significance of those figures.

The court ultimately concludes that it was unfair to Roche for the trial court to have precluded such "numbers" counter-proof and that the court abused its discretion on this evidentiary issue. Had Roche been allowed to present the statistics showing five million Accutane users and other related counter-proofs, the jury would have had a fuller and more balanced picture of the data bearing upon the company's actions in changing its label. "Principles of completeness and fairness warranted the presentation of this contextual information to the fact-finder."

 

 

FDA Introduces Nanotechnology Initiative

Last week the FDA introduced the "Nanotechnology Initiative", a collaborative effort between FDA and the Alliance for NanoHealth (ANH) and its eight member institutions. The alliance's eight academic institutions are the Baylor College of Medicine, the University of Texas' M.D. Anderson Cancer Center, Rice University, the University of Houston, the University of Texas Health Science Center at Houston, Texas A & M Health Science Center, the University of Texas Medical Branch at Galveston and the Methodist Hospital Research Institute in Houston.


The initiative is designed to push for the development of safe and effective implementation of nanotechnology into medical products. Under a Memorandum of Understanding, the FDA/ANH Nanotechnology Initiative will work to expand knowledge of how nanoparticles behave and affect biologic systems, and to facilitate the development of tests and processes that might mitigate the risks associated with nanoengineered products. The nanotechnology initiative with the Alliance for NanoHealth is an effort to engage resources and technical expertise in this rapidly advancing field.

FDA recognizes that nanotechnology holds great promise for the advancement of novel medical products. All outcomes from this public-private partnership will be placed in the public domain.
Readers of MassTortDefense know that nanotechnology involves the creation and use of materials at the level of molecules and atoms; it presents opportunities but also challenges for the FDA's entire regulatory product jurisdiction, from food to medical devices to therapeutics. Products from the new technology may also present product liability issues for manufacturers.

Supreme Court Decides Levine v. Wyeth

The Supreme Court has issued its decision in the much-anticipated Levine preemption case.

Readers of MassTortDefense will recall that Wyeth manufactures the anti-nausea drug Phenergan. After a clinician injected plaintiff Levine with Phenergan by the “IV push” method, whereby a drug is injected directly into a patient’s vein, the drug entered Levine’s artery, she developed gangrene, and doctors amputated her forearm. Levine brought a state law damages action, alleging, inter alia, that Wyeth had failed to provide an adequate warning about the significant risks of administering Phenergan by the IV-push method. The jury determined that Levine’s injury would not have occurred if Phenergan’s label included an adequate warning, and it awarded damages for her pain and suffering, substantial medical expenses, and loss of her livelihood as a musician. The trial court rejected Wyeth’s argument that Levine’s failure-to-warn claims were pre-empted by federal law because Phenergan’s labeling had been approved by FDA. The Vermont Supreme Court affirmed.


Today, the Supreme Court affirmed, 6-3, J. Stevens writing for the majority, holding that federal law does not pre-empt Levine’s claim that Phenergan’s label did not contain an adequate warning about the IV-push method of administration. The argument that Levine’s state law claims are pre-empted because it is impossible for Wyeth to comply with both the state law duties underlying those claims and its federal labeling duties was rejected. Although a manufacturer generally may change a drug label only after the FDA approves a supplemental application, the agency’s “changes being effected” (CBE) regulation permits certain preapproval labeling changes that add or strengthen a warning to improve drug safety. Pursuant to the CBE regulation, Wyeth could have unilaterally added a stronger warning about IV-push administration, said the Court, as there was no good evidence that the FDA would ultimately have rejected such a labeling change. Wyeth’s reading of the CBE regulation and its assertion that unilaterally changing the Phenergan label would have violated federal law governing unauthorized distribution and misbranding of drugs are based on the “fundamental misunderstanding” that the FDA, rather than the manufacturer, bears primary responsibility for drug labeling.

The Court also rejected Wyeth’s argument that requiring it to comply with a state law duty to provide a stronger warning would interfere with Congress’ purpose of entrusting an expert agency with drug labeling decisions, because it relies on an overbroad view of an agency’s power to preempt state law. The history of the FDCA shows that Congress did not intend to pre-empt state law failure to warn actions, said the majority. The preamble to the 2006 FDA regulation declaring that state law failure to warn claims threaten the FDA’s statutorily prescribed is merely an agency’s assertion that state law is an obstacle to achieving its statutory objectives. The weight the Court accords the agency’s explanation of state law’s impact on the federal scheme depends on its thoroughness, consistency, and persuasiveness. Skidmore v. Swift & Co., 323 U. S. 134. Under this standard, the FDA’s 2006 preamble did not merit much deference, said the Court. It was limited in light of the FDA’s failure to offer interested parties notice or opportunity for comment on the preemption question; it is at odds with the available evidence of Congress’ purposes; and it reverses the FDA’s own longstanding position that state law is a complementary form of drug regulation.

Quick reactions: The Court was able to get around some facts that made the case appear strong for Wyeth, noting the findings below that that a stronger warning would have made a factual difference (getting around the issues of possible medical malpractice), and that this was indeed a failure to warn and not a duty to contraindicate case. Second, it seems that congressional intent is the touchstone of not only express preemption, but also implied preemption. Third, the presumption against preemption, which some argued really applies only in express cases, also applies to implied preemption cases. Fourth, the Court recognized that some state-law claims might well frustrate the achievement of congressional objectives, but “this is not the case." Defendants will have to carefully explore that opening, develop a robust regulatory record, and see where that may take them.
 

Eleventh Circuit Affirms Exclusion of Expert Testimony on General Causation

The 11th Circuit has affirmed a trial court’s exclusion of key expert causation proof in a suit against the manufacturer of Remicade, finding the expert evidence was not adequately supported by scientific studies or literature. Goldstein v. Centocor Inc., 2009 WL 275322 (11th Cir. 2/05/09).

Plaintiff-appellant contended that the prescription medication Remicade caused his pulmonary fibrosis, requiring a bilateral lung replacement. The trial court excluded plaintiff’s expert testimony on general causation, pursuant to Fed.R.Evid. 702 and Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993). The court of appeals reviews a trial court's Daubert rulings under an abuse of discretion standard. McClain v. Metabolife Intern'l, Inc., 401 F.3d 1233, 1238 (11th Cir.2005).

Plaintiff’s expert did not rely on any epidemiological studies that connect Remicade with pulmonary fibrosis. This is not necessarily fatal, said the 11th Circuit, but it makes a plaintiff’s task to show general causation more difficult. See Rider v. Sandoz Pharmaceuticals Corp., 295 F.3d 1194, 1198 (11th Cir.2002).

In the absence of epidemiological studies, the expert reviewed four sources to make his general causation assessment. The first category, plaintiff's lung and bowel pathology reports, was not relevant to general causation; its focus on the plaintiff made it relevant to specific causation. See McClain, 401 F.3d at 1239 (“General causation is concerned with whether an agent increases the incidence of disease in a group and not whether the agent caused any given individual's disease.”). The second category, MedWatch case reports submitted by doctors who observed possible reactions to Remicade, have a limited weight. Such reports are made without medical controls or scientific assessment, and while they may support other proof of causation, alone they cannot prove causation. Id. at 1199. (putting aside an expert’s reliance on such reports, they are hearsay and do not fall within any of the exceptions to the hearsay rule; also, the prejudicial effect of these reports outweighs their probative value.)

The third category, a review of medical textbooks, revealed no relevant general causation information, only extended analogies. The fourth category, a review of abstracts of four articles linking Remicade with pulmonary fibrosis, is relevant to general causation but provided only very limited information.

A court may conclude that there is simply too great an analytical gap between the data and the opinion proffered. General Elec. Co. v. Joiner, 522 U.S. 136, 146, (1997). The district court did so here, and the 11th Circuit found no abuse of discretion in its determination.
 

Federal Claims Court Finds Against Plaintiffs On Vaccine General Causation Link To Autism

The U.S. Court of Federal Claims ruled last week in three bellwether cases that thimerosal vaccines do not cause autism in children. Three special masters of the Court ruled against plaintiffs in three separate test cases, finding insufficient evidence of a casual link between autism and the MMR (measles, mumps, rubella) vaccine.


Thimerosal has been widely used for decades as a preservative in a number of biologic and pharmaceutical products, including vaccines. It prevents life-threatening contamination. Increasing concern over the potential toxicity of the chemical has led to the removal or reduction to trace amounts of the preservative in most vaccines routinely given children aged 6 and under.


That same concern is behind numerous legal claims alleging that that routine childhood shots are to blame for the rising incidence of autism. The National Vaccine Injury Compensation Program, 42 U.S.C. §300aa-10, et seq., governs such claims, requiring plaintiffs to file a special no-fault compensation petition with the Court of Federal Claims, rather than a traditional suit against manufacturers. Part of the policy behind the program is the potential impact on public health of a traditional mass tort type of litigation involving life-saving vaccines, ranging from polio to chicken pox. Approximately 12,000 cases have been filed under the program.

To be eligible for compensation under the Vaccine Act, a petitioner must either demonstrate a "Vaccine Table" injury, to which a statutory presumption of causation attaches, or prove by a preponderance of the evidence that a vaccine listed caused or significantly aggravated an alleged injury. Althen v. Sec’y, HHS, 418 F.3d 1274, 1278 (Fed. Cir. 2005).  Autism claims fall in that latter category.  In 2002, the Court set up an Omnibus Autism Proceeding to test the three main theories of general causation: that the vaccines and thimerosal combine to cause autism; that thimerosal-containing vaccines cause autism; or that MMR vaccines can cause autism.


Separate opinions covered the Snyder, Hazelhurst, and Cedilllo test cases, but each represent the first, and major, theory, that the vaccines and thimerosal somehow combine to cause autism. The three cases involved some 5,000 pages of transcripts, 939 medical articles and 50 expert reports. The vast majority of credible scientific studies have shown -- and all federal health agencies have strenuously argued -- that there is no connection between vaccines and autism. And public health officials have repeatedly warned that fewer immunizations will endanger children. Indeed, at least in part because of the scare, about one in 12 children does not receive the MMR vaccine in the United States.


The Cedillos contended that their daughter fell sick a week after she received an MMR shot when she was about 16 months old. Today, at age 14, she requires round-the-clock care, suffers from seizures, has lost nearly all her vision and has constant abdominal pain.The Court found that the Cedillos have been misled by physicians who are guilty, in the Court’s view, of gross medical misjudgment on the issue of causation.


The Snyders argued that the MMR vaccine, or the mercury-based preservative in it, had triggered in their son pervasive developmental disorder -- part of the autism spectrum. But, the Court found that the experts contending there is no link between autism and vaccines were far more qualified, better supported by the weight of scientific research and authority, and simply more persuasive on nearly every point in contention.


In the Hazlehurst claim, parents alleged that the MMR vaccine had caused "regressive autism" in their son. Agreeing with the other special masters, the Court found their causation evidence fell short, concluding that the combination of the thimerosal-containing vaccines and the MMR vaccine are not causal factors in the development of autism and therefore, could not have contributed to the development of their child's autism. The weight of the presented evidence that is scientifically reliable and methodologically sound does not support petitioners’ claims.
 

Second Circuit to Hear Appeal of Class Certification Decision in Zyprexa RICO Case

The U.S. Court of Appeals for the Second Circuit recently agreed to hear Eli Lilly’s appeal of a federal district court's orders granting class certification and denying summary judgment in litigation over its anti-psychotic medication, Zyprexa. See In re Zyprexa Products Liability Litigation, 08-4685-mv (2d Cir. 1/15/09).

Judge Jack B. Weinstein of the the Eastern District of New York had granted class certification last fall to a group of third-party payers, including insurance companies, who were suing Eli Lilly for alleged overpayment after the company allegedly exaggerated the benefits of the drug and supposedly failed to disclose certain side effects. The 2d Circuit has now granted the 23(f) motion for leave to appeal.

Readers of MassTortDefense may recall that the 2d Circuit just last year in McLaughlin v. American Tobacco Co., 522 F.3d 215 (2d Cir. 2008), overruled Judge Weinstein's certification of a class of “light” cigarette smokers, finding that individualized issues regarding reliance, loss causation, damages and injury all precluded a finding that common issues predominated over individualized ones as required by Federal Rule of Civil Procedure 23(b)(3). The Zyprexa class claim was brought under the Racketeer Influenced and Corrupt Organizations Act (RICO), 18 U.S.C. § 1964, as plaintiffs seek to take advantage of their reading of the U.S. Supreme Court’s ruling in Bridge v. Phoenix Bond & Indemnity Co., 128 S. Ct. 2131 (2008), regarding reliance in a RICO fraud claim.

In certifying the class in Zyprexa, Judge Weinstein applied his take on the reasoning in Bridge, finding that third-party payers had colorable claims based on the allegedly fraudulent statements made to and relied upon by doctors who prescribed the drugs (not parties). As warned of in our post here last year, the Supreme Court had appeared to reject the defense argument that the proximate cause requirement inherent in the “by reason of” language of the RICO statute demands that a civil RICO plaintiff asserting a claim based on fraud establish his reliance on a misrepresentation by the defendant. In the context of a civil RICO claim predicated on fraud, the required causal link demands a showing that the plaintiff relied on an alleged misrepresentation made to the plaintiff by the defendant. Otherwise, the causal relationship between the alleged injury and the alleged fraud is too attenuated.

The Court appeared to reject petitioners' arguments that under the “common-law meaning” rule, Congress should be presumed to have made reliance an element of a civil RICO claim predicated on a violation of the mail fraud statute. And rejected the argument that a plaintiff bringing a RICO claim based on mail fraud must show reliance on the defendant's misrepresentations in order to establish proximate cause. The Court felt it had no ability to respond to the policy argument that RICO should be interpreted to require first-party reliance for fraud-based claims in order to avoid the “overfederalization” of traditional state law claims. A RICO plaintiff who alleges injury by reason of a pattern of mail fraud cannot prevail without showing that someone relied on the defendant's misrepresentations. But that does not mean, under one reading of Bridge, that the only injuries proximately caused by the misrepresentation are those suffered by the recipient.

The Court’s decision on reliance was based on statutory interpretation, rather than logic or common sense. We predicted that the absence of a clear reliance requirement may in fact make this type of claim even more popular with mass tort plaintiffs. And we are seeing its potential effect on class certification decisions in some district courts.
 

GAO Adds To Critiques of FDA

The Government Accountability Office issued a report last week that listed the FDA as a "high-risk" area of the federal government. The GAO said the U.S. Food and Drug Administration was being hampered by globalization, more complex products, and laws that have made it more difficult for the FDA to ensure the safety of pharmaceuticals, biologic drugs, and medical devices. GAO says its work examining a variety of issues at FDA echoes the conclusions reached by others (think IOM) that the agency is facing significant challenges that compromise its ability to protect Americans from unsafe and ineffective products. FDA needs to, among other things, improve the data it uses to manage the foreign drug inspection program, conduct more inspections of foreign establishments, systematically prioritize and track promotional materials for review, and adopt management tools to ensure that drug sponsors comply with regulations on the presentation of clinical trial results.
 

The perception of the FDA and its ability to do an effective job is a crucial underlying feature in product liability litigation involving regulated drugs, devices, and food products. Jurors’ perceptions of the agency can affect a myriad of issues and themes the defense may wish to present.

Meanwhile, the Pharmaceutical Research and Manufacturers of America (PhRMA) asserts that the issue is a need for more resources for the FDA, to keep drugs safe. The agency “is being asked to do more than it can do” with current resources, the trade group says. Specifically, FDA needs more resources to conduct foreign inspections so the drug supply can be kept safe. PhRMA also said that FDA needs more resources to modernize because, for example, the agency still looks at clinical trial information on paper.
 

FDA Issues Guidance On Distribution Of Medical And Scientific Articles Regarding Off-Label Usage

The FDA has finalized guidelines for how manufacturers can distribute information to doctors about unapproved uses for drugs or medical devices. The ‘‘Good Reprint Practices for the
Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices’’
allows for the limited dissemination of medical journal articles describing off-label uses. The FDA proposed the guidelines in February, 2008 and took public comments before finalizing them.
 

Allegations of off-label promotion are common in mass tort litigation involving drugs and medical devices. Off-label promotion is illegal, but many critics of the industry and plaintiff lawyers seem to forget that doctors can prescribe drugs for any use they see as medically appropriate. The FDA in its guidelines confirms that the public health can be served when health-care professionals receive truthful and non-misleading scientific and medical information on unapproved uses. It will likely help practitioners to receive timely and accurate medical information in an environment where off-label use is common. The FDA's guidance will help assure that medical professionals receive timely and accurate medical information prior to the lengthy process of securing FDA approval for wider use. Such off-label use can save lives, especially in practice areas where there are few effective treatments. These off-label uses or treatment regimens thus may be quite important and may even constitute the medically recognized standard of care. Accordingly, the public health may be advanced by healthcare professionals' receipt of medical journal articles and medical or scientific reference publications on unapproved new uses of approved or cleared medical products that are truthful and not misleading.

This guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115), and suggest that the distribution be in the form of an unabridged reprint, copy of an article, or reference publication;  not be marked, highlighted, summarized, or characterized by the manufacturer in any way (except to provide the accompanying disclosures discussed in the guidance), and be accompanied by the approved labeling for the drug or medical device.

The guidance represents the agency’s current thinking on the dissemination of medical journal articles and medical or scientific reference publications on unapproved uses of approved drugs and approved or cleared medical devices to healthcare professionals and healthcare entities.
 

Eighth Circuit Affirms Dismissal of Nuisance Claim Against OTC Drug Makers

The 8th Circuit has affirmed the dismissal of nuisance claims against the makers of over-the-counter cold and cough medicines containing ephedrine or pseudoephedrine. Ashley County v. Pfizer, No. 08-1491, slip op. (8th Cir. Jan. 5, 2009) (here's a link to the opinion at the Eighth Circuit website).  Important to readers of MassTortDefense, this may be the first appellate court to address whether the lawful distribution of an FDA-approved product can be actionable under a nuisance theory.

Several Arkansas Counties sought to hold the drug companies liable because the lawful cold medicines were being converted by criminals into methamphetamine, an addictive illegal drug. The Counties pleaded theories of unjust enrichment, statutory unfair trade practices, nuisance, and the Arkansas crime victims civil liability statute.

The Counties claimed that the defendants were unjustly enriched at the Counties' expense when methamphetamine cooks purchased the defendants' products for use in the illegal manufacture of methamphetamine. Unjust enrichment is an equitable doctrine that allows a party to recover for benefits conferred on another. It is restitutionary in nature and focuses on the benefit received. It is not enough, however, to establish a benefit received by another party. There must also be some operative act, intent, or situation to make the enrichment unjust and compensable. A party who is free from fault cannot be held to be unjustly enriched merely because it has chosen to exercise a legal or contractual right.

Here, the Counties did not provide the services for which they sought compensation, i.e., law enforcement, inmate housing, social services, and treatment, with the expectation that the defendants–manufacturers and wholesalers of products containing pseudoephedrine–would pay for those services. In other words, the cold medicine manufacturers cannot be said to be the beneficiaries of the services provided by the Counties. The circumstances connecting the sales of cold medication to the provision of these government services were simply too attenuated to give rise to an implied contract between the manufacturers and the county providers to state a cause of action for unjust enrichment.

The remaining nuisance and statutory claims all failed for lack of proximate cause. Arkansas law incorporates the doctrine of intervening acts, which reflects the limits that society places on a defendant's liability for his actions. An original act is eliminated as a proximate cause by an intervening cause if the latter is of itself sufficient to stand as the cause of the injury, and the intervening act is independent of the original act. On this, the Eighth Circuit relied on a Third Circuit gun case, City of Philadelphia v. Beretta U.S.A. Corp., 277 F.3d 415 (3d Cir. 2002), to hold that intervening criminal misconduct can break the chain of proximate cause to product manufacturers. The allegations in the Third Circuit case were nearly identical to the allegations here–that the defendant manufacturers failed to take steps to restrict access to the products containing pseudoephedrine when they knew (an alleged fact the court had to take as true at the judgment on the pleadings stage) that the pseudoephedrine-containing products were being purchased and used illegally to make methamphetamine. "The criminal actions of the methamphetamine cooks and those further down the illegal line of manufacturing and distributing methamphetamine are 'sufficient to stand as the cause of the injury' to the Counties in the form of increased government services, and they are 'totally independent' of the Defendants' actions of selling cold medicine to retail stores . . . . " Slip opin. at 15.

 
 

New Article: Platitudes From Plaintiffs About Product Stewardship

A recent academic paper may be worth a look. Noah, Lars, “Platitudes about 'Product Stewardship' in Torts: Continuing Drug Research and Education,” 15 Michigan Telecommunications and Technology Law Review 2009.

This paper focuses on one emerging aspect of tort litigation against pharmaceutical manufacturers that, if it gained traction, might portend a dramatic (and potentially counterproductive, in the author’s view) expansion in the prescription drug industry's exposure to liability. A growing number of liberal commentators would seek to impose on pharmaceutical manufacturers a broader duty to test and educate (aspects of what they call an obligation of "product stewardship"). This paper explains some of  the serious flaws in such proposals.

The article is thus part of the overall debate about what role tort law may have to play in drug research and development. Does the threat of liability create important safety incentives (and make up for perceived, alleged failings in regulatory oversight), or, instead, does it unduly interfere with innovation and patient access to life-saving therapies? These and related questions have
inspired an active debate among commentators, the author notes;  courts and legislators have also made occasional forays into the area by constricting the scope of potential tort liability in particular circumstances. The Restatement (Third) of Torts: Products Liability, which ALI published a decade ago, included special provisions governing prescription drug cases, and the pitched battle over using implied preemption as a defense, which the United States Supreme Court may address in 2009, represents only the latest manifestation of these sharp disagreements.

Worth a read.
 

Severance Ordered In Digitek MDL

The Digitek MDL judge earlier this month issued a pretrial order regarding multi-plaintiff complaints. In Pretrial Order No. 7, the court ordered the severance of most multi-plaintiff cases (other than spouses). In Re: Digitek Products Liability Litigation, MDL No. 1968 (S.D. W.Va.). The court noted that several complaints in this MDL action join multiple plaintiffs whose only apparent connection with one another is that they allegedly ingested the drug at issue. Other MDL judges have noted the case management, tracking, and other difficulties often accompanying that joinder practice, citing Vioxx and diet drugs.
 

No later than December 31, 2008, plaintiffs’ Co-Lead Counsel are to submit to the court a report identifying multi-plaintiff actions docketed prior to this Order that are subject to severance, and submit on that same date a suitable proposed severance order. One of the reasons plaintiffs resist such severance is the need to pay separate filing fees for all the separate claims filed, but the Order requires the fees.

MassTortDefense has posted on this MDL.  Defendant initiated a nationwide recall of Digitek products, saying tablets with double the appropriate dosage may have been released to the public, with possible side effects. More than 50 Digitek product liability cases were transferred to Chief Judge Joseph R. Goodwin of the Southern District of West Virginia in August.

Consolidated trials are something most mass tort defendants may want to oppose. The pre-trial severance of multi-plaintiff actions here is without prejudice to any party’s right under Federal Rule of Civil Procedure 42 to request consolidation of severed actions upon future remand to a transferor court for trial. But better that plaintiffs have the burden of putting cases together than defendant have to overcome the "inertia" of cases that have been consolidated since day one.
 

9th Circuit Affirms Summary Judgment In Failure To Warn Case

The Ninth Circuit has affirmed that the trial court did not err in granting summary judgment for defendant Merck under California's learned intermediary doctrine in a failure to warn case. Latiolais v. Merck & Company, Inc., 2008 WL 5157705 (9th Cir. 2008).

Latiolais appealed the district court's grant of summary judgment on her claim that Merck failed to adequately warn, as a result of inadequate testing, of claimed suicide risks associated with the cholesterol-lowering medication Zocor.

Under California's learned intermediary doctrine, a prescription drug manufacturer's duty to warn runs to the physician. A product defect claim based on insufficient warnings cannot survive summary judgment if stronger warnings would not have altered the prescribing physician's conduct. See Motus v. Pfizer, Inc., 358 F.3d 659, 661 (9th Cir.2004).

Here, there was no genuine issue of material fact as to causation made out by the prescriber’s deposition testimony. It indicated that the drug inserts accompanying Zocor did not play a role in his decision to prescribe that medication. Furthermore, Dr. Oppenheim was not equivocal regarding whether he would have prescribed Zocor in light of a supposed warning of suicide risk associated with Zocor. Such a warning was deemed “hypothetical” by the court, and, in any event, could come into play only after one makes several assumptions on issues that include whether Merck was obligated to issue a suicide risk warning for Zocor, whether Dr. Oppenheim would have read or heeded such a warning, and what information Mr. Davis would have disclosed to Dr. Oppenheim with respect to his mental state. Such speculation did not create an issue of fact.

 

Opposition To Cert Petition In Colaccico: That Other Preemption Case

While much preemption focus has been on Levine v. Wyeth, including by posts here at MassTortDefense, other preemption decisions are winding there way through the federal appellate courts. Defendants Pfizer Inc., GlaxoSmithKline, and Apotex Inc. last week asked the U.S. Supreme Court to uphold a ruling by the U.S. Court of Appeals for the Third Circuit that failure to warn claims are impliedly preempted by federal law based on the regulatory history of the antidepressants at issue. Colacicco v. Apotex Inc., 521 F.3d 253 (3d Cir. 2008), Petition for Certiorari Filed, 77 USLW 3229 (Oct 02, 2008). 

Readers of MassTortDefense know that plaintiff Colacicco filed suit after his wife allegedly committed suicide while under treatment with a generic equivalent to Paxil. The district court for the E.D. of Pennsylvania found preemption. The appeal was consolidated with a contrasting preemption decision in the McNellis case out of the district court in New Jersey, involving Zoloft. The Third Circuit's decision was the first by a federal appeals court to address the preemptive effect of prescription drug law and regulation since the FDA had expanded on its guidance on the issue.

Plaintiffs sought certiorari, asking the Court to review the Third Circuit's decision; alternatively, they asked the court to hold the petition pending resolution of Levine, argued last month. But the Court should do neither, the manufacturers argued, and cert should just be denied.

Pfizer Brief

According to Pfizer's brief, the Third Circuit properly determined that plaintiff below McNellis sought a warning about suicidal behavior that conflicted with the federal warning requirements for Zoloft. For more than 15 years, the FDA had considered whether SSRIs were associated with an increased risk of suicidality in adult patients. The agency repeatedly determined that the scientific evidence did not support such a warning.

Pfizer notes there is no disagreement among appellate courts (a well-established basis for Supreme Court review) on preemption in SSRI litigation.  No other federal appeals court has ruled in a contrary way on the preemptive effect of the type of conflict at issue here. The 3d Circuit found preemption based on “the direct, real conflict” between plaintiff’s claim that New Jersey law required a warning about adult suicidality and the FDA's requirement—based on its repeated finding of no reasonable evidence of such an association—that only the FDA's approved warning be given. McNellis relied on the Court's decision in Sprietsma v. Mercury Marine, 537 U.S. 51 (2002) to argue that the FDA merely failed to act with respect to suicidality warnings, and that a federal agency's failure to act does not create a federal requirement triggering preemption. But the FDA “regulated with great specificity and care” in repeatedly finding no reasonable association between SSRIs and suicidality, and by requiring the manufacturer to provide the specified warnings.

As to the claim that the manufacturers failed to disclose information to the FDA, defendants assert that the lower court correctly found that this claim should be presented to the FDA first. In addition, Buckman preemption likewise prevents plaintiffs from evading a definitive FDA regulatory record by arguing that the FDA was somehow defrauded; the appellate court found that the preemption doctrine of Buckman v. Plaintiffs' Legal Committee, 531 U.S. 341 (2001), bars claims that the manufacturer withheld information from the FDA.

Direct Conflict

Arguing against even staying the petition until Levine is decided, Pfizer said the issues in the cases are distinct, asserting that the 3d Circuit's decision in this case is correct regardless of whether Levine is affirmed or reversed. Respondents point out what they see as distinct regulatory facts in that case, involving contraindication claims.

Brief for Apotex, GlaxoSmithKline

Apotex, a maker of generic Paxil, and GlaxoSmithKline, the maker of brand-name Paxil, also argued against review. Like Pfizer, they contended the 3d Circuit properly concluded that the FDA's repeated rejection of suicidality warnings preempts plaintiff Colacicco's claims.

The brief also argued that state law failure to warn claims challenging FDA-approved labeling should be preempted. To allow this sort of tort action to continue would place state-law juries in the position of second-guessing FDA decisions regarding the proper warnings for drugs. Lay juries should not be able to undermine the agency's expertise by second-guessing the agency's warning decisions. At its base, Colacicco's argument against preemption is the theory that a court, applying state law, has authority to decide whether GSK could have under federal law, and should have under state law, unilaterally added a suicidality warning to the Paxil labeling, despite FDA regulation.

Courts do not share concurrent jurisdiction with the FDA over drug labeling; there should be no preemption test that would require a court to delve deeply into internal FDA decision making. Specifically, the lower courts do not share jurisdiction with the FDA over the CBE regulation, which is the basis for the “could have, should have” argument, Apotex and GSK both wrote. FDA has made clear that CBE supplements fall squarely within its regulatory jurisdiction. Under Colacicco's theory, the lower court would be authorized to decide, without reference to the FDA, that a CBE supplement adding the putative warning could have been submitted, that the added warning would have been consistent with the FDCAct, and that FDA would have approved it. Thus, the lower courts would become “shadow” FDAs. That is not the scheme adopted by Congress for drug regulation.

 


 

FDA Issues Guidance For Industry On Retaining Data From Clinical Trials

Limiting mass tort/class action exposure is a key part of the role of in-house litigators. In the drug and device areas, limiting plaintiffs' ability to take unfair advantage of clinical trials research is becoming a real focus. Issues include limiting liability due to alleged inadequate monitoring during trials, and preventing off-label and product liability claims associated with alleged under-reporting and over-reporting of data. Litigators need to offer their input on the company's determination of the extent to which data from ongoing clinical trials will be distributed, helping the company to assess the liability risks of disclosing and failing to disclose clinical trial data related to off-label uses. A thorny legal issue is the degree to which the First Amendment is a viable defense, and in a complex regulatory world the company needs to understand and comply with state as well as federal disclosure obligations.


Ideally, the company will be developing a framework for deciphering where scientific exchange ends and drug promotion begins, as a guide to avoiding language in describing clinical trials that could be construed as promotional while still providing fair and balanced information on clinical trials involving their products. The most prudent may be developing a strategic, long-term plan to protect clinical trial information from turning into grist for the plaintiff ’s case (and outside counsel can help with that too). That program may include training employees to recognize the litigation potential arising from clinical trials; maintaining protocols as to the language and terms that will be used in clinical trial reports; and minimizing common liability risks arising from posting of data by establishing thorough review processes.


Into this complex situation the FDA has issued new guidance for drug, biologic, and medical device companies about retaining data from clinical trial participants who no longer are participating in the trial, according to a notice just published in the Federal Register (73 Fed. Reg. 72807). The guidance document on Data Retention When Subjects Withdraw from FDA-Regulated Clinical Trials states that data must be retained for participants who decide to discontinue participation in a clinical study of an investigational product, who are withdrawn by their legally authorized representative, or who were discontinued from participation by the clinical investigator.
FDA's reasoning is that data resulting from these clinical investigations are used to support research applications and new product approvals;  thus it is critical that it has a complete and accurate data set available. While it may be appropriate to remove data from various reported figures, based on the study protocols, FDA worries that if data were to be removed from the study database altogether, the FDA may miss something that may be relevant to their decision-making.
 

The agency said it issued this guidance for immediate implementation to prevent the potential loss of important clinical trial data. If comments are received on the guidance, FDA said it will review the comments and revise the guidance as appropriate.
 

White Paper On Combination Products

Dr. Steven Richter has issued a white paper, “Combination Products: Navigating Two FDA Quality Systems.” Dr. Richter founded the consulting firm Microtest after working at the U.S. Food & Drug Administration. Combination products involve medical devices embedded with pharmaceutical or biologics components, like a drug-coated stent.

While none currently exist, the white paper predicts that FDA will issue guidelines specific to combination products, and the result will be increased GMP regulatory action that affects both laboratory and manufacturing.

The combination products market is moving forward with a new direction and emphasis regarding product safety and FDA requirements. The paper quotes an estimate that the market for such products will reach approximately $9.5 billion in 2009. The FDA received 275 combination product submissions in 2005, and that number has been growing. According to one survey, an estimated 30% of new products under development are “combo products.”

Such combination products can raise thorny legal issues if products liability litigation arises.  E.g., In re St. Jude Medical, Inc. Silzone Heart Valves Products Liability, 2004 WL 45503
(D. Minn., January 05, 2004)(discussing which preemption doctrine may apply to such). 
 

Digitek MDL Proceeds And State Mass Tort Designation Looms

Certain plaintiffs in the Digitek litigation have filed for mass tort designation in the State of New Jersey, according to a notice filed on the New Jersey Judiciary mass tort web site. Earlier this year, defendant initiated a nationwide recall of Digitek products, stating that tablets with double the appropriate dosage had possibly been released to the public. It said digitalis toxicity was possible in patients with renal failure.

Previously, some plaintiffs had moved for centralized management, but not mass tort designation, of all New Jersey state-court litigation involving the drug Digitek and assignment of that litigation to Bergen County. Anyone wishing to comment on or object to this second application regarding the Digitek  state-court litigation is to provide such comments or objections in writing, with relevant supporting documentation, to the Administrative Office of the Courts, by December 1, 2008. After that date the N.J. Supreme Court will consider and act on both applications regarding Digitek and any comments received.

At the federal level, the judge in the newly-created Digitek federal multidistrict litigation issued an order appointing lead and liaison counsel for the plaintiffs as well as the Plaintiffs' Steering Committee. See In Re: Digitek Products Liability Litigation, MDL No. 1968, JPMDL.; No. 08-md-1968, S.D. W.Va.). Chief Judge Joseph R. Goodwin of the Southern District of West Virginia appointed Carl N. Frankovitch of Frankovitch, Anetakis, Conatonio & Simon, Fred Thompson III of Motley Rice, and Harry F. Bell Jr. of Bell & Bands, as co-lead counsel for the plaintiffs. Bell is also liaison counsel for the plaintiffs. Previously, Chief Judge Goodwin appointed Rebecca A. Betts of Allen, Guthrie & Thomas as defendants' liaison counsel.


Earlier in the fall, the federal court held a pretrial conference jointly with Magistrate Judge Mary E. Stanley and advised the parties of its intention to coordinate heavily with the judges and counsel involved in the state Digitek cases, especially in West Virginia and New Jersey where a majority of the state cases have been filed.
 

Punitive Damages Claim Against Patch Maker Found Preempted

A federal court has found that federal law preempts a state law that allows plaintiffs to seek punitive damages from the makers of defective drug products if the drug company knowingly withheld information from the Food and Drug Administration. Grange v. Mylan Laboratories Inc., 2008 WL 4813311 (D.Utah 10/31/08).

Plaintiffs’ estate sued over an allegedly defective drug patch. Defendants sold the Fentanyl Patch, which is applied directly to the skin to deliver fentanyl, a strong pain medicine. Doctors prescribe the Fentanyl Patch to relieve chronic moderate to severe pain. The patch should be worn for seventy-two hours and is supposed to deliver the medicine at a regulated rate. Plaintiff alleged that due to a design and/or manufacturing defect, some Fentanyl Patches contain and deliver fentanyl in amounts far in excess of what is advertised. Plaintiff alleged that defendants knew that the Fentanyl Patch was defective, but did not warn of the potential risk of overdose.

Defendants moved to dismiss the claims for punitive damages. A Utah statute, Utah Code Ann. § 78B-8-203, completely bars punitive damages for harm caused by FDA approved drugs. But that statute has an exception for cases where a plaintiff can show that a defendant withheld information from the FDA. Plaintiffs, of course, alleged that the exception applied here. But defendants contended that this exception is preempted by federal law.

As the court noted, this statutory limitation on liability for punitive damages does not apply if it is shown by clear and convincing evidence that the drug manufacturer knowingly withheld or misrepresented information required to be submitted to the Federal Food and Drug Administration under its regulations, which information was material and relevant to the claimant's harm. Defendants contended that the statutory exception amounts to a de facto “fraud on the FDA” claim, which is preempted by federal law.

In support of this argument, defendants relied on Buckman Co. v. Plaintiff's Legal Comm'n., 531 U.S. 341, 348 (2000), which held that state law fraud-on-the-FDA claims conflict with, and are therefore impliedly preempted by, federal law. The Buckman Court gave two primary reasons for this holding. First, allowing state law claims of fraud on the FDA would interfere with the FDA's objectives and judgment. See id. at 350-51. Second, such claims could cause the FDA to face a deluge of unnecessary information in the approval process by drug companies attempting to avoid state law liability, jamming up the regulatory system.

The court decided that the decision in Buckman did not directly reach the issue presented here. In this case, unlike in Buckman, the state statute does not predicate liability on fraud on the FDA, but rather would allow certian damages based on such fraud. The question of whether this type of statute is preempted, said the court, has created a split of authority. Compare Garcia v. Wyeth-Ayerst Labs., 385 F.3d 961 (6th Cir.2004)(extending Buckman's logic to a statute similar to Utah's), with Desiano v. Warner-Lambert & Co., 467 F.3d 85, 97 (2d Cir.2006)(same Michigan statute was not preempted by Buckman), affirmed sub nom, Warner-Lambert Co., LLC v. Kent, 128 S.Ct. 1168 (2008)(4-4 vote).

Despite a mention of the so-called presumption against preemption, the court found that the Sixth Circuit's decision in Garcia was more persuasive here. The chief problems that Buckman sought to counteract are present whenever a plaintiff, as a prerequisite to collecting damages, is required to put on evidence that there was what amounts to fraud on the FDA. When such evidence is considered, state courts are essentially second-guessing the FDA, and drug companies, nervous about state litigation, will have an incentive to flood the FDA with information. To the extent that the Utah law allows for an exception in cases where a plaintiff puts on his or her own independent evidence of information being withheld from the FDA, this statute was found to be preempted. There is no preemption, however, in a situation where a plaintiff invokes the Act to seek punitive damages in cases where the FDA itself has found that there was fraud in the application process.
 

Federal Court Grants Summary Judgment To Defense On Accutane Warnings

A federal district court has granted summary judgment to drugmaker defendants Hoffmann-LaRoche Inc. and Roche Laboratories Inc. in an Accutane failure to warn case. Snyder v. Hoffman-LaRoche, Inc., 2008 WL 4790666 (M.D.Fla., October 30, 2008). Plaintiffs alleged their teenage son was prescribed Accutane in 2000 to treat young Snyder's severe acne condition. He had three courses of treatment through April, 2003. On February 28, 2005, Snyder committed suicide.

Prior to prescribing Snyder's first course of Accutane treatment, Dr. Kalb received and reviewed the drug’s 1998 Package Insert, the 1998 Dear Doctor Letter, the 1999 issue of the PDR, the February 25, 1998 FDA Talk Paper, and the Seventh Edition of the Accutane Brochure, all of which discussed the potential suicide risks. Dr. Kalb testified that he discussed the risks and benefits of Accutane with Snyder before prescribing the drug, including specifically the potential risk of depression and suicide. Such discussion was consistent with his regular practice, as was his practice of providing each patient with a copy of the then current Accutane Brochure. Throughout Snyder's courses of treatment, Dr. Kalb continued to monitor him for symptoms of depression.  According to Dr. Kalb, who would know, no symptoms of depression were reported or observed while Snyder was taking Accutane.

Plaintiff's Complaint included claims for negligence, strict products liability, breach of implied warranty, and negligent and fraudulent misrepresentation. Each of these claims was predicated upon defendants' alleged failure to warn that Accutane could cause Snyder to commit suicide. Defendants moved for summary judgment on the issue of the adequacy of the warnings. Snyder resided and was prescribed Accutane in the State of New York. Accordingly, the Court considered whether Defendant's warnings were adequate under New York law.

Under New York law, a prescription drug manufacturer may avoid liability for injuries that would ordinarily render the manufacturer strictly liable by distributing proper directions and warnings with the drug. To avoid liability, a manufacturer must warn of all potential dangers in its prescription drugs that it knew, or, in the exercise of reasonable care, should have known to exist. New York employs the learned intermediary doctrine, under which physicians act as “informed intermediaries” between manufacturers and patients regarding warnings for prescription drugs. Thus, a manufacturer's duty to caution against a drug's side effects is fulfilled by giving adequate warning through the prescribing physician, not directly to the patient.

Because the defendant had issued a warning about this specific risk, plaintiffs were left to try to argue that defendant's warnings were not direct, unequivocal and sufficiently forceful to convey the risk of suicide. Plaintiff argued defendants' warnings equivocated in stating that Accutane “may” cause depression and suicidal ideation, that emotional instability “may” bear no relation to therapy, and that the side effect of suicide is “uncommon” and/or “rarely” occurs. Moreover, Plaintiff argued that the defendants' statement that “no one knows if Accutane caused these suicidal behaviors” further dilutes the warning.

The Court disagreed with plaintiffs. The February 1998 warnings specifically warned that Accutane treatment may cause suicide. MassTortDefense notes that the drug does not always cause suicide, if it ever does (which is unproven), so “may” is perfectly accurate. The statements that Accutane “may” cause suicide, or that such a result “rarely” occurs, do not inappropriately diminish the seriousness of the warning; rather they describe the medical record. The Court properly viewed the extensive warning language as a prescriber would, in full context, not isolating a word or phrase. Taken as a whole, the warnings clearly, accurately, and consistently conveyed to Dr. Kalb that Accutane might cause suicide, with or without prior symptoms of depression. Accordingly, the Court concluded that defendants' warnings were adequate as a matter of law. Defendants were entitled to summary judgment as to plaintiff's failure to warn claims

 

Drug And Medical Device Conference

The second week of December in New York marks the return of one of the premier products liability litigation events, geared to the pharmaceutical and medical device industries. Now in its 13th year, ACI’s DRUG AND MEDICAL DEVICE LITIGATION is a gathering of many of those involved in defense of product liability litigation, with a faculty of in-house and outside counsel (including your faithful blogger) and 8 renowned federal and state jurists.

Readers of MassTortDefense know that in the past year, the Supreme Court ruled in favor of preemption for PMA-approved medical devices, and it is now poised to make a potentially significant decision on preemption for drugs that could change that aspect of the product liability landscape. The liberal Democratic Congressional backlash against preemption has already started, with attempts to legislatively overturn the Reigel decision. In addition, government enforcement agencies and State Attorneys General have stepped-up investigations against drug and device manufacturers, and plaintiffs’ attorneys are taking every opportunity to highlight this fact in civil litigation. So, plenty to talk about.

This year’s conference takes place in the 1903 landmark Hudson Theatre at the Millennium Broadway Hotel. And MassTortDefense is looking forward to the visit the the Big Apple.
 

FDA Updates Plans For Foreign Offices

The Food & Drug Administration (FDA) should be opening its new China office later in 2008. In the past couple years, as posted here at MassTortDefense, multiple imports from China have been at the center of safety concerns. Earlier this year, heparin allegedly contaminated with a counterfeit ingredient was blamed by some plainitff attorneys for some patient deaths; FDA has issued recalls of several foods imported from China that may have apparently been tainted with the industrial chemical melamine, which has been added to dairy products and resulted in hospitalization of thousands of children in China.

FDA staff posted at the China office will inspect facilities, provide guidance on U.S. quality standards, and later train local experts to conduct inspections on behalf of the FDA. The FDA will eventually open offices in the Chinese cities of Shanghai and Guangzhou, for a total of eight planned FDA staffers. The agency hopes a greater on the ground presence in China will help prevent unsafe imports, and the opening of a Beijing, China office later this year is just the first step in the FDA’s plan to expand its presence overseas. Over the next year, the agency plans to place as many as 60 food and drug regulators in offices worldwide, focusing on India, Latin America and the Middle East. The plan for permanent outposts marks a break from the agency's current practice of sending inspectors abroad on individual assignments.

Part of an updated import inspection plan may be to allow voluntary inspection, where manufacturers would pay third-party inspectors to verify that their plants meet FDA standards, although past attempts at a voluntary inspections system haven’t been well received by some overseas manufacturers. Democrats in the House of Representatives, offering yet another alternative, have proposed a program that would require companies to pay mandatory user fees to help finance additional FDA inspections.

Health and Human Services Secretary Michael Levitt is scheduled to travel to China next month to meet with health officials there to review joint efforts to ensure the safety of food and medical imports. The Consumer Product Safety Commission also worked to get people stationed in China. Under the current plan, the CPSC staffers who will be sent there eventually are not full inspectors. Their purpose will be to provide technical assistance to Chinese manufacturers and regulators.
 

FDA Holds Public Hearing on OTC Cough and Cold Medications In Kids

As previewed by MassTortDefense, the Food and Drug Administration held a public hearing on October 2, 2008, to obtain input regarding over-the-counter (OTC) cough and cold drugs marketed for pediatric use. Many of these nonprescription cough and cold drug products are marketed under the OTC Drug Review, which published a monograph describing the conditions under which certain OTC ingredients are considered to be generally recognized as safe and effective. These products contain ingredients that have been classified by the FDA as generally recognized as safe and effective since the 1970’s Recently, some potential safety and efficacy concerns have been raised regarding the pediatric dosing and use of certain active ingredients in OTC cough and cold drug products.

FDA is developing a proposed rule to revise the pediatric labeling guidance contained in the Final Monograph for Cough, Cold, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use.  Each year, U.S. consumers buy about 95 million packages of oral pediatric cough and cold medicines. 

Some doctors at the hearing urged regulators to seek removal of children's cough and cold medicines from store shelves until the products are found safe and effective. For example, Dr. Michael Shannon, professor at Harvard Medical School, testified that it is time for these products to be re-evaluated regarding their risk-benefit ratio. The American Academy of Pediatrics doesn't recommend any use of OTC cold and cough  medicines in children. In January, the FDA recommended against their use in children up to 2 years old. Treatment alternatives include providing fluids, nose drops, humid air and appropriate pain relievers.

The Consumer Healthcare Products Association pointed out that most reported side effects are caused by accidental overdose and misuse, which might suggest that changed packaging and improved education, rather than other measures, might be appropriate. The Association has begun a comprehensive, national education program that focuses on the root causes of adverse events and speaks directly to parents, day care providers, healthcare providers, and other caregivers. CHPA is partnering with a number of organizations in these efforts, including the American Pharmacists Association and the American Association of Family Physicians. These education campaigns underscore the importance of following the directions on the label, using the correct dose, storing medicines safely and consulting with a doctor if there are any questions.

Arguably, if pediatric cough and cold products are no longer available over the counter, parents may turn to other alternatives that may result in even more dangerous consequences for children. The industry is undertaking a comprehensive and scientifically rigorous efficacy and safety program for children age 2 to 12 in order to advance the science and ensure the highest level of scientific rigor. This program includes pharmacokinetic studies to confirm the dosing for the eight most commonly used OTC oral cough and cold ingredients. Once these dosing studies are finalized, they will begin other studies to revalidate the effectiveness of these medicines.

In reaction to the public hearing, FDA did not call for an immediate ban on over-the-counter cough and cold medicines for young children. John Jenkins, director of the FDA's Office of New Drugs, said the agency will propose changing its rules which could further restrict use of the products in children.

In response to the issues, following the hearing, makers of OTC cold and cough drugs announced they would start adding warnings against use in children younger than 4 years. That is, the leading manufacturers of these medicines are voluntarily transitioning the labeling on oral OTC pediatric cough and cold medicines to state “do not use” in children under four years of age.  (The risk of overdose is greatest in 2- and 3-year-olds, according to the Consumer Healthcare Products Association.) Pediatric antihistamines will also carry new labels telling parents not to use the medicines to sedate children of any age. The move comes out of an abundance of caution in an effort to promote the safe and effective use of these medicines.  FDA was quoted as being in support of these voluntary actions by CHPA, in part because the rulemaking process can take significant time.
 

Third Circuit Rejects Vaccine Plaintiffs' General Causation Expert Opinion

The Third Circuit recently upheld a judgment for the U.S. following a bench trial, in a suit by a couple who alleged that contaminated polio vaccine caused the husband's brain cancer. Gannon v. United States, 2008 WL 4151665 (3d Cir. 2008).

Plaintiffs alleged that an oral polio vaccine (OPV) received between 1973 and 1976 was contaminated with SV40, a simian virus found in both monkeys and humans. The Gannons claimed that the government was negligent in failing to prevent the manufacturer from making the OPV available to the public, and as a result, the contaminated vaccine caused Mr. Gannon to develop a form of brain cancer. Gannon and his wife filed an administrative claim against the government under the Federal Tort Claims Act and, later, a suit in the Eastern District of Pennsylvania.

The Court, for the convenience of the witnesses and to prevent recalling the experts later in the trial, decided to combine a Daubert hearing with the expert bench trial testimony on the issue of causation. Thus, the trial began with the Daubert examination of plaintiffs' expert, Dr. Adi Gazdar, who presented his full testimony on the issue of causation. He testified that SV40 plays a causal role in this type of cancer.

The district court denied the Daubert motion, but rejected the testimony as insufficient on the issue of general causation.  Safe approach in a bench trial, here it and then decide. The ruling came pursuant to Rule 52(c), which states that a trial court can enter judgment after hearing evidence on only one issue, provided the party against whom judgment has been entered is fully heard. (The appeals court rejected the plaintiffs' argument that they were not fully heard on causation: The plaintiffs asserted they would have called two other witnesses to testify, but those witnesses were not relevant to causation because their testimony would principally address the issue of contamination.) Interestingly, the United States did not offer an alternate source of causation but merely asserted that SV40 did not cause brain tumors and offered expert testimony to that effect.

Although Dr. Gazdar testified that it was his opinion that to a reasonable degree of medical certainty SV40 plays a causal role in the formation of medulloblastomas, the Court decided that the plaintiffs had not met their burden of proof on causation. Specifically, the Court found that Dr. Gazdar's testimony failed to satisfy the “Bradford Hill” criteria. The Bradford Hill criteria are broadly accepted criteria for evaluating general causation based on epidemiology;  they are: (1) Strength of Association, (2) Consistency, (3) Specificity, (4) Temporality, (5) Biologic Gradient, (6) Plausibility, (7) Coherence, (8) Experimental Evidence, and (9) Analogy.

On appeal, the Third Circuit observed that causation is an essential part of the plaintiffs' negligence claim. Based upon its thorough consideration of the record evidence, the Third Circuit could not say that the district court clearly erred in its findings of fact or that it erred in concluding that the Gannons had not met their burden of proof on the issue of causation.
 

  • The Court relied upon the fact that all three defense experts used established scientific frameworks and cited both biological and epidemiological evidence. Each of those experts opined that the evidence did not support the conclusion that SV40 causes human cancer.
  • The Court relied upon a 2003 Institute of Medicine report, which concluded that “ ‘the evidence is inadequate to accept or reject a causal relationship’ “ between SV40 and cancer.
  • Dr. Gazdar, the plaintiffs' expert, testified that he agreed that current epidemiological evidence does not support the conclusion that SV40 causes brain cancer.
  • He relied upon testing on rodents, which defense experts stated were not a good brain model for humans; even Dr. Gazdar admitted the results could not necessarily be extrapolated to humans.

Most importantly, the court considered each of the nine Bradford Hill criteria for causation and found that Dr. Gazdar's opinion did not meet the criteria.  The general causation opinion was thus rejected on the merits.
 

Discovery Battles Continue In Zyprexa MDL

Two interesting developments in the ongoing discovery battles in the Zyprexa MDL, which involves claims by several states and health entities alleging that defendant Eli Lilly made misleading statements about the medication. The states allege that they would not have funded Medicaid patients taking Zyprexa had they known about the risks of the drug...But don't seem eager to prove it.

First, the magistrate judge denied defendant’s motion for sanctions against Montana, New Mexico, Louisiana, and Mississippi, but ordered the states that have not yet produced their complete Medicaid databases as requested to do so on pain of sanctions.

Second, the court ordered the states to produce non-party medical records requested by Lilly. The defendant, not surprisingly, wanted to be able to compare the records of other antipsychotic medications in the relevant periods. As the court said, "the records are in fact relevant to Lilly’s defenses. For example, as Lilly notes, the use of a statistically significant sample of Medicaid patient records can help to explain information obtained from Medicaid databases, and may provide information on potential confounding variables."

The states argued that their respective physician-patient privilege laws prohibited discovery of the patient medical records. It is axiomatic that state privilege laws do not govern in federal question cases. Although several of the plaintiff states did not allege violations of federal law in their
complaints, and each has vigorously challenged the basis for federal jurisdiction, Judge
Weinstein has held that jurisdiction lies under federal law. 

The court also felt that the states’ doctor-patient privilege argument was not well taken, because the order was for the production of de-identified medical records with patient names redacted. Federal statutes and regulations make clear that de-identified health information is discoverable in litigation in federal court, with or without patient consent, and it appears that the states’
respective privilege laws would not apply to de-identified information either.

The court also denied the states' request that Lilly subpoena the records, as a step that would needlessly prolong discovery.  Significantly, Lilly does not know the identities of the patients whose medical records it seeks. Moreover, the states are in a better position to ensure that the medical records produced are a randomly selected, statistically significant sample. If Lilly were constrained to subpoena the medical records, it would likely target only certain records, which would inevitably lead to protracted argument over whether the records subpoenaed represent a statistically significant sample, said the court.

MassTortDefense has posted on this litigation before. It continues to be an excellent example of the type of attenuated and indirect injury claim that requires in-depth and detailed discovery to defend. Also an example of plaintiffs who are more willing to assert complex damages theories than to provide the evidence to test those claims.
 

Maryland Court Resists Imposing "Duty To The World" On Pharmaceutical Maker

Maryland's top court recently affirmed summary judgment for defendant Eli Lilly & Co., in a case brought by a widow whose husband was killed in an auto accident. His car was allegedly hit by a diabetic who blacked out while under treatment with two insulin medications. Gourdine v. Crews, No. 134 (Md. Ct. App. 9/4/08).

Background
Ellen Crews, a Type I diabetic who was taking a combination of insulin medications from Lilly, while operating her car, allegedly suffered some kind of debilitating episode and struck a vehicle driven by Isaac Gourdine, resulting in his death. The issue for the Court was whether Lilly owed a duty to Mr. Gourdine, the third-party who did not ingest the drugs. Plaintiff, the wife of Mr. Gourdine, argued that it was somehow foreseeable to Lilly that Ms. Crews, might allegedly suffer an adverse reaction to the medications, which in turn would cause injury and death to third persons while she was operating a motor vehicle. If she had not been adequately warned about the dangers that allegedly were associated with the specified medications, that would supposedly impact a duty owed to Mr. Gourdine.

Specifically, Ms. Crews took a combination of Humalog, a quick-acting form of insulin taken with meals, and Humulin N, a medication designed to supply a constant source of insulin to the body. Ms. Gourdine contended that, at the time of the accident, Ms. Crews suffered a hypoglycemic reaction and experienced a “blackout” causing her to lose control of her vehicle. Defendant Lilly, plaintiff alleged, owed a duty to protect users of the highway from drivers suffering from hypoglycemia induced by the allegedly misbranded drug.

Lilly sought and obtained summary judgment below on the basis it owed no duty to decedent Gourdine, a nonuser of the drug, to warn about alleged risks associated with the medications. Plaintiff appealed, and the Maryland Court of Special Appeals affirmed; the case then went up again.

Reasoning
The Court began with a discussion of the elements of plaintiff’s causes of action, noting that duty is an essential element of both negligence and strict liability causes of action for failure to warn. In contrast to the reasoning of the lower courts, however, the Court stated that the duty issue should not be analyzed in the context of the learned intermediary rule – which holds that the manufacturer’s duty to warn is to the prescriber – but as an issue of the common law of torts.

At its core, the determination of whether a duty exists represents a policy question whether the specific plaintiff is entitled to protection from the acts of the defendant; ultimately, the determination of whether a duty should be imposed is made by weighing the various policy considerations and reaching a conclusion that the plaintiff's interests are, or are not, entitled to legal protection against the conduct of the defendant. The foreseeability test relied on by plaintiff  “is simply intended to reflect current societal standards with respect to an acceptable nexus between the negligent act and the ensuing harm.”  While foreseeability is often considered among the most important of the relevant factors, its existence alone does not suffice to establish a duty under Maryland law.

In this case, there was no direct connection between Lilly’s warnings, or the alleged lack thereof, and Mr. Gourdine’s in jury. In fact, there was no contact between Lilly and Mr. Gourdine whatsoever. To impose the requested duty from Lilly to Mr. Gourdine would expand traditional tort concepts beyond manageable bounds, because such duty could apply to all individuals who could have been affected by Mr. Crews after her ingestion of the drugs. Essentially, Lilly would owe a duty to the world, an indeterminate class of people, for which the Court has “resisted the establishment of duties of care.”

Gourdine attempted to draw support from cases in other jurisdictions, in which she asserted that a doctor's duty to warn his or her patient of the risks associated with medication extends to nonpatients who are foreseeably at risk. The Court responded that it has not historically embraced the belief that duty should be defined mainly with regard to foreseeability, without regard to the size of the group to which the duty would be owed, which the courts in Alabama, Hawaii, and Washington, according to plaintiff, have.

On the other hand, numerous jurisdiction had rejected this kind of universal duty, the Court noted. See Kirk v. Michael Reese Hospital & Medical Center, 513 N.E.2d 387 (Ill. 1987); Gilhuly v. Dockery, 615 S.E.2d 237, 239 (Ga. Ct. App. 2005) (patient who was involved in a car accident in which sons were injured filed suit on their behalf based on physician’s alleged failure to warn patient not to drive after taking certain medications; the Court of Appeals of Georgia rejected the claims on behalf of the sons because “[t]o expand a doctor’s duty to his patient to generally include members of the public at large in a case such as this one would be contrary to Georgia public policy”); Lester ex rel. Mavrogenis v . Hall, 970 P.2d 590, 597 (N.M. 1998) (holding that physician owed no duty non-patient injured in automobile accident with patient because the “consequences of placing a legal duty on physicians to warn may subject them to substantial liability even though their warnings may not be effective to eliminate the risk in many cases”); Rebollal v. Payne, 145 A.D.2d 617, 618 (N.Y. App. Div. 1988) (“There is no duty on the part of the operator of a methadone clinic to control the travel activities of a methadone patient giving rise to liability for accidents to a third party such as plaintiff’s decedent.”); Praesel v. Johnson, 967 S.W.2d 391, 398 (Tex. 1998) (stating that treating physicians do not owe a duty to third parties to warn epileptic patients not to drive, for purposes of negligence claims against physicians for failure to warn if patient has accident and injures third party during seizure; “Balancing both the need for and the effectiveness of a warning to a patient who already knows that he or she suffers from seizures against the burden of liability to third parties, we conclude that the benefit of warning an epileptic not to drive is incremental but that the consequences of imposing a duty are great.”).

Gourdine also argued that the Federal Food, Drug, and Cosmetic Act, which prohibits drug manufacturers from placing a misbranded product into interstate commerce, conferred a duty on Lilly. This statute and its regulations, however, are framed to protect the public in general, and, a statutory obligation which “runs to everyone in general and no one in particular” cannot impose a duty between two parties.
 

Wyeth Files Reply Brief in Levine Preemption Case

Wyeth has filed its reply brief in the Levine case.

The reply stresses that this case is not a conventional failure to warn case, but an alleged failure to contraindicate case. Thus, plaintiff is directly challenging the FDA’s balancing of the risks and benefits of a labeled, warned-about indication. State law cannot obstruct federal regulation of pharmaceuticals by seeking to impose a different outcome to this balancing process than the one reached by the FDA.

When the FDA did address the risks and benefits of the particular method of drug delivery at issue, the agency told the defendant to use labeling which the state court jury held was inadequate under state law. 

Wyeth also stressed what the case was not: no allegations of concealment from the agency or of failure to make a label change in response to any new risk information. The FDA had all the important information, and made a regulatory decision, which plaintiffs told the jury they could, and should, simply reject.

Note also an interesting discussion of CBE issues, with the arguments that this was not a CBE case, especially where methods of use are at issue, and that the FDA's interpretation of the CBE is entitled to Auer- level deference. (As noted in a post by MassTortDefense, the CBE regulation was always intended to apply solely to new, emerging, significant information.) Finally the plaintiff’s argument that the defendant must prove that a CBE submission would have been unsuccessful before qualifying for preemption would create the untenable and frequently dis-approved situation in which juries are deciding hypothetical situations full of what-ifs.
 

FDA Releases First Quarterly Safety Signals Report

The U.S. Food and Drug Administration has posted on its website its first quarterly report listing certain drugs that are being evaluated for potential safety issues. FDA posted the reports in accordance with Section 921 of the Food and Drug Administration Amendments Act of 2007, which, among other things, directs FDA to inform the public each quarter of new safety information or potential signals of serious risk, based on the agency's review of adverse event reports. Specifically, FDA is to "conduct regular, bi-weekly screening of the Adverse Event Reporting System [AERS] database and post a quarterly report on the Adverse Event Reporting System Web site of any new safety information or potential signal of a serious risk identified by Adverse Event Reporting System within the last quarter."

FDA released the first quarterly report, listing 20 drugs. The information is provided based on a review of reports in AERS. The FDA staff in the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) regularly examine the AERS database as part of routine safety monitoring. When a potential signal of a possible risk is identified from AERS data, it is entered as a possible safety issue into CDER's Document Archiving, Reporting, and Regulatory Tracking System (DARRTS) or into CBER's Therapeutics and Blood Safety Branch Safety Signal Tracking (SST) system. Potential signals of serious risks are normally based upon groups of AERS reports.

Drugs that appear on the agency's new "Potential Signals of Serious Risks/New Safety Information," are thus identified by FDA reviewers based on reports from the FDA's AERS database, which contains millions of reports of adverse events submitted to FDA by drug manufacturers, health care professionals and patients. For a drug to appear on this report, an FDA reviewer will have determined there is some reason to examine a drug more closely based on either the seriousness or number of AERS reports associated with the drug. The drugs for which issues have been identified are under evaluation for the listed potential risk. Each year, FDA receives about 400,000 reports of adverse events that people experienced around the same time period in which they were taking a drug.

An adverse event report does not establish a causal relationship between the drug and a particular event. The FDA itself has warned that for any given ADE case, there is no certainty that the suspected drug caused the event. This is because physicians and consumers are encouraged to report all suspected ADEs, not just those that are known or even suspected to be caused by the drug. The adverse event may have been related to an underlying disease for which the drug was given, to other concomitant drug usage, or may have occurred by chance at the same time the suspect drug was administered. The courts have characterized ADEs as “complaints called in by product consumers without any medical controls or scientific assessment.” McClain v. Metabolife Intern., Inc., 401 F. 3d 1233, 1250 (11th Cir. 2005). Because the reporting system is not subject to scientific controls, data from it is subject to various statistical biases. It is likely that the mix of reported events does not represent an accurate sampling of those events that can occur while a person is taking any medication. Moreover, medical or media attention can stimulate reporting in a distorted manner, and known adverse reactions are more likely to be diagnosed and reported than others. See DeLuca v. Merrell Dow Pharmaceuticals, Inc., 791 F. Supp. 1042, 1050 (D. N.J. 1992), aff’d 6 F. 3d 778 (3d Cir. 1993), cert. denied, 510 U.S. 1044 (1994) (ADEs “have inherent biases as they are second-or-third hand reports, are affected by medical or mass media attention, and are subject to other distortions.”).

MassTortDefense notes, that in contrast to how plaintiff attorneys seek to use the adverse event reports, or how the media has portrayed this new list, the appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk. It means that FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk. It may be too early to know whether there is an actual safety problem, and FDA’s analysis may ultimately conclude that there is no safety problem. If after further evaluation the FDA determines that the drug is associated with the risk, it may take a variety of actions including requiring changes to the labeling of the drug, requiring development of a Risk Evaluation and Mitigation Strategy (REMS), or gathering additional data to better characterize the risk. FDA also emphasizes that the listing of a drug does not mean that FDA is suggesting that prescribers should not prescribe the drug or that patients taking the drug should stop taking the medication. 

Thus, the new quarterly reports should not change the existing view of the majority of courts that adverse event reports are ordinarily too unreliable to be used as proof of causation. See McClain, 401 F. 3d at 1250; Hollander v. Sandoz Pharmaceuticals Corp., 289 F. 3d 1193, 1211 (10th Cir. 2001); cert. denied, 537 U.S. 1088 (2002) (characterizing the case reports before the court as unreliable evidence of causation); Haggerty v. Upjohn Co., 950 F.Supp. 1160, 1165 (S.D. Fla. 1996), aff’d, 158 F. 3d 588 (11th Cir. 1998); In re Accutane Products Liability Litig., 511 F. Supp.2d 1288, 1298-1303 (M.D. Fla. 2007); Benkwith v. Matrixx Initiatives, Inc., 467 F. Supp. 2d 1316, 1327 (M.D. Ala. 2006); Leathers v. Pfizer, Inc., 233 F.R.D. 687, 694 (N.D. Ga. 2006). See also Glastetter v. Novartis Pharmaceuticals Corp., 252 F. 3d 986, 990-91 (8th Cir. 2001) (“Case reports make little attempt to screen out alternative causes for a patient’s condition. They frequently lack analysis. And they often omit relevant facts about the patient’s condition.”); Dunn v. Sandoz Pharmaceutical Corp., 275 F. Supp.2d 672, 682 (M.D.N.C. 2003) (“Case reports are not scientific proof of causation.”); Caraker v. Sandoz Pharmaceuticals Corp., 172 F. Supp. 2d 1046, 1050 (S.D. Ill. 2001) (rejecting expert opinions insofar as they relied upon case reports); Nelson v. American Home Products Corp., 92 F. Supp. 2d 954, 969 (W.D. Mo. 2000) (“At most, these case reports relay a basis for scientific hypotheses; they do not demonstrate a causal link sufficient for admission to a finder of fact in court.”); DeLuca v. Merrell Dow Pharmaceuticals, Inc., 791 F. Supp. 1042, 1051 (D. N.J. 1992), aff’d, 6 F. 3d 778 (3d Cir. 1993), cert. denied, 510 U.S. 1044 (1994) (ADEs “are not of a type of data that are reasonably relied upon by experts in the fields of epidemiology and public health.”); Siharath v. Sandoz Pharmaceuticals Corp., 131 F. Supp. 2d 1347, 1359-63 (N.D. Ga. 2001); Cartwright v. Home Depot USA, Inc., 936 F. Supp. 900, 905 (M.D. Fla. 1996).
 

FDA Considering Revised Rule For Pediatric Cough and Cold Medications

The Food and Drug Administration has announced a public hearing on October 2, 2008, to obtain input regarding over-the-counter (OTC) cough and cold drugs marketed for pediatric use. Many of these nonprescription cough and cold drug products are marketed under the OTC Drug Review, which published a monograph describing the conditions under which certain OTC ingredients are considered to be generally recognized as safe and effective. Recently, some potential safety and efficacy concerns have been raised regarding the pediatric dosing and use of certain active ingredients in OTC cough and cold drug products. FDA is developing a proposed rule to revise the pediatric labeling guidance contained in the Final Monograph for Cough, Cold, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use. At this public hearing, FDA is interested in obtaining public comment about certain scientific, regulatory, and product use issues as it proceeds with the rule-making and reviews new drug applications (NDAs) for these ingredients.

MassTortDefense notes that there has been significant litigation in the past concerning ingredients used in many over-the-counter and prescription cough and cold medications as a decongestant to relieve stuffy nose or sinus congestion. At one point, Americans took 6 billion doses of the ingredient PPA each year from as many as 400 over-the-counter products containing PPA. A Yale Univ. study suggesting possible increased hemorrhagic stroke risks led manufacturers to remove PPA from their products. This in turn led to a mass tort, MDL and all. The epidemiology of the Yale study, according to plaintiffs, indicated that there were about 10,000 PPA-related strokes in the ten years preceding the FDA withdrawal. As it turned out, of nine PPA verdicts 2000-2006, only one was a plaintiff victory. As a result, PPA defendants were reportedly able to settle hundreds of the plaintiffs' best PPA cases for relatively modest amounts. Multiple PPA cases have been dismissed, either by plaintiffs lawyers or by the MDL court.

Today, FDA estimates that there are approximately 10,000 products being marketed for cold, cough, or combined indications under the OTC Drug Review. Depending on the dosage form and strength of these products, many of them are labeled for pediatric use, including some that are labeled for use in both adults and children. There are approximately 38 active ingredients in the final Monograph. Some combination cough and cold products contain as many as four of these active ingredients in a single dosage form, meaning that patients may be exposed to four different active ingredients when using a single product. From 2002 to 2006, there were approximately 36 billion units of combination cough and cold products sold each year in the United States. For liquid formulations used for the youngest children, there were approximately 190 million units sold each year in the combined cough and cold categories during this period. Cough and cold products are commonly used in children. A recent report suggested that 1 in 10 children uses one or more cough and cold products during a given week with exposure being highest among 2 to 5 year-olds.

FDA is interested in obtaining public comment on several issues, including:
1. What types of studies should be conducted to assess effectiveness and/or safety, and determine appropriate dosing of cough and cold ingredients in the pediatric population?
2. Should cough and cold products for the pediatric population continue to be available OTC, or should they be made available only by prescription?
3. If the pediatric indications and dosing for cough and cold products were no longer available OTC, would the public use the adult formulations of the products for children, and thus create a greater potential risk of misuse or overdose?
4. Current standards permit extrapolation of pediatric efficacy  -- but not safety-- based upon sufficient adult data. Does it remain appropriate to recommend in the cough and cold monograph that children 12 and over should receive the same dose of medication as adults, without requiring any additional studies in children in this age group?
 

FDA Finalizes CBE Rule, Reinforcing Preemption

The Food and Drug Administration has finalized the updated rule on using supplemental applications for changes to prescription drug, biologics, and medical device labels. The final rule, 73 Fed. Reg. 49603, allows manufacturers to submit a supplemental application to amend the labeling for an approved product to reflect newly acquired information. These supplements are commonly referred to as "changes being effected supplements" or "CBE supplements." The final rule becomes effective on Sept. 22, 2008. The final rule modifies 21 C.F.R. Sections 314, 601 and 814.

MassTortDefense would disagree with the media reports describing this as a “new” rule. In fact, the final rule affirms FDA’s longstanding position that a CBE supplement is appropriate to amend the labeling for an approved product only to reflect newly acquired information. But even though when it originally adopted this regulation FDA intended it as a limited, narrow, emergency exception to the general rule of Agency pre-approval of changes to prescription drug labeling, after preemption became a huge issue in prescription drug product liability litigation the regulation has been at times cited by courts as applying far more broadly than the FDA intended.

Plaintiffs argued that, since manufacturers are supposedly free to change their labels without prior FDA approval, there can be no conflict with state law holding them liable for not doing what the regulation supposedly allows. The plaintiffs thus have argued that the narrow exception swallows the rule that drug labeling changes are subject FDA pre-approval. Some courts have accepted this argument, and for example ruled that pharmaceutical defendants should have unilaterally strengthened suicide warnings for antidepressants – despite the FDA having evaluated the evidence of this alleged risk multiple times, concluding that there is no sufficient scientific basis for including a suicide warning. Compare McNellis v. Pfizer, Inc., 2006 WL 2819046 (D.N.J. Sept. 29, 2006) with Colacicco v. Apotex, Inc., 432 F. Supp.2d 514, 523, 527-28 (E.D. Pa. 2006). The Third Circuit's  take on this split is at Colacicco v. Apotex, 521 F.3d 253 (3d Cir. 2008).

FDA proposed the CBE procedure in 1982, making clear at the time that CBE supplements were intended to apply only if the sponsor became aware of newly discovered safety information that was appropriate for inclusion in the labeling for the product. Since then, the FDA has repeatedly tried, through amicus briefs, and in the 2006 preemption preamble, to inform courts of the limited scope of the regulation, with arguably mixed success. In briefs recently filed in the Supreme Court and in testimony before Congress, FDA has also stated a more generally applicable rule that is consistent with the examples of  cases finding preemption, and the principles set forth in the preamble to the 2006 Physician Labeling Rule,  that: (1) The labeling requirements are not a mere minimum safety standard, but rather strike a balance between risks and benefits, and (2) FDA's regulations permit changes in labeling without prior approval only in narrow circumstances. Specifically, FDA has explained that State law claims that "challenge labeling that FDA approved after being informed of the relevant risk" are preempted.

So now, the agency decided to change the regulation to say precisely what the agency has said it meant all along, with the hope that the lawyers and judges who have been ignoring it can’t do so any longer.

In January, several liberal Democrats in Congress wrote a letter to FDA questioning the basis for the proposed CBE rule, saying it appeared to be designed to shield pharmaceutical and medical device companies from liability sustained by consumers. But the rule does not alter the agency's current practices with respect to accepting or rejecting labeling changes proposed by a CBE supplement, reiterating the agency's longstanding view that the changes-being-effected mechanism is a narrow exception to the FDA's requirement of prior approval for labeling changes to approved products.

Under the rule, newly acquired information means data, analyses, or other information not previously submitted to the agency, which may include (but are not limited to) data derived from new clinical studies, reports of adverse events, or new analyses of previously submitted data (e.g., meta-analyses) -- if the studies, events or analyses reveal risks of a different type or greater severity or frequency than previously included in submissions to FDA. The final rule thus clarifies the meaning of "newly acquired information," such that the data, whether derived from new clinical studies, reports of adverse events, etc., needs to be new and different -- of a different type or greater severity or frequency than previously submitted to FDA. This limitation applies to data derived from new clinical studies, reports of adverse events, and new analyses of previously submitted data, alike. The final rule notes thus that there must be reasonable evidence of a causal association before a CBE supplement may be used to add or strengthen a contraindication, warning, precaution, or adverse reaction language.

The FDA rejected comments suggesting that a lower standard should be used under CBE for when a sponsor may warn, reiterating that it "interprets the Act to establish both a 'floor' and a 'ceiling', such that additional disclosures of risk information can expose a manufacturer to liability under the act if the additional statement is unsubstantiated or otherwise false or misleading." 

The new rule may be of some assistance in dealing with those courts that seem reluctant to recognize the longstanding view of the narrow scope of the CBE rule.  The rule limits the scenarios in which manufacturers of drugs, biologics, or medical devices can change a previously approved label in advance of the FDA’s formal review and approval mechanism. And the smaller the scope of things permitted in a CBE change, the greater the scope of conflict between FDA-approved labels and state court second-guessing of the warnings.  

More Amicus Briefing in Wyeth v. Levine

A number of entities have continued to weigh in as amici in the Wyeth v. Levine preemption case pending before the Supreme Court. In an amicus brief filed earlier this summer, BIO and PhRMA argued from a policy perspective that state law tort suits challenging the adequacy of FDA approved prescription drug labeling pose significant risks to public health. (BIO is the world's largest biotechnology organization, providing advocacy, business development and communications services for more than 1,150 members worldwide.) Those suits imperil FDA's ability to accomplish its mission because they allow state court juries to second guess FDA's balancing of the risks and benefits of a prescription medicine. State court verdicts inconsistent with FDA guidance will simply encourage manufacturers to warn physicians and patients about risks that are speculative and scientifically unsupported; this ultimately dilutes the impact of scientifically valid warnings and can discourage physicians from prescribing and patients from using beneficial drugs.

On the legal side, these amici argued that the Vermont Supreme Court's decision now on appeal was at odds with a core premise of the Supremacy Clause: that state law cannot require what federal law prohibits. Absent new scientific information, federal regulations prohibit a manufacturer from changing prescription drug labeling without prior FDA approval. In this case, FDA knew of and considered the relevant risk over a long period of time, and approved carefully crafted warnings and instructions designed to minimize those risks while still encouraging beneficial drug use.

The Latest

Last week, in what appears to be a first, the editors of the New England Journal of Medicine  weighed in on the preemption legal battle -- on the side of the plaintiff below, Levine. While the brief attacks the track record of the FDA, arguing that the agency lacks the resources to do its job, it does not answer the next question: whether experts at the FDA, even with allegedly inadequate funding, are more or less likely to decide difficult scientific questions correctly than are juries of lay people “educated” by trial lawyers. The NEJM spouts the rhetoric of juries "policing" the industry.  But a dramatic gulf separates the competence of the FDA from that of state jurors who, absent preemption, are called on to assess the safety of prescription drugs and second-guess federal regulators. Laypersons applying state law cannot substitute for the FDA, the expert agency congressionally delegated the role of meticulously balancing nuanced and sometimes competing nationwide goals. The FDA’s regulation of prescription drugs is governed by a sweeping network of federal law individually applied to each drug. A lay jury lacks the expertise and the broader perspective of the FDA, and thus cannot adequately adjudicate individual plaintiff/patient risks in the context of population benefits – quintessentially the kind of issue that the FDA must confront every day. Without preemption, however, state juries are asked to do just that.

Similarly, the NEJM brief bemoans the fact that FDA is reliant upon information gathered and produced by the drug company, but the fact is that no entity other than the drug company has any incentive or ability to study a not-yet-approved drug. And permitting after the fact tort suits to second-guess the FDA won’t change that. Moreover, how is the situation any different in a tort suit? If a new study comes out about the risks or benefits of a drug or device after a tort suit has been concluded, we don’t go back and start the case again. Would the NEJM advise unwinding the results in Bendectin litigation? Breast implants? The state of the art is by definition time-dependent.

And as pointed out in DRI’s amicus brief, there was an enhancement of the FDA’s powers by the recent FDAAA. This contrasts a one possible way (congressional action) and a clearly worse way (complaining in state court litigation) to deal with perceived deficiencies in FDA action.
 

Lone Pine Order Entered in Celebrex MDL

The federal judge overseeing the MDL for Celebrex and Bextra has sided with defendants' view that a “Lone Pine” order is appropriate for managing the claims of the remaining, non-settling plaintiffs. In re: Bextra and Celebrex Marketing Sales Practices and Product Liability Litigation, No. M:05-cv-01699 (N.D. Cal.) (Pretrial Order No. 29, Aug. 1, 2008).

“Lone Pine” orders take their name from a 1986 New Jersey Superior Court case involving toxic tort claims; they refer to case management orders that require the plaintiffs to make a showing regarding causation, injury, and/or damages to demonstrate, typically at an early stage, some minimal level of evidentiary support for the key components of their claims which will be in dispute.

Defendants had first asked the court for a Lone Pine order in late June, arguing that each plaintiff should be required to submit a case-specific expert report on the issue of medical causation. The motion also sought to compel each plaintiff to turn over medical records that documented an injury, prescription records that showed medication history and dosages prescribed, and proof of dosage in relation to the confirmed injury. The benefits to the court of requiring plaintiffs to supply this information is that the parties would not have to engage in protracted discovery in thousands of cases just to see whether each one has some threshold evidence of medical causation. The production of such basic and threshold evidence was argued to be simply a part of a good-faith investigation that should precede the filing of a lawsuit.

Plaintiffs argued that the proposed order would be overly burdensome, was not needed, and was a retaliation for not settling. Plaintiffs also suggested that Lone Pine orders are generally issued as sanctions against plaintiffs who provide no other information to the defendants about the filed case. But the court disagreed with plaintiffs.

The court appeared mindful of what had happened on the eve of the first trial in the MDL, as the scheduled cases began to disappear. Thus, under the Order, plaintiffs will have 45 days to have a physician or other medical expert offer a case-specific expert report for each plaintiff including a review of the plaintiffs’ medical records, the dates they used Celebrex and/or Bextra, and whether they experienced a myocardial infarction, ischemic stroke, sudden death, or any other injury while taking the medications.

The court observed that all of this information should be already readily available to plaintiffs through the plaintiff fact sheets process. The court apparently expects that cases in which plaintiffs cannot show drug usage, injury, or causation, will drop from the docket before being scheduled for trial. Without threshold proof of Celebrex or Bextra usage, a compensable injury, and a link between usage and an injury, there could have been no good-faith basis for a lawsuit in the first place.

Moreover, requiring plaintiffs to identify basic information about injuries and causation is not unreasonable given the costs that mass tort claims have on the legal system, and on defendants. Lone Pine orders allow courts to weed out the frivolous suits where there is insufficient exposure, or no sufficient scientific connection between injury and exposure. Accordingly, Lone Pine orders can be effective when entered early in the game. Early disposal of frivolous claims allows the parties to focus their attention on the serious cases. Ideally, the order will actually phase discovery, and motions practice as well, with the Lone Pine issues pushed up front.

With their focus on causation, Lone Pine orders are especially useful when multiple plaintiffs claim a variety of different injuries, allege injuries incurred over a long period of time, and/or when plaintiffs allege diverse exposures.

 

Partial Summary Judgment Granted in Aredia MDL

Novartis Pharmaceuticals Corp. has prevailed in a motion to end certain failure-to-warn claims in cases in the MDL relating to its bone cancer drugs Aredia and Zometa. The U.S. District Court for the Middle District of Tennessee granted defendant’s motion for partial summary judgment, dismissing claims of eight Texas-based plaintiffs. In Re: Aredia and Zometa Products Liability Litigation, No. 06-md-01760 (M.D. Tenn.) Opinion found here.

The motion was based upon a Texas statute which protects a defendant from any products liability claims involving failure to provide adequate warnings if the drug at issue and accompanying warnings were approved by the FDA. The statute creates the presumption such warnings were adequate, and then specifically explains how a claimant can rebut this presumption:

(b) The claimant may rebut the presumption in Subsection (a) as to each defendant by establishing that: (1) the defendant, before or after pre-market approval or licensing of the product, withheld from or misrepresented to the United States Food and Drug Administration required information that was material and relevant to the performance of the product and was causally related to the claimant’s injury. Tex. Civ. Prac. & Rem. Code Ann. § 82.007(b)(1).

The court noted that plaintiffs were correct that the language of the Texas statute specifically creates a rebuttable presumption that a defendant is not liable for failure-to-warn claims if the warnings provided with the product were approved by the FDA. The Texas Legislature, however, went on to establish certain evidentiary standards for rebutting this presumption. The presumption of adequate warnings, therefore, is unrebuttable unless one of the specific statutory provisions applies.  Here, the only possible exception was the so-called fraud-on-the-FDA exception. However, in Buckman Co. v. Plaintiffs’ Legal Comm., 121 S.Ct. 1012 (2001), the Supreme Court found that the plaintiffs’ state law fraud-on-the-FDA claims conflicted with and were therefore impliedly preempted by the Federal Food, Drug and Cosmetic Act. Noting that policing fraud against federal agencies is hardly a “field which the States have traditionally occupied,” the Court held that it is the FDA’s exclusive responsibility to police fraud or wrongdoing in connection with approval of products before the FDA. Id. at 1017.   The Court stated that fraud-on-the-FDA claims would “inevitably conflict with the FDA’s responsibility to police fraud consistently with the Administration’s judgment and objectives.” Id. at 1018. In sum, the Court opined, this sort of litigation would exert an extraneous pull on the scheme established by Congress, and it is therefore preempted by that scheme. Id. at 1020.

Under the Texas law, in order to rebut the presumption plaintiffs must establish that defendant withheld or misrepresented “required information” to the FDA. The Court found that the task of determining whether certain information was “required” by the FDA would raise the federalism concerns expressed in Buckman.

Second, the Texas statute also requires that the information which was withheld or misrepresented be “material and relevant” to the performance of the product. Because subsection (b) concerns misrepresentations to the FDA, it is reasonable to infer that the information must be “material and relevant” to the FDA. Determining what information would have been important to the FDA would also create the federalism concerns noted by the Court in Buckman.

Finally, the information which was allegedly withheld or misrepresented must, under the Texas statute, be causally related to plaintiffs’ injuries. Unless the withheld information would have resulted in some definite change by the FDA, such as either non-approval of the drug or a labeling change, such withheld information could not be causally related to a plaintiff’s injury. Again, in order to establish that the FDA would have acted differently if defendant had submitted accurate information, plaintiffs would have to “go behind” the FDA processes, raising the concerns sought to be avoided in Buckman.

The Court thus found that the requisite showing under the Texas statute is analogous to and sufficiently equivalent to asserting a claim of fraud on the FDA that the fraud claim/presumption defense/statutory exception is itself preempted under Buckman. For all these reasons, Defendant’s Motion for Partial Summary Judgment was granted.

The ruling on the Texas claims follows the MDL court's April ruling dismissing claims by Michigan plaintiffs. The court had relied on Garcia v. Wyeth-Ayerst Laboratories, 385 F.3d 961 (6th Cir. 2004), for the proposition that the Michigan fraud exception was also preempted under the U.S. Supreme Court's decision in Buckman.

Recent Preemption Ruling: Wait For Levine

A recent trial court decision shows the state of flux in applying the preemption doctrine in pharmaceutical cases. In the Celexa/ Lexapro MDL, the court denied without prejudice the defendant’s preemption motion, to allow further discovery and expressly because the United States Supreme Court has granted certiorari in Levine v. Wyeth, 128 S.Ct. 1118 (2008), to consider the extent to which prescription drug labeling judgments imposed on manufacturers by the FDA, pursuant to FDA's comprehensive safety and efficacy authority under the Federal Food, Drug, and Cosmetic Act, preempt state law product liability claims premised on the theory that different labeling judgments were necessary to make drugs reasonably safe for use. See In re Celexa and Lexapro Products Liability Litigation, 2008 WL 2906713 (E.D.Mo. July 24, 2008), found here.

 

FDA Advisory Committee Discusses Nano-technology Issues

The FDA’s Advisory Committee for Pharmaceutical Science and Clinical Pharmacology met last week. Among the agenda topics was a discussion of current thinking on issues pertaining to the use of nanotechnology in drug manufacturing, drug delivery, or drug products. (The general function of this committee is to provide advice and recommendations to the agency on regulatory issues.) Scheduled to speak were representatives of the Office of Pharmaceutical Science at CDER, nano-medicine industry leaders, and academics.

MassTortDefense has posted on nano-technology here.

As CDER grapples with questions regarding how to regulate nanomaterial-containing products, several issues have surfaced, including 1) what are the types of nanotechnology applications that will be reviewed by CDER, 2) what are the unique features of these applications that may pose a scientific and/or regulatory challenge to reviewers, 3) are FDA’s current regulatory requirements adequate for the evaluation of nanomaterial-containing products, and 4) what can FDA do to expedite the development of safe and effective nanomaterial-based pharmaceuticals.

Nanotechnology applications in drug development are likely to have a significant impact on the products that FDA regulates. Products containing nanomaterials are being investigated for potential applications as therapeutics, and some products containing nanoscale materials are already on the market. While some of these nanomaterials are nanoscale versions of larger materials used in approved products, other nanomaterials are novel and have never been used in drug products. CDER has initiated a number of activities in order to evaluate how this new technology fits into the current regulatory framework. There have been questions raised about the need for “nano”-specific requirements, in part to aid the development of products containing nanomaterials, and in part because nanomaterial containing products may need to fulfill different regulatory requirements prior to approval.

The FDA established a Nanotechnology Task Force, which issued a report in July 2007. In the task force report, recommendations were made regarding FDA’s future direction for regulating nanomaterial-containing products. Guidance development was included as one the recommendations. FDA believes, however, that the preclinical studies currently required of sponsors are very comprehensive, and include many studies that measure endpoints that could predict possible injury in many organ systems. While general issues have been raised, no one has clearly communicated in what respect the current requirements might be lacking in their capacity to assess safety concerns from such products, and what might be other tests that would improve the predictive value of the current regulatory preclinical requirements.

Nevertheless, because it is widely accepted that there are unique features associated with
nanotherapeutic products, these unique features may lead to future challenges for the development, manufacturing, and possibly safety evaluation and review of these products. Accordingly, the committee was set to discuss:

1. Is CDER guidance needed for the development of nanotechnology-derived drug applications?
2. If guidance is needed from CDER, what areas should this guidance focus on?
3. In light of the many definitions of nanotechnology available, how should CDER define nanotechnology, for the purposes of guidance development?
4. Should particle size information be routinely requested of drug developers, regardless of whether nanomaterials are included in the product? How might this information help in the assessment of safety and efficacy of drugs?

Clearly this is no small issue.

 

Federal Court Reverses Self On Drug Preemption

Judge David F. Hamilton of the U.S. District Court for the Southern District of Indiana has reversed a prior decision and reinstated a Paxil suicide case that had been dismissed – properly in the view of MassTortDefense --  on preemption grounds last year. See Tucker v. SmithKline Beecham Corp./d/b/a Glaxosmithkline, No. 04-1748, (S.D. Ind. 7/18/08). See opinion here.  In granting plaintiff’s motion for reconsideration, the court violated the rule “if it ain’t broke, don’t fix it.”

Plaintiff Debra Tucker sued GSK on behalf of her brother, Rick Tucker, alleging that her brother committed suicide in September 2002 as a result of taking Paxil for three weeks. The claim was that GSK breached a duty to warn of an alleged increased suicide risk among Paxil patients. (MassTortDefense notes that the scientific evidence actually does not establish that paroxetine (the active ingredient in Paxil) causes suicide, suicide attempts, self-harm or suicidal thinking. On the basis of research in tens of thousands of patients taking antidepressants, including Paxil, there is no significantly increased risk of suicidal thinking or behavior in people age 24 and older and, in fact, in patients older than 65, there was a reduction in risk in suicidal thoughts and behavior.)

The defendant sought summary judgment on preemption grounds. The court correctly determined in September, 2007, that her claims conflicted with the FDA's labeling requirements for Paxil. The court said it believed the record showed that the FDA had rejected the hypothesis that there is a causal link between Paxil and suicide.

In granting the plaintiff's motion for reconsideration, the court said it had "failed to appreciate the fact that the ongoing ability, authority, and responsibility to strengthen a label still rest squarely with the drug manufacturer." In its new decision, the court first noted that under 21 C.F.R. §201.80, a manufacturer must revise labeling "to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved." Under 21 C.F.R. §314.70(c), a manufacturer may unilaterally add or strengthen a contraindication, warning, precaution or adverse reaction upon submission of a "changes being effected" [CBE] supplement. The court now thinks that the FDA's power to disapprove a label "does not make the manufacturer's voluntarily strengthened label a violation of federal law, which is what it would take to establish an actual conflict between state tort law and federal law.”  If the agency disapproves the revised label, the manufacturer simply stops distribution; there is no retroactive illegality.

The court’s new order rejected the FDA’s position that such failure to warn claims are preempted, calling the agency's position on preemption an "180-degree reversal" of its earlier stance. On reconsideration, the court thus gave "relatively little weight to the FDA's opinion on the preemptive effects of its regulations." In 2006, the FDA amended its regulations governing prescription drug labeling, clarifying the preemption of certain warning claims. The court adopted plaintiff’s argument that the 2006 Preamble was promulgated without notice-and-comment.

GSK argued that drug manufacturers will be forced to place scientifically unsubstantiated warnings on their drug products unless state law tort claims are preempted. But the causation requirements on plaintiffs will guard against this risk, the court said. In fact, thought the court, failure to warn litigation can reinforce the FDA's regulations, which already place the obligation to strengthen the warnings on a drug's label “squarely on the shoulders of the drug's manufacturer."  GSK's possible future risk of prosecution for distributing a misbranded drug would present a conflict only if GSK could say with absolute certainty that it will never have new evidence sufficient to trigger its regulatory obligations to revise its label to strengthen a warning with Paxil-specific language, but is forced to do so by state tort law, stated the new opinion.

Here’s why the new opinion got it wrong.
Regarding CBE, proposed changes in labeling typically are first submitted to the FDA for
approval. 21 C.F.R. § 314.70(a)-(d). A limited exception is with the use of a changes being effected supplement. 21 C.F.R. § 314.70(c). When a new safety issue emerges with a product, the pharmaceutical company may temporarily add to the product's labeling under this rule, which describes "changes that may be made before FDA approval." 21 C.F.R. § 314.70(c). Nonetheless, the FDA must still be notified and will subsequently review the modified labeling to ensure compliance with FDA regulations. In 1982, when the CBE procedure was proposed, the FDA stated, "these supplements would describe changes placed into effect to correct concerns about newly discovered risks from the use of the drug." 73 Fed. Reg. 2849 (Jan. 16, 2008) (quoting 47 Fed. Reg. 46622, 46623 (Oct. 19, 1982)). FDA’s longstanding position is that a CBE supplement “is appropriate to amend the labeling for an approved product only to reflect newly acquired information . . . to add or strengthen a contraindication, warning, precaution, or adverse reaction only if there is sufficient evidence of a causal association." 73 Fed. Reg. 2848 (Jan. 16, 2008). The FDA explicitly defines "newly acquired" as "data, analyses, or other information not previously submitted to the agency." Id. at 2850.

The holding of the court that any label change adding or strengthening warnings could always be made unilaterally, without FDA pre-approval, would lead to absurd and unreasonable results. If manufacturers were free to make unilateral changes to labeling the day after FDA’s approval based on information that was previously available to the agency, the approval process would be greatly undermined and the agency’s careful balancing of risks and benefits thwarted. And plaintiff’s proposed reading of the rule would require manufacturers to make the same CBE change over and over again – despite FDA rejection of the change – in order to avoid liability, because a jury would be free to say – despite the FDA decision – that the manufacturer was free to make the change anyway. It just doesn’t make any sense for the CBE process to permit (and thus obligate, under plaintiffs’ view), a manufacturer to ignore an FDA-mandated label by unilaterally changing the warning to something else. Plaintiffs' construction of the current CBE regulation would permit (and thus obligate) manufacturers to repeat such changes again and again, each time the FDA rejects the proposed change – all without any new scientific evidence to warrant any change at all. Plaintiffs could argue that the “weight” or “accumulation” of evidence required a label change, even as the FDA has rejected changes based on each individual “new” evidence. The only way to prevent the CBE exception from becoming a vehicle for ignoring FDA labeling decisions is to limit it to new information. Any changes to a drug’s labeling without prior FDA approval must be based on new information establishing that risks arising from use of the drug are of a different type or greater severity than the risks of which FDA had previously been made aware – not cumulative new information that does not add to the information that was previously available to the agency.

Second, since this part of the argument is about interpretation of the scope of the FDA’s own CBE regulation, government views concerning that regulation are entitled to substantial deference, not the little weight given. Judicial deference to administrative positions on preemption, typically expressed in amicus briefs, has more or less been the rule, rather than the exception.

Third, regarding the supposed “reinforcing” aspect of tort claims, the new decision in this case would allow a jury to determine whether an FDA-approved label adequately informs physicians about a medication's risks and benefits, as the label generally has to be found to be inadequate before the manufacturer can be held liable. This could result in a patchwork of labels/warning information that vary from state to state for no good reason – the science in Maine is the same in California, even if the juries are not. And this would place doctors and patients in an untenable position. Indeed, state common-law tort actions based on the manufacturers’ failure to warn present the pharmaceutical manufacturers with particular difficulties. State standards of care undoubtedly would differ from state to state. Absent a determination that the FDA-approved labeling and the FDA’s refusal to require the warnings suggested by plaintiffs in this case preempt state tort actions, the manufacturers may be subjected to considerable liability based on varying standards, with no benchmark that they should follow.

The FDA, rather than a jury, has the responsibility to determine whether the labels on medicines offered in the U.S. are appropriate. The FDA has actively monitored the possible association between SSRIs and suicide for nearly twenty years, and has concluded that the suicide warnings desired by plaintiffs are without sufficient scientific basis and would therefore be false and misleading. This claim of supposed harmony or reinforcement by tort law is belied by what the plaintiffs always ask for:  that state courts provide a check on agency power; that state juries be allowed to make their own judgment on whether the label was adequate; and that FDA approval of a label, or rejection of an alternate label, doesn’t mean anything to the company’s potential liability.

Finally, regarding misbranding, a pharmaceutical company that independently institutes a change in labeling may be subject to penalty or seizure if the drug is deemed misbranded by the FDA. See 21 U.S.C. § 333 (authorizing penalties); 21 U.S.C. § 334 (authorizing seizure); 21 C.F.R. § 7.45(a) (providing authority to request recall). And it has never been required, for a conflict to exist, to show how many times the federal law was applied, or how significant the sanctions were. That the federal agency has the legal power to enforce the federal rule is, and ought to be, sufficient.

In its next term, the U.S. Supreme Court will take up a preemption question in Wyeth v. Levine, and we may see if the court got it right the first time or the second time.

Shoe On The Other Foot: State/Plaintiff Criticized For Discovery Reponses

Managing the potentially vast scope of discovery requests in life sciences industry litigation can be daunting. The discovery requests in such litigation may be quite broad, following the product through its entire life cycle, and under the new(ish) Federal Rules can be even broader than in the past. They may now involve requests for samples, requests for access to databases, requests for technical support and IT depositions.

Companies in the life sciences area know well that multiple kinds of litigation now regularly arise from same product issue or nucleus of facts, including
– product liability
– medical monitoring
– securities
– consumer fraud class action
– DOJ and government investigations

The vast array of litigation raises the potential for inconsistent positions in the different parts of the litigation concerning same subject. In addition, defendants must be on guard against spoliation attacks and the plaintiffs’ new favorite, the “Gotcha” Game, in which plaintiffs seek discovery not for information, but to find and challenge wherever defendant drew the line in document or data preservation. All in all, the management and conduct of e-discovery has become an area of true specialization.

Defendants may have wondered whether discovery is a two-way street under the new rules. Plaintiffs don’t have as much data, perhaps, and courts have been reluctant to hold individual plaintiffs to the same standards as corporate defendants. In a recent decision in the Zyprexa litigation, a governmental plaintiff may have been, however.

The magistrate judge overseeing discovery in the MDL has weighed in on the state of New Mexico’s apparent failure to properly respond to discovery requests in a lawsuit it filed against Eli Lilly & Co. over Zyprexa. Madrid v. Eli Lilly & Co., No. 07-cv-1749 (MDL-1596 E.D.N.Y.).

As is typical in this branch of the litigation, the state alleges that it would not have spent Medicaid funds on Zyprexa if it had known more about the supposed risks of the drug. The lawsuit was removed to the U.S. District Court for the District of New Mexico in 2006 after it was originally filed in state court. It was transferred for pretrial proceedings to the U.S. District Court of the Eastern District of New York by the panel on multidistrict litigation.

Earlier this month, Eli Lilly challenged the adequacy of the state's responses to interrogatories and document demands it had made in June. The magistrate judge's Order concluded that New Mexico had neither replied to Lilly's attempts to confer in good faith on this issue nor had it provided the court with any justification whatsoever for its boilerplate objections. The state's silence on this issue “underscores the indefensible nature of its responses.” Apparently, the state had ignored the specificity requirement for objection and merely labeled each request as “unintelligible” or “irrelevant.” The court also faulted the state for not including a privilege log.

Discovery is supposed to be a two-way street.

Parties Spar Over Possible Bifurcation In Mirapex MDL

Pfizer and the other defendants in the Mirapex litigation are seeking a bifurcated trial plan. In motions filed with the U.S. District Court for the District of Minnesota, where MDL-1310 is based, the defendants asked for separate liability and punitive damages phases. Defendants raised the legitimate concern that the jury may be swayed by financial considerations when determining liability.

In this litigation, plaintiffs allege that the drug causes a compulsive urge to gamble. The plaintiffs claim that Mirapex triggered compulsive behaviors, and that the defendants knew the risks but failed to properly study the effects or warn patients. As is so often the case, a label change (in February 2006) seems to have prompted litigation.

Defendants assert that bifurcation is warranted because evidence of defendants' finances is irrelevant to the issues of liability; introduction of such evidence during the liability phase would be unduly prejudicial. Bifurcation is thus necessary to prevent unfair prejudice to defendants during the liability determination. The motions note that the 8th Circuit has recognized bifurcated trial plans in a number of settings. Indeed, bifurcation is a common feature of pharmaceutical mass torts.

Plaintiffs oppose the proposal, arguing that the issue of liability and punitive damages are somehow “intertwined.” Meaning, of course, that they would like for the jury to consider the company’s financials when judging its conduct. Plaintiffs insist on a single trial where the fact finder considers “all the evidence at once.” To the extent some of that evidence should not be considered on the issues of liability, plaintiffs propose that the jury could be instructed to consider the financial information only in the proper context.

MassTortDefense has posted on the importance of proper trial plans here. The Mirapex motions present perhaps the most basic form of bifurcation or trial plan issue.  The timing of the punitive damages issues in class actions or other complex aggregated litigation can become highly complex and controversial. The questions as to punitive damages may include: a) whether they can be awarded; b) if so, whether as a lump sum, as a multiplier of individual compensatory damages, or on a per class member basis, c) whether they can be tried before individual liability as to specific class members, or as to absent class members, or non-bellwether plaintiffs has been decided; d) whether they can be awarded before the actual amount of compensatory damages has been determined; and e) how punitive damages are allocated among class members or the aggregated plaintiffs if not determined on a per plaintiff basis. State Farm Mutual Auto Insurance Co. v. Campbell, 538 U.S. 408 (2003). See In re Simon II, 407 F.3d 125 (2d Cir. 2005); Beck v. Boeing Co., 60 Fed. Appx. 38 (9th Cir. 2003); Allison v. Citgo Petroleum Corp., 151 F.3d 402 (5th Cir. 1998); Johnson v. Ford Motor Co., 35 Cal.4th 1191,113 P.3d 82 (Cal. 2005) (rejecting aggregate disgorgement); Engle v. Liggett Group, Inc., 945 So.2d 1246, 1265 (Fla. 2006); In re Chevron Fire Cases, 2005 WL 1077516, at *14-15 (Cal. App. May 6, 2005); Colindres v. QuitFlex Manufacturing, 235 F.R.D. 347, 378 (S.D. Tex. 2006).

Punitive damages are designed to punish a defendant for egregious conduct and deter future reprehensible conduct on the part of the defendant or others. Particularly in the context of juries unchecked by proper legal instructions and unorthodox trial plans that prematurely address the punitive damages issue, they constitute a serious litigation threat to product sellers today. In aggregated litigation, such damages have the potential to lead to crippling verdicts, and thus the threat of punitive damages may coerce “blackmail” settlements.

In recent years, the United States Supreme Court has identified a variety of constitutional limits on punitive damage awards. Specifically, such awards cannot be arbitrary punishments and cannot be grossly excessive. In Philip Morris USA v. Williams, 127 S.Ct. 1057 (2007), the Court confirmed a significant constitutional principle limiting punitive damages awards: the Due Process Clause prohibits juries from basing punitive damages awards in part upon the desire to punish a defendant for harm to persons that are not before the court. Williams arose from an Oregon trial wherein a jury awarded $821,000 in compensatory damages and $79.5 million in punitive damages against cigarette manufacturer Philip Morris. At trial, the plaintiff’s attorney had urged the jury to punish Philip Morris for alleged harm to smokers other than the plaintiff by referring to the defendant’s market share and the number of smokers not only in the state of Oregon, but nationwide, who had allegedly contracted a smoking-related illness in the last 40 years. The Supreme Court held that the Due Process Clause forbids a jury from assessing punitive damages to punish a defendant for injury that it inflicts upon non-parties or “strangers” to this litigation. While a jury may consider the actual or potential harm to non-parties in the narrow context of determining “reprehensibility” of the conduct, which in turn is one of the factors relevant to an analysis whether the punitive damages award is excessive or not, it may not punish the defendant for the impact of its alleged misconduct on other people, who may bring lawsuits of their own in which other juries can resolve their claims. The Court cautioned state courts that they must make sure that the “jury will ask the right question, not the wrong one.” That is, evidence regarding alleged injuries of those not before the court must be used solely to judge the reprehensibility of the conduct, not to assess damages for the harm caused to those strangers. While the Court commented on the Oregon court’s refusal to give a jury instruction clarifying this distinction, it noted that state courts cannot authorize any procedures that create an unreasonable and necessary risk of any such confusion occurring. When evidence is introduced or argument made that risks this confusion, the state court must take steps to protect against that risk.

One implication of the Court’s emphasis on avoiding misuse of evidence of harm to “strangers” clearly relates to the employment of reverse-bifurcated trial plans in aggregated cases, in particular trial plans in which the entitlement and amount of punitive damages (by ratio or dollar amount) is set in an early phase of the trial, well before the jury has considered whether the vast bulk of the plaintiffs have actually been injured by the alleged conduct of the defendant. E.g., In re Tobacco Litigation, 624 S.E.2d at 740 (W. Va. 2005)(holding that an aggregated, reverse-bifurcated punitive damage multiplier trial before adjudication of any affirmative defense would not be per se invalid). Some state courts favor this approach because it puts pressure on defendants to settle by creating the risk of a huge punitive damages burden before it has even been established whether many or most of the plaintiffs have any compensatory damages. Such a trial plan clearly creates an unnecessary and unreasonable risk of a due process violation under Williams, one that a simple jury instruction about the distinction between entitlement and reprehensibility cannot hope to address adequately. See, e.g., In re Simon II Litig., 407 F.3d at 138 (“In certifying a class that seeks an assessment of punitive damages prior to an actual determination and award of compensatory damages, the district court’s Certification Order would fail to ensure that a jury will be able to assess an award that, in the first instance, will bear a sufficient nexus to the actual and potential harm to the plaintiff class, and that will be reasonable and proportionate to those harms.”); Allison v. Citgo Petroleum Corp., 151 F.3d at 417–418 (stating that “because punitive damages must be reasonably related to the reprehensibility of the defendant’s conduct and to the compensatory damages awarded to the plaintiffs, . . . recovery of punitive damages must necessarily turn on the recovery of compensatory damages”); Southwestern Ref. Co. v. Bernal, 22 S.W.3d at 433 (“Under the [trial plan], the jury would decide punitive damages for the entire class without knowing the severity of the offense or the extent of compensatory damages, if any, for each of the 885 plaintiffs…. the modified trial plan is … prejudicial because it fails to ensure that punitive damages have some understandable relationship to compensatory damages and are not grossly out of proportion to the severity of the offense for each of the 885 plaintiffs.”).

Daubert Ruling And Summary Judgment In Lymphoma Case

Judge Stewart Dalzell of the U.S. District Court for the Eastern District of Pennsylvania granted summary judgment to Novartis Pharmaceuticals Corp. in a suit that alleged the company's eczema drug, Elidel, caused plaintiff’s lymphoma. Perry v. Novartis Pharmaceuticals Corp., 2008 WL 2683047 (E.D. Pa. July 09, 2008). Although we typically focus on appellate opinions at MassTortDefense, this well-reasoned opinion is worth a look.

The Perrys filed suit against Novartis in October, 2005 alleging that the company had failed to warn about the risks of Elidel. Their son allegedly developed eczema shortly after his birth, and a pediatrician prescribed Elidel in 2003. He was diagnosed with lymphoma a few months later.

Defendant challenged plaintiffs’ expert evidence on causation. As is frequently the case, if plaintiffs’ expert testimony does not meet the Daubert standard, summary judgment for failure of proof on causation follows. The court noted that the core issue that the jury would have to address in this case is whether Perry's exposure to Elidel was a substantial cause of his disease. Courts in toxic tort cases often separate the causation inquiry into general causation (whether the substance is capable of causing the observed harm in general), and specific causation (whether the substance actually caused the harm a particular individual suffered). Plaintiffs' experts did the same, each drawing conclusions about both the capacity of the drug to cause Non-Hodgkins Lymphoma (NHL) in humans and its particular effect in Perry's case.

An expert's journey from general causation to specific causation need not be just a two-step process. So long as, taken together, the expert is able to draw a chain of scientifically reliable causal links that meets plaintiff's requirements under the substantive tort law, the evidence is admissible, and it will be left to the jury to establish the relative credibility of the parties' competing experts. Where, however, the expert reports leave wide, unexplained gaps in the causal chain, the evidence is not helpful to the trier of fact and must be excluded. In Daubert terms, just as there is no fit where there is simply too great an analytical gap between the data and the opinion offered, see Soldo v. Sandoz Pharms. Corp., 244 F.Supp.2d 434, 527 (W.D. Pa. 2003) (quoting General Electric Co. v. Joiner, 522 U.S. 136, 146 (1997)), “there is also no fit when there is too great an analytical gap between an expert's general causation conclusion and the specific causation question the jury must ultimately answer,” said the court.

One problematic gap concerned epidemiology. Although it has not been held by the Third Circuit that epidemiological studies are an indispensable element in the presentation of a prima facie drug product liability case, Lanzilotti v. Merrell Dow Pharms. Inc., 1986 WL 7832 (E.D.Pa. July 10, 1986) at *2, epidemiology is the primary generally accepted methodology for demonstrating a causal relation between a chemical compound and a set of symptoms or a disease. See Soldo, 244 F.Supp. at 532 (quoting Conde v. Velsicol Chem. Corp., 804 F.Supp. 972, 1025-26 (S.D. Ohio 1992)). Thus, while an expert's conclusions reached on the basis of other studies could perhaps be sufficiently reliable where no epidemiological studies have been conducted, no reliable scientific approach can simply ignore the epidemiology that does exist.

A second issue concerned the state of the art. The court made clear that the non-existence of good data does not allow expert witnesses to speculate or base their conclusions on inadequate supporting science. In cases where no adequate study shows the link between a substance and a disease, expert testimony will generally be inadmissible, even if there are hints in the data that some link might exist. This may mean that early victims of toxic torts are left without redress because they are unable to prove their cases with the scientific data that currently exists. While this is a “regrettable result in those individual cases,” said the court, it is an unavoidable reality of the structure of our legal system and is necessary to protect the interests of defendants who might otherwise be subject to crippling verdicts on the basis of slender scientific evidence. As the Seventh Circuit has noted, the courtroom is not the place for scientific guesswork, even of the inspired sort. “Law lags science; it does not lead it.” Rosen v. Ciba-Geigy Corp., 78 F.3d 316, 319 (7th Cir.1996).

Focusing next on specific causation, the court noted that each plaintiff expert engaged in a differential diagnosis. MassTortDefense notes the increasing use, and misuse, by plaintiffs of so-called differential diagnosis. The process by which a doctor views symptoms and test results to rule out possible alternative diseases in the diagnostic process to arrive at a conclusion concerning what ails the patient, has morphed into a process by which experts can tell the jury what caused the condition of the plaintiff – a far different thing. Here, after finding that no other risk factor for NHL was present, the experts concluded that because the drug was the only risk factor present and because the disease is rare, plaintiff’s treatment with Elidel was a substantial factor in his presentation with the disease. However, in order to result in an admissible conclusion, a differential diagnosis should reliably rule out reasonable alternative causes of the alleged harm including idiopathic causes. Soldo, 244 F.Supp.2d at 567. Admissible expert testimony need not rule out all alternative causes, but where a defendant points to a plausible alternative cause and the doctor offers no explanation for why he or she has concluded that it was not the sole cause, that doctor's methodology is unreliable.

Here, the differential diagnoses by plaintiff experts failed to exclude the likelihood that Perry's lymphoma had no known cause. Most NHL cases are idiopathic, having no known cause. Courts have excluded experts' differential diagnoses where they failed to adequately account for the likelihood that the disease was caused by an unknown factor. Doe v. Ortho-Clinical Diagnostics, Inc., 440 F.Supp.2d 465, 478 (M.D.N.C. 2006); Whiting v. Boston Edison Co., 891 F.Supp. 12 (D. Mass.1995). This is not to say, cautioned the court, that where most diagnoses of a disease are idiopathic it is impossible to prove specific causation. But in those cases, analysis beyond a differential diagnosis will likely be required.

Plaintiffs' experts' general causation conclusions were primarily based on animal studies and their failure to satisfactorily address epidemiology (and the gap related to dosage levels in the studies vs. plaintiff’s exposure) undermined the usefulness of those conclusions to a jury. Since plaintiffs' experts failed to form a scientifically grounded chain of inference between their general causation finding and their specific causation finding, their opinions were excluded. Summary judgment followed.

How To Deal With Litigation-Related Concerns In "REMS" For Biologics

Last year’s Food and Drug Administration Amendments Act gave the FDA increased authority to require Risk Evaluation and Mitigation Strategies (REMS)— safety plans similar to those previously known as Risk Minimization Action Plans (RiskMAP). A recent article in Corporate Counsel offers in-house counsel a note of caution concerning the relationship between REMS and the claims made in a typical personal injury or consumer fraud litigation.

For example, the authors note that if REMS are needed, identifying and implementing the appropriate measures will involve a substantial amount of internal work by the manufacturer as well as significant interaction with the FDA. Both include opportunities and pitfalls that could have a significant effect on future litigation involving the product. The REMS process may engender “bad documents” (a paper trail that casts the company or its products in a bad light). On the other hand, one of the common claims asserted in product litigation is that a manufacturer was aware of and failed to adequately warn about its product’s risk. As the REMS process is specifically designed to increase the warnings to the health care  and patient communities, the authors (full disclosure: colleagues of MassTortDefense) suggest it may constitute a solid defense against the assertion that the manufacturer failed to provide adequate warnings.


Is There A New Tom Clancy Novel?

For those readers of MassTortDefense thinking about a new book to read on the beach this weekend, a recent contribution to the Wall Street Journal by Mark Herrmann entitled “The Plaintiff Was Unhappy” reviews, critiques, and balances the recent release Side Effects by Alison Bass. The book is an attack on the FDA and the drug industry in the context of antidepressant medications.

Herrmann shows how one-sided the book/attack is, concluding that Side Effects “belongs to a genre of investigative journalism that involves talking to plaintiffs, their lawyers and their expert witnesses, taking their stories as gospel, and denigrating the opposing view because corporate money (apparently less pure than money from the plaintiffs' side) supposedly has a corrupting effect” on science. 

Herrmann (along with Jim Beck) is an author of the popular Drug and Device Law blog.

Waxman Seeks Preemption Drafts From FDA

Preemption of state law claims, particularly in the area of medical devices and drugs, has been a hot topic lately. MassTortDefense has posted on it here and here, and there are numerous good posts on the topic at Drug and Device Law.

In the latest development, Congressman Henry A. Waxman (D-Calif.), Chair of the House Committee on Oversight and Government Reform recently sent a letter to Food and Drug Administration Commissioner Andrew C. von Eschenbach, requesting information about the agency's stance on federal preemption issues under the Bush administration.

The FDA believes, correctly, that state product liability lawsuits which challenge or undermine or invite conduct inconsistent with the federal agency's authority can have a detrimental effect on public health.  Waxman calls this a "reversal of FDA's long-standing position on preemption.”  Waxman’s view about the FDA’s position isn’t so firmly grounded, as seen in the back and forth between the majority and the dissent in Colacicco v. Apotex Inc., 2008 WL 927848 (3d Cir. Apr. 8, 2008), concerning whether the FDA has been “inconsistent” in its positions towards preemption. Going back to the Clinton era (Bill), for example, the FDA has repeatedly stated that FDA regulations may displace both state legislative requirements and state common law duties. In 2000, the FDA fretted that consumers in court would have to prove that harm was linked to the substance based on a standard that might vary by jurisdiction or at the “whim of a jury.” 65 Fed. Reg. 43269, 43278-79 (FDA July 13, 2000). And in an FDA final rule regarding FDA-mandated adverse event reports in state-law civil litigation, the agency stated that implied preemption was appropriate because state or local laws, rules, regulations, or other requirements would impede FDA’s ability to monitor product safety after approval to ensure that human drug products, biologics, and medical devices are safe and effective for their intended uses. “Thus, under principles of preemption law, congressional intent to preempt State law can be inferred.” 60 Fed. Reg. 16962, 16963 (FDA Apr. 3, 1995). See also 59 Fed. Reg. 3944, 3948 (FDA Jan. 27, 1994).

Nevertheless, Waxman is asking for numerous documents from the agency, including:

-all documents since Jan. 20, 2001, concerning communications between FDA and private individuals about preemption;
-all documents since that date, relating to internal FDA communications about preemption;
-all documents since Jan. 20, 2001, relating to communications between FDA officials and officials in the Department of HHS, the White House, and other federal agencies about preemption;
-all amicus briefs since Jan. 20, 2001, filed by FDA in product liability suits; and
-all drafts since that date of the final drug labeling rules issued Jan. 24, 2006.

Liberal Democrats in Congress have been buzzing about the Supreme Court’s decision in Riegel v. Medtronic Inc., in which the Court held that federal law preempted state-law claims against the manufacturer of a medical device that went through the Food and Drug Administration's premarket approval process. And they introduced H.R. 6381 that would reverse the effects of Riegel in medical device lawsuits. Waxman’s letter also comes in anticipation of the Court’s consideration of the extent to which the Food, Drug and Cosmetic Act impliedly preempts state law claims against drug makers. See Wyeth v. Levine, U.S., No. 06-1249, review granted 1/18/08. Of course, DOJ/FDA filed an amicus brief arguing in favor of preemption in that case.

PhRMA Revises Marketing Code Regarding Interactions With Healthcare Professionals

The Pharmaceutical Research and Manufacturers of America (PhRMA) has just adopted measures to enhance the PhRMA Code dealing with Interactions with Healthcare Professionals. (PhRMA represents research-based pharmaceutical and biotechnology companies.) Attacks on the marketing practices of drug makers is a common feature in pharmaceutical mass torts, including criticisms of the relationships between healthcare providers and pharmaceutical companies.

Informative professional relationships between healthcare providers and pharmaceutical research companies are instrumental to effective patient care. While plaintiffs frequently malign interactions between the companies and prescribers, doctors appropriately rely on information about new medicines in order to enhance the quality of care they give patients. Providing doctors with up-to-date information on the medicines they prescribe improves patient care. Thus, reasons for interaction include:

• inform healthcare professionals about the benefits and risks of products to help advance appropriate patient use,
• provide scientific and educational information,
• support medical research and education, and
• obtain feedback and advice about our products through consultation with medical experts.

The new code will take effect in January, 2009. The code is voluntary, reflecting the fact that different companies may approach the issues differently, all well within the range of choices available to a reasonable manufacturer in a competitive environment.

Federal Court Tosses Punitive Damages Award in HRT Case

A federal district court has thrown out a jury award of more than $27 million in punitive damages awarded to a Little Rock, Ark. woman who developed breast cancer allegedly as a result of taking hormone replacement therapy. In re: Prempro Products Liability Litig. (Scroggin v. Wyeth, et. al.), MDL No. 1507-WRW, 4:04CV01169.  Plaintiff Donna Scroggin developed breast cancer and had a double mastectomy, and blamed the hormone drugs she allegedly took for 11 years to combat menopausal symptoms. Defendants noted their products have carried a label warning of a heightened risk of breast cancer at all relevant times. In February, a federal jury returned a verdict in favor of Scroggin in her lawsuit against drug makers Wyeth and Upjohn, awarding her $2.75 million in compensatory damages and $27 million in punitive damages.

In an opinion July 8th on post-trial motions, Judge Wilson, of the E.D. of Arkansas, threw out the punitive damages award, finding he should not have permitted certain key testimony from a former Food and Drug Administration official, Dr. Suzanne Parisian. She had testified as the plaintiff's regulatory expert. The Court concluded, as defendants had asserted, that Dr. Parisian testified to a bottom line conclusion without sufficient explanation, failed to provide expert analysis, testified beyond limitations established by pretrial orders, testified in areas beyond her expertise, and invaded areas that required no expert testimony. Specifically, the expert failed to provide convincing testimony that Wyeth's actions had violated FDA regulations in any way that would warrant a punitive award.

In a part of the ruling particularly useful for readers of MassTortDefense, the judge said the expert did little more than read select portions of exhibits without providing further comment. Contrary to plaintiff’s position during the Daubert hearing, and during the punitive damages stage, Dr. Parisian, generally, did not give the jury the tools they need to look at those documents, or to understand them in the context of a regulatory background -- she simply read the documents to the jury. He hadn’t admitted such “so that [the expert] could simply engage in recitation of those exhibits; jurors are capable of reading documents.” Ironically, on cross-examination, Dr. Parisian, on at least one occasion, took the position that the document “speaks for itself.”

If an expert does nothing more than read exhibits, is there really any point in her testifying as an expert? The Court said “no.” As was seen during the punitive damages stage, the use of the “regulatory expert” to deal with large volumes of conduct documents is subject to abuse. MassTortDefense has seen this same technique in asbestos, in tobacco, in other pharma cases. The expert here did not explain the documents, provide summaries, or tie them in to her proposed regulatory testimony. Dr. Parisian did not provide analysis or expertise. Instead, improperly, she was a mere document delivery device.

The promised expert testimony simply was not delivered, said the Court, “so I should have struck this testimony at the time.”  Without Parisian's testimony, plaintiff had not presented sufficient other evidence to meet the clear and convincing standard required for punitive damages. The Court said plaintiff tried to present evidence of what, out of context and at first blush, might be considered questionable practices (e.g., alleged ghostwriting, countering negative press, etc.), but all this fell far short of establishing a submissible jury issue on punitives.

Two Recent Canadian Pharmaceutical Class Action Decisions

Two recent decisions illustrate just how difficult Canada is becoming as a jurisdiction for class actions defendants, particularly companies in the pharmaceutical industry. Frequently, identical consumer products, drugs, and medical devices are marketed in Canada as well as the U.S.  When a product is recalled, or new science suggests risks in a product leading to American product liability and mass tort litigation, Canadian plaintiff attorneys have not been bashful about bringing copycat litigation, borrowing from U.S.-conducted theories and discovery.  However, Canada appears not to be mimicking the trend against personal injury class actions in the U.S.

Background

Quebec was the first Canadian province to enact class action procedures in 1978, and a 2003 amendment to the Quebec Code of Civil Procedure simplified the class “authorization” process. In practice, the amendment may have made it easier for plaintiffs to obtain certification. The requirements are that the claims of the members raise identical, similar or related questions of law or fact (true commonality not required); the facts alleged seem to justify the conclusions sought; the composition of the group makes joinder difficult or impracticable; and the member to whom the court intends to ascribe the status of representative is in a position to represent the members adequately. Not a daunting challenge in some fact patterns.  Notice the absence of predominance, superiority, and manageability as explicit factors.

In Ontario, class action procedures were developed much more recently, dating back only to 1992. They permit certification when there is an identifiable class of two or more persons that would be represented by the representative plaintiff or defendant; the claims or defenses of the class members raise common issues; a class proceeding would be the preferable procedure for the resolution of the common issues; and there is a representative plaintiff who would fairly and adequately represent the interests of the class, has produced a plan for the proceeding that sets out a workable method of advancing the proceeding on behalf of the class and of notifying class members of the proceeding, and does not have an interest in conflict with the interests of other class members.

Wyeth

First, in the latest ruling in the HRT litigation against Wyeth, the Supreme Court of British Columbia refused to dismiss a putative class action in which plaintiffs in Canada allege that Premarin and Premplus therapy treatments caused breast cancer. Stanway v. Wyeth Canada Inc., 2008 BCSC 847 (June 27, 2008). The company denies the claims alleged in the litigation, insisting the products have carried an adequate label warning of a heightened risk of breast cancer, based on state of the art. Indeed, HRT drugs are still approved by the FDA as safe and effective and remain on the market.

The Canadian plaintiffs asserted two causes of action against the defendants. The first is for negligence, and the second is a statutory cause of action for deceptive acts and practices under the province's Business Practices and Consumer Protection Act. Wyeth’s motion asserted that the court lacked “territorial competence” over the U.S. entities of the company pursuant to the Court Jurisdiction and Proceedings Transfer Act, S.B.C. 2003, c. 28 (the “CJPTA”).

The U.S. Wyeth entities offered the position that there is no real and substantial connection between British Columbia and the facts upon which the proceeding against the U.S. defendants is based. Wyeth presented affidavits showing that the executives and staff of the U.S. defendants have not managed and do not manage North America as a single market. They have not interfered and do not interfere with the Canadian market. The U.S. defendants do not play a controlling or decision-making role in the pharmaceutical operations of the Canadian defendants. Individuals within Wyeth Canada reported directly or indirectly to the president of Wyeth Canada, not to anyone at Wyeth Pharmaceuticals. Employees of Wyeth Canada may have liaised with counterparts at Wyeth Pharmaceuticals but did not answer to them. Wyeth Canada owns the Canadian patents and trademarks for Premarin, holds various approvals for Premarin from Health Canada.

Moreover, Wyeth Canada runs its own marketing campaign and designs its own packaging, independently from U.S. Wyeth. The U.S. defendants do not conduct any sales or promotional activity related to Premarin or Premplus in Canada. Wyeth Canada runs its own marketing campaigns and designs its own packaging. Wyeth Canada generates its own promotional literature and a copy review committee of Wyeth Canada signs off. Warnings and other information are the responsibility of Wyeth Canada. It has its own independent training group and there is no functional reporting relationship between Wyeth Canada and Wyeth. Wyeth Canada’s marketing employees meet with their worldwide counterparts to exchange ideas and practices. Wyeth Canada tracks sales and decides whether or not to market a particular product.

The only Premarin tablets sold in Canada during the period the plaintiff says that she was prescribed the product would have been manufactured in Canada. At no time have any packages of Premarin or Premplus sold in Canada identified any association with U.S. Wyeth.

The plaintiff’s allegation was that Premarin and Premplus were introduced into and maintained within the Canadian stream of commerce. She alleged that the defendants are jointly involved with or responsible for the negligent manufacturing, testing, marketing, labeling, distribution, promotion and sale of Premarin and Premplus to consumers in British Columbia, and that they failed to warn her about the dangers of taking these drugs.

The Court noted that the plaintiff must prove circumstances that constitute a real and substantial connection between British Columbia and the facts on which a proceeding is based. The statute gives a non-exhaustive list of relevant factors, including whether the tort was committed in British Columbia, and whether the claim concerns a business carried on in British Columbia.


Despite the powerful showing by Wyeth, the Court concluded that the plaintiff successfully established a link between British Columbia and the tort allegedly committed by the U.S. defendants under the CJPTA. The Court concluded that there is no dispute that the plaintiff alleges that she suffered damage in British Columbia. It is in the interest of the forum to protect the legal rights of its residents, and to allow injured plaintiffs "generous access" to litigation. The defendants engaged in “harmonization” and “coordination” of matters involving core monograph and labeling requirements, the efficacy of the products, and the collecting and sharing of other clinical research or trial information, said the Court.  Wyeth Pharmaceuticals’ role as a central repository and coordinator for adverse event reporting for all the Wyeth affiliates worldwide demonstrated, the Court concluded, a sufficient involvement of the U.S. defendants in promoting the efficacy of the drug and its safety.

Lilly
In the second recent decision, involving Eli Lilly and its Zyprexa schizophrenia drug, an Ontario appeal court affirmed the lower court's decision that class action plaintiffs may proceed with an attempt to recover damages tied to company sales rather than individual damages. Andrea Heward vs. Eli Lilly & Co., No. 181/07, Ontario Superior Court of Justice, Divisional Court (Toronto) (July 2, 2008).


Plaintiffs accused Lilly of failing to warn that Zyprexa may allegedly cause diabetes and other disorders. Zyprexa is approved by the FDA and Canadian regulators to treat schizophrenia and bipolar disorder. The proposed national class (excluding British Columbia and Quebec) has an estimated 575,000 members. In addition to claims sounding in negligence, plaintiffs allege a so-called “waiver of tort” theory that resembles an unjust enrichment theory seeking disgorgement of profits and/or a constructive trust of the proceeds of the defendants’ sale of the drug. The interlocutory appeal was confined to the issues whether the motion court had erred in concluding that the damages (accounting, disgorgement, constructive trust) was a common issue, and whether the class proceeding is the preferable procedure to resolve the claim of waiver of tort.


Defendants asserted that the amount of damages would implicate individual issues because all class members would not have taken Zyprexa even if they had been warned as plaintiffs asserted they should have been, and plaintiffs could not show that Health Canada would not have approved Zyprexa for sale if the warnings had been different. Indeed, Zyprexa continued to be used for years after the label was amended to change the language about diabetes risks.

 
The Superior Court noted that “waiver of tort” is confusing nomenclature. It does not refer to waiving a right to sue, but an election to base a claim in restitution. The Court acknowledged the debate over whether the waiver of tort theory constitutes an independent cause of action or a remedy in Ontario. It is an “uncertain area of law” raising “policy concerns” which “require clarification in our jurisprudence.”


However, the Court concluded that the embryonic nature of the waiver of tort doctrine simply meant that no decisions should be made absent a full evidentiary record. The class action procedures provide options for the common issues phase to create subclasses, and craft the boundaries of the remedy of disgorgement to fit the requisite causal link, and even decertify common issues when necessary. The Court concluded that individual issues that factor into the determination of the quantum of the restitutionary disgorgement or constructive trust would not undermine the applicability of waiver of tort on a class-wide basis. This seems to confuse two issues: individual issues on quantum of damage might not alone defeat certification, but that does not make them common questions, which was the issue on appeal.

 
Regarding the second issue, the Court concluded that even if the amount of relief based in waiver of tort cannot be assessed in aggregate, a class action remains the preferable procedure for this claim. In potentially troubling language for defendants, the Court noted that “the only necessary evidence with respect to waiver of tort may well be simply the wrongful conduct of the defendants.” While conditional, such an interpretation of this type of claim may affect future certification decisions and stands to make future defendants liable for truly enormous amounts of damages unless clarified.

Institute Releases Report on Drug Innovation Through Industry Research

A report just released by the Center For Medical Progress At The Manhattan Institute indirectly undercuts a favorite theme of plaintiffs in pharmaceutical mass torts.

Entitled “The Truth About Drug Innovation: Thirty-Five Summary Case Histories On Private Sector Contributions To Pharmaceutical Science,” the analysis assesses -- and rejects -- the argument that most of the important scientific advances that yield new and improved medicines do not result from private sector research, but instead are the fruits of research efforts financed or conducted by public agencies, such as the National Institutes of Health. The paper also indirectly undercuts a favorite plaintiff theme that scientific research undertaken by, or funded by, private industry is biased, tainted, poor science, and not worthy of a jury’s serious consideration.

The study compiled summary case histories of thirty-five drugs and drug classes (a group of drugs used to treat a given medical condition in similar ways) identified in the scholarly literature as important and/or that were among the most prescribed in 2007. The authors’ conclusions:


• the scientific contributions of the private sector were crucial for the discovery and/or development of virtually all of the thirty-five drugs and drug classes examined in this study.
• The companies’ scientific advances included topics within the basic science of biology and disease, processes relevant for given medical conditions, the applied science of discovering compounds that treat particular conditions; and the development of compounds with improved clinical (medical) effects.

In short, almost all of the drugs and drug classes examined in this study would not have been developed—or their development would have been delayed significantly—in the absence of the scientific or technical contributions of the pharmaceutical firms.

Government Files Amicus Brief in Levine v. Wyeth

For those readers of MassTortDefense following the Levine v. Wyeth matter, here is the BRIEF FOR THE UNITED STATES AS AMICUS CURIAE SUPPORTING PETITIONER.

The agency, via the Solicitor General, argues that the FDA’s decision to approve a drug and its labeling reflects the agency’s expert evaluation of the health risks and benefits the product can provide; respondent’s claims are preempted because they challenge labeling that FDA approved after being informed of the relevant facts. When federal regulation is designed to strike a balance between competing risk/benefit considerations, state laws that strike a different balance are impliedly preempted because they interfere with the federal balancing. The amicus brief also notes that FDA’s labeling requirements do not qualify as a mere minimum safety standard, or floor, upon which state laws could add more stringent requirements.

The SG also addresses the Vermont Supreme Court’s conclusion that the FDA’s regulations allow drug manufacturers to easily change drug labels unilaterally. “Petitioner was not free to disregard FDA’s judgment concerning previously known risks.” Brief at 21. The “limited exception” to the general rule requiring FDA to approve any label changes requires submission of a supplemental new drug application to, albeit not prior approval by, the agency. And substantive changes may be made without prior FDA approval only to correct concerns about newly discovered risks from the use of the drug. If manufacturers were free to make unilateral changes to labeling the day after FDA’s approval based on information that was previously available to the agency, the approval process would be greatly undermined and the agency’s careful balancing of risks and benefits thwarted.

New Jersey Supreme Court Decides Medical Monitoring Case in Drug Context

The Supreme Court of New Jersey has just issued its opinion in the closely watched medical monitoring case, Phyllis Sinclair v. Merck & Co. Because your faithful blogger’s firm is involved in the Vioxx litigation, MassTortDefense presents you with the opinion and, as Joe Friday said, just the facts. No commentary or editorializing.

In this products liability case the Court considered whether plaintiffs may recover the costs of medical monitoring despite their failure to allege a physical injury. This litigation arises from the use of Vioxx, a prescription drug manufactured and sold by Merck. In November 2004, plaintiffs filed a class action complaint on behalf of a proposed national class of individuals who ingested Vioxx and who allegedly may suffer from serious latent injury for which they may require medical monitoring. Plaintiffs later refined the factual allegations advanced in the complaint and alleged that as a result of the direct consumption of Vioxx, they are at enhanced risk of serious undiagnosed and unrecognized myocardial infarction, and other latent injuries. Plaintiffs sought the cost of medical testing in the form of a court-administered screening program to provide medical diagnostic tests for each member of the proposed class and follow-up with an epidemiologist.

The trial court reviewed the standards governing pleadings and motions to dismiss, as well as the
facts and holdings of several cases that addressed medical monitoring: Ayers v. Township of Jackson, 106 N.J. 557 (1987), Mauro v. Raymark Industries, Inc., 116 N.J. 126 (1989), and Theer v. Philip Carey Co., 133 N.J. 610 (1993). The trial court granted Merck’s motion and dismissed plaintiffs’ complaint. It found that the PLA limits compensation to harm as defined by N.J.S.A. 2A:58C-1b(2), and reasoned that medical monitoring has not been applied to a products liability action to which the PLA applies. Additionally, the trial court noted that the medical monitoring is an unavailable remedy under the New Jersey Consumer Fraud Act.

On appeal, the Appellate Division reversed and remanded for further proceedings. Sinclair v. Merck & Co., 389 N.J. Super. 493 (2007). The panel noted the lack of facts and expert testimony at the motion stage of the proceedings, and remanded for discovery and an evidentiary hearing. The state Supreme Court granted Merck’s petition for certification and also granted amicus curiae status to various entities.

Today’s opinion holds that the N.J. Products Liability Act, which is the sole source of remedy for plaintiffs’ defective product claim, does not include the remedy of medical monitoring when no manifest injury is alleged. This Court reads the PLA to require a physical injury. And thus medical monitoring plaintiffs cannot satisfy the definition of harm to state a product liability claim under the PLA. The Court further holds that claims for harm caused by a product are governed by the PLA irrespective of the theory underlying the claim. The heart of plaintiffs’ case is the alleged potential for harm allegedly caused by Merck’s drug. It is thus a product liability claim. Consequently, plaintiffs may not maintain a CFA claim.

Chief Justice Rabner and Justices Lavecchia, Rivera-Soto and Hoens joined in Justice Wallace’s majority opinion. Justice Long filed a separate, dissenting opinion. Justice Albin did not participate.

Wyeth Files Supreme Court Brief in Levine Case

Wyeth filed its brief yesterday in the U.S. Supreme Court in the Levine case, the closely-watched, much-anticipated, case regarding FDA preemption. The drug at issue is the company’s anti-nausea drug, Phenergan. Levine claims that the drug's labeling should have foreclosed IV push injection of Phenergan because of the risk of injury. Wyeth has argued that the FDA's approval of the Phenergan labels/warnings preempted any such state-law claims over the product.

In October 2006, the Vermont Supreme Court upheld a $7 million judgment for Levine and ordered Wyeth to modify the drug's label to reflect the alleged risk, citing a “presumption against preemption.”

The Supreme Court granted cert in January, and in the brief, Wyeth notes that the FDCA prohibited it from modifying the drug's label in most cases without approval from the FDA. Vermont law, by contrast, imposed a tort-law requirement that Wyeth alter that labeling (to foreclose IV administration) regardless of FDA action.

In the FDCA, Congress established a drug-approval regime in which an expert scientific agency makes uniform, national judgments about the safety and effectiveness of prescription drugs by balancing therapeutic benefits against safety risks ex ante, taking into account the interests of all potential patients. Wyeth argues that FDA struck precisely that type of balance in approving IV administration of Phenergan and in determining what warnings and instructions were appropriate to manage its associated risks.

Plaintiff has until August 1 to file the reply brief.

FDA Launches Sentinel Initiative

On May 22, 2008, FDA launched the “Sentinel Initiative” – a new program with the goal of creating and implementing the Sentinel System--a national, integrated, electronic system for monitoring medical product safety.


The Sentinel System, once in place, will enable FDA to pose targeted queries (consistent with privacy and security safeguards) of patient registry data, insurance claims data, and other large health care information databases, for information about medical products. FDA says this new system will strengthen the agency's ability to monitor the performance of a product throughout its entire life cycle, thus enhancing the protection and promotion of public health.

 
FDA's current post-market surveillance programs generate very important new risk information, but the adverse event reporting system depends on health care professionals and patients first recognizing a potential association between an adverse effect and a medical product, and then report it to FDA or the manufacturer. Some adverse events are never reported.


Once the Sentinel System is up and running, FDA will have the tools to query specific adverse event data in large databases, like the Medicare database and in claims data and electronic health information maintained by private and federal entities who volunteer to participate in the Sentinel System. That is, the System will be created through public-private partnerships. It will rely on existing large electronic claims and medical records data sources maintained by private and government entities that agree to participate in this nationwide effort.

Creating an advanced surveillance system like Sentinel was one of the recommendations made by the Institute of Medicine in its 2006 report on ways to improve the safe use of drugs. The Food and Drug Administration Amendments Act of 2007 includes provisions that call for the development of such a system. FDA believes patients will benefit because the agency will be able to identify potential problems sooner, better understand those problems, and ultimately, help health professionals and patients use medical products more safely.

 
The overall initiative is described in an FDA white paper titled, “The Sentinel Initiative—A National Strategy for Monitoring Medical Product Safety.” The report is available at here.

Such a system could also ultimately facilitate data mining and other research-related activities. Researchers have said its full effects would take years to realize, however.


It is interesting to speculate about the potential impact of the system, especially on products liability litigation. Medicare collects data typically only when a medical provider is seeking payment. This claims data is less complete, and potentially less accurate than actual patient health records. Thus, utilizing Medicare data to assess health outcomes of drug use may be problematic. Of course, the new system doesn’t change the reality that sometimes patients suffer adverse events after receiving drugs because they are sick, not because the drug has a problem. And Medicare recipients use an average of 28 prescriptions in a year, compared with an average among all Americans of something like 12 prescriptions. Sorting out which medicine caused any single problem – if any did -- can be difficult.


In mass tort litigation, as readers of MassTortDefense know, plaintiffs frequently will attack defendants’ AER system, the resources devoted, the quality of the reporting. Even more frequently, plaintiffs will allege that the AE reports revealed a “signal” far sooner and far more clearly than the company thought; that the defendant missed or ignored the signal about potential adverse events in order to avoid the financial impact of a new label with a stronger warning. But if the FDA will eventually be able to query databases of tens of millions of patients almost simultaneously, presumably it will no longer have to wait for reports from the field, and the allegations of “missed signals” may lose all force.


To assess the accuracy of the Sentinel system, the FDA will initially conduct studies of drug side-effects that are already well known. And despite the issues, the Pharmaceutical Research and Manufacturers of America supported the FDA initiative, see here,  because it will allow regulators and health care professionals to move from reliance on voluntary reporting of side effects to a more proactive monitoring of medicines. 

Bellwether Trials Proposed in Aredia MDL

The MDL

The parties in the MDL concerning the bone cancer drugs, Aredia and Zometa, have proposed 10 bellwether cases for the first round of trials. The MDL court reported last week that it had received the list of cases the plaintiffs and Novartis propose for “Wave 1-A” of the trials. The court set a status conference for May 28 to discuss the list and make further decisions for the first round of trials.

The MDL No. 1760 consists of about 285 cases alleging that the bone-cancer drugs cause osteonecrosis of the jaw, a condition involving the deterioration of the jawbone. The cases were consolidated in the U.S. District Court for the Middle District of Tennessee in April 2006. In October, 2007, the court denied certification of a class of asymptomatic persons treated with Aredia and/or Zometa, seeking medical monitoring. Plaintiffs had alleged that they were at an increased risk for developing osteonecrosis of the jaw because of their treatments with the drugs, and sought periodic dental monitoring, including dental radiographs, which they claimed would help prevent the development the disease. In re: Aredia & Zometa Products Liability Litigation, No. 3:06-MD-1760  (M.D. Tenn. October 10, 2007).

Bellwether Cases

This raises an important issue and gives MassTortDefense the opportunity to make some general observations about bellwether trials.

Particularly in non-class mass tort litigation, such as MDL’s, statewide coordinated proceedings, and large consolidations, judges often resort to use of bellwether trials. Such trials may force plaintiffs' counsel to prepare their standard trial package, and the trials may give some sense of how sound that package is. The bellwether trials may give the court a context to resolve legal questions that arise at a trial as witnesses begin to take the stand. Bellwether trials may test the expert witnesses and theories, and give both parties a sense of how much it costs to try a case to verdict. In theory, test trials are to produce valuable information that will allow the parties to assess the strength and settlement value of all the related cases. Cf. In re Bridgestone/Firestone, Inc. Tires Prods. Liab. Litig., 288 F.3d 1012, 1020 (7th Cir. 2002) (central planning model: one case, one court, one set of rules, one settlement price for all involved, suppresses information that is vital to accurate resolution), cert. denied, 537 U.S. 1105 (2003).

In order for that to occur, however, it is imperative that there be a sufficient number of cases tried, and that the cases selected be representative of the range of cases. Trying one or two cases out of a collection of hundreds, or thousands, certainly doesn't give any statistically significant information about the value of the cases. Test cases should produce a sufficient number of representative verdicts to enable the parties to determine what range of value the cases may have if resolved in the aggregate. Manual For Complex Litigation (4th) § 22.315. If the cases are randomly selected, they will reflect the full range and diversity of the claims at issue, including in terms of factual issues, choice of law, legal theories and defenses, and perhaps counsel as well.

At times, courts have permitted each side to select one-half of the test cases, a practice that will likely not offer a representative sample, but rather a mix of the “best” and “worst” cases for each side. See In re Chevron USA, Inc., 109 F.3d 1016, 1019 (5th Cir. 1997). This approach has an element of fairness, and may offer the benefit of allowing each side to test out issues that are important to its strategy, or which each party feels will be persuasive to the other side once resolved.

And while it would seem self-evident that trial of plaintiffs selected by one side only will not provide meaningful information (unless the other side manages to prevail anyway), it is not unusual for courts to allow plaintiffs to select the “test” cases, as has occurred in aspects of the Vioxx mass tort. In re Vioxx Lit., Case. No. 619 (N.J. Super. Ct., Atlantic Cty.) (ordering plaintiff to select a grouping of eight plaintiffs, with trials consisting of two or more plaintiffs). The danger is, of course, how a few early trial results can have significant unfortunate effects, decreasing rather than increasing the prospects of any early global resolution, raising to unreasonable heights the expectations of the plaintiffs' bar. That plaintiffs secure verdicts in their handful of best cases out of hundreds or thousands, which may bear no resemblance to the best few, should come as no surprise. And may not encourage rational defendants to alter their views about the merits of the bulk of cases.

Even when the court randomly selects bellwethers, or permits the defendants to select some bellwethers, plaintiffs' counsel often seek to exercise control over the process by refusing to go forward with the selected unfavorable cases, either by convincing the client to dismiss or by withdrawing as counsel. This has happened in tobacco, HRT, and Vioxx litigation, for example. Defendants should ask the court to put safeguards in place to minimize plaintiffs’ ability to undermine the selection process, and in no event should plaintiff who dismisses rather than proceed with the selected bellwether have the ability to select the next bellwether. There really ought to be a system to supply substitutes that achieves the same goals as the original selections.

Peer Review (Part II)

In yesterday’s post, MassTortDefense began discussion of a peer review issue commented on in this week's New England Journal of Medicine. The editorial comments on two cases in which Pfizer served discovery on the journal, seeking peer-review and other editorial documents on manuscripts concerning Pfizer's Bextra and Celebrex, which of course have been the subject of litigation. Pfizer sought peer-review documents, including the critiques prepared by reviewers for the authors. The logic is that the critiques might help reveal flaws in methodology in the research. This was seen as particularly important given significant imprimatur of the NEJM and the use of its published studies in the cases.

In the case In re Bextra and Celebrex Marketing Sales Practices and Product Liability Litigation,
2008 WL 859207 (D.Mass. March 31, 2008) the court rejected the discovery, and granted the journal’s motion for a protective order. The court began by noting that the NEJM is the world's oldest and most frequently-cited medical journal. Physicians rely on information presented in the NEJM to follow medical developments and improve patient care. Manuscripts submitted for publication by the NEJM are subject to “peer review,” i.e., to screening and analysis conducted by experts in the subject matter discussed within the submitted articles. Peer reviewers are given a draft manuscript and are asked to provide a confidential, frank, honest evaluation of the manuscript's scientific validity and to provide an overall opinion with respect to a manuscript's “worthiness for publication.” Information from peer reviewers which is communicated to the authors does not reveal the identity of the peer reviewer. The NEJM informs prospective peer reviewers that it will maintain the confidentiality of their identities, unless the reviewer grants specific permission to the contrary. None of the peer reviewers for the eleven Bextra and Celebrex articles published had given the NEJM permission to disclose his or her identity.


The published articles were relevant to the MDL litigation and to plaintiffs’ allegations that Pfizer failed to act upon the results of studies described in the scientific literature, and that it was on notice from those studies of the alleged risks presented by the drugs.

 
At a hearing on the motion, Pfizer apparently narrowed the scope of its request, and withdrew its requests seeking certain documents reflecting the peer reviewer comments which were not shared with the authors, internal editorial comments or processes

Rule 26 and Rule 45 require application of a balancing test looking at whether the information can be obtained from some other source that is more convenient, less burdensome, or less expensive, the burden or expense of the proposed discovery, and its likely benefit, considering the needs of the case, the amount in controversy, the parties' resources, the importance of the issues at stake in the action, and the importance of the discovery in resolving the issues. Specifically here that would include the objector's interest in confidentiality and the potential injury to the free flow of information that disclosure may create. Another factor entitled, said the court, to special weight in conducting this balancing test is that the NEJM was a non-party to the MDL.

The district court concluded that the materials were relevant, but their probative value was limited. The reasoning was that plaintiffs' claims focus on what Pfizer knew, or should have known, via published articles in the scholarly literature. The peer reviewers' confidential comments don’t speak directly to that issue, the court thought. Of course, what a product seller should take from a published article does depend in great measure on the quality of the article, its methodology, is biases, its power, and other aspect peer reviewers are likely to comment upon. But the court felt that Pfizer's own experts were able to review and analyze the articles for flaws in methodology, and the peer reviewer comments contain no new data.


Peer review comments could also potentially be useful to impeach any causation experts of plaintiffs who rely on the studies, and to provide ammunition for defense causation experts. The court however, worried that this reflected a “growing problem” with the use of subpoenas to compel the giving of evidence and information by unretained experts. That seems a somewhat narrow and uniformed view of what defendants typically do when confronted with a mass tort or MDL: they retain as many of the best experts they can find.

Balancing against that probative value, the court analogized the peer review process to the level of protection offered academics engaged in pre-publication research. Because the peer review contributes to the advancement of medicine and science by helping to ensure that faulty, incomplete, or misleading results are not published, and because a journal’s ability to advance medical knowledge in this way might be impaired, resulting in adverse consequences for physicians, patient care, and for society as a whole, the Journal’s objections seemed persuasive to the court. If reviewers thought their names or reviews would be subject to disclosure in unrelated litigation, there would be “chilling effect” on the peer review process and as a result, upon the medical community. The comments are both part of scholarly research efforts as well as part of the editorial process of a print publication. The court concluded that any wholesale disclosure by the NEJM of the peer reviewer comments communicated to authors will be harmful to the NEJM's ability to fulfill both its journalistic and scholarly missions, and by extension harmful to the medical and scientific communities, and to the public interest. Thus the subpoena was quashed.

The Northern District of Illinois, similarly, declined to compel compliance with similar subpoenas served by Pfizer in the same MDL on the Journal of the American Medical Association and the Archives of Internal Medicine. In re Bextra and Celebrex, C.A. No. 08C 402 (N.D.Ill. March 14, 2008). The district court there found that the any probative value of the requested information was outweighed by the burden imposed on the journals in invading the sanctity of the peer review process. In short, it was not unreasonable to believe that compelling production of peer review documents would compromise the process.

But it raises an interesting, perhaps test-able, question whether disclosure of comments would discourage people from submitting articles to the journal, or peer reviewers from commenting on manuscripts.  Isn't a prestigious thing to be able to say "I am a peer reviewer for the NEJM"? After all, a large part of the the academic world involves defending one's scholarly work in public, in symposia, in class rooms, etc.  And scientists frequently publish comments, letters to the editor, publicly critiquing others' work. Wonder if any respected journal conduct peer review in which complete confidentiality is not promised the reviewers?

Yesterday’s editorial commented that confidential peer review is a key component of the manuscript selection process. The Journal’s stand was consistent with the views of the International Committee of Medical Journal Editors. The ICMJE is a group of about 500 general medical journal editors whose participants meet annually and has produced a number of editions of uniform requirements for manuscripts submitted to biomedical journals. See Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication.


In its Uniform Requirements, the ICMJE states that unbiased, independent, critical assessment is an intrinsic part of all scholarly work, including the scientific process. Peer review is the critical assessment of manuscripts submitted to journals by experts who are not part of the editorial staff. Peer review can therefore be viewed as an important extension of the scientific process. Reviewers have rights to confidentiality, which must be respected by the editor. Editors must not disclose information about manuscripts (including their receipt, content, status in the reviewing process, criticism by reviewers, or ultimate fate) to anyone other than the authors and reviewers. “This includes requests to use the materials for legal proceedings.”

It will be interesting to watch and see if the issue arises again in a case in which the party seeking the information -- and might it be plaintiffs under the proper facts? -- can show a higher degree of probative value.

Peer Review, Daubert, and the New England Journal of Medicine

The new England Journal of Medicine weighed in today with an editorial on a topic that should be important for readers of MassTortDefense – peer review. Curfman, et al., Peer Review in the Balance, 358 NEJM 2276 (May 22, 2208).

The editorial weighs in on two recent decisions in the Celebrex litigation involving product liability defendant’s attempts to go beyond the veil of the published article and obtain discovery on information created in the peer review process as manuscripts were assessed. Those manuscripts related to studies of science relevant to the litigation, and the argument was advanced that commentary, discussion, and analysis of those studies by expert peer reviewers likely also contained relevant information about that pertinent science.

Legal Setting

Expert testimony is essential in virtually every mass tort or complex product liability litigation. Under the gate-keeping function of the trial judge, designed to keep junk science out of the courtroom, the Daubert opinion lists important factors to consider in admission of expert testimony, including whether the theory or technique has been subjected to peer review and publication. This factor is relevant, but not dispositive, because sometimes well-grounded but innovative theories will not yet have been published, and sometimes a topic may be of too limited interest to be published. But the Court believed that peer review increases likelihood that substantive flaws will be detected in an article, and publication places the work within the test of the marketplace of ideas. The theory is available to be scrutinized, and has been scrutinized by experts in the relevant field. In essence, submission of the method, theory, reasoning, to scrutiny of scientific community is considered component of good science.


The Daubert Court was aware from amicus briefing of another view of peer review, emphasizing that the peer review system is not a litmus test for truth, not a guarantor of scientific certainty, and does not guarantee that the particular data, research and analytical methodologies, or conclusions of the accepted papers represent the consensus opinion of the relevant community. Brief of Amici Curiae Chubin et al., Daubert, 1992 U.S. S.Ct. Briefs LEXIS 938. But the Court generally rejected this view.


There is some lower court variation in application of Daubert and Frye on peer review; some courts emphasize the mere fact of peer review, Doe v. Ortho-Clinical Diagnostics Inc., 440 F.Supp. 2d 465 (M.D.N.C. 2006)(thimerosal), with others offering a more nuanced view of peer reviewed publication serving as a validity enhancer. The presence of the limited view encourages plaintiffs to seek to get theory published somewhere to “check the box” of peer reviewed publication. The more rigorous view reads the Supreme Court as clearly intending that judges use their own evaluation of peer review and publication as a tool for exploring whether substantive flaws in an expert's methodology have been or could have been exposed. Black v. Rhone-Poulenc, Inc., 19 F.Supp.2d 592 (S.D.W.Va. 1998) (depends upon how the peer review was performed; who did it; plaintiffs failed to provide sufficient information to assess).

Now, before getting into the two recent decisions and the editorial, a brief background on peer review.

Brief History of Peer Review

Modern medical journals came into existence during the 19th century. They were originally a vehicle for personal journalism, with the models for medical editors including the crusading newspaper writer. Publication was a personal vehicle for the editor. Over time, newspapers came to resemble newspapers, with correspondents to cover medicine in different geographic and specialty areas. But in many medical journals, the editors wrote much or all of content. A second type of journal also arose, in addition to those journals that followed the newspaper model, and that was the official publications of research institutes, typically specializing in one kind of research.


In the 19th century editors often could not fill their columns. The problem was finding publishable manuscripts, not turning down original contributions. Editorial board members would help round up material for the editor to publish, rather than review and reject manuscripts. In the 20th century, the supply/demand ratio gradually reversed. The number of passable manuscripts began to increase greatly, so that choosing among good articles became an option. Between 1913 and 1925, the Journal of the American Medical Association received 1500-2000 manuscripts for consideration. And the end of World War II marked the beginning of a dramatic increase in the volume of research and the subsequent reporting of research results. So by the 1990’s, JAMA was receiving 4500 papers/year, plus 5500 letters to editor. Yet JAMA publishes about 500 articles a year. Or the NEJM, which was getting more than 4000 article submissions/year, and publishing less than 10%.

Today there are more than 10,000 medical and scientific journals, and more than 2 million scientific and medical articles published each year. Most are never cited again.

There are examples of historical scientific journals in France and England with well thought-out peer review process to select reports to be published in journals and memoirs. In 1752, the Royal Society of London, a medical society, began publishing Philosophical Transactions and established a "Committee on Papers" to review articles submitted for publication. But in the U.S., most journals were personal fiefdoms of editors. (E.g., James McKeen Cattell, who for 50 years edited (and owned) Science and other major journals at the same time. ) As noted, editors wrote much of the content; they considered themselves as expert as anyone to assess content. The only mechanism that resembled modern peer review, perhaps, was book publishers seeking outside advice regarding textbook manuscripts in technical fields.


Peer review developed in part to deal with situations in which an editor lacked the specialized knowledge to make decisions about highly technical articles. Particularly after WWII, more specialists in subject matter, in terms of technique and, especially, in medicine, and laboratory materials were needed. And when physicians began to specialize in particular fields, it also spawned a demand for specialized journals catering to that specialty.  The supply/demand ratio gradually reversed and there was a growing need to discriminate high-quality articles and turn down others in the growing volume of at least plausibly good submissions that they had to consider.

Fast Forward to Today
An example of rigorous peer review is the New England Journal of Medicine, which publishes less than 10% of the unsolicited manuscripts it receives. There is a multi-step process including an initial screen by and editor; and internal review by an associate editor; submission to at least 2 peer reviewers/referees; presentation of the article to an editorial meeting; a statistical/math review, etc. There is a step for an additional review and revision by the author.


Today, scientific and medical journal have a significant role in shaping the views and behavior of scientists, clinicians, and policy makers. Contrary to the theory that journals act as passive conduits for scientific content, studies show the impact of an article is strongly influenced by which journal published it, and authors know that. There is a potential for a few high-impact journals to shape heavily the use of scientific information. At the same time, the increasing number of biomedical journals, the advent of online publication, and the increasingly interdisciplinary nature and impact of research, are forcing journals to compete for the best research.

With that background, the current controversy in the next posting.

Congressional Committee Holds Hearing on Preemption

The House Committee on Oversight and Government Reform held a hearing last week entitled, “Should FDA Drug and Medical Device Regulation Bar State Liability Claims?” Chairman Waxman’s opening statement opined that preemption was a "radical legal doctrine" being advocated by the pharmaceutical and device industries and the Food and Drug Administration (FDA). Patients allegedly injured by defective drugs and medical devices would no longer have the ability to seek compensation. “The result is that one of the most powerful incentives for safety - the threat of liability - would vanish.”  Waxman and other Democrats are of the view that FDA approval of drugs and medical devices before they are marketed “does not necessarily guarantee safety.”

Of course, the politicos' simplistic view ignores the fundamental reality that prescription products are typically unavoidably unsafe. Nothing guarantees complete safety.  They are complex products that carry risks, at least to some users. That is why the FDA weighs the risks and benefits for an indicated population, and a learned intermediary – doctor – is needed to obtain the product, someone who can balance the risks with the benefits for the particular patient.

The hearing follows on the Supreme Court decision in Riegel v. Medtronic,128 S. Ct. 999 (2008), and in anticipation of the Court’s decision in Levine v. Wyeth.


The witnesses included some leading opponents of preemption, from actor Dennis Quaid (who has a suit against Baxter), former FDA official David Kessler, and an editor from the New England Journal of Medicine (who editorializes against preemption). No one from the industry was scheduled to appear, apparently. The only two witnesses in favor of preemption were buried in later witness panels.  This led Congressman Christopher Shays (R-Conn.) to note that the hearing was more about plaintiff lawyers than public health. 


Most of the press coverage focused on Quaid (MassTortDefense liked him in “The Rookie”), who urged Congress on Wednesday to preserve patients' rights to sue drug makers for injuries, and recounted the story of his newborn twins’ medical scare – which apparently resulted from human error at the hospital and was unrelated to the safety and efficacy of Baxter's product. "I believe if preemption of lawsuits is allowed to prevail, it will basically make all of us, the public, uninformed and uncompensated lab rats," Quaid said.


The FDA currently and correctly believes that the important decisions it makes about the safety, efficacy and labeling of medical products should not be second-guessed by state court juries.  But should the Supreme Court recognize the role of preemption in the Levine case, this is yet another sign that some in Congress may seek to take action to overturn any ruling in favor of the doctrine.


 

Rehearing Rejected in Colacicco

Although coming as no big surprise, it is good to note that the 3d Circuit refused to revisit its recent decision that federal law preempts claims against antidepressant manufacturers for failing to warn of suicide-related risks (Colacicco v. Apotex Inc., 3d Cir., No. 06-3107, 5/5/08).


Readers of MassTortDefense know that plaintiff Colacicco filed suit after his wife allegedly committed suicide while under treatment with a generic equivalent to Paxil. The EDPA found preemption. However, the DNJ reached the opposite conclusion in a claim by plaintiff McNellis, whose father allegedly committed suicide while taking Zoloft. Both decisions were appealed, and the appeals were consolidated. The Third Circuit's decision was the first by a federal appeals court to address the preemptive effect of prescription drug law and regulation since the FDA’s clarified guidance on the issue.


Plaintiffs sought a rehearing. Only two judges on the panel, including Judge Thomas L. Ambro, who dissented from the panel’s preemption decision, would have granted the petition for rehearing en banc. (Judge Fisher also would have granted the petition for rehearing en banc.)

Many eyes turn now to Wyeth v. Levine, in the US Supreme Court, on the crucial issue of preemption. 

5th Circuit Clarifies Heeding Presumption in Learned Intermediary Case

In a previous post, MassTortDefense began analysis of the 5th Circuit's decision in Ackermann v. Wyeth Pharmaceuticals, 2008 WL 1821379 (5th Cir, April 24, 2008), in which the Fifth Circuit addressed a couple of very important issues affecting the learned intermediary doctrine. The Court emphasized that the prescriber testified that he reviewed the plaintiff’s proposed “fuller” warning, concluding that if the proposed warning had been communicated to him effectively and in a prominent manner before he prescribed Effexor to plaintiff, he would have considered it, but it would not have changed his prescription decision. What about the heeding presumption?

Heeding Presumption 

Appellant also contended that, regardless of Dr. Sonn’s testimony, Texas law created a presumption supporting a causal link between Wyeth’s inadequate warning and her husband’s death. The Court rejected that broad argument: Texas law creates no such presumption. In general, when a manufacturer fails to give adequate warnings or instructions, a rebuttable presumption arises that the product user would have read and heeded such warnings or instructions (the “read and heed” presumption). This presumption’s effect is to shift the burden of producing evidence to the party against whom it operates. But, significantly, the Court found that neither Texas nor federal courts applying Texas law have applied the read-and-heed presumption to pharmaceutical cases involving learned intermediaries. In fact, Texas has explicitly rejected the Restatement (Second) of Torts  § 402A, Comment j’s “read-and-heed” presumption for policy reasons, and because it has been superseded by the Third Restatement  § 2. See Uniroyal Goodrich Tire Co. v. Martinez, 977 S.W.2d 328, 336–37 (Tex. 1998). 2008 WL 1821379 *6. [Indeed the comment 1 to Section 2 calls the prior language “unfortunate.”]

Further, the Fifth Circuit doubted that the Texas Supreme Court would apply such a presumption here, when it would not serve its intended purposes. The read-and heed presumption has been justified because it excuses plaintiff from the necessity of making self-serving assertions that he would have followed adequate instructions, simply to put the issue of causation in sufficient dispute to avoid summary judgment or directed verdict, and it assists plaintiffs in cases where the person injured has died and evidence of what he would have done is unavailable for that reason. In the learned-intermediary context, however, it is the prescribing physician, not plaintiff, who has to testify about his or her decision to prescribe. 2008 WL 1821379 *7.

Moreover, MassTortDefense would point out that applying the read and heed presumption to prescription product contexts confuses two very different warnings: unavoidable risk warnings, and preventable risk warnings. The latter describe risks that can be avoided by the consumer by using a product in certain manner. The former, however, associated with prescription products, can only be avoided if the consumer chooses not to use the product at all. Thus, the question becomes whether the potential benefit of the prescription product outweighs a potential risk. The choice is not between a safe, or less safe use, or unsafe use, of the product, but whether to use the product at all. With prescription products, the FDA has determined that for indicated populations, the risks do not outweigh the benefits. A good albeit older discussion of why the heeding presumption doesn't make sense in this context is found in Thomas v. Hoffman-LaRoche, 949 F.2d 806, 812-14 (5th Cir. 1992).

Further, even if the presumption applied, it arguably would not have changed the result here. It is a rebuttable presumption, and Dr. Sonn remained firm in stating that even if Ackermann’s proposed “black box” warning had been given to him, he would have considered it -- but it would not have changed his decision to prescribe Effexor. For all these reasons, the Fifth Circuit concluded that the district court properly granted summary judgment to Wyeth on appellant’s failure-to-warn and strict-liability claims because she failed to show that an inadequate warning was a producing cause of her husband’s death.

5th Circuit Clarifies Learned Intermediary Doctrine and Heeding Presumption

In Ackermann v. Wyeth Pharmaceuticals, 2008 WL 1821379 (5th Cir, April 24, 2008), the Fifth Circuit addressed a couple of very important issues affecting the learned intermediary doctrine. Readers of MassTortDefense recognize that the LI doctrine is an important exception to the rule that a manufacturer must warn the end user or consumer of its product. In the case of prescription drugs and medical devices, which a patient may receive through the advice and with the permission of a prescribing physician, the duty to warn extends to this learned intermediary, who in turn uses his or her expertise, judgment, and knowledge of the specific patient, to decide not only which product the patient should receive, but which aspects of the long and detailed warning information should be emphasized with the patient.

Background of Decision

In Ackermman, plaintiff’s decedent alleged that defendant Wyeth failed adequately to warn about the drug-induced risk of suicide from its drug Effexor, and this deficiency led to her husband’s suicide. Effexor is a member of the class of drugs referred to as “selective serotonin and norepinephrine reuptake inhibitors” (“SNRI”). SNRIs are used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, premenstrual dysphoric disorder, and social anxiety disorder. The FDA generally groups Effexor with the selective serotonin reuptake inhibitor (“SSRI”) class of antidepressants, which includes Celexa, Prozac, Paxil, and Zoloft.

Plaintiff apparently suffered from clinical depression brought on by severe business and family problems. Martin sought treatment from psychiatrist Dr. Thomas Sonn on January 4, 2002. Martin saw Dr. Sonn four times in the following eight days. During that time, Dr. Sonn changed Martin’s medication to Effexor. On January 12, Martin complained to Dr. Sonn of various side effects he attributed to Effexor, including anxiety. Martin announced he would no longer take the medication. Dr. Sonn changed Martin’s medication from Effexor to Celexa because of the apparent side effects. Plaintiff terminated his relationship with Dr. Sonn. Nevertheless, Martin continued to take Celexa for five days until January 17, 2002, when he apparently committed suicide with a revolver. At the time of his death, Martin had detectable levels of Celexa, but not Effexor, in his bloodstream. 2008 WL 1821379 *1.

Dr. Sonn testified at deposition that he believed the package insert for Effexor as it existed in January 2002 adequately warned him of the risks of suicide and that he would continue to prescribe the drug to depressed patients. Wyeth filed for summary judgment, which was granted by the district court on the basis of the learned intermediary doctrine.

The Learned Intermdiary Doctrine

The Fifth Circuit noted that under the doctrine, a patient-purchaser’s doctor stands between the patient and the manufacturer, professionally evaluating the patient’s needs, assessing the risks and benefits of available drugs, prescribing one, and supervising its use. If the doctor is properly warned of the possibility of a side effect and is advised of the symptoms normally accompanying the side effect, it is anticipated that injury to the patient will be avoided. Accordingly, the doctrine excuses a drug manufacturer “from warning each patient who receives the product when the manufacturer properly warns the prescribing physician of the product’s dangers.” Porterfield v. Ethicon, Inc., 183 F.3d 464, 467–68 (5th Cir. 1999). Under Texas law, the learned-intermediary doctrine is not an affirmative defense, but it delineates to whom a defendant owes the duty to warn. 2008 WL 1821379 *2-3.

To recover for failure to warn under this doctrine, a plaintiff typically must show that (1) the warning was defective, and (2) the failure to warn was a producing cause of the injury. In other words, under Texas law, a plaintiff who complains that a prescription drug warning is inadequate must also show that the alleged inadequacy caused her doctor to prescribe the drug for her. If the physician was aware of the possible risks involved in the use of the product but decided to use it anyway, the adequacy of the warning is not a producing cause of the injury and the plaintiff’s recovery must be denied. And even if the physician is not aware of a risk, the plaintiff must show that a proper warning would have changed the decision of the treating physician, i.e., that but for the inadequate warning, the treating physician would have not used or prescribed the product. 2008 WL 1821379 *3.

Application To The Facts

Applying that review to the facts here, the Fifth Circuit noted that the January 2002 package insert warning mentions the risk for suicide twice, cautions that close supervision of high-risk patients should accompany initial drug therapy, and identifies the frequencies of suicidal behavior observed in patients taking Effexor. Even if not as explicit as plaintiff demanded post hoc, taken all together, the insert’s discussions of suicide establish that at least some risk of suicide exists when a patient takes Effexor.

The Court allowed the possibility that some issue of fact could be made out about whether the defendant’s characterization of the infrequent risks, was within a requisite degree of accuracy or was misleading. 2008 WL 1821379 *4.

However, the appeal could be resolved on the second prong of the analysis, namely, whether any defect in the Effexor warning was a substantial cause of Martin’s death. There must be a genuine issue of material fact whether the physician, here Dr. Sonn, would have prescribed Effexor even had the warning been “adequate” in plaintiff's terms. Here the court had to look at Dr. Sonn’s testimony about the certainty of his decision to prescribe Effexor, and alternatively, at the so-called “read-and-heed” presumption presuming that when an adequate warning is given by the manufacturer, it is heeded by the learned intermediary. 

Prescriber Testimony Key

Dr. Sonn testified that he reviewed the plaintiff’s proposed “fuller” warning, concluding that if the [proposed] warning had been communicated to him effectively and in a prominent manner before he prescribed Effexor to plaintiff, he would have considered it “but it would not have changed my decision to prescribe Effexor XR to Martin Ackermann to treat his depression, beginning with low-dose pills. It also would have not changed my decision to monitor and observe Martin Ackermann closely for suicide-related risks as I did… and as I did with Martin Ackermann, I would address the suicide-related risks reflected in that warning by close monitoring and observation, rather than through discussions with the patient expressly mentioning the risk of suicide or drug-triggered suicide.” 2008 WL 1821379 *5.

The Court rejected plaintiff’s argument that this was somehow contradictory testimony; his testimony was unequivocal. That he said he would have read it and heeded it did not mean anything other than he would have considered it, would have included it in his decision-making calculus. In his deposition and in his later declaration, Dr. Sonn affirmed that he would have prescribed Effexor to Martin and adhered to the treatment regimen he used regardless whether he had received the proposed stronger warning. In December 2005, he testified that he would not have warned Martin about the possibility of an increased risk of suicide primarily based on his belief that the suggestion would either plant seeds in the patient’s mind that suicide was an option or would discourage the patient from pursuing pharmacological treatment. And that, MassTortDefense readers, is a crucial notion. Any argument from the plaintiff that the prescriber was or would be legally required to pore over all the details of the warnings with a sick patient [and thus scare plaintiff into not taking the drug] is fundamentally inconsistent with the ethical duties of the physician.

Dr. Sonn was also asked to review the warning label accompanying Effexor that was in effect at the time of his deposition in December 2005, which included a “black box” warning for potential increased suicide in children and adolescents. When asked a follow-up question about a proposed similar warning for adults, Dr. Sonn reiterated his prior testimony and confirmed that it would not have changed his decision to prescribe Effexor XR to Martin Ackermann to treat his depression.

Because she construed this as a “no warnings” case, plaintiff's decedent argued that Wyeth completely sabotaged the intermediary, who, in turn, failed to warn of the risk of suicide. For this reason, she viewed Dr. Sonn’s testimony that he would have given a required warning to mean, “if Wyeth had given me a better warning, I would have warned.” This interpretation, however, is incompatible with Dr. Sonn’s testimony that his treatment protocol would not have changed and he still would have prescribed Effexor regardless of the warning given by the manufacturer.

This part of the decision is consistent with some other useful cases out there, including Motus v. Pfizer Inc., 358 F.3d 659 (9th Cir. 2004)(Zoloft); Porter v. Eli Lilly & Co., 2008 WL 544739 (N.D. Ga. Feb. 25, 2008)(Prozac); Longs ex rel. Estate of Buchanan v. Wyeth, 536 F.Supp.2d 843 (N.D. Ohio 2008)(Redux); Allgood v. Glaxosmithkline Plc, 2008 WL 483574 (E.D. La. Feb.20, 2008)(Paxil); Vanderwerf v. SmithKlineBeecham Corp., 529 F. Supp.2d 1294 (D. Kans. 2008)(Paxil).


In our next post, MassTortDefense will switch focus to the 5th Circuit's handling of the heeding presumption.