MDL Court Rejects Plaintiffs' New Causation Experts

The MDL judge in the Denture Cream Products coordinated litigation has rejected all of plaintiffs' general causation experts. See In re Denture Cream Prods. Liab. Litig., No. 09-2051-MD-Altonaga (S.D. Fla. Jan.. 28, 2015).

Over three and a half years ago, in Chapman. v. Procter & Gamble Distributing LLC, Case No. 9:09-
CV-80625, the MDL court had granted Procter & Gamble’s motion to exclude the opinions of Plaintiffs’ general causation experts. See In re Denture Cream Prods. Liab. Litig., 795 F. Supp. 2d 1345 (S.D. Fla. 2011) . Since Chapman, Plaintiffs claimed to have obtained new evidence in support of their argument that products like Fixodent can cause copper deficiency myeloneuropathy (“CDM”), including clinical, epidemiological, background risk of disease, and dose-response relationship. Defendants filed an omnibus Daubert Motion challenging the reliability and significance of Plaintiffs’ alleged new general causation evidence and opinions — in particular a Fixodent Blockade Study and "Dr. Lautenbach’s cohort study."  The motion argued the previously identified analytical gaps in Plaintiffs’ chain of general causation still remained. In particular, Defendants contended that Plaintiffs still could not establish any of the following, that: (1) someone can ingest enough zinc from Fixodent to place the body in a negative copper balance; (2) a prolonged negative copper balance from denture cream use can lead to a copper deficiency; (3) a dose-response relationship exists between Fixodent and copper deficiency, much less myeloneuropathy; (4) Fixodent users face a greater risk of developing myeloneuropathy than the general population; or (5) a physiological mechanism explains how a copper deficiency can lead to a myeloneuropathy.

The alleged decades’ worth of underlying scientific literature” Plaintiffs relied on to prove general causation — most of which was presented in Chapman — pertained to excess zinc and copper deficiency, or copper deficiency and neurological disorders; it is not specific to the zinc compound in Fixodent. Particularly in light of the millions of consumers who have regularly used Fixodent for
decades without complaint, see Chapman, 766 F.3d at 1304 , the Court concluded first that Plaintiffs had not demonstrated the medical community generally recognizes the zinc compound in Fixodent as a known toxin, and thus the Court undertook an extensive Daubert analysis on the general question of whether Fixodent can cause CDM, in light of the allegedly new evidence. The Court examined Plaintiffs’ new evidence in support of proving general causation, including epidemiological studies, dose-response analysis, and the background risk in particular.

The opinion is quite lengthy, and worth a close read for readers with Daubert issues in toxic tort cases.  A few highlights:  Plaintiffs sought to rely on a recently conducted study supposedly showing the short term effects of zinc in the body.  But the Court could not "turn a blind eye to the myriad, serious methodological flaws in the Fixodent Blockade Study," which did not go just to the weight of the evidence. While some of these flaws, on their own, might not have been serious enough to justify exclusion of the Fixodent Blockade Study; taken together, the Court found this Fixodent Blockade Study was not “good science,” and was not admissible.   Consequently, Plaintiffs still had no evidence of the zinc in Fixodent’s ability to inhibit copper absorption at the relevant site of action — the intestines.

Plaintiffs relied on the opinions of a Dr. Grainger, on dose-response and relying on in vitro studies. Defendants argued Dr. Grainger’s opinions were unreliable because Dr. Grainger did not offer any explanation of how zinc dissociation properties observed in in vitro release designs would transfer to a live human, and did not consider factors that might allow him to make such an extrapolation. The court agreed that Dr. Grainger’s opinions were unreliable. The in vitro dissociation studies were the foundation for all of Dr. Grainger’s conclusions. The portion of his report dedicated to these studies was completely devoid of any pertinent details or analysis. His comments regarding “various in vitro release designs”  lacked support citations, and lacked any discussion about the study designs or methodology, and any details about the individual study results. See Ballard v. Keen Transp., Inc., No. 4:10-cv-54, 2011 WL 474814, at *4 (S.D. Ga. Feb. 3, 2011) (expert’s failure to cite any specific chapter, page, or line on which he based his conclusions “makes it appear that he is not being as careful in his litigation consulting as he is in his ordinary professional work.”).  Dr. Grainger’s failure to explain the relevancy of the in vitro studies to humans or to account for factors needed to make a proper extrapolation was notable given his critique of studies the defendants had relied on.  Accordingly, the court concluded, "In short, Plaintiffs are not much better off than they were at the time of Chapman."

The MDL court also noted that epidemiology is “generally considered to be the best evidence of causation in toxic tort cases.” Kilpatrick, 613 F.3d at 1337 n.8.  Epidemiology is the field of public health and medicine that studies the incidence, distribution, and etiology of disease in human populations. . . . Epidemiologic evidence identifies agents that are associated with an increased risk of disease in groups of individuals, quantifies the amount of excess disease that is associated with an agent, and provides a profile of the type of individual who is likely to contract a disease after being exposed to an agent. Epidemiology focuses on the question of general causation (i.e., is the agent capable of causing disease?) Green, REFERENCE MANUAL ON SCIENTIFIC EVIDENCE 3d ed., at 551–52.  There are two classes of epidemiological evidence: analytical and descriptive. See In re Denture Cream Prods. Liab. Litig., 795 F. Supp. 2d at 1353–54.  Analytical evidence consists of randomized controlled trials, case control studies, and cohort studies, while descriptive evidence consists of case studies and case series. 

Plaintiffs claimed they now had analytical epidemiological evidence to support their theory of general causation — Dr. Lautenbach’s cohort study.  However, Dr. Lautenbach’s cohort study did not account for the lack of information pertaining to the subjects’ denture cream usage, and it was based on the assumption this information was appropriately taken into account by the underlying treating physicians.  Dr. Lautenbach also assumed the treating physicians took into account the amount of denture cream use, claiming it was obviously a volume high enough to trigger that as a designation for physicians.  The court concluded that the extent of Dr. Lautenbach’s reliance was a
complete delegation of his responsibilities as an epidemiologist to assess the subjects’ exposure. The study had severe limitations as a reliable foundation for building a cohort study to formally assess the association between zinc-containing denture cream and CDM. At its core, the basis for Dr. Lautenbach’s cohort study was merely a summary of a collection of case reports, with severely inadequate information about denture cream usage. The layers of unsupportable estimations and
approximations, added to this already shaky foundation, confirmed the Court’s finding that Dr.
Lautenbach’s cohort study was unreliable evidence of general causation.

While plaintiffs had presented "a superficially appealing hypothesis that prolonged use of very large amounts of Fixodent may cause copper deficiency," the law requires more than a general theme to support causation, said the court.  Without Dr. Lautenbach’s cohort study, Plaintiffs continued to have no analytical epidemiological evidence on which to base their inference of causation. In addition to the absence of any analytical epidemiological studies, the absence of data on the background risk of CDM also remained a substantial weakness in Plaintiffs’ experts’ causal reasoning. When analyzing an expert’s methodology in toxic tort cases, the court should pay careful attention to the expert’s testimony about the dose-response relationship. The dose-response  relationship is a relationship in which a change in amount, intensity, or duration of exposure to an agent is associated with a change — either an increase or decrease — in risk of disease. For most types of dose-response relationships following chronic (repeated) exposure, thresholds exist, such that there is some dose below which even repeated, long-term exposure would not cause an effect in any individual.  See generally CASARETT AND DOULL’S TOXICOLOGY: THE BASIC SCIENCE OF POISONS Chs. 1, 4 (McGraw Hill 6th ed.2001).  Often low dose exposures — even for many years — will have no consequence at all, since the body is often able to completely detoxify low doses before they do any damage.  Even Plaintiffs conceded that Fixodent “is safe when used in moderate amounts.” 

So, the Court again found Plaintiffs had not presented sufficient proof of general causation using the indispensable primary methodologies identified by the Eleventh Circuit.

 

Cancer Study of 9/11 Responders

Your humble blogger was quoted in a recent article in a Product Liability Law 360 story on the recent JAMA stud, which found no significant increase in most cancers among first responders and others exposed to dust and debris from the 9/11 terrorist attacks.  The study included more than 55,000 people enrolled in a 9/11-related health registry and examined data from 2003 to 2008.

 

Third Circuit Upholds Exclusion of Plaintiff's Causation Expert

The Third Circuit last week affirmed the exclusion of expert testimony in a toxic tort suit in which plaintiff alleged defendants' insecticide products gave him non-Hodgkin's lymphoma. Pritchard v. Dow AgroSciences, et al., No.10-2168 (3d Cir. 2011).

Plaintiff claimed that he contracted cancer from a pesticide produced by defendant Dow AgroSciences. His wife claimed to have suffered derivative injuries. In support of their complaint, the Pritchards solicited the expert testimony of Dr. Bennet I. Omalu, who provided the District Court with a report and, later, a declaration, stating that Dursban caused the cancer.  Although the trial court found Dr. Omalu to be a qualified expert, it ruled (on Dow's motion) that his proposed testimony was unreliable and therefore inadmissible at trial under Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993). The exclusion of Dr. Omalu's testimony doomed the lawsuit, because plaintiffs had no other evidence of causation.  Plaintiffs appealed.

The appeal tried to raise the issues surrounding the intersection of federal law, rules of evidence underlying Daubert, and state law, which supplies the elements of a claim (including causation) in a diversity case. Plaintiffs argued that in the course of finding that Dr. Omalu's testimony was unreliable, the District Court erroneously relied on principles that were supposedly at odds with state (Pennsylvania) substantive law governing the level of certainty required to establish causation, having to do with idiopathic disease and epidemiological studies.

It is true that the trial court noted that Dr. Omalu did not rule out unknown or idiopathic causes; that the court considered the fact that the epidemiological study on which the doctor wished to rely showed only a relative risk of 2.0; and that the court observed that the proposed testimony was not grounded in science as Dr. Omalu has not presented any statistically significant evidence showing an association between the chemical agent at issue and non-Hodgkins lymphoma. See Pritchard v. Dow Agro Sciences, 705 F. Supp. 2d 471, 492, 486, 493 (W.D. Pa. 2010).

However, the trial court considered these factors among “a host of other deficiencies,” as components of a determination that the proffered testimony failed to satisfy the admissibility standard. The trial court did not adopt any bright-line rules, but instead evaluated the plaintiffs' proffer using a flexible approach as directed by the Court of Appeals in Heller v. Shaw Industries, 167 F.3d 146 (3d Cir. 1999).  This was an evidentiary ruling, separate and distinct from any substantive question regarding causation (which the court never had reason to reach).

Plaintiffs also argued that the court had engaged in some kind of improper balancing of plaintiffs' scientific evidence vs. defendants'. But the district court engaged in no such balancing. Instead, it rightly concluded that Dr. Omalu's proposed testimony was unreliable due to numerous cracks in its scientific foundation.  He cited only one specific study in support of his general causation conclusion that Dursban causes cancer — and in fact, he relied not on the study itself but on his own reinterpretation of the study's findings using a lower confidence interval. (That is, he recalculated the study's conclusions so as to serve plaintiff's litigation needs, said the court.)   Moreover, the plaintiffs offered no clear explanation of the methods through which he recalculated the study's results, leaving the court unable to evaluate the reliability of his methodology.

And the expert's specific causation conclusion that Dursban had caused Mr. Pritchard's illness was not supported by evidence in the medical records, discovery responses, deposition testimony, application records, or any other information regarding Mr. Pritchard's exposure to pesticides.  Significantly, Dr. Omalu also failed to adequately address possible alternative causes of the cancer.

Accordingly, the trial committed no error in excluding the expert testimony, and in the absence of proof of causation, the case was properly dismissed. Affirmed.

 

Court Excludes Toxic Tort Causation Testimony

A federal court has excluded plaintiffs' expert testimony in litigation alleging personal injury and property damage from releases at a Midwest refinery.  Baker, et al. v. Chevron USA Inc., et al., No. 05-cv-00227 (S.D. Ohio Jan. 6, 2010). In the absence of necessary expert testimony, the claims were subject to summary judgment.

Plaintiffs in this case were residents of the villages of Hooven and Cleves, Ohio, who asserted claims for personal injury and property damage allegedly resulting from the Gulf Oil refinery, now owned by defendant Chevron USA.  Gulf operated a gasoline refinery which was situated on the eastern edge of Hooven from 1930 to 1985. Gulf also refined diesel fuel, jet fuel, and fuel oil at the refinery and operated an asphalt plant at this location. Gulf and Chevron merged in 1985, and Chevron closed the refinery in 1986.

Plaintiffs alleged that Gulf’s operation of the refinery resulted in the release of millions of gallons of gasoline and diesel fuel.  But these plaintiffs did not claim injuries resulting from groundwater contamination. Rather, they asserted injuries allegedly caused by air emissions from the refinery and, in particular, the benzene contained in those emissions. Benzene is ubiquitous in the ambient air and is a component or constituent of vehicle exhaust and cigarette smoke. In the petroleum industry, benzene is found in small amounts in gasoline.

For case management purposes, the matter was bifurcated between personal injury claimants and property damage claimants. The parties were permitted to select bellwether plaintiffs for each trial group. This opinion dealt with the claims of the bellwether personal injury claimants, and a key issue, as is often the case in toxic tort litigation, was causation.

Regarding their alleged benzene exposure, plaintiffs offered a three-step procedure. First, expert Dr. Cheremisinoff calculated a gross amount of benzene released from the refinery through emissions. Then, using those calculations, Dr. Rosenfeld, plaintiffs’ second expert, used an air flow model to calculate the cumulative dose of benzene to which each plaintiff was exposed. Third, using those dose estimates, a third expert, Dr. Dahlgren, submitted opinions that each plaintiff’s dose of benzene was sufficient to cause her illness. 

Chevron moved to exclude Dr. Dahlgren's opinions under Daubert, and for summary judgment contingent  upon the striking of  plaintiffs' causation evidence. The principal argument raised was that Dr. Dahlgren’s opinions were unreliable because there was an insufficient scientific or medical basis to conclude that the doses of benzene to which plaintiffs’ were exposed were large enough to have caused their illnesses. Relatedly, Chevron contended that there is an insufficient scientific or medical basis to conclude that benzene even causes some of the illnesses alleged. The Court held a hearing on Chevron’s Daubert motion during which Dr. Dahlgren and Chevron’s medical expert also testified.

In a toxic tort case, the plaintiff must present evidence of both general causation and specific causation. General causation establishes whether the substance or chemical at issue is capable of causing a particular injury or condition. Specific causation relates to whether the substance or chemical in fact caused this plaintiff’s medical condition. Without expert medical testimony on both general causation and specific causation, a plaintiff’s toxic tort claim will fail.

In this case, Dr. Dahlgren offered causation opinions based largely on epidemiological studies. (Epidemiology is the study of the incidence, distribution, and etiology of disease in human populations.) Epidemiology is usually considered highly probative evidence on general causation in toxic tort cases. The court may nonetheless exclude expert testimony based on epidemiological studies where the studies are insufficient, whether considered individually or collectively, to support the expert’s causation opinion. Nothing in either Daubert or the Federal Rules of Evidence requires a district court to admit opinion evidence that is connected to existing data only by the ipse dixit of the expert. A court may thus conclude that there is simply too great an analytical gap between the data and the opinion proffered.

A couple of parts of the court's detailed analysis are worth highlighting for readers of  MassTortDefense:

First, Dr. Dahlgren’s reliance on the “one-hit” or “no threshold” theory of causation in which exposure to one molecule of a cancer-causing agent has some finite possibility of causing a genetic mutation leading to cancer. The court noted that while the one-hit theory has been accepted for purposes of establishing regulatory safety standards, it has not been accepted as a reliable theory for causation under Daubert standards.  See Allen v. Pennsylvania Eng’g Corp., 102 F.3d 194, 199 (5th Cir. 1996) (“Scientific knowledge of the harmful level of exposure to a chemical, plus knowledge that the plaintiff was exposed to such quantities, are minimal facts necessary to sustain the plaintiffs’ burden in a toxic tort case.”); McClain v. Metabolife Int’l, Inc., 401 F.3d 1233, 1240 (11th Cir. 2005) (holding that district court erred by not excluding plaintiff’s expert’s causation opinion because he neglected dose-response relationship); Henricksen v. ConocoPhillips Co., 605 F. Supp.2d 1142, 1162 (E.D. Wash. 2009) (excluding expert’s opinion pursuant to Daubert where “he presumed that exposure to benzene in gasoline can cause AML in any dose.”); National Bank of Commerce v. Associated Milk Producers, Inc., 22 F. Supp.2d 942, 961 (E.D.Ark. 1998), aff’d, 191 F.3d 858 (8th Cir. 1999); Sutera v. Perrier Group of Am., Inc., 986 F. Supp. 655, 667 (D. Mass.
1997). Moreover, since benzene is ubiquitous, causation under the one-hit theory could not be established because it would be just as likely that ambient benzene was the cause of plaintiffs’ asserted illnesses.

Second, the court noted that to the extent that Dr. Dahlgren relied on the evidence that plaintiffs were exposed to benzene in excess of regulatory levels, that is insufficient to make his opinions admissible. The mere fact that plaintiffs were exposed to benzene emissions in excess of mandated limits is insufficient to establish causation. Nelson v. Tennessee Gas Pipeline Co., 243 F.3d 244, 252-53 (6th Cir. 2001); David L. Eaton, Scientific Judgment and Toxic Torts- A Primer in Toxicology for Judges and Lawyers, 12 J.L. & Pol’y 5, 39 (2003) (“regulatory levels are of substantial value to public health agencies charged with ensuring the protection of the public health, but are of limited value in judging whether a particular exposure was a substantial contributing factor to a particular individual’s disease or illness.”). This is because regulatory agencies are charged with protecting public health and thus reasonably employ a lower threshold of proof in promulgating their regulations than is used in tort cases. Allen, 102 F.3d at 198.

Third, the court focused on the issue of the link between cited literature and the actual specific opinion given. The court recognized that an expert’s opinion does not have to be unequivocally supported by all epidemiological studies in order to be admissible under Daubert. But here, the opinions expressed in Dr. Dahlgren’s revised report were based "on a scattershot of studies and articles which superficially touch on each of the illnesses at issue." The expert had not differentiated the cases in any way and simply assumed that each reference supported his causation opinion on each and every illness. That clearly was not the case. Also, none of the cited studies supported an opinion that benzene can cause the illnesses from which plaintiffs suffer at the extremely low doses or exposures experienced in this case. Even if it is medically accepted that benzene can cause disease at high doses, Dr. Dahlgren could not cite any paper finding that the relevant low cumulative exposure significantly increases the risk of developing the injuries.

The court, therefore, found that the expert's causation opinions were not reliable under the standards enunciated by Daubert and, consequently, inadmissible. Without Dr. Dahlgren's testimony, the plaintiffs were unable to establish that their illnesses were caused by alleged emissions from the plant, the court observed, and so granted Chevron's motion for summary judgment on all four bellwether personal injury plaintiffs.
 

Nano-particle Study Generates More Heat Than Light

A new study published in the European Respiratory Journal is generating media attention, and some observers assert it may have far-reaching implications for the nano-tech industry. Is this warranted?

In this study, Song, et al., Exposure to nano-particles is related to pleural effusion, pulmonary fibrosis and granuloma, 34(3) Eur. Respir. J. 559-567 (2009), researchers at China's Capital University of Medical Sciences linked lung disease in seven Chinese workers, two of whom reportedly died, to nano-particle exposures in a print plant where a paste containing nano-particles was sprayed onto a polystyrene substrate, with subsequent heat-curing.

The study reported that seven young female workers (ages 18–47), exposed to nano-particles for 5–13 months, were admitted to the hospital, all with shortness of breath and pleural effusions. Polyacrylate, consisting of nano-particles, was confirmed in the workplace. Pathological examinations of the patients' lung tissue displayed non-specific pulmonary inflammation, pulmonary fibrosis, and foreign-body granulomas of pleura. By transmission electron microscopy, nano-particles were observed to have lodged in the cytoplasm and caryoplasm of pulmonary epithelial and mesothelial cells, but also were located in the chest fluid.

The authors expressed concern that long-term exposure to some nano-particles may be related to serious damage to human lungs.  But, putting the media reception aside, this study appears to do more to highlight the common sense need to follow good industrial hygiene practices than to provide compelling evidence of any unique health risks posed by engineered nano-particles. The plant sprayed a strong chemical paste and then heated plastic material in an enclosed space apparently lacking ventilation.  The room in which the women worked was small and unventilated for a significant part of their exposure period. Only on occasion, they wore mere "cotton gauze masks." 

From the study it appears that the workers had a complicated exposure history to a mix of chemicals; while there was a reported association of nano-particles with lung disease, it is unclear which, if any, of the chemical exposures might have contributed to the lung issues. Readers of MassTortDefense know that an association is not causation.  For example, formation of thermodegradation fume products are known to cause significant occupational disease, and paint spraying has been shown to be potentially harmful long before nano-sizing of chemicals was utilized. 

Moreover, sufficient exposure information necessary to even begin to think about a causal connection between exposure to nano-sized particles in the paste/dust and lung and heart disease in the workers was missing.  Clearly, there may be alternative explanations for what the study authors described finding in the patients.

As noted here before, NIOSH emphasizes the use of a variety of engineering control techniques, implementation of a risk management program in workplaces where exposure to nanomaterials exists, and use of good work practices to help to minimize worker exposures to nanomaterials.
 

 

 

New Study On Diet And Heart Disease Makes Important Point About Epidemiology

Readers may have heard the response by the person warned by a family member that what he or she was eating was bad for their heart. “Wait a month and there will be a different study showing it is good for me.”  What we know for sure about diet and the heart is actually a surprisingly short list.

This week comes the study, A Systematic Review of the Evidence Supporting a Causal Link Between Dietary Factors and Coronary Heart Disease, by Drs. Mente, de Koning, et al. , 2009 Arch Intern Med. 169(7):659-669. This review study did an analysis of nearly 200 studies involving millions of people.


The authors concluded that strong evidence supports valid associations of protective factors for vegetables, nuts, and "Mediterranean" diet patterns, but that associations of harmful factors included intake of trans–fatty acids and foods with a high glycemic index.


Significantly, insufficient evidence of association was present for intake of supplementary vitamin E and ascorbic acid (vitamin C); saturated and polyunsaturated fatty acids; total fat; meat; eggs; and milk. 


One of the interesting features is that the authors used the traditional Bradford Hill guidelines on drawing causation conclusions from evidence of association to derive a causation score, basing it on 4 criteria (strength, consistency, temporality, and coherence) for each dietary exposure in cohort studies; they also examined the results for consistency with the findings of randomized trials.

Epidemiology involves judgment; it is not an absolute science, and the presence of confounding factors and the difficulty in finding an adequate control/comparison group for many food issues are similar to the issues seen in toxic tort litigation. 


No surprise, then, that the authors conclude that future evaluation of dietary patterns, including their nutrient and food components, in cohort studies and randomized trials is recommended.