In In re Neurontin Marketing, Sales Practices, and Products Liability Litigation, 612 F. Supp. 2d 116 (D. Mass. 2009), numerous plaintiffs sued the manufacturers of an anti-epilepsy drug in various courts alleging they or their decedents had suffered various injuries including suicidal behavior or ideation (“suicidality”). The federal court actions were consolidated in the United States District Court for the District of Massachusetts, where defendants moved to exclude the testimony of three of plaintiffs’ expert witnesses pertaining to the plaintiffs’ product liability claims. The experts intended to opine that the drug increased the level of the chemical neurotransmitter GABA in the brain, which in turn led to a decrease in the level of several other neurotransmitters, particularly serotonin, causing adverse mood and behavioral disturbances, some of which ultimately led to suicidality. The opinions pertained only to the issue of the drug’s alleged general causation, rather than plaintiff-specific causation, of suicidality.
The court first described its “gatekeeping” role under Federal Rule of Evidence 702 and Daubert v. Merell Down Pharmaceuticals, Inc., 509 U.S. 579 (1993). The court emphasized that its task was to assess the reliability of the plaintiffs’ experts’ methods and data, not the proffered opinions’ ultimate correctness. The court used as a framework for its analysis the “Bradford Hill criteria” developed by the British epidemiologist of the same name, particularly the criteria pertaining to the strength of the association between the drug’s use and an increased risk of suicidality and the biological plausibility of a causal relationship. Applying that framework, the court found that plaintiffs’ experts’ opinions were based on sufficiently reliable methods and data to be admissible.
The court first considered defendants’ contention that, because no epidemiological or other evidence associated the drug with suicidality, any expert testimony regarding how the drug causes suicidality was irrelevant and inadmissible. The court observed that, although epidemiological studies are not necessary, establishing causation without some evidence associating alleged cause with alleged effect “can be an uphill battle.” The court, however, credited plaintiffs’ invocation of a 2008 Food and Drug Administration study (“FDA study”) that found that a group of anti-epilepsy drugs, which included the drug at issue, was associated with an increase in suicidality, but that the drug at issue was associated with suicidality events only in a non-statistically-significant fashion. The court acknowledged defendants’ criticisms of aspects of the study’s methodology and analysis—notably that its conclusion was driven by drugs other than the one at issue—but concluded that these criticisms went to the weight of the study rather than its admissibility. The court also concluded that, although the FDA study found no statistically significant association between the drug at issue and increased suicidality, plaintiffs’ experts could reliably opine that the study’s conclusion that a sub-group of drugs including the drug at issue had a statistically significant association with increased suicidality could be extrapolated to apply to the drug at issue. The court, however, acknowledged that the study alone was insufficient to establish causation because the FDA’s standard for finding association differed from the standards for establishing causation for the purpose of tort liability.
The court then assessed the biological plausibility of the experts’ causation theory. As to the first step of that theory, the court noted that it was undisputed that the drug increased the level of GABA in the brain. As to the second step, that the increase in GABA led to a decrease in other neurotransmitters including serotonin, the court noted that plaintiffs’ experts claimed that certain published, peer-reviewed in vitro animal studies showed such a decrease, while defendants’ experts disputed that those studies applied to humans; and defendants’ experts claimed that certain published, peer-reviewed in vivo human studies showed no such decrease, while plaintiffs’ experts interpreted those studies differently. The court concluded that the studies cited by plaintiffs’ experts, as well as certain internal and external communications by defendants which supported the conclusion that an increase in GABA led to a decrease in serotonin, constituted “good grounds” to support that conclusion. The court further noted that the difference in opinion between plaintiffs’ and defendants’ experts suggested that reasonable experts might differ on the issue and therefore supported the court’s conclusion to submit the issue to the jury. Finally, as to the third step, the court noted that there was wide acceptance in the scientific community that decreased levels of serotonin were associated with depression, aggression and suicide, and that defendants’ expert admitted as much.
Defendants challenged plaintiffs’ proffer in support of their causation theory of reports of alleged adverse events experienced in patients taking the drug as irrelevant, on the ground that many of the events concerned patients’ depression, hostility, confusion and other behaviors short of actual suicidality. The court, however, concluded that such events were relevant because such abnormal behaviors were antecedent to actual suicidality under plaintiffs’ causation theory. Finally, the court concluded that one of plaintiffs’ experts—who had a doctorate in pharmacology and toxicology and served as a consultant to pharmaceutical companies in preparing submissions to the FDA and evaluating post-marketing adverse event reports—was qualified to testify about the adverse event data and “other sources of information regularly used by the FDA and industry professionals,” even if not as to the medical aspects of plaintiffs’ theory of causation.