In another blow to the plaintiffs alleging that Pfizer’s antidepressant, Zoloft, causes birth defects, the federal judge handling the case rejected the testimony of three of their expert witnesses.
In June, the judge tossed their key expert on causation. The three witnesses at issue in the most recent opinion will be allowed to testify to their conclusions about general biological plausibility regarding the drug’s effect on developing embryos, but they won’t be allowed to testify to the drug’s causation of birth defects in humans.
Zoloft has been on the market for 20 years, said U.S. District Judge Cynthia Rufe of the Eastern District of Pennsylvania, and it has been prescribed to pregnant women that whole time, so there is a significant amount of epidemiological research available.
The experts—Thomas Sadler, a teratologist and embryologist; Robert Cabrera, a teratologist; and Michael Levin, a molecular developmental biologist—needed to address the existing epidemiological research, some of which is at odds with their opinions about human causation, the judge said. But, they didn’t.
“The experts’ failure to reconcile inconsistent epidemiological research with their opinions regarding human causation is a significant methodological flaw, undermining their reliability under Daubert,” Rufe said.
In April, she had held a weeklong Daubert hearing—so named for the 1993 U.S. Supreme Court case Daubert v. Merrell Dow Pharmaceuticals, which created a route for parties to challenge expert testimony before the start of trial—which had focused primarily on Dr. Anick Bérard, who was a key expert for the plaintiffs.
Rufe excluded Bérard’s testimony in an opinion issued in June.
“The court notes that Drs. Cabrera, Sadler, and Levin were retained for their expertise on biological mechanisms, and although they each reviewed the epidemiological literature, it was Dr. Bérard who was retained for her expertise in that field,” Rufe said in a footnote. “Had the court found Dr. Bérard’s methodology was sound, they would have been justified in relying upon her report as evidence in support of their own human causation opinions. However, without Dr. Bérard’s opinion to rely upon, the court must examine whether each of these experts adequately addressed the epidemiological evidence in forming their opinions on human causation.”
Rufe had found that Bérard’s methods wouldn’t pass muster for the court.
Bérard, a professor at the University of Montreal, researches the effect of medications on pregnancy, within the field of teratology, which is the study of congenital abnormalities.
“The court finds that the expert report prepared by Dr. Bérard does selectively discuss studies most supportive of her conclusions, as Dr. Bérard admitted in her deposition, and fails to account adequately for contrary evidence, and that this methodology is not reliable or scientifically sound,” Rufe said in her opinion excluding Bérard’s testimony.
Sadler, Cabrera and Levin, however, are experts in biological mechanisms and their testimony in that regard will be allowed at trial, Rufe said.
“Biological plausibility is one of the criteria scientists need to address in opining as to whether an association between a substance and an adverse outcome reflects a causal relationship (i.e., whether the substance is a teratogen),” Rufe said, explaining that the plaintiffs’ steering committee had intended to use Sadler, Cabrera and Levin to testify as to Zoloft’s adverse impact on fetal development.
“All three experts opine that there is at least one plausible biological mechanism by which SSRIs generally, and Zoloft particularly, may alter embryonic development,” Rufe said.
Zoloft is part of a class of antidepressant drugs called selective serotonin reuptake inhibitors, or SSRIs, which regulate the amount of serotonin available to the brain.
The experts’ research on in vitro and in vivo animal studies—an example of an in vitro study being an animal embryo removed from the mother and observed in a lab dish as it was exposed to medication, whereas in vivo studies observe the impact of a drug on the whole animal system—is sufficient to establish their views that there is a plausible biological mechanism triggered by altered concentrations of serotonin in a developing embryo that could cause birth defects.
So, they can testify to the issue of plausible biological mechanisms.
That research doesn’t necessarily translate to show that Zoloft causes defects in human embryos, Rufe said, ruling that they can’t testify as to human causation.
One of the reasons that those studies can’t be used directly to show human causation, the judge stressed, is that the dosage level for the drug can be much higher in those studies than would be prescribed for people.
“In order to reliably opine as to human causation, the experts must address whether the children of pregnant women taking Zoloft in typical (or even maximum) clinical doses are at an increased risk of birth defects. The in vitro and in vivo animal studies have found associations between exposure and adverse outcomes only at concentrations well above the maximum recommended human dose,” Rufe said. “The experts have not reconciled the dose-response evidence with their opinions on human causation.”
Pfizer released a statement about the ruling, saying, “We are pleased that the court agreed to limit the testimony of the plaintiffs’ expert witnesses under the Federal Rules of Evidence.” It also noted Rufe’s earlier ruling on Bérard’s testimony, saying that it “plainly describes the difficulty plaintiffs will have in establishing general causation in this litigation, an essential element to prove their case.”
Dianne Nast of NastLaw, who is on the plaintiffs’ steering committee, couldn’t be reached for comment.
(Copies of the 24-page opinion in In re Zoloft, PICS No. 14-1263, are available from The Legal Intelligencer. Please call the Pennsylvania Instant Case Service at 800-276-PICS to order or for information.) •