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.

 

Absence of Causation Evidence Leads to Reversal of Accutane Verdict

An appellate court in Florida last week overturned a verdict in favor of a plaintiff in the Accutane litigation.  Hoffmann-LaRoche Inc. v. Mason, 2009 WL 3430190 (Fla. 1st DCA 10/27/09). The opinion reminds readers of the crucial nature of the causation inquiry during discovery, especially in a warnings context.

Plaintiff developed severe acne while in middle school, which caused him to seek treatment from  a dermatologist. After the acne failed to respond to topical agents and antibiotics, Dr. Fisher prescribed Accutane, which was also later prescribed by plaintiff's family practitioner, Dr. Kenneth Counselman, until November 2000, at which time he was diagnosed with Crohn's Disease, a form of Inflammatory Bowel Disease (for which the epidemiology, BTW, does not show any association with the drug).

Plaintiff filed suit under theories of strict liability and negligent failure to warn alleging that Accutane's warning label was inadequate to warn his physicians about the risk of developing IBD. Specifically, plaintiff presented an expert witness who testified that the warning was insufficient because it allegedly did not adequately describe the relationship between Accutane and IBD. At the close of plaintiff's case, defendant moved for a directed verdict, arguing that plaintiff had failed to establish that his injury was proximately caused by any inadequacies in the warning. The trial court denied the motion after the jury returned its verdict in favor of plaintiff in the amount of $7 million.

The issue on appeal was the adequacy of the warnings testimony, and on particular, the causation issue. 

While plaintiff presented testimony that the warning label was allegedly inadequate to warn physicians that Accutane use could lead to IBD, Dr. Fisher, the prescribing physician, testified that he understood the warning label to mean that there was at least a possibility of a causal relationship between Accutane and IBD. (Dr. Fisher testified that he understood the phrase “temporally associated” to mean that there was a possibility of a causal relationship; virtually all doctors understand that this means an association in time; you take the drug and later you get the effect).  He testified that he would still be willing to prescribe Accutane to his patients even if there was evidence showing that it could cause IBD in rare cases. He also testified that even if the warning label contained all of the additional information suggested by plaintiff's expert, he would still have prescribed the medication. Thus, any alleged inadequacies in Accutane's warning label could not have been the proximate cause of plaintiff's injury because Dr. Fisher understood that there was a possibility that use of the drug could lead to plaintiff developing IBD. And he made an informed decision to prescribe the drug for this patient despite this risk.  Dr. Counselman admitted that he did not consult a prescribing reference manual before prescribing the drug, and thus a different warning would not have mattered to him. 

While a jury somehow found that the alleged failure to provide an adequate warning was a substantial contributing cause of plaintiff's development of IBD, plaintiff actually presented no evidence to establish proximate cause. The trial court erred in denying the motion for a directed verdict. Again, because plaintiff presented no evidence from either prescribing physician that a differently worded warning would have resulted in either physician not prescribing Accutane for his extreme acne, plaintiff failed to establish that the allegedly deficient warning was the proximate cause of his injury; judgment reversed.

 

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."

 

 

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