Opinion ID: 212992
Heading Depth: 2
Heading Rank: 1

Heading: The Evidentiary Basis of Dr. Smith's Opinion

Text: The district court's exclusion of Dr. Smith's testimony was based to a significant extent on its rejection of what it took to be his three key subsidiary conclusions regarding the weight of the mechanistic evidence. We briefly summarize the court's analysis on these points before turning to our discussion of the ways in which the court erred in its analysis. First, the court held that there was insufficient evidence to support Dr. Smith's opinion that all subtypes of AML likely have a common etiology. The court reasoned that the clear differences among AML subtypesin particular, APL's unique response to certain types of therapy, and the subtypes' different chromosomal abnormalitiesmade a broad extrapolation from AML generally to APL specifically inappropriate. [14] Milward, 664 F.Supp.2d at 144. The court also noted that a series of recent studies had led investigators to think that the `leukemic stem cell' may exist in more mature, differentiated cell lines, such that the `leukemic stem cell' may not be a stem cell in the usual sense, but rather a differentiated cell that has somehow acquired the ability to reproduce itself, as a stem cell can. Id. at 145. If the various AML subtypes did not arise from the same progenitor or stem cell, the court reasoned, they might well not share a common etiology. [15] Finally, the court emphasized that there was no scientific consensus on this issue, and that the question of when the key chromosomal translocation occurs was considered by researchers to be  a question that remains unanswered in the APL field. Id. (quoting S. Wojiski et al., PML-RARα Initiates Leukemia by Conferring Properties of Self-Renewal to Committed Promyelocytic Progenitors, 23 Leukemia 1462, 1469 (2009) (emphasis added)) (internal quotation marks omitted). Second, the court held that what was known about the types of chromosomal translocations caused by benzene did not offer sufficient support for Dr. Smith's opinion that it is biologically plausible that benzene causes the characteristic t(15;17)(q22;q12) translocation seen with APL. The court explained that this opinion would be warranted if benzene's impact on chromosomes were randomly experienced, but it noted that a paper co-authored by Dr. Smith concluded that benzene can initiate or promote leukemia induction by a nonrandom selective effect on specific chromosomes. Id. at 147 (emphasis added). This defeated the generalization that because . . . benzene causes damage to some chromosomes, it is `biologically plausible' that it causes damage to other chromosomes. Id. Third, the court held that there was insufficient evidence to support the inference that benzene metabolites inhibit topo II in such a way as to cause the chromosomal translocation seen in cases of APL. The court's conclusion was in part based on evidence that [t]here are different classes of topo II inhibitors and the different classes have been associated with different AML subtypes. Id. Highlighting one article's finding that leukemias induced by benzene do not appear to exhibit the defining characteristics associated with four other classes of topo II inhibitors, id. at 148, the court held that to the extent that Dr. Smith's opinion rests on the proposition that all topo II inhibitors act similarly to cause a similar effect, then, it does not appear to be based on reliable scientific knowledge, id. at 147. In reaching these three conclusions about some of the evidence on which Dr. Smith based his opinion, the court both placed undue weight on the lack of general acceptance of Dr. Smith's conclusions and crossed the boundary between gatekeeper and trier of fact. Although general acceptance is still a relevant consideration under Daubert, the court's demands went too far. Cf. Smith v. Ford Motor Co., 215 F.3d 713, 721 (7th Cir.2000) (reversing district court that had treated lack of peer review as dispositive grounds for excluding expert opinion). On the question of the origins of APL, for example, the court explained that in the absence of consensus about the target cell for the leukemic mutation, Dr. Smith's opinion that all forms of AML likely share a common origin was at best a plausible hypothesis. Milward, 664 F.Supp.2d at 146. The court explained that the fact that other plausible hypotheses ... might be true as well, including the hypothesis that the genetic mutation that leads to APL occurs in relatively mature cells, meant that Dr. Smith's opinion was not based on sufficient facts and data to be accepted as a reliable scientific conclusion. Id.; see also id. at 148 (focusing on lack of consensus as to the topo II question). But the fact that another explanation might be right is not a sufficient basis for excluding Dr. Smith's testimony. Lack of certainty is not, for a qualified expert, the same thing as guesswork. Primiano v. Cook, 598 F.3d 558, 565 (9th Cir.2010). In addition, the alleged flaws identified by the court go to the weight of Dr. Smith's opinion, not its admissibility. There is an important difference between what is unreliable support and what a trier of fact may conclude is insufficient support for an expert's conclusion. The court's analysis repeatedly challenged the factual underpinnings of Dr. Smith's opinion, and took sides on questions that are currently the focus of extensive scientific research and debate and on which reasonable scientists can clearly disagree. In this, the court overstepped the authorized bounds of its role as gatekeeper. The soundness of the factual underpinnings of the expert's analysis and the correctness of the expert's conclusions based on that analysis are factual matters to be determined by the trier of fact. Smith, 215 F.3d at 718. When the factual underpinning of an expert's opinion is weak, it is a matter affecting the weight and credibility of the testimonya question to be resolved by the jury. Vargas, 471 F.3d at 264 (quoting Int'l Adhesive Coating Co. v. Bolton Emerson Int'l, 851 F.2d 540, 545 (1st Cir.1988)) (internal quotation marks omitted); see also Quiet Tech. DC-8, Inc. v. Hurel-Dubois UK Ltd., 326 F.3d 1333, 1345 (11th Cir.2003); Amorgianos v. Nat'l R.R. Passenger Corp., 303 F.3d 256, 267 (2d Cir.2002). Of course, following Joiner, a district court properly may exclude expert testimony if the court concludes too great an analytical gap exists between the existing data and the expert's conclusion. Kennedy v. Collagen Corp., 161 F.3d 1226, 1230 (9th Cir.1998). Here, however, the gap was of the district court's making. Id. Dr. Smith's opinion was based on a reliable methodology and substantial evidence that he carefully explained. The questions that the court posed were sensible ones, but ones for the jury to resolve. At times, the court's error in excluding Dr. Smith's testimony derived from a mistake in its understanding of the weight of the evidence methodology employed by Dr. Smith. The court treated the separate evidentiary components of Dr. Smith's analysis atomistically, as though his ultimate opinion was independently supported by each. For example, the court referred to Dr. Smith's opinion that because benzene metabolites inhibit topo II and because some classes of topo II inhibitors appear to have a causal relationship to APL, therefore benzene has a causal relationship to APL. Milward, 664 F.Supp.2d at 148 (emphasis added). This overstates Dr. Smith's conclusion as to the topo II evidence, and is indicative of an error in the court's understanding of the nature of Dr. Smith's analysis. In Dr. Smith's weight of the evidence approach, no body of evidence was itself treated as justifying an inference of causation. Rather, each body of evidence was treated as grounds for the subsidiary conclusion that it would, if combined with other evidence, support a causal inference. The district court erred in reasoning that because no one line of evidence supported a reliable inference of causation, an inference of causation based on the totality of the evidence was unreliable. Cf. Nutra-Sweet Co. v. X-L Eng'g Co., 227 F.3d 776, 789 (7th Cir.2000) (holding that an expert's reliance on individual pieces of evidence, insufficient in themselves to prove a point, did not render his opinion speculative). [16] The hallmark of the weight of the evidence approach is reasoning to the best explanation for all of the available evidence. Cf. Dalkon Shield, 156 F.3d at 253 (reversing district court's exclusion of expert testimony as guesswork or without basis when testimony was based on differential diagnosis and there was no showing that any one of the expert's premises was so faulty that it could not even be tendered to the jury for its consideration); see also Hardyman v. Norfolk & W. Ry. Co., 243 F.3d 255, 261 (6th Cir.2001).
As to the epidemiological evidence on which Dr. Smith based his opinion in part, the court held that the published articles on which Dr. Smith relied did not support his opinion, and that in any event, the evidence was not statistically significant. On these grounds, the court rejected Dr. Smith's conclusion that the available epidemiological evidence offered some support for an inference of causation. In concluding that the papers cited by Dr. Smith did not support his opinion, the court reasoned that Dr. Garabrant convincingly demonstrated, especially with respect to the Golomb and Travis papers, that Dr. Smith's conclusions that there was a positive association between exposure to benzene and APL were based on faulty calculations of odds ratios. Milward, 664 F.Supp.2d at 149. An odds ratio represents the difference in the incidence of a disease between a population that has been exposed to benzene and one that has not. In Dr. Garabrant's opinion, Dr. Smith should have used the incidence rate of APL for the general population as a baseline, rather than the rate for non-benzene-exposed workers. In the Daubert hearing and in his supplemental report, however, Dr. Smith explained that he disagreed with Dr. Garabrant on this point, but that in any event, the odds ratio was still elevated, consistent with an inference of causation. Where, as here, both experts' opinions are supported by evidence and sound scientific reasoning, the question of who is right is a question for the jury. [17] The court explained, however, that even if some of the data reported in the various studies could be properly understood to suggest a positive association, the findings are not statistically significant, id., and that although epidemiological evidence is not always essential, the defendants were correct that sound epidemiological studies are ordinarily needed to confirm, by consistent observation, an hypothesis of causation, id. at 148. In context, the district court read too much into the paucity of statistically significant epidemiological studies. The absence of peer-reviewed epidemiological studies does not, as defendants contend, make it almost impossible for Dr. Smith's opinion to be admissible. Epidemiological studies are not per se required as a condition of admissibility regardless of context. See Rider v. Sandoz Pharm. Corp., 295 F.3d 1194, 1198 (11th Cir.2002) (It is well-settled that while epidemiological studies may be powerful evidence of causation, the lack thereof is not fatal to a plaintiff's case.); Restatement § 28 reporters' note cmt. c(3) (listing federal circuit cases holding that epidemiological data is not necessary). Nor are such studies treated as always essential in the relevant scientific communities. To be clear, this is not a situation in which the available epidemiological studies found that there is no causal link, or even one in which no cases of APL were found among benzene-exposed workers. Cf. Norris v. Baxter Healthcare Corp., 397 F.3d 878, 882 (10th Cir.2005) (holding that epidemiological studies are not required to prove causation, but that a substantial body of epidemiological evidence challenging causation cannot be ignored); Allen v. Pa. Eng'g Corp., 102 F.3d 194, 197 (5th Cir.1996) (finding it significant that numerous reputable epidemiological studies covering in total thousands of workers indicated that there was no causation). Rather, this is a case in which there is a lack of statistically significant epidemiological evidence, and in which the rarity of APL and difficulties of data collection in the United States make it very difficult to perform an epidemiological study of the causes of APL that would yield statistically significant results. [18] Dr. Smith estimated that in order to obtain statistically significant results, one would need hundreds of thousands of highly exposed workers, the same number of controls, and millions of dollars in funding. The court erred in treating the lack of statistical significance as a crucial flaw. See Collagen Corp., 161 F.3d at 1229 (finding that the district court placed too much emphasis on lack of epidemiological studies where such studies would be almost impossible to perform); see also Primiano, 598 F.3d at 566-67 (noting that peer-reviewed studies are not necessary, especially when there are good reasons why such studies have not been performed). Under these circumstances, the court erred in holding that Dr. Smith's attempt to support his conclusion with data that concededly lacks statistical significance was a deviation from sound practice of the scientific method that provided grounds for exclusion. Milward, 664 F.Supp.2d at 149. The court's evaluation of the epidemiological evidence is also in tension with the weight of the evidence methodology. Dr. Smith explained that his citation to epidemiological data was meant to challenge the theory that benzene exposure could not cause APL, and to highlight that the limited data available was consistent with the conclusions that he had reached on the basis of other bodies of evidence. He stated that [i]f epidemiologic studies of benzene-exposed workers were devoid of workers who developed APL, one could hypothesize that benzene does not cause this particular subtype of AML. The fact that, on the contrary, APL is seen in studies of workers exposed to benzene where the subtypes of AML have been separately analyzed and has been found at higher levels than expected suggested to him that the limited epidemiological evidence was at the very least consistent with, and suggestive of, the conclusion that benzene can cause APL. The court rejected Dr. Smith's reasoning, stating that a `suggestion' may give rise to a plausible hypothesis, but not a reliable inference. Milward, 664 F.Supp.2d at 149. But as noted above, this is inconsistent with the scientifically accepted methodology employed by Dr. Smith. Dr. Smith did not infer causality from this suggestion alone, but rather from the accumulation of multiple scientifically acceptable inferences from different bodies of evidence.