Delaware Zantac Court Fails to Keep the Gate

This post is from the non-Reed Smith, non-Dechert, and non-Holland & Knight side of the blog. 

We have covered the ranitidine litigation before. As we explained in prior posts (including here and here), plaintiffs allege that ranitidine, the active ingredient in Zantac, breaks down into N-Nitrosodimethylamine (“NDMA”), particularly at higher temperatures.  NDMA is a known carcinogen and a ubiquitous substance present in the environment and in all manner of foods including bacon, beer, and cheese.  Readers will remember that in a sweeping, 341-page opinion, the MDL court cut the head off the federal Zantac litigation by excluding plaintiffs’ experts.  But other parts of the snake keep slithering. 

Delaware has long been known as a jurisdiction where corporations can receive reasonable, fair-minded treatment.  This opinion significantly jeopardizes that reputation and should concern the many companies that can be hauled into court in the state of Delaware by virtue of being incorporated there. 

In this disappointing decision, In re Zantac (Ranitidine) Litig., 2024 WL 2812168 (Del. Sup. June 3, 2024), the Court overseeing the Delaware coordinated Zantac litigation denied each and every Rule 702 challenge before it.  As the Advisory Committee Notes for the 2023 amendments to Rule 702 stated, “many courts have held that the critical questions of the sufficiency of an expert’s basis, and the application of the expert’s methodology, are questions of weight and not admissibility.  These rulings are an incorrect application of Rules 702 and 104(a).”  The Delaware court’s Zantac opinion epitomizes the outdated and incorrect thinking that the Rule 702 amendments were designed to correct. 

Delaware courts apply Delaware Rule of Evidence 702, which is “nearly identical to Federal Rule of Evidence 702” and the Delaware Supreme Court professes to follow “the holdings of Daubert v. Merrell Dow Pharm., Inc. (“Daubert”) and its progeny.”  Zantac, 2024 WL 2812168, *3.  The Delaware Zantac court acknowledged this, and yet still sought to distinguish itself from the MDL court by saying Delaware law applies.  The Delaware court also took great pains to distinguish the issues before it from the MDL court’s ruling, noting that the experts were not the same, and that Plaintiffs included a slightly broader list of cancers than those pursued in the MDL court (presumably because they have even weaker support).  But even though the experts were not the same, their logic was.  Rather than following the thorough, well-reasoned decision of the MDL court, the court found more support in a pre-Rule 702 amendments decision from another litigation in the Northern District of California.  The court also relied on such dubious propositions as “[t]he reliability requirement is not a tool for the Court to use to exclude questionably reliable evidence.”  Id. at *4.  What is it for, then? 

Threshold Issues

In framing the question of general causation, the court signaled from the get-go that gatekeeping would be non-existent.  Rather than focusing on whether ranitidine causes cancer—the highest quality medical evidence says it does not—the court stated that “[t]he discrete issue before the Court at this stage is whether NDMA can cause cancer.”  Id. at *8.  The court therefore refused to “constrain its gatekeeping function solely to the studies related to ranitidine.”  Id. at *10.

The court stumbled over another threshold, the “threshold dose.”  A key issue in this litigation is “threshold dose”—that is, what the MDL court described as “the minimum amount of a substance below which the substance would not cause the disease or effect, even where exposure occurs repeatedly over the long-term.”  In re Zantac (Ranitidine) Products Liab. Litig., 644 F. Supp. 3d 1075, 1266 (S.D. Fla. 2022).  The MDL court held that the plaintiffs had to “identify a threshold dose, even if the dose is described only as a range.”  Id. at 1109.   This makes good sense.  As the MDL court observed, “NDMA is a ubiquitous substance found in trace amounts in air, water, and food.”  Id. at 1106.  It is therefore logical that a plaintiff must establish some threshold where the exposure could be actionable.  As the MDL court also observed, “[c]ourts universally reject general causation theories based upon the idea that any amount of a carcinogen, no matter how small, is actionable because an infinitesimal risk can neither be proven nor disproven.”  Id. at 1109.  The Delaware court entirely missed this fundamental logic.

Instead, the Delaware court relied on the bold statement that “Delaware does not recognize a threshold dose requirement.”  Zantac, 2024 WL 2812168, *6 (quotation marks omitted).  The only Delaware cases it cited for this broad statement were unpublished Delaware trial court decisions.  Based on this tenuous support, the court concluded that threshold dose “remains, like general acceptance and statistical significance, one of the factors enumerated by Daubert and its progeny to be considered in the general causation analysis.”  Id. at *14.  It declined to impose a “bright line threshold dose requirement”—even though the MDL court did not impose a “bright line” at all, but at least demanded that plaintiffs establish a range at which there was any real risk of cancer.

Expert-Specific Challenges

At the beginning of this year, we hoped that Maybe New Rule 702 Can Rein in Bradford-Hill Abuse.  That hope was certainly not realized in this opinion.  Over and over, the court cited Bradford Hill as a talisman of reliability, without any serious consideration of the actual analysis or criteria.

For the sake of brevity, we will not repeat the court’s expert-by-expert analysis.  It would be redundant, repeating the cop-outs of “weight not admissibility,” “fodder for cross-examination,” and “battle of the experts.”  As noted above, these well-worn excuses for failure to keep the gate should no longer be accepted.  Throughout the opinion, the court held that serious challenges to methodology, such as cherry-picking data; not giving appropriate weight to studies; using outcome-driven reasoning; expert contradicting themselves both in and out of court; and generally relying on improper studies, including studies that weren’t peer-reviewed, were simply matters for cross-examination.  For example, one expert opined that ranitidine caused kidney cancer in his report while stating in peer-reviewed literature published after his deposition that the data was insufficient to demonstrate a causal connection.  Even this was not ground for exclusion.

The court pointed out that the experts at issue in its opinion were not the same experts addressed in the MDL court’s opinion.  Yet the studies were the same, and the court did not meaningfully distinguish these experts’ analysis from that of the MDL experts.  For instance, Defendants attacked Plaintiffs’ experts’ reliance on the Hidajat study, which “did not involve ranitidine at all.”  Id. at *17.  The MDL court had roundly rejected reliance on this study, which focused on the effects of inhaled fumes from a 1967 rubber factory.  In the MDL court, Dr. Hidajat herself filed a rebuttal report, admitting that her study was not designed to assess NDMA exposure through an oral medication.  Nevertheless, the Delaware court rejected Defendants’ challenges to this study.  Even while acknowledging that “[p]erhaps . . . [the expert’s] science may be a bridge too far,” the court denied exclusion, stating “the criticisms go to weight.”  Id.

Similarly, Plaintiffs’ expert Dr. Dan J. Raz considered seven epidemiological studies and gave more weight to two of them:  Wang and Habel.  The MDL court criticized reliance on these studies for a number of reasons, including that Wang employed “situational science,” (i.e., not consistent, reliable science) and concluded that there was a “lack of concrete evidence” that ranitidine causes cancer and “further studies are necessary.” Zantac, 644 F. Supp. 3d at 1258.  And Habel was not even designed to measure the effects of ranitidine, but rather another drug.  Rejecting these serious concerns, the Delaware court found this too was all a matter for the jury.

Even though the epidemiological studies reported no statistically significant, positive associations between ranitidine use and prostate cancer, that did not deter Plaintiffs’ epidemiologist Dr. Bruce Trock, who found reason to disagree with them all.  Defendants argued that even if not the conclusive standard, general acceptance is still an indicator of reliability.  The court would hear none of it, stating that “[t]his evidence is to be used flexibly when evaluating reliability.”  Zantac, 2024 WL 2812168, *30.  Dr. Trock ignored epidemiological ranitidine studies in favor of studies on rubber workers and animals, which the MDL court rejected.  But, the Delaware court said, “as presented through these experts, in Delaware, it is not the role of this Court to substitute its scientific conclusions for those of an expert scientist.”  Id.  How the court could reach this conclusion with the same studies and purportedly the same Rule 702 standard is perplexing indeed. 

Emery Pharma Testing

The second half of the court’s opinion was devoted to Defendants’ challenges to testing conducted by Emery Pharma, which was retained by Plaintiffs to “conduct further testing on the levels of NDMA in ranitidine provided by Defendants and specifically the levels in Plaintiffs’ own pills and opine on the nature of ranitidine’s ability to degrade and transform into NDMA.” Id. at *31.  The court observed that “the somewhat more aggressive and pejorative rhetoric in the briefs suggests the Emery opinion lies at the heart of the Daubert debate, for both sides.”  Id.  Defendants offered nine challenges to the admissibility of the Emery Opinion, including unvalidated methodology and improper protocols, unfollowed protocols, failure to keep proper documentation, failure to submit methodology for testing or peer review, lack of “fit,” and simulated studies and other tests that were unreliable and did not meet Daubert standards.

Defendants challenged the use of Hydrophilic Interaction Chromatography (“HILIC”) to test for NDMA in ranitidine.  The MDL court observed that “[n]o scientist outside of Emery Pharma has used or validated HILIC for the specific purpose of measuring NDMA in ranitidine,” concluding that it failed each of the Rule 702 factors.  Zantac, 644 F. Supp. 3d at 1119. Emery’s own assurances were not enough to establish reliability.  The Delaware court rejected the MDL court’s reasoning, stating that “[f]ollowing Delaware jurisprudence, this Court finds that HILIC has been validated and determined reliable, and its use in measuring ranitidine constitutes sound methodology to survive a Daubert challenge.”  Zantac, 2024 WL 2812168, *32.  Why Delaware would allow this technology where federal standards would not is entirely unexplained.

Defendants also challenged Emery’s use of manual data integration, where analysts had unfettered discretion over the use of manual integration. The court was reassured by the Emery representative’s testimony that he supervised the work and double-checked the lab, lab notebooks, and synthesized the data.  As to the manual versus electronic data integration question, the court held “these are complicated questions well beyond the wisdom of this trial judge, who, consistent with Daubert and its progeny, will not pick a winner. The answer rests with the jury.”  Id. at *33.

The court dismissed all remaining challenges to the reliability of Emery’s work, ruling:

• Lack of documentation of lab results was no problem. 
• Dr. Najafi could rely on the work of his team and he was not improperly “parroting” work done by others.  
• Lack of publication or peer review was not a basis for exclusion, but just more fodder for cross-examination. 
• The lack of “fit” between the baseline testing of the “active pharmaceutical ingredients” alone as opposed to the finished pill did not compel exclusion.
• Emery’s “simulated consumer experience” tests were admissible. What, you might be wondering, is a simulated consumer experience test?  It involved Emery simulating conditions where the product might end up, like a car or bathroom.  But instead of putting the tablets actually in a car or bathroom, Emery put them in a chamber producing those simulated conditions and different climatic zones.  The MDL court analyzed these “unrealistic” and “exaggerated” tests in detail.  Zantac, 644 F. Supp. 3d at 1146–53.  For instance, for the car test, Emery used the temperature of a sun-exposed car dashboard, as though that is where people would keep their ranitidine.  The Delaware court waved away all these arguments, stating that “[t]his dispute is appropriate grist for the jury’s mill.”  Zantac, 2024 WL 2812168, *36.
• The same was true of a host of other tests conducted by Emery.  Without much individual discussion the court found all manner of testing had sufficient fit and any challenges went to weight, not admissibility.  Id. at *37–38.
• The court was not deterred by the fact that the results reported in the Delaware Report do not match the results reported in the MDL Report “due to tabulation and sorting errors.”  The court declined, yet again, “to defer to the MDL decision on reproducibility,” adding to the large pile of fodder for cross-examination.  Id. at *38. 

Again and again, the court held that Defendants’ “challenges. . . . fall victim to the wisdom of Daubert: they belong to the jury.”  Id. at *27.  If this is the “wisdom of Daubert” that is all the more reason to Don’t Say Daubert.  The court’s reasoning is out-of-step with post-amendment Rule 702 rulings. 

Defendants have filed an Application for Interlocutory Review of this decision.  We hope the appellate court will course-correct this shift in Delaware jurisprudence.