WOLLMAN, Circuit Judge.
Pamela Kuhn and Shirley Davidson were prescribed Prempro, a hormone therapy drug comprised of estrogen and progestin and manufactured by Wyeth.
On behalf of Kuhn and Davidson (collectively, Plaintiffs), Donald F. Austin, M.D., opined that short-term use of Prempro increases the risk of breast cancer. The magistrate judge to whom the evidentiary matter was referred concluded that Dr. Austin's opinion was not sufficiently reliable to meet the admissibility standard set forth in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S.Ct. 2786, 125 L.Ed.2d 469 (1993), and thus granted Wyeth's motion. Thereafter, the district court overruled Plaintiffs' objections to the Daubert order, granted Wyeth's motion for summary judgment, entered judgment dismissing the two cases, and denied Plaintiffs' post-trial motions.
Kuhn and Davidson appeal. They argue that the magistrate judge abused his discretion in granting Wyeth's motion to preclude
Prempro is a combination hormone therapy composed of conjugated equine estrogen and medroxyprogesterone acetate.
In the 1990s, the National Institutes of Health began studying the effects of hormone therapy drugs as part of its Women's Health Initiative (WHI).
Following the publication of the WHI study results, thousands of women filed lawsuits against Wyeth and other hormone therapy drug manufacturers, alleging that hormone therapy increased the risk of breast cancer and that the companies had failed to warn of that risk. In 2003, the federal lawsuits were consolidated in the Eastern District of Arkansas.
In late October 2010, the district court selected Kuhn's and Davidson's cases to go to trial. Earlier that month, the district court had directed the parties to provide "a list of all `short-term use' Plaintiffs who filed cases in either the Eastern District or Western District of Arkansas." Kuhn App. 49. The district court selected Davidson from the list of plaintiffs who had used Prempro for three years or less. The court also selected Kuhn, who had
On October 29, 2010, Wyeth advised the court that a short-term use case was proceeding to trial in the District of Puerto Rico and that it planned to file a Daubert challenge to the general causation opinions of the plaintiff's experts. Because Wyeth would file similar challenges in both Puerto Rico and Arkansas, Wyeth suggested that the two courts hear together the Daubert challenge. The courts agreed, and a joint hearing was scheduled for November 29, 2010, in Puerto Rico.
Prior to the hearing, Wyeth filed its motion to preclude expert testimony.
In opposition, Plaintiffs set forth their position that estrogen plus progestin (E+P) is a "growth promoting agent" that causes cancer-susceptible cells to become cancerous. Kuhn App. 168. According to Plaintiffs, the promotion effect can be seen in a matter of months. Hormone therapy plaintiffs typically have relied on the WHI study to show that use of Prempro causes an increased risk of breast cancer, but Kuhn and Davidson argued that the study was not powerful
In its reply, Wyeth argued that Plaintiffs' evidence failed to establish a reliable basis for concluding that short-term use of Prempro increases the risk of breast cancer. Wyeth argued that Plaintiffs' criticisms of the WHI study's findings were misguided, particularly because hormone therapy litigation experts had relied so heavily on the study in the past and because
The day before the evidentiary hearing in Puerto Rico, Plaintiffs filed the declaration of Dr. Austin, who opined that "E+P can, and often does cause clinically detectable breast cancer in short-term durations including a matter of months." Kuhn App. 3905. Dr. Austin set forth in his declaration his standards for reviewing observational studies, including that he would not rely on "underpowered" studies, which he defined as studies that were not likely to identify an association or an effect, if one existed.
Dr. Austin also opined that the WHI study's estimate of short-term risk was "quite poor" due to shortcomings "that diminish the estimate of the effect of short-term exposure." Kuhn App. 3902. He explained that the WHI study participants were more than ten years past the onset of menopause, meaning that they were much older than the women who typically start hormone therapy. Moreover, the study tended to exclude women who were experiencing moderate hot flashes. According to Dr. Austin, those women were more likely to be estrogen deficient and more likely to be susceptible to the carcinogenic effects of E+P. Dr. Austin also explained that the WHI study's analysis necessarily underestimates the relative risk because approximately forty percent of the participants dropped out of the study and about eleven percent of the placebo group began taking E+P.
Given that Dr. Austin's declaration was filed on November 28, 2010, it was not
Shortly after the hearing, the district court asked Plaintiffs and Wyeth to address the WHI study's finding that breast cancer incidents were lower among the participants taking Prempro than those who were taking the placebo during the first three years. Specifically, the court asked, "With respect to short term use, please give me a short, pointed, pithy brief explaining what evidence of your's meets the WHI findings on this point." Kuhn App. 3912. Plaintiffs reiterated the arguments they had made in opposition to Wyeth's motion to preclude, including that the WHI study was not powerful enough to detect a short-term risk, that it was not designed to do so, and that other studies established a short-term effect. After reviewing the parties' submissions, the district court ordered a second Daubert hearing and called for live testimony from the parties' experts.
On January 12, 2011, the magistrate judge held a lengthy Daubert hearing. Dr. Austin and Wyeth's expert, Kurt Barnhart, M.D., testified, fielding questions from the attorneys and the court. During the hearing, Dr. Austin conceded that the Li (2000) and Saxena (2010) studies should not have been included in his expert report. Dr. Austin thus based his opinion that short-term use of Prempro causes breast cancer on the Million Women Study, the Fournier study, and the American Cancer Society Study (Calle study).
The magistrate judge issued an order the following week, granting Wyeth's motion to preclude expert testimony.
We review the decision to exclude expert evidence for an abuse of discretion. Gen. Elec. Co. v. Joiner, 522 U.S. 136, 143, 118 S.Ct. 512, 139 L.Ed.2d 508
"[T]he requirement that an expert's testimony pertain to `scientific knowledge' establishes a standard of evidentiary reliability." Daubert, 509 U.S. at 590, 113 S.Ct. 2786. The Supreme Court explained that evidentiary reliability means trustworthiness. Id. at 591 n. 9, 113 S.Ct. 2786. "Proposed testimony must be supported by appropriate validation — i.e., `good grounds,' based on what is known." Id. at 590, 113 S.Ct. 2786. The standard for judging the evidentiary reliability of expert evidence is "lower than the merits standard of correctness." In re Paoli R.R. Yard PCB Litig., 35 F.3d 717, 744 (3d Cir.1994). Proponents of expert testimony need not demonstrate that the assessments of their experts are correct, and trial courts are not empowered "to determine which of several competing scientific theories has the best provenance." Milward v. Acuity Specialty Prods. Grp., 639 F.3d 11, 15 (1st Cir.2011) (quoting Ruiz-Troche v. Pepsi Cola of Puerto Rico Bottling Co., 161 F.3d 77, 83 (1st Cir. 1998)); see Fed.R.Evid. 702 advisory committee's note (discussing 2000 amendments) ("When a trial court, applying this amendment, rules that an expert's testimony is reliable, this does not necessarily mean that contradictory expert testimony is unreliable."). "Vigorous cross-examination, presentation of contrary evidence, and careful instruction on the burden of proof are the traditional and appropriate means of attacking shaky but admissible evidence." Daubert, 509 U.S. at 596, 113 S.Ct. 2786.
The Supreme Court identified in Daubert a number of factors that might assist the district court in determining the admissibility of expert evidence: (1) whether the theory or technique applied can be tested, (2) whether the theory or technique has been subject to peer review or publication, (3) the known or potential rate of error, and (4) whether it is accepted in the relevant discipline. Id. at 593-94, 113 S.Ct. 2786. It instructed district courts to focus on "principles and methodology, not on the conclusions that they generate." Id. at 595, 113 S.Ct. 2786. The Court later recognized that "conclusions and methodology are not entirely distinct from one another." Joiner, 522 U.S. at 146, 118 S.Ct. 512. Accordingly, a district court's focus on principles and methodology "need not completely pretermit judicial consideration of an expert's conclusions." Milward, 639 F.3d at 15 (quoting Ruiz-Troche, 161 F.3d at 81). Expert evidence may be excluded if the court determines "that there is simply too great an analytical gap between the data and the opinion proffered." Joiner, 522 U.S. at 146, 118 S.Ct. 512.
Plaintiffs involved in hormone therapy litigation have long relied on the WHI study to prove general causation: that is, that use of Prempro increases the risk of breast cancer. A 2003 article about the WHI study reported:
Ex.App. 55.
The magistrate judge found that Dr. Austin failed to meet his burden "to present reliable science to support his conclusion regarding the unreliability of the WHI." Order of Jan. 19, 2011, at 9. Plaintiffs, as the proponents of Dr. Austin's testimony, however, do not necessarily have a burden to disprove the WHI study's finding that short-term use of Prempro does not increase the risk of breast cancer. Instead, it is their burden to show that Dr. Austin arrived at his contrary opinion in a scientifically sound and methodological fashion. If they can meet that burden, the question becomes one for the jury to decide. See Bonner v. ISP Techs., Inc., 259 F.3d 924, 930 (8th Cir.2001) ("[Q]uestions of conflicting evidence must be left for the jury's determination.").
As an initial matter, we note that the magistrate judge did not address Dr. Austin's testimony that women who took Prempro had "[l]ower recorded rates of breast cancer in the first two years, not three years." Hr'g Tr. 152. Dr. Austin distinguished between annual incidents of breast cancer and cumulative incidents of breast cancer, acknowledging that a graph contained in a 2006 article showed that the placebo group had higher rates of breast cancer during the first three years of the trial. See Ex.App. 19.
Hr'g Tr. 154. The magistrate judge's opinion addresses only Dr. Austin's testimony that the cumulative incidents showed no increase in the breast cancer risk in the first three years. When asked at oral argument before this court whether the magistrate judge had made a mistake in interpreting the graph, Wyeth's counsel responded that he had not because the magistrate judge was interpreting Dr. Austin's testimony, not the underlying evidence, and because Dr. Austin previously had testified that the WHI study shows no increased risk when Prempro is taken for three years or less. Dr. Austin's hearing testimony, however, distinguished between the cumulative and annual incidents, and any conflict with his previous testimony,
We conclude that the magistrate judge abused his discretion in deciding that Dr. Austin's criticisms of the WHI study were unfounded and inconsistent with his reliance on the study in other hormone therapy cases. When asked by the court how the WHI could be the "gold standard" to show that E+P is a carcinogen but could not be relied upon to show that its short-term use does not increase the risk of breast cancer, Dr. Austin replied that the WHI study was an ideal study design — "the gold standard for what it was designed for" — but that it was designed to show what effect E+P had on heart disease. Hr'g Tr. 69. He explained that although the study monitored incidents of breast cancer, the women were not selected to test whether Prempro causes breast cancer. According to Dr. Austin, this resulted in a study population that was at a much lower risk because (1) the study discouraged the participation of women with moderate menopausal symptoms and (2) the participants had a longer gap time between menopause and beginning hormone therapy treatment than women who begin hormone therapy on their own volition. Dr. Austin went on to explain that, despite its shortcomings, the study showed that E+P causes breast cancer:
Id. at 69-70. In light of this testimony and its supporting evidence, Dr. Austin's reliance on the WHI study to prove general causation does not foreclose his opinion that the study did not accurately assess the risk of breast cancer associated with the short-term use of Prempro.
The magistrate judge also found that Dr. Austin previously had contradicted his opinion that the WHI study lacked power to detect an increased risk of breast cancer from short-term use of Prempro. The court noted that "previously, Dr. Austin agreed that WHI, as a clinical trial, had the greatest power when assessing HRT [hormone therapy] and women's health." Order of Jan. 19, 2011, at 7. Dr. Austin now offers a more nuanced opinion than he has in the past, setting forth the foundation for his present concerns, for as he explained,
Hr'g Tr. 71-72.
Wyeth will certainly challenge Dr. Austin's credibility based on his previous testimony, including his agreement that the WHI study would be a "good study to look at in determining whether a certain duration of exposure to Prempro increases the risk of breast cancer." Id. at 145. But his previous reliance on and testimony regarding the WHI study does not render his
Finally, in determining that Dr. Austin failed to support his criticisms of the WHI study, the magistrate judge found that Dr. Austin's opinions were "hastily formed in an attempt to overcome overwhelmingly reliable evidence to the contrary." Order of January 19, 2011, at 9. Dr. Austin testified that the short-term use issue was presented to him shortly before the Daubert hearing in Puerto Rico. He wrote the expert report in approximately five hours, with the assistance of Plaintiffs' counsel. The magistrate judge's concerns about Dr. Austin's opinions, however, go to his credibility as a witness, not to the admissibility of his testimony as an expert. Wyeth argues that, like the expert testimony in In re TMI Litigation, 193 F.3d 613 (3d Cir. 1999), Dr. Austin's testimony should be excluded based on his reliance on Plaintiffs' counsel. In that case, however, the expert relied on medical history summaries prepared at the direction of plaintiffs' counsel, which the court found unreliable. Id. at 697-98. Here, Dr. Austin relied on epidemiological studies that, at most, were compiled for him by Plaintiffs' counsel. Unlike the medical history summaries, the supporting observational studies provide adequate foundation for Dr. Austin's testimony.
Dr. Austin ultimately relied on three observational studies to support his opinion: the Calle study, the Million Women Study, and the Fournier study. The magistrate judge analyzed each study separately and concluded that the studies failed to reliably support Dr. Austin's position. On appeal, Kuhn and Davidson argue that the magistrate judge usurped the role of factfinder and that any problems with the studies go to the weight of the evidence, not to the studies' validity. Wyeth responds that the magistrate judge properly determined that the studies were insufficient to support Dr. Austin's opinion because there existed too great an analytical gap between the underlying studies and Dr. Austin's opinion, see Joiner, 522 U.S. at 146-47, 118 S.Ct. 512, and because in relying on the studies, he failed to employ the rigorous methods that he uses in other contexts, see Kumho Tire Co., 526 U.S. at 152, 119 S.Ct. 1167.
Dr. Austin relied on the Calle study, a study of 67,754 American women that "examined prospectively the relation between postmenopausal hormone use and the risk of incident of breast cancer...." Ex. App 32. When the participants enrolled in 1992, they completed self-administered mailed questionnaires that collected information regarding demographic, medical, behavioral, environmental, occupational, and dietary factors. Follow-up questionnaires were sent in 1997, 1999, 2001, and 2003 "to update exposure information and to ascertain newly diagnosed cancers." Id. According to the authors, "[i]nformation regarding postmenopausal hormone use was collected at the time of enrollment and on all follow-up questionnaires." Id. at 33. Women with unknown type or duration of hormone use were excluded from the analysis. The authors observed no increase in risk with use of E+P in the first two years of use. "However, we observed a significant increase in risk for both types of breast cancer at 2 to 3 years of use ... and all years thereafter." Id. at 37.
The magistrate judge found the study unreliable because "there was no way to measure how it accounted for previous use [of hormone therapy]" and because it
Dr. Austin also relied on two foreign studies: the Million Women Study from England and the Fournier study from France. "The Million Women Study was set up to investigate the effects of specific types of [hormone therapy] on incident and fatal breast cancer." Ex.App. 165. As its name suggests, the study involved more than one million women between fifty and sixty-four years of age, including more than 20,000 participants who took medroxyprogesterone acetate combined with conjugated equine estrogen, the same formulation as Prempro. It found that combined estrogen and progestin therapy increased the risk of breast cancer and that "[r]esults varied little between specific oestrogens and progestagens or their doses; or between continuous and sequential regimens." Id. Specifically, the study reported:
Id. at 172. Upon joining the Million Women Study, the participants reported information regarding their hormone therapy use including their "ever use; current use; age at first and last use; total duration of use; and the name of the proprietary preparation used most recently and duration of its use." Id. at 165. The participants thus reported their duration of use when they enrolled, but the study did not measure their use after enrollment. Instead, it found that "[t]he breast cancers were diagnosed on average 1.2 years after recruitment" to the study. Id. at 167.
A table in the Million Women Study shows an elevated relative risk of breast cancer among women who reported using estrogen plus progestagen for less than one year. Because the study measured duration of use at enrollment rather than diagnosis, the precise duration of use by those women diagnosed with breast cancer was unknown. Dr. Austin suggested that by adding the average 1.2 years from enrollment to diagnosis to the less than one
Dr. Austin also relied upon the Fournier study, which investigated "whether the relation between estrogen-progestagen menopausal hormone therapy (EP-MHT) and breast cancer risk varies according to the delay between menopause onset and treatment initiation." Ex.App. 83. More than 50,000 postmenopausal French women participated in the study. The results suggested that "in recent users of some EP-MHT, the timing of treatment initiation modulates the risk of breast cancer: short durations (≤2 years) of use were associated with significant increases in risk — with the exception of MHT containing progesterone — when initiated in the 3-year period following menopause, but not when initiated later."
French women typically use a different type of hormone therapy than American women. In the Fournier study's cohort, "the estrogenic component consisted almost exclusively of estradiol compounds, with progesterone and dydrogesterone as the most frequently associated progestagens." Id. at 87. Although relatively few participants took formulations comprised of conjugated estrogens combined with medroxyprogesterone acetate, like Prempro, more than one hundred participants using hormone therapy comprised of progestagens were diagnosed with breast cancer.
Id. In an editorial commenting on the Fournier study, Leslie Bernstein, M.D., thus wrote, "[I]t will be important for other cohorts that focus on use of HT in United States populations to evaluate breast cancer risk associated use immediately after menopause." Id. at 28.
Dr. Austin acknowledged that the Fournier study did not separate Prempro's formulation from other hormone therapy formulations. He testified that medroxyprogesterone acetate is combined only with conjugated estrogens and that its risk estimates are similar to those of other of synthetic progesterones that are combined with other estrogens. "Since
The magistrate judge concluded that the foreign studies did not reliably support Dr. Austin's opinion because most participants in the studies took hormone therapy formulations other than Prempro and because the studies did not analyze Prempro separately from other hormone therapy formulations after three years.
Although the foreign studies have important limitations, they nonetheless provide support for Dr. Austin's opinion. As set forth above, the Million Women Study explained that there exists no material difference in risk among the combined estrogen and progestin hormone therapy formulations, including Prempro. With this finding, and its finding that less than one year's use of combined hormone therapy increases the risk of breast cancer, the Million Women Study provides support for Dr. Austin's opinion regarding short-term use. Likewise, the differences between Prempro and the French combined hormone therapy formulation do not render the study unreliable to support Dr. Austin's opinion.
Citing Glastetter v. Novartis Pharmaceuticals Corp., 252 F.3d 986 (8th Cir.2001) (per curiam), Wyeth argues that Dr. Austin's testimony relating the European formulations to the American formulations constitutes an unsupported assumption. In Glastetter, the plaintiff's experts hypothesized that the chemical at issue, bromocriptine, "may behave like its chemical cousins," ergot alkaloids, which were known to cause a condition that was a known risk factor for the plaintiff's injury. Id. at 989-90. We concluded that the "generic assumption that bromocriptine behaves like other ergot alkaloids carries little scientific value." Id. at 990. Here, Dr. Austin presented evidence that the Million Women Study considered estrogen plus progestin hormone therapy formulations separately and found little difference between the effects of the different formulations.
As set forth above, the magistrate judge relied on Dr. Austin's testimony in other cases and his earlier statements to find that the foreign studies did not reliably support his opinion. Specifically, the court found that the studies failed to meet Dr. Austin's criteria of (1) accurately characterizing exposure to the drug, (2) identifying the specific drug formulations, and (3) analyzing the Prempro formulation separately. At the hearing, Dr. Austin acknowledged that, ideally, a study would measure exposure precisely and analyze the Prempro formulation separately, but he did not concede that the studies on which he based his opinion were unreliable. Instead, he explained,
Hr'g Tr. 51-52. Although the foreign studies are not perfect, they provide useful information that, along with the Calle study, provides an adequate foundation for Dr. Austin's opinion. His prior testimony may well call his credibility into question, but it does not prove that he failed to follow his own general practice or that he relied on unfounded assumptions in his analysis. Cf. Junk, 628 F.3d at 448 (holding that the expert's "failure to follow his own general practice and his reliance on unfounded assumptions in his comparative method created `too great an analytical gap' between his opinion and the data on which it relied" (quoting Joiner, 522 U.S. at 146, 118 S.Ct. 512)); Fireman's Fund Ins. Co. v. Canon U.S.A., Inc., 394 F.3d 1054, 1059 (8th Cir.2005) (noting that the sudden reversal of opinion regarding the meaning of burn pattern evidence "seriously undermine[d] the reliability of the experts' opinions").
Dr. Austin's testimony is admissible because the studies upon which he relied were sufficient to support his opinion that short-term use of Prempro increases the risk of breast cancer. Taken together, the Calle study and the foreign studies constitute appropriate validation of and good grounds for Dr. Austin's opinion. The studies' limitations may be presented to the jury, and Dr. Austin's reliance on the studies may be tested through the traditional means of cross examination and presentation of contrary evidence.
Wyeth argues that Dr. Austin "cherry picked" the Calle study and the two foreign studies from a wealth of studies showing no increased risk of breast cancer from short-term Prempro use. Wyeth compares this case to Norris v. Baxter Healthcare Corp., 397 F.3d 878 (10th Cir.2005), in which the defendant presented at least seventeen epidemiological studies in support of its contention that silicone breast implants do not cause disease. The plaintiffs in Norris offered no epidemiological studies to support their contrary position, instead relying upon differential diagnosis and case studies. The Norris court concluded that "[p]laintiff's experts' differential diagnoses and case studies are unreliable because they assume what science has largely shown does not exist-a causal connection between silicone breast implants and disease." Id. at 886. Unlike those experts, Dr. Austin has presented reliable epidemiological evidence to support his opinion that short-term use of Prempro increases the risk of breast cancer. There may be several studies supporting Wyeth's contrary position, but it is not the province of the court to choose between the competing theories when both are supported by reliable scientific evidence.
The grant of summary judgment in favor of Wyeth was based on the preclusion of Dr. Austin's opinion. Because we hold Dr. Austin's opinion is admissible, we reverse the order granting summary judgment.
We reverse the orders granting Wyeth's motions to preclude expert testimony and for summary judgment. Because our reversal is based on the conclusion that Dr. Austin's opinion is admissible, we do not reach the merits of Kuhn's argument that the Daubert order did not apply to her because she had used Prempro for more than three years. The case is remanded for further proceedings.
LOKEN, Circuit Judge, dissenting.
Early in its lengthy analysis, the district court described the "methodology" of plaintiffs' expert, Dr. Donald Austin:
After thoroughly reviewing the bases for Dr. Austin's opinion in an analysis the court now finds statistically faulty in some respects, the district court concluded:
Like the district court in General Electric Co. v. Joiner, 522 U.S. 136, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997), the district court excluded opinion testimony of plaintiffs' only expert. In my view, the district court's Daubert analysis is supported by the record and properly focused on the gate-keeping function mandated by the Supreme Court and by Rule 702. We review that ruling for abuse of discretion and must affirm unless it is "manifestly erroneous." Joiner, 522 U.S. at 142, 118 S.Ct. 512. We may not subject the ruling to "a more searching standard of review" because it was "`outcome determinative.'" Id. at 142-43, 118 S.Ct. 512. I conclude that, like our sister circuit the Supreme Court reversed in Joiner, the court has "appl[ied] an overly `stringent' review to that ruling [and] failed to give the trial court the deference that is the hallmark of abuse of discretion review." Id. at 143, 118 S.Ct. 512. Accordingly, I respectfully dissent.