Zantac was one of some seven anti-acid remedies available - until April 1, 2020 [1], when the FDA asked for its voluntary recall. It wasn’t that the drug, known as ranitidine, per se, was a concern. Rather, it was the fear that, over time, the drug could degrade to a compound called N-Nitrosodimethylamine (NDMA), a probable human carcinogen at sufficient doses. [2]
The manufacturers promptly complied, and just as promptly, plaintiffs’ lawyers brought class actions and individual suits nationwide, so optimistic were they of an outcome of liability. In August 2022, generic manufacturers agreed to a $500,000 Zantac settlement a week before the first trial, escalating expectations and exciting invitations to file lawsuits on plaintiffs’ attorney’s websites. It is estimated that 200,000 people are claiming Zantac injuries.
“[T]he science linking Zantac and the carcinogenic molecule has been clear, so even without the FDA's recent move, causation would be solid.”
- Jason Zweig of Hagens, Berman, Sobol, Shapiro
Some 50,000 claims were registered in federal courts across the country and consolidated in Florida via Multi-District Litigation (MDL), a procedure that expeditiously resolves overriding questions affecting all plaintiffs, such as negligence (claiming failure to warn that ranitidine is unstable and can form NDMA in the stomach) and the admissibility of scientific evidence supporting its alleged cancer causation. In what appeared to be a further mark of serious appraisal of the likelihood of success and strength of their evidence, the lead plaintiff attorneys limited these federal cases to five cancers: esophageal, bladder, stomach, liver, and pancreatic - cases, which appeared the strongest.
Admissibility of Scientific Evidence
Admissibility of scientific evidence in all federal courts and 43 states is governed by the Daubert standard, named after the 1993 Supreme Court case of Daubert v. Merrell Dow. The ultimate test, codified in the Federal Rules of Evidence (Rule 702), requires that the evidentiary basis of the testimony is
- based on sufficient facts or data
- the product of reliable principles and methods, and
- that the expert has reliably applied the principles and methods to the facts of the case.
As Daubert explains, the expert testimony must be reliable, relevant, and fit the facts of the case. The case suggests a non-exclusive and non-mandatory list of five “tests” against which the experts’ proffered testimony might be assessed. A later case, Joiner, requires that the expert’s conclusions must be reasonably tethered to the methodology used. Ipse dixit (or “because I say so”) is insufficient, no matter who the expert is.
The first step in evaluating the scientific evidence involves evaluating the plaintiff’s proffered proof of general causation, i.e., that the substance in question can cause cancer (leaving the question of whether the dose to which individual plaintiffs were exposed was sufficient to individual cases determining specific causation). But for ranitidine, that question is murkier.
After conducting a three-day “Daubert hearing,” Judge Robin Rosenberg dismissed the entire cadre of plaintiffs’ scientific evidence in a blistering 341-page opinion. Daubert charges judges with being the “gatekeeper of scientific evidence,” and Judge Rosenberg took her job seriously, determining that all ten plaintiffs’ experts proffered testimony failed to meet the minimum standard to assure scientific reliability, relevance, and fit.
If NDMA is well-recognized as a probable carcinogen, how could the judge reject the experts’ causal testimony?
The issue, stated the judge citing a litany of cases, is not whether the alleged breakdown product, NDMA, is a probable carcinogen but whether ranitidine itself is a probable carcinogen. And that depends, to a large extent, on:
- The amount of NDMA which accumulates over time and to which a potential plaintiff is exposed, i.e., the dose. and
- Epidemiological evidence proving a causal relationship between ranitidine and cancer – which until the last moment -- was non-existent.
NDMA is ubiquitous, found, for example, in grilled and processed meats and water. The FDA’s acceptable daily intake (allowable limit) in consumer products is 96ng – considered a protective level, not a level signifying causation.
In 2019 along came a citizen suit based on a study by Valisure, a private company, claiming it found NDMA in ranitidine in excess of three million nanograms! It was this finding that launched the current lawsuits (and spurred further FDA investigation), raising, among other issues, the question of dose-response (which ACSH’s stellar toxicologist, Susan Goldhaber, addresses here).
To produce a three million nanogram potential dose, Valisure manipulated the evidence - heating the ranitidine to 266 degrees Fahrenheit rather than normal storage levels or a human body temperature of 98.6 degrees. To be sure, they also tested ranitidine at 98 degrees- but now they mixed it with salt. This time they got a dose of 300,000 nanograms. Does this comport with the relevance test required in Daubert? The court said not.
“[A]ccording to a Plaintiff’s expert… the amount of salt used to generate 300,000 ng of NDMA was so great that it was close to the level where, upon consumption, the salt intake would cause death. When Valisure tested ranitidine with salt concentrations more closely approximating what a human could safely ingest, Valisure detected no NDNA.”
- Judge Rosenberg
The decision begins with a review of the Valisure studies before Judge Rosenberg laces into the plaintiffs’ chemical expert, Dr. Najafi, who bases his assessment of grossly excessive NDMA from ranitidine breakdown on his own studies, which the judge found unreliable. She follows with a rather unusual didactic and detailed review of the epidemiological and laboratory studies on which the other experts base their testimony, finding that all ten experts’ proffered testimony was internally inconsistent, irrelevant, and unreliable. Demonstrating that their “pick and choose” methodology (using cherry-picked data where it was favorable and ignoring unfavorable data- without explanation where it wasn’t) was inherently and fatally unreliable, she dismisses the case.
The judge examined each and every piece of evidence and data in a fashion that one typically sees only on cross-examination by astute defense lawyers. While the judge is allowed some discretion to dismiss a case where the evidence is so outrageous (e.g., internally inconsistent) that no reasonable jury would accept it, it is unclear if Judge Rosenberg overstepped her role here.
The federal plaintiffs are appealing. It remains to be seen what the appellate courts will make of Judge Rosenberg’s extensive judicial review.
But even if the federal decision is sustained, that doesn’t end the matter. Tens of thousands of plaintiffs have filed cases claiming 15 other types of cancer in state courts.
“I’m continuing to pursue those claims because I think they’re valid claims… I think the plaintiffs have a good case and the science is strong. I’m not going to drop a valid claim when I think that my client has the possibility of recovering.”
– Plaintiffs’ lawyer Ashley Keller, handling 7000 cases in California.
Various reasons are given for the state court filings: procedural necessities, past decisions by the federal judge adverse to the plaintiffs (forum shopping), state experience in managing complex litigation, and state courts generally are preferable for plaintiffs. The state cases are concentrated in five states: Delaware, Pennsylvania, New York, Illinois, and California. And there’s an unarticulated reason for this, one which concerns anyone interested in excluding junk science from the courtroom.
The admissibility (and soundness) of the plaintiff’s scientific evidence, which is critical to the plaintiff’s proof, differs in these five states from the rest of the country. Seven states, including the five where the remaining Zantac cases are being brought, are governed by the Frye standard after a case decided in 1923. The Frye standard governed the admissibility of scientific evidence nationally until the Daubert decision was decided 70 years later as a response to the “junk science in the courts” epidemic. Frye requires that the evidence needs to comport with the consensus of opinion in the scientific community. Daubert’s tests are more fluid and allow -but don’t require - consideration of the Frye standard.
Thousands of scholarly articles have debated which standard favors which side. Some profess that Daubert is more amenable to novel claims and might be more hospitable to the Zantac cases. Thousands of plaintiffs and their lawyers must think otherwise - most likely because the FDA decided to recall the drug (presumably demonstrating scientific consensus) in 2020.
We’ll have to wait and see.
[1] Zantac has been replaced by an alternative, Sanofi’s famotidine, which is not part of the recall, still leaving seven anti-acid remedies available.
[2] “According to the FDA, if one were to consume 96 ng of NDMA every day for 70 years in succession, the risk of cancer would be 1 in 100,000 or .001%” – Judge Robin Rosenberg
