’Then you should say what you mean’, the March Hare went on.
‘I do’, Alice hastily replied; ‘at least–at least I mean what I say–that’s the same thing, you know’.
‘Not the same thing a bit!’ said the Hatter. ‘You might just as well say that “I see what I eat” is the same thing as “I eat what I see!”’Lewis Carroll, Alice’s Adventures in Wonderland, Chapter VII (1865)
Anick Bérard is an epidemiologist at the Université de Montréal. Most of her publications involve birth outcomes and maternal medication use, but Dr. Bérard’s advocacy also involves social media (Facebook, YouTube) and expert witnessing in litigation against the pharmaceutical industry.
When the FDA issued its alert about cardiac malformations in children born to women who took Paxil (paroxetine) in their first trimesters of pregnancy, the agency characterized its assessment of the “early results of new studies for Paxil” as “suggesting that the drug increases the risk for birth defects, particularly heart defects, when women take it during the first three months of pregnancy.”1 The agency also disclaimed any conclusion of “class effect” among the other selective serotonin reuptake inhibitors (SSRIs), such as Zoloft (sertraline), Celexa (citalopram), and Prozac (fluoxetine). Indeed, the FDA requested the manufacturer of paroxetine to undertake additional research to look at teratogenicity of paroxetine, as well as the possibility of class effects. That research never showed an SSRI teratogenicity class effect.
A “suggestion” from the FDA of an adverse effect is sufficient to launch a thousand litigation complaints, which were duly filed against GlaxoSmithKline. The plaintiffs’ counsel recruited Dr. Bérard to serve as an expert witness in support of a wide array of birth defects in Paxil cases. In her hands, the agency’s “suggestion” of causation became a conclusion. The defense challenged Bérard’s opinions, but the federal court motion to exclude her causal opinions were taken under advisement, without decision. Hayes v. SmithKline Beecham Corp., 2009 WL 4912178 (N.D. Okla. Dec. 14, 2009). One case in state court went to trial, with a verdict for plaintiffs.
Despite Dr. Bérard;s zealous advocacy for a causal association between Paxil and birth defects, she declined to assert any association between maternal use of the other, non-paroxetine SSRIs and birth defects. Here is an excerpt from her Rule 26 report in a paroxetine case:
“Taken together, the available scientific evidence makes it clear that Paxil use during the first trimester of pregnancy is an independent risk factor that at least doubles the risk of cardiovascular malformations in newborns at all commonly used doses. This risk has been consistent and was further reinforced by repeated observational study findings as well as meta-analyses results. No such associations were found with other types of SSRI exposures during gestation.”2
In her sworn testimony, Dr. Bérard made clear that she really meant what she had written in her report, about exculpating the non-paroxetine SSRIs of any association with birth defects:
“Q. Is it fair to say that you will not be offering an opinion that SSRIs as a class, or individual SSRIs other than Paxil increased the risk of cardiovascular malformations in newborns?
A. This is not what I was asked to do.
Q. But in fact you actually write in your report that you don’t believe there’s sufficient data to reach any conclusion about other SSRIs, true?
A. Correct.”3
In 2010, Dr. Bérard, along with two professional colleagues, published what they called a systematic review of antidepressant use in pregnancy and birth outcomes.4 In this review, Bérard specifically advised that paroxetine should be avoided by women of childbearing age, but she and her colleagaues affirmatively encouraged use of other SSRIs, such as fluoxetine, sertraline, and citalopram:
“Clinical Approach: A Brief Overview
“For women planning a pregnancy or when a treatment initiation during pregnancy is deemed necessary, the decision should rely not only on drug safety data but also on other factors such as the patient’s condition, previous response to other antidepressants, comorbidities, expected adverse effects and potential interactions with other current pharmacological treatments. Since there is a more extensive clinical experience with SSRIs such as fluoxetine, sertraline, and citalopram, these agents should be used as first-line therapies. Whenever possible, one should refrain from prescribing paroxetine to women of childbearing potential or planning a pregnancy. However, antenatal screening such as fetal echocardiography should be considered in a woman exposed prior to finding out about her pregnancy.”5
When Bérard wrote and published her systematic review, she was still actively involved as an expert witness for plaintiffs in lawsuits against the manufacturers of paroxetine. In her 2010 review, Dr. Bérard gave no acknowledgment of monies earned in her capacity as an expert witness, and her disclosure of potential conflicts of interest was limited to noting that she was “a consultant for a plaintiff in the litigation involving Paxil.”6 In fact, Bérard had submitted multiple reports, testified at deposition, and had been listed as a testifying expert witness in many cases involving Paxil or paroxetine.
Not long after the 2010 review article, Glaxo settled most of the pending paroxetine birth defect cases, and the plaintiffs’ bar pivoted to recast their expert witnesses’ opinions as causal teratogenic conclusions about the entire class of SSRIs. In 2012, the federal courts established a “multi-district litigation,” MDL 2342, for birth defect cases involving Zoloft (sertraline), in the Philadelphia courtroom of Judge Cynthia Rufe, in the Eastern District of Pennsylvania.
Notwithstanding her 2010 clinical advice that pregnant women with depression should use fluoxetine, sertraline, or citalopram, Dr. Bérard became actively involved in the new litigation against the other, non-Paxil SSRI manufacturers. By 2013, Dr. Bérard was on record as a party expert witness for plaintiffs, opining that setraline causes virtually every major congenital malformation.7
In the same year, 2013, Dr. Bérard published another review article on teratogens, but now she gave a more equivocal view of the other SSRIs, claiming that they were “known carcinogens,” but acknowledging in a footnote that teratogenicity of the SSRIs was “controversial.”8 Incredibly, this review article states that “Anick Bérard and Sonia Chaabane have no potential conflicts of interest to disclose.”9
Ultimately, Dr. Bérard could not straddle her own contradictory statements and remain upright, which encouraged the MDL court to examine her opinions closely for methodological shortcomings and failures. Although Bérard had evolved to claim a teratogenic “class effect” for all the SSRIs, the scientific support for her claim was somewhere between weak to absent.10 Perhaps even more distressing, many of the pending claims involving the other SSRIs arose from pregnancies and births that predated Bérard’s epiphany about class effect. Finding ample evidence of specious claiming, the federal court charged with oversight of the sertraline birth defect claims excluded Dr. Bérard’s causal opinions for failing to meet the requirements of Federal Rule of Evidence 702.11
Plaintiffs sought to substitute Nicholas Jewell for Dr. Bérard, but Dr. Jewell fared no better, and was excluded for other methodological shenanigans.12 Ultimately, a unanimous panel of the United States Court of Appeals, for the Third Circuit, upheld the expert witness exclusions.13
1 See “FDA Advising of Risk of Birth Defects with Paxil; Agency Requiring Updated Product Labeling,” P05-97 (Dec. 8, 2005) (emphasis added).
2 Bérard Report in Hayes v. SmithKline Beecham Corp, 2009 WL 3072955, at *4 (N.D. Okla. Feb. 4, 2009) (emphasis added).
3 Deposition Testimony of Anick Bérard, in Hayes v. SmithKline Beecham Corp., at 120:16-25 (N.D. Okla. April 2009).
4 Marieve Simoncelli, Brigitte-Zoe Martin & Anick Bérard, “Antidepressant Use During Pregnancy: A Critical Systematic Review of the Literature,” 5 Current Drug Safety 153 (2010).
5 Id. at 168b.
6 Id. at 169 (emphasis added).
7 See Anick Bérard, “Expert Report” (June 19, 2013).
8 Sonia Chaabanen & Anick Bérard, “Epidemiology of Major Congenital Malformations with Specific Focus on Teratogens,” 8 Current Drug Safety 128, 136 (2013).
9 Id. at 137b.
10 See, e.g., Nicholas Myles, Hannah Newall, Harvey Ward, and Matthew Large, “Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations,” 47 Australian & New Zealand J. Psychiatry 1002 (2013).
11 See In re Zoloft (Sertraline Hydrochloride) Prods. Liab. Litig., MDL No. 2342; 26 F.Supp. 3d 449 (E.D.Pa. 2014) (Rufe, J.). Plaintiffs, through their Plaintiffs’ Steering Committee, moved for reconsideration, but Judge Rufe reaffirmed her exclusion of Dr. Bérard. In re Zoloft (Sertraline Hydrochloride) Prods. Liab. Litig., MDL No. 2342; 12-md-2342, 2015 WL 314149 (E.D. Pa. Jan. 23, 2015) (Rufe, J.) (denying PSC’s motion for reconsideration). See “Zoloft MDL Relieves Matrixx Depression” (Jan. 30, 2015).
12 See In re Zoloft Prods. Liab. Litig., No. 12–md–2342, 2015 WL 7776911 (E.D. Pa. Dec. 2, 2015) (excluding Jewell’s opinions as scientifically unwarranted and methodologically flawed); In re Zoloft Prod. Liab. Litig., MDL NO. 2342, 12-MD-2342, 2016 WL 1320799 (E.D. Pa. April 5, 2016) (granting summary judgment after excluding Dr. Jewell). See also “The Education of Judge Rufe – The Zoloft MDL” (April 9, 2016).
13 In re Zoloft Prod. Liab. Litig., 858 F.3d 787 (3d Cir. 2017). See “WOE — Zoloft Escapes a MDL While Third Circuit Creates a Conceptual Muddle” (July 31, 2017).
