For your delectation and delight, desultory dicta on the law of delicts.

Dodgy Data Duck Daubert Decisions

March 11th, 2020

Judges say the darndest things, especially when it comes to their gatekeeping responsibilities under Federal Rules of Evidence 702 and 703. One of the darndest things judges say is that they do not have to assess the quality of the data underlying an expert witness’s opinion.

Even when acknowledging their obligation to “assess the reasoning and methodology underlying the expert’s opinion, and determine whether it is both scientifically valid and applicable to a particular set of facts,”[1] judges have excused themselves from having to look at the trustworthiness of the underlying data for assessing the admissibility of an expert witness’s opinion.

In McCall v. Skyland Grain LLC, the defendant challenged an expert witness’s reliance upon oral reports of clients. The witness, Mr. Bradley Walker, asserted that he regularly relied upon such reports, in similar contexts of the allegations that the defendant misapplied herbicide to plaintiffs’ crops. The trial court ruled that the defendant could cross-examine the declarant who was available trial, and concluded that the “reliability of that underlying data can be challenged in that manner and goes to the weight to be afforded Mr. Walker’s conclusions, not their admissibility.”[2] Remarkably, the district court never evaluated the reasonableness of Mr. Walker’s reliance upon client reports in this or any context.

In another federal district court case, Rodgers v. Beechcraft Corporation, the trial judge explicitly acknowledged the responsibility to assess whether the expert witness’s opinion was based upon “sufficient facts and data,” but disclaimed any obligation to assess the quality of the underlying data.[3] The trial court in Rodgers cited a Tenth Circuit case from 2005,[4] which in turn cited the Supreme Court’s 1993 decision in Daubert, for the proposition that the admissibility review of an expert witness’s opinion was limited to a quantitative sufficiency analysis, and precluded a qualitative analysis of the underlying data’s reliability. Quoting from another district court criminal case, the court in Rodgers announced that “the Court does not examine whether the facts obtained by the witness are themselves reliable – whether the facts used are qualitatively reliable is a question of the weight to be given the opinion by the factfinder, not the admissibility of the opinion.”[5]

In a 2016 decision, United States v. DishNetwork LLC, the court explicitly disclaimed that it was required to “evaluate the quality of the underlying data or the quality of the expert’s conclusions.”[6] This district court pointed to a Seventh Circuit decision, which maintained that  “[t]he soundness of the factual underpinnings of the expert’s analysis and the correctness of the expert’s conclusions based on that analysis are factual matters to be determined by the trier of fact, or, where appropriate, on summary judgment.”[7] The Seventh Circuit’s decision, however, issued in June 2000, several months before the effective date of the amendments to Federal Rule of Evidence 702 (December 2000).

In 2012, a magistrate judge issued an opinion along the same lines, in Bixby v. KBR, Inc.[8] After acknowledging what must be done in ruling on a challenge to an expert witness, the judge took joy in what could be overlooked. If the facts or data upon which the expert witness has relied are “minimally sufficient,” then the gatekeeper can regard questions about “the nature or quality of the underlying data bear upon the weight to which the opinion is entitled or to the credibility of the expert’s opinion, and do not bear upon the question of admissibility.”[9]

There need not be any common law mysticism to the governing standard. The relevant law is, of course, a statute, which appears to be forgotten in many of the failed gatekeeping decisions:

Rule 702. Testimony by Expert Witnesses

A witness who is qualified as an expert by knowledge, skill, experience, training, or education may testify in the form of an opinion or otherwise if:

(a) the expert’s scientific, technical, or other specialized knowledge will help the trier of fact to understand the evidence or to determine a fact in issue;

(b) the testimony is based on sufficient facts or data;

(c) the testimony is the product of reliable principles and methods; and

(d) the expert has reliably applied the principles and methods to the facts of the case.

It would seem that you could not produce testimony that is the product of reliable principles and methods by starting with unreliable underlying facts and data. Certainly, having a reliable method would require selecting reliable facts and data from which to start. What good would the reliable application of reliable principles to crummy data?

The Advisory Committee Notes to Rule 702 hints at an answer to the problem:

“There has been some confusion over the relationship between Rules 702 and 703. The amendment makes clear that the sufficiency of the basis of an expert’s testimony is to be decided under Rule 702. Rule 702 sets forth the overarching requirement of reliability, and an analysis of the sufficiency of the expert’s basis cannot be divorced from the ultimate reliability of the expert’s opinion. In contrast, the ‘reasonable reliance’ requirement of Rule 703 is a relatively narrow inquiry. When an expert relies on inadmissible information, Rule 703 requires the trial court to determine whether that information is of a type reasonably relied on by other experts in the field. If so, the expert can rely on the information in reaching an opinion. However, the question whether the expert is relying on a sufficient basis of information—whether admissible information or not—is governed by the requirements of Rule 702.”

The answer is only partially satisfactory. First, if the underlying data are independently admissible, then there may indeed be no gatekeeping of an expert witness’s reliance upon such data. Rule 703 imposes a reasonableness test for reliance upon inadmissible underlying facts and data, but appears to give otherwise admissible facts and data a pass. Second, the above judicial decisions do not mention any Rule 703 challenge to the expert witnesses’ reliance. If so, then there is a clear lesson for counsel. When framing a challenge to the admissibility of an expert witness’s opinion, show that the witness has unreasonably relied upon facts and data, from whatever source, in violation of Rule 703. Then show that without the unreasonably relied upon facts and data, the witness cannot show that his or her opinion satisfies Rule 702(a)-(d).

[1]  See, e.g., McCall v. Skyland Grain LLC, Case 1:08-cv-01128-KHV-BNB, Order (D. Colo. June 22, 2010) (Brimmer, J.) (citing Dodge v. Cotter Corp., 328 F.3d 1212, 1221 (10th Cir. 2003), citing in turn Daubert v. Merrill Dow Pharms., Inc., 509 U.S. 579,  592-93 (1993).

[2]  McCall v. Skyland Grain LLC Case 1:08-cv-01128-KHV-BNB, Order at p.9 n.6 (D. Colo. June 22, 2010) (Brimmer, J.)

[3]  Rodgers v. Beechcraft Corp., Case No. 15-CV-129-CVE-PJC, Report & Recommendation at p.6 (N.D. Okla. Nov. 29, 2016).

[4]  Id., citing United.States. v. Lauder, 409 F.3d 1254, 1264 (10th Cir. 2005) (“By its terms, the Daubert opinion applies only to the qualifications of an expert and the methodology or reasoning used to render an expert opinion” and “generally does not, however, regulate the underlying facts or data that an expert relies on when forming her opinion.”), citing Daubert v. Merrill Dow Pharms., Inc., 509 U.S. 579, 592-93 (1993).

[5]  Id., citing and quoting United States v. Crabbe, 556 F. Supp. 2d 1217, 1223
(D. Colo. 2008) (emphasis in original). In Crabbe, the district judge mostly excluded the challenged expert witness, thus rendering its verbiage on quality of data as obiter dicta). The pronouncements about the nature of gatekeeping proved harmless error when the court dismissed the case on other grounds. Rodgers v. Beechcraft Corp., 248 F. Supp. 3d 1158 (N.D. Okla. 2017) (granting summary judgment).

[6]  United States v. DishNetwork LLC, No. 09-3073, Slip op. at 4-5 (C.D. Ill. Jan. 13, 2016) (Myerscough, J.)

[7]  Smith v. Ford Motor Co., 215 F.3d 713, 718 (7th Cir. 2000).

[8]  Bixby v. KBR, Inc., Case 3:09-cv-00632-PK, Slip op. at 6-7 (D. Ore. Aug. 29, 2012) (Papak, M.J.)

[9]  Id. (citing Hangarter v. Provident Life & Accident Ins. Co., 373 F.3d 998, 1017 (9th Cir. 2004), quoting Children’s Broad Corp. v. Walt Disney Co., 357 F.3d 860, 865 (8th Cir. 2004) (“The factual basis of an expert opinion goes to the credibility of the testimony, not the admissibility, and it is up to the opposing party to examine the factual basis for the opinion in cross-examination.”).

Science Journalism – UnDark Noir

February 23rd, 2020

Critics of the National Association of Scholars’ conference on Fixing Science pointed readers to an article in Undark, an on-line popular science site for lay audiences, and they touted the site for its science journalism. My review of the particular article left me unimpressed and suspicious of Undark’s darker side. When I saw that the site featured an article on the history of the Supreme Court’s Daubert decision, I decided to give the site another try. For one thing, I am sympathetic to the task science journalists take on: it is important and difficult. In many ways, lawyers must commit to perform the same task. Sadly, most journalists and lawyers, with some notable exceptions, lack the scientific acumen and English communication skills to meet the needs of this task.

The Undark article that caught my attention was a history of the Daubert decision and the Bendectin litigation that gave rise to the Supreme Court case.[1] The author, Peter Andrey Smith, is a freelance reporter, who often covers science issues. In his Undark piece, Smith covered some of the oft-told history of the Daubert case, which has been told before, better and in more detail in many legal sources. Smith gets some credit for giving the correct pronunciation of the plaintiff’s name – “DAW-burt,” and for recounting how both sides declared victory after the Supreme Court’s ruling. The explanation Smith gives of the opinion by Associate Justice Harry Blackmun is reasonably accurate, and he correctly notes that a partial dissenting opinion by Chief Justice Rehnquist complained that the majority’s decision would have trial judges become “amateur scientists.” Nowhere in the article will you find, however, the counter to the dissent: an honest assessment of the institutional and individual competence of juries to decide complex scientific issues.

The author’s biases eventually, however, become obvious. He recounts his interviews with Jason Daubert and his mother, Joyce Daubert. He earnestly reports how Joyce Daubert remembered having taken Bendectin during her pregnancy with Jason, and in the moment of that recall, “she felt she’d finally identified the teratogen that harmed Jason.” Really? Is that how teratogens are identified? Might it have been useful and relevant for a scientific journalist to explain that there are four million live births every year in the United States and that 3% of children born each year have major congenital malformations? And that most malformations have no known cause? Smith ingenuously relays that Jason Daubert had genetic testing, but omits that genetic testing in the early 1990s was fairly primitive and limited. In any event, how were any expert witnesses supposed to rule out base-line risk of birth defects, especially given weak to non-existent epidemiologic support for the Daubert’s claims? Smith does answer these questions; he does not even acknowledge the questions.

Smith later quotes Joyce Daubert as describing the litigation she signed up for as “the hill I’ll die on. You only go to war when you think you can win.” Without comment or analysis, Smith gives Joyce Daubert an opportunity to rant against the “injustice” of how her lawsuit turned out. Smith tells us that the Dauberts found the “legal system remains profoundly disillusioning.” Joyce Daubert told Smith that “it makes me feel stupid that I was so naïve to think that, after we’d invested so much in the case, that we would get justice.”  When called for jury duty, she introduces herself as

“I’m Daubert of Daubert versus Merrell Dow … ; I don’t want to sit on this jury and pretend that I can pass judgment on somebody when there is no justice. Please allow me to be excused.”

But didn’t she really get all the justice she deserved? Given her zealotry, doesn’t she deserve to have her name on the decision that serves to rein in expert witnesses who outrun their scientific headlights? Smith is coy and does not say, but in presenting Mrs. Daubert’s rant, without presenting the other side, he is using his journalistic tools in a fairly blatant attempt to mislead. At this point, I begin to get the feeling that Smith is preaching to a like-minded choir over there at Undark.

The reader is not treated to any interviews with anyone from the company that made Bendectin, any of its scientists, or any of the scientists who published actual studies on whether Bendectin was associated with the particular birth defects Jason Daubert had, or for that matter, with any birth defects at all. The plaintiffs’ expert witnesses quoted and cited never published anything at all on the subject. The readers are left to their imagination about how the people who developed Bendectin felt about the litigation strategies and tactics of the lawsuit industry.

The journalistic ruse is continued with Smith’s treatment of the other actors in the Daubert passion play. Smith describes the Bendectin plaintiffs’ lawyer Barry Nace in hagiographic terms, but omits his bar disciplinary proceedings.[2] Smith tells us that Nace had an impressive background in chemistry, and quotes him in an interview in which he described the evidentiary rules on scientific witness testimony as “scientific evidence crap.”

Smith never describes the Daubert’s actual affirmative evidence in any detail, which one might expect in a sophisticated journalistic outlet. Instead, he described some of their expert witnesses, Shanna Swan, a reproductive epidemiologist, and Alan K. Done, “a former pediatrician from Wayne State University.” Smith is secretive about why Done was done in at Wayne State; and we learn nothing about the serious accusations of perjury on credentials by Done. Instead, Smith regales us with Done’s tsumish theory, which takes inconclusive bits of evidence, throws them together, and then declares causation that somehow eludes the rest of the scientific establishment.

Smith tells us that Swan was a rebuttal witness, who gave an opinion that the data did not rule out “the possibility Bendectin caused defects.” Legally and scientifically, Smith is derelict in failing to explain that the burden was on the party claiming causation, and that Swan’s efforts to manufacture doubt were beside the point. Merrell Dow did not have to rule out any possibility of causation; the plaintiffs had to establish causation. Nor does Smith delve into how Swan sought to reprise her performance in the silicone gel breast implant litigation, only to be booted by several judges as an expert witness. And then for a convincer, Smith sympathetically repeats plaintiffs’ lawyer Barry Nace’s hyperbolic claim that Bendectin manufacturer, Merrell Dow had been “financing scientific articles to get their way,” adding by way of emphasis, in his own voice:

“In some ways, here was the fake news of its time: If you lacked any compelling scientific support for your case, one way to undermine the credibility of your opponents was by calling their evidence ‘junk science’.”

Against Nace’s scatalogical Jackson Pollack approach, Smith is silent about another plaintiffs’ expert witness, William McBride, who was found guilty of scientific fraud.[3] Smith reports interviews of several well-known, well-respected evidence scholars. He dutifully report Professor Edward Cheng’s view that “the courts were right to dismiss the [Bendectin] plaintiffs’ claims.” Smith quotes Professor D. Michael Risinger that claims from both sides in Bendectin cases were exaggerated, and that the 1970s and 1980s saw an “unbridled expansion of self-anointed experts,” with “causation in toxic torts had been allowed to become extremely lax.” So a critical reader might wonder why someone like Professor Cheng, who has a doctorate in statistics, a law degree from Harvard, and teaches at Vanderbilt Law School, would vindicate the manufacturers’ position in the Bendectin litigation. Smith never attempts to reconcile his interviews of the law professors with the emotive comments of Barry Nace and Joyce Daubert.

Smith acknowledges that a reformulated version of Bendectin, known as  Diclegis, was approved by the Food and Drug Administration in the United States, in 2013, for treatment of  nausea and vomiting during pregnancy. Smith tells us that Joyce is not convinced the drug should be back on the market,” but really why would any reasonable person care about her view of the matter? The challenge by Nav Persaud, a Toronto physician, is cited, but Persaud’s challenge is to the claim of efficacy, not to the safety of the medication. Smith tells us that Jason Daubert “briefly mulled reopening his case when Diclegis, the updated version of Bendectin, was re-approved.” But how would the approval of Diclegis, on the strength of a full new drug application, somehow support his claim anew? And how would he “reopen” a claim that had been fully litigated in the 1990s, and well past any statute of limitations?

Is this straight reporting? I think not. It is manipulative and misleading.

Smith notes, without attribution, that some scholars condemn litigation, such as the cases involving Bendectin, as an illegitimate form of regulation of medications. In opposition, he appears to rely upon Elizabeth Chamblee Burch, a professor at the University of Georgia School of Law for the view that because the initial pivotal clinical trials for regulatory approvals take place in limited populations, litigation “serves as a stopgap for identifying rare adverse outcomes that could crop up when several hundreds of millions of people are exposed to those products over longer periods of time.” The problem with this view is that Smith ignores the whole process of pharmacovigilance, post-registration trials, and pharmaco-epidemiologic studies conducted after the licensing of a new medication. The suggested necessity of reliance upon the litigation system as an adjunct to regulatory approval is at best misplaced and tenuous.

Smith correctly explains that the Daubert standard is still resisted in criminal cases, where it could much improve the gatekeeping of forensic expert witness opinion. But while the author gets his knickers in a knot over wrongful convictions, he seems quite indifferent to wrongful judgments in civil action.

Perhaps the one positive aspect of this journalistic account of the Daubert case was that Jason Daubert, unlike his mother, was open minded about his role in transforming the law of scientific evidence. According to Smith, Jason Daubert did not see the case as having “not ruined his life.” Indeed, Jason seemed to approve the basic principle of the Daubert case, and the subsequent legislation that refined the admissibility standard: “Good science should be all that gets into the courts.”

[1] Peter Andrey Smith, “Where Science Enters the Courtroom, the Daubert Name Looms Large: Decades ago, two parents sued a drug company over their newborn’s deformity – and changed courtroom science forever,” Undark (Feb. 17, 2020).

[2]  Lawyer Disciplinary Board v. Nace, 753 S.E.2d 618, 621–22 (W. Va.) (per curiam), cert. denied, 134 S. Ct. 474 (2013).

[3] Neil Genzlinger, “William McBride, Who Warned About Thalidomide, Dies at 91,” N.Y. Times (July 15, 2018); Leigh Dayton, “Thalidomide hero found guilty of scientific fraud,” New Scientist (Feb. 27, 1993); G.F. Humphrey, “Scientific fraud: the McBride case,” 32 Med. Sci. Law 199 (1992); Andrew Skolnick, “Key Witness Against Morning Sickness Drug Faces Scientific Fraud Charges,” 263 J. Am. Med. Ass’n 1468 (1990).

Judicial Gatekeeping Cures Claims That Viagra Can Cause Melonoma

January 24th, 2020

The phosphodiesterases 5 inhibitor medications (PDE5i) seem to arouse the litigation propensities of the lawsuit industry. The PDE5i medications (sildenafil, tadalafil, etc.) have multiple indications, but they are perhaps best known for their ability to induce penile erections, which in some situations can be a very useful outcome.

The launch of Viagra in 1998 was followed by litigation that claimed the drug caused heart attacks, and not the romantic kind. The only broken hearts, however, were those of the plaintiffs’ lawyers and their expert witnesses who saw their litigation claims excluded and dismissed.[1]

Then came claims that the PDE5i medications caused non-arteritic anterior ischemic optic neuropathy (“NAION”), based upon a dubious epidemiologic study by Dr. Gerald McGwin. This litigation demonstrated, if anything, that while love may be blind, erections need not be.[2] The NAION cases were consolidated in a multi-district litigation (MDL) in front of Judge Paul Magnuson, in the District of Minnesota. After considerable back and forth, Judge Manguson ultimately concluded that the McGwin study was untrustworthy, and the NAION claims were dismissed.[3]

In 2014, the American Medical Association’s internal medicine journal published an observational epidemiologic study of sildenafil (Viagra) use and melanoma.[4] The authors of the study interpreted their study modestly, concluding:

“[s]ildenafil use may be associated with an increased risk of developing melanoma. Although this study is insufficient to alter clinical recommendations, we support a need for continued investigation of this association.”

Although the Li study eschewed causal conclusions and new clinical recommendations in view of the need for more research into the issue, the litigation industry filed lawsuits, claiming causality.[5]

In the new natural order of things, as soon as the litigation industry cranks out more than a few complaints, an MDL results, and the PDE5i – melanoma claims were no exception. By spring 2016, plaintiffs’ counsel had collected ten cases, a minion, sufficient for an MDL.[6] The MDL plaintiffs named the manufacturers of sildenafil and tadalafil, two of the more widely prescribed PDEi5 medications, on behalf of putative victims.

While the MDL cases were winding their way through discovery and possible trials, additional studies and meta-analyses were published. None of the subsequent studies, including the systematic reviews and meta-analyses, concluded that there was a causal association. Most scientists who were publishing on the issue opined that systematic error (generally confounding) prevented a causal interpretation of the data.[7]

Many of the observational studies found statistically significantly increased relative risks about 1.1 to 1.2 (10 to 20%), typically with upper bounds of 95% confidence intervals less than 2.0. The only scientists who inferred general causation from the available evidence were those who had been recruited and retained by plaintiffs’ counsel. As plaintiffs’ expert witnesses, they contended that the Li study, and the several studies that became available afterwards, collectively showed that PDE5i drugs cause melanoma in humans.

Not surprisingly, given the absence of any non-litigation experts endorsing the causal conclusion, the defendants challenged plaintiffs’ proffered expert witnesses under Federal Rule of Evidence 702. Plaintiffs’ counsel also embraced judicial gatekeeping and challenged the defense experts. The MDL trial judge, the Hon. Richard Seeborg, held hearings with four days of viva voce testimony from four of plaintiffs’ expert witnesses (two on biological plausibility, and two on epidemiology), and three of the defense’s experts. Last week, Judge Seeborg ruled by granting in part, and denying in part, the parties’ motions.[8]

The Decision

The MDL trial judge’s opinion is noteworthy in many respects. First, Judge Richard Seeborg cited and applied Rule 702, a statute, and not dicta from case law that predates the most recent statutory version of the rule. As a legal process matter, this respect for judicial process and the difference in legal authority between statutory and common law was refreshing. Second, the judge framed the Rule 702 issue, in line with the statute, and Ninth Circuit precedent, as an inquiry whether expert witnesses deviated from the standard of care of how scientists “conduct their research and reach their conclusions.”[9]

Biological Plausibility

Plaintiffs proffered three expert witnesses on biological plausibility, Drs. Rizwan Haq, Anand Ganesan, and Gary Piazza. All were subject to motions to exclude under Rule 702. Judge Seeborg denied the defense motions against all three of plaintiffs’ plausibility witnesses.[10]

The MDL judge determined that biological plausibility is neither necessary nor sufficient for inferring causation in science or in the law. The defense argued that the plausibility witnesses relied upon animal and cell culture studies that were unrealistic models of the human experience.[11] The MDL court, however, found that the standard for opinions on biological plausibility is relatively forgiving, and that the testimony of all three of plaintiffs’ proffered witnesses was admissible.

The subjective nature of opinions about biological plausibility is widely recognized in medical science.[12] Plausibility determinations are typically “Just So” stories, offered in the absence of hard evidence that postulated mechanisms are actually involved in a real causal pathway in human beings.

Causal Association

The real issue in the MDL hearings was the conclusion reached by plaintiffs’ expert witnesses that the PDE5i medications cause melanoma. The MDL court did not have to determine whether epidemiologic studies were necessary for such a causal conclusion. Plaintiffs’ counsel had proffered three expert witnesses with more or less expertise in epidemiology: Drs. Rehana Ahmed-Saucedo, Sonal Singh, and Feng Liu-Smith. All of plaintiffs’ epidemiology witnesses, and certainly all of defendants’ experts, implicitly if not explicitly embraced the proposition that analytical epidemiology was necessary to determine whether PDE5i medications can cause melanoma.

In their motions to exclude Ahmed-Saucedo, Singh, and Liu-Smith, the defense pointed out that, although many of the studies yielded statistically significant estimates of melanoma risk, none of the available studies adequately accounted for systematic bias in the form of confounding. Although the plaintiffs’ plausibility expert witnesses advanced “Just-So” stories about PDE5i and melanoma, the available studies showed an almost identical increased risk of basal cell carcinoma of the skin, which would be explained by confounding, but not by plaintiffs’ postulated mechanisms.[13]

The MDL court acknowledged that whether epidemiologic studies “adequately considered” confounding was “central” to the Rule 702 inquiry. Without any substantial analysis, however, the court gave its own ipse dixit that the existence vel non of confounding was an issue for cross-examination and the jury’s resolution.[14] Whether there was a reasonably valid association between PDE5i and melanoma was a jury question. This judicial refusal to engage with the issue of confounding was one of the disappointing aspects of the decision.

The MDL court was less forgiving when it came to the plaintiffs’ epidemiology expert witnesses’ assessment of the association as causal. All the parties’ epidemiology witnesses invoked Sir Austin Bradford Hill’s viewpoints or factors for judging whether associations were causal.[15] Although they embraced Hill’s viewpoints on causation, the plaintiffs’ epidemiologic expert witnesses had a much more difficult time faithfully applying them to the evidence at hand. The MDL court concluded that the plaintiffs’ witnesses deviated from their own professional standard of care in their analysis of the data.[16]

Hill’s first enumerated factor was “strength of association,” which is typically expressed epidemiologically as a risk ratio or a risk difference. The MDL court noted that the extant epidemiologic studies generally showed relative risks around 1.2 for PDE5i and melanoma, which was “undeniably” not a strong association.[17]

The plaintiffs’ epidemiology witnesses were at sea on how to explain away the lack of strength in the putative association. Dr. Ahmed-Saucedo retreated into an emphasis on how all or most of the studies found some increased risk, but the MDL court correctly found that this ruse was merely a conflation of strength with consistency of the observed associations. Dr. Ahmed-Saucedo’s dismissal of the importance of a dose-response relationship, another Hill factor, as unimportant sealed her fate. The MDL court found that her Bradford Hill analysis was “unduly results-driven,” and that her proffered testimony was not admissible.[18] Similarly, the MDL court found that Dr. Feng Liu-Smith similarly conflated strength of association with consistency, which error was too great a professional deviation from the standard of care.[19]

Dr. Sonal Singh fared no better after he contradicted his own prior testimony that there is an order of importance to the Hill factors, with “strength of association,” at or near the top. In the face of a set of studies, none of which showed a strong association, Dr. Singh abandoned his own interpretative principle to suit the litigation needs of the case. His analysis placed the greatest weight on the Li study, which had the highest risk ratio, but he failed to advance any persuasive reason for his emphasis on one of the smallest studies available. The MDL court found that Dr. Singh’s claim to have weighed strength of association heavily, despite the obvious absence of strong associations, puzzling and too great an analytical gap to abide.[20]

Judge Seeborg thus concluded that while the plaintiffs’ expert witness could opine that there was an association, which was arguably plausible, they could not, under Rule 702, contend that the association was causal. In attempting to advance an argument that the association met Bradford Hill’s factors for causality, the plaintiffs’ witnesses had ignored, misrepresented, or confused one of the most important factors, strength of the association, in a way that revealed their analyses to be result driven and unfaithful to the methodology they claimed to have followed. Judge Seeborg emphasized a feature of the revised Rule 702, which often is ignored by his fellow federal judges:[21]

“Under the amendment, as under Daubert, when an expert purports to apply principles and methods in accordance with professional standards, and yet reaches a conclusion that other experts in the field would not reach, the trial court may fairly suspect that the principles and methods have not been faithfully applied. See Lust v. Merrell Dow Pharmaceuticals, Inc., 89 F.3d 594, 598 (9th Cir. 1996). The amendment specifically provides that the trial court must scrutinize not only the principles and methods used by the expert, but also whether those principles and methods have been properly applied to the facts of the case.”

Given that the plaintiffs’ witnesses purported to apply a generally accepted methodology, Judge Seeborg was left to question why they would conclude causality when no one else in their field had done so.[22] The epidemiologic issue had been around for several years, and addressed not just in observational studies, but systematically reviewed and meta-analyzed. The absence of published causal conclusions was not just an absence of evidence, but evidence of absence of expert support for how plaintiffs’ expert witnesses applied the Bradford Hill factors.

Reliance Upon Studies That Did Not Conclude Causation Existed

Parties challenging causal claims will sometimes point to the absence of a causal conclusion in the publication of individual epidemiologic studies that are the main basis for the causal claim. In the PDE5i-melanoma cases, the defense advanced this argument unsuccessfully. The MDL court rejected the defense argument, based upon the absence of any comprehensive review of all the pertinent evidence for or against causality in an individual study; the study authors are mostly concerned with conveying the results of their own study.[23] The authors may have a short discussion of other study results as the rationale for their own study, but such discussions are often limited in scope and purpose. Judge Seeborg, in this latest round of PDE5i litigation, thus did not fault plaintiffs’ witnesses’ reliance upon epidemiologic or mechanistic studies, which individually did not assert causal conclusions; rather it was the absence of causal conclusions in systematic reviews, meta-analyses, narrative reviews, regulatory agency pronouncements, or clinical guidelines that ultimately raised the fatal inference that the plaintiffs’ witnesses were not faithfully deploying a generally accepted methodology.

The defense argument that pointed to the individual epidemiologic studies themselves derives some legal credibility from the Supreme Court’s opinion in General Electric Co. v. Joiner, 522 U.S. 136 (1997). In Joiner, the SCOTUS took plaintiffs’ expert witnesses to task for drawing stronger conclusions than were offered in the papers upon which they relied. Chief Justice Rehnquist gave considerable weight to the consideration that the plaintiffs’ expert witnesses relied upon studies, the authors of which explicitly refused to interpret as supporting a conclusion of human disease causation.[24]

Joiner’s criticisms of the reliance upon studies that do not themselves reach causal conclusions have gained a foothold in the case law interpreting Rule 702. The Fifth Circuit, for example, has declared:[25]

“It is axiomatic that causation testimony is inadmissible if an expert relies upon studies or publications, the authors of which were themselves unwilling to conclude that causation had been proven.”

This aspect of Joiner may properly limit the over-interpretation or misinterpretation of an individual study, which seems fine.[26] The Joiner case may, however, perpetuate an authority-based view of science to the detriment of requiring good and sufficient reasons to support the testifying expert witnesses’ opinions.  The problem with Joiner’s suggestion that expert witness opinion should not be admissible if it disagrees with the study authors’ discussion section is that sometimes study authors grossly over-interpret their data.  When it comes to scientific studies written by “political scientists” (scientists who see their work as advancing a political cause or agenda), then the discussion section often becomes a fertile source of unreliable, speculative opinions that should not be given credence in Rule 104(a) contexts, and certainly should not be admissible in trials. In other words, the misuse of non-rigorous comments in published articles can cut both ways.

There have been, and will continue to be, occasions in which published studies contain data, relevant and important to the causation issue, but which studies also contain speculative, personal opinions expressed in the Introduction and Discussion sections.  The parties’ expert witnesses may disagree with those opinions, but such disagreements hardly reflect poorly upon the testifying witnesses.  Neither side’s expert witnesses should be judged by those out-of-court opinions.  Perhaps the hearsay discussion section may be considered under Rule 104(a), which suspends the application of the Rules of Evidence, but it should hardly be a dispositive factor, other than raising questions for the reviewing court.

In exercising their gatekeeping function, trial judges should exercise care in how they assess expert witnesses’ reliance upon study data and analyses, when they disagree with the hearsay authors’ conclusions or discussions.  Given how many journals cater to advocacy scientists, and how variable the quality of peer review is, testifying expert witnesses should, in some instances,  have the expertise to interpret the data without substantial reliance upon, or reference to, the interpretative comments in the published literature.

Judge Seeborg sensibly seems to have distinguished between the absence of causal conclusions in individual epidemiologic studies and the absence of causal conclusions in any reputable medical literature.[27] He refused to be ensnared in the Joiner argument because:[28]

“Epidemiology studies typically only expressly address whether an association exists between agents such as sildenafil and tadalafil and outcomes like melanoma progression. As explained in In re Roundup Prod. Liab. Litig., 390 F. Supp. 3d 1102, 1116 (N.D. Cal. 2018), ‘[w]hether the agents cause the outcomes, however, ordinarily cannot be proven by epidemiological studies alone; an evaluation of causation requires epidemiologists to exercise judgment about the import of those studies and to consider them in context’.”

This new MDL opinion, relying upon the Advisory Committee Notes to Rule 702, is thus a more felicitous statement of the goals of gatekeeping.

Confidence Intervals

As welcome as some aspects of Judge Seeborg’s opinion are, the decision is not without mistakes. The district judge, like so many of his judicial colleagues, trips over the proper interpretation of a confidence interval:[29]

“When reviewing the results of a study it is important to consider the confidence interval, which, in simple terms, is the ‘margin of error’. For example, a given study could calculate a relative risk of 1.4 (a 40 percent increased risk of adverse events), but show a 95 percent ‘confidence interval’ of .8 to 1.9. That confidence interval means there is 95 percent chance that the true value—the actual relative risk—is between .8 and 1.9.”

This statement is inescapably wrong. The 95 percent probability attaches to the capturing of the true parameter – the actual relative risk – in the long run of repeated confidence intervals that result from repeated sampling of the same sample size, in the same manner, from the same population. In Judge Seeborg’s example, the next sample might give a relative risk point estimate 1.9, and that new estimate will have a confidence interval that may run from just below 1.0 to over 3. A third sample might turn up a relative risk estimate of 0.8, with a confidence interval that runs from say 0.3 to 1.4. Neither the second nor the third sample would be reasonably incompatible with the first. A more accurate assessment of the true parameter is that it will be somewhere between 0.3 and 3, a considerably broader range for the 95 percent.

Judge Seeborg’s error is sadly all too common. Whenever I see the error, I wonder whence it came. Often the error is in briefs of both plaintiffs’ and defense counsel. In this case, I did not see the erroneous assertion about confidence intervals made in plaintiffs’ or defendants’ briefs.

[1]  Brumley  v. Pfizer, Inc., 200 F.R.D. 596 (S.D. Tex. 2001) (excluding plaintiffs’ expert witness who claimed that Viagra caused heart attack); Selig v. Pfizer, Inc., 185 Misc. 2d 600 (N.Y. Cty. S. Ct. 2000) (excluding plaintiff’s expert witness), aff’d, 290 A.D. 2d 319, 735 N.Y.S. 2d 549 (2002).

[2]  “Love is Blind but What About Judicial Gatekeeping of Expert Witnesses? – Viagra Part I” (July 7, 2012); “Viagra, Part II — MDL Court Sees The Light – Bad Data Trump Nuances of Statistical Inference” (July 8, 2012).

[3]  In re Viagra Prods. Liab. Litig., 572 F.Supp. 2d 1071 (D. Minn. 2008), 658 F. Supp. 2d 936 (D. Minn. 2009), and 658 F. Supp. 2d 950 (D. Minn. 2009).

[4]  Wen-Qing Li, Abrar A. Qureshi, Kathleen C. Robinson, and Jiali Han, “Sildenafil use and increased risk of incident melanoma in US men: a prospective cohort study,” 174 J. Am. Med. Ass’n Intern. Med. 964 (2014).

[5]  See, e.g., Herrara v. Pfizer Inc., Complaint in 3:15-cv-04888 (N.D. Calif. Oct. 23, 2015); Diana Novak Jones, “Viagra Increases Risk Of Developing Melanoma, Suit Says,” Law360 (Oct. 26, 2015).

[6]  See In re Viagra (Sildenafil Citrate) Prods. Liab. Litig., 176 F. Supp. 3d 1377, 1378 (J.P.M.L. 2016).

[7]  See, e.g., Jenny Z. Wang, Stephanie Le , Claire Alexanian, Sucharita Boddu, Alexander Merleev, Alina Marusina, and Emanual Maverakis, “No Causal Link between Phosphodiesterase Type 5 Inhibition and Melanoma,” 37 World J. Men’s Health 313 (2019) (“There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.”); Xinming Han, Yan Han, Yongsheng Zheng, Qiang Sun, Tao Ma, Li Dai, Junyi Zhang, and Lianji Xu, “Use of phosphodiesterase type 5 inhibitors and risk of melanoma: a meta-analysis of observational studies,” 11 OncoTargets & Therapy 711 (2018).

[8]  In re Viagra (Sildenafil Citrate) and Cialis (Tadalafil) Prods. Liab. Litig., Case No. 16-md-02691-RS, Order Granting in Part and Denying in Part Motions to Exclude Expert Testimony (N.D. Calif. Jan. 13, 2020) [cited as Opinion].

[9]  Opinion at 8 (“determin[ing] whether the analysis undergirding the experts’ testimony falls within the range of accepted standards governing how scientists conduct their research and reach their conclusions”), citing Daubert v. Merrell Dow Pharm., Inc. (Daubert II), 43 F.3d 1311, 1317 (9th Cir. 1995).

[10]  Opinion at 11.

[11]  Opinion at 11-13.

[12]  See Kenneth J. Rothman, Sander Greenland, and Timothy L. Lash, “Introduction,” chap. 1, in Kenneth J. Rothman, et al., eds., Modern Epidemiology at 29 (3d ed. 2008) (“no approach can transform plausibility into an objective causal criterion).

[13]  Opinion at 15-16.

[14]  Opinion at 16-17.

[15]  See Austin Bradford Hill, “The Environment and Disease: Association or Causation?” 58 Proc. Royal Soc’y Med. 295 (1965); see also “Woodside & Davis on the Bradford Hill Considerations” (April 23, 2013).

[16]  Opinion at 17 – 21.

[17]  Opinion at 18. The MDL court cited In re Silicone Gel Breast Implants Prod. Liab. Litig., 318 F. Supp. 2d 879, 893 (C.D. Cal. 2004), for the proposition that relative risks greater than 2.0 permit the inference that the agent under study “was more likely than not responsible for a particular individual’s disease.”

[18]  Opinion at 18.

[19]  Opinion at 20.

[20]  Opinion at 19.

[21]  Opinion at 21, quoting from Rule 702, Advisory Committee Notes (emphasis in Judge Seeborg’s opinion).

[22]  Opinion at 21.

[23]  SeeFollow the Data, Not the Discussion” (May 2, 2010).

[24]  Joiner, 522 U.S. at 145-46 (noting that the PCB studies at issue did not support expert witnesses’ conclusion that PCB exposure caused cancer because the study authors, who conducted the research, were not willing to endorse a conclusion of causation).

[25]  Huss v. Gayden, 571 F.3d 442  (5th Cir. 2009) (citing Vargas v. Lee, 317 F.3d 498, 501-01 (5th Cir. 2003) (noting that studies that did not themselves embrace causal conclusions undermined the reliability of the plaintiffs’ expert witness’s testimony that trauma caused fibromyalgia); see also McClain v. Metabolife Internat’l, Inc., 401 F.3d 1233, 1247-48 (11th Cir. 2005) (expert witnesses’ reliance upon studies that did not reach causal conclusions about ephedrine supported the challenge to the reliability of their proffered opinions); Happel v. Walmart, 602 F.3d 820, 826 (7th Cir. 2010) (observing that “is axiomatic that causation testimony is inadmissible if an expert relies upon studies or publications, the authors of which were themselves unwilling to conclude that causation had been proven”).

[26]  In re Accutane Prods. Liab. Litig., 511 F. Supp. 2d 1288, 1291 (M.D. Fla. 2007) (“When an expert relies on the studies of others, he must not exceed the limitations the authors themselves place on the study. That is, he must not draw overreaching conclusions.) (internal citations omitted).

[27]  See Rutigliano v. Valley Bus. Forms, 929 F. Supp. 779, 785 (D.N.J. 1996), aff’d, 118 F.3d 1577 (3d Cir. 1997) (“law warns against use of medical literature to draw conclusions not drawn in the literature itself …. Reliance upon medical literature for conclusions not drawn therein is not an accepted scientific methodology.”).

[28]  Opinion at 14

[29]  Opinion at 4 – 5.

Is the IARC Lost in the Weeds?

November 30th, 2019

A couple of years ago, I met David Zaruk at a Society for Risk Analysis meeting, where we were both presenting. I was aware of David’s blogging and investigative journalism, but meeting him gave me a greater appreciation for the breadth and depth of his work. For those of you who do not know David, he is present in cyberspace as the Risk-Monger who blogs about risk and science communications issues. His blog has featured cutting-edge exposés about the distortions in risk communications perpetuated by the advocacy of non-governmental organizations (NGOs). Previously, I have recorded my objections to the intellectual arrogance of some such organizations that purport to speak on behalf of the public interest, when often they act in cahoots with the lawsuit industry in the manufacturing of tort and environmental litigation.

David’s writing on the lobbying and control of NGOs by plaintiffs’ lawyers from the United States should be required reading for everyone who wants to understand how litigation sausage is made. His series, “SlimeGate” details the interplay among NGO lobbying, lawsuit industry maneuvering, and carcinogen determinations at the International Agency for Research on Cancer (IARC). The IARC, a branch of the World Health Organization, is headquartered in Lyon, France. The IARC convenes “working groups” to review the scientific studies of the carcinogencity of various substances and processes. The IARC working groups produce “monographs” of their reviews, and the IARC publishes these monographs, in print and on-line. The United States is in the top tier of participating countries for funding the IARC.

The IARC was founded in 1965, when observational epidemiology was still very much an emerging science, with expertise concentrated in only a few countries. For its first few decades, the IARC enjoyed a good reputation, and its monographs were considered definitive reviews, especially under its first director, Dr. John Higginson, from 1966 to 1981.[1] By the end of the 20th century, the need for the IARC and its reviews had waned, as the methods of systematic review and meta-analyses had evolved significantly, and had became more widely standardized and practiced.

Understandably, the IARC has been concerned that the members of its working groups should be viewed as disinterested scientists. Unfortunately, this concern has been translated into an asymmetrical standard that excludes anyone with a hint of manufacturing connection, but keeps the door open for those scientists with deep lawsuit industry connections. Speaking on behalf of the plaintiffs’ bar, Michael Papantonio, a plaintiffs’ lawyer who founded Mass Torts Made Perfect, noted that “We [the lawsuit industry] operate just like any other industry.”[2]

David Zaruk has shown how this asymmetry has been exploited mercilessly by the lawsuit industry and its agents in connection with the IARC’s review of glyphosate.[3] The resulting IARC classification of glyphosate has led to a litigation firestorm and an all-out assault on agricultural sustainability and productivity.[4]

The anomaly of the IARC’s glyphosate classification has been noted by scientists as well. Dr. Geoffrey Kabat is a cancer epidemiologist, who has written perceptively on the misunderstandings and distortions of cancer risk assessments in various settings.[5] He has previously written about glyphosate in Forbes and elsewhere, but recently he has written an important essay on glyphosate in Issues in Science and Technology, which is published by the National Academies of Sciences, Engineering, and Medicine and Arizona State University. In his essay, Dr. Kabat details how the IARC’s evaluation of glyphosate is an outlier in the scientific and regulatory world, and is not well supported by the available evidence.[6]

The problems with the IARC are both substantive and procedural.[7] One of the key problems that face IARC evaluations is an incoherent classification scheme. IARC evaluations classify putative human carcinogenic risks into five categories: Group I (known), Group 2A (probably), Group 2B (possibly), Group 3 (unclassifiable), and Group 4 (probably not). Group 4 is virtually an empty set with only one substance, caprolactam ((CH2)5C(O)NH), an organic compound used in the manufacture of nylon.

In the IARC evaluation at issue, glyphosate was placed into Group 2A, which would seem to satisfy the legal system’s requirement that an exposure more likely than not causes the harm in question. Appearances and word usage, however, can be deceiving. Probability is a continuous scale from zero to one. In Bayesian decision making, zero and one are unavailable because if either was our starting point, no amount of evidence could ever change our judgment of the probability of causation. (Cromwell’s Rule) The IARC informs us that its use of “probably” is quite idiosyncratic; the probability that a Group 2A agent causes cancer has “no quantitative” meaning. All the IARC intends is that a Group 2A classification “signifies a greater strength of evidence than possibly carcinogenic.”[8]

In other words, Group 2A classifications are consistent with having posterior probabilities of less than 0.5 (or 50 percent). A working group could judge the probability of a substance or a process to be carcinogenic to humans to be greater than zero, but no more than five or ten percent, and still vote for a 2A classification, in keeping with the IARC Preamble. This low probability threshold for a 2A classification converts the judgment of “probably carcinogenic” into a precautionary prescription, rendered when the most probable assessment is either ignorance or lack of causality. There is thus a practical certainty, close to 100%, that a 2A classification will confuse judges and juries, as well as the scientific community.

In IARC-speak, a 2A “probability” connotes “sufficient evidence” in experimental animals, and “limited evidence” in humans. A substance can receive a 2A classification even when the sufficient evidence of carcinogenicity occurs in one non-human animal specie, even though other animal species fail to show carcinogenicity. A 2A classification can raise the thorny question in court whether a claimant is more like a rat or a mouse.

Similarly, “limited evidence” in humans can be based upon inconsistent observational studies that fail to measure and adjust for known and potential confounding risk factors and systematic biases. The 2A classification requires little substantively or semantically, and many 2A classifications leave juries and judges to determine whether a chemical or medication caused a human being’s cancer, when the basic predicates for Sir Austin Bradford Hill’s factors for causal judgment have not been met.[9]

In courtrooms, IARC 2A classifications should be excluded as legally irrelevant, under Rule 403. Even if a 2A IARC classification were a credible judgment of causation, admitting evidence of the classification would be “substantially outweighed by a danger of … unfair prejudice, confusing the issues, [and] misleading the jury….”[10]

The IARC may be lost in the weeds, but there is no need to fret. A little Round Up™ will help.

[1]  See John Higginson, “The International Agency for Research on Cancer: A Brief History of Its History, Mission, and Program,” 43 Toxicological Sci. 79 (1998).

[2]  Sara Randazzo & Jacob Bunge, “Inside the Mass-Tort Machine That Powers Thousands of Roundup Lawsuits,” Wall St. J. (Nov. 25, 2019).

[3]  David Zaruk, “The Corruption of IARC,” Risk Monger (Aug. 24, 2019); David Zaruk, “Greed, Lies and Glyphosate: The Portier Papers,” Risk Monger (Oct. 13, 2017).

[4]  Ted Williams, “Roundup Hysteria,” Slate Magazine (Oct. 14, 2019).

[5]  See, e.g., Geoffrey Kabat, Hyping Health Risks: Environmental Hazards in Everyday Life and the Science of Epidemiology (2008); Geoffrey Kabat, Getting Risk Right: Understanding the Science of Elusive Health Risks (2016).

[6]  Geoffrey Kabat, “Who’s Afraid of Roundup?” 36 Issues in Science and Technology (Fall 2019).

[7]  See Schachtman, “Infante-lizing the IARC” (May 13, 2018); “The IARC Process is Broken” (May 4, 2016). See also Eric Lasker and John Kalas, “Engaging with International Carcinogen Evaluations,” Law360 (Nov. 14, 2019).

[8]  “IARC Preamble to the IARC Monographs on the Identification of Carcinogenic Hazards to Humans,” at Sec. B.5., p.31 (Jan. 2019); See alsoIARC Advisory Group Report on Preamble” (Sept. 2019).

[9]  See Austin Bradford Hill, “The Environment and Disease: Association or Causation?” 58 Proc. Royal Soc’y Med. 295 (1965) (noting that only when “[o]ur observations reveal an association between two variables, perfectly clear-cut and beyond what we would care to attribute to the play of chance,” do we move on to consider the nine articulated factors for determining whether an association is causal.

[10]  Fed. R. Evid. 403.