Epidemiology Expert Witness’ General Causation Opinion Rejected
Posted on May 6, 2024 by Expert Witness Profiler
This is a multidistrict litigation (“MDL”) in which over 5,000 individual Plaintiffs allege that they developed Parkinson’s disease because of their exposure to an herbicide, paraquat dichloride (“paraquat”). Paraquat is a restricted-use quaternary ammonium herbicide that is used to control weeds in farming operations and other settings around the United States. Defendants, Syngenta Crop Protection, LLC and Syngenta AG (collectively “Syngenta”), currently manufacture and distribute paraquat for use in the United States, whereas Defendant, Chevron U.S.A., Inc. (“Chevron”), manufactured and distributed paraquat until 1986.
Facts of the Case
Dr. Martin Wells serves as Plaintiffs’ sole expert witness on the critical issue of general causation, offering an opinion that occupational exposure to paraquat can cause Parkinson’s disease. Defendants filed a motion to exclude Wells’ proffered testimony which raised complex issues related to the study of epidemiology and the scientific methodologies of systematic review and meta-analysis. Defendants’ motion is brought in four of the six member cases that were selected for case-specific discovery in the Court’s April 13, 2022 order. These four cases have gone through fact and expert discovery and now serve as this MDL’s first set of trial selection cases.
Plaintiffs retained Martin Wells to “analyze the epidemiological evidence relating the association and causation of the occupational exposure of paraquat to the onset of Parkinson’s disease.” To accomplish this task, Wells conducted a meta-analysis of seven epidemiological studies that measured a potential association between paraquat and Parkinson’s disease. Wells determined, based on this meta-analysis, that there was a “near tripling of PD occurrence in [study] participants occupationally exposed to paraquat.”
After establishing a positive association between occupational exposure to paraquat and Parkinson’s disease, Wells conducted a weight of the evidence review to determine whether the association was attributable to a causal relationship. He found that it was and drew the following conclusions: (i) the available epidemiological evidence supports a causal relationship between paraquat and Parkinson’s disease; and (ii) the trial selection Plaintiffs fit the exposure and diagnostic criteria of the seven studies in his meta-analysis, meaning that they were at “near tripl[e]” the risk of developing Parkinson’s disease.
Epidemiology Expert Witness
Dr. Martin Wells boasts of an impressive career as an academic, researcher, and prolific publisher in the fields of biostatistics and epidemiology. He received his Ph.D. in Mathematics from the University of California in 1987 and became an Assistant Professor at Cornell University that same year. Furthermore, Wells currently serves as a Professor of Clinical Epidemiology and Health Services Research at Weill Medical School and as the Chair of the Department of Statistics and Data Science at Cornell. Moreover, he has published 250 scholarly articles on statistics, human health, and other topics and has received research grants from numerous governmental and non-governmental institutions, including the U.S. Department of Agriculture, the U.S. Army, and the National Institutes of Health.
Discussion by the Court
Legal Standard
In his own words, Wells offers an opinion that “the available epidemiological evidence supports a causal relationship between occupational paraquat exposure and PD.”
The admissibility of expert testimony under the Federal Rules of Evidence is governed by the well-known and oft-cited standards of Federal Rule of Evidence 702 and Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S. Ct. 2786, 125 L. Ed. 2d 469 (1993). Under Rule 702, “[a] witness who is qualified as an expert by knowledge, skill, experience, training, or education may testify in the form of an opinion or otherwise if the proponent demonstrates to the court that it is more likely than not that:
(a) the expert’s scientific, technical, or other specialized knowledge will help the trier of fact to understand the evidence or to determine a fact in issue;
(b) the testimony is based on sufficient facts or data;
(c) the testimony is the product of reliable principles and methods; and
(d) the expert’s opinion reflects a reliable application of the principles and methods to the facts of the case.”
Amended Rule 702
This amended version of Rule 702 took effect on December 1, 2023, after the Parties submitted their briefing. The Advisory Committee on the Rules of Evidence explained that the amendment does not “impose[] any new, specific procedures.”
Rather, the amendment emphasized that the proponent bears the burden of demonstrating compliance with Rule 702 by a preponderance of the evidence, and that “each expert opinion must stay within the bounds of what can be concluded from a reliable application of the expert’s basis and methodology.”
The Advisory Committee cautions that “expert testimony may not be admitted unless the proponent demonstrates to the court that it is more likely than not that the proffered testimony meets the admissibility requirements set forth in [Rule 702].”
In providing this instruction, the Advisory Committee noted that some courts had “incorrect[ly]” held that an expert’s basis of opinion and application of her methodology were questions of weight, not admissibility. The Advisory Committee thus appears to have found that courts had erroneously admitted unreliable expert testimony based on the assumption that the jury would properly judge reliability by assigning appropriate weight to an expert’s opinion.
Bradford Hill Analysis
To judge causation, researchers ordinarily consider how the following nine “Bradford Hill” factors (named after the British epidemiologist and statistician, Sir Austin Bradford Hill) apply to an observed association:
(1) temporal relationship (the exposure must occur before the disease develops);
(2) strength of association (the higher the RR or OR, the greater the likelihood that the relationship is causal);
(3) dose-response relationship (whether a higher dose increases the incidence or severity of the disease);
(4) replication of findings (whether research findings have been replicated in different populations with consistent results);
(5) biological plausibility (whether the association is consistent with current biological knowledge about the disease);
(6) consideration of alternative explanations (whether the research has properly accounted for bias and confounding variables);
(7) cessation of exposure (whether the cessation of exposure reduces the risk of disease);
(8) specificity of association (an association is specific and more likely to be causal if the exposure is associated with only a single or a small number of diseases); and
(9) consistency with other knowledge (whether a causal inference is consistent with relevant general knowledge or data).
After establishing a positive association, Wells conducted a Bradford Hill analysis to determine whether occupational exposure to paraquat was causally related to Parkinson’s disease. Wells discussed six of the nine Bradford Hill factors (strength of association, consistency, temporality, dose-response, experimental evidence regarding the cessation of exposure, and specificity) in his first report, and assumed that the other three factors (biological plausibility, coherence, and analogy) were satisfied based on the report of Plaintiffs’ toxicology expert. He appears to have found that the six factors he evaluated were all satisfied, and on that basis, concluded that “drawing general causal inferences related to occupational paraquat exposure and PD is merited.”
Legal Analysis
A. Qualifications
Defendants first attacked Wells on the basis that he was not qualified to offer an opinion about the causal relationship between occupational paraquat exposure and Parkinson’s disease. This argument purported to show that although Wells possessed impressive credentials as a statistician, his qualifications were limited to just that type of work—calculating a summary risk estimate from a pre-selected universe of epidemiological studies.
The Court held that Wells is not just a statistician; he is a professor of epidemiology with an impressive record of scholarly publications on epidemiological issues. As such, he is well-equipped to judge the relative quality of the epidemiological studies at issue.
Simply put, as a biostatistician and epidemiologist, Wells is well qualified to offer a general causation opinion based on a Bradford Hill analysis and to evaluate the relative quality of epidemiological studies relevant to the causation question at issue.
B. Reliability
1. The Scope of Dr. Wells’ General Causation Opinion
An epidemiological causation assessment ordinarily proceeds in two steps: (i) a determination of whether a disease is associated with exposure to a particular agent; and (ii) if a positive association is found, a Bradford Hill analysis to determine whether the association is the result of a cause-and-effect relationship. At a high level, Wells followed these steps as well. First, he surveyed the epidemiological literature and established a positive association by conducting a meta-analysis of seven case-control studies that examined a possible association between paraquat exposure and Parkinson’s disease. Second, he conducted a Bradford Hill/weight of the evidence analysis to determine whether the totality of the evidence supported a causal relationship between occupational paraquat exposure and Parkinson’s disease. Wells then offered the opinion that the elevated odds ratio from his meta-analysis applied to the four trial selection Plaintiffs, Mr. Richter, Mr. Burgener, Mr. Fuller, and Mr. Coward.
Wells offered an expert opinion that “occupational” paraquat exposure was causally related to Parkinson’s disease. Any exposure that did not qualify as “occupational” is therefore not within the scope of his opinion. The Court observed that Wells redefined “occupational” exposure no less than three times, creating more questions than answers about the types of paraquat exposures that, according to him, can cause Parkinson’s disease.
2. Wells’ Meta-Analysis
Wells’ violations of the rules of meta-analysis are evident from the very beginning of his process. One of the initial steps in a meta-analysis involves the search for relevant studies that are then further analyzed for potential inclusion in the analysis. Wells’ first report is entirely devoid of a search narrative that would allow other researchers to validate his process.
The next methodological red flag in Wells’ meta-analysis is that until he submitted his rebuttal report, he failed to clearly articulate the inclusion/exclusion criteria that purportedly governed a study’s eligibility for his analysis. Indeed, Wells testified at his first deposition that he reviewed the relevant studies “holistically” to determine “whether or not [they were] reliable enough for inclusion.” This “holistic” approach was neither reduced to writing, nor did it offer any discernible objective criteria that would allow others to replicate Wells’ eligibility determinations.
Moreover, Wells relied on an evolving set of quality criteria to determine which studies ultimately warranted inclusion in his meta-analysis. This alone undermines the methodological soundness of his qualitative evaluation of the literature.
Another methodological issue in Wells’ meta-analysis concerned his apparent failure to follow even his own articulated reliability standards. Wells appeared to have violated this guideline for the most important study in his meta-analysis, Liou (1997).
The Court took no position on the relative merit of the various epidemiological studies at issue in Wells’ analysis. Indeed, the Court did not find Wells’ meta-analysis unreliable because it excluded van der Mark (2014), Shrestha (2020), or any other relevant study for that matter. Rather, Wells’ meta-analysis did not pass muster under Rule 702 because its methodology was unclear, inconsistently applied, not replicable, and at times transparently reverse-engineered.
3. Dr. Wells’ Weight of the Evidence / Bradford Hill Analysis
a. General Observations
After he generated his odds ratio of 2.8, Wells conducted a “weight of the evidence” review utilizing the Bradford Hill framework to determine whether the association was attributable to a cause-and-effect relationship between occupational paraquat exposure and Parkinson’s disease. This analysis involved the “combination of two methods”—weight of the evidence review and application of the Bradford Hill factors. Although this approach is generally reliable, there is “very little” circuit-level authority guiding its application in toxic tort cases.
In short, experts in toxic tort actions commonly employ this methodology to answer complex epidemiological causation questions. Because of its widespread adoption in the scientific community and in other litigations, the general reliability of this approach is not in dispute. However, the method gives researchers significant flexibility to decide how to analyze the evidence and weight each Bradford Hill factor in relation to the others. An expert could “theoretically assign the most weight to only a few factors, or draw conclusions about one factor based on a particular combination of evidence.” So, while the methodology offers the benefit of flexibility, it is vulnerable to results-driven analysis, which, of course, raises significant reliability concerns.
b. The Reliability of Dr. Wells’ Bradford Hill Analysis
Wells’ weight of the evidence/Bradford Hill analysis is a textbook example of the type of standardless presentation of evidence that courts have cautioned against. The most obvious methodological defect is the absence of any discernible weighting methodology. Neither Wells’ first report nor his rebuttal report offer any explanation of the relative weight or importance assigned to each of the six Bradford Hill factors he analyzed.
c. Isolation from the Scientific Community
This Court has focused, as it must, on the methodological soundness of Wells’ analyses in support of his conclusions, not the conclusions themselves. However, the line between methodology and conclusion is “not always an easy [one] to draw.”
Daubert expressly addressed the importance of independent validation of an expert’s opinion when it observed that “[w]idespread acceptance can be an important factor in ruling particular evidence admissible.” The Advisory Committee on the Federal Rules of Evidence therefore cautions that “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.”
In conclusion, Wells’ causation theory has not been adopted or independently validated in any peer-reviewed scientific analysis outside of this litigation.
4. Dr. Wells’ Plaintiff-specific Opinions
Wells’ third and final proffered opinion concerned the individual Plaintiffs in the four trial selection cases, Mr. Burgener, Mr. Coward, Mr. Fuller, and Mr. Richter. According to Wells, “these individuals fit the inclusion criteria in the referenced seven studies in my meta-analysis.” As a result, “[t]he elevated odds ratio of 2.8[] and the [Bradford] Hill criteria apply to these individuals.”
This opinion will be excluded because it is not severable from Wells’ meta-analysis and his weight of the evidence/Bradford Hill analysis. Plaintiffs conceded this point at the Daubert hearing by noting that Wells’ meta-analysis is “critical for specific causation.” Moreover, without testimony concerning (i) a positive association between occupational paraquat exposure and Parkinson’s disease, and (ii) a causal relationship between occupational paraquat exposure and Parkinson’s disease, there is no testimony for Wells to give as it pertains to the four trial selection Plaintiffs.
Held
To sum it up, the Court concluded that Martin Wells’ proffered opinions were not admissible under Federal Rule of Evidence 702 and Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S. Ct. 2786, 125 L. Ed. 2d 469 (1993).
Key Takeaways:
- Moreover, in addition to the Bradford Hill factors of strength of association, consistency, and temporality (which he also considered in Monroe), Wells discusses experimental evidence related to the cessation of exposure, evidence of a dose-response relationship, and specificity. Nonetheless, the Court is not persuaded that his discussion of these considerations pushes his testimony beyond the limits of his qualifications as a biostatistician and epidemiologist. Furthermore, Wells’ Bradford Hill analysis is appropriately limited to the epidemiological studies he reviewed. He does not purport to venture into the realm of toxicology or other disciplines that are beyond his area of expertise.
- Wells’ reliance on an unwritten, “holistic” methodology presents an ideal example of “because I said so” expertise that is impermissible under Rule 702. Wells insisted that he “ha[s] the credentials to do this” and that he “had a process that [he] followed.” But these assurances, without more, do not show that Wells faithfully applied the necessary steps of his chosen methodology as Daubert requires.
- Against the backdrop of Wells’ departure from the most basic methodological requirements of a weight of the evidence review, it is not surprising that his analysis reveals extensive selection bias. Wells appears to have fallen prey to the temptations of selection bias in his discussion of several Bradford Hill factors, most notably those concerning a dose-response relationship and strength of association.
Case Details:
| Case Caption: | Richter v. Syngenta AG (In re Paraquat Prods. Liab. Litig.) |
| Docket Number: | 3:21md3004 |
| Court Name: | United States District Court, Illinois Southern |
| Order Date: | April 17, 2024 |
