The U.S. District Court for the District of New Jersey is home to Multi-District Litigation relating to thousands of claims against Johnson & Johnson and others, alleging that ovarian cancer was caused by exposure to cosmetic talcum powder products. On April 27, 2020, Chief U.S. District Judge Freda L. Wolfson ruled on Daubert motions filed by the defense, seeking to bar the testimony of five experts used by the plaintiffs in the MDL. Judge Wolfson partially granted the defense motion, and limited components of the plaintiffs’ expert testimony, but ultimately allowed each of the five challenged witnesses to testify. Plaintiffs, in turn, had challenged three defense experts, and Judge Wolfson denied those motions entirely, permitting the defense experts to testify as to all of their proffered opinions. This ruling is the first Daubert challenge to these experts in talc litigation in federal court, and could have persuasive impact on state courts throughout the country.
MKCI has analyzed the Court’s extensive 141-page decision and provides this analysis of the ruling as to the various experts. The plaintiffs’ experts at issue were: 1) Dr. Ghassan Saed, a professor in obstetrics and gynecology; 2) Dr. William Longo, a material scientist and electron microscopist; 3) Dr. Arch Carson, a medical toxicologist and occupational medicine specialist; 4) Dr. Anne McTiernan, an epidemiologist; and 5) Dr. Daniel Clarke-Pearson, a gynecologic oncologist. The defense experts were: 1) Dr. Benjamin Neel; 2) Dr. Gregory Diette; and 3) Dr. Cheryl Saenz.
Dr. Ghassan Saed, Ph.D.
Dr. Saed is an expert in inflammation and oxidative stress. He was contacted by the plaintiffs in August of 2017, to discuss his involvement in the MDL as an expert. After that meeting, Dr. Saed began in vitro studies to e valuate the role of talc in the carcinogenesis of ovarian cancer, and the relationship between inflammation and other pathologic conditions. He concluded: 1) that J&J’s baby powder elicited an inflammatory response in ovarian and tubal cells; 2) that the carcinogenic process involves oxidative stress; 3) that powder exposure results in elevation of the biomarker for ovarian cancer; 4) that there was a clear dose response pattern; and, 5) that use of J&J baby powder can cause ovarian cancer. Dr. Saed claims that his study demonstrated that the use of talcum powder induces inflammation and alters the redox balance favoring a pro-oxidant state – i.e., that it creates an environment for oxidative stress to occur.
The defense motion challenged Dr. Saed’s methodology and conclusions based on the in vitro study. Dr. Saed conceded that cell proliferation can occur as a normal response of all normal cells, and that he could not determine from his study whether proliferation was an acute response to talc. He did not conduct animal studies, and his in vitro study did not show tumor initiation or progression. Further, his study did not establish that oxidative stress was a key mechanism to initiate and allow cancer to progress. Ultimately, the Court determined that Dr. Saed will be allowed to testify that the biomarker is a marker for inflammation, and on the association of the use of talc and cellular oxidative stress – but not on the central question of causation. Other challenges to Dr. Saed’s opinions were found to go to its weight, and not admissibility, including: 1) Dr. Saed’s testing was unreliable because he determined his conclusion before conducting the study and failed to follow his own method; 2) Dr. Saed failed to conduct a neoplastic transformation assay; 3) Dr. Saed did not use the same dose of powder that women who actually use J&J products would have used; 4) Dr. Saed’s experiment was not replicated; and 5) the errors and inconsistencies in Dr. Saed’s lab books indicate the unreliability of the study.
Dr. William Longo, Ph.D.
Dr. Longo tested seventy-two (72) historical J&J and Imerys talc samples from the 1960s through the early 2000s for asbestos presence using TEM and PLM (transmission electron microscopy and polarized light microscopy). He found asbestos contamination in fifty (50) containers, and therefore concluded that individuals who used J&J powder would have been exposed to significant airborne levels of regulated amphibole asbestos and fibrous (asbestiform) talc.
The Court found Dr. Longo’s TEM analysis to be reliable, but excluded his testimony to the extent that his opinions were based on PLM, or when he opined on the exposure to asbestos. Defendants argued that Dr. Longo had failed to distinguish between asbestiform and cleavage fragments (i.e. disagreeing with his “counting rules”, relied upon in prior years in the asbestos litigation). Dr. Longo maintained that step one of TEM – which is a three-step process – accounted for cleavage fragments, but that steps two and three of the method would exclude them from being counted.
Defendants also challenged Dr. Longo’s finding that 93% of the asbestiform particles were bundles because this was an increase from Dr. Longo’s original report. The analyst had no objective way of determining whether the particle was a single fiber or bundle. The Court determined that this went to weight, not admissibility, and defendants failed to express any views on how the inconsistency between fibers and bundles impacted Dr. Longo’s overall test results regarding amount of asbestos found.
Defendants further challenged Dr. Longo’s application of step three of the TEM analysis, because he did not take multiple diffraction patterns at different zone axis orientations. The Court disagreed, finding that Dr. Longo had applied methodology based upon AHERA and ISO standards, which seldom require zone axis measurements. Lastly, the Defendants challenged step two of the TEM method as being unreliable and deliberately designed to be unverifiable, as Dr. Longo failed to include numeric data which would allow verification of results. The Court noted that this was not required under the methodology.
The Court found Dr. Longo’s PLM method to be unreliable, in part because Dr. Longo conceded that PLM was not an appropriate method for testing asbestos in cosmetic talc. In addition to ISO 22262-1 PLM method, Dr. Longo also performed heavy liquid separation before conducting the PLM analysis to increase analytical sensitivity. Defendants maintain Dr. Longo should have used ISO 22262-2 as ISO 22262-1 requires its use when asbestos concentration is between 0% and 5% and under TEM, Dr. Longo found concentrations between .0092% and .0000033% asbestos. Dr. Longo also used MAS standards to quantify asbestos using visual examination and this methodology was not disclosed to defendants making replication difficult. This is further supported by the fact that he asked Lee Poye to evaluate 22 samples and Dr. Poye did not find asbestos in any of them under PLM ISO 22262-1. Lastly, defendants argued that Dr. Longo’s testimony on causation be excluded because he did not conduct any exposure analysis. The Court ultimately agreed that Dr. Longo failed to offer scientific support for his opinion that J&J’s talc products causes exposure, let alone significant exposure to asbestos. However, he will be permitted to testify about the “ultra-trace” presence of asbestos in the talc.
Dr. Arch Carson; Dr. Anne McTiernan; and Dr. Daniel Clarke-Pearson
Plaintiffs offered these three experts to establish general causation, and they evaluated epidemiology studies to weigh the nine “Bradford Hill” factors for determining general causation. These experts placed significant weight on the “strength of association” factor of the analysis, relying on meta-analyses and pooled analysis from epidemiological studies. Defendants maintained that the experts mischaracterized the objective magnitude of the association reported in the studies, and rested on inapposite comparisons to causal relationships. Defendants also argued that the experts relied more on case control studies than cohort studies – the latter providing more reliable results – making their opinions unreliable.
The Court’s analyzed the experts’ opinions and discussed application of each Bradford Hill factor. The Court found that the experts provided “good grounds” for their decision to place significant weight on the strength of association factor. If the relative risk is greater than 1, the risk in exposed individuals is greater than the risk in unexposed individuals (e.g., a relative risk of 2 means the risk has doubled). Whether the relative risk is weak or strong was held to be up to the jury to decide, but as to reliability, the Court believed the experts used sound methodology in determining that the relative risk range creates an association between talc powder use and ovarian cancer. Defendants did not challenge the methodology or calculation, but just the strength of the findings. As to case control versus cohort studies, the experts explained that there are benefits and drawbacks to both. They believed case control studies are better suited for assessing causal relationships because case control studies best describe a woman’s use and lifetime exposure. They pointed out that the three applicable cohort studies each have their own drawbacks, but were also included in the meta-analysis which showed a significant and positive relative risk between serous epithelial ovarian cancers. The Court could not deem the opinions unreliable on the basis that the experts determined the case control studies were entitled to greater weight.
As to the consistency factor, the experts explained that 24 of the 28 case control studies showed relative risks greater than 1.1 for women’s perineal use of talcum powder and of these, 16 were statistically significant. As to the cohort studies, on average they showed more attenuated relative risks of ovarian cancer because they were not well designed to determine true risk. Nonetheless, the experts believe these also showed a positive association. Defendants’ objections to their conclusions is a dispute over the role that statistical significance plays in determining consistency of epidemiological studies; however, the experts considered statistical significance with respect to both cohort and case control studies in a reliable fashion. Inconsistent statistical significance from one study to the next was found not to show inconsistency under Bradford Hill.
As to “biological plausibility”, plaintiffs’ experts have two theories: 1) Talc migrates up and through the female reproductive system when applied to the perineum or 2) Inhaled particles travel through the lymphatic system to the ovaries and fallopian tubes. Once the talc is present in the ovaries it causes chronic inflammation leading to ovarian cancer. Defendants maintained that the studies cited by the experts do not establish migration theory. However, the Court noted that biological plausibility does not require certainty but whether the causal link is credible in light of what is known about science and medicine. The fact that there is a debate about the mechanisms which permit migration was insufficient to preclude admission of the testimony. In addition, the experts provided “a solid basis” for their inflammation theory through in vitro studies which demonstrated an inflammation response. Defendants did not put forth any evidence that this theory had been disproven and therefore, there was no basis to find that the hypothesis is implausible. Importantly, the Court did exclude the inhalation theory, as the studies cited to did not mention how the talc ended up in the pelvic lymph nodes. The experts failed to provide any scientific basis to establish that the talc somehow moved through the lymphatic system to the ovaries.
As to the “dose response factor”, plaintiffs’ experts conceded that while some studies have failed to establish same, more recent reports showed a clear dose response when the number of subjects rose to a level producing sufficient statistical power to allow the analysis. In reviewing the data, they tried to determine whether increasing the dose increases the risk of ovarian cancer and the pooled analysis appeared to establish this. Defendants maintained that the experts’ testimony establishes that dose response data are absent in many studies and the data that does exist is inconsistent. The Court agreed that strong evidence of dose response would show a stronger causative relationship, however, based on epidemiology principles, a strong dose response is not necessarily needed for an expert to find a causal nexus as long as there is reliable evidence of a dose response. Further, the experts relied upon certain meta-analysis and pooled studies which plaintiffs maintained establish a dose response relationship and they provided “good grounds” for concluding same through their explanation of how they evaluated the data.
As to “specificity”, while same may strengthen the case for causation, lack of same does not undermine it where there is a good biological explanation for its absence. Plaintiffs’ experts opined that talc use is specific to the development of ovarian cancer and not any other genital cancer.
As to “temporality” (exposure occurred before disease), the experts weighed this factor heavily as exposure to talc occurred before the development of ovarian cancer. The weight to be given to this factor was determined to be for a jury to decide.
As to “coherence” (cause and effect interpretation of the data should not significantly conflict with the known facts bout the natural history and biology of the disease), plaintiffs’ experts did not weigh this heavily because the data was not conflicting in their opinion. Increased inflammation has been linked to increased risk in ovarian cancer and talc elicits an inflammatory response. Defendants argued: 1) there are numerous subtypes of ovarian cancer and the notation that talc causes all of them is incoherent; 3) No animal studies have shown talc causes ovarian cancer; and 3) Plaintiffs’ experts did not reconcile their opinions with studies that have investigated talcum powder use on diaphragms and condoms which found no increased risk. In assessing this factor, it is sufficient that the causation experts examined known facts regarding inflammation and cancer and opined that they are coherent with their theory. The fact that there are different types of ovarian cancers was found not to undermine the experts’ opinion on coherence. Defendants’ remaining arguments showed disagreement with the experts’ conclusions as the experts have evaluated the studies.
As to the “experiment” factor (whether there is experimental evidence to support the association), defendants maintained there was no reliable support for the experts’ conclusions. Plaintiffs’ experts did not afford this great weight given the ethical implications of conducting trials on women to explore the relationship between talc use and ovarian cancer. They did though rely on in vitro experiments and animal studies to form their opinions.
As to the “analogy” factor (substantiation of relationships similar to the putative causal relationship increases the likelihood of causation), plaintiffs’ experts compared the relationship between talc and ovarian cancer to asbestos and the development of lung and ovarian cancer. The mechanisms which cause both are similar. Judge Wolfson found the weighing of this factor by plaintiffs’ experts to be reasonable as there was no dispute that asbestos is carcinogenic. Defendants maintained this analogy is inappropriate because crocidolite, which is most associated with ovarian cancer, was not found in talc. The Court pointed out that crocidolite is in the same family as anthophyllite and tremolite which were found in talc.
Lastly, defendants argued that plaintiffs’ general causation experts should be excluded because their opinions are inconsistent with the scientific community. Plaintiffs maintained that the scientific community has not reached any consensus as to whether talcum powder use causes ovarian cancer. IARC’s categorization of talc as a possible carcinogen supports plaintiffs’ position as does the Health Canada 2018 report. The Court agreed there does not appear to be consensus on the issue of association between talc use and ovarian cancer, however, there is scientific evidence supporting both side’s opinions, and permitted the general causation testimony based on epidemiological evidence.
The Court’s opinion spent far less time evaluating the defense experts’ opinions, and denied plaintiffs’ motions to bar those experts in their entirety.
Dr. Gregory B. Diette
The defense relied upon Dr. Gregory B. Diette, an epidemiologist, who also performed a Bradford Hill analysis to explain his opinion that there was no causal connection between perineal use of talc and ovarian cancer. The plaintiffs challenged his evaluation of the consistency of association, dose response, and biological plausibility factors, arguing that he misapplied those factors and that his methodology for statistical significance testing was flawed.
The Court found that Dr. Diette’s opinions reasonably flowed from the epidemiological studies, and that he followed reliable methodology in reaching his conclusions on consistency of association. He considered the totality of the studies and his assessment is based on “good grounds”. As to dose response, Dr. Diette explained that the cohort studies did not establish causation and found the results of case controls studies to be highly inconsistent. Judge Wolfson concluded this was a fair reading of the epidemiologic studies. Dr. Diette reviewed the results of the studies and assessed whether they were sufficient to show a dose-response relationship. Based on the inconsistent data, Dr. Diette determined there is no relationship and this determination rested on “good grounds” and is therefore reliable. As to biological plausibility, Dr. Diette reviewed the available data and finds there is no basis to conclude talc travels to the ovaries causing inflammation. The parties fundamentally disagreed as to which experts’ opinion and interpretation is best and, further, which experts reached the correct conclusions. It will be up to the jury to make this determination.
Dr. Cheryl Saenz
Dr. Saenz, a gynecologic oncologist, did not complete a full Bradford Hill analysis as part of her methodology. However, she considered certain of the Bradford Hill criteria in rendering her opinion, and criticized the Bradford Hill analyses conducted by plaintiffs’ experts. Plaintiffs argue that she failed to consider the totality of the evidence in giving greater weight to cohort studies, and challenged her testimony as to biological plausibility.
As to the totality of the evidence, Dr. Saenz identified certain internal inconsistencies in the case-control studies, and highlighted the high risk of recall to support her basis for relying heavily on cohort studies. The Court determined that whether case control studies or cohort studies were more reliable would be up to the jury to decide. As to biological plausibility, the plaintiffs maintain that Dr. Saenz incorrectly required proof of mechanism, and that her testimony was unreliable because she did not review all of the studies cited by plaintiffs’ experts. Dr. Saenz knew of those studies, and that they did not show malignant transformation, and therefore had determined that they were not important to her analysis. There is no requirement that an expert review every single study in a relevant body of literature. Her deliberate choice to not review those articles identified by plaintiffs did not render her opinion inadmissible. Dr. Saenz explained that because the studies referred to, but did not reveal, any malignancy from talc, they were irrelevant on the question of biological plausibility.
Dr. Benjamin Neel
Dr. Benjamin Neel was challenged by Plaintiffs, arguing that his opinions as to biological plausibility were not reliable because he was unaware of the constituent compounds of talc products, and further that Dr. Neel was not qualified to testify regarding the strengths and weaknesses of the epidemiological studies or to conduct a Bradford Hill analysis. Defendants countered that Dr. Neel did not need to consider the components of talc because his report focused on criticizing plaintiffs’ exerts methods, and to the extent he offered opinions on biological plausibility, he focused on in vitro studies notwithstanding talc’s components. Further, as a medical doctor, he is qualified to opine on epidemiological evidence. The Court agreed that there is no requirement that Dr. Neel opine as to the components of talc as he has been proffered as an expert to rebut the methodology employed by Dr. Saed in conducting his in vitro study. That study does not make any finding as to whether any component of talc is carcinogenic, but instead opines that talc itself can cause inflammation and oxidative stress. Further, Dr. Neel has extensive medical training, which establishes his qualifications to interpret the relevant epidemiologic literature. Last, Dr. Neel presented “good grounds” for his opinion that, where an association is weak and inconsistent, biological plausibility may become more important in the overall Bradford Hill analysis.
The above discussion demonstrates some of the larger scientific debates that have unfolded throughout the national talc litigation. For more information on the litigation, or to discuss this ruling in the MDL, please feel free to contact MKCI’s Joel Clark, Pooja Patel, or Bob Baum.