WOE — Zoloft Escapes a MDL While Third Circuit Creates a Conceptual Muddle

Multidistrict Litigations (MDLs) can be “muddles” that are easy to get in, but hard to get out of. Pfizer and subsidiary Greenstone fabulously escaped a muddle through persistent lawyering and the astute gatekeeping of a district judge, in the Eastern District of Pennsylvania. That judge, the Hon. Cynthia Rufe, sustained objections to the admissibility of plaintiffs’ epidemiologic expert witness Anick Bérard. When the MDL’s plaintiffs’ steering committee (PSC) demanded, requested, and begged for a do over, Judge Rufe granted them one more chance. The PSC put their litigation industry eggs in a single basket, carried by statistician Nicholas Jewell. Unfortunately for the PSC, Judge Rufe found Jewell’s basket to be as methodologically defective as Bérard’s, and Her Honor excluded Jewell’s proffered testimony. Motions, paper, and appeals followed, but on June 2, 2017, the Third Circuit declared that the PSC and its clients had had enough opportunities to get through the gate. Their baskets of methodological deplorables were not up to snuff. In re Zoloft Prod. Liab. Litig., No. 16-2247 , __ F.3d __, 2017 WL 2385279, 2017 U.S. App. LEXIS 9832 (3d Cir. June 2, 2017) (affirming exclusion of Jewell’s dodgy opinions, which involved multiple methodological flaws and failures to follow any methodology faithfully) [Slip op. cited below as Zoloft].

Plaintiffs Attempt to Substitute WOE for Depressingly Bad Expert Witness Opinion

The ruse of conflating “weight of the evidence,” as used to describe the appellate standard of review for sustaining or reversing a trial court’s factual finding with a purported scientific methodology for inferring causation, was on full display by the PSC in their attack on Judge Rufe’s gatekeeping. In their appellate brief in the Court of Appeals for the Third Circuit, the PSC asserted that Jewell had used a “weight of the evidence method,” even though that phrase, “weight of the evidence” (WOE) was never used in Jewell’s litigation reports. The full context of the PSC’s argument and citations to Milward make clear a deliberate attempt to conflate WOE as an appellate judicial standard for reviewing jury fact finding and a purported scientific methodology. See Appellants’ Opening Brief at 54 (Aug. 10, 2016) [cited as PSC] (asserting that “[a]t all times, the ultimate evaluation of the weight of the evidence is a jury question”; citing Milward v. Acuity Specialty Products Group, Inc., 639 F.3d 11, 20 (1st Cir. 2011), cert. denied, 133 S. Ct. 63 (2012).

Having staked the ground that WOE is akin to a jury’s factual finding, and thus immune to any but the most extraordinary trial court action or appellate intervention, the PSC then pivoted to claim that Jewell’s WOE-ful method was nothing much more than an assessment of “the totality of the available scientific evidence, guided by the well-accepted Bradford-Hill criteria.” PSC at 3, 4, 7. This maneuver allowed the PSC to argue, apparently with a straight face, that WOE methodology as used by Jewell, had been generally accepted in the scientific community, as well as by the Third Circuit, in previous cases in which the court accepted the use of Bradford Hill’s considerations as a reliable method for establishing general causation. See PSC at 4 (citing Gannon v. United States, 292 F. App’x 170, 173 n.1 (3d Cir. 2008)). Jewell then simply plugged in his expertise and “40 years of experience,” and the desired conclusion of causation popped out. Id. Quod erat demonstrandum.

In pressing its point, the PSC took full advantage of loose, inaccurate language from the American Law Institute’s Restatement’s notorious comment C:

No algorithm exists for applying the Hill guidelines to determine whether an association truly reflects a causal relationship or is spurious.”

PSC at 33-34, citing Restatement (Third) of Torts: Physical and Emotional Harm § 28 cmt. c(3) (2010). Well true, but the absence of a mathematical algorithm hardly means that causal judgments are devoid of principles and standards. The PSC was undeterred, by text or by shame, from equating an unarticulated use of WOE methodology with some vague invocation of Bradford Hill’s considerations for evaluating associations for causality. See PSC at 43 (citing cases that never mentioned WOE but only Bradford Hill’s 50-plus year old heuristic as somehow supporting the claimed identity of the two approaches)1.

Pfizer Rebuffs WOE

Pfizer filed a comprehensive brief that unraveled the PSC’s duplicity. For unknown reasons, tactical or otherwise, however, Pfizer did not challenge the specifics of PSC’s equation of WOE with an abridged, distorted application of Bradford Hill’s considerations. See generally Opposition Brief of Defendants-Appellees Pfizer Inc., Pfizer International LLC, and Greenstone LLC [cited as Pfizer]. Perhaps given page limits and limited judicial attention spans, and just how woefully bad Jewell’s opinions were, Pfizer may well have decided that a more directed approach of assuming arguendo WOE’s methodological appropriateness was a more economical, pragmatic approach. A close reading of Pfizer’s brief, however, makes clear that it never conceded the validity of WOE as a scientific methodology.

Pfizer did point to the recasting of Jewell’s aborted attempt to apply Bradford Hill considerations as an employment of WOE methodology. Pfizer at 46-47. The argument reminded me of Abraham Lincoln’s famous argument:

How many legs does a dog have if you call his tail a leg?

Four.

Saying that a tail is a leg doesn’t make it a leg.”

Allen Thorndike Rice, Reminiscences of Abraham Lincoln by Distinguished Men of His Time at 242 (1909). Calling Jewell’s supposed method WOE or Bradford Hill or WOE/Bradford Hill did not cure the “fatal methodological flaws in his opinions.” Pfizer at 47.

Pfizer understandably and properly objected to the PSC’s attempt to cast Jewell’s “methodology” at such a high level of generality that any consideration of the many instances of methodological infidelity would be relegated to mere jury questions. Acquiescence in the PSC’s rhetorical move would constitute a complete abandonment of the inquiry whether Jewell had used a proper method. Pfizer at 15-16.

Interestingly, none of the amici curiae addressed the slippery WOE arguments advanced by the PSC. See generally Brief of Amici Curiae American Tort Reform Ass’n & Pharmaceutical Research and Manufacturers of America (Oct. 18, 2016); Brief of Washington Legal Fdtn. as Amicus Curiae (Oct. 18, 2016). There was no meaningful discussion of WOE as a supposedly scientific methodology at oral argument. See Transcript of Oral Argument in In re Zoloft Prod. Liab. Litig., No. 16-2247 (Jan. 25, 2017).

The Third Circuit Acknowledges that Some Methodological Infelicities, Flaws, and Fallacies Are Properly the Subject of Judicial Gatekeeping

Fortunately, Jewell’s methodological infidelities were easily recognized by the Circuit judges. Jewell treated multiple studies, which were nested within one another, and thus involved overlapping and included populations, as though they were independent verifications of the same hypothesis. When the population at issue (from the Danish cohort) was included in a more inclusive pan-Scandivanian study, the relied-upon association dissipated, and Jewell utterly failed to explain or account for these data. Zoloft at 5-6.

Jewell relied upon a study by Anick Bérard, even though he later had to concede that the study had serious flaws that invalidated its conclusions, and which flaws caused him to have a lack of confidence in the paper’s findings.2 In another instance, Jewell relied innocently upon a study that purported to report a statistically significant association, but the authors of this paper were later required by the journal, The New England Journal of Medicine, to correct the very calculated confidence interval upon which Jewell had relied. Despite his substantial mathematical prowess, Jewell missed the miscalculation and relied (uncritically) upon a finding as statistically significant when in fact it was not.

Jewell rejected a meta-analysis of Zoloft studies for questionable methodological quibbles, even though he had relied upon the very same meta-analysis, with the same methodology, in his litigation efforts involving Prozac and birth defects. Not to be corralled by methodological punctilio, Jewell conducted his own meta-analysis with two studies Huybrechts (2014) and Jimenez-Solem (2012), but failed to explain why he excluded other studies, the inclusion of which would have undone his claimed result. Zoloft at 9. Jewell purported to reanalyze and recalculate point estimates in two studies, Jimenez-Solem (2012) and Huybrechts (2014), without any clear protocol or consistency in his approach to other studies. Zoloft at 9. The list goes on, but in sum, Jewell’s handling of these technical issues did not inspire confidence, either in the district or in the appellate court.

WOE to the Third Circuit

The Circuit gave the PSC every conceivable break. Because Pfizer had not engaged specifically on whether WOE was a proper, or any kind of, scientific method, the Circuit treated the issue as virtually conceded:

Pfizer does not seem to contest the reliability of the Bradford Hill criteria or weight of the evidence analysis generally; the dispute centers on whether the specific methodology implemented by Dr. Jewell is reliable. Flexible methodologies, such as the “weight of the evidence,” can be implemented in multiple ways; despite the fact that the methodology is generally reliable, each application is distinct and should be analyzed for reliability.”

Zoloft at 18. The Court acknowledged that WOE arose only in the PSC’s appellate brief, which would have made the entire dubious argument waived under general appellate jurisdictional principles, but the Court, in a footnote, indulged the assumption, “for the sake of argument,” that WOE was Jewell’s purported method from the inception. Zoloft at 18 n. 39. Without any real evidentiary support or analysis or concession from Pfizer, the Circuit accepted that WOE analyses were “generally reliable.” Zoloft at 21.

The Circuit accepted, rather uncritically, that Jewell used a combination of WOE analysis and Bradford Hill considerations. Zoloft at 17. Although Jewell had never described WOE in his litigation report, and WOE was not a feature of his hearing testimony, the Circuit impermissibly engrafted Carl Cranor’s description of WOE as involving inference to the best explanation. Zoloft at 17 & n.37, citing Milward v. Acuity Specialty Prods. Grp., Inc., 639 F.3d 11, 17 (1st Cir. 2011) (internal quotation marks and citation omitted).

There was, however, a limit to the Circuit’s credulousness and empathy. As the Court noted, there must be some assurance that the purported Bradford Hill/WOE method is something more than a “mere conclusion-oriented selection process.” Zoloft at 20. Ultimately, the Court put its markers down for Jewell’s putative WOE methodology:

there must be a scientific method of weighting that is used and explained.”

Zoloft at 20. Calling the method WOE did not, in the final analysis, exclude Jewell from Rule 702 gatekeeping. Try as the PSC might, there was just no mistaking Jewell’s approach as anything other than a crazy patchwork quilt of numerical wizardry in aid of subjective, result-oriented conclusion mongering.

In the Court’s words:

we find that Dr. Jewell did not 1) reliably apply the ‘techniques’ to the body of evidence or 2) adequately explain how this analysis supports specified Bradford Hill criteria. Because ‘any step that renders the analysis unreliable under the Daubert factors renders the expert’s testimony inadmissible’, this is sufficient to show that the District Court did not abuse its discretion in excluding Dr. Jewell’s testimony.”

Zoloft at 28. As heartening as the Circuit’s conclusion is, the Court’s couching its observation as a finding (“we find”) is disheartening with respect to the Third Circuit’s apparent inability to distinguish abuse-of-discretion review from de novo appellate findings. Equally distressing is the Court’s invocation of Daubert factors, which were dicta in a Supreme Court case that was superseded by an amended statute over 17 years ago, in Federal Rule of Evidence 702.

On the crucial question whether Jewell had engaged in an unreliable application of methods or techniques that superficially, at a very high level of generality, claim to be generally accepted, the Court stayed on course. The Court “found” that Jewell had applied techniques, analyses, and critiques so obviously inconsistently that no amount of judicial indulgence, assumptions arguendo, or careless glosses could save Jewell and his fatuous opinions from judicial banishment. Zoloft 28-29. Returning to the correct standard of review (abuse of discretion), but the wrong governing law (Daubert instead of Rule 702), the Court announced that:

[b]ecause ‘any step that renders the analysis unreliable under the Daubert factors renders the expert’s testimony inadmissible’, this is sufficient to show that the District Court did not abuse its discretion in excluding Dr. Jewell’s testimony.”

Zoloft at 21 n.50 (citation omitted). The Court found itself unable to say simply and directly that “the MDL trial court decided the case well within its discretion.”

The Zoloft case was not the Third Circuit’s first WOE rodeo. WOE had raised its unruly head in Magistrini v. One Hour Martinizing Dry Cleaning, 180 F. Supp. 2d 584, 602 (D.N.J. 2002), aff’d, 68 F. App’x 356 (3d Cir. 2003), where an expert witness, David Ozonoff, offered what purported to be a WOE opinion. The Magistrini trial court did not fuss with the assertion that WOE was generally reliable, but took issue with how Ozonoff tried to pass off his analysis as a comprehensive treatment of the totality of the evidence. In Magistrini, Judge Hochberg noted that regardless of the rubric of the methodology, the witness must show that in conducting a WOE analysis:

all of the relevant evidence must be gathered, and the assessment or weighing of that evidence must not be arbitrary, but must itself be based on methods of science.”

Magistrini, 180 F. Supp. 2d at 602. The witness must show that the methodology is more than a “mere conclusion-oriented selection process,” and that it has a “a scientific method of weighting that is used and explained.” Id. at 607. Asserting the use of WOE was not an excuse or escape from judicial gatekeeping as specified by Rule 702.

Although the Third Circuit gave the Zoloft MDL trial court’s findings a searching review (certainly much tougher than the prescribed abuse-of-discretion review), the MDL court’s finding that Jewell “failed to consistently apply the scientific methods he articulates, has deviated from or downplayed certain well-established principles of his field, and has inconsistently applied methods and standards to the data so as to support his a priori opinion” were ultimately vindicated by the Court of Appeals. Zoloft at 10.

All’s well that ends well. Perhaps. It remains unfortunate, however, that a hypothetical method, WOE — which was never actually advocated by the challenged expert witnesses, which lacks serious support in the scientific community, and which was merely assumed arguendo to be valid — will be taken by careless readers to have been endorsed the Third Circuit.


1 Among the cases cited without any support for the PSC’s dubious contention were Gannon v. United States, 292 F. App’x 170, 173 n.1 (3d Cir. 2008); Bitler v. A.O. Smith Corp., 391 F.3d 1114, 1124-25 (10th Cir. 2004); In re Joint E. & S. Dist. Asbestos Litig., 52 F.3d 1124, 1128 (2d Cir. 1995); In re Avandia Mktg., Sales Practices & Prods. Liab. Litig., No. 2007-MD-1871, 2011 WL 13576, at *3 (E.D. Pa. Jan. 4, 2011) (“Bradford-Hill criteria are used to assess whether an established association between two variables actually reflects a causal relationship.”).

2 Anick Bérard, Sertraline Use During Pregnancy and the Risk of Major Malformations, 212 Am. J. Obstet. Gynecol. 795 (2015).

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