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What follows is from the non-Dechert side of the Blog.

In the Zantac MDL, the plaintiffs’ causation problems were plainly visible on the horizon, as we mentioned in our post last year about the Zantac ruling on medical monitoring, In re Zantac (Ranitidine) Products Liability Litigation, 546 F. Supp.3d 1152 (S.D. Fla. 2021).  The Zantac MDL plaintiffs’ claims regarding risk of injury and exposure levels to purported ranitidine-derived nitrosamines (“NDMA” for short) seemed not only trivial, but in many ways bizarre (use of extreme temperatures and other parameters).  They even relied on a retracted study.  That’s why we referred to the “wheels coming off” the plaintiffs’ scientific case in that post.

Now the plaintiffs’ wheels are fully off in Zantac MDL – as we mentioned before, all of their causation experts for the five types of cancer that plaintiffs themselves considered the most plausible have been excluded under F.R. Evid. 702, and summary judgment entered.  In re Zantac (Ranitidine) Products Liability Litigation, ___ F. Supp.3d ___, 2022 WL 17480906 (S.D. Fla. Dec. 6, 2022).  This is a lengthy opinion, 341 pages in slip form.  To keep this post as short as possible, we’ll be summarizing (at best) large parts of it.

Lab Rats – Or at Least A Ratty Lab

Both the “independent” laboratory whose questionable product testing sparked this litigation, and the plaintiffs’ experts, used every trick in the book to inflate the amount of NDMA supposedly generated by the purported “normal” breakdown of ranitidine.

The sketchy testing by the lab, Valisure, was the “best starting point” for why this litigation was bogus from the beginning.  2022 WL 17480906, at *1.  Filing a citizen’s petition, Valisure shocked the FDA into an ill-advised recall by reporting that “tests found NDMA in ranitidine in excess of 3,000,000 ng [nanograms] per pill” – far above FDA’s 96 ng/day “daily limit.”  Id.  In a case of “garbage in, garbage out,” Valisure used extreme methods to generate that badly skewed result:

To achieve a test result of 3,000,000 ng, however, Valisure had to heat the ranitidine to a temperature well above the 98 degrees Fahrenheit found in the human body; Valisure used a temperature of 266 degrees Fahrenheit.  When Valisure tested ranitidine with a temperature of 98 degrees Fahrenheit, Valisure detected no NDMA.

2022 WL 17480906, at *2 (emphasis added).

There’s plenty more unscientific method where that came from.  Valisure tested ranitidine metabolism using what is called “artificial stomach.”  “Artificial,” indeed.  Salt was thought to enhance NDMA metabolizing, so Valisure dumped plenty into its testing device.  Sure enough, it coaxed out a big number − 300,000 ng.  Id.  The Zantac opinion observed that the amount of salt “was so great that it was close to the level where, upon consumption, the salt intake would cause death.”  Id.

The FDA recognized these results as bogus, “conclud[ing] that . . . Valisure’s laboratory equipment created the very substance for which it was testing.”  Id.  The FDA ran its own tests, and while “the FDA’s tests revealed NDMA levels far below Valisure’s,” some tests were above the agency’s “conservative, protective” 96 ng daily limit.  Id.  So it “initiated” a “voluntary recall.”  Id.  However, the FDA’s standard was about as far from tort causation (“more likely than not”) standards as it could be:

According to the FDA, one could expect to consume this much NDMA from eating a meal of grilled or smoked meats, yet those foods are lawful to sell.  Also, 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%.

Id. (emphasis added again).

The usual MDL attorney solicitation generated the usual indiscriminate mass of claims.  Plaintiffs gradually whittled down the range of claims until five targeted types of cancer remained − bladder, esophageal, gastric, liver, and pancreatic.  2022 WL 17480906, at *7.  Then plaintiffs had to select experts and prove up a causation case.

They couldn’t.

First, plaintiffs attempted to argue that they didn’t have to prove general causation at all, because the NDMA breakdown product from ranitidine was allegedly a “generally recognized” carcinogen.  Id. at *13.  That didn’t work – because, math.  NDMA is a trace impurity, not an intended product component, like asbestos or tobacco.

Plaintiffs must show that ranitidine consumption can result in sufficient NDMA ingestion to cause their alleged injuries. . . .  Plaintiffs’ position leads to untenable results.  NDMA is a ubiquitous substance found in trace amounts in air, water, and food.  Taken to its logical conclusion, the Plaintiffs’ . . . reasoning would mean that the scientific community generally accepts the proposition that air, water, vegetables, and many meats cause cancer − so much so that no plaintiff . . . need produce evidence for those propositions.

Zantac, 2022 WL 17480906, at *14 (citation omitted).  “The product in this MDL is ranitidine.  A jury would decide whether ranitidine caused any Plaintiff’s cancer.”  Id. at *16.

A Numbers Racket

The “lack of validity” of Valisure’s testing was so glaring that even plaintiffs “ultimately elected not to rely upon Valisure’s test results.”  Id. at *3.  So they made up their own.  Because plaintiffs’ experts used practically every possible trick to cook their own results, every last one got the Rule 702 boot.  Plaintiffs used parallel approaches:  (1) hiring a chemist (Najafi) to conduct his own methodologically impaired tests for NDMA in ranitidine pills, and (2) engaging epidemiologists (Moorman and to some extent Davis) to ignore existing epidemiology and gin up more plaintiff-friendly results  using “the raw data found in studies that analyzed NDMA-rich food and NDMA-rich air” rather than ranitidine  Id.

The chemist’s results were almost as deficient as Valisure’s.  His non-litigation work had been in line with everybody else’s results, id. at *3 n.1, but after being hired −

[He] used laboratory equipment that differed from the laboratory equipment used by the FDA.  Using his equipment, he found NDMA levels in ranitidine far, far higher than those found by any governmental body in the world.

Zantac, 2022 WL 17480906, at *3 (footnote omitted).

Thus, the chemist purported to prove that “one ranitidine pill has the same NDMA as several pounds of bacon.”  Id. at *18.  That didn’t work so well.

  • The FDA’s testing determined “that the average amount of NDMA . . . was less than [its] daily limit for NDMA of 96 ng per pill.”  Id. at *19.
  • The chemist’s testing “resulted in an average amount of NDMA per pill (approximately 1,000 ng) that far exceeded the results of FDA testing.”  Id.
  • Those results could not be validated.  He used a method of chromatography (“HILIC column”), that had never been peer reviewed and had no established error rate.  Id. at *26-27.
  • His “laboratory has no standard operating procedures, parameters, or criteria for manual integration” of data.  Id. at *25.
  • His chromatography method heated the ranitidine being tested, thus generating more NDMA, just like Valisure.  Id. at *28-29.
  • Almost every test was subjected to “manual integration, a process by which a laboratory analyst may manipulate the results,” without laboratory protocols, beyond “use your own judgment,” for when it was to occur.  Id. at *29-33.
  • Documentation for the testing was jumbled and incomprehensible, making reproduction of their results impossible.  Id. at *36-38.
  • The chemist did none of the testing himself, and “left operational decisions to the professional judgment of his employees” with “no written procedures, instructions, or guidance that would inform analysts of how to perform manual integrations.”  Id. at *40-41.
  • Due to supposed litigation “confidentiality,” none of his testing was peer reviewed.  Id. at *42.
  • Over a third of the tests were conducted on expired products, which produced NDMA readings more than twice as high.  Id. at *43.
  • Many of the tests were on pills that the laboratory itself “manufactured” from bulk raw ranitidine although “consumers do not ingest ranitidine API [active product ingredient] not manufactured into a finished drug product.”  Id. at *45-47.
  • The chemist tested ranitidine deliberately “using exaggerated storage conditions” including unrealistically high temperatures (up to 167° F) and humidity (often 100%).  Id. at *48-54.
  • The chemist’s artificial stomach testing using simulated “high-nitrite” “food” (pulverized processed meats) that did not attempt to “simulate” “gastric pH” (that is, the effect of stomach acid), or follow serving instructions for the meat.  He omitted negative tests with other types of food from the report.  Id. at *54-57.

After “weigh[ing] all of the Daubert factors, Zantac “conclude[d] that [the chemist’s] expert report is a product of an unreliable methodology and is based upon facts that are not a fit for this case.”  Id. at *58.  Not only was his report excluded, but so were the opinions of several other experts that relied on the chemist’s report for their data.  Id. at *58-60.

Hiding the Ball

Beyond the chemist’s (very) artificial stomach testing, several of plaintiffs’ experts “opine[d] that ranitidine transforms into NDMA inside the digestive tract through a chemical process called ‘nitrosation.’”  Zantac, 2022 WL 17480906, at *60.  These experts relied on four in vivo studies, as well as four in vitro studies, for their opinions.  Id. at *62-64 (in vivo), *71-73 (in vitro).

Plaintiffs alleged that their “weight of the evidence” methodology precluded examination of any particular study.  Id. at *66.  Zantac rejected that argument.  “Weight of the evidence” did “not mean the Court’s role is limited to determining whether the expert relied upon a ‘wide array’ of evidence.”  Id. at 3 *65.  Rather, “every aspect of the expert’s analysis − including his methodology, the combination of facts and scientific evidence on which he relies, and the links between the evidence and his conclusions − must be shown to satisfy Rule 702.”  Id. (citation and quotation marks omitted).  Plaintiff’s “weight of the evidence” approach was merely a fancy jargon for hiding the ball.

[T]he Court has been unable to find any significant descriptions of the steps that the Plaintiffs’ experts took when gathering and assessing studies.  Each of the experts provide only bare-bones description of their methodologies. . . .  None of the Plaintiffs’ . . . experts provide descriptions sufficient to inform the Court of the steps he or she took in gathering and assessing the relevant studies. . . .  This factor weighs strongly against the[ir] admissibility.”

Zantac, 2022 WL 17480906, at *66-67.

How Do Experts Fake It – Let Us Count the Ways

Nor, to the extent plaintiffs’ experts’ methodologies were comprehensible, were those approaches scientifically reliable.

  • “Their reasons for discounting [an adverse study] are internally inconsistent with their decisions to rely upon and assign greater weight to other in vivo studies.”  Id. at *67
  • “It is internally inconsistent for the Plaintiffs to pull individual data points from a study in support of their own conclusions, while simultaneously arguing that the same study is unreliable and that it must be discounted as a whole.”  Id. at *68 (citation omitted).
  • Raising additional, “take my word for it” arguments “in contravention of the Court’s order that new arguments not be raised.”  Id. at *69.
  • Plaintiffs’ studies failed to control “for the diets of their participants.”  Id.
  • Polypharmacy confounded several of plaintiffs’ studies.  Id. at *70.
  • Since NDMA peaks “5 minutes after administration,” it was not reliable to measure for it “four to six weeks” later.  Id.

In sum, plaintiffs’ experts failed to explain their reliance, did so inconsistently “deviat[ing] from their own principles,” and “rel[ied] upon studies that do not support their conclusions.”  Id.

Their reliance on in vitro studies was equally flawed.

  • They once again failed to explain their methodology.  Id. at *74.
  • Once again, they “apply internally inconsistent reasons for discounting” opposing studies.  Id.
  • They fail to “explain how the in vitro data can be reliably extrapolated to predict a drug’s effects in humans.”  Id. at *75 (citation and quotation marks omitted).
  • “[A] human would die with a nitrite concentration [as] high” as used in one of the in vitro studies.  Id. at *76.
  • The experts failed “to explain how the amounts of nitrite tested in the in vitro studies relate to the levels of nitrite found in the human stomach.”  Id.

In sum “[p]laintiffs’ failure to provide an extrapolation explanation means that there is simply too great an analytical gap between the data and the opinion proffered.”  Id. at  *77.

Thus, plaintiffs experts’ attempts to estimate the amount of NDMA − either in the ranitidine pills themselves, or as released into the body by metabolizing the pills – failed miserably and were all excluded.  This exclusion meant that plaintiffs were without evidence of the “dose” side of the dose-response relationship for purposes of general causation.

Statistics for Support Rather Than Illumination

In default of direct experimentation, plaintiffs also sought to use epidemiology as “primary evidence” of general causation.  Zantac, 2022 WL 17480906, at *78.  In general, Zantac found the plaintiffs’ experts’ methodology was utterly inadequate:

Plaintiffs’ scientists within this litigation systemically utilized unreliable methodologies with a lack of documentation on how experiments were conducted, a lack of substantiation for analytical leaps, a lack of statistically significant data, and a lack of internally consistent, objective, science-based standards for the evenhanded evaluation of data.

Id. at *4.  Their conclusions from these unreliable methodologies were, to put it mildly, not generally accepted.  “[N]o scientist outside this litigation [has] concluded ranitidine causes cancer.”  Id.

After a useful primer on epidemiology generally, Zantac, 2022 WL 17480906, at *79-82, the decision addressed defendants’ “generalized” epidemiology challenges.  It was tough for those experts to defend opinions at odds with all non-litigation-generated research.

  • “When an expert purports to apply principles and methods in accordance with professional standards, and yet reaches a conclusion that other experts in the field would not reach, the trial court may fairly suspect that the principles and methods have not been faithfully applied.”  Id. at 83 (citation and quotation marks omitted).
  • None of the ten epidemiological studies on ranitidine (summarized at id. at *84-86) “concluded that there was evidence of an association − let alone causation − between ranitidine and cancer.”  Id. at *84.
  • The FDA believed its testing found “‘low levels’ that ‘would not be expected to lead to an increase in the risk of cancer.’”  Id. at *87 (citation and quotation marks omitted).
  • “[I]t is certainly true that there is no published study or governmental finding that agrees with the Plaintiffs’ experts − there is no published conclusion or finding, outside of this litigation, that concludes that ranitidine causes cancer of any kind.”  Id.
  • “[A] substantial number of studies,” but not all “conclude that there is not a statistically significant, observable association between ranitidine and cancer.”  Id. at *88.
  • “[T]here is no widespread acceptance in the scientific community of an observable, statistically significant association between ranitidine and cancer.”  Id.
  • Studies involving “processed meat” or “rubber factory fumes” cannot fill the epidemiological gap because they also implicate other carcinogens.  Id. at *88-89.

In addition, Zantac contains an extensive, granular analysis of the ten studies at issue, which we are omitting here for reasons of case specificity (and brevity).  See Zantac, 2022 WL 17480906, at *89-94.

Nor is an increased overall cancer rate in the exposed population (“comparator analysis”) of great moment.

It is a very intuitive, common-sense proposition that those who suffer from chronic symptoms that generate the need for many years of acid suppressant consumption are, at least on average, less healthy than a population of people who do not need to consume acid suppressants for many years − a non-user population.

Id. at *95 (footnote omitted).  Rather, “users of other H2-blockers make for a more reliable comparison than people who do not use acid suppressants at all.”  Id. at *96 (footnote omitted).  This was because “the same symptoms that can cause cancer can also generate a need for acid suppressants.”  Id. at *94 n.95. Since that comparison group did not show any significant difference in cancer incidence, plaintiffs’ experts made the wild accusation “that every H2-blocker and every PPI [proton pump inhibitor], all of them, cause cancer.”  Id.  That, Zantac held, was utterly fantastical:

Neither [expert] provides support for the proposition that any researcher or governmental body has concluded that every (or any) H2-blocker and PPI causes cancer, nor have they provided any support for the proposition that it is generally known that such drugs cause cancer.  And since the Plaintiffs’ experts disavow that they have, in this litigation, a specific expert opinion that those drugs cause cancer, they have provided no scientific explanation or methodology to support such an opinion.

2022 WL 17480906, at *98 (emphasis original).  Plaintiffs’ epidemiological opinions also failed the test of statistical significance.  Seven studies “compared ranitidine users to the users of H2-blockers” and all seven” found no statistically significant association between ranitidine and a Designated Cancer.”  Id. at *100.

Since they struck out with ranitidine studies, plaintiffs’ experts “rel[ied] in great part upon epidemiology that did not study ranitidine” – studies of peculiar diets and exposure in rubber factories.  Id.  That got them precisely nowhere.

  • Dietary epidemiology was not a sound basis for an opinion because:  (1) the confounding effects of other carcinogens; (2) plaintiffs’ NDMA exposure opinions were already excluded; and (3) “an apparent discrepancy in risk assessments.”  Id. at *100-03.
  • Retrospective dietary epidemiology is notoriously inaccurate because participants “struggle to remember what their diets were over the course of their lifetime and thus accurately estimate the volume of the unhealthy foods that they ate.”  Id. at *104.
  • “Rubber creation leads to the formation of many different types of carcinogens.”  Id. at *106.

Thus reliance on these non-ranitidine studies was an “unreliable methodology because:  (1) “there are too many inherent uncertainties . . . for such data to be reliably applied to the causation question in this MDL,” id. at *107; (2) they “have only attenuated relevance to the question at hand,” id. at *109; and (3) “for the lifetime-based . . . studies to be part of a reliable methodology, an expert would have to account for the historical amount of NDMA in ranitidine,” and (4) “they have no data to make any conclusions about historical ranitidine NDMA levels.”  Id. at *111.

In addition, Zantac contains an extensive granular and expert-specific critique of the scientific misdeeds of each of plaintiffs’ epidemiological experts.  We simply list the sins that the opinion addresses, since that could be useful in making similar arguments in future cases.

  • Reliance on studies, but not on their conclusions.  Zantac, 2022 WL 17480906, at *113, 116, 119-20, 129 n.133, 136-37, 139, 143, 148.
  • Disregard of relative risk and statistical significance.  Id. at *113-17, 120-23, 127-28 & n.132.
  • Selective reliance on some long-term risk rates while ignoring others.  Id. at *115.
  • Reliance on studies involving other drugs, while ignoring ranitidine-related epidemiology.  Id. at *117.
  • Reliance upon numerically tiny data subsets.  Id. at *117-18.
  • Drawing “impossible” risk estimates from intermingled data.  Id. at *121, 123.
  • Mischaracterization of statistically insignificant data as significant.  Id. at *122-23.
  • “[A]bandon[ing] the concept of statistical significance completely.”  Id. at 123.
  • That “no independent scientist or governmental body has made the [expert’s] analytical leap from the existing data” is “evidence of an unreliable methodology.”  Id. at *124, 139.
  • Incomplete and inadequately explained analysis of Bradford-Hill factors.  Id. at *125-27, *138-39.
  • Failure to publish and obtain peer review.  Id. at *127.
  • Cherry-picking (“selective disregard for”) data.  Id. at *128, *139-40, 143, 145-46.
  • Failure to address existing epidemiology.  Id. at *129, 140.
  • Lack of any dose-response relationship.  Id. at *130.
  • Taking inconsistent positions on dose-response relationship.  Id. at *131-32.
  • Use of “results-based,” “conclusion-oriented,” and “situational science” methods.  Id. at *138, 142 (the expert “applies whatever method is expedient to get to her desired conclusion.  That is the antithesis of reliable science.”), 146.
  • Mixing apples and oranges, particularly with “active comparator analysis.”  Id. at 145-47.

No Dose, No Threshold, No Problem – No Causation

Zantac also addressed a second type of “primary” causation evidence – dose-response relationship.  2022 WL 17480906, at *148-58.  Once again, plaintiffs’ experts’ methodologies were woefully lacking in anything resembling the scientific method.  “[T]he relationship between dose and response is the hallmark of basic toxicology and the single most important factor to consider in evaluating the toxicity of a drug.”  Id. at *149 (citations and quotation marks omitted).  “[R]elated to” dose-response is “threshold dose” – “the minimum amount of a substance below which the substance would not cause the disease or effect” even if sub-minimum exposure was “repeated[]” or “long-term.”  Id.  Threshold dose (or “amount” of “exposure”) was another of those problems we saw coming down the Zantac MDL pike in our “Wheels Fall Off” post.  Zantac excluded plaintiffs’ primary dose-response/threshold dose expert’s (Salmon) opinions for no less than seven reasons:

  • Making grossly excessive assumptions that utilized only the rubber and dietary studies previously excluded as too far afield to be relevant.
  • Relying on the grossly excessive ranitidine exposure lab tests previously excluded for their bizarre results and shoddy methodologies.
  • Reliance on “animal data” – another notorious and frequent error common in unreliable expert testimony.
  • Peculiar methodology (not results) that is not “generally accepted.”
  • The same cherry-picking common to all Zantac plaintiffs’ experts – “us[ing] only certain data from studies showing a positive dose-response relationship” while “omit[ting] data from studies showing either no dose-response relationship or a negative dose-response relationship.”
  • Fudging – using “like” − about whether he followed certain methodology (World Health Organization) or not.
  • Applying the same sort of “internally inconsistent principles” common to all Zantac plaintiffs’ experts.

Zantac, 2022 WL 17480906, at *152-53.  In addition Salmon “assume[d] that every pill contained the maximum amount of NDMA ever found by reliable testing.  Id. at *152 n.158.  Thus, Salmon’s opinions were all very fishy.  Plaintiffs’ other experts, who opined less extensively on dose-response/threshold dose issues, shared the same disqualifying reliance and methodology issues.  Id. at *153-55.

As for threshold dose, after failing in their effort to massage the numbers, plaintiffs turned around and argued that numbers (at least significant ones) were not necessary after all.  They sought to prove causation without reference to any “threshold dose.”  They lost again.  “[B]inding,” “published” precedent required identifying a threshold exposure level in toxic tort cases.

[A]ll substances have the potential to become toxic if exposure to it is high enough. . . .  [A] plaintiff [must] produce evidence on how much product must be used for how long to increase the risk. . . .  [A] general causation expert must demonstrate the levels of exposure that are hazardous to human beings generally. . . .  Dose is critical to any evaluation of toxicity of a drug.

Zantac, 2022 WL 17480906, at *17 (citations, quotation marks, and emphasis omitted).  Thus, the plaintiffs had to “identify a threshold dose, even if the dose is described only as a range.”  Id.  Any theoretical risk, however minor, does not a product liability case make.

[G]eneral causation is not satisfied simply because an infinitesimal risk of cancer is more than zero risk.  Courts 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.  Thus, since an actionable exposure threshold dose cannot, as a matter of law, be merely anything, that means it must be something provable.

Id.  Thus, plaintiffs had to prove that ranitidine was “capable” of causing one of the five cancers at “the highest realistic exposure level” encountered by a plaintiff.  Id. at *18

The plaintiffs’ experts followed the common dodge of denying that any threshold exists – a bogus ploy common in non-drug (think asbestos and benzene) toxic tort litigation – claiming “that they are not required as a matter of law to provide a threshold dose.”  Id. at *156.  Their experts “testified . . . that any amount of a carcinogen is dangerous.”  Id.  But, with their characteristic inconsistency, the Zantac plaintiffs also claimed that certain experts “did in fact provide” threshold opinions – “just with the caveat that lower doses could still cause cancer, too.”  Id. at *157.

In trying to have it both ways on threshold dose, plaintiffs got neither.  They lost as a matter of law on their no threshold dose claims.

The Eleventh Circuit is clear that the Plaintiffs are required to provide a threshold dose . . . to meet their general causation burden.  That threshold dose is a potential floor for whether the specific dose a Plaintiff was exposed to was enough to cause his cancer at the specific causation stage. . . .  

The Court rejects the Plaintiffs’ attempt to recharacterize their experts’ no-threshold opinions as “merely” a “scientific reality” rather than a “legal opinion on threshold dose.”  General causation experts are not tasked with providing legal opinions or legal analysis.  Rather, a general causation expert’s role is to provide a scientific opinion supported by the available facts or data.

Zantac, 2022 WL 17480906, at *157.  Further:

  • Zantac refused to “accept the Plaintiffs’ experts’ no-threshold opinions without any analysis as to their admissibility.”
  • “Plaintiffs have failed to evaluate any of the Daubert factors which bear upon the admissibility of their experts’ no-threshold opinions.”
  • Plaintiffs could not rely on inconclusive language in a single corporate document as some sort of admission.
  • Asserting a level at which ranitidine purportedly “can cause cancer” was not “reliable evidence of threshold dose.”

Id. at 157-58.

Mopping Up

The final form of “primary evidence of general causation” – background risk – was not asserted by plaintiffs and thus not briefed by defendants.  Plaintiffs’ belated attempt to bring it up at oral argument on the Rule 702 motions was rejected.  Id. at 158-59.  Thus Zantac concluded that plaintiffs had presented no “primary” general causation at all

[B]ased upon a review of the totality of the evidence, the Plaintiffs have not met their burden to show that their experts relied upon any form of reliable primary evidence in support of their general causation opinions.  Because the Plaintiffs lack primary evidence, under Eleventh Circuit case law, all of the Plaintiffs’ general causation experts are stricken, and the Defendants are entitled to summary judgment.

Zantac, 2022 WL 17480906, at *159.

One would think that would be the end of it – but no, plaintiffs also threw “secondary evidence” against the wall to see if it would stick.  Specifically, plaintiffs raised animal studies and FDA “regulatory risk assessments.”  Neither stuck.

As for animal studies, Zantac followed the Reference Manual on Scientific Evidence, which states that they “have two significant disadvantages”:

First, animal study results must be extrapolated to another species − human beings − and differences in absorption, metabolism, and other factors may result in interspecies variation in responses. . . .  The second difficulty with inferring human causation from animal studies is that the high doses customarily used in animal studies require consideration of the dose–response relationship and whether a threshold no-effect dose exists.

Zantac, 2022 WL 17480906, at *162 (quoting Reference Manual, at 563).

Plaintiffs’ experts failed to explain either extrapolation.  Id. (“Plaintiffs confirmed that they did not put forward such an explanation”).  Arguing that government agencies use animal studies did plaintiffs no good:

  • “[G]overnment agencies typically utilize a lower threshold of proof than is required in tort law because agencies operate from the cautious perspective of preventing public exposure to potentially harmful substances.”
  • “Plaintiffs’ reliance on other institutions’ use of animal studies does not substitute for or explain to the Court their experts’ own rationale as to why they choose to rely upon the studies.”
  • “Plaintiffs do not explain species extrapolation for any of the other animal species tested in the studies that they rely upon.”
  • Plaintiffs’ “arguments do not address the question of how the [their] experts reliably extrapolate from the dosage of NDMA administered to animals to the dosage consumed by Plaintiffs via ranitidine.”
  • “Plaintiffs have failed to compare rodent livers to either the rodent or human esophagus, stomach, bladder, or pancreas to support this explanation.”

Zantac, 2022 WL 17480906, at *162-65.

Last, and probably least, Zantac rejected plaintiffs’ experts’ reliance on FDA regulatory risk assessments.  “[A] regulatory agency’s risk-benefit analysis does not directly focus on the question of causation in a toxic tort case.”  Id. at *166 (citation and quotation marks omitted).  Such assessments involve “protective, often ‘worst-case’ assumptions.”  Id. (citation and quotation marks omitted).  That was certainly true of the daily limits the FDA set for ranitidine:

[T]he 96 ng ADI limit represents a 1 in 100,000 cancer risk (meaning 1 in 100,000 persons could develop cancer) when exposed to 96 ng every day for a lifetime.  That threshold − 1 in 100,000 − unquestionably falls short of the preponderance of the evidence standard required here.

Id. (footnote omitted).  “Because the FDA sets ADI limits and recalls drugs upon a lesser showing of harm to the public than the preponderance-of-the-evidence or the more-likely-than-not standards used to assess tort liability, the ADI standard is simply incompatible with the standard of proof that the Plaintiffs bear in establishing causation.”  Id. at *167 (quoting Glastetter v. Novartis Pharmaceuticals Corp., 252 F.3d 986, 991 (8th Cir. 2001)).

A Not-at-All Bitter End – How Sweet It Is

Having excluded all of the Zantac plaintiffs’ experts as inadmissible under Rule 702, summary judgment for the defendants followed as a matter of course.  Id.  Thus, at the district court level, the Zantac Chronicles have come to an end, with a massive defense success.  At least now, plaintiffs don’t have to worry about having appealable orders.  Congratulations to defense counsel and their clients on the MDL-wide win.