New Jersey Trial Court Ruling in Accutane: Another Example Of Science Driving Outcomes in Pharmaceutical Litigation

The New Jersey Superior Court recently issued another decision in a line of decisions in which courts have looked to the science to determine the outcome of large-scale pharmaceutical litigation at the pre-trial stage. ¹See Opinion, In re Accutane Litig., 2015 BL 59277, N.J. Super. Ct. Law Div. 2/20/15. The opinion is available at http://op.bna.com/exer.nsf/r?Open=bkan-9u9kg8.Other courts have issued similar rulings, excluding expert evidence and barring all or large categories of claims in consolidated litigation. See, e.g.,
In re Phenylpropanolamine (PPA) Prods. Liab. Litig., 289 F. Supp. 2d 1230, W.D. Wash. (excluding certain categories of claims alleging that PPA caused stroke); In re Heparin Prods. Liab. Litig., 803 F. Supp. 2d 712, N.D. Ohio (excluding certain categories of claims alleging that contaminated heparin caused injury and death). In re Accutane Litigation involved claims alleging that the acne medication Accutane (Isotretinoin) causes irritable bowel disease (IBD), and in particular Crohn’s disease.

In a thorough and comprehensive opinion in which the court examined the scientific evidence in detail, the court excluded the testimony of the plaintiffs’ experts as scientifically unreliable and failing to meet the standards for admissible scientific evidence articulated by the New Jersey Supreme Court in Kemp v. State of New Jersey, 174 N.J. 412

The decision stands as a strong precedent requiring plaintiffs in pharmaceutical cases to support their claims with scientifically reliable evidence. Where, as in the case of Accutane, there is a body of scientific evidence that is contrary to plaintiffs’ claims, expert opinions asserting a causal association are inherently unreliable. Plaintiffs’ experts cannot simply ignore such scientific data. Nor can they seek to evade it by using non-standard and unreliable methodologies.

The Scientific Evidence

Plaintiffs in the Accutane litigation alleged that ingestion of Accutane could cause Crohn’s disease, a disease that is characterized by inflammation that can occur anywhere in the gastrointestinal tract, leading to abdominal pain, chronic diarrhea, gastrointestinal bleeding, rashes, mouth ulcers and an increased risk of colon cancer.

Whether Accutane was associated with Crohn’s disease was not a question that the scientific community had failed to investigate. To the contrary, cases of Crohn’s disease appearing in individuals who had taken the medication led to a series of scientific studies designed to determine whether there was any increased incidence of the disease in the population taking the drug.

These studies were fairly uniform in their findings. At least eight studies found no statistically significant association between Accutane and irritable bowel disease. ²In re Accutane Litig., Opinion at 12. Seven found no statistically significant association between Accutane and Crohn’s disease. ³Id. at 13. Moreover, the scientific literature did not identify any biological mechanism that would explain such an association. ⁴Id. at 5.

It is in this context that plaintiffs submitted the reports of two experts, Arthur Kornbluth, a physician certified in internal medicine and gastroenterology, and David Madigan, a professor of statistics. Dr. Kornbluth offered theories regarding potential mechanisms by which Accutane could contribute to Crohn’s disease, and reviewed the epidemiological evidence examining whether there was an association. Dr. Madigan critiqued the epidemiological studies relied upon by defendant’s experts.

Both experts sought to explain away the contrary epidemiological data while singling out certain results from specific studies that they claimed supported a potential association between Accutane and Crohn’s disease. ⁵See id. at 10. The court, however, found neither expert’s analysis reliable.

Court’s Analysis of the Science

The Accutane decision is significant in many respects, the first of which is the order in which the court conducted its analysis. While it is often said that evaluating the admissibility of expert evidence focuses on the expert’s methodology rather than the substance of the expert’s opinions, frequently the science—and the expert’s attempts to deal with the science—dictates the outcome in product liability and mass tort litigation. This proved true in Accutane, where the court began its analysis with the affirmative scientific evidence finding no relationship between Accutane and Crohn’s disease.

The legal framework in which admissibility determinations are made supports such an analysis. As the Accutane court observed, “[i]n order to be valid methodology (viz., accepted by others in the scientific community) the expert’s opinions must be supported by ‘prolonged, controlled, consistent, and validated experiences of scientific research.’” ⁶Id. at 6. Similarly, there must be “‘some expert consensus that the methodology and underlying data are followed by experts in the field.’” ⁷Id. at 9, quoting Rubanick v. Witco Chem. Corp., 125 N.J. 421

However, as noted above, in the case of Accutane, there was a fairly significant body of epidemiological evidence finding no statistically significant association between the drug and irritable bowel disease or Crohn’s disease. This evidence was particularly powerful given that, as the court observed, “[e]pidemiological studies provide ‘the primary generally accepted methodology for demonstrating a causal relation between a chemical compound and a set of symptoms or disease.’” ⁸Id. at 17, quoting Conde v. Velsicol Chem. Corp., 804 F. Supp. 972, S.D. Ohio Indeed, the court noted that “‘[t]he very purpose of epidemiology is to serve the type of testing function required by Daubert, i.e., to discern accurately the effect of a particular agent on a disease against the background of the natural occurrence of the disease in the relevant population.’” ⁹Id. at 19, quoting Soldo v. Sandoz Pharms. Corp., 244 F. Supp. 2d 434, W.D. Pa.

Moreover, as the court observed, there was no agreed upon biological mechanism by which Accutane could cause IBD or Crohn’s disease. As a result, there were “no studies” that had asserted that Accutane caused IBD. ¹⁰Id. at 14. As the court noted, “[s]uch a statement would, of necessity, require an explication of a precise biological mechanism of the cause of IBD and no one has yet to venture more than alternate and speculative hypotheses on that question.” ¹¹Id. “Other than symptoms and risk factors, there appears to be little-to-no consensus in the medical/scientific community as to Isotretinoin’s correlation to CD or IBD generally.” ¹²Id.

Indeed, it turned out that one of plaintiffs’ own experts had declined to include a statement referencing Accutane as a cause of IBD in one of his own peer-reviewed publications. ¹³Id. at 16. This lack of scientific consensus supporting plaintiffs’ causal theories undermined their experts’ opinions.

Another way the court framed the issue was in terms of the peer review process. Plaintiffs’ experts’ opinions were not only at odds with the consensus view in the scientific community, but they had not even been subject to peer review. In excluding plaintiffs’ experts’ opinions, the court noted the importance of whether the expert’s “‘theory or technique has been subjected to peer review and publication.’” ¹⁴Id., quoting Daubert, 509 U.S. at 593.

As the court observed, relying on the Supreme Court’s decision in Daubert v. Merrell Dow Pharmaceuticals, Inc. ¹⁵509 U.S. 579 “‘[e]xpert opinions generated as the result of litigation have less credibility than opinions generated as the result of academic research or other forms of “pure” research.’” ¹⁶In re Accutane Litig., Order at 17, quoting Soldo v. Sandoz Pharms. Corp., 244 F. Supp. 2d 434, W.D. Pa.

The lack of scientific evidence supporting plaintiffs’ theories, and indeed the large body of contrary scientific evidence, was particularly significant given that, as is frequently the case in pharmaceutical litigation, there are a number of established alternative causes of Crohn’s disease and IBD. Genetics, for example, is a “prominent risk factor” for these diseases, and indeed as the court observed, “the treatises provided to the court recite an extensive list of factors commonly associated as ‘risks’ for CD and IBD” relating to diet, lifestyle, and common medications. ¹⁷Id. at 14.

Court’s Analysis of Plaintiffs’ Expert Opinions

This body of contrary scientific evidence proved fatal to plaintiffs’ claims and illustrates the way in which affirmative presentation of the scientific case is critical in arguing for the exclusion of contrary scientific theories. Offering opinions contrary to the scientific data is a fundamental methodological flaw that often provides a compelling basis for excluding an expert’s opinions. That was certainly the case in Accutane, where the court focused heavily on the scientific evidence suggesting that there was no association between Accutane and IBD and Crohn’s disease before proceeding to its analysis of plaintiffs’ experts’ specific opinions.

Nonetheless, the court’s analysis of those opinions is also significant for its insights into the types of arguments that are frequently made in the face of contrary epidemiological data. As the court observed, plaintiffs’ experts made frequent reference to individual case reports of IBD or Crohn’s disease in patients who were taking Accutane, citing in particular adverse event reports made to the FDA’s Adverse Event Reporting System.

However, as the court observed, “[t]he FDA Adverse Event Reporting System (FAERS) typically yields information that is not evidentiary in a court of law,” given that such anecdotal data suffer from “serious limitations.” ¹⁸Id. at 23. These limitations are recognized by the FDA itself, which has cautioned against using the data it collects in making conclusions regarding causality.

While such data may be used to detect signals or develop hypotheses for further investigation, it is not a basis for drawing causal conclusions, and indeed as the FDA has observed, “‘there is no certainty that the reported event (adverse event or medication error) was actually due to the product.’” ¹⁹Id., quoting FDA Adverse Event Reporting System (FAERS), available at http://www.fda.gov/Drugs/ GuidanceComplianceRegulatory Information/Surveillance/AdverseDrugEffects/default.htm.

Moreover, the Accutane court made a particularly insightful observation regarding the inherent bias in such data, noting the effect that the existence of litigation itself may have in increasing the number of reports of adverse events made to the FDA—what the court described as the “potential abuse of the FAERS.” ²⁰Id. at 24 (“The legal profession is a bulwark of our society, yet the courts should never underestimate the resourcefulness of some attorneys.”). In the case of Accutane and IBD, the court noted that more than 87 percent of the reports were made by attorneys, not physicians. This stood in contrast to other kinds of adverse events reported with the drug, only 3.6 percent of which were submitted to the FDA by attorneys. ²¹Id. This bias in reporting associated with litigation is another reason, the court noted, that adverse event reports were an unreliable basis for assessing causation.

The court similarly rejected animal studies as a basis for assessing causation, noting that such studies could not be extrapolated to human beings. In particular, the court rejected the notion that studies in dogs could be used to show that Accutane caused IBD in humans, and indeed, observed that “IBD is not a condition from which dogs ever suffer.” ²²Id. at 26. Moreover, as is often the case with animal studies that are typically used as screening devices rather than formal methods to establish causation, the particular studies plaintiffs cited suffered from a number of methodological flaws that rendered them an unfit basis for making causal determinations.

Finally, because the epidemiological evidence was so uniform in finding a lack of an association between Accutane and IBD and Crohn’s disease, by necessity plaintiffs’ experts’ discussion of that evidence suffered from a “finely-tuned selectivity” that rendered their opinions “slanted away from objective science and in the direction of advocacy.” ²³Id. at 27. Plaintiffs’ experts singled out two studies upon which to base their opinions, rejecting the rest as “unreliable.” However, the court concluded that the methodologies of the two remaining studies upon which plaintiffs’ experts relied rendered them of limited value, and that they did not provide reliable support for the experts’ conclusions.

Neither of the two studies were population-based studies. Moreover, one of the studies used referrals to obtain study participants, which the court concluded amounted to “cherry-picking the subjects,” and the other study collected information by questionnaire, which the court concluded was “subject to recall bias and poor recollection.” ²⁴Id. at 27-28. Both studies had only a limited number of subjects, which the court found rendered them of limited value: “[t]he scientific literature does not support reliance upon such insignificant studies to arrive at conclusions.” ²⁵Id. at 30.

Indeed, the court noted that plaintiffs’ experts had interpreted the results of one of the studies in a manner that was “contrary to the authors’ own stated conclusions.” ²⁶Id. at 27. While the study’s authors concluded that their results did not appear to show any increased risk, plaintiffs’ experts attempted to cite the study for the opposite conclusion. In doing so, plaintiffs’ experts used data from the study that failed to adjust for the possibility that antibiotics taken by study participants biased the results. The court concluded that “[t]he reliance upon these two studies is fatal and reveals the lengths to which legal counsel and their experts are willing to contort the facts and torture the logic associated with Plaintiffs’ hypothesis.” ²⁷Id. at 29.

The court simultaneously concluded that the experts’ failure to consider the remaining studies represented an independent basis for excluding their opinions and was “not valid methodology.” ²⁸Id. at 30. The court noted that ignoring this epidemiological evidence was not “methodology based,” but rather was “conclusion-driven.” ²⁹Id. at 31.

The court concluded that such an approach was an example of the “‘hired gun phenomenon’’” that the rules governing admissibility of expert evidence were designed to prevent. ³⁰Id., quoting Rubanick, 125 N.J. at 453. “[T]he examination of the ‘lines of evidence’ by Plaintiffs’ experts was highly selective, looking no further than they wanted to—cherry picking the evidence—in order to find support for their conclusion-driven testimony in support of a hypothesis made of disparate pieces, all at the bottom of the medical evidence hierarchy.” ³¹Id. at 34.

As the court noted, “It is one thing to stand alone in the world of science, advancing a hypothesis that others do not accept. It is quite another thing to advance a hypothesis that can only be supported by disregarding valid scientific research.” ³²Id.

Conclusion

In re Accutane illustrates how science frequently drives the outcome in pharmaceutical and other large-scale product liability litigation.

Demonstrating that an expert’s opinions are contrary to the body of scientific evidence is frequently a powerful method for resolving mass litigation at the pre-trial stage.

Moreover, in confronting such scientific evidence, plaintiffs’ experts frequently are forced to make other methodological errors, which form a further basis for excluding their opinions as unreliable and inadmissible under the standards governing scientific evidence.