Court Opinion

ID: 9940265
Source: CourtListenerOpinion
Date Created: 2024-02-13 20:00:45.896729+00
Date Added: 2024-06-11T13:44:42.136699
License: Public Domain

RECOMMENDED FOR PUBLICATION
                               Pursuant to Sixth Circuit I.O.P. 32.1(b)
                                        File Name: 24a0028p.06

                   UNITED STATES COURT OF APPEALS
                                 FOR THE SIXTH CIRCUIT

                                                                          ┐
In re: ONGLYZA (SAXAGLIPTIN) AND KOMBIGLYZE (SAXAGLIPTIN AND
                                                                          │
METFORMIN) PRODUCTS LIABILITY LITIGATION - MDL 2809.
                                                                          │
 _______________________________________________________                  │
                                                                          >      No. 22-6078
LEATHA TAYLOR, individually and as administratrix of the estate of
David Taylor, et al.,                                                     │
                                                                          │
                                             Plaintiffs-Appellants,       │
                                                                          │
       v.                                                                 │
                                                                          │
                                                                          │
BRISTOL-MYERS      SQUIBB    COMPANY;      ASTRAZENECA
                                                                          │
PHARMACEUTICALS LP; IPR PHARMACEUTICALS INC.; MCKESSON
                                                                          │
CORPORATION; ASTRAZENECA LP,
                                                                          │
                                    Defendants-Appellees.                 │
                                                                          ┘

                         Appeal from Multi-District Litigation 2809.
                  No. 5:18-md-02809—Karen K. Caldwell, District Judge,
        United States District Court for the Eastern District of Kentucky at Lexington.
                                 _______________________
                                    ORIGINATING CASES

      18-cv-00053–57   18-cv-00127–32      18-cv-00250       18-cv-00320–21   18-cv-00578–79
      18-cv-00062–63   18-cv-00134         18-cv-00252–53    18-cv-00325–26   18-cv-00596
      18-cv-00065–67   18-cv-00139         18-cv-00256       18-cv-00328      18-cv-00598
      18-cv-00070      18-cv-00145         18-cv-00258       18-cv-00330–31   18-cv-00634
      18-cv-00072–74   18-cv-00148         18-cv-00260       18-cv-00333      18-cv-00648
      18-cv-00076–78   18-cv-00150–51      18-cv-00266       18-cv-00336–39   19-cv-00023
      18-cv-00080–82   18-cv-00154–55      18-cv-00268–71    18-cv-00341–45   19-cv-00025–26
      18-cv-00085      18-cv-00162         18-cv-00279       18-cv-00347–49   19-cv-00055
      18-cv-00087      18-cv-00167         18-cv-00281       18-cv-00354–56   19-cv-00068
      18-cv-00089–91   18-cv-00170         18-cv-00285       18-cv-00372–75   19-cv-00070–71
      18-cv-00094      18-cv-00180         18-cv-00287       18-cv-00394      19-cv-00076
      18-cv-00098–01   18-cv-00217         18-cv-00297–98    18-cv-00448–49   19-cv-00078
      18-cv-00104–05   18-cv-00219         18-cv-00300–02    18-cv-00496      19-cv-00089–92
      18-cv-00107–08   18-cv-00223         18-cv-00308       18-cv-00505      19-cv-00095
      18-cv-00110–11   18-cv-00233–34      18-cv-00312       18-cv-00562      19-cv-00112
 No. 22-6078               In re Onglyza (Saxagliptin) and Kombiglyze                      Page 2
                        (Saxagliptin and Metformin) Prods. Liability Litig.

       18-cv-00116        18-cv-00237–39   18-cv-00314      18-cv-00568       19-cv-00122–23
       18-cv-00118–24     18-cv-00247      18-cv-00316      18-cv-00571–72    19-cv-00125–30
       19-cv-00134        19-cv-00218      19-cv-00398      20-cv-00124       20-cv-00340
       19-cv-00138–45     19-cv-00221      19-cv-00401      20-cv-00141       20-cv-00383
       19-cv-00147–56     19-cv-00223      19-cv-00403      20-cv-00143       20-cv-00405
       19-cv-00161        19-cv-00227      19-cv-00422      20-cv-00153       20-cv-00419
       19-cv-00166        19-cv-00230–32   19-cv-00439      20-cv-00206–08    20-cv-00438
       19-cv-00169        19-cv-00252      19-cv-00461–63   20-cv-00236
       19-cv-00173        19-cv-00287      19-cv-00499      20-cv-00247
       19-cv-00190        19-cv-00350      20-cv-00007      20-cv-00281
       19-cv-00194        19-cv-00393      20-cv-00072–73   20-cv-00330

                                       _________________

                                    Argued: December 7, 2023

                              Decided and Filed: February 13, 2024

                 Before: SILER, NALBANDIAN, and DAVIS, Circuit Judges.
                                  _________________

                                           COUNSEL

ARGUED: Ashton Rose Smith, MOORE LAW GROUP, PLLC, Louisville, Kentucky, for
Appellants. Paul W. Schmidt, COVINGTON & BURLING LLP, New York, New York, for
Appellees. ON BRIEF: Ashton Rose Smith, Jennifer A. Moore, MOORE LAW GROUP,
PLLC, Louisville, Kentucky, for Appellants. Paul W. Schmidt, COVINGTON & BURLING
LLP, New York, New York, Carol Dan Browning, STITES & HARBISON PLLC, Louisville,
Kentucky, Emily S. Ullman, COVINGTON & BURLING LLP, Washington, D.C., for
Appellees.

                                       _________________

                                            OPINION
                                       _________________

       NALBANDIAN, Circuit Judge.           In this multi-district litigation, plaintiffs claim that
saxagliptin, a diabetes drug, caused their heart failure.     During expert discovery, plaintiffs
presented a single expert to show the drug can cause heart failure. After a Daubert hearing and
expert motions, the district court excluded the expert, finding that methodological flaws rendered
his testimony unreliable under Federal Rule of Evidence 702. The district court then granted
summary judgment for defendants, rejecting plaintiffs’ claim that other evidence created a
 No. 22-6078                In re Onglyza (Saxagliptin) and Kombiglyze                        Page 3
                         (Saxagliptin and Metformin) Prods. Liability Litig.

genuine issue of material fact as well as their request for ninety days to find a replacement
expert.

           On appeal, plaintiffs challenge the district court’s exclusion of their expert, its grant of
summary judgment, and its refusal to give plaintiffs more time to find another expert witness.
Because we conclude all three claims lack merit, we AFFIRM.

                                                   I.

          Defendants (Bristol-Myers Squibb, AstraZeneca, and McKesson) manufacture and sell
FDA-approved type 2 diabetes drugs containing saxagliptin, a dipeptidyl-peptidase-4 (DPP-4)
inhibitor.

          In 2008, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee
recommended more clinical studies evaluating the link between diabetes drugs and
cardiovascular risk.

          SAVOR (“Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with
Diabetes Mellitus”), a randomized-controlled trial (RCT), was commissioned in response.
SAVOR “randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were
at risk for, cardiovascular events to receive saxagliptin or placebo and followed them for a
median of 2.1 years.” Benjamin M. Scirica et al., Saxagliptin and Cardiovascular Outcomes in
Patients with Type 2 Diabetes Mellitus, 369 New Eng. J. Med. 1317, 1317 (2013). SAVOR
examined cardiovascular risk on a primary endpoint (“a composite of cardiovascular death,
myocardial infarction, or ischemic stroke”), as well as a secondary endpoint (“a composite of
cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary
revascularization, or heart failure”). Id. SAVOR found no statistically significant difference
between the groups for the primary endpoint or for five components of the secondary endpoint.
Id. at 1322.

          But the study did find a statistically significant difference between saxagliptin and a
placebo on hospitalizations for heart failure (HHF). Id. at 1317, 1321–22. The study observed a
statistically significant 27% increase in hospitalization for heart failure rates in patients
 No. 22-6078               In re Onglyza (Saxagliptin) and Kombiglyze                            Page 4
                        (Saxagliptin and Metformin) Prods. Liability Litig.

administered saxagliptin compared to patients receiving a placebo (3.5% vs. 2.8%). Id. at 1317.
But the study cautioned that the observed association “was unexpected and should be considered
within the context of multiple testing that may have resulted in a false positive.” Id. at 1324.
The study also noted that the HHF “finding merits further investigation and needs to be
confirmed in other ongoing studies, and a class effect should not be presumed.” Id.

        Saxagliptin’s drug label was updated in response. The warning, directed at prescribing
physicians, states:

        In a cardiovascular outcomes trial enrolling participants with established ASCVD
        [atherosclerotic cardiovascular disease] or multiple risk factors for ASCVD
        (SAVOR trial), more patients randomized to [saxagliptin] (289/8280, 3.5%) were
        hospitalized for heart failure compared to patients randomized to placebo
        (228/8212, 2.8%). In a time-to-first-event analysis the risk of hospitalization for
        heart failure was higher in the [saxagliptin] group (estimated Hazard Ratio: 1.27,
        95% CI: 1.07, 1.51).

R.749-2, Prescribing Information at 3, PageID 17379.

                                                   II.

        SAVOR’s HHF finding sparked this multi-district litigation. Plaintiffs sued defendants in
federal courts across the country, asserting claims for strict product liability, negligence, failure
to warn, breach of warranty of merchantability, and breach of express and implied warranties, all
stemming from heart failure allegedly caused by saxagliptin. In February 2018, the Judicial
Panel on Multidistrict Litigation consolidated 41 actions pending in 23 districts (as well as 43
potential tag-along actions in 26 districts), transferring them to the Eastern District of Kentucky
as MDL 2809.1

        The district court ordered phased discovery, with the first phase dedicated to the issue of
general causation: whether saxagliptin “is capable of causing any person to develop heart failure
or other conditions alleged by the plaintiffs such as congestive heart failure, myocardial

        1
          Another 13 actions filed in California state court were managed by a California Judicial Council
coordination proceeding (JCCP), which followed the MDL’s discovery plan and schedule. See Onglyza Prod.
Cases, 307 Cal. Rptr. 3d 480, 484 (Ct. App. 2023).
 No. 22-6078                  In re Onglyza (Saxagliptin) and Kombiglyze                                    Page 5
                           (Saxagliptin and Metformin) Prods. Liability Litig.

infarction and/or cardiovascular injury.” R.179, Case Management Order No. 1 at 1, PageID
1049.

         Plaintiffs presented a single general causation expert: Dr. Parag Goyal. Dr. Goyal, a
cardiology professor at Weill Cornell Medicine was to testify that “it is more likely than not that
saxagliptin is capable of causing heart failure.” R.633-10, Goyal Report at 14, PageID 12297.

         Defendants moved to exclude Dr. Goyal, arguing that he: (1) unreliably based his
causation finding on SAVOR alone while ignoring all subsequent human data, (2) unreliably
used animal data, and (3) unreliably applied the Bradford Hill criteria.2

         The district court conducted a Daubert hearing on Dr. Goyal’s testimony on August 10,
2021, before granting defendants’ motion to exclude Dr. Goyal’s testimony on January 5, 2022.3

         After Dr. Goyal’s exclusion, defendants moved for summary judgment, arguing that Dr.
Goyal’s exclusion meant that plaintiffs now lacked admissible evidence raising a triable issue of
material fact on general causation. Plaintiffs opposed this motion, contending other evidence in
the record was sufficient to create a disputed material fact as to general causation. Meanwhile,
plaintiffs moved to modify the scheduling order to allow them another ninety days to identify a
replacement general causation expert for Dr. Goyal.

         On August 2, 2022, the district court denied plaintiffs’ motion for more time to identify a
substitute general causation expert, concluding they could not show “good cause” to modify a
scheduling order as required by Federal Rule of Civil Procedure 16(b)(4).

         2
          Bradford Hill is a scientific framework used to analyze whether an association between two variables is
causal, named after epidemiologist Sir Austin Bradford Hill. See Austin Bradford Hill, The Environment and
Disease: Association or Causation?, 58 Proc. Royal Soc’y Med. 295 (1965). Bradford Hill identifies nine relevant
factors: (1) strength of association, (2) consistency of association, (3) specificity, (4) temporal relationship,
(5) biological gradient, (6) biological plausibility, (7) coherence, (8) experiment, and (9) analogy. Id. at 295–99.
Dr. Goyal arrived at his opinion that saxagliptin could cause heart failure after applying the Bradford Hill criteria.
         3
          This was a joint hearing with the California JCCP court. See Onglyza Prod. Cases, 307 Cal. Rptr. 3d at
485. The California court likewise excluded Dr. Goyal’s expert testimony under its own Sargon standard for expert
testimony. See id. (citing Sargon Enters., Inc. v. Univ. of S. Cal., 288 P.3d 1237 (Cal. 2012)). Dr. Goyal’s
exclusion was affirmed on appeal. Id. at 487–92.
 No. 22-6078                  In re Onglyza (Saxagliptin) and Kombiglyze                                     Page 6
                           (Saxagliptin and Metformin) Prods. Liability Litig.

         In the same order, the district court granted defendants’ motion for summary judgment,
concluding that plaintiffs failed to produce admissible expert testimony that saxagliptin can
cause heart failure.

         Plaintiffs timely appealed, arguing the district court erred thrice: (1) by excluding Dr.
Goyal, (2) by granting summary judgment, and (3) by refusing to grant plaintiffs more time to
find a substitute general causation expert.

                                                         III.

         We review the district court’s decision to exclude Dr. Goyal’s expert testimony for abuse
of discretion. See United States v. LaVictor, 848 F.3d 428, 440 (6th Cir. 2017). Federal Rule of
Evidence 702 entrusts district courts with a “gatekeeping role” to “ensur[e] that an expert’s
testimony both rests on a reliable foundation and is relevant.” Daubert v. Merrell Dow Pharms.,
Inc., 509 U.S. 579, 597 (1993). Before admitting expert testimony, the district court needed to
ensure that Dr. Goyal’s testimony was (a) helpful to the trier of fact, (b) “based on sufficient facts
or data,” and (c) “the product of reliable principles and methods” that (d) have been “reliably
applied” to the “facts of the case.” Fed. R. Evid. 702 (2011) (amended 2023).4

         The party proffering the expert (here plaintiffs) bears the burden of showing by a
preponderance of the evidence that the expert satisfies Rule 702. Sigler v. Am. Honda Motor
Co., 532 F.3d 469, 478 (6th Cir. 2008). “The task for the district court in deciding whether an
expert’s opinion is reliable is not to determine whether it is correct, but rather to determine
whether it rests upon a reliable foundation, as opposed to, say, unsupported speculation.” In re
Scrap Metal Antitrust Litig., 527 F.3d 517, 529–30 (6th Cir. 2008).

         4
          On December 1, 2023, two changes to Rule 702 went into effect. First, language was added to clarify that
the proponent bears the burden of showing the expert testimony more likely than not complies with the rule.
Second, 702(d) was rephrased to emphasize that an expert opinion must “reflect[] a reliable application” of the
expert’s methodology. We employ the old rule because it was still in force at the time of the district court’s decision
(January 5, 2022). See In re Cooper Tire & Rubber Co., 568 F.3d 1180, 1186 n.4 (10th Cir. 2009). But the district
court’s reasoning aligns with the updated Rule 702, since it placed the burden of showing that Dr. Goyal was
admissible on plaintiffs. And our decision here would be the same under either version of the Rule.
 No. 22-6078              In re Onglyza (Saxagliptin) and Kombiglyze                       Page 7
                       (Saxagliptin and Metformin) Prods. Liability Litig.

                                                  A.

       First, Dr. Goyal’s reliance on SAVOR, to the exclusion of all other studies involving
human data, was unreliable.

       As Dr. Goyal conceded, no clinical study beyond SAVOR has found a statistically
significant association between saxagliptin and heart failure.         Instead, four post-SAVOR
observational studies, collectively following 175,000 saxagliptin users, found no association. Dr.
Goyal conceded that these observational studies were “reasonably designed” and that “the
number of patients” was “a strength.” R.710, Tr. of Dr. Goyal’s Daubert Hearing at 90–91,
PageID 16078–79. Even so, Dr. Goyal’s report failed to engage with these studies, dismissing
them as “generally limited due to issues related to confounding.” R.633-10, Goyal Report at 9,
PageID 12292. But Dr. Goyal identified no specific issues or confounders in the observational
studies. Dr. Goyal’s failure “to adequately account for contrary evidence is not reliable or
scientifically sound.” In re Lipitor (Atorvastatin Calcium) Mktg., Sales Pracs. & Prods. Liab.
Litig., 174 F. Supp. 3d 911, 932 (D.S.C. 2016).

       Yet, despite admitting that basing causation on a single study is improper, Dr. Goyal still
found causation based only on SAVOR. Indeed, Dr. Goyal stated that SAVOR’s findings “should
be interpreted as cause-and-effect unless there is compelling evidence to prove otherwise.”
R.633-10, Goyal Report at 8, PageID 12291. But Dr. Goyal’s conclusion that SAVOR shows
causation in the absence of “compelling evidence” showing otherwise reverses the burden of
proof. See Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997) (Exclusion is proper for “opinion
evidence that is connected to existing data only by the ipse dixit of the expert.”). And SAVOR is
no smoking gun: the study only observed “higher incidence of hospitalization among patients
treated with saxagliptin,” not a causal link between the two. Scirica, supra, 369 New Eng. J.
Med. at 1324. SAVOR’s authors cautioned that there “are presently no known mechanisms” by
which saxagliptin “could precipitate heart failure,” Benjamin M. Scirica et al., Heart Failure,
Saxagliptin, and Diabetes Mellitus: Observations from the SAVOR-TIMI 53 Randomized Trial,
130 Circulation: Am. Heart Ass’n J. 1579, 1585 (2014), and that the observed association “may
have resulted in a false positive,” Scirica et al., supra, 369 New Eng. J. Med. at 1324.
 No. 22-6078                  In re Onglyza (Saxagliptin) and Kombiglyze                                     Page 8
                           (Saxagliptin and Metformin) Prods. Liability Litig.

         So Dr. Goyal drew “unauthorized conclusions from limited data—conclusions the authors
of the study d[id] not make,” betraying a “lack of scientific rigor.” McClain v. Metabolife Int’l,
Inc., 401 F.3d 1233, 1248 (11th Cir. 2005). By ignoring all other human studies, besides
SAVOR, without an adequate explanation, Dr. Goyal failed to base his opinion on “sufficient
facts or data.” Fed. R. Evid. 702(b).

         Plaintiffs raise two main arguments on appeal. Neither is persuasive. First, plaintiffs
claim that the district court “erroneously concluded that a study—including an RCT—must be
replicated to be reliable.” Appellant Br. at 21.5 Not so. The district court did not exclude Dr.
Goyal based on a per se rule against studies that still haven’t been replicated. Indeed, the district
court clarified that Dr. Goyal’s views on replication came into play because “there are multiple
studies on the issue of whether saxagliptin can cause heart failure.” R.740, Experts Order at 31
n.3, PageID 17089. And the court concluded that Dr. Goyal acted unreliably by agreeing on the
importance of replication but, without explanation, ignoring all human studies beyond SAVOR.

         Second, plaintiffs claim that the district court “improperly concluded that Dr. Goyal could
not make a causation finding based on an epidemiological study . . . that does not itself make a
causal determination.” Appellant Br. at 21 (citing In re Bair Hugger Forced Air Warming
Devices Prods. Liab. Litig., 9 F.4th 768, 779 (8th Cir. 2021)).6 Again, not so. The district court
did not fault Dr. Goyal for considering an epidemiological study. It faulted him for basing his
opinion on SAVOR’s finding without adequately explaining how he inferred a causal relationship
from SAVOR, an epidemiological study that did not come to a conclusion about causation.

         5
          Along these lines, plaintiffs dedicate pages of their briefing defending RCTs like SAVOR as “the gold
standard” for assessing causation, rather than “junk science” subject to exclusion. Appellant Br. at 24–28; Reply Br.
at 7–10. But the district court never questioned the reliability of SAVOR itself. Instead, the court focused on how
Dr. Goyal used SAVOR in forming his general causation opinion. So do we, rendering plaintiffs’ defense of RCTs
like SAVOR beside the point.
         6
           The Eighth Circuit in Bair Hugger found that it is not “per se unreliable for an expert to draw an inference
of causation from an epidemiological study that disclaimed proving causation.” 9 F.4th at 779. But the court
cautioned that epidemiology studies only allow “experts to find associations, which by themselves do not entail
causation”—experts must still do “the work to bridge the gap between association and causation.” Id. (internal
quotation marks omitted). Unlike Dr. Goyal, the experts there did not rest their opinion on only an epidemiological
study, but also identified plausible causal mechanisms to explain the observed association and created models to test
their theories. Id. at 785–86, 788.
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                       (Saxagliptin and Metformin) Prods. Liability Litig.

According to the district court, Dr. Goyal’s sin was methodological inconsistency, not reliance on
an un-replicated epidemiological study.

       The district court did not abuse its discretion in concluding that Dr. Goyal’s reliance on
SAVOR to prove causation, disregarding all other human studies, was unreliable.

                                                B.

       Second, Dr. Goyal’s use of animal data was unreliable because he has no expertise in
interpreting animal studies.

       Dr. Goyal conceded multiple times he is unqualified to analyze animal studies. He
specifically conceded he was unqualified to conclude either that the animals in the studies he
cited “actually had heart failure” or whether “saxagliptin is capable of causing heart failure in
animals.” R.710, Hearing Tr. at 148, PageID 16136. Further, Dr. Goyal admitted to ignoring
multiple peer-reviewed animal studies dispelling a causal link between saxagliptin and heart
failure. And, since none of the studies diagnosed animals with heart failure, Dr. Goyal simply
claimed that particular animals showed symptoms of heart failure, such as anemia or congestion.
Since Dr. Goyal was admittedly unqualified to make these diagnoses, the district court did not err
in finding Dr. Goyal’s use of animal studies unreliable.

                                                C.

       Third, Dr. Goyal did not reliably apply Bradford Hill.

       Courts must ensure both that expert opinions are “the product of reliable principles and
methods,” and that these methods have been “reliably applied” to the “facts of the case.” Fed. R.
Evid. 702 (2011) (amended 2023). Bradford Hill is undeniably a reliable methodology. See,
e.g., Milward v. Acuity Specialty Prods. Grp, Inc., 639 F.3d 11, 17–18 (1st Cir. 2011). Indeed, as
plaintiffs point out, defendants’ experts used the same methodology. But the district court had an
independent duty to ensure that all experts “reliably applied” Bradford Hill. Fed. R. Evid. 702(d)
(2011) (amended 2023); see also Kumho Tire Co. v. Carmichael, 526 U.S. 137, 152 (1999)
(Courts must “make certain that an expert . . . employs in the courtroom the same level of
 No. 22-6078              In re Onglyza (Saxagliptin) and Kombiglyze                        Page 10
                       (Saxagliptin and Metformin) Prods. Liability Litig.

intellectual rigor that characterizes the practice of an expert in the relevant field.”). And the
court had multiple grounds to find that Dr. Goyal had not reliably applied Bradford Hill.

       On the one hand, Dr. Goyal cherry-picked data to bolster his case. When considering the
analogy factor, Dr. Goyal looked at thiazolidinedione (TZD) drugs (a different kind of second-
line diabetes medication), rather than DPP-4 inhibitors (the class of drugs to which saxagliptin
belongs).   Dr. Goyal explained this unconventional choice simply by claiming that TZDs
“provide[] an appropriate analogy” because they have been shown to “worsen heart failure.”
R.633-10, Goyal Report at 14, PageID 12297. This cherry-picking “undermines principles of the
scientific method and is a quintessential example of applying methodologies (valid or otherwise)
in an unreliable fashion.” In re Lipitor (Atorvastatin Calcium) Mktg., Sales Pracs. & Prod. Liab.
Litig. (No II) MDL 2502, 892 F.3d 624, 634 (4th Cir. 2018).

       On the other hand, Dr. Goyal inconsistently applied several Bradford Hill factors. For
instance, Dr. Goyal’s report claimed that two of the factors (specificity and biological gradient)
were satisfied, but he later testified that they were not. These changes in Dr. Goyal’s Bradford
Hill analysis—neither explained nor justified—cast doubt on the reliability of his testimony.

       Plaintiffs don’t defend Dr. Goyal’s application of Bradford Hill per se. Instead, they
contend that exclusion was improper because a “jury, not the trial judge, must evaluate and
weigh conflicting expert testimony.” Appellant Br. at 33 (internal quotation marks omitted). To
be sure, “competing expert opinions present the classic battle of the experts and it is up to a jury
to evaluate what weight and credibility each expert opinion deserves.” Phillips v. Cohen, 400
F.3d 388, 399 (6th Cir. 2005) (internal quotation marks omitted). And “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. But district courts may allow juries to evaluate and weigh only relevant and reliable
expert testimony. See Sardis v. Overhead Door Corp., 10 F.4th 268, 284 (4th Cir. 2021) (citing
 No. 22-6078                  In re Onglyza (Saxagliptin) and Kombiglyze                                 Page 11
                           (Saxagliptin and Metformin) Prods. Liability Litig.

Daubert, 509 U.S. at 589). Since Dr. Goyal’s opinion is unreliable, the district court properly
exercised its “gatekeeping role.” Daubert, 509 U.S. at 597.7

                                                       ***

        In sum, the district court had three good reasons to find Dr. Goyal’s testimony unreliable:
(1) improper reliance on SAVOR to the exclusion of all other human studies, (2) unqualified
analysis of animal studies, and (3) cherry-picking and inconsistent consideration of the Bradford
Hill factors. So we conclude that excluding Dr. Goyal was not an abuse of its discretion.

                                                        IV.

        Plaintiffs claim that, even if Dr. Goyal were properly excluded, summary judgment was
improper because “there is extensive other evidence from which a jury could properly determine
that saxagliptin can cause heart failure.” Appellant Br. at 19.

        We review a district court’s grant of summary judgment de novo. Baggs v. Eagle-Pitcher
Indus., Inc., 957 F.2d 268, 271 (6th Cir. 1992). Summary judgment is appropriate only where
“there is no genuine dispute as to any material fact and the movant is entitled to judgment as a
matter of law.” Fed. R. Civ. P. 56.

        As a preliminary point, plaintiffs claim that the district court erred by finding they cannot
establish general causation without expert testimony. Instead, plaintiffs argue that “[j]uries are
permitted to decide issues of causation without guidance from experts.” Appellant Br. at 40.

        The district court concluded that, as an MDL, the issue was governed by “the substantive
state law of the transferor state.” R.769, Summary Judgment Order at 14, PageID 18470; see,
e.g., In re Ford Motor Co. Ignition Switch Prods. Liab. Litig., 194 F.R.D. 484, 490 (D.N.J.
2000).8 So the court reviewed the law of all fifty states, concluding that all states require “the

        7
           Indeed, Rule 702’s recent amendments, see supra n.5, were drafted to correct some court decisions
incorrectly holding “that the critical questions of the sufficiency of an expert’s basis, and the application of the
expert’s methodology, are questions of weight and not admissibility.” Fed. R. Evid. 702 advisory committee’s note
to 2023 amendments.
        8
          Since both parties agreed, we see no need to revisit this choice-of-law issue. See AtriCure, Inc. v. Meng,
12 F.4th 516, 525 (6th Cir. 2021).
 No. 22-6078               In re Onglyza (Saxagliptin) and Kombiglyze                    Page 12
                        (Saxagliptin and Metformin) Prods. Liability Litig.

plaintiff in cases involving complex issues of medical causation to present expert testimony on
the subject.”     R.769, Summary Judgment Order at 14, PageID 18470 (citing R.746-2,
Jurisdiction Survey of the Laws on Causation in Product Liability Actions).

        The district court does not stand alone: other district courts have agreed that all
jurisdictions require expert testimony to show general causation, “at least where the issues are
medically complex and outside common knowledge and lay experience.”                 In re Lipitor
(Atorvastatin Calcium) Mktg., Sales Pracs. & Prod. Liab. Litig., 227 F. Supp. 3d 452, 469–78
(D.S.C. 2017) (collecting cases); see also In re Mirena IUS Levonorgestrel-Related Prods. Liab.
Litig. (No. II), 387 F. Supp. 3d 323, 341 (S.D.N.Y. 2019) (“It is well established that ‘expert
testimony is required to establish causation’ where the issue of causation is ‘beyond the
knowledge of lay jurors.’”) (quoting Wills v. Amerada Hess Corp., 379 F.3d 32, 46 (2d Cir.
2004)). Indeed, we often apply such a requirement in our diversity cases. See, e.g., Nocilla v.
Bridges, No. 23-3184, 2023 WL 7550019, at *4 (6th Cir. Nov. 14, 2023) (applying Ohio’s
requirement “that a plaintiff must present scientific or medical evidence if an untrained layperson
would not have the expertise necessary to decide whether a defendant’s actions could cause a
plaintiff’s injury”).

        While plaintiffs contest this requirement, they identify no state without a requirement of
expert testimony to establish general causation in complex medical cases. Instead, plaintiffs
resort to selectively quoting cases. Most important is a decision of this circuit, which plaintiffs
claim affirmed a district court’s finding that causation could be shown “based simply on the
warning language in product inserts.” Appellant Br. at 40–41 (citing Meridia Prods. Liab. Litig.
v. Abbott Lab’ys, 447 F.3d 861, 866 (6th Cir. 2006)). But plaintiffs incorrectly characterize the
district court opinion: it merely “assume[d] arguendo that no states’ laws erect” a requirement of
expert testimony to establish general causation, because “[r]egardless, the Court ends up in the
same place: summary judgment for Defendants.” In re Meridia Prods. Liab. Litig., 328 F. Supp.
2d 791, 802 (N.D. Ohio 2004). Plaintiffs’ string citation to four state-court cases is similarly
inapposite and misleading.
 No. 22-6078               In re Onglyza (Saxagliptin) and Kombiglyze                       Page 13
                        (Saxagliptin and Metformin) Prods. Liability Litig.

        So we conclude that the district court did not err in finding that all jurisdictions require
expert testimony to show general causation in complex medical cases such as this MDL.
Dr. Goyal’s exclusion warranted the district court’s grant of summary judgment to defendants.

                                                   V.

        For their third and final issue on appeal, plaintiffs argue that the district court abused its
discretion when it refused to grant them leave to identify a new general causation expert.

        District courts may modify scheduling orders “only for good cause.” Fed. R. Civ. P.
16(b)(4). We review district courts’ decisions whether to modify scheduling orders for abuse of
discretion. Leary v. Daeschner, 349 F.3d 888, 909 (6th Cir. 2003). And we give district courts
“wide discretion to manage their own dockets and to decide issues which have consumed
considerable resources.” Reed v. Rhodes, 179 F.3d 453, 471 (6th Cir. 1999).

        We have specified that district courts should measure “good cause” mainly by reference
to two factors. “[T]he moving party’s diligence in attempting to meet the case management
order’s requirements” is the “primary measure,” but “possible prejudice to the party opposing the
modification” is also relevant. Inge v. Rock Fin. Corp., 281 F.3d 613, 625 (6th Cir. 2002). Both
factors cut against plaintiffs.

        First, plaintiffs’ diligence in attempting to meet the scheduling order. Plaintiffs are right
that they “were diligent and timely in identifying Dr. Goyal.” Appellant Br. at 57. But that
misses the point. As the district court noted, “plaintiffs do not really request an extension of
deadlines,” since expert discovery and motions were already done when they filed their motion.
R.769, Summary Judgment Order at 10, PageID 18466. Instead, plaintiffs are asking to reopen
expert discovery. And plaintiffs cannot explain why they have failed to identify other, reliable,
general causation experts—despite years of expert discovery. See R.769, Summary Judgment
Order at 11–12, PageID 18467–68; Appellant Br. at 55–59. So plaintiffs were not diligent in
identifying a reliable general causation expert.

        Second, prejudice to defendants. Plaintiffs claim that granting their motion would cause
defendants “no prejudice” because of the “minimal amount of delay.” Appellant Br. at 58. But
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                      (Saxagliptin and Metformin) Prods. Liability Litig.

granting plaintiffs’ request would essentially restart expert discovery, requiring depositions,
briefing, hearings, and motions on plaintiffs’ new expert. This would delay the MDL’s resolution
for years—just consider that plaintiffs requested three months to simply identify an expert. So
granting the motion would likely impose significant costs on defendants in the form of
substantial legal expenses and years of delay. See Com. Benefits Grp., Inc. v. McKesson Corp.,
326 F. App’x 369, 377–78 (6th Cir. 2009) (“[A]ny further delay in discovery would have resulted
in additional time and expense incurred by both the parties and the court and would have unfairly
prejudiced defendants.”).

       We conclude the district court did not abuse its discretion by denying plaintiffs’ request
for more time to identify a general causation expert to replace Dr. Goyal. The court properly
refused to reward plaintiffs for their failure to identify a reliable general causation expert by
imposing significant costs on defendants. To find otherwise would set a precedent that parties
may drag out litigation by identifying “only one expert witness on a crucial issue who is later
excluded.” R.769, Summary Judgment Order at 11, PageID 18467.

                                              VI.

       For these reasons, we AFFIRM.