Back in the first week of this month, I posted about a paper (Prada 2025),[1] which featured a so-called navigation-guide systematic review of the scientific evidence on the issue whether pregnant women’s ingestion of acetaminophen causes their children to develop autism.[2] The focus of my post was on some dodgy aspects of the Prada review, such as its anemic disclosures of interest, and its squirrely claim to have been “NIH funded.”
Since posting, the Prada review has been very much in the news. Last week, President Trump held a news conference, where we learned that he cannot pronounce acetaminophen and that he has a strongly held opinion that acetaminophen causes autism.[3] Trump was surrounded by officials in his administration, including plaintiffs’ lawyer Robert Kennedy, Jr., and three physicians, Drs. Oz, Makary, and Bhattacharya, who looked on in apparent approval. Once upon a time, a risk communication such as this one about acetaminophen, would have come out from a non-political FDA employee, such as Janet Woodcock, who was head of Drug Safety, and for many years the Director of Center for Drug Evaluation and Research. Over her tenure, Dr. Woodcock weighed in on many pharmaceutical safety issues. Those of us who have been involved in litigation of those safety issues remember that Dr. Woodcock chose her language very carefully. She did not just give opinions; she marshalled facts.
Admittedly, Trump’s autism press conference was not as deranged as his 2020 press conference at which he suggested that injecting sodium hypochlorite (bleach) into patients would cure Covid-19 infections. Still, most of the world was left with the impression that Trump was replacing (DOGE-ing) scientific research and replacing it with irrational speculation. Trump’s press conference on acetaminophen and vaccines was widely met with skepticism and disbelief. Medical ethicist Dr. Arthur Caplan, who is not given to hyperbole, called the conference “the saddest display of a lack of evidence, rumors, recycling old myths, lousy advice, outright lies, and dangerous advice I have ever witnessed by anyone in authority.”[4]
When the administration physicians communicated with the public, they said something very different from Trump’s presentation. In her press release, Press Secretary Karoline Leavitt used the meaningless locution, “suggested link,” and cited the Prada review, which eschewed causal conclusions:[5]
“Andrea Baccarelli, M.D., Ph.D., Dean of the Faculty, Harvard T.H. Chan School of Public Health: “Colleagues and I recently conducted a rigorous review, funded by a grant from the National Institutes of Health (NIH), of the potential risks of acetaminophen use during pregnancy… We found evidence of an association between exposure to acetaminophen during pregnancy and increased incidence of neurodevelopmental disorders in children.
Harvard University: Using acetaminophen during pregnancy may increase children’s autism and ADHD risk.”
Of course, saying that something “may increase risk” is not even close to saying that something causes the outcome in question. And Baccarelli’s description of his paper, Prada review, as funded by the National Institutes of Health is misleading at best.[6]
Leavitt went on to declare that “[t]he Trump Administration does not believe popping more pills is always the answer for better health.” Unless of course, it is Propecia for Mr. Trump, testosterone for Mr. Kennedy, or ketamine for Mr. Musk.
FDA Commissioner Martin A. Makary issued a Notice, the same day, in which he declared:
“In recent years, evidence has accumulated suggesting that the use of acetaminophen by pregnant women may be associated with an increased risk of neurological conditions such as autism and ADHD in children.
* * *
To be clear, while an association between acetaminophen and autism has been described in many studies, a causal relationship has not been established and there are contrary studies in the scientific literature.”[7]
So the FDA is clearly not declaring that acetaminophen causes autism.
Dr. Mehmet Oz, former surgeon and television talking head, who stood mute by Trump’s side at the infamous press conference, found his voice later in the week, when he acknowledged that pregnant women of course should take acetaminophen when physicians direct them to do so.
In Europe, where pharmaceutical regulation is typically more precautionary than in the United States, both the European Medicines Agency and the U.K.’s Medicines and Healthcare Products Regulatory Agency announced that using acetaminophen during pregnancy was safe with no showing that it causes autism in offspring.[8] Steffen Thirstrup, the EMA’s Chief Medical Officer, announced a day after the Trump bungle, that:
“Paracetamol [acetaminophen] remains an important option to treat pain or fever in pregnant women. Our advice is based on a rigorous assessment of the available scientific data and we have found no evidence that taking paracetamol during pregnancy causes autism in children.”
Most medical organizations were appalled at the administration’s sloppy messaging. The day after the press conference, the American College of Medical Toxicology (ACMT) issued a statement in response, to affirm the safety of acetaminophen in pregnancy.[9] The ACMT noted that its position was in agreement with the American College of Obstetrics and Gynecologists, the Society for Maternal-Fetal Medicine, the American Academy of Pediatrics, and the Society for Developmental and Behavioral Pediatrics.
The acetaminophen kerfuffle seems always to come back to the Prada “navigation guide” systematic review and its authors, including the Harvard Dean, Andrea Baccarelli, who was the well-paid member of the plaintiffs’ expert witness team in acetaminophen litigation.[10] Why did Dr. Andrea Baccarelli in the Prada review use this curious, arcane, and infrequently used method of review? Why did Baccarelli and his co-authors publish this review in Environmental Health, which is dedicated to publishing “manuscripts on important aspects of environmental and occupational medicine,” which places maternal ingestion of a licensed pharmaceutical outside its stated competence? Why did Baccarelli offer a litigation opinion that acetaminophen causes autism, but retreat to “association” when writing for the scientific community? And why did Baccarelli and his co-authors not disclose that Baccarelli had submitted essentially the same navigation guide systematic review as his proffered expert witness testimony, and that a federal court had rejected his opinion as not “the product of reliable principles and methods,” and not “a reliable application of the principles and methods to the facts of the case”[11]? Perhaps the answers are obvious to most observers, but candid disclosures certainly would have provided important context, and saved some people the embarrassment of relying upon the Prada review.
In digging deeper into the history of the navigation guide method itself, the earliest citation I could find to such systematic reviews was in 2009, in a conference paper that discussed this approach as a proposal.[12] The authors that made up the Navigating the Scientific Evidence to Improve Prevention Workshop Organizing Committee were not particularly well known or distinguished in the field of research synthesis. Still, there must be other reasons that “navigation guide” reviews are not more prevalent if the Organizing Committee had been truly on to something important.
The Committee never identified a rationale for a new systematic review approach. When the Organizing Committee outlined its approach in 2009, there were well over three decades of experience with systematic reviews,[13] with well-regarded full-length textbook treatment by experts in the field.[14]
In addition to the lack of experience among its authors and the preemption of the subject by comprehensive treatments elsewhere, there were three additional curious take aways from a cursory reading of the Organizing Committee’s 2009 manuscript. First, Committee emphasized the alleged need for a review methodology for environmental exposures. This emphasis was never accompanied by a showing that well-described methodologies long in use were somehow inadequate or inappropriate for environmental exposures.
Second, the authors urged the need for precautionary assessments, which might make their method fine where syntheses for precautionary pronouncements were called for. In the United States, regulatory assessments vary depending up the governing statutes that create the regulatory mandate. In personal injury litigation, the precautionary principle is nothing less than an end run around the burden of proof on the party claiming harm and suing in tort. The designated subject matter of environmental exposures for the proposed systematic review technique offers an insight into why these authors believed that they had to propose a new fangled systematic review methodology. Previously described methods interfered with authors’ ability to elevate “iffy” associations into conclusions of causality in the name of the precautionary principle.
The third curiosity in the 2009 manuscript is that the authors never described the need for a pre-specified protocol. Later articles on this proposed methodology similarly failed to describe the need for such a protocol,[15] although by 2014, authors from the original Organizing Committee reversed course to add a pre-specified protocol to the requirements for a navigation guide systematic review.[16]
A recent article defines a systematic review essentially in terms of a protocol:
“Systematic review (SR) is a rigorous, protocol-driven approach designed to minimise error and bias when summarising the body of research evidence relevant to a specific scientific question.”[17]
The purpose of a protocol may be obvious to anyone who has been paying attention to the replication crisis in biomedical literature, but the same article offers a helpful description of its rationale:
“The purposes of the protocol are to discourage ad-hoc changes to methodology during the review process which may introduce bias, to allow any justifiable methodological changes to be tracked, and also to allow peer-review of the work that it is proposed, to help ensure the utility and validity of its objectives and methods.”[18]
Systematic reviews vary widely in quality, methodological rigor, and validity, but one of the key determinants of their validity is whether they were preceded by pre-specified protocol. Although systematic reviews are often described the “gold standard” for evidence synthesis, their methodological rigor vary widely. Reviews that lack a pre-specified protocol are decidedly less rigorous than those reviews that employ a protocol.[19] The absence of a protocol is thus an important tell that a systematic review may be untrustworthy.
The Prada paper put together by Baccarelli’s team has no protocol. It may satisfy the Trump administration’s Fool’s Gold Standard for Science, but that is far short of the requirements of Federal Rule of Evidence 702. Given Baccarelli’s abridgement of scientific method, we should not be overly surprised by Judge Cote’s judgment of the failures of Baccarelli’s and the other plaintiffs’ expert witnesses’ proffered opinions in the acetaminophen litigation:
“their analyses have not served to enlighten but to obfuscate the weakness of the evidence on which they purport to rely and the contradictions in the research. As performed by the plaintiffs’ experts, their transdiagnostic analysis has obscured instead of informing the inquiry on causation.”[20]
Judge Cote carefully reviewed Baccarelli’s proffered testimony and found it replete with cursory analyses, cherry-picked data, and result-driven assessments of studies.[21] Her Honor’s findings would seem to apply with equal measure to the Prada review.
[1] Diddier Prada, Beate Ritz, Ann Z. Bauer and Andrea A. Baccarelli, “Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology,” 24 Envt’l Health 56 (2025).
[2] See Schachtman, “Acetaminophen & Autism – Prada Review Misleadingly Claims to Be NIH Funded,” Tortini (Sept. 9, 2025).
[3] Jeff Mason, Ahmed Aboulenein, and Julie Steenhuysen, “Trump Links Autism to Tylenol and Vaccines, Claims Not Backed by Science,” Reuters (Sept. 22, 2025); Brianna Abbott & Andrea Petersen, “The Trump administration said acetaminophen could cause autism. Doctors maintain it is safe during pregnancy,” Wall St. J. (Sept. 22, 2025) (“Studies looking at a link [sic] between acetaminophen and autism are inconclusive.”); Will Weissert, “Dr. Trump? The president reprises his COVID era, this time sharing unproven medical advice on autism,” Wash. Post (Sept. 23, 2025).
[4] Ali Swenson & Lauran Neergaard, “Trump makes unfounded claims about Tylenol and repeats discredited link between vaccines and autism,” Assoc. Press (Sept. 23, 2025).
[5] Leavitt, “FACT: Evidence Suggests Link Between Acetaminophen, Autism,” The White House (Sept. 22, 2025).
[6] See Schachtman, “Acetaminophen & Autism – Prada Review Misleadingly Claims to Be NIH Funded,” Tortini (Sept. 9, 2025). The referenced grants had nothing to do with acetaminophen and autism, or even autism generally. The NIEHS granted Dr. Baccarelli money to study air pollution and brain aging. The exposure of interest was not acetaminophen, and the outcome of interest was not autism. By claiming that his research was “NIH funded,” Baccarelli was attempting to boost the prestige of the research even though his acetaminophen review was done for litigation, not for the federal government. Apparently the NIEHS acquiesces in this charade because it suggests to the uninitiated that its research grants result in more published papers, even though the topics of those papers are unrelated to the funded research proposal, and the unrelated topics never receiving committee peer review.
[7] Martin A. Makary, “Notice to Physicians on the Use of Acetaminophen During Pregnancy,” (Sept. 22, 2025).
[8] E.M.A., “Use of paracetamol during pregnancy unchanged in the EU,” (Sept. 23, 2025).
[9] ACMT Supports the Safe Use of Acetaminophen in Pregnancy (Sept. 23, 2025).
[10] Rebecca Robbins & Azeen Ghorayshi, “Harvard Dean Was Paid $150,000 as an Expert Witness in Tylenol Lawsuits,” N.Y. Times (Sept. 23, 2025).
[11] Fed. R. Evid. 702.
[12] Patrice Sutton, Heather Sarantis, Julia Quint, Mark Miller, Michele Ondeck, Rivka Gordon, and Tracey Woodruff, “Navigating the Scientific Evidence to Improve Prevention: A Proposal to Develop A Transparent and Systematic Methodology to Sort the Scientific Evidence Linking Environmental Exposures to Reproductive Health Outcomes,” (July 29, 2009).
[13] See Quan Nha Hong & Pierre Pluye, “Systematic reviews: A brief historical overview,” 34 Education for Information 261, 261 (2018) (describing the evolution of systematic reviews as made up of a “foundation period 1970-1989,” an “institutionalization period 1990-2000, and a “diversification period” from 2001 forward.)
[14] Matthias Egger, Julian P. T. Higgins, and George Davey Smith, Systematic Reviews in Health Research: Meta-Analysis in Context (3rd ed. 2022). The first edition of this text was published in 1995.
[15] Tracey J. Woodruff, Patrice Sutton, and The Navigation Guide Work Group, “An Evidence-Based Medicine Methodology To Bridge The Gap Between Clinical And Environmental Health Sciences,” 30 Health Affairs 931 (2011); Julia R. Barrett, “The Navigation Guide Systematic Review for the Environmental Health Sciences,” 122 Envt’l Health Persp. A283 (2014).
[16] Tracey J. Woodruff & Patrice Sutton, “The Navigation Guide Systematic Review Methodology: A Rigorous and Transparent Method for Translating Environmental Health Science into Better Health Outcomes,” 122 Environ Health Perspect. 1007 (2014).
[17] Paul Whaley, Crispin Halsall, Marlene Ågerstrand, Elisa Aiassa, Diane Benford, Gary Bilotta, David Coggon, Chris Collins, Ciara Dempsey, Raquel Duarte-Davidson, Rex Fitzgerald, Malyka Galay-Burgos, David Gee, Sebastian Hoffmann, Juleen Lam, Toby Lasserson, Len Levy, Steven Lipworth, Sarah Mackenzie Ross, Olwenn Martin, Catherine Meads, Monika Meyer-Baron, James Miller, Camilla Pease, Andrew Rooney, Alison Sapiets, Gavin Stewart, and David Taylor, “Implementing systematic review techniques in chemical risk assessment: Challenges, opportunities and recommendations,” 92-93 Env’t Internat’l 556 (2016).
[18] Id. at 560.
[19] Julia Menon, Fréderique Struijs & Paul Whaley, “The methodological rigour of systematic reviews in environmental health,” 52 Critical Rev Toxicol. 167 (2022).
[20] In re Acetaminophen ASD-ADHD Prods. Liab. Litig., 707 F. Supp. 3d 309, 334, 2023 WL 8711617 (S.D.N.Y. 2023) (Cote, J.).
[21] Id. at 354-56.
