Law

This week, as Drug and Device Law Jews, we are preparing for Passover, which, like most Jewish holidays, begins with a multi-generational dinner at the home of the Drug and Device Law Bubbie (our mother).  Although we of the second generation (there are now four) still fancy ourselves to be the "kids' table" at this dinner – giggling at the solemn points of the reading, singing endless choruses of our favorite Passover song in defiance of the "just one time" edict, and generally disrupting the proceedings as much as possible – the reality is that we are all upper-middle-aged adults.  And, as our matriarch ages (at least on paper), we assume more and more of the food preparation for the Seder dinner.  And there's the rub.  For, much as we would enjoy the occasional stroke of rogue creativity, we know that nothing unfamiliar will be allowed on the table and that each of the traditional dishes must taste exactly as it has tasted for the past 50-plus (if not 2,000) years.  Every ingredient and every step of preparation is subject to scrutiny, and Bubbie is the gatekeeper.   (You know where this is going). 

As everyone knows, under SCOTUS's Daubert decision, the trial court is the gatekeeper when it comes to admitting or excluding the testimony of expert witnesses.  We who practice in the mass tort space have gratefully experienced judges who take this responsibility seriously and have endured those who "punt" these determinations, nearly always to the benefit of plaintiffs whose dime-store experts – lacking qualifications, methodologies, or both – are permitted to peddle their wares to unsuspecting juries. 

The Lipitor MDL judge falls resoundingly into the former camp.  In In re Lipitor (Atorvastatin Calcium) Marketing, Sales Practices, and Prods. Liab. Litig., 2016 WL 1251828 (D.S. C. Mar. 30, 2016), considered the defendant's Daubert motions addressed to the plaintiffs' four causation experts, and wholly or partially excluded all four.  But there is backstory.  Lipitor is prescribed in four different doses – 10 mg, 20 mg, 40 mg, and 80 mg.  This is an MDL, so our readers can guess which doses most of these plaintiffs took.  While several studies show a statistically significant association between higher doses and new-onset diabetes, none shows such an association at the lowest dose.  After the plaintiffs' experts submitted their initial reports, the court "was concerned as to whether Plaintiffs' experts had sufficient facts and data to support their causation opinions at all doses . . . , and even whether the experts would be willing to offer an opinion at low doses, given the available data." In re Lipitor, 2016 WL 1251828 at *3.   Over the defendant's objections, the court allowed all four of the plaintiffs' experts to submit supplemental reports addressing whether the drug caused diabetes at particular doses.   Id. at *5.  The defendant's Daubert motions followed submission of the supplemental reports.

Expert No. 1

Plaintiff's first expert was an epidemiologist.   He used "standard epidemiological methodology;" namely, he performed a systematic literature search, searched relevant databases, reviewed studies, and conducted his own meta-analysis, noting that "multiple studies found a statistically significant association between statins and incident diabetes."  Id. at *6.  Once he identified this association, the expert applied the Bradford Hill factors (strength of the association, replication of the findings, specificity of the association, temporal relationship, dose-response relationship, biological plausibility, consistency with other knowledge, consideration of alternative explanations, and cessation of exposure) to determine whether the association reflected a causal relationship.  Though the defendant attacked the expert's methodology, the court rejected this argument, holding that the expert had applied the Bradford Hill factors in an acceptable manner, and that the defendant's disagreement with the expert's conclusions was a matter for cross-examination, not exclusion of the expert's testimony.   Id. at *7.

Reiterating that each expert was required provide opinions with regard to specific doses, the court next considered whether the expert had identified sufficient facts and data to support his causation opinion at all of the various doses.  With respect to all except the highest (80 mg) dose, the court held that the expert had not.  The court explained, "The critical guide . . . in determining whether the evidence, taken as a whole, is sufficient to support an opinion under Rule 702 is whether it would be sufficient in the relevant field or is sufficient under the applied methodology."  Id. at *9.   With respect to the expert's 10 mg opinion, the court held, that the opinion "was not based on sufficient facts and data and that [the expert] did not reliably apply the epidemiological/Bradford Hill method, which requires at the outset a statistically significant association before applying the Bradford Hill factors to make a judgment about whether the observed association is causal."  Id. at *11.  There was no such association, and the expert had (improperly) skipped directly to application of the Bradford Hill factors. 

With respect to the 20 mg and 40 mg doses, the expert had testified in deposition that he could identify no study that produced a statistically significant finding that either dose increased the risk of Type 2 diabetes.  As such, by his own testimony, the expert was unable to offer causation opinions about the 20 mg and 40 mg doses. 

Expert No. 2

The plaintiff's second expert was "not an expert in epidemiology, and his deposition highlight[ed] the fact that he [was] unfamiliar with basic principles of the field.  Id. at *12.   The expert had not heard of common epidemiological phrases, testified that, in clinical trials, the patient's own baseline was "a more important and better control" than a placebo group, id., and confused "association" with "causation."

With respect to the expert's methodology, the court commented, "Given that [he] is not an epidemiologist, it is unsurprising that he does not use the epidemiological/Bradford Hill method" to determine causation.  Id. at *13.  However, "neither of his reports state[d] what methodology he is using or attempting to use to reach his conclusions, and the method [was] not obvious from the face of his reports."  Id.  Plaintiffs argued that the expert used the method of a literature review; however, the court found that he did not review the "totality of the literature."  Rather, he impermissibly cherry-picked data to support his conclusions and failed to adequately account for contrary evidence.   As such, the court held that the expert had not utilized a reliable methodology and had not employed adequate intellectual rigor in reaching his conclusions.

Expert No. 3

The plaintiffs' third expert's supplemental report reached a single causation conclusion that swept across the four dosage levels, thus failing to comply with the court's order that the four dosages be considered separately.  In addition, "[the expert's] other methodological flaws only compound[ed] her reliability problem."  Id. at *17.  Admitting that she was not an expert in epidemiology, the expert "[did] not state what, if any, methodology she used, [could not] identify the limitations of different types of epidemiological studies and [was] not even able to give a basic definition of some types of epidemiological studies . . . ."  Id.  She "believe[d] that observational studies provide better evidence than randomized control trials, . . . appear[ed] to confuse association and causation. . . , and, in her deposition, "seemingly forgot what methodology she employed to reach her opinions."  Id.   Asked to explain her methodology, the expert stated, "I read the articles.  And I don't really understand the question.  I don't – I didn't use any – I don't know what you mean by what method did I use to analyze them."  Id.  Finally, the court held that, whether the expert used the Bradford Hill method or the literature review method that the plaintiffs claim she used, the method was not reliably applied. Deliciously nailing the coffin, the court held:

Because [the expert] had no methodology for determining which studies to consider and which to disregard, apparently just choosing those that she remembered or found supportive of her opinion, because she fails to adequately account for contrary evidence, because she confuses association and causation, because she lacks the epidemiological expertise to evaluate epidemiological studies in a Bradford Hill analysis, and because she fails to provide any analysis at all as to whether particular dosages are capable of causing diabetes, the Court excludes [the expert's] opinions as unreliable under Rule 702.

Id. at *18.

Expert No. 4

The plaintiffs' fourth expert, a retired professor of diabetic medicine, "discusse[d] several observational studies, clinical trials, and meta-analyses,, and offer[ed] the opinion that 'atorvastatin increases the risk of diabetes in a sustained dose-dependent manner.'"  Id.   He did not conduct a systematic review of the literature, but stated that he "put his reliance on meta-analyses using powerful methodology. "  Id.  Finally, he did not submit the required supplemental report, but simply "ascribe[d] the risk of [the drug] to all doses". . . . The court held that the expert's opinion was unreliable and excluded it in its entirety.

And so, out of four experts' reports, all was excluded except for one expert's opinion about the very highest dose of the drug.  As a practical matter, this left most plaintiffs without causation experts and unable to meet their burdens of proof.  You can bet those claims were poor, otherwise the MDL plaintiffs would have been able to offer better expert opinions.  We applaud this gutsy judge.  No doubt over Bubbie's objections, we will sing a final joyful chorus of our favorite Passover song in his honor.