The MDL judge in the Denture Cream Products coordinated litigation has rejected all of plaintiffs' general causation experts. See In re Denture Cream Prods. Liab. Litig.,No. 09-2051-MD-Altonaga (S.D. Fla. Jan.. 28, 2015).

Over three and a half years ago, in Chapman. v. Procter & Gamble Distributing LLC, Case No. 9:09- CV-80625, the MDL court had granted Procter & Gamble’s motion to exclude the opinions of Plaintiffs’ general causation experts. See In re Denture Cream Prods. Liab. Litig., 795 F. Supp. 2d 1345 (S.D. Fla. 2011) . Since Chapman, Plaintiffs claimed to have obtained new evidence in support of their argument that products like Fixodent can cause copper deficiency myeloneuropathy (“CDM”), including clinical, epidemiological, background risk of disease, and dose-response relationship. Defendants filed an omnibus Daubert Motion challenging the reliability and significance of Plaintiffs’ alleged new general causation evidence and opinions — in particular a Fixodent Blockade Study and "Dr. Lautenbach’s cohort study."  The motion argued the previously identified analytical gaps in Plaintiffs’ chain of general causation still remained. In particular, Defendants contended that Plaintiffs still could not establish any of the following, that: (1) someone can ingest enough zinc from Fixodent to place the body in a negative copper balance; (2) a prolonged negative copper balance from denture cream use can lead to a copper deficiency; (3) a dose-response relationship exists between Fixodent and copper deficiency, much less myeloneuropathy; (4) Fixodent users face a greater risk of developing myeloneuropathy than the general population; or (5) a physiological mechanism explains how a copper deficiency can lead to a myeloneuropathy.

The alleged decades’ worth of underlying scientific literature” Plaintiffs relied on to prove general causation — most of which was presented in Chapman — pertained to excess zinc and copper deficiency, or copper deficiency and neurological disorders; it is not specific to the zinc compound in Fixodent. Particularly in light of the millions of consumers who have regularly used Fixodent for decades without complaint, see Chapman, 766 F.3d at 1304 , the Court concluded first that Plaintiffs had not demonstrated the medical community generally recognizes the zinc compound in Fixodent as a known toxin, and thus the Court undertook an extensive Daubert analysis on the general question of whether Fixodent can cause CDM, in light of the allegedly new evidence. The Court examined Plaintiffs’ new evidence in support of proving general causation, including epidemiological studies, dose-response analysis, and the background risk in particular.

The opinion is quite lengthy, and worth a close read for readers with Daubert issues in toxic tort cases.  A few highlights:  Plaintiffs sought to rely on a recently conducted study supposedly showing the short term effects of zinc in the body.  But the Court could not "turn a blind eye to the myriad, serious methodological flaws in the Fixodent Blockade Study," which did not go just to the weight of the evidence. While some of these flaws, on their own, might not have been serious enough to justify exclusion of the Fixodent Blockade Study; taken together, the Court found this Fixodent Blockade Study was not “good science,” and was not admissible.   Consequently, Plaintiffs still had no evidence of the zinc in Fixodent’s ability to inhibit copper absorption at the relevant site of action — the intestines.

Plaintiffs relied on the opinions of a Dr. Grainger, on dose-response and relying on in vitro studies. Defendants argued Dr. Grainger’s opinions were unreliable because Dr. Grainger did not offer any explanation of how zinc dissociation properties observed in in vitro release designs would transfer to a live human, and did not consider factors that might allow him to make such an extrapolation. The court agreed that Dr. Grainger’s opinions were unreliable. The in vitro dissociation studies were the foundation for all of Dr. Grainger’s conclusions. The portion of his report dedicated to these studies was completely devoid of any pertinent details or analysis. His comments regarding “various in vitro release designs”  lacked support citations, and lacked any discussion about the study designs or methodology, and any details about the individual study results. See Ballard v. Keen Transp., Inc., No. 4:10-cv-54, 2011 WL 474814, at *4 (S.D. Ga. Feb. 3, 2011) (expert’s failure to cite any specific chapter, page, or line on which he based his conclusions “makes it appear that he is not being as careful in his litigation consulting as he is in his ordinary professional work.”).  Dr. Grainger’s failure to explain the relevancy of the in vitro studies to humans or to account for factors needed to make a proper extrapolation was notable given his critique of studies the defendants had relied on.  Accordingly, the court concluded, "In short, Plaintiffs are not much better off than they were at the time of Chapman."

The MDL court also noted that epidemiology is “generally considered to be the best evidence of causation in toxic tort cases.” Kilpatrick, 613 F.3d at 1337 n.8.  Epidemiology is the field of public health and medicine that studies the incidence, distribution, and etiology of disease in human populations. . . . Epidemiologic evidence identifies agents that are associated with an increased risk of disease in groups of individuals, quantifies the amount of excess disease that is associated with an agent, and provides a profile of the type of individual who is likely to contract a disease after being exposed to an agent. Epidemiology focuses on the question of general causation (i.e., is the agent capable of causing disease?) Green, REFERENCE MANUAL ON SCIENTIFIC EVIDENCE 3d ed., at 551–52.  There are two classes of epidemiological evidence: analytical and descriptive. See In re Denture Cream Prods. Liab. Litig., 795 F. Supp. 2d at 1353–54.  Analytical evidence consists of randomized controlled trials, case control studies, and cohort studies, while descriptive evidence consists of case studies and case series. 

Plaintiffs claimed they now had analytical epidemiological evidence to support their theory of general causation — Dr. Lautenbach’s cohort study.  However, Dr. Lautenbach’s cohort study did not account for the lack of information pertaining to the subjects’ denture cream usage, and it was based on the assumption this information was appropriately taken into account by the underlying treating physicians.  Dr. Lautenbach also assumed the treating physicians took into account the amount of denture cream use, claiming it was obviously a volume high enough to trigger that as a designation for physicians.  The court concluded that the extent of Dr. Lautenbach’s reliance was a complete delegation of his responsibilities as an epidemiologist to assess the subjects’ exposure. The study had severe limitations as a reliable foundation for building a cohort study to formally assess the association between zinc-containing denture cream and CDM. At its core, the basis for Dr. Lautenbach’s cohort study was merely a summary of a collection of case reports, with severely inadequate information about denture cream usage. The layers of unsupportable estimations and approximations, added to this already shaky foundation, confirmed the Court’s finding that Dr. Lautenbach’s cohort study was unreliable evidence of general causation.

While plaintiffs had presented "a superficially appealing hypothesis that prolonged use of very large amounts of Fixodent may cause copper deficiency," the law requires more than a general theme to support causation, said the court.  Without Dr. Lautenbach’s cohort study, Plaintiffs continued to have no analytical epidemiological evidence on which to base their inference of causation. In addition to the absence of any analytical epidemiological studies, the absence of data on the background risk of CDM also remained a substantial weakness in Plaintiffs’ experts’ causal reasoning. When analyzing an expert’s methodology in toxic tort cases, the court should pay careful attention to the expert’s testimony about the dose-response relationship. The dose-response  relationship is a relationship in which a change in amount, intensity, or duration of exposure to an agent is associated with a change — either an increase or decrease — in risk of disease. For most types of dose-response relationships following chronic (repeated) exposure, thresholds exist, such that there is some dose below which even repeated, long-term exposure would not cause an effect in any individual.  See generally CASARETT AND DOULL’S TOXICOLOGY: THE BASIC SCIENCE OF POISONS Chs. 1, 4 (McGraw Hill 6th ed.2001).  Often low dose exposures — even for many years — will have no consequence at all, since the body is often able to completely detoxify low doses before they do any damage.  Even Plaintiffs conceded that Fixodent “is safe when used in moderate amounts.” 

So, the Court again found Plaintiffs had not presented sufficient proof of general causation using the indispensable primary methodologies identified by the Eleventh Circuit.