We’ve blogged several times already about the Alliance for Hippocratic Medicine v. FDA litigation that is now before the Supreme Court. Briefly, a Texas District Court, in a decision that we’ve already described as “results-driven and shoddy,” purported to invalidate more than 20 years of FDA regulation – back to and including the original 2000 agency approval – of the abortifacient drug mifepristone, which would have had the effect of immediately removing from the market nationwide the safest and most commonly used drug for medication abortions. See Alliance for Hippocratic Medicine v. FDA, ___ F. Supp.3d ___, 2023 WL 2825871 (N.D. Tex. April 7, 2023) (“AHM I”).

On appeal, the Fifth Circuit overturned the District Court’s nullification of the FDA’s approvals of both branded and generic versions of mifepristone but affirmed that court’s voiding of both the 2016 risk evaluation and mitigation strategy (“REMS”) and 2021 non-enforcement decision that allowed telemedicine prescription of mifepristone. See Alliance for Hippocratic Medicine v. FDA, 78 F.4th 210 (5th Cir. 2023) (“AHM II”). We chastised both of these decisions for, on the one hand setting a very low bar for standing to challenge FDA drug approval decisions (mere stress to physicians from treating purported mifepristone adverse reactions being sufficient), and on the other for simultaneously dumbing down the previously rigorous “arbitrary and capricious” standard of review for FDA drug approval decisions (placing the burden on the agency to demonstrate the negative, for one).

We were hardly alone. We quoted the FDA’s description of the decisions to overturn its regulation of mifepristone:

While FDA justified its scientific conclusions in multiple detailed reviews, including a medical review spanning more than 100 pages and assessing dozens of studies and other scientific information, the district court swept the agency’s judgments aside by substituting its own lay understanding of purportedly contrary studies, offering demonstrably erroneous characterizations of the record.

(quoting FDA appellate brief). Another of our posts quoted similar concerns raised by our clients in the pharmaceutical industry as the matter was being successfully appealed to the United States Supreme Court:

The Fifth Circuit’s ruling threatens to stifle pharmaceutical innovation by disrupting industry’s reasonable investment-backed expectations. Congress created an FDA approval process that is both rigorous and thorough, and pharmaceutical companies invest billions of dollars in research and development to meet FDA’s scientific standards. Considering the rigorousness of this process and the due process interests of drug sponsors, Congress also mandated by statute a process for withdrawal or suspension of an FDA approval decision − a process the Fifth Circuit circumvented. But if every FDA drug approval decision − and subsequent supplemental drug approval decision − can be retroactively invalidated by a court based on extra-statutory, judicially created requirements, biopharmaceutical companies will likely invest less in the advancement of new and existing medicines that benefit patients.

(Quoting PhRMA Amicus Brief, at 3-4).

Last week these concerns were graphically confirmed when two of the “purportedly contrary studies” mentioned by the FDA, and relied upon six times by the District Court in its unprecedented opinion, were withdrawn by the academic journal in which they were published − for apparently pervasive academic fraud. See Health Services Research & Managerial Epidemiology retraction notice, available here.

The journal retracted the following three articles:

  • Studnicki J., Longbons T., Harrison D.J., et al., “A Post Hoc Exploratory Analysis: Induced Complications Mistaken for Miscarriage in the Emergency Room Are a Risk Factor for Hospitalization,” 9 H. Servs. Res. & Man’l Epid’y. 1 (2022).
  • Studnicki J, Harrison D.J., Longbons T., et al., “A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical & Surgical Abortions, 1999–2015,” 8 H. Servs. Res. & Man’l Epid’y. 1, (2021).
  • Studnicki J., Longbons T., Fisher J.W., Harrison D.J., Skop I., MacKinnon S.J., “Doctors Who Perform Abortions: Their Characteristics & Patterns of Holding & Using Hospital Privileges,” 6 . Servs. Res. & Man’l Epid’y. 1 (2019).

The first two of these articles were cited no fewer than six times in the District Court’s decision. See AHM I, 2023 WL 2825871, at *4 n.9 (“Longitudinal” for the proposition that “adverse events from chemical abortion drugs can overwhelm the medical system and place ‘enormous pressure and stress’ on doctors during emergencies and complications”), at *14 n.22 (both articles for the proposition that there are “‘many intense side effects’ and ‘significant complications requiring medical attention’” resulting” from FDA’s regulation of mifepristone), at *22 n.37 (one or both articles for the proposition that “chemical abortions are over fifty percent more likely than surgical abortion to result in an emergency room visit within thirty days”), at *23 n.45 (“Longitudinal” for the proposition that “over sixty percent of women and girls’ emergency room visits after chemical abortions are miscoded as ‘miscarriages’ rather than adverse effects to mifepristone”) (emphasis original). AHM I thus relied on these retracted articles both to support its standing analysis and substantively to justify its injunction that would have removed mifepristone from the market.

Neither article, however, could have passed muster under Fed. R. Evid. 702 in product liability litigation. Here’s why they were retracted. The publishing journal’s investigation identified both disclosure and substantive scientific errors. The journal determined, first, that the authors had undisclosed conflicts of interest:

[We] confirmed that all but one of the article’s authors had an affiliation with one or more of Charlotte Lozier Institute, Elliot Institute, and American Association of Pro-Life Obstetricians and Gynecologists, all pro-life advocacy organizations, despite having declared they had no conflicts of interest when they submitted the article for publication or in the article itself.

See Retraction Notice. These undisclosed conflicts of interest tainted not only the articles themselves, but also their initial peer review – the publisher “became aware that a peer reviewer who evaluated” all three articles “for initial publication also was affiliated with Charlotte Lozier Institute at the time of the review.” Id. Thus, the publisher also “determined the peer review for initial publication was unreliable.” Id.

These undisclosed conflicts of interest further affected the AHM litigation itself – the aforementioned American Association of Pro-Life Obstetricians and Gynecologists is one of the plaintiffs in AHM. The AHM I opinion contains no indication that the ties between the researchers in the cited articles and one of the plaintiffs was any more disclosed during the litigation than it was during the articles’ original peer review process. AHM I thus relied, presumably unknowingly, on articles generated by one or more of the plaintiffs’ members. Moreover, all three articles appear to have been covertly generated for litigation purposes, as the lead author for the articles has also acted as an “expert” witness in other abortion-related litigation. See, e.g., Whole Woman’s Health Alliance v. Rokita, 2021 WL 650589, at *12-17 (Mag. S.D. Ind. Feb. 19, 2021) (admitting and excluding Studnicki testimony); Whole Woman’s Health Alliance v. Hill, 2020 WL 7129727, at *2-3 (Mag. S.D. Ind. Dec. 3, 2020) (addressing litigant’s attempt to correct various errors in Studnicki report).

Substantively, as well, the three articles cited in AHM I were junk science. After learning of the conflict-of-interest problems with the articles’ original peer review, the publisher engaged “[t]wo subject matter experts” to conduct a second “post-publication peer review.” See Retraction Notice. Those unbiased experts determined:

In the 2021 and 2022 articles, which rely on the same dataset, both experts identified fundamental problems with the study design and methodology, unjustified or incorrect factual assumptions, material errors in the authors’ analysis of the data, and misleading presentations of the data that, in their opinions, demonstrate a lack of scientific rigor and invalidate the authors’ conclusions in whole or in part. In the 2019 article, which relies on a different dataset, both experts identified unsupported assumptions and misleading presentations of the findings that, in their opinions, demonstrate a lack of scientific rigor and render the authors’ conclusion unreliable.

Id.

Thus, the attempted invalidation of over 20 years of FDA regulatory activity concerning mifepristone stands exposed as based in large part on junk science: “fundamental problems” with “study design and methodology,” “unjustified or incorrect factual assumptions,” “material errors” of data analysis, “misleading presentations of the data,” “lack of scientific rigor” – all of which “invalidate the authors’ conclusions” and “render” those conclusions “unreliable.” Those are not our words; they are the findings of the same scientific journal that was duped into publishing these articles.

If this outright repudiation of the claimed basis of an opponent’s litigation experts had occurred in the prescription medical product liability litigation in which we participate, it would have merited inclusion in our “stupid expert tricksblogposts. But the scientific fraud that has evidently been perpetrated in the AHM litigation is far worse. It is not about some plaintiff being awarded, or not, money for some claimed injury. Rather these bogus articles have been employed in a political attack against the linchpin of prescription medical product regulation in this country – the congressionally conferred responsibility of the FDA to determine what medical products (here, drugs) are available in the American market and under what conditions.

No judge should have the power, as has been attempted in the AHM litigation, to overturn an FDA product approval on the behest of litigants who cannot possibly duplicate the FDA’s scientific expertise and comprehensive data review. Biased litigants (and equally biased judges) cannot be allowed to second-guess FDA product determinations. Buckman Co. v. Plaintiffs Legal Committee, 531 U.S. 341, 351 (2001) (rejecting the “sort of litigation [that] would exert an extraneous pull on the scheme established by Congress”). Nothing more graphically demonstrates that “[a] court is ill-equipped to second-guess” the FDA’s “scientific judgment” than what has been happening in AHM. Cytori Therapeutics, Inc. v. FDA, 715 F.3d 922, 927 (D.C. Cir. 2013) (Kavanaugh, J.).