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AAAS Conference on Scientific Evidence and the Courts

September 8th, 2025

Back in September 2023, the American Association for the Advancement of Science (AAAS), with its Center for Scientific Responsibility and Justice, sponsored a two day meeting on Scientific Evidence and the Courts. If there were notices for this conference, I missed them. The meeting presentations are now available online. Judging from camera views of the audience, the conference did not appear to be well attended. Most of the material was forgettable, but some of the presentations are worth watching.

Jennifer L. Mnookin opened the conference with a keynote presentation on “Where Law and Science Meet.” Chancellor Mnookin presented a broad overview and some interesting insights on the development of the evidence law of expert witness testimony.

Following Mnookin, Professors Ronald Allen and Andrew Jurs presented on the “Unintended Impacts [sic] of the Daubert Standard.” The conference took place only a few months before amendment to Rule 702 became effective, and the reference to a “Daubert” standard was untoward. Allen’s comments followed the path of his previous articles. Jurs presented some empirical legal research, which seemed flawed for its assumption that the Frye standard was universally applied in federal court before the advent of Daubert. Assessing whether these standards lead to different outcomes when both standards have been applied heterogeneously, and one standard, Frye, is often not applied at all, and Daubert is often flyblown by judges hostile to the gatekeeping enterprise, Jurs’ empirical research seemed both invalid and very much beside the point. Both presenters missed the key point of Daubert, in which case plaintiff’s counsel advocated for no standard at all, beyond basic subject-matter qualification, for giving expert opinions in court.

A Session on “An International Perspective,” Scott Carlson discussed the efforts of the American Bar Association (ABA), and its Center of Global Programs, on supporting judges in foreign countries. Prateek Sibal discussed the history and work of the UNESCO Global Judges Initiative. My sincere wish is that the ABA would support judges more in the United States.

Panelists Valerie P. Hans, Emily Murphy, and Dr. Michael J. Saks presented on various jury issues, in a session “In the Minds of the Jury.” The presentations on how foreign countries process expert witness testimony were lacking any mention of how juries rarely if ever sit in civil cases that involve complex technical and scientific issues.

Two editors of scientific journals, Adriana Bankston and Valda Vinson, along with law professor Michael Sakes, spoke about peer review and publication, in  a session “As a Matter of Fact: ‘General Acceptance’ in Emerging vs. Established Science.” Their discussion on the publication process shed very little light on how courts and juries should assess the validity of specific papers, particularly in view of the lax practices at many journals. Towards the end of this session, a question from the audience proved to be very revealing of the prejudices of the law professor on the panel. The questioner rose to complain that after beginning research on a topic that has litigation relevance her research is now frequently questioned. She asked the panel how she might deal with the annoyance of being questioned. Some on the panel basically urged her to buck up, but the law professor invoked the spirit of agnothologist, and lawsuit industry expert witness, David Michael, to suggest that “manufacturing doubt” was just a corporate tactic in the face of scientific evidence. The prejudice against corporate speech is remarkable when the lawsuit industry has a long history of playing the ad hominem game in advancing its pecuniary interests.

The session that followed addressed how trustworthy science might best be put before courts. The organizers described this session, Utilizing Scientific and Technical Expertise, as going to the heart of the issues targeted by the conference. Joe S. Cecil, Deanne M. Ottaviano, and Shari Seidman Diamond discussed how scientific expertise enters into the evidentiary record in American courtrooms. Their presentations were interesting, but curiously no one mentioned that the primary avenue for expert witness opinion is through oral testimony!

Joe Cecil discussed methods judges have to obtain scientific and technical evidence to advance justice. (By this I hope he meant the truth, and not just the outcome preferred by social justice warriors.) As noted, Joe Cecil did not focus on the ordinary methods of direct and cross-examination of party expert witnesses, but rather, he identified other methods of introducing expertise into the courtroom for the benefit of the judge or the jury. Only one suggestion really affects jury comprehension, namely the appointment of non-party expert witnesses by the court. The other methods really only provide expertise to the trial judge, who perhaps is challenged to make a ruling under Federal Rule of Evidence 702. The federal courts have the inherent supervisory power to appoint technical advisors to act as special law clerks on issues. Similarly, appointed special masters can address technical implementation issues, subject to the district judges’ control. The judges are always free to read outside the briefs and testimony, but there are ethical and notice issues for such conduct. The Reference Manual on Scientific Evidence (RMSE) sits on the shelves on every federal judge’s bookshelf, even if in pristine, unused condition. Judges can at least read the RMSE on specific issues without having to disclose their extra-curricular research to the parties.  Of course, parties are well advised to consider any materials in the RMSE, which support or oppose their contentions.

In discussing the RMSE, Cecil noted that the fourth edition was in the works. He also mentioned that all the old chapter topics would be carried forward to the fourth edition, and that new topics would include eyewitness identification, computer science, artificial intelligence, and climate science. Sadly, there will be no chapter on genetic determination of disease, but perhaps the clinical medicine chapter will take on the subject in greater detail than previous editions. This conference took place two years ago, and yet the RMSE, fourth edition, is still not published. The National Academies website previously listed the project as completed, but the site now describes the work as “in progress.”

Joe Cecil’s analysis of the various extraordinary expert techniques was pretty much spot on, especially his assessment that “experiments” with court-appointed experts were often failures or at best modest successes. The discussion of Judge Pointer’s Rule 706 independent expert witnesses in the silicon [sic] breast implant litigation, MDL926, seemed to lack context. Cecil acknowledged that the court’s expert witnesses contributed some value to admissibility decisions, but Judge Pointer notoriously did not believe that he, as the MDL judge, had any responsibility for Rule 702 determinations, and he made none except in cases that he tried in the Northern District of Alabama. (And these decisions were before the Science Panel was appointed.) So the Rule 706 witnesses really could not have aided in admissibility decisions.

The real value – in my view – of the Science Panel was that it demonstrated that Judge Pointer was quite wrong in believing that both sides’ expert witnesses were simply “too extreme,” or too partisan, and that the truth was somehow in the middle. Indeed, Judge Pointer said so on many occasions, and he was judicially gobsmacked when all four of his experts roundly rejected the plaintiffs’ distortions of the science of immunology, epidemiology, toxicology, and rheumatology. The courts’ expert witnesses sat for discovery depositions, and then gave testimony de bene esse. To my knowledge, their testimony was never admitted in any of the subsequent trials.

Judge Jed Rakoff gave an interesting presentation, “Strengthening Cooperation Between the Scientific Enterprise and the Justice System,” on the intersection between scientific and legal expertise and the need for their better integration. Judge Rakoff focused on the astonishing lack of compliance of trial judges with the gatekeeping requirements of Rule 702 in addressing the admissibility of forensic evidence. Several subsequent panels also addressed forensic topics, including “A Texas Case Study in Accountability for Forensic Sciences,” “Innovations in Investigative Technologies Improvements and Drawbacks,” and “Artificial Intelligence and the Courts,” “Wrongful Convictions and Changed Science: Statutes,” and “Standing Up for Justice: When the Law and Science Work Hand-in-Hand.”

One of the more curious sessions was on “Statistical Modeling and Causation Science,” presented by the American Statistical Association along with the AAAS. Maria Cuellar, from the University of Pennsylvania, discussed the role of statistical thinking in causal assessment, with slides that referred to a nonparametric estimator for the probability of causation. Cuellar, however, never defined what an estimator was; nor did she differentiate nonparametric from parametric estimators. She displayed other equations, again without explaining their origin and meaning, or identifying symbols or meanings. Similarly, Rochelle E. Tractenberg, discussed the use of statistics as evidence and as part of inferring causal inference in litigation, in a model of unclarity. At one point, Tractenberg appeared to suggest that general causation could be taken from regulatory pronouncements. Her discussion of glyphosate implied that general causation was established, which may have led me to disregard her presentation.

Finally, the conference sported a discussion, “Toxic Tort 2.0: Emerging Trends in Climate Change Related Litigation,” The two presenters were Dr. L. Delta Merner, the “Lead Scientist” for the Science Hub for Climate Litigation, Union of Concerned Scientists, and Dr. Paul A. Hanle, Visiting Scholar and  Founder of the Climate Judiciary Project, Environmental Law Institute. The Science Hub actively promotes climate change litigation, which made me wonder whether its scientists are involved in that new chapter in the upcoming fourth edition of the Reference Manual.

Posted in Causation, Reference Manual on Scientific Evidence, Rule 702, Scientific Evidence, Scientific Publishing | 6 Comments »

Lack of Trust in Science – The Situation Our Situation Is In

August 29th, 2025

The United States is in political crisis as its citizens are frogmarched into an authoritarian, illiberal, and unlawful dystopia. The seriousness of the political situation makes it difficult to focus on scientific issues, but as with past fascist regimes in history, the crisis is not limited to any one sphere of life in the United States.

Scholars of fascism have pointed out that not all fascist regimes are the same, but there are some key features that give them all a family resemblance. In the political realm, fascist leaders point to an idyllic history, however mythical or false, in which the country was once great. The greatness has been eroded and squandered by the country’s enemies, internal and external. Confronting enemies within and without is an emergency, which cannot be addressed within the rule of law. Only an authoritarian leader can fix it by suspending the rule of law.

Fascism does not operate solely in the political sphere, but insists upon ideological purity in art, culture, education, business, finance, military, law, and science.[1]

Yes, even science. Nazi Germany had its bogus science of racial purity. The Soviet Union had its Lysenkoism. Theocratic fascist regimes, such as Iran or the United States, have their “god talk” and blasphemy squads, which suppress scientific curiosity, experimentation, and development, except for the creation of weapons (where replicability, validity, and predictive accuracy really matter).

There are various reasons for Felonious Trump’s election, but the epistemic sin of credulousness of the American people is certainly one of them. We are living in Orwell’s 1984 world where many people have been tethered to TV screens to receive their daily influx of state-approved propaganda. Character for truth has ceased to be a virtue. “And even truth can become a lie in the mouth of a born liar.”[2]

The credulity of the American people has manifested as distrust in scientific expertise and willingness to believe charlatans such as Robert Kennedy, Jr. The phenomenon of transferring trust from legitimate scientists to charlatans is probably one of the clearest and strongest symptom of our current malaise.

Professor Arthur L. Caplan[3] is a scientist and medical ethicist who has never been shy about asking discomforting questions. Not surprisingly, Caplan has spoken out against some of the bone-headed anti-science actions of the present regime in Washington.[4]

In an essay entitled “How Stupid has Science Been?” Caplan asks:

“So how can U.S. President Trump, Secretary of Health Robert F. Kennedy, Jr., or Director of the Centers for Medicare and Medicaid Mehmet Oz and their enthusiastic followers be succeeding in defunding research and installing ideological oversight and censorship that is crushing science, technology and engineering and will for many years to come?”[5]

Caplan blames the scientific community itself, in part, for the current crisis by disparaging and discouraging scientists from engaging with the public. Obviously, Caplan is not thinking of the cadre of scientists who seek phony validation by becoming highly paid expert witnesses for the lawsuit industry. Nor is he thinking of the dodgy TV doctors such as Dr. Oz. Caplan’s focus is on the harm done to the careers of accomplished scientists, such as the late Carl Sagan, who was denied tenure at Harvard University and membership in the National Academies of Science because his popularizing efforts eclipsed his substantial scientific accomplishments. Caplan thus blames the American scientific establishment itself for having “disparaged its public communication as unnecessary and looked down on those few who tried to educate broader audiences about the wonders, benefits, methods and advancements of science.”

Professor Caplan argues that in popularizing scientific ideas, theories, and methods, scientists – such as the late Carl Sagan – undermined their own careers. The result is that high-achieving scientists ignored the public square and retreated into their own scientific community’s ivory tower. Caplan’s critique of the detachment of the scientific community could well be extended to its frequent failures to speak out against charlatans in its own midsts, and politicians who distort and misrepresent scientific research in the public arena.

Caplan is, however, very clear that the scientific community’s insularity, and its “resulting failure to communicate about science to the public is a major factor in explaining why so few have rallied to science’s defense today against government policies promoting ignorance, illiteracy and quackery.”  Indeed, although at this point, it is also clear that frank communications about the government’s promotion of scientific quackery will be punished by the Regime’s cancellation of grants, firing from advisory councils, and retaliations against scientists’ universities.

I take Caplan’s critique to be an invitation to engage in counter-factual thinking about what our current situation might look like if scientists had robustly “occupied the field” of communication and education of the public. Citing a recent article in a Nature journal,[6] Caplan observes that populists and right-wing thinkers have been losing faith in science for years. This diagnosis, however, is not quite accurate. Populists, left and right, have succumbed to motivated reasoning in learning to ignore scientific conclusions, regardless of validity concerns, on emotive or political grounds. This mode of (non)-thinking allows populists, left and right, to subscribe to putative scientific claims without any appreciation of the nuances of scientific inference and threats to validity.

Caplan is right to call out the right-wing attack on science, but some of the attack on science is coming from left-wing populists, such as the worm-brained Robert F. Kennedy, Jr. And historically, there have been many instances in which environmental and occupational health advocates have outrun their headlights to press claims based upon hypothetical models and unvalidated assumptions.

All people, whether they hang politically left or right, are vulnerable to the emperor of all cognitive biases – apophenia, the psychological tendency to discern causal patterns in random noise. Although apophenia was originally thought of an abnormal psychological process,[7] the phenomenon is common to “normal” as well as mentally ill persons.[8]

Many people, left and right, are willing to endorse, or subscribe to, pseudo-scientific claims based upon their motivations to accept claims, without regard to the methods used to support those claims. Professor Caplan is correct that serious scientists have been too shy to step into the public square, and the scientific community should encourage, not punish, engagement with the public. (Caplan passes over the problem of how university publicists often misrepresent and exaggerate the findings and research of university scientists.)

The problem of lack of trust in science, however, is a much bigger problem. On average, American education and acumen in math and science lags that of many countries in the world,[9] even as post-secondary education in the United States excels and attracts many of the best and the brightest domestically and internationally. Immigrants have helped American universities keep their leadership role in the world, despite shortfalls in domestic funding of primary and secondary science education. Of course, this international leadership in science and math university education, gained with the help of immigrants, is now under attack from the MAGAT regime.[10]

No one is eager to blame those who evidence their lack of trust in science, and to be sure, there is plenty of blame to go around. There are multiple systemic causes of poor quality science and improvident claims to scientific knowledge.[11] In assessing the causes of the prevalent distrust in science, we should not lose sight of the responsibility of those who claim that scientists cannot be trusted. There is at bottom a widespread moral failure in the land.  “It is wrong always, everywhere, and for anyone, to believe anything upon insufficient evidence.”[12]

доверяй, но проверяй!

[1] Zachary Basu, “Trump knee-caps America’s institutions,” Axios (Aug. 27, 2025); Elisabeth Zerofsky, “Robert Paxton, A Leading Historian Of Fascism, Long Resisted Applying The Label To Trumpism. Then He Changed His Mind..,” N.Y. Times Mag. 45 (Oct. 27, 2024).

[2] Thomas Mann, “The Problem of Freedom: An Address to the Undergraduates and Faculty of Rutgers University at Convocation,” (April 28, 1939).

[3] Arthur L. Caplan, PhD., is the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics, Department of Population Health, and the founder of  the Division of Medical Ethics at NYU Grossman School of Medicine’s Department of Population Health in New York City. I had the pleasure to meet Professor Caplan, and present to one of his classes, back when he taught at the University of Pennsylvania.

[4] See, e.g., Arthur L. Caplan, “Fed Action Toward Medical Journals Is ‘Dangerous’, Ethicist Says,” Medscape (Aug. 26, 2025).

[5] Arthur L. Caplan, entitled “How Stupid has Science Been?” EMBO reports (Aug. 2025).

[6] Vukašin Gligorić, Gerben A. van Kleef, and Bastiaan T. Rutjens, “Political ideology and trust in scientists in the USA,” 9 Nature Human Behaviour 1501 (2025) (“Since the 1980s, trust of science among conservatives in America has been plummeting”).

[7] See Aaron L Mishara, “Klaus Conrad (1905–1961): Delusional Mood, Psychosis, and Beginning Schizophrenia,” 36 Schizophr Bull. 9 (2009); Scott D. Blain, Julia M. Longenecker, Rachael G. Grazioplene, Bonnie Klimes-Dougan, and Colin G. DeYoung, “Apophenia as the disposition to false positives: A unifying framework for openness and psychoticism,” 129 J. Abnormal Psych. 279 (2020).

[8] Donna L Roberts, “Apophenia: The Human Tendency to Find Patterns in Randomness,” Medium (Jan. 9, 2024); Ahmed S. Sultan & Maryam Jessri, “Pathology is Always Around Us: Apophenia in Pathology, a Remarkable Unreported Phenomenon,” 7 Diseases 54 (2019).

[9] Drew DeSilver, “U.S. students’ academic achievement still lags that of their peers in many other countries,” Pew Research Center (Feb. 15, 2017).

[10] Is it not high time that we call the movement by its essential motivation: make American great again for the Trumps?

[11] See, e.g., Lex Bouter, Mai Har Sham & Sabine Kleinert, “The Lancet–World Conferences on Research Integrity Foundation Commission on Research Integrity,” 406 The Lancet 896 (2025).

[12] William K. Clifford, “The Ethics of Belief,” 29 Contemporary Rev. 289, 295 (1877).

Posted in Causation, Cognitive Biases, Scientific Evidence, Scientific Misconduct | No Comments »

Junk Journalism

August 19th, 2025

There is plenty of room for a healthy science-based environmentalism, but finding the room in the American political house has always been difficult. The current administration brings together the horseshoe wacko excesses of the worm-brained Robert Kennedy, Jr., and the crony capitalism of Felonious Trump. In this toxic, post-truth milieu, environmental groups such as Sierra Club and Greenpeace are both complaining about their setbacks,[1] as well as stepping up their own propaganda.

In the face of advocacy group propaganda, journalists should provide a strong science filter before allowing misinformation and emotive appeals to be passed off as scientific truth. Sadly, well-motivated manufacturing industry can rarely count on either the main stream media for sympathy or accuracy in reporting environmental issues. Readers of major newspapers, however, deserve careful reporting and the separation from hyperbole and fact.

A recent article in the Washington Post makes the point. Activist journalist Amudalat Ajasa reported her story this week that “Her dogs kept dying, and she got cancer. Then they tested her water.”[2] Oh my goodness; that must be a scandal; right? Queue the outrage.

Now widespread journalistic practice means that Ms. Ajasa may not have written the headline, and it was likely an editor who concocted the click-bait headline that suggested that something in the water killed some woman’s dogs and caused her cancer. Upon reading the story, however, readers would be justified in concluding that the author was clearly in on the ploy to misinform. So shame on both the would-be journalist and her editor.

Ms. Ajasa tells us that the residents of Elkton, Maryland, worry about “forever chemicals” in their water, a worry instigated in large measure by mass and social media, advocacy NGOs, state and federal agencies, and the lawsuit industry. Focusing on her anecdotal datum, Ajasa reports that Ms. Debbie Blankenship, a resident of the Elkton area, had “chalked up her health problems, including losing her right leg to an infection, to bad luck.” Bad luck? Ajasa must have gotten a HIPAA release and waiver to discuss Ms. Blankenship’s medical condition in a very public forum because the WaPo story discusses health details and features photographs of Ms. Blankenship, who is clearly obese, has had one leg amputated, and is confined to a wheel chair. Apparently, neither Ms. Blankenship nor Ms. Ajasa ever considered that lifestyle factors combined to cause Ms. Blankenship to develop diabetes mellitus and cancer (of some unspecified type).

The obvious, however, is ignored or pushed aside by Ajasa’s reporting that in 2023, W.L. Gore & Associates, a manufacturer of Gore-Tex, telephoned with a request to test the Blankenship water well for perfluorooctanoic acid (PFOA), which had been used in its manufacture of Teflon (polytetrafluoroethylene or PFTE). PFOA is one of the family of PFAS chemicals that has been the subject of a regulatory furor in recent years, including the issuance of action levels below the limits of detection for many laboratories.

The request to test the Blankenship water well was triggered by a lawsuit, filed in 2022, by a former W.L. Gore employee, Stephen Sutton. The lawsuit industry jumped on Sutton’s lawsuit with a class action environmental complaint in 2024. In any event, according to Ms. Ajasa, the company’s request to test the Blankenship well led to the eureka moment of scientific insight. Ms. Blankenship and her dogs drank well water, but her husband and children always drank bottled water. She was poisoned by the well water. Quod erat demonstrandum!

Ajasa’s reporting forces the reader to wade through a lot of activist propaganda and scientific hooey, such as claims that there is no safe level of PFOA, passed off as scientific fact. Agency assumptions and precautionary principle statements are not facts. Ignorance about no observable effect level is not knowledge that there is no safe level.

The WaPo readers are similarly regaled with a claim, masquerading as a statement of fact, that PFAS chemicals have “been linked to serious health problems including high cholesterol, cardiovascular disease, infertility, low birth weight and certain cancers.” Use of the verb “link” is a meaningless term in science, and thus a favorite of sloppy journalists. Whether a link is an association, a cause, a suggestion from an anecdote, a lawyer’s allegation, or a claim by an environmental group is anyone’s guess, and is left to the reader’s imagination. Whether Ms. Blankenship’s cancer is one of the “certain cancers” is not reported. Sloppy journalism of this sort, whether intentional, reckless, or negligent, undermines evidence-based legislation, regulation, and adjudication. “The credulous man is father to the liar and the cheat.”[3]

Ms. Ajasa eventually gets around to telling her readers that the water samples from Ms. Blankenship’s well contained PFOA concentrations of 3.4 parts per trillion (ppt), below the Environmental Protection Agency’s precautionary and unsupported maximum action level of 4 ppt. Rather than looking for other potential causes of Ms. Blankenship’s health problems, Ms. Ajasa glibly channels the EPA’s unsupported assertions that “that small amounts of the chemical can cause serious health impacts [sic], including cancer.” The reader is left to believe that this is a fact and that the undefined “small amounts” must include the 3.4 ppt detected in Blankenship’s well. Ajasa uses innuendo to substitute for the absence of evidence.

Journalists have an important role in informing and educating the public about scientific issues and controversies. Innuendo, unquestioned assumptions, and sloppy thinking – this is how the junk journalism sausage is made. Junk journalism is much like junk science. If we understand that junk journalism is a form of information pollution, then a well-considered, evidence-based environmentalism calls for remediation. 

[1] David Gelles, Claire Brown and Karen Zraick, “Environmental Groups Face ‘Generational’ Setbacks Under Trump,” N.Y. Times (Aug. 16, 2025). The list of aggrieved seems endless: Sierra Club, Greenpeace, Climate and Communities Institute, Natural Resources Defense Council, Earthjustice, the Southern Environmental Law Center, etc.

[2] Amudalat Ajasa, “Her dogs kept dying, and she got cancer. Then they tested her water,” Wash. Post (Aug. 14, 2025).

[3] William Kingdon Clifford, “The Ethics of Belief” (1877), in Leslie Stephen & Sir Frederick Pollock, eds., The Ethics of Belief and Other Essays 70, 77 (1947).

Posted in Causation, Regulation, Scientific Evidence, Scientific Publishing | No Comments »

The FDA Expert Panel on Talc – More Malarky     

June 18th, 2025

On May 20, 2025, as announced, FDA Commissioner Martin Makary held his panel discussion on talc in food and medications.[1] The discussion lasted just under two hours, and is available on YouTube for your viewing and perhaps your amusement. Makary opened and closed the event with what could have been the plaintiffs’ opening and closing statements from one of the many talc trials that have clouded courtrooms across the land. He asked rhetorically: “Why don’t we talk about at our oncology meetings the 1993 National Toxicology Program results that found clear evidence of carcinogenic activity of talc in animal studies?’” Perhaps because the talc findings were questionable at best, and the asbestos findings with respect to gastrointestinal cancers were exculpatory for talc.

Makary’s introductory remarks were followed by the panelists’ introducing themselves by their training and involvement with talc issues. Other than Makary, the participants were FDA Deputy Commissioner Sara Brenner, George Tidmarsh, John Joseph Godleski, Sandra McDonald, Daniel Cramer, Joellen Schildkraut, Malcolm Sim, Steven Pfeiffer, Nicolas Wentzensen, and Nicole C. Kleinstreuer. Godleski and Cramer have served as plaintiffs’ expert witnesses in ovarian cancer litigation, which was not particularly germane to the panel discussion. In their initial discussions of qualifications and background, neither Godleski nor Cramer disclosed his potential conflicts of interest, or the amount of fees earned. Sandra McDonald described her experience in assisting Godleski, but she did not declare whether she earned any money for consulting services to the lawsuit industry. Later in the panel discussion, when George Tidmarsh stated that no one should be vilified for past practices in using talc, Daniel Cramer jumped in to vilify Johnson & Johnson with the suggestion that somehow that company had surreptitiously arranged for the National Cancer Institute to remove a statement about how talc “may be associated with talc use” from its website just before he was about to testify in his first talc trial for plaintiffs.

None of the panelists had served as a defense expert witness. Steven Pfeiffer works for a pharmaceutical company, but not one that had any experience with the safety or efficacy of talc as an ingredient in medications.

None of the panelists had participated in any toxicologic or epidemiologic study of talc on cancers or diseases of the digestive organs. None of the panelists made it his or her business to become familiar with the extensive studies of the asbestos and talc on gastrointestinal cancers. The lack of experience, or specific citations to any study, did not stop Daniel Cramer from suggesting that talc was responsible for inflammatory bowel disease, autoimmune diseases, and gastrointestinal cancers.  Like Cramer, epidemiologist Joellen Schildkraut, focused on ovarian cancer, and made the false assertion that the relationship between talc and gastrointestinal cancers is understudied. Schildkraut held back from asserting that talc causes ovarian cancer, but she heartily endorsed banning talc on the precautionary principle. All the panelists concurred with the suggestion that talc be eliminated from food and drugs, without waiting for “the epidemiologists to catch up.”

Two issues were grossly misrepresented by the panelists. None of them, however, was well informed enough for the misrepresentations to have been overt lies. The first whopper was that National Toxicology Program (NTP) testing had shown carcinogenicity of talc in its inhalational studies for the lung and other organs. The second whopper was that rice on talc was used prevalently in the United States, and that it was responsible for digestive organ cancers. Nicole C. Kleinstreuer, who has worked at the NTP, and accurately described its activities gave a description of its animal talc studies, perhaps a bit slanted, but not too inaccurate. When George Tidmarsh later misrepresented NTP talc findings, however, Kleinsteuer was silent.

NTP Ingestion Studies

Makary did not identify the NTP studies to which he referred, but Kleinsteuer described a talc inhalation study that has only one referent. The NTP conducted long-term rodent inhalation and ingestion assays for both talc and different kinds of asbestos, in the 1980s and 1990s. For talc, the NTP published, in 1993, only one long-term inhalational study in rats and mice.[2] In mice, exposed to talc by inhalation for up to two years, there was no evidence of any “neoplastic” effects. The results in rats were more difficult to interpret. In male rats, exposed for over two years, there was weak evidence of neoplastic effects based upon an increased incidence of benign or malignant adrenal gland pheochromocytomas. In female rats, the NTP reported “clear evidence” of excess alveolar/bronchiolar (lung) adenomas and carcinomas and benign or malignant adrenal gland pheochromocytomas of the adrenal gland. The meaning of these rodent studies obviously varies depending upon whether you are a rat or a mouse of a certain breed; the meaning for humans is even murkier, even for humans that are rodent-like. The multiple comparisons across exposure levels for dozens if not hundreds of outcomes, and the lumping of benign and malignant effects together, certainly makes the NTP statistical analyses suspect. This report was marked by significant controversy, and some scientists refused to endorse its finding because adrenal gland pheochromocytomas were not treatment-related; the maximum-tolerated dose was exceeded for female rats at the higher exposure level, thus violating the study’s protocol; and talc is thus not expected to cause tumors in rats (and mice) exposed at levels that do not cause “marked chronic lung toxicity.”[3]

One of the lawsuit industry’s, and Makary’s, theories about the harmfulness of ingested talc is based upon the supposition that talc has asbestos contaminants. This theory is as vague as is the term asbestos, which has no mineralogical meaning; instead, the term asbestos was historically used to refer to six different minerals: actinolite, anthophyllite, amosite (cummingtonite-grunerite), chrysotile, crocidolite, and tremolite. All of these minerals, except for chrysotile, are amphibole minerals. Some of the amphibole minerals occur in both fibrous and non-fibrous form, and the ill health effects of the amphibole fibers are generally attributed to their resistance to biological degradation and their high aspect ratio. Things get a bit crazy because the federal government, for purposes of standardizing aerosol measurements, set the aspect ratio for counting “fibers,” at 3:1. The pathogenicity of “federal fibers,” which are not really fibers, is highly disputed.

The NTP never conducted long-term talc ingestion studies; it did something much better. The NTP tested dietary high-dose, long-term ingestion of various asbestos types in multiple species. The NTP did not leave the exposure issue vague with “asbestos” as the dietary source. Instead, the NTP was more precise when testing whether ingesting “asbestos” was harmful to rodents. The NTP ran separate ingestion experiments on chrysotile, amosite, and crocidolite, with the different form of asbestos making up one percent of the animals’ lifetime diet. Overall, these experiments were “null”; that is, they provided no support for the carcinogenicity of ingested asbestos of the types tested.

The NTP conducted lifetime ingestion studies in male and female rats with a diet of one percent crocidolite asbestos, the most toxic and carcinogenic form of asbestos in human beings. The NTP experiments showed that under these conditions, long-term ingestion of crocidolite asbestos was neither overtly toxic nor carcinogenic in male or in female rats.[4] After crocidolite, amosite asbestos, fibrous cummingtonite-grunerite, named for “asbestos mines of South Africa, is the most toxic and carcinogenic of the asbestos fibers. The NTP showed that feeding male and female rats amosite asbestos for one percent of their diet, for their lifetimes, was not overtly toxic, did not affect their survival, and was not carcinogenic.[5] The NTP repeated its life-time one percent amosite diet in Syrian Golden hamsters, again without toxic or carcinogenic response in either the male or female hamsters.[6]

Looking at the least toxic and carcinogenic asbestos mineral, chrysotile, the NTP’s conducted long-term one percent feed studies of both “short range” and “long range” (chrysotile fiber length) in Syrian Golden hamsters. Again the results were “null”; that is, there was no treatment-related toxicity or carcinogenicity.[7] There were no increases in adrenal cortical adenomas (benign growths) when compared with concurrent controls, but there was an increase of these benign tumors when compared with pooled control groups from other experiments. Ultimately, the NTP concluded that the biological importance of these benign adrenal growths in the absence of cancers or tumors of the gastrointestinal tract (which was the target organ) was questionable, at best.

Because of prior research suggesting that carcinogencity was a function of fiber rigidity and length, the NTP tested ingested chrysotile in rats, at two different fiber lengths. For its experiments, the NTP defined “short-range chrysotile (SR)” as short fibers with a median length of 0.66 microns, and a range of 0.088 to 51.1 microns. “Intermediate-range (IR) chrysotile fibers had a median length of 0.82 microns, with a range from 0.104 to 783.4 microns. The NTP did not use long-range chrysotile fibers, which are generally greater than 5 microns in length. Male and female F344/N rats ingested an NTP one percent diet of chrysotile, in the two lengths of chrysotile, SR and IR, for a lifetime. There were no neoplastic or non-neoplastic diseases, overt toxicity, or decrease in survival associated with SR chrysotile ingestion, in either the male or the female rats.[8] In the female rats, there was no effect on fertility or litter, overt toxicity, or carcinogenicity from IR chrysotile ingestion. The male rats also did not show any adverse clinical signs, but they experienced a statistically insignificant increase in benign colonic polyps, which the NTP stretched to characterize as “some” (but not clear) evidence of carcinogenicity.

Rice is Nice, With or Without Talc

The FDA panelists’ inaccurate claims about talc on rice also cry out for rebuttal, which no panelist seemed able or willing to give. Given that the panel was convened with only four days notice, and without public comment, it operated in a fact-free zone, and operated mostly as a propaganda exercise. The history of the ingested asbestos and talc controversy goes back over half a century. Some background is needed to understand exactly how outlandish the rice-on-talc claim is.

The causal association between asbestosis and lung cancer was well established by the early 1960s,[9] as was the causal association between crocidolite asbestos exposure and mesothelioma.[10] Some sources carelessly credit Irving Selikoff with these discoveries, but he was not so much of a discoverer, as he was a zealous spokesman for the safety of asbestos-exposed workers. Selikoff worked hand-in-hand with various labor unions to publicize and politicize asbestos risks that had been shown by other workers. Credit for the lung cancer connection properly goes to earlier work done by Sir Richard Doll and others, and the crocidolite-mesothelioma connection was shown by J. Christopher Wagner, in 1960. Where Selikoff deserves credit is in tireless efforts to expand the scope of asbestos-related diseases beyond lung cancer and mesothelioma, with or without sufficient evidence, and thus to expand the compensability of other diseases of ordinary life in asbestos workers.

In his efforts to extend the scope of compensation, Selikoff did not limit himself to risks that had been scientifically established; he sought to expand the list of asbestos-related diseases. He advanced the unsubstantiated notions that all six kinds of asbestos minerals carried the same risks, that asbestos caused virtually every kind of cancer in humans, that any asbestos in the environment required extreme remedial action, and that asbestos was responsible for a very high percentage of all human cancers.

No doubt Selikoff wanted credit for scientific discoveries, but he also wanted science that would support compensation. Selikoff understood that if the asbestos workers stopped smoking, their risks of lung cancer would fall, and their cancer morbidity and mortality would be more influenced by gastrointestinal cancers, given that colorectal cancer was the leading cause of cancer-related death in non-smoking men, in the 1960s.

By 1950, Selikoff had already become an advocate, who testified and wrote reports as a claimants’ expert witness in many asbestos cases. In the early 1950s, New Jersey lawyer Carl Gelman retained Selikoff to examine 17 workers from the Paterson plant of Union Asbestos and Rubber Company (UNARCO). Gelman filed workers’ compensation claims on behalf of these UNARCO workers, and Selikoff supported Gelman’s claims with reports and testimony. In the early 1950s, Anton Szczesniak, one of the UNARCO claimants, with Selikoff’s support as an expert witness, sought compensation for “intestinal cancer.” In 1965, Selikoff testified to support an asbestos insulator’s claim that asbestos exposure caused his colorectal cancer.[11] In 1974, Selikoff wrote a review article on asbestos exposure and gastrointestinal cancers, without any disclosure of his pro-plaintiff testimonial adventures.[12] Serious epidemiologists such as Sir Richard Doll and Sir Richard Peto pushed back on Selikoff’s exaggerated projections of asbestos-related mortality,[13] and his assertion that asbestos caused digestive system cancers.[14] Forty years after Selikoff testified for the claimant in an asbestos colorectal cancer case, the Institute of Medicine published a systematic review of the evidence available to Selikoff and later evidence, which showed that the evidence was insufficient “to infer a causal relationship between asbestos exposure and pharyngeal, stomach, and colorectal cancers.”[15]

Selikoff’s rent-seeking and fear-mongering spawned many asbestos scares. Some scientists accepted Selikoff’s dogma that a single asbestos fiber, of any variety, could cause any human cancer. The Mt. Sinai jihad against “asbestos” extended to any exposures involving asbestos, or even other minerals that contained “elongated mineral particles,” that nominally met the crude definition of asbestos. This jihad led to a prolonged litigation against the Reserve Mining Company, which had permits to dump taconite tailings in Lake Superior, since the late 1940s. Using Selikoff’s claim that “asbestiform” mineral particles had entered the water supply, the U.S. Environmental Protection Agency was able to obtain an injunction against the mining company.[16]

Regulatory overreach, Selikoff’s exaggerated testimony, and the trial judge’s partiality and bias marred the litigation.[17] After decades of research on asbestos in drinking water, there remains no substantial evidence that supports a conclusion that ingested asbestos in drinking water causes gastrointestinal or any other cancer.[18]

Selikoff was the head of an anti-asbestos lobby that promoted the fiction that asbestos was responsible for all manners of human ailments, regardless of dose or route of administration.[19] One of the panics he helped initiate involved the claim that talc-dusted rice was responsible for the high rate of stomach cancer among Japanese in Japan.

Reuben Merliss published an article in Science, in 1971, in which he attempted to attribute the high rate of stomach cancer in Japan to the Japanese custom of dusting rice with talc. Merliss relied upon overall population rates and trends to draw an ecologic inference that the Japanese rice (with talc and any asbestos contaminants) was responsible for the Japanese higher incidence of stomach cancer.[20]

The Merliss hypothesis, inspired by Selikoff, was sunk by a much more careful analysis (which got less media coverage). Two epidemiologists analyzed data about use of talc-coated rice in Japan and Hawaii, and found no support for the claim that talc-coated rice increased the risk of developing stomach cancer.[21]

Their more careful dietary assessment found high rates of stomach cancer among Japanese in Japan who did not consume talc-coated rice, while Japanese in Hawaii, who consumed considerable quantities of talc-coated rice had intermediate rates of stomach cancer (lower than in Japan). Filipinos in Hawai had very low rates of gastric cancer, even though they consumed the greatest amounts of talc-coated rice of any of the observed groups. The secular incidence trend of stomach cancer decreased more substantially among the talc-exposed Japanese living in Hawaii than among the non-exposed Japanese living in Japan.

Although the asbestos perpetual motion litigation machine continues to churn, the lawsuit industry has been hampered by the bankruptcy of virtually every company that made an asbestos-containing product, and the reduction of asbestos use and exposures over the last 50 years. The lawsuit industry’s shift to demonize and monetize talc as the next mineral target was predictable. What was not predictable was that we would have a Secretary of Health & Human Services whose sole experience in medicine has been in suing pharmaceutical and other manufacturing industries, perpetuating medieval beliefs in the miasma theory of disease causation,[22] and spreading conspiracies, misinformation, and disinformation. FDA Commissioner Makary has shown himself to be a willing accomplice in advancing the Secretary’s agenda. In his closing remarks, Makary made unsupported assertions, then retreated to the dodge that he was just asking questions. Makary strongly suggested that the recent increase in colorectal cancer among young people has been caused by the use of talc in food and medications. He failed to reference any evidence for his suggestion, which is, in any event, hard to square with the history of use of talc in medications for centuries, and the steady overall decline in the incidence of colorectal cancer in men and women.[23]

The Center for Truth in Science has sponsored rigorous systematic reviews of the evidence on cosmetic talc use and female reproductive cancers,[24] and respiratory cancers.[25] The systematic review of talc on reproductive organ cancers integrated evidence across toxicologic and epidemiologic studies, and found suggestive evidence of no association between the use of perineal talc and ovarian and endometrial cancers. The systematic review of talc use and respiratory cancers similarly integrated the available toxicologic and epistemiologic evidence, and rejected a causal association. The review reached a conclusion of suggestive evidence in the opposite direction – of no association between inhaled talc and mesothelioma or lung cancer.

The FDA talc panel was fool’s gold, and not the promised “gold standard” science. Rather than engaging with the systematic reviews sponsored by the Center, or for that matter with any systematic reviews, Commissioner Makary and his panel wallowed in anecdotes, stories, and isolated study results, without trying to identify and synthesize all the available evidence.

[1] FDA Expert Panel on Talc, “Independent Expert Panel to Evaluate Safety and Necessity of Talc in Food, Drug, and Cosmetic Products,” FDA (May 20, 2025).

[2] NTP Technical Report on the Toxicology and Carcinogenesis Studies of Talc (CAS No. 14807-96-6) in F344/N Rats and B6C3F Mice (Sept. 1993).

[3] Jay I. Goodman, “An Analysis of the National Toxicology Program’s (NTP) Technical Report (NTP TR 421) on the Toxicology and Carcinogenesis Studies of Talc,” 21 Regulatory Toxicol. & Pharmacology 244 (1995). See also Robyn L. Prueitt, Nicholas L. Drury, Ross A. Shore, Denali N. Boon & Julie E. Goodman, “Talc and human cancer: a systematic review of the experimental animal and mechanistic evidence,”  54 Critical Reviews in Toxicology  359 (2024).

[4] NTP TR-280 Toxicology and Carcinogenesis Studies of Crocidolite Asbestos (CASRN 12001-28-4) In F344/N Rats (Feed Studies) (1988).

[5] NTP TR-279 Toxicology and Carcinogenesis Studies of Amosite Asbestos (CASRN 12172-73-5) in F344/N Rats (Feed Studies) (1990).

[6] NTP TR-249 Lifetime Carcinogenesis Studies of Amosite Asbestos (CASRN 12172-73-5) in Syrian Golden Hamsters (Feed Studies) (1983).

[7] NTP TR-246 Lifetime Carcinogenesis Studies of Chrysotile Asbestos (CASRN 12001-29-5) in Syrian Golden Hamsters (Feed Studies) (1990).

[8] NTP – TR-295 Toxicology and Carcinogenesis Studies of Chrysotile Asbestos (CASRN 12001-29-5) in F344/N Rats (Feed Studies) (1985).

[9] See Richard Doll, “Mortality from Lung Cancer in Asbestos Workers,”  12 Br. J. Indus. Med. 81 (1955).

[10] See J. Christopher Wagner, C.A. Sleggs, and Paul Marchand, “Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province,” 17 Br. J. Indus. Med. 260 (1960); J. Christopher Wagner, “The discovery of the association between blue asbestos and mesotheliomas and the aftermath,” 48 Br. J. Indus. Med. 399 (1991).

[11] See “Health Hazard Progress Notes,”16 The Asbestos Worker 13 (May 1966) (“A recent decision has widened the range of compensable diseases for insulation workers even further. A member of Local No. 12. Unfortunately died of a cancer of the colon. Dr. Selikoff reported to the compensation court that his research showed that these cancers of the intestine were at least three times as common among the insulation workers as in men of the same age in the general population. Based upon Dr. Selikoff’s testimony, the Referee gave the family a compensation award, holding that the exposure to many dusts during employment was responsible for the cancer. The insurance company appealed this decision. A special panel of the Workman’s Compensation Board reviewed the matter and agreed with the Referee’s judgment and affirmed the compensation award. This was the first case in which a cancer of the colon was established as compensable and it is likely that this case will become an historical precedent.”).

[12] Irving J. Selikoff, “Epidemiology of Gastrointestinal Cancer,” 9 Envt’l Health Persp. 299 (1974).

[13] Richard Doll & Richard Peto, “The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today,” 66 J. Nat’l Cancer Instit. 1191 (1981).

[14] Richard Doll and Julian Peto, Asbestos: Effects on Health of Exposure to Asbestos 8 (1985).

[15] Jonathan M. Samet, et al., Asbestos: Selected Cancers – Institute of Medicine (2006).

[16] See Wendy Wriston Adamson, Saving Lake Superior: A Story of environmental action (1974); Frank D. Schaumburg, Judgment Reserved: A Landmark Environmental Case (1976); Robert V. Bartlett, The Reserve Mining Controversy: Science, Technology, and Environmental Quality (1980); Thomas F. Bastow, This Vast Pollution: United States of America v. Reserve Mining Company (1986); Michael E. Berndt & William C. Brice, “The origins of public concern with taconite and human health: Reserve Mining and the asbestos case,” 52 Regulatory Toxicol. & Pharmacol. S31 (2008).

[17] Reserve Mining Co. v. Lord, 529 F.2d 181 (8th Cir. 1976) (removing Judge Lord from case).

[18] See World Health Organization, Asbestos in Drinking Water (4th ed. 2021) (“no causal association between asbestos exposure via drinking-water and cancer development has been reported for any asbestos fibre type”); Jennifer Go, Nawal Farhat, Karen Leingartner, Elvin Iscan Insel, Franco Momoli, Richard Carrier & Daniel Krewski, “Review of epidemiological and toxicological studies on health effects from ingestion of asbestos in drinking water,” 54 Critical Reviews in Toxicology 856 (2024) (“Based on high-quality animal studies, an increased risk for cancer or non-cancer endpoints was not supported, aligning with findings from human studies. Overall, the currently available body of evidence is insufficient to establish a clear link between asbestos contamination in drinking water and adverse health effects.”); Kenneth D. MacRae, “Asbestos in drinking water and cancer,” 22 J. Royal Coll. Physicians 7 (1988).

[19] Francis Douglas Kelly Liddell, “Magic, Menace, Myth and Malice,” 41 Ann. Occup. Hyg. 3, 3 (1997) (“[A]n anti-asbestos lobby, based in the Mount Sinai School of Medicine of the City University of New York, promoted the fiction that asbestos was an all-pervading menace, and trumped up a number of asbestos myths for widespread dissemination, through media eager for bad news.”).

[20] Rueben R. Merliss, “Talc-Treated Rice and Japanese Stomach Cancer,” 173 Science 1141 (1971). The claim persists in the underworld of medical speculation. See E. Whitin Kiritani, “Asbestos and Stomach Cancer in Japan – A Connection?” 33 Medical Hypotheses 159 (1990).

[21] Grant N. Stemmermann & Lawrence N. Kolonel, “Talc-coated rice as a risk factor for stomach cancer,” 31 Am. J. Clin. Nutrition 2017 (1978).

[22] Paul Offit, “Understanding RFK Jr.,” Beyond the Noise (Feb. 11, 2025).

[23] American Cancer Society, “Key Statistics for Colorectal Cancer” (last revised April 28, 2025).

[24] Heather N. Lynch, Daniel J. Lauer, Olivia Messina Leleck, Rachel D. Freid, Justin Collins, Kathleen Chen, William J. Thompson, A. Michael Ierardi, Ania Urban, Paolo Boffetta & Kenneth A. Mundt, “Systematic review of the association between talc and female reproductive tract cancers,” 5 Front. Toxicol. 1157761 (2023).

[25] Heather N. Lynch, Daniel J. Lauer, William J. Thompson, Olivia Leleck, Rachel D. Freid, Justin Collins, Kathleen Chen, A. Michael Ierardi, Ania M. Urban, Michael A. Cappello, Paolo Boffetta & Kenneth A. Mundt, “Systematic review of the scientific evidence of the pulmonary carcinogenicity of talc,” 10 Front. Public Health 989111 (2022).

Posted in Asbestos, Causation, Conflicts of Interest, Evidence, Expert Witnesses, Regulation, Toxicological Evidence | No Comments »

Genetic Causes of Mesothelioma – Part One

February 17th, 2025

In serving as a peer reviewer of legal publications, I have encountered authors who assert in manuscripts that all human mesotheliomas are caused by asbestos. This assertion was false back in the 1980s when I was trying mesothelioma cases, but today the assertion is demonstrably false. The lawsuit industry and its expert witnesses have propagated the assertion relentlessly for the last four decades, and their over-zealous advocacy has distorted the discussion of causal claims in legal venues. When I have encountered these statements in manuscripts, I have suggested more accurate and felicitous descriptions, which only sometimes were adopted.

Scientists have long suspected that there were genetic determinants, and indeed causes, of human mesothelioma. Establishing this suspicion as fact has proven difficult in part because of the difficulty in conducting full genome sequencing of large numbers of mesothelioma patients. For some time, scientists have been publishing studies, however, which have undermined the dogma of the lawsuit industry. Last month, an important study was peer-reviewed and published in Science Reports, a journal in the Nature family, which further chipped away at the dogma, by showing the importance of certain BAP1 mutations in the rate of spontaneous malignant mesothelioma, in in-bred mice without asbestos exposure. The article is open access, and should be on the reading list of practicing lawyers and commentators who concern themselves with asbestos, and the issue of supposed pathognomonic diseases in the courts.[1] The medico-legal implications of the publication are obvious. Mesothelioma can result from highly penetrant genetic mutations in the absence of any asbestos exposure. I have reproduced the authors’ abstract below, but interested readers should obtain and study the entire study.

“Cancers of the mesothelium, such as malignant mesothelioma (MM), historically have been attributed solely to exposure to asbestos. Recent large scale genetic and genomic functional studies now show that approximately 20% of all human mesotheliomas are causally linked to highly penetrant inherited (germline) pathogenic mutations in numerous cancer related genes. The rarity of these mutations in humans makes it difficult to perform statistically conclusive genetic studies to understand their biological effects. This has created a disconnect between functional and epidemiological studies. However, since the molecular pathogenesis of MM in mice accurately recapitulates that of human disease, this disconnect between functional and epidemiological studies can be overcome by using inbred mouse strains that harbor mutation(s) in genes involved in the disease. Most mouse studies have focused on the effect of asbestos exposure, leaving the effects of genetic mutations in the absence of exposure understudied. Here, using existing peer-reviewed studies, we investigate the rate of spontaneous MM among mice with and without germline genetic mutations, in the absence of asbestos exposure. We leveraged these published data to generate a historical control dataset (HCD) to allow us to improve statistical power and account for genetic heterogeneity between studies. Our Bayesian analyses indicate that the odds of spontaneous MM among germline BAP1 mutant mice is substantially larger than that of wildtype mice. These results support the existing biological study findings that mesotheliomas can arise in the presence of pathogenic germline mutations, independently of asbestos exposure.”

[1] Dahlia M. Nielsen, Mei Hsu, Michael Zapata III, Giovanni Ciavarra & Leonel van Zyl, “Bayesian analysis of the rate of spontaneous malignant mesothelioma among BAP1 mutant mice in the absence of asbestos exposure,” 15 Sci. Reports 169 (2025).

Posted in Asbestos, Causation | No Comments »

Blame It On Delaney – Rats to You

January 16th, 2025

Yesterday, the FDA gave notice that it was banning Red Dye number 3 from foods and pharmaceuticals. Technically, it revoked the authorization for the use of the dye.[1]

Formally, FDA granted a petition by an “white hat” and “empty head” consortium of individuals and NGOs that included the Center for Science in the Public Interest, Breast Cancer Prevention Partners, Center for Environmental Health, Center for Food Safety, Chef Ann Foundation, Children’s Advocacy Institute, Consumer Federation of America, Consumer Reports, Defend Our Health, Environmental Defense Fund, Environmental Working group, Feingold Association of the United States, Food & Water Watch, Health Babies Bright Futures, Life Time Foundation, Momsrising Prevention Institute, Public Citizen, Public Health Institute, Public Interest Research Research Group, Real Food for Kids, Lisa Y. Lefferts, Linda S. Birnbaum, and Philip J. Landrigan.[2]

As the FDA notice explained, a federal statute known as the “the Delaney Clause,” which was added by Congress in 1960 to the Color Additives Amendment to the Food, Drug and Cosmetics Act, prohibits FDA authorization of a food color additive that has been found to induce cancer in humans or animals. The FDA agreed with petitioners that there were two studies that found higher rates of cancer in laboratory male rats exposed to high levels of red dye #3. The agency pointed out that:

“The way that FD&C Red No. 3 causes cancer in male rats does not occur in humans. Relevant exposure levels to FD&C Red No. 3 for humans are typically much lower than those that cause the effects shown in male rats. Studies in other animals and in humans did not show these effects; claims that the use of FD&C Red No. 3 in food and in ingested drugs puts people at risk are not supported by the available scientific information.”

The FDA rule making extrapolates across species, across dose levels, across sex, without evidence and indeed against evidence. Nonetheless, the 65 year old Delaney Clause, based upon out-dated and invalidated scientific methods, required the FDA action. Even the IARC does not consider red dye #3 a human carcinogen. While we can all agree that inbred laboratory male rats should not be fed food colored with red dye number 3, we have to ask ourselves are we more like this subset of the rat world, or more like mice and hamsters?

The formal FDA decision is dated today, January 16, 2025, and can be found in the Federal Register.[3] Richard Williams, a former FDA officer, called the rule making “another failed attempt” at educating and protecting consumers.[4]

[1] FDA, “FDA to Revoke Authorization for the Use of Red No. 3 in Food and Ingested Drugs,” (Jan. 15, 2025).

[2] Color additive petition pursuant to 21 U.S.C. §§ 379e, 721(b)(1) to remove FD&C Red No. 3 from the permanent list of color additives approved for use in food and dietary supplements, 21 C.F.R. § 74.303, and for use in ingested drugs, 21 C.F.R. § 74.1303, because the FDA has found that the additive induces cancer and is unsafe (Oct. 24, 2022).

[3] “Color Additive Petition From Center for Science in the Public Interest, et al.; Request To Revoke Color Additive Listing for Use of FD&C Red No. 3 in Food and Ingested Drugs – A Rule by the Food and Drug Administration,” Fed. Reg. (Jan. 16, 2025).

[4] Richard Williams, “Red Dye 3, New Nutrition Labels, and More,” (Jan. 16, 2025).

Posted in Causation, Regulation, Scientific Misconduct | 1 Comment »

Professor Lahav’s Radically Misguided Treatment of Chancy Tort Causation

September 27th, 2024

In the 19th and early 20th century, scientists and lay people usually conceptualized causation as “deterministic.” Their model of science was perhaps what was called Newtonian, in which observations were invariably described in terms of identifiable forces that acted upon antecedent phenomena. The universe was akin to a pool table, with the movement of the billiard balls fully explained by their previous positions, mass, and movements. There was little need for probability to describe events or outcomes in such a universe.

The 20th century ushered in probabilistic concepts and models in physics and biology. Because tort law is so focused on claims of bodily integrity and harms, I am focused here on claimed health effects. Departing from the Koch-Henle postulates and our understanding of pathogen-based diseases, the latter half of the 20th century saw the rise of observational epidemiology and scientific conclusions about stochastic processes and effects that could best be understood in terms of probabilities, with statistical inferences from samples of populations. The language of deterministic physics failed to do justice to epidemiologic evidence or conclusions. Modern medicine and biology invoked notions of base rates for chronic diseases, which rates might be modified by environmental exposures.

In the wake of the emerging science of epidemiology, the law experienced a new horizon on which many claimed tortogens did not involve exposures uniquely tied to the harms alleged. Rather, the harms asserted were often diseases of ordinary life, but with that suggested the harms were quantitatively more prevalent or incident among people exposed to the alleged tortogen. Of course, the backwaters of tort law saw reactionary world views on trial, as with claims of trauma-induced cancer cases, which are with us still. Nonetheless, slowly but not always steadily, the law came to grips with probability and statistical evidence.

In law, as in science, a key component of causal attribution is counterfactual analysis. If A causes B, then if in the same world, ceteris paribus, we do not have A, then we don’t have B. Counterfactual analysis applies as much to stochastic processes that are causally influenced by rate changes, as they apply to the Newtonian world of billiard balls. Some writers in the legal academy, however, would opportunistically use the advent of probabilistic analyses of health effects to dispose of science altogether. No one has more explicitly exploited the opportunity than Professor Alexandra Lahav.

In an essay published in 2022, Professor Lahav advanced extraordinary claims about probabilistic causation, or what she called “chancy causation.”[1] The proffered definition of chancy causation is bumfuzzling. Lahav provides an example of an herbicide that is “associated” with the type of cancer that the heavily exposed plaintiff developed. She tells us that:

“[t]here is a chance that the exposure caused his cancer, and a chance that it did not. Probability follows certain rules, or tendencies, but these regular laws do not abolish chance. This is a common problem in modern life, where much of what we know about medicines, interventions, and the chemicals to which we are exposed is probabilistic. Following the philosophical literature, I call this phenomenon chancy causation.”[2]

So the rules of probability do not abolish chance? It is hard to know what Lahav is trying to say here. Probability quantifies chance, and gives us an understanding of phenomena and their predictability. When we can model an empirical process with a probability distribution, such as one that is independent and identically distributed, we can often make and test quantitative inferences about the anticipated phenomena.

Lahav vaguely acknowledges that her term, “chancy causation” is borrowed, but she does not give credit to the many authors who have used it before.[3] Lahav does note that the concept of probabilistic causation used in modern-day risk factor epidemiology is different from the deterministic causal claims that dominated tort law in the 19th and the first half of the 20th century. Lahav claims that chancy causation is inconsistent with counterfactual analysis, but she cites no support for her claim, which is demonstrably false. If we previously saw the counterfactual of if A then B, as key to causality, we can readily restate the counterfactual as a probability: A probably causes B. On a counterfactual analysis, then if we do not have A as an antecedent, then we probably do not have B. For a classic tortogen such as tobacco smoking, we can say confidently that tobacco smoking probably causes lung cancer. And for a given instance of lung cancer, we can say based upon the entire evidentiary display, that if a person did not smoke tobacco, he would probably not have developed lung cancer. Of course, the correspondence is not 100 percent, which is only to say that it is probabilistic. There are highly penetrant genetic mutations that may be the cause of a given lung cancer case. We know, however, that such mutations do not cause or explain the large majority of lung cancer cases.

Contrary to Lahav’s ipse dixits, tort law can incorporate, and has accommodated, both general and specific causation in terms of probabilistic counterfactuals. The modification requires us, of course, to address the baseline situation as a rate or frequency of events, and the post-exposure world as one with a modified rate or frequency. Without confusion or embarrassment, we can say that the exposure is the cause of the change in event rates. Modern physics similarly addresses whether we must be content with probability statements, rather than precise deterministic “billiard ball” physics, which is so useful in a game of snooker, but less so in describing the position of sub-atomic particles. In the first half of the 20th century, the biological sciences learned with some difficulty that it must embrace probabilistic models, in genetic science, as well as in epidemiology. Many biological causation models are completely stated in terms of probabilities that are modified by specified conditions.

Lahav intends for her rejection of counterfactual causality to do a lot of work in her post-modern program. By falsely claiming that chancy causation has no factual basis, Lahav jumps to the conclusion that what the law calls for is nothing but “policy,”[4] and “normative decision.”[5] Having fabricated the demise of but-for causation in the context of probabilistic relationships, Lahav suggests that tort law can pretend that the causation question is nothing more than a normative analysis of the defendant’s conduct. (Perhaps it is more than a tad revealing that she does not see that the plaintiff’s conduct is involved in the normative judgment.) Of course, tort law already has ample room for policy and normative considerations built into the concepts of duty and breach of duty.

As we saw with the lung cancer example above, the claim that tobacco smoking probably caused the smoker to develop lung cancer can be entirely factual, and supported by a probabilistic judgment. Lahav calls her erroneous move “pragmatic,” although it has no relationship to the philosophical pragmatism of Peirce or Quine. Lahav’s move is an incorrect misrepresentation of probability and of epidemiologic science in the name of compensation free-for-alls. Obtaining a heads in the flip of a fair coin has a probability of 50%; that is a fact, not a normative decision, even though it is, to use Lahav’s vocabulary, “chancy.”

Lahav’s argument is not always easy to follow. In one place, she uses “chancy” to refer to the posterior probability of the correctness of the causal claim:

“the counterfactual standard can be successfully defended against by the introduction of chance. The more conflicting studies, the “more chancy” the causation. By that I do not mean proving a lower probability (although this is a good result from a defense point of view) but rather that more, different study results create the impression of irreducible chanciness, which in turn dictates that the causal relation cannot be definitively proven.”[6]

This usage, which clearly refers to the posterior probability of a claim, is not necessarily limited to so-called non-deterministic phenomena. People could refer to any conclusion, based upon conflicting evidence of deterministic phenomena, as “chancy.”

Lurking in her essay is a further confusion between the posterior probability we might assign to a claim, or to an inference from probabilistic evidence, and the probability of random error. In an interview conducted by Felipe Jiménez,[7] Lahav was more transparent in her confusion, and she explicitly commited the transpositional fallacy with her suggestion that customary statistical standards (statistical significance) ensure that even small increased risks, say of 30%, are known to a high degree of certainty.

Despite these confusions, it seems fairly clear that Lahav is concerned with stochastic causal processes, and most of her examples evidence that concern. Lahav poses a hypothetical in which epidemiologic studies show smokers have a 20% increased risk of developing lung cancer compared with non-smokers.[8] Given that typical smoking histories convey relative risks of 20 to 30, or increased risks of 2,000 to 3,000%, Lahav’s hypothetical may readers think she is shilling for tobacco compaies. In any event, in the face of a 20% increased risk (or relative rsk of 1.2), Lahav acknowledges that the probability of a smoker’s developing lung cancer is higher than that of a non-smoker, but “in any particular case the question whether a patient’s lung cancer was caused by smoking is uncertain.” This assertion, however, is untrue; the question is not “uncertain.” She has provided a certain quantification of the increased risk. Furthermore, her hypothetical gives us a good deal of information on which we can say that smoking probably did not result in the patient’s lung cancer. Causation may be chancy because it is based upon a probabilistic inference, but the chances are actual known, and they are low.

Lahav posits a more interesting hypothetical when she considers a case in which there is an 80% chance that a person’s lung cancer is attributable to smoking.[9] We can understand this hypothetical better if we reframe it as classic urn probability problem. In a given (large) population of non-smokers, we expect 100 lung cancers per year. In a population of smokers, otherwise just like the population of non-smokers, we observe 500 lung cancers. Of the observed number, 100 were “expected” because they happen without exposure to the putative causal agent, and 400 are “excess.”The relative risk would be 5, or 400% increased risk, and still well below the actual measure of risk from long-term smoking, but the attributable risk would be [(RR-1)/RR] or 0.8 (or 80%). If we imagine an urn with 100 white “expected” balls, and 400 red “excess” balls added, then any given draw from the urn, with replacement, yields an 80% probability of a red ball, or an excess case. Of course, if we can see the color, we may come to a consensus judgment that the ball is actually red. But on our analogy to discerning the cause of a given lung cancer, we have at present nothing by way of evidence with which to call the question, and so it remains “chancy” or probabilistic. The question is not, however, in any way normative. The answer is different quantitatively in the 20% and in the 400% hypotheticals.

Lahav asserts that we are in a state of complete ignorance once a smoker has lung cancer.[10] This is not, however, true. We have the basis for a probabilistic judgment that will probably be true. It may well be true that the probability of attribution will be affected by the probability that the relative risk = 5 is correct. If the posterior probability for the claim that smoking causes lung cancer by increasing its risk 400% is only 30%, then of course, we could not make the attribution in a given case with an 80% probability of correctness. In actual litigation, the argument is often framed on an assumption arguendo that the increased risk is greater than two, so that only the probability of attribution is involved. If the posterior probability of the claim that exposure to the tortogen increased risk by 400% or 20,000% was only 0.49, then the plaintiff would lose. If the posterior probability of the increased risk was greater than 0.5, the finder of fact could find that the specific causation claim had been carried if the magnitude of the relative risk, and the attributable risk, were sufficiently large. This inference on specific causation would not be a normative judgment; it would be guided by factual evidence about the magnitude of the relevant increased risk.

Lahav advances a perverse skepticism that any inferences about individuals can be drawn from information about rates or frequencies in groups of similar individuals.  Yes, there may always be some debate about what is “similar,” but successive studies may well draw the net tighter around what is the appropriate class. Lahav’s skepticism and her outright denialism about inferences from general causation to specific causation, are common among some in the legal academy, but it ignores that group to individual inferences are drawn in epidemiology in multiple contexts. Regressions for disease prediction are based upon individual data within groups, and the regression equations are then applied to future individuals to help predict those individuals’ probability of future disease (such as heart attack or breast cancer), or their probability of cancer-free survival after a specific therapy. Group to individual inferences are, of course, also the basis for prescribing decisions in clinical medicine.  These are not normative inferences; they are based upon evidence-based causal thinking about probabilistic inferences.

In the early tobacco litigation, defendants denied that tobacco smoking caused lung cancer, but they argued that even if it did, and the relative risk were 20, then the specific causation inference in this case was still insecure because the epidemiologic study tells us nothing about the particular case. Lahav seems to be channeling the tobacco-company argument, which has long since been rejected on the substantive law of causation. Indeed, as noted, epidemiologists do draw inferences about individual cases from population-based studies when they invoke clinical prediction models such as the Framingham cardiovascular risk event model, or the Gale breast cancer prediction model. Physicians base important clinical interventions, both pharmacologic and surgical, for individuals upon population studies. Lahav asserts, without evidence, that the only difference between an intervention based upon an 80% or a 30% probability is a “normative implication.”[11] The difference is starkly factual, not normative, and describes a long-term likelihood of success, as well as an individual probability of success.

Post-Modern Causation

What we have in Lahav’s essay is the ultimate post-modern program, which asserts, without evidence, that when causation is “chancy,” or indeterminate, courts leave the realm of science and step into the twilight zone of “normative decisions.” Lahav suggests that there is an extreme plasticity to the very concept of causation such that causation can be whatever judges want it to be. I for one sincerely doubt it. And if judges make up some Lahav-inspired concept of normative causation, the scientific community would rightfully scoff.

Establishing causation can be difficult, and many so-called mass tort litigations have failed for want of sufficient, valid evidence supporting causal claims. The late Professor Margaret Berger reacted to this difficulty in a more forthright way by arguing for the abandonment of general causation, or cause-in-fact, as an element of tort claims under the law.[12] Berger’s antipathy to requiring causation manifested in her hostility to judicial gatekeeping of the validity of expert witness opinions. Her animus against requiring causation and gatekeeping under Rule 702 was so strong that it exceeded her lifespan. Berger’s chapter in the third edition of the Reference Manual on Scientific Evidence, which came out almost one year after her death, embraced the First Circuit’s notorious anti-Daubert decision in Milward, which also post-dated her passing.[13]

Professor Lahav has previously expressed a distain for the causation requirement in tort law. In an earlier paper, “The Knowledge Remedy,” Lahav argued for an extreme, radical precautionary principle approach to causation.[14] Lahav believes that the likes of David Michaels have “demonstrated” that manufactured uncertainty is a genuine problem, but not one that affects her main claims. Remarkably, Lahav sees no problem with manufactured certainty in the advocacy science of many authors or the lawsuit industry.[15] In “Chancy Causation,” Lahav thus credulously repeats Michaels’ arguments, and goes so far as to describe Rule 702 challenges to causal claims as having the “negative effect” of producing “incentives to sow doubt about epidemiologic studies using methodological battles, a strategy pioneered by the tobacco companies … .”[16] Lahav’s agenda is revealed by the absence of any corresponding concern about the negative effect of producing incentives to overstate the findings, or the validity of inferences, in order to obtain an unwarranted and unsafe verdicts for claimants.

[1] Alexandra D. Lahav, “Chancy Causation in Tort,” 15 J. Tort L. 109 (2022) [hereafter Chancy Causation].

[2] Chancy Causation at 110.

[3] See, e.g., David K. Lewis, Philosophical Papers: Volume 2 175 (1986); Mark Parascandola, “Evidence and Association: Epistemic Confusion in Toxic Tort Law,” 63 Phil. Sci. S168 (1996).

[4] Chancy Causation at 109.

[5] Chancy Causation at 110-11.

[6] Chancy Causation at 129.

[7] Felipe Jiménez, “Alexandra Lahav on Chancy Causation in Tort,” The Private Law Podcast (Mar. 29, 2021).

[8] Chancy Causation at 115.

[9] Chancy Causation at 116-17.

[10] Chancy Causation at 117.

[11] Chancy Causation at 119.

[12] Margaret A. Berger, “Eliminating General Causation: Notes towards a New Theory of Justice and Toxic Torts,” 97 Colum. L. Rev. 2117 (1997).

[13] Milward v. Acuity Specialty Products Group, Inc., 639 F.3d 11 (1st Cir. 2011), cert. denied sub nom., U.S. Steel Corp. v. Milward, 132 S. Ct. 1002 (2012).

[14] Alexandra D. Lahav, “The Knowledge Remedy,” 98 Texas L. Rev. 1361 (2020). See “The Knowledge Remedy Proposal” Tortini (Nov. 14, 2020).

[15] Chancy Causation at 118 (citing plaintiffs’ expert witness David Michaels, The Triumph of Doubt: Dark Money and the Science of Deception (2020), among others).

[16] Chancy Causation at 129.

Posted in Causation, Evidence, Rule 702, statistical evidence | 1 Comment »

800 Plaintiffs Fail to Show that Glyphosate Caused Their NHL

September 11th, 2024

Last week, Barbara Billauer, at the American Council on Science and Health[1] website, reported on the Australian court that found insufficient scientific evidence to support plaintiffs’ claims that they had developed non-Hodgkin’s lymphoma (NHL) from their exposure to Monsanto’s glyphosate product. The judgment had previously been reported by the Genetic Literacy Project,[2] which republished an Australian news report from July.[3] European news media seemed more astute in reporting the judgment, with The Guardian[4] and Reuters reporting the court decision in July.[5] The judgment was noteworthy because the mainstream and legal media in the United States generally ignored the development.  The Old Gray Lady and the WaPo in the United States, both of which have covered previous glyphosate cases in the United States, sayeth naught. Crickets at Law360.

On July 24, 2024, Justice Michael Lee, for the Federal Court of Australia, ruled that there was insufficient evidence to support the claims of 800 plaintiffs that their NHL had been caused by glyphosate exposure.[6] Because plaintiffs’ claims were aggregated in a class, the judgment against the class of 800 or so claimants, was the most significant judgment in glyphosate litigation to date.

Justice Lee’s opinion is over 300 pages long, and I have had a chance only to skim it. Regardless of how the Australian court handled various issues, one thing is indisputable: the court has given a written record of its decision processes for the world to assess, critique, validate, or refute. Jury trials provide no similar opportunity to evaluate the reasoning processes (vel non) of the decision maker. The absence of transparency, and an opportunity to evaluate the soundness of verdicts in complex medical causation, raises the question whether jury trials really satisfy the legal due process requirements of civil adjudication.

[1] Barbara Pfeffer Billauer, “The RoundUp Judge Who Got It,” ACSH (Aug. 29, 2024).

[2] Kristian Silva, “Insufficient evidence that glyphosate causes cancer: Australian court tosses 800-person class action lawsuit,” ABC News (Australia) (July 26, 2024).

[3] Kristian Silva, “Major class action thrown out as Federal Court finds insufficient evidence to prove weedkiller Roundup causes cancer,” ABC Australian News (July 25, 2024).

[4] Australian Associated Press, “Australian judge dismisses class action claiming Roundup causes cancer,” The Guardian (July 25, 2024).

[5] Peter Hobson and Alasdair Pal, “Australian judge dismisses lawsuit claiming Bayer weedkiller causes blood cancer,” Reuters (July 25, 2024).

[6] McNickle v. Huntsman Chem. Co. Australia Pty Ltd (Initial Trial) [2024] FCA 807.

Posted in Causation, Rule 702, Scientific Evidence, Toxicological Evidence | 2 Comments »

Zhang’s Glyphosate Meta-Analysis Succumbs to Judicial Scrutiny

August 5th, 2024

Back in March 2015, the International Agency for Research on Cancer (IARC) issued its working group’s monograph on glyphosate weed killer. The report classified glyphosate as a “probable carcinogen,” which is highly misleading. For IARC, the term “probable” does not mean more likely than not, or for that matter, probable does not have any quantitative meaning. The all-important statement of IARC methods, “The Preamble,” makes this clear.[1] 

In the case of glyphosate, the IARC working group concluded that the epidemiologic evidence for an association between glyphosate exposure and cancer (specifically non-Hodgkins lymphoma (NHL)), was limited, which is IARC’s euphemism for insuffcient. Instead of epidemiology, IARC’s glyphosate conclusion was based largely upon rodent studies, but even the animal evidence relied upon by IARC was dubious. The IARC working group cherry picked a few arguably “positive” rodent study results with increases in tumors, while ignoring exculpatory rodent studies with decreasing tumor yield.[2]

Although the IARC hazard classification was uncritically embraced by the lawsuit industry, most regulatory agencies, even indulging precautionary principle reasoning, rejected the claim of carcinogenicity. The United States  Environmental Protection Agency (EPA), European Food Safety Authority, Food and Agriculture Organization (in conjunction with World Health Organization, European Chemicals Agency, Health Canada, German Federal Institute for Risk Assessment, among others, found that the scientific evidence did not support the claim that glyphosate causes NHL. The IARC monograph very quickly after publication became the proximate cause of a huge litigation effort by the lawsuit industry against Monsanto.

The personal injury cases against Monsanto, filed in federal court, were aggregated for pre-trial hearing, before Judge Vince Chhabria, of the Northern District of California, as MDL 2741. Judge Chhabria denied Monsanto’s early Rule 702 motions, and thus cases proceeded to trial, with mixed results.

In 2019, the Zhang study, a curious meta-analysis of some of the available glyphosate epidemiologic studies appeared in Mutation Research / Reviews in Mutation Research, a toxicology journal that seemed an unlikely venue for a meta-analysis of epidemiologic studies. The authors combined selected results from one large cohort study, the Agricultural Health Study, along with five case-control studies, to reach a summary relative risk of 1.41 (95% confidence interval 1.13-1.75).[3] According to the authors, their “current meta-analysis of human epidemiological studies suggests a compelling link between exposures to GBHs [glyphosate] and increased risk for NHL.”

The Zhang meta-analysis was not well reviewed in regulatory and scientific circles. The EPA found that Zhang used inappropriate methods in her meta-analysis.[4] Academic authors also panned the Zhang meta-analysis in both scholarly,[5] and popular articles.[6] The senior author of the Zhang paper, Lianne Sheppard, a Professor in the University of Washington Departments of Environmental  and  Occupational Health Sciences, and Biostatistics, attempted to defend the study, in Forbes.[7] Professor Geoffrey Kabat very adeptly showed that this defense was futile.[8] Despite the very serious and real objections to the validity of the Zhang meta-analysis, plaintiffs’ expert witnesses, such as Beate Ritz, an epidemiologist with U.C.L.A. testified that she trusted and relied upon the analysis.[9]

For five years, the Zhang study was a debating point for lawyers and expert witnesses in the glyphosate litigation, without significant judicial gatekeeping. It took the entrance of Luoping Zhang herself as an expert witness in the glyphosate litigation, and the procedural oddity of her placing exclusive reliance upon her own meta-analysis, to bring the meta-analysis into the unforgiving light of judicial scrutiny.

Zhang is a biochemist and toxicologist, in the University of California, Berkeley. Along with two other co-authors of her 2019 meta-analysis paper, she had been a board member of the EPA’s 2016 scientific advisory panel on glyphosate. After plaintiffs’ counsel disclosed Zhang as an expert witness, she disclosed her anticipated testimony, as is required by Federal Rule of Civil Procedure 26, by attaching and adopting by reference the contents of two of her published papers. The first paper was her 2019 meta-analysis; the other paper discussed putative mechanisms. Neither paper concluded that glyphosate causes NHL. Zhang’s disclosure did not add materially to her 2019 published analysis of six epidemiologic studies on glyphosate and NHL.

The defense challenged the validity of Dr. Zhang’s proffered opinions, and her exclusive reliance upon her own 2019 meta-analysis required the MDL court to pay attention to the failings of that paper, which had previously escaped critical judicial scrutiny. In June 2024, after an oral hearing in Bulone v. Monsanto, at which Dr. Zhang testified, Judge Chhabria ruled that Zhang’s proffered testimony, and her reliance upon her own meta-analysis was “junk science.”[10]

Judge Chhabria, perhaps encouraged by the recently fortifying amendment to Rule 702, issued a remarkable opinion that paid close attention to the indicia of validity of an expert witness’s opinion and the underlying meta-analysis. Judge Chhabria quickly spotted the disconnect between Zhang’s published papers and what is required for an admissible causation opinion. The mechanism paper did not address the extant epidemiology, and both sides in the MDL had emphasized that the epidemiology was critically important for determining whether there was, or was not, causation.

Zhang’s meta-analysis did evaluate some, but not all, of the available epidemiology, but the paper’s conclusion stopped considerably short of the needed opinion on causation. Zhang and colleagues had concluded that there was a “compelling link” between exposures to [glyphosate-based herbicides] and increased risk for NHL. In their paper’s key figure, show casing the summary estimate of relative risk of 1.41 (95% C.I., 1.13 -1.75), Zhang and her co-authors concluded only that exposure was “associated with an increased risk of NHL.” According to Judge Chhabria, in incorporating her 2019 paper into her Rule 26 report, Zhang failed to add a proper holistic causation analysis, as had other expert witnesses who had considered the Bradford Hill predicates and considerations.

Judge Chhabria picked up on another problem that has both legal and scientific implications. A meta-analysis is out of date as soon as a subsequent epidemiologic study becomes available, which would have satisfied the inclusion criteria for the meta-analysis. Since publishing her meta-analysis in 2019, additional studies had in fact been published. At the hearing, Dr. Zhang acknowledged that several of them would qualify for inclusion in the meta-analysis, per her own stated methods. Her failure to update the meta-analysis made her report incomplete and inadmissible for a court matter in 2024.

Judge Chhabria might have stopped there, but he took a closer look at the meta-analysis to explore whether it was a valid analysis, on its own terms. Much as Chief Judge Nancy Rosenstengel had done with the made-for-litigation meta-analysis concocted by Martin Wells in the paraquat litigation,[11] Judge Chhabria examined whether Zhang had been faithful to her own stated methods. Like Chief Judge Rosenstengel’s analysis, Judge Chhabria’s analysis stands as a strong rebuttal to the uncharitable opinion of Professor Edward Cheng, who has asserted that judges lack the expertise to evaluate the “expert opinions” before them.[12]

Judge Chhabria accepted the intellectual challenge that Rule 702 mandates. With the EPA memorandum lighting the way, Judge Chhabria readily discerned that “the challenged meta-analysis was not reliably performed.” He declared that the Zhang meta-analysis was “junk science,” with “deep methodological problems.”

Zhang claimed that she was basing the meta-analysis on the subgroups of six studies with the heaviest glyphosate exposure. This claim was undermined by the absence of any exposure-response gradient in the study deemed by Zhang to be of the highest quality. Furthermore, of the remaining five studies, three studies failed to provide any exposure-dependent analysis other than a comparison of NHL rates among “ever” versus “never” glyphosate exposure. As a result of this heterogeneity, Zhang used all the data from studies without exposure characterizations, but only limited data from the other studies that analyzed NHL by exposure levels. And because the highest quality study was among those that provided exposure level correlations, Zhang’s meta-analysis used only some of the data from it.

The analytical problems created by Zhang’s meta-analytical approach were compounded by the included studies’ having measured glyphosate exposures differently, with different cut-points for inclusion as heavily exposed. Some of the excluded study participants would have heavier exposure than those included in the summary analysis.

In the universe of included studies, some provided adjusted results from multi-variate analyses that included other pesticide exposures. Other studies reported only unadjusted results. Even though Zhang’s method stated a preference for adjusted analyses, she inexplicably failed to use adjusted data in the case of one study that provided both adjusted and unadjusted results.

As shown in Judge Chhabria’s review, Zhang’s methodological errors created an incoherent analysis, with methods that could not be justified. Even accepting its own stated methodology, the meta-analysis was an exercise in cherry picking. In the court’s terms, it was, without qualification, “junk science.”

After the filing of briefs, Judge Chhabria provided the parties an oral hearing, with an opportunity for viva voce testimony. Dr. Zhang thus had a full opportunity to defend her meta-analysis. The hearing, however, did not go well for her. Zhang could not talk intelligently about the studies included, or how they defined high exposure. Zhang’s lack of familiarity with her own opinion and published paper was yet a further reason for excluding her testimony.

As might be expected, plaintiffs’ counsel attempted to hide behind peer review. Plaintiffs’ counsel attempted to shut down Rule 702 scrutiny of the Zhang meta-analysis by suggesting that the trial court had no business digging into validity concerns given that Zhang had published her meta-analysis in what apparently was a peer reviewed journal. Judge Chhabria would have none of it. In his opinion, publication in a peer-reviewed journal cannot obscure the glaring methodological defects of the relied upon meta-analysis. The court observed that “[p]re-publication editorial peer review, just by itself, is far from a guarantee of scientific reliability.”[13] The EPA memorandum was thus a more telling indicator of the validity issues than the publication in a nominally peer-reviewed journal.

Contrary to some law professors who are now seeking to dismantle expert witness gatekeeping as beyond a judge’s competence, Judge Chhabria dismissed the suggestion that he lacked the expertise to adjudicate the validity issues. Indeed, he displayed a better understanding of the meta-analytic process than did Dr. Zhang. As the court observed, one of the goals of MDL assignments was to permit a single trial judge to have time to engage with the scientific issues and to develop “fluency” in the relevant scientific studies. Indeed, when MDL judges have the fluency in the scientific concepts to address Rule 702 or 703 issues, it would be criminal for them to ignore it.

The Bulone opinion should encourage lawyers to get “into the weeds” of expert witness opinions. There is nothing that a little clear thinking – and glyphosate – cannot clear away. Indeed, now that the weeds of Zhang’s meta-analysis are cleared away, it is hard to fathom that any other expert witness can rely upon it without running afoul of both Federal Rules of Evidence 702 and 703.

There were a few issues not addressed in Bulone. As seen in her oral hearing testimony, Zhang probably lacked the qualifications to proffer the meta-analysis. The bar for qualification as an expert witness, however, is sadly very low. One other issue that might well have been addressed is Zhang’s use of a fixed effect model for her meta-analysis. Considering that she was pooling data from cohort and case-control studies, some with and some without adjustments for confounders, with different measures of exposure, and some with and some without exposure-dependent analyses, Zhang and her co-authors were not justified in using a fixed effect model for arriving at a summary estimate of relative risk. Admittedly, this error could easily have been lost in the flood of others.

Postscript

Glyphosate is not merely a scientific issue. Its manufacturer, Monsanto, is the frequent target of media outlets (such as Telesur) from autocratic countries, such as Communist China and its client state, Venezuela.[14]

天安门广场英雄万岁

[1] “The IARC-hy of Evidence – Incoherent & Inconsistent Classifications of Carcinogenicity,” Tortini (Sept. 19, 2023).

[2] Robert E Tarone, “On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen,” 27 Eur. J. Cancer Prev. 82 (2018).

[3] Luoping Zhang, Iemaan Rana, Rachel M. Shaffer, Emanuela Taioli, Lianne Sheppard, “Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: A meta-analysis and supporting evidence,” 781 Mutation Research/Reviews in Mutation Research 186 (2019).

[4] David J. Miller, Acting Chief Toxicology and Epidemiology Branch Health Effects Division, U.S. Environmental Protection Agency, Memorandum to Christine Olinger, Chief Risk Assessment Branch I, “Glyphosate: Epidemiology Review of Zhang et al. (2019) and Leon et al. (2019) publications for Response to Comments on the Proposed Interim Decision” (Jan. 6, 2020).

[5] Geoffrey C. Kabat, William J. Price, Robert E. Tarone, “On recent meta-analyses of exposure to glyphosate and risk of non-Hodgkin’s lymphoma in humans,” 32 Cancer Causes & Control 409 (2021).

[6] Geoffrey Kabat, “Paper Claims A Link Between Glyphosate And Cancer But Fails To Show Evidence,” Science 2.0 (Feb. 18, 2019).

[7] Lianne Sheppard, “Glyphosate Science is Nuanced. Arguments about it on the Internet? Not so much,” Forbes (Feb. 20, 2020).

[8] Geoffrey Kabat, “EPA Refuted A Meta-Analysis Claiming Glyphosate Can Cause Cancer And Senior Author Lianne Sheppard Doubled Down,” Science 2.0 (Feb. 26, 2020).

[9] Maria Dinzeo, “Jurors Hear of New Study Linking Roundup to Cancer,” Courthouse News Service (April 8, 2019).

[10] Bulone v. Monsanto Co., Case No. 16-md-02741-VC, MDL 2741 (N.D. Cal. June 20, 2024). See Hank Campbell, “Glyphosate legal update: Meta-study used by ambulance-chasing tort lawyers targeting Bayer’s Roundup as carcinogenic deemed ‘junk science nonsense’ by trial judge,” Genetic Literacy Project (June 24, 2024).

[11] In re Paraquat Prods. Liab. Litig., No. 3:21-MD-3004-NJR, 2024 WL 1659687 (S.D. Ill. Apr. 17, 2024) (opinion sur Rule 702 motion), appealed sub nom., Fuller v. Syngenta Crop Protection, LLC, No. 24-1868 (7th Cir. May 17, 2024). See “Paraquat Shape-Shifting Expert Witness Quashed,” Tortini (April 24, 2024).

[12] Edward K. Cheng, “The Consensus Rule: A New Approach to Scientific Evidence,” 75 Vanderbilt L. Rev. 407 (2022). See “Cheng’s Proposed Consensus Rule for Expert Witnesses,” Tortini (Sept. 15, 2022); “Further thoughts on Cheng’s Consensus Rule,” Tortini (Oct. 3, 2022).

[13] Bulone, citing Valentine v. Pioneer Chlor Alkali Co., 921 F. Supp. 666, 674-76 (D. Nev. 1996), for its distinction between “editorial peer review” and “true peer review,” with the latter’s inclusion of post-publication assessment of a paper as really important for Rule 702 purposes.

[14] Anne Applebaum, Autocracy, Inc.: The Dictators Who Want to Run the World 66 (2024).

Posted in Causation, Confounding, Expert Witnesses, Meta-analysis, Rule 702, Rule 703, statistical evidence | 37 Comments »

Paraquat Shape-Shifting Expert Witness Quashed

April 24th, 2024

Another multi-district litigation (MDL) has hit a jarring speed bump. Claims for Parkinson’s disease (PD), allegedly caused by exposure to paraquat dichloride (paraquat), were consolidated, in June 2021, for pre-trial coordination in MDL No. 3004, in the Southern District of Illinois, before Chief Judge Nancy J. Rosenstengel. Like many health-effects litigation claims, the plaintiffs’ claims in these paraquat cases turn on epidemiologic evidence. To make their causation case in the first MDL trial cases, plaintiffs’ counsel nominated a statistician, Martin T. Wells, to present their causation case. Last week, Judge Rosenstengel found Wells’ opinion so infected by invalid methodologies and inferences as to be inadmissible under the most recent version of Rule 702.[1] Summary judgment in the trial cases followed.[2]

Back in the 1980s, paraquat gained some legal notoriety in one of the most retrograde Rule 702 decisions.[3] Both the herbicide and Rule 702 survived, however, and they both remain in wide use. For the last two decades, there has been a widespread challenges to the safety of paraquat, and in particular there have been claims that paraquat can cause PD or parkinsonism under some circumstances.  Despite this background, the plaintiffs’ counsel in MDL 3004 began with four problems.

First, paraquat is closely regulated for agricultural use in the United States. Under federal law, paraquat can be used to control the growth of weeds only “by or under the direct supervision of a certified applicator.”[4] The regulatory record created an uphill battle for plaintiffs.[5] Under the Federal Insecticide, Fungicide, and Rodenticide Act (“FIFRA”), the U.S. EPA has regulatory and enforcement authority over the use, sale, and labeling of paraquat.[6] As part of its regulatory responsibilities, in 2019, the EPA systematically reviewed available evidence to assess whether there was an association between paraquat and PD. The agency’s review concluded that “there is limited, but insufficient epidemiologic evidence at this time to conclude that there is a clear associative or causal relationship between occupational paraquat exposure and PD.”[7] In 2021, the EPA issued its Interim Registration Review Decision, and reapproved the registration of paraquat. In doing so, the EPA concluded that “the weight of evidence was insufficient to link paraquat exposure from pesticidal use of U.S. registered products to Parkinson’s disease in humans.”[8]

Second, beyond the EPA, there were no other published reviews, systematic or otherwise, which reached a conclusion that paraquat causes PD.[9]

Third, the plaintiffs claims faced another serious impediment. Their counsel placed their reliance upon Professor Martin Wells, a statistician on the faculty of Cornell University. Unfortunately for plaintiffs, Wells has been known to operate as a “cherry picker,” and his methodology has been previously reviewed in an unfavorable light. Another MDL court, which reviewed a review and meta-analysis propounded by Wells, found that his reports “were marred by a selective review of data and inconsistent application of inclusion criteria.”[10]

Fourth, the plaintiffs’ claims were before Chief Judge Nancy J. Rosenstengel, who was willing to do the hard work required under Rule 702, specially as it has been recently amended for clarification and emphasis of the gatekeeper’s responsibilities to evaluate validity issues in the proffered opinions of expert witnesses. As her 97 page decision evinces, Judge Rosenstengel conducted four days of hearings, which included viva voce testimony from Martin Wells, and she obviously read the underlying papers, reviews, as well as the briefs and the Reference Manual on Scientific Evidence, with great care. What followed did not go well for Wells or the plaintiffs’ claims.[11] Judge Rosenstengel has written an opinion that may be the first careful judicial consideration of the basic requirements of systematic review.

The court noted that systematic reviewers carefully define a research question and what kinds of empirical evidence will be reviewed, and then collect, summarize, and, if feasible, synthesize the available evidence into a conclusion.[12] The court emphasized that systematic reviewers should “develop a protocol for the review before commencement and adhere to the protocol regardless of the results of the review.”[13]

Wells proffered a meta-analysis, and a “weight of the evidence” (WOE) review from which he concluded that paraquat causes PD and nearly triples the risk of the disease among workers exposed to the herbicide.[14] In his reports, Wells identified a universe of at least 36 studies, but included seven in his meta-analysis. The defense had identified another two studies that were germane.[15]

Chief Judge Rosenstengel’s opinion is noteworthy for its fine attention to detail, detail that matters to the validity of the expert witness’s enterprise. Martin Wells set out to do a meta-analysis, which was all fine and good. With a universe of 36 studies, with sub-findings, alternative analyses, and changing definitions of relevant exposure, the devil lay in the details.

The MDL court was careful to point out that it was not gainsaying Wells’ decision to limit his meta-analysis to case-control studies, or to his grading of any particular study as being of low quality. Systematic reviews and meta-analyses are generally accepted techniques that are part of a scientific approach to causal inference, but each has standards, predicates, and requirements for valid use. Expert witnesses must not only use a reliable methodology, Rule 702(d) requires that they must reliably apply their chosen methodology to the facts at hand in reaching their conclusions.[16]

The MDL court concluded that Wells’ meta-analysis was not sufficiently reliable under Rule 702 because he failed faithfully and reliably to apply his own articulated methodology. The court followed Wells’ lead in identifying the source and content of his chosen methodology, and simply examined his proffered opinion for compliance with that methodology.[17] The basic principles of validity for conducting meta-analyses were not, in any event, really contested. These principles and requirements were clearly designed to ensure and enhance the reliability of meta-analyses by pre-empting results-driven, reverse-engineered summary estimates of association.

The court found that Wells failed clearly to pre-specify his eligibility criteria. He then proceeded to redefine exposure criteria and study inclusion or eligibility criteria, and study quality criteria, after looking at the evidence. He also inconsistently applied his stated criteria, all in an apparently desired effort to exclude less favorable study outcomes. These ad hoc steps were some of Wells’ deviations from the standards to which he played lip service.

The court did not exclude Wells because it disagreed with his substantive decisions to include or exclude any particular study, or his quality grading of any study. Rather, Dr. Wells’ meta-analysis does not pass muster under Rule 702 because its methodology was unclear, inconsistently applied, not replicable, and at times transparently reverse-engineered.[18]

The court’s evaluation of Wells was unflinchingly critical. Wells’ proffered opinions “required several methodological contortions and outright violations of the scientific standards he professed to apply.”[19] From his first involvement in this litigation, Wells had violated the basic rules of conducting systematic reviews and meta-analyses.[20] His definition of “occupational” exposure meandered to suit his desire to include one study (with low variance) that might otherwise have been excluded.[21] Rather than pre-specifying his review process, his study inclusion criteria, and his quality scores, Wells engaged in an unwritten “holistic” review process, which he conceded was not objectively replicable. Wells’ approach left him free to include studies he wanted in his meta-analysis, and then provide post hoc justifications.[22] His failure to identify his inclusion/exclusion criteria was a “methodological red flag” in Dr. Wells’ meta-analysis, which suggested his reverse engineering of the whole analysis, the “very antithesis of a systematic review.”[23]

In what the court described as “methodological shapeshifting,” Wells blatantly and inconsistently graded studies he wanted to include, and had already decided to include in his meta-analysis, to be of higher quality.[24] The paraquat MDL court found, unequivocally, that Wells had “failed to apply the same level of intellectual rigor to his work in the four trial selection cases that would be required of him and his peers in a non-litigation setting.”[25]

It was also not lost upon the MDL court that Wells had shifted from a fixed effect to a random effects meta-analysis, between his principal and rebuttal reports.[26] Basic to the meta-analytical enterprise is a predicate systematic review, properly done, with pre-specification of inclusion and exclusion criteria for what studies would go into any meta-analysis. The MDL court noted that both sides had cited Borenstein’s textbook on meta-analysis,[27] and that Wells had himself cited the Cochrane Handbook[28] for the basic proposition that that objective and scientifically valid study selection criteria should be clearly stated in advance to ensure the objectivity of the analysis.

There was of course legal authority for this basic proposition about prespecification. Given that the selection of studies that go into a systematic review and meta-analysis can be dispositive of its conclusion, undue subjectivity or ad hoc inclusion can easily arrange a desired outcome.[29] Furthermore, meta-analysis carries with it the opportunity to mislead a lay jury with a single (and inflated) risk ratio,[30] which is obtained by the operator’s manipulation of inclusion and exclusion criteria. This opportunity required the MDL court to examine the methodological rigor of the proffered meta-analysis carefully to evaluate whether it reflects a valid pooling of data or it was concocted to win a case.[31]

Martin Wells had previously acknowledged the dangers of manipulation and subjective selectivity inherent in systematic reviews and meta-analyses. The MDL court quoted from Wells’ testimony in Martin v. Actavis:

QUESTION: You would certainly agree that the inclusion-exclusion criteria should be based upon objective criteria and not simply because you were trying to get to a particular result?

WELLS: No, you shouldn’t load the – sort of cook the books.

QUESTION: You should have prespecified objective criteria in advance, correct?

WELLS: Yes.[32]

The MDL court also picked up on a subtle but important methodological point about which odds ratio to use in a meta-analysis when a study provides multiple analyses of the same association. In his first paraquat deposition, Wells cited the Cochrane Handbook, for the proposition that if a crude risk ratio and a risk ratio from a multivariate analysis are both presented in a given study, then the adjusted risk ratio (and its corresponding measure of standard error seen in its confidence interval) is generally preferable to reduce the play of confounding.[33] Wells violated this basic principle by ignoring the multivariate analysis in the study that dominated his meta-analysis (Liou) in favor of the unadjusted bivariate analysis. Given that Wells accepted this basic principle, the MDL court found that Wells likely selected the minimally adjusted odds ratio over the multiviariate adjusted odds ratio for inclusion in his meta-analysis in order to have the smaller variance (and thus greater weight) from the former. This maneuver was disqualifying under Rule 702.[34]

All in all, the paraquat MDL court’s Rule 702 ruling was a convincing demonstration that non-expert generalist judges, with assistance from subject-matter experts, treatises, and legal counsel, can evaluate and identify deviations from methodological standards of care.

[1] In re Paraquat Prods. Prods. Liab. Litig., Case No. 3:21-md-3004-NJR, MDL No. 3004, Slip op., ___ F.3d ___ (S.D. Ill. Apr. 17, 2024) [Slip op.]

[2] In re Paraquat Prods. Prods. Liab. Litig., Op. sur motion for judgment, Case No. 3:21-md-3004-NJR, MDL No. 3004 (S.D. Ill. Apr. 17, 2024). See also Brendan Pierson, “Judge rejects key expert in paraquat lawsuits, tosses first cases set for trial,” Reuters (Apr. 17, 2024); Hailey Konnath, “Trial-Ready Paraquat MDL Cases Tossed After Testimony Axed,” Law360 (Apr. 18, 2024).

[3] Ferebee v. Chevron Chem. Co., 552 F. Supp. 1297 (D.D.C. 1982), aff’d, 736 F.2d 1529 (D.C. Cir.), cert. denied, 469 U.S. 1062 (1984). See “Ferebee Revisited,” Tortini (Dec. 28, 1017).

[4] See 40 C.F.R. § 152.175.

[5] Slip op. at 31.

[6] 7 U.S.C. § 136w; 7 U.S.C. § 136a(a); 40 C.F.R. § 152.175. The agency must periodically review the registration of the herbicide. 7 U.S.C. § 136a(g)(1)(A). See Ruckelshaus v. Monsanto Co., 467 U.S. 986, 991-92 (1984).

[7] See Austin Wray & Aaron Niman, Memorandum, Paraquat Dichloride: Systematic review of the literature to evaluate the relationship between paraquat dichloride exposure and Parkinson’s disease at 35 (June 26, 2019).

[8] See also Jeffrey Brent and Tammi Schaeffer, “Systematic Review of Parkinsonian Syndromes in Short- and Long-Term Survivors of Paraquat Poisoning,” 53 J. Occup. & Envt’l Med. 1332 (2011) (“An analysis the world’s entire published experience found no connection between high-dose paraquat exposure in humans and the development of parkinsonism.”).

[9] Douglas L. Weed, “Does paraquat cause Parkinson’s disease? A review of reviews,” 86 Neurotoxicology 180, 180 (2021).

[10] In re Incretin-Based Therapies Prods. Liab. Litig., 524 F.Supp. 3d 1007, 1038, 1043 (S.D. Cal. 2021), aff’d, No. 21-55342, 2022 WL 898595 (9th Cir. Mar. 28, 2022) (per curiam). See “Madigan’s Shenanigans and Wells Quelled in Incretin-Mimetic Cases” Tortini (July 15, 2022).

[11] The MDL court obviously worked hard to learn the basics principles of epidemiology. The court relied extensively upon the epidemiology chapter in the Reference Manual on Scientific Evidence. Much of that material is very helpful, but its exposition on statistical concepts is at times confused and erroneous. It is unfortunate that courts do not pay more attention to the more precise and accurate exposition in the chapter on statistics. Citing the epidemiology chapter, the MDL court gave an incorrect interpretation of the p-value: “A statistically significant result is one that is unlikely the product of chance. Slip op. at 17 n. 11. And then again, citing the Reference Manual, the court declared that “[a] p-value of .1 means that there is a 10% chance that values at least as large as the observed result could have been the product of random error. Id.” Id. Similarly, the MDL court gave an incorrect interpretation of the confidence interval. In a footnote, the court tells us that “[r]esearchers ordinarily assert a 95% confidence interval, meaning that ‘there is a 95% chance that the “true” odds ratio value falls within the confidence interval range’. In re Zoloft (Sertraline Hydrochloride) Prod. Liab. Litig., MDL No. 2342, 2015 WL 7776911, at *2 (E.D. Pa. Dec. 2, 2015).” Slip op. at 17n.12.  Citing another court for the definition of a statistical concept is a risky business.

[12] Slip op. at 20, citing Lisa A. Bero, “Evaluating Systematic Reviews and Meta-Analyses,” 14 J.L. & Pol’y 569, 570 (2006).

[13] Slip op. at 21, quoting Bero, at 575.

[14] Slip op. at 3.

[15] The nine studies at issue were as follows: (1) H.H. Liou, et al., “Environmental risk factors and Parkinson’s disease; A case-control study in Taiwan,” 48 Neurology 1583 (1997); (2) Caroline M. Tanner, et al., “Rotenone, Paraquat and Parkinson’s Disease,” 119 Envt’l Health Persps. 866 (2011) (a nested case-control study within the Agricultural Health Study (“AHS”)); (3) Clyde Hertzman, et al., “A Case-Control Study of Parkinson’s Disease in a Horticultural Region of British Columbia,” 9 Movement Disorders 69 (1994); (4) Anne-Maria Kuopio, et al., “Environmental Risk Factors in Parkinson’s Disease,” 14 Movement Disorders 928 (1999); (5) Katherine Rugbjerg, et al., “Pesticide exposure and risk of Parkinson’s disease – a population-based case-control study evaluating the potential for recall bias,” 37 Scandinavian J. of Work, Env’t & Health 427 (2011); (6) Jordan A. Firestone, et al., “Occupational Factors and Risk of Parkinson’s Disease: A Population-Based Case-Control Study,” 53 Am. J. of Indus. Med. 217 (2010); (7) Amanpreet S. Dhillon,“Pesticide / Environmental Exposures and Parkinson’s Disease in East Texas,” 13 J. of Agromedicine 37 (2008); (8) Marianne van der Mark, et al., “Occupational exposure to pesticides and endotoxin and Parkinson’s disease in the Netherlands,” 71 J. Occup. & Envt’l Med. 757 (2014); (9) Srishti Shrestha, et al., “Pesticide use and incident Parkinson’s disease in a cohort of farmers and their spouses,” Envt’l Research 191 (2020).

[16] Slip op. at 75.

[17] Slip op. at 73.

[18] Slip op. at 75, citing In re Mirena IUS Levonorgestrel-Related Prod. Liab. Litig. (No. II), 341 F. Supp. 3d 213, 241 (S.D.N.Y. 2018) (“Opinions that assume a conclusion and reverse-engineer a theory to fit that conclusion are . . . inadmissible.”) (internal citation omitted), aff’d, 982 F.3d 113 (2d Cir. 2020); In re Zoloft (Sertraline Hydrochloride) Prod. Liab. Litig., No. 12-md-2342, 2015 WL 7776911, at *16 (E.D. Pa. Dec. 2, 2015) (excluding expert’s opinion where he “failed to consistently apply the scientific methods he articulat[ed], . . . deviated from or downplayed certain well established principles of his field, and . . . inconsistently applied methods and standards to the data so as to support his a priori opinion.”), aff’d, 858 F.3d 787 (3d Cir. 2017).

[19] Slip op. at 35.

[20] Slip op. at 58.

[21] Slip op. at 55.

[22] Slip op. at 41, 64.

[23] Slip op. at 59-60, citing In re Lipitor (Atorvastatin Calcium) Mktg., Sales Pracs. & Prod. Liab. Litig., 892 F.3d 624, 634 (4th Cir. 2018) (“Result-driven analysis, or cherry-picking, undermines principles of the scientific method and is a quintessential example of applying methodologies (valid or otherwise) in an unreliable fashion.”).

[24] Slip op. at 67, 69-70, citing In re Zoloft (Sertraline Hydrochloride) Prod. Liab. Litig., 858 F.3d 787, 795-97 (3d Cir. 2017) (“[I]f an expert applies certain techniques to a subset of the body of evidence and other techniques to another subset without explanation, this raises an inference of unreliable application of methodology.”); In re Bextra and Celebrex Mktg. Sales Pracs. & Prod. Liab. Litig., 524 F. Supp. 2d 1166, 1179 (N.D. Cal. 2007) (excluding an expert witness’s causation opinion because of his result-oriented, inconsistent evaluation of data sources).

[25] Slip op. at 40.

[26] Slip op. at 61 n.44.

[27] Michael Borenstein, Larry V. Hedges, Julian P. T. Higgins, and Hannah R. Rothstein, Introduction to Meta-Analysis (2d ed. 2021).

[28] Jacqueline Chandler, James Thomas, Julian P. T. Higgins, Matthew J. Page, Miranda Cumpston, Tianjing Li, Vivian A. Welch, eds., Cochrane Handbook for Systematic Reviews of Interventions (2ed 2023).

[29] Slip op. at 56, citing In re Zimmer Nexgen Knee Implant Prod. Liab. Litig., No. 11 C 5468, 2015 WL 5050214, at *10 (N.D. Ill. Aug. 25, 2015).

[30] Slip op. at 22. The court noted that the Reference Manual on Scientific Evidence cautions that “[p]eople often tend to have an inordinate belief in the validity of the findings when a single number is attached to them, and many of the difficulties that may arise in conducting a meta-analysis, especially of observational studies such as epidemiological ones, may consequently be overlooked.” Id., quoting from Manual, at 608.

[31] Slip op. at 57, citing Deutsch v. Novartis Pharms. Corp., 768 F. Supp. 2d 420, 457-58 (E.D.N.Y. 2011) (“[T]here is a strong risk of prejudice if a Court permits testimony based on an unreliable meta-analysis because of the propensity for juries to latch on to the single number.”).

[32] Slip op. at 64, quoting from Notes of Testimony of Martin Wells, in In re Testosterone Replacement Therapy Prod. Liab. Litig., Nos. 1:14-cv-1748, 15-cv-4292, 15-cv-426, 2018 WL 7350886 (N.D. Ill. Apr. 2, 2018).

[33] Slip op. at 70.

[34] Slip op. at 71-72, citing People Who Care v. Rockford Bd. of Educ., 111 F.3d 528, 537-38 (7th Cir. 1997) (“[A] statistical study that fails to correct for salient explanatory variables . . . has no value as causal explanation and is therefore inadmissible in federal court.”); In re Roundup Prod. Liab. Litig., 390 F. Supp. 3d 1102, 1140 (N.D. Cal. 2018). Slip op. at 17 n. 12.

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