Opinion ID: 4174106
Heading Depth: 4
Heading Rank: 4

Heading: the expert has reliably applied the

Text: principles and methods to the facts of the case. Fed. R. Evid. 702. Pursuant to the Federal Rules of Evidence, the district court judge must ensure that all admitted expert testimony is both relevant and reliable. See Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 589 (1993). Defendants do not contest that the opinions of Dr. Weisenburger and Dr. Shustov are relevant; the only question, therefore, is whether they are reliable. 10 WENDELL V. GLAXOSMITHKLINE Scientific evidence is reliable “if the principles and methodology used by an expert are grounded in the methods of science.” Clausen v. M/V New Carissa, 339 F.3d 1049, 1056 (9th Cir. 2003). The focus of the district court’s analysis “must be solely on principles and methodology, not on the conclusions that they generate.” Daubert, 509 U.S. at 595. As we explained in Daubert v. Merrell Dow Pharmaceuticals, Inc., the court’s “task . . . is to analyze not what the experts say, but what basis they have for saying it.” 43 F.3d 1311, 1316 (9th Cir. 1995) (hereinafter Daubert II). To assist courts with this task, the Supreme Court has listed several non-exclusive factors that judges can consider when determining whether to admit expert testimony under Rule 702. See Daubert, 509 U.S. at 593–95. These include: “whether the theory or technique employed by the expert is generally accepted in the scientific community; whether it’s been subjected to peer review and publication; whether it can be and has been tested; and whether the known or potential rate of error is acceptable.” Daubert II, 43 F.3d at 1316. We also consider whether experts are testifying “about matters growing naturally” out of their own independent research, or if “they have developed their opinions expressly for purposes of testifying.” Id. at 1317. These factors are illustrative, and they are not all applicable in each case. Id. The inquiry is “flexible,” Daubert, 509 U.S. at 594, and “Rule 702 should be applied with a ‘liberal thrust’ favoring admission,” Messick, 747 F.3d at 1196 (quoting Daubert, 509 U.S. at 588). The district court concluded that the expert testimony of Dr. Shustov and Dr. Weisenburger did not meet the Daubert standard of reliability. The district court first focused on the fact that the experts developed their opinions specifically for litigation, and had never conducted independent research on WENDELL V. GLAXOSMITHKLINE 11 the relationship between 6-MP and anti-TNF drugs and the development of HSTCL. The court also noted that both doctors conceded that although their opinions were based on a reasonable degree of medical certainty, they “would not satisfy the standards required for publication in peer-reviewed medical journals.” It concluded that the lack of independent research combined with the doctors’ reluctance to publish, “casts doubt [on] the reliability of their methodologies under Rule 702.” Second, the district court determined that the lack of animal or epidemiological studies showing a causal link between HSTCL and the combination of 6MP and anti-TNF drugs also undermined the experts’ methodology. The court concluded that although it might be difficult to conduct such studies, given the rarity of HSTCL, that type of causal evidence was “especially important here in light of the fact that more than seventy percent of observed HSTCL cases are idiopathic.”3 “[W]ithout some reliable evidence of a positive link between the drugs at issue and the disease,” the district court concluded that the experts “cannot reasonably eliminate other potential causes of Maxx’s HSTCL.” Finally, the district court found that the studies Drs. Weisenburger and Shustov cited did not “purport[] to show that the specific combination of drugs prescribed to Maxx actually causes HSTCL.” Although these studies contained statistics about the incidence of HSTCL in different patient populations, the court found that the experts did not show “that all of the observed differences in these incidence rates are statistically significant or that they account for plausible 3 A disease that is idiopathic, or de novo, is one that does not have a known cause. 12 WENDELL V. GLAXOSMITHKLINE alternative causes of HSTCL, such as IBD itself.” Further, the doctors did not present scientific evidence to support their opinion that IBD is not a risk factor for HSTCL. Although we think it a close question, we conclude that the district court erred by excluding the experts’ testimony. The district court looked too narrowly at each individual consideration, without taking into account the broader picture of the experts’ overall methodology. It improperly ignored the experts’ experience, reliance on a variety of literature and studies, and review of Maxx’s medical records and history, as well as the fundamental importance of differential diagnosis by experienced doctors treating troubled patients. The district court also overemphasized the facts that (1) the experts did not develop their opinions based on independent research and (2) the experts did not cite epidemiological studies. We hold that all together, these mistakes warrant reversal. Cf. Kennedy v. Collagen Corp., 161 F.3d 1226, 1228–30 (9th Cir. 1998) (concluding that the expert’s reliance on studies that showed a connection between collagen and autoimmune disorders combined with the expert’s observations of the patient and review of her medical history was a sufficiently reliable methodology even though the cause-effect relationship between the collagen and the disease was not conclusively established). To begin, the experts were highly qualified doctors. Dr. Shustov is a licensed, board-certified physician and an Associate Professor of Medicine at the University of Washington Medical Center. He specializes in the diagnosis and treatment of lymphomas, with a clinical research focus on T-cell leukemia and lymphomas. He has treated “hundreds of patients with T-cell lymphomas,” and “thousands of patients with lymphomas,” including seven patients with WENDELL V. GLAXOSMITHKLINE 13 HSTCL. Two of those patients were treated with the combination of drugs at issue here. Given the rarity of HSTCL, Dr. Shustov estimated that he has seen more cases of the disease than 99% of oncologists in the country. Dr. Weisenburger is an expert hematopathologist—a physician trained in the study and diagnosis of diseases of the bone marrow and the immune system—with more than 30 years of experience diagnosing non-Hodgkin lymphoma. He is the professor and Chair of the Department of Pathology at City of Hope Medical Center. Although he has not written specifically on HSTCL, he has written hundreds of papers on the subject of non-Hodgkin’s lymphoma, including some on the potential causes of non-Hodgkin’s lymphoma. The doctors employed sound methodologies to reach their conclusions. Dr. Shustov based his opinions “on medical records as well as [his] education, training and experience, knowledge of the pertinent medical literature and [his] knowledge of the epidemiology, diagnosis and natural history of HSTCL.” He explained: “I reviewed the literature, I pulled the facts out of the literature.” He found that the literature shows there is an increased risk of HSTCL in patients taking 6-MP over the general population. After reviewing the literature, he “compiled the numbers about frequency of diseases, about frequency of inflammatory bowel disease and [he] looked at the biological causation of lymphoma pertaining to this case.” Dr. Shustov stated that he performs differential diagnosis in attempting to diagnose every patient, and that he has applied the same technique to determine the cause of a disease. When performing a differential diagnosis, he first assumes the pertinence of all potential causes, then rules out the ones as to which there is no plausible evidence of 14 WENDELL V. GLAXOSMITHKLINE causation, and then determines the most likely cause among those that cannot be excluded. We have recognized that this method of conducting a differential diagnosis is scientifically sound. See Clausen, 339 F.3d at 1057–58. For cases of HSTCL in patients that have taken 6-MP, like Maxx, Dr. Shustov recognized: that 6-MP is a well-known mutagen and carcinogen and puts every person who takes it at risk. And given the frequency of hepatosplenic lymphoma in [the] general population as . . . [compared to] those who take 6-MP, it makes it plausible or biologically plausible that that’s [an] etiologic factor. You construct your differential diagnosis . . . [of] what might have caused lymphoma. You come up with the strongest probability that patient was taking carcinogen and developed lymphoma and you start thinking again what can cause his lymphoma, you can’t identify anything else in the patient’s history or his medical records. Regarding Maxx specifically, Dr. Shustov stated that there was a one in six million chance that Maxx would have developed HSTCL without being exposed to 6-MP. In light of those odds, Dr. Shustov stated that “based on [his] experience in T-cell lymphomas, knowledge of the literature and being involved in T-cell lymphoma research in the past ten years” he determined “that it’s much more likely that exposure to mutagen and immunosuppressants caused the lymphoma.” Dr. Shustov did not need to eliminate all potential causes; “[i]t is enough that a [proposed cause] be a substantial causative factor.” Messick, 747 F.3d at 1199. WENDELL V. GLAXOSMITHKLINE 15 Dr. Weisenburger described his methodology for reaching his opinions as follows: I reviewed the medical records. I reviewed the pathology slides and confirmed the diagnosis. I reviewed all of the pathology records. I reviewed the literature on the disease, hepatosplenic lymphoma. And I reviewed all the literature I could find on causes of hepatopathic T-cell lymphoma, including literature on inflammatory bowel disease and treatments for inflammatory bowel disease. And then I used the Bradford Hill methodology to come to the conclusion that I did.[4, 5] Regarding Maxx specifically, Dr. Weisenburger based his opinion on “a summary of the medical records of [Maxx] as well as copies of the pathology reports, and the original slides of the diagnostic bone marrow,” which he evaluated with over 30 years of experience diagnosing non-Hodgkin lymphoma. He stated that he considered that Maxx’s HSTCL might have been idiopathic, and that although he was not entirely able to rule that possibility out, “[w]hen you have a patient with obvious and known risk factors, you tend to assume that those risk factors were the cause.” He did not base that assumption on pure conjecture. As he discussed throughout his deposition testimony and in his expert report, 4 The Bradford Hill methodology refers to a set of criteria that are well accepted in the medical field for making causal judgments. 5 Dr. Weisenburger also identified at least one paper that showed there was no risk of lymphoma in IBD patients. 16 WENDELL V. GLAXOSMITHKLINE the literature shows that patients exposed to 6-MP and antiTNF drugs are at an increased risk for HSTCL. Dr. Weisenburger also weighed other risk factors, including Maxx’s sex and age, and determined that those were “weak risk factors; whereas, the disease he had, particularly in the setting of the drugs he received would be considered very strong risk factors.” The proposed testimony was sufficiently reliable that the Plaintiffs’ experts should have been allowed to testify under Daubert. The district court improperly required more. The Supreme Court in Daubert aimed at screening out unreliable or bogus expert testimony. Nothing in Daubert, or its progeny, properly understood, suggests that the most experienced and credentialed doctors in a given field should be barred from testifying based on a differential diagnosis. First, the district court was wrong to put so much weight on the fact that the experts’ opinions were not developed independently of litigation and had not been published. While independent research into the topic at issue is helpful to establish reliability, its absence does not mean the experts’ methods were unreliable. Where “the proffered expert testimony is not based on independent research,” the experts can instead present “other objective, verifiable evidence that the testimony is based on ‘scientifically valid principles.’” Daubert II, 43 F.3d at 1317–18. To be sure, “[o]ne means of showing [that the testimony is based on scientifically valid principles] is by proof that the research and analysis supporting the proffered conclusions have been subjected to normal scientific scrutiny through peer review and publication.” Id. at 1318. However, expert testimony may still be reliable and admissible without peer review and publication. See Clausen, 339 F.3d at 1056. That is WENDELL V. GLAXOSMITHKLINE 17 especially true when dealing with rare diseases that do not impel published studies. See Milward v. Acuity Specialty Prods. Grp., Inc., 639 F.3d 11, 24 (1st Cir. 2011) (recognizing that the “rarity” of a particular form of leukemia was one reason that it would be “very difficult to perform an epidemiological study of the causes of [the disease] that would yield statistically significant results.”). The district court also wrongly conflated the standards for publication in a peer-reviewed journal with the standards for admitting expert testimony in a courtroom. Dr. Weisenburger stated on cross-examination that to publish his opinion he would use a “more rigorous” standard than the one he used to come up with his expert opinion. Dr. Shustov stated that he would not be comfortable publishing his opinion because he did not have any new data, and any meta-analysis or review of the literature could only be published upon invitation. The district court viewed these statements regarding the experts’ willingness to publish as evidence that their methods were not up to snuff. But this analysis misses that while an expert must “employ[] in the courtroom the same level of intellectual rigor that characterizes the practice of an expert in the relevant field,” Kumho Tire Co., Ltd. v. Carmichael, 526 U.S. 137, 152 (1999), the standards for courtroom testimony do not necessarily parallel those of the professional publications, see Ambrosini v. Labarraque, 101 F.3d 129, 138 (D.C. Cir. 1996) (“[T]he fact ‘that science would require more evidence before conclusively considering the causation question resolved is irrelevant [to the admissibility of expert testimony].’”) (quoting Ferebee v. Chevron Chem. Co., 736 F.2d 1529, 1536 (D.C. Cir. 1984)). For example, Dr. Shustov explained that, “[o]pinions are not publishable. Data is publishable. What I’m reporting here is my opinion.” Although unwillingness to publish weighs against 18 WENDELL V. GLAXOSMITHKLINE admissibility, it alone is not determinative. See Daubert II, 43 F.3d at 1318 n.9 (“That plaintiffs’ experts have been unable or unwilling to publish their work undermines plaintiffs’ claim that the findings these experts proffer are ‘ground[ed] in the methods and procedures of science’ and ‘derived by the scientific method.’” (alteration in original) (quoting Daubert, 509 U.S. at 590)). We have previously held expert opinions to be reliable that were not subject to peer review through publication. See Clausen, 339 F.3d at 1056, 1061. The district court also wrongfully required that the experts’ opinions rely on animal or epidemiological studies. Neither are necessary for an expert’s testimony to be found reliable and admissible. See Kennedy, 161 F.3d at 1229. We have long recognized that it may not always be possible to conduct certain types of studies. See, e.g., Daubert II, 43 F.3d at 1318 n.9 (“There may well be good reasons why a scientific study has not been published. For example, it may be too recent or of insufficiently broad interest.”). HSTCL is an exceedingly rare cancer, with only 100 to 200 cases reported since it was first recognized. It is not surprising that the scientific community has not invested substantial time or resources into investigating the causes of such a rare disease. Although they did not rely on animal or epidemiological studies, the experts here did rely on other published studies and articles. The district court only addressed a few of these, quickly dismissing them because they are case reports and do not control or account for alternative causes of HSTCL. Although case studies alone generally do not prove causation, they “may support other proof of causation.” Rider v. Sandoz Pharm. Corp., 295 F.3d 1194, 1199 (11th Cir. 2002). Here, WENDELL V. GLAXOSMITHKLINE 19 the experts relied not just on these studies—which not only examined reported cases but also used statistical analysis to come up with risk rates—but also on their own wealth of experience and additional literature.6 We also note that “[n]ot knowing the mechanism whereby a particular agent causes a particular effect is not always fatal to a plaintiff’s claim. Causation can be proved even when we don’t know precisely how the damage occurred, if there is sufficiently compelling proof that the agent must have caused the damage somehow.” Daubert II, 43 F.3d at 1314 (emphasis in original). That there is no study that definitively states HSTCL is caused by the ingestion of 6-MP and antiTNF drugs does not prevent the admission of Plaintiffs’ experts’ testimony. See Kennedy, 161 F.3d at 1230. Finally, the district court erred when it excluded Plaintiffs’ experts’ opinion testimony because of the high rate of idiopathic HSTCL and the alleged inability of the experts to rule out an idiopathic origin or IBD itself. We do not require experts to eliminate all other possible causes of a condition for the expert’s testimony to be reliable. Messick, 747 F.3d at 1199. It is enough that the proposed cause “be a substantial causative factor.” Id. This is true in patients with multiple risk factors, and analogously, in cases where there is a high rate of idiopathy. See id. (holding that the district court abused its discretion when it excluded expert testimony as unreliable because the expert could not determine which of 6 Teva argues that its own experts highlight the dearth of scientific evidence to support Plaintiffs’ claims and undermine any assertion that Drs. Shustov and Weisenburger employed sound scientific methodology. The district court did not consider this evidence, and we decline to do so in the first instance. 20 WENDELL V. GLAXOSMITHKLINE multiple risk factors caused plaintiff’s disease). Moreover, when an expert establishes causation based on a differential diagnosis, the expert may rely on his or her extensive clinical experience as a basis for ruling out a potential cause of the disease. See id. at 1198. The district court abused its discretion by excluding Dr. Shustov’s and Dr. Weisenburger’s testimony because they could not completely rule out the possibility that Maxx’s HSTCL was idiopathic. Perhaps in some cases there will be a plethora of peer reviewed evidence that specifically shows causation. However, such literature is not required in each and every case. “The first several victims of a new toxic tort should not be barred from having their day in court simply because the medical literature, which will eventually show the connection between the victims’ condition and the toxic substance, has not yet been completed.” Clausen, 339 F.3d at 1060 (quoting Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1209 (8th Cir. 2000)). In the case of a rare disease like HSTCL, the Supreme Court’s mandate that in determining the admissibility of expert testimony, the focus “must be solely on principles and methodology, not on the conclusions that they generate,” is especially important. Daubert, 509 U.S. at 595. Where, as here, the experts’ opinions are not the “junk science” Rule 702 was meant to exclude, see Estate of Barabin v. AstenJohnson, Inc., 740 F.3d 457, 463 (9th Cir. 2014), the interests of justice favor leaving difficult issues in the hands of the jury and relying on the safeguards of the adversary system—“[v]igorous cross-examination, presentation of contrary evidence, and careful instruction on the burden of proof”—to “attack[] shaky but admissible evidence,” Daubert, 509 U.S. at 596. Because we conclude WENDELL V. GLAXOSMITHKLINE 21 that the district court erred in excluding the testimony of Dr. Shustov and Dr. Weisenburger, we reverse the district court’s grant of summary judgment. See Messick, 747 F.3d at 1199. As explained in Messick, “[m]edicine partakes of art as well as science.” Id. at 1198. Where, as here, two doctors who stand at or near the top of their field and have extensive clinical experience with the rare disease or class of disease at issue, are prepared to give expert opinions supporting causation, we conclude that Daubert poses no bar based on their principles and methodology. That defendants may be able to offer other equally qualified medical opinion opposing causation also does not support the idea that Daubert should bar the admission of the testimony of the doctors offered as experts by Plaintiffs. Instead, the testimony of Dr. Weisenburger and of Dr. Shustov should have been admitted as expert testimony under Federal Rules of Evidence 702. The defendants’ expert testimony could have been offered in opposition. Then, the jury, as the trier of fact, would be empowered to decide, based on the law given in proper jury instructions and the facts as determined by the jury.