Taylor et al v. Bristol-Myers Squibb Company, Inc. et al

Filing 332

OPINION AND ORDER ON MOTION TO EXCLUDE EXPERTS (DE 626, 630, 633, 635): 1. The defendant's motion to exclude testimony of Dr. Parag Goyal 636 is GRANTED; 2. The plaintiff's motion to excluded the testimony of Dr. Suneil Koliwad 630 is DENIED; 3. The plaintiff's motion to exclude testimony of Dr. Eric Adler 633 is DENIED; 4. The plaintiff's motion to exclude the testimony of Dr. Todd Lee 635 is DENIED. Signed by Judge Karen K. Caldwell on 1/5/2022.Associated Cases: 5:18-md-02809-KKC-MAS et al.(KM)cc: COR

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 1 of 38 - Page ID#: 7098

UNITED STATES DISTRICT COURT
EASTERN DISTRICT OF KENTUCKY
CENTRAL DIVISION
LEXINGTON
IN RE: ONGLYZA (SAXAGLIPTIN) AND
KOMBIGLYZE XR (SAXAGLIPTIN AND
METFORMIN) PRODUCTS LIABILITY
LITIGATION

Master File No. 5:18-md-2809-KKC
MDL No. 2809
ALL CASES

OPINION AND ORDER ON MOTIONS TO EXCLUDE EXPERTS
(DE 626, 630, 633, 635)
This matter is before the Court on the parties' motions to exclude expert testimony.
The plaintiffs have moved to exclude three of the defendants' experts: Drs. Suneil Koliwad
(DE 630)1, Eric Adler (DE 633), and Todd Lee (DE 635).2 The defendants have moved to
exclude one of the plaintiffs' experts: Dr. Parag Goyal (DE 626).
The parties have fully briefed the motions. This Court and the Superior Court of
California, which is presiding over the coordinated proceedings in California state court,
conducted joint hearings, after which the parties filed supplemental briefs. For the
following reasons, the Court will grant the motion to exclude Dr. Goyal and will deny the
remaining motions.
I.

Background

This action is a multidistrict litigation that involves medications that the defendants
manufacture, which are aimed at treating type 2 diabetes. The medications are Onglyza

1

All docket entry (DE) numbers refer to the docket entry numbers in the MDL Master File, 5:18-2809.
2
Plaintiffs have also moved to exclude the testimony of defense expert Dr. Michael Fowler (DE 630). Dr. Fowler
was unable to attend the hearings the week of August 9, 2021 due to a serious illness. Accordingly, the Court ruled it
would conduct the hearing on the motion to exclude him at a later date. (DE 696, Order.)

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 2 of 38 - Page ID#: 7099

and Kombiglyze, both of which contain saxagliptin as an active ingredient. Onglyza is the
brand name under which saxagliptin is sold. Kombiglyze is a single pill that combines
saxagliptin and metformin, another diabetes medication. (DE 635-10, Adler Report at 11.)
The plaintiffs allege that saxagliptin caused them to suffer heart failure and other
conditions. The Court bifurcated discovery into two phases with the first phase addressing
the general causation issue, i.e., whether saxagliptin can cause any person to develop heart
failure or the other conditions alleged by the plaintiffs. (DE 179, Case Mgmt. Order.) Each
of the experts targeted on these motions opines on that issue.
A.

Saxagliptin

Saxagliptin is one of several drugs in a class of medications known as dipeptidyl
peptidase-4 inhibitors ("DPP-4 inhibitors"). (DE 626-27, Abraham Report at 14.) This class
of drugs is generally a second-line treatment for diabetes patients. Id. Physicians often
initially prescribe metformin to diabetic patients because of "its long history of efficacy,
safety, and tolerability." Id. at 15. If metformin no longer sufficiently controls glucose
levels, then physicians will often add a second-line medication such as a DPP-4 inhibitor.
Other classes of second-line medications are thiazolidinedione (TZD), sulfonylurea (SU),
and a sodium-glucose cotransporter-2 inhibitor (SGLT-2 inhibitor). Id at 15. Prescribing
multiple drugs to diabetic patients is common because the "the disease is progressive, so
that a single medication or medication combination that previously provided adequate
glucose control no longer does." Id.
B.

Bradford Hill causation analysis

In reaching their opinions on causation, each of the experts at issue employed what
is known as the "Bradford Hill" analysis to determine whether the available data indicates
that exposure to saxagliptin can cause an increased risk of hospitalization for heart failure.
The analysis is meant to apply when "observations reveal an association between two
2 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 3 of 38 - Page ID#: 7100

variables." It addresses the aspects of that association that researchers should analyze
"before deciding that the most likely interpretation of [the association] is causation." (DE
626-41, Bradford Hill article at 295.) The framework was developed by epidemiologist Sir
Austin Bradford Hill, who identified nine factors that he "suggested were particularly
relevant for assessing whether an observed association may be causal." (DE 635-10, Adler
Report at 30.) "These nine factors are standard features generally considered relevant for
determining whether an apparent association is causal." (DE 626-27, Abraham Report at
35-36.) The nine factors are:
1) Strength of association: this factor asks how strong the alleged association is
between exposure to the drug and the outcome. (DE 626-27, Abraham Report at
36.) The strength of association is measured by relative risk. The higher the
relative risk, the greater the likelihood that relationship is causal and the less
the likelihood that chance, bias, or any "confounding factor" might account for
the association. Federal Judicial Center, Reference Manual on Scientific
Evidence (3rd Ed. 2011) 572, 602. "Confounding occurs when another causal
factor (the confounder) confuses the relationship between the agent of interest
and outcome of interest." Id. at 591. A relationship "is deemed confounded []
where there is a third factor that is related to both the exposure and the outcome
that can result in it looking like there is an association when one does not exist.
One classic example is the association between ice cream sales and sunburns. It
is not ice cream sales that causes the sunburns." DE 631-3, Lee Report at 7.)
Instead, there is a "confounder," namely sunny weather that is related to both
the ice cream sales and sunburns. Id. at 8.
2) Consistency of association: this factor asks, has the observed association
"been repeatedly observed by different persons, in different places, circumstances
and times?" (DE 626-41, Bradford-Hill article at 296.) Researchers look at
"whether the association has been found consistently across studies." (DE 62627, Abraham Report at 38.) "Consistency is upheld when the same finding is
shown in multiple studies across different populations and settings." (DE 628-3,
Goyal Report at 9.) "Rarely, if ever, does a single study persuasively demonstrate
a cause-effect relationship." Reference Manual on Scientific Evidence at 604. It is
important that a study be replicated in different populations and by different
investigators before a causal relationship is accepted by epidemiologists and
other scientists. Id.
3) Specificity: "The questions asked in evaluating specificity of the association are:
1) does the event ever occur without the exposure; and 2) does the exposure ever
happen without the event occurring?" (DE 631-3, Lee Report at 30-31.) "Although
perfect specificity almost never exists, the degree of specificity can be
informative. For instance, if the vast majority of events occur without the
3 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 4 of 38 - Page ID#: 7101

exposure, and the vast majority of exposures do not result in the event, these
factors weigh against causation." Id. at 31.
4) Temporal relationship: this factor asks whether the exposure occurred before
the outcome. "If an exposure causes disease, the exposure must occur before the
disease develops. If the exposure occurs after the disease develops, it cannot have
caused the disease." Reference Manual on Scientific Evidence 601. A temporal
relationship is necessary but not sufficient to find a causal relationship between
exposure and outcome (DE 626-27, Abraham at 40; DE 630-3, Koliwad at 51.)
5) Biological gradient: this factor asks whether there is a "dose-response"
relationship between exposure and outcome, namely "whether patients who take
a higher dose of a medication are more likely to develop heart failure than
patients who take a lower dose." (DE 630-3, Koliwad at 52.) "[I]f causation is
present, higher exposure should either [] more likely lead to the outcome or lead
to more severe outcome." (DE 628-3, Goyal Report at 11.)
6) Biological plausibility: this factor "is focused on whether or not the observed
association make sense given what we know about the disease and the exposure."
(DE 631-3, Lee Report at 32.) For this factor, researchers consider "existing
knowledge about human biology and disease pathology to provide judgment
about the plausibility that an agent causes a disease." Reference Manual on
Scientific Evidence 620.
7) Coherence: this factor asks whether "a causal relationship between saxagliptin
and new or worsened heart failure would be coherent with our current
understanding of either saxagliptin's effects, or coherent with our understanding
of heart failure and its mechanisms." (DE 626-27, Abraham Report at 42.) The
"cause-and-effect interpretation of [] data should not seriously conflict with the
generally known facts of the natural history and biology of the disease." (DE 62641, Bradford Hill article at 298.)
8) Experiment: this factor asks "whether removing an exposure affects the
likelihood of the outcome occurring." (DE 630-3, Koliwad at 56.) "If an agent is a
cause of a disease, then one would expect that cessation of exposure to that agent
ordinarily would reduce the risk of the disease." Reference Manual on Scientific
Evidence at 605.
9) Analogy: this factor asks whether exposure to analogous medications can cause
the outcome. (DE 626-27, Abraham Report at 43.) "[W]hen one medication within
a class has been found to cause an adverse event, this finding may help inform
causation assessments for other medications in the class. Similarly . . . the
absence of analogous effects in other medications of the same class or with the
same mechanism of action weighs against finding a causal relationship between
the original medication and outcome." (DE 631-3, Lee Report at 33.)

4 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 5 of 38 - Page ID#: 7102

C.

Available data regarding Saxagliptin and heart failure

As to the data regarding saxagliptin that was available for the experts in their
Bradford Hill analyses, medications undergo various studies to evaluate whether they are
associated with a risk. (DE 631-3, Lee Report at 4.) One such study is a randomized
controlled trial (RCT), in which the subjects are "randomly assigned to one of two groups:
one group exposed to the agent of interest and the other not exposed." Reference Manual on
Scientific Evidence 555. This kind of study is considered "the gold standard for determining
the relationship of an agent to a health outcome or adverse side effect." Id. This is because,
"[r]andomization minimizes the likelihood that there are differences in relevant
characteristics between those exposed to the agent and those not exposed." Id. An RCT is
the "best way to ensure that any observed difference in outcome between the two groups is
likely to be the result of exposure to the drug or medical treatment." Id. Some such studies
are single blinded, meaning the patient does not know which treatment he or she is
receiving, and some are doubled blinded, meaning that neither the researcher nor the
patient know which treatment the patient is receiving. (DE 631-3, Lee Report at 6.)
A second kind of study is an observational study, in which the drug is not prescribed
randomly but as part of a clinical practice. Id.at 4. The "investigator identifies a group of
subjects who have been exposed and compares their rate of disease or death with that of an
unexposed group." Reference Manual on Scientific Evidence 556. One disadvantage of this
study as compared to an RCT is that an RCT can control for potential risk factors. The
researcher cannot directly control for these risk factors in an observational study. The
researcher can, however, address the possible role of risk factors by considering them in the
design of the study and in the analysis and interpretation of the results. Id.
One type of observational studies is a cohort study. A "cohort" is a "designated group
of persons followed or traced over a period of time to examine health or mortality
5 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 6 of 38 - Page ID#: 7103

experience." Reference Manual on Scientific Evidence at 621. A cohort study follows two
groups of patients – those who have taken medication and those who have not – and then
measures and compares the incidence of the disease in the two groups. Id. at 557.
A third kind of study is a meta-analysis, which is "a systematic review" of multiple
studies. (DE 631-3, Lee Report at 7.) "Meta-analysis is a method of pooling study results to
arrive at a single figure to represent the totality of the studies reviewed." Reference Manual
on Scientific Evidence at 607.
Finally, animal studies may be used to determine toxicity in humans. Id. at 563.
Each of these kinds of evidence carries different weight in a causation analysis. At
the Daubert hearing, the experts described a "pyramid" of evidence with the bottom
consisting of evidence that carries the least weight in a causational analysis and the top
consisting of evidence that carries the most weight. (Pfs.' Ex. 10; DE 707, Wells Test. at 40.)
At the bottom of the pyramid are animal studies. (DE 707, Well Test. at 41-42.) Above
animal studies are observational studies. Id. at 43-44. At the top of the pyramid are RCTs,
with double-blinded RCTs at the very top. Id.at 46.
1) Pre-FDA approval pre-clinical animal studies and clinical trials
Defendants assert that, prior to the FDA approval of saxagliptin, they conducted
over 100 pre-clinical studies of saxagliptin involving thousands of animals and also
conducted various clinical trials involving thousands of human patients. (DE 628, Mem. at
2.) None of these studies found that saxagliptin posed any cardiovascular risk or that it
increased the risk of heart failure. (DE 626-4, Pollack 2017; DE 626-5, Iqbal 2014; 626-6,
FDA Medical Review). Thus, the U.S. Food and Drug Administration (FDA) approved
Onglyza on July 31, 2009 and Kombiglyze on November 5, 2010. (DE 363-6, 363-7, FDA
Approval Letters.)

6 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 7 of 38 - Page ID#: 7104

2) SAVOR study (2013)
In 2008, the FDA required that sponsors conduct cardiovascular outcomes trials
("CVOTs") for medications aimed at treating type 2 diabetes. (DE 630-3, Koliwad Report at
23.) The so-called SAVOR (Saxagliptin Assessment of Vascular Outcomes Recorded in
Patients with Diabetes Mellitus) study of saxagliptin was a large RCT published in 2013. It
involved 16,492 patients with Type 2 diabetes who were followed for a median of 2.1 years.
(DE 626-27, Abraham Report at 16.) It was a double-blinded, randomized clinical trial
studying saxagliptin and cardiovascular outcomes in high-risk patients. (DE 626-27,
Abraham Report at 16.)
SAVOR tested for multiple endpoints. The primary endpoints included
cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. There
were also multiple secondary endpoints including hospitalization for heart failure. (DE 62627, Abraham Report at 16-17; DE 646-11, Scirica 2013 at 1319.) SAVOR found no
statistically significant difference between saxagliptin and placebo with regard to any
endpoint except hospitalization for heart failure. (DE 626-27, Abraham Report at 17.) Of
patients who received saxagliptin in the SAVOR trial, 3.5 percent were hospitalized for
heart failure compared to 2.8 percent of patients who received the placebo. (DE 646-19,
FDA Drug Safety Communication.) In other words, "35 out of every 1,000 patients
compared to 28 out of every 1,000 patients." Id. The association between saxagliptin and
hospitalization for heart failure appeared at the six-month treatment mark and then
dissipated within 10 to 11 months of treatment. (DE 626-27, Abraham Report at 17.)
As a result of the SAVOR finding, the FDA added new warnings about the risk of
hospitalization for heart failure to saxagliptin drug labels. (DE 646-19, April 5, 2016, FDA
Drug Safety Communication.) The warning states, "In a cardiovascular outcomes trial
enrolling participants with established [atherosclerotic cardiovascular disease (ASCVD)] or
7 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 8 of 38 - Page ID#: 7105

multiple risk factors for ASCVD (SAVOR Trial), more patients randomized to ONGLYZA
(289/8280, 3.5%) were hospitalized for heart failure compared to patients randomized to
placebo (228/8212, 2.8%)." (Pfs.' Ex. 5, ONGLYZA prescribing information.) The warning
continues, "Consider the risks and benefits of ONGLYZA prior to initiating treatment in
patients at a higher risk for heart failure." Id.
3) CVOTs of other DPP-4 inhibitors
Consistent with the FDA requirement, CVOTs were also conducted on other DPP-4
inhibitors. These trials (and the DPP-4 inhibitor studied) were EXAMINE (alogliptin),
TECOS (sitagliptin), CARMELINA (linagliptin), CAROLINA (linagliptin), and VIVIDD
(vildagliptin). (DE 630-3, Koliwad Report at 29-30.) The outcomes of all these CVOTs,
including SAVOR, "were remarkably similar" except for SAVOR's finding regarding
hospitalization for heart failure. Id. None of these CVOTs showed that DPP-4 inhibitors
posed a statistically significant risk of heart failure. (DE 710, Goyal Test. at 107.)
4) Post-SAVOR studies
As discussed, the SAVOR study tested for multiple endpoints. A problem with
testing for multiple endpoints is that "the more statistical tests conducted, the greater
likelihood of having at least one false positive where the result is statistically significant by
chance." (DE 631-3, Lee Report at 13.) For example, "when you list the signs of the zodiac,
if you add enough things, you can find an association between Libras and heart disease. It
doesn't mean that really exists. It's just if you list enough things, you may find an
association. That does not establish causation." (DE 712, Adler Test. at 29.)
Thus, the SAVOR authors explained that "the observation of a higher incidence of
hospitalization for heart failure among patients treated with saxagliptin was unexpected
and should be considered within the context of multiple testing that may have resulted in a
false positive result." (DE 646-11, Scirica 2013 at 1324.) The authors cautioned, "[t]his
8 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 9 of 38 - Page ID#: 7106

finding merits further investigation and needs to be confirmed in other ongoing studies, and
a class effect should not be presumed." Id. In a follow-up study, the authors stated that,
"[a]lthough unexpected, the incremental risk of heart failure hospitalization observed with
saxagliptin is likely valid, given the large number of events and the prespecification of
heart failure hospitalizations as a component of the secondary endpoint, together with
central blinded adjudication." (DE 626-10, Scirica 2014 at 1585.) The authors again
cautioned, however, that "the observation of an increased risk of hospitalization for heart
failure with saxagliptin must be taken in the context of multiple testing and the risk of a
'false-positive' result, although there was a statistically significant difference between the 2
groups after post hoc adjustment for multiple comparisons." Id.
Consistent with the SAVOR authors' urging, five sets of researchers undertook
observational studies of saxagliptin after SAVOR was published: 1) Fu et al., 2016; 2) Toh
et al., 2016; 3) Fadini, et al., 2017; 4) Chang et al, 2016; and 5) Kim 2017. None of them
found an association between saxagliptin and heart failure. (DE 635-10, Adler Report at 20;
Defs.' Ex. 10; DE 710, Goyal Test. at 87-88, 91, 99.) There were also multiple observational
studies that examined the risk of heart failure posed by other DPP-4 inhibitors. "Overall,
the vast majority of these studies found no association between heart failure and the DPP-4
inhibitor(s) under examination." (DE 635-10, Adler Report at 29.)
In addition to the observational studies, several research groups performed metaanalyses of saxagliptin and DPP-4 inhibitor clinical trials. The meta-analyses of saxagliptin
found no increased risk of heart failure when SAVOR data was excluded. (DE 630-3,
Koliwad Report at 38; DE 626-27, Abraham Report at 31; Defs.' Ex. 9, Iqbal 2014,
Discussion.) Other meta-analyses were conducted on class-wide DPP-4 inhibitor data. The
most recent of these are Singh et al. (2019) and Sinh et al. (2019), both of which found no

9 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 10 of 38 - Page ID#: 7107

increased risk of hospitalization for heart failure among DPP-4 inhibitor users. (DE 630-3,
Koliwad at 38; DE 626-27, Abraham Report at 31.)
II.

Analysis

Under Federal Rule of Evidence 702, expert testimony will be admitted where the
proponent shows that it satisfies three requirements. "First, the witness must be qualified
by 'knowledge, skill, experience, training, or education.'” In re Scrap Metal Antitrust Litig.,
527 F.3d 517, 529 (6th Cir. 2008) (quoting Fed. R. Evid. 702). "Second, the testimony must
be relevant, meaning that it 'will assist the trier of fact to understand the evidence or to
determine a fact in issue.'” Id. "Third, the testimony must be reliable." Id. The party
proffering the expert has the burden of proving 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).
As to reliability, in Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S. 579
(1993), "the Court charged trial judges with the responsibility of acting as gatekeepers to
exclude unreliable expert testimony." Fed. R. Evid. 702, advisory committee notes to 2000
amendment. Rule 702 provides "general standards to assess reliability: whether the
testimony is based upon 'sufficient facts or data,' whether the testimony is the 'product of
reliable principles and methods,' and whether the expert 'has applied the principles and
methods reliably to the facts of the case.'” In re Scrap Metal Antitrust Litig., 527 F.3d at 529
(quoting Fed. R. Evid. 702).
A court's inquiry must focus "solely on principles and methodology, not on the
conclusions they generate." Daubert, 509 U.S. at 595. "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 at 529-30. Courts
should confirm that “the factual underpinnings of the expert's opinion [are] sound,”
10 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 11 of 38 - Page ID#: 7108

Greenwell v. Boatwright, 184 F.3d 492, 498 (6th Cir. 1999), but generally “[v]igorous crossexamination, 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. “Rule 702 should be broadly interpreted on the basis of
whether the use of expert testimony will assist the trier of fact.” Morales v. Am. Honda
Motor Co., 151 F.3d 500, 516 (6th Cir. 1998) (citation omitted). “Mere weaknesses in the
factual basis of an expert witness's opinion . . . bear on the weight of the evidence rather
than on its admissibility.” McLean v. 988011 Ontario, Ltd., 224 F.3d 797, 801 (6th Cir.
2000) (quotations and citation omitted); United States v. Davis, 103 F.3d 660, 674 (8th Cir.
1996) (noting defendant was “free to challenge the expert's conclusions and point out the
weaknesses of the [expert's] analysis to the jury during cross-examination” but “[w]eight
and credibility are the province of the jury.”)
A.

Plaintiffs' motion to exclude the testimony of Dr. Suneil
Koliwad (DE 630)

Defense expert Suneil Koliwad is a medical doctor with a Ph.D. in molecular
physiology. He is a board-certified endocrinologist and a clinical researcher and associate
professor at the University of California at San Francisco (UCSF) School of Medicine's
Diabetes Center, where he is also the Chief of the Division of Endocrinology. (DE 630-4,
Koliwad CV; DE 630-3, Koliwad Report at 1-2.) Dr. Koliwad opines that "the evidence does
not support the presence of a causal relationship between saxagliptin use and heart
failure." (DE 630-3, Koliwad Report at 1, 45.)
In his report, Dr. Koliwad explains that, in assessing whether there is a causal
relationship between saxagliptin and heart failure, he employed the same methodology that
he uses when making causal assessments in his regular clinical practice and scientific
research. Id. at 45. As discussed, like all the experts at issue on these motions, Dr. Koliwad
11 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 12 of 38 - Page ID#: 7109

employed the Bradford Hill criteria to assesses the causal link. In assessing the Bradford
Hill factors, Dr. Koliwad considered SAVOR, the CVOTs of other DPP-4 inhibitors, the
post-SAVOR observational studies of saxagliptin and other DPP-4 inhibitors, and the metaanalyses of saxagliptin and other DPP-4 inhibitors. Id. at 23-29.
In their motion to exclude Dr. Koliwad's testimony, the plaintiffs do not question his
methodology. Instead, they argue that he is not qualified to opine on whether saxagliptin
can cause heart failure because he is an endocrinologist who has no expertise in cardiology.
(DE 630-1, Mem. at 1.) Plaintiffs argue that, as an endocrinologist, Dr. Koliwad does not
treat heart failure. Instead, he refers his patients with heart failure to a cardiologist for
treatment.
Dr. Koliwad testified that endocrinology is "the study of diseases related to
dysfunctions and/or imbalances in hormones and the impact that those dysfunctions or
imbalances have on tissues throughout our body, including the cardiovascular system" and
the heart. (DE 712, Koliwad Test. at 191.) Dr. Koliwad testified that he regularly treats
people with diabetes as part of his clinical practice. Id. at 191-92. He testified that over 80
percent of his patients have diabetes, and that diabetes treatment and management is the
core of his clinical practice. Id. He further testified that about 50 percent of his diabetes
patients have cardiovascular disease and that about 20 to 25 percent of those patients have
heart failure. Id. at 200.
As part of his treatment of diabetes patients, Dr. Koliwad must prescribe medicines
to them. Id. at 201. In making prescribing decisions, Dr. Koliwad must understand and
consider the risks and benefits of the medications. Id. at 201-02. Among the medications
that Dr. Koliwad prescribes are DPP-4 inhibitors including saxagliptin. Id. at 202. He
testified that prescribing this class of medications is "central" to his practice. Id. at 207.

12 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 13 of 38 - Page ID#: 7110

Plaintiffs argue that Dr. Koliwad testified that he prescribes saxagliptin for only two
to three patients each year and, therefore, is not qualified to assess whether the scientific
literature indicates that it can cause heart failure. Id. at 229. Regardless of the number of
times that Dr. Koliwad prescribes saxagliptin, he testified that he was very familiar with
the risks and benefits of DPP-4 inhibitors, including saxagliptin, before becoming involved
in this litigation. Id. at 202. As part of his practice, he was familiar with the SAVOR study
and the issue of whether saxagliptin contributes to heart failure. Id. at 208. Dr. Koliwad
testified that assessing the scientific literature to determine whether it shows that
saxagliptin can cause heart failure, as he did in this case, is "emblematic" of the kinds of
questions he addresses in his regular clinical practice as an endocrinologist and diabetes
specialist. Id. at 233. Thus, Dr. Koliwad's testimony in this case is about a matter "growing
naturally and directly out of research [he has] conducted independent of the litigation." In
re Meridia Prod. Liab. Litig., 328 F. Supp. 2d 791, 804 (N.D. Ohio 2004) (quoting advisory
committee notes to Fed. R. Evid. 702.)
Moreover, Dr. Koliwad has extensive experience in clinical research and, thus, is
qualified to assess current research related to whether saxagliptin can cause heart failure.
Dr. Koliwad conducts diabetes research at UCSF's School of Medicine's Diabetes Center.
(DE 630-3, Report at 1.) He conducted advanced research on cardiovascular disease for
seven years (2004-11). Id. at 2. He has been the director of the Koliwad Laboratory in the
UCSF Diabetes Center since 2011. Id. at 3. He is a member of the American Society of
Clinical Investigators, (DE 712, Koliwad Test. at 196), and is a peer reviewer for numerous
journals, meaning he critiques medical and scientific studies. (DE 630-3, Report at 4.)
Plaintiffs argue that Dr. Koliwad's research and laboratory work have not focused on
heart failure or its causes. He testified, however, that as part of his work as a researcher,

13 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 14 of 38 - Page ID#: 7111

he regularly reviews clinical research and scientific literature focusing on diabetes
medications and their impact on the vascular system and heart. (DE 712, Tr. at 196.)
Accordingly, Dr. Koliwad is qualified to assess current scientific evidence and render an
opinion on whether it supports "the presence of a causal relationship between saxagliptin
and heart failure." (DE 630-3, Report at 1.) Plaintiffs may attack Dr. Koliwad's opinion by
pointing out on cross examination that he is not a cardiologist, but the Court cannot find
that only a cardiologist can analyze studies related to saxagliptin and heart failure to
determine whether they indicate a causal association pursuant to the Bradford Hill criteria.
The motion to exclude Dr. Koliwad's testimony will be denied.
B.

Plaintiffs' motion to exclude Dr. Eric Adler's testimony (DE
633)

Plaintiffs move to exclude the expert testimony of Dr. Eric Adler, a board-certified
cardiologist who practices at University of California San Diego (UCSD) Hospital and is a
medical professor at UCSD. In his cardiology practice, Dr. Adler cares for patients
experiencing heart failure, 30 percent of whom have diabetes. (DE 635-10, Adler Report at
1-3.) Like Dr. Koliwad, Dr. Adler employed the Bradford Hill criteria to analyze the
relevant scientific studies and literature and concluded that "there is insufficient evidence
to demonstrate a causal relationship between saxagliptin use and either new heart failure
or worsened heart failure." Id. at 1.
Plaintiffs argue that it is unlikely that Dr. Adler wrote his report. They argue that
Dr. Adler's opinion is a "near replica" of the report of Dr. William T. Abraham, who is
another defense expert. (DE 634-1, Mem. at 2.) Plaintiffs argue that the reports of Drs.
Adler and Abraham cite many of the same sources, cover many of the same topics, and that
the "syntax, sentence structure, and organization" of the reports are "virtually identical."
(DE 668, Reply at 21.)
14 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 15 of 38 - Page ID#: 7112

In his deposition and at the hearing, Dr. Adler testified that he had not even read
Dr. Abraham's report or the report of any other defense expert. (DE 644-1, Adler Dep. at 21;
DE 712, Hr'g Tr. at 46.) Likewise, Dr. Abraham testified in his deposition that he had never
spoken with Dr. Adler about this matter and had not reviewed Dr. Adler's expert report.
(DE 642-14, Abraham Dep. at 56-57.) Dr. Adler testified at his deposition and at the
hearing that he wrote his report and that he did not use a ghost writer although defense
counsel did edit sentence structure and formatting. (DE 644-1, Adler Dep. at 51-52; DE 712
at 45.) Plaintiffs give the Court no reason to question that testimony.
Drs. Adler and Abraham are both cardiologists and both have been asked to proffer
an opinion on the same issue: whether saxagliptin can cause heart failure. As would be
expected, both consulted the finite body of literature relevant to that question. It is not
surprising that they cite many of the same sources. As to plaintiffs' argument that the
reports of the two doctors contain the same phrases, most of the phrases plaintiffs cite in
support of this argument are exact quotes from the relevant literature as indicated by the
internal quotations and citations in the sample quotes from the doctors' reports cited by the
plaintiffs. (DE 634-1, Mem. at 10.) Dr. Adler did not copy Dr. Abraham's sentences in these
instances as plaintiffs argue. Instead, both doctors quoted the relevant literature.
Plaintiffs also argue that Dr. Adler incorrectly relied on the MEASURE-HF study,
which they argue is "scientifically inferior data" when compared to the SAVOR study. The
Court ruled at the Daubert hearings that neither party may use the MEASURE-HF study
either to support its own case or to attack the opposing party's case. This is because the
study has still not been published and it would be confusing to ask jurors to consider an
incomplete study that is not yet published in reliable medical journals. (DE 710, Tr. at 18687.) Accordingly, at trial, Dr. Adler will not be permitted to rely on the MEASURE-HF
study.
15 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 16 of 38 - Page ID#: 7113

The Court's ruling that no party may rely on MEASURE-HF does not require that
Dr. Adler's opinion be excluded because he did not rely solely on the MEASURE-HF study
in formulating his opinions. Dr. Adler considered the scientific data discussed above
consisting of the SAVOR trial, the observational studies that used "real-world data" to
examine saxagliptin and heart failure after the SAVOR study, and the meta-analyses of
clinical trials examining saxagliptin and heart failure, and the CVOTs and meta-analyses
of other DPP-4 inhibitors. (DE 635-10, Report at 13-29),
Plaintiffs also argue that Dr. Adler is not qualified to opine that the authors of the
SAVOR study should have applied the so-called "Bonferroni correction" differently. (DE
634-1, Mem. at 12-13.) The Bonferroni correction is a statistical adjustment used to correct
for the risk described above of a false positive when a clinical trial tests for multiple
endpoints. (DE 712, Adler Test. at 29-31.) Dr. Adler explained that he teaches medical
students how to adjust for multiple endpoints, or multiplicity, and that it is a "central
question" he addresses when designing trials. (DE 712, Adler Test. at 29.)
As discussed, the SAVOR authors identified three primary endpoints and three
secondary endpoints of the study. (DE 646-11, SAVOR 2013 at CM-ECF p. 4.) Thus, they
published a follow-up study that applied a post-hoc adjustment for six endpoints. (DE 62610, SAVOR 2014 at 1580.) Dr. Adler opines that the SAVOR authors should have adjusted
for 11 endpoints. (DE 635-10, Adler Report at 17.) He testified at the hearing that there
were actually 11 tests performed and that, when the test results are adjusted for 11
endpoints, SAVOR shows no association between saxagliptin use and hospitalization for
heart failure. (DE 712, Adler Test. at 33; DE 635-10, Adler Report at 18.) Dr. Adler testified
that he was familiar with at least three other papers by scientists who had similarly
criticized the Bonferroni correction applied by the SAVOR authors. (DE 712, Adler Test. at

16 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 17 of 38 - Page ID#: 7114

34-35; Defs.' Ex. 34.) His report discusses Pocock 2016, Centrian-Cuenca 2016, and Scheen
2018. (DE 635-10, Adler Report at 18.)
Plaintiffs argue that Dr. Adler is not qualified to opine on how the Bonferroni
correction should be applied because he does not have experience in applying it. Defendants
point out that Dr. Adler has extensive research experience, including 20 years of experience
in conducting clinical trials. (DE 712, Adler Test. at 7.) Dr. Adler testified that he has been
involved in designing clinical trials and generating hypotheses; monitoring clinical trials
while they are proceeding to make sure that they are being performed adequately and
accurately; and assisting with the interpretation and presentation of trial results when
they are concluded. Id.
He leads the Adler Lab at UCSD, which is a research lab devoted to studying how
genetic mutations cause cardiomyopathy. Further, he has participated in the design and
evaluation of preclinical primate studies and has been the principal investigator in
numerous clinical trials studying all stages of heart failure. In addition, he participates in
the peer-review process for numerous medical journals. (DE 635-10, Report at 2.)
At the hearing, Dr. Adler testified that he had experience dealing with adjustments
for multiplicity in clinical trials. (DE 712, Adler Tr. at 30.) He did testify in his deposition
that he relies on a biostatistician to apply a Bonferroni correction in his own research and
that he was unsure if he had ever applied the correction himself. (DE 634-2, Adler Dep. at
116.) When asked further questions about applying the Bonferroni correction, he conceded
it was not his "complete area of expertise." (DE 634-2, Adler Dep. at 122.)
Nevertheless, at the hearing, Dr. Adler gave step-by-step instructions regarding how
the correction is applied. (DE 712, Adler Test. at 32.) Further, applying the correction is
relatively straightforward. As Dr. Adler explained, it consists of dividing the false-positive
rate by the number of endpoints. In other words, applying the correction involves "dividing
17 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 18 of 38 - Page ID#: 7115

one number by another." (DE 712, Adler Tr. at 33.) Dr. Adler's opinion that an 11-point
adjustment should be applied is supported by other scientists. Accordingly, the Court will
permit Dr. Adler to opine that he believes an 11-point Bonferroni correction should be
applied to the SAVOR study. Plaintiffs may of course point out on cross examination any
deficiencies in Dr. Adler's experience or qualifications on this issue.
The Court further notes, however, that Dr. Adler's causation opinion does not
depend on his application of the 11-point Bonferroni correction as plaintiffs argue. (DE 718,
Post-Hr'g Br. at 6.) As Dr. Adler explained, the Bonferroni correction for 11 endpoints only
affects whether the SAVOR study should be construed to find any association between
saxagliptin and hospitalization for heart failure at all. (DE 712, Adler Test. at 35-36.)
According to Dr. Adler, if the SAVOR study is construed to find no such association, then
there is no need to undertake the Bradford Hill causation analysis because the analysis is
only undertaken if there is a "clear-cut association" between an exposure and outcome. (DE
635-10, Adler Report at 30.)
Nevertheless, in his report, Dr. Adler goes on to undertake the Bradford Hill
analysis, and he found no causation relationship. Thus, he testified, that "[e]ven if this
association [between saxagliptin and hospitalization for heart failure from SAVOR data]
was valid, it doesn't change the fact that there there's no establishment of causation." (DE
712, Adler Test. at 35-36.) Dr. Adler's Bradford Hill analysis is not affected by the
Bonferroni correction, whether it is a 6- or 11-point correction.
Likewise, Dr. Adler's opinion that the SAVOR study should not be interpreted to
establish causation on its own applies regardless of what Bonferroni correction is applied.
Even after applying the six-point multiplicity adjustment, the SAVOR authors cautioned
that the risk of a false positive remained and, thus, further testing was necessary. (DE 62610, Scirica 2014 at 1585.) Further, Dr. Adler points out that hospitalization for heart failure
18 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 19 of 38 - Page ID#: 7116

was not a primary endpoint of the study. Instead, it was a secondary endpoint and thus, not
the "main focus of the trial." (DE 635-10, Adler Report at 15-16.). Dr. Adler opines that, "a
statistically significant finding in a component of a secondary endpoint is considered
hypothesis generating and worthy of further investigation, but is cannot be considered
proof of a 'causal' relationship between use of the medication and outcome." (DE 635-10,
Adler Report at 16.)
Further, Dr. Adler noted that other SAVOR findings were "inconsistent with the
presence of a causal relationship between saxagliptin and heart failure." (DE 635-10, Adler
Report at 18.) Dr. Adler found that "the absence of any other elevated cardiovascular risk
factor," the absence of any increased risk of edema (a condition associated with heart
failure), and the absence of elevated levels of NT-proBNP (a substance that is elevated in
patients with heart failure) among saxagliptin patients in the study were all inconsistent
with causation. (DE 635-10, Adler Report at 18-19.) Further, Dr. Adler noted that the
CVOTs for other DPP-4 inhibitors did not find an elevated risk of heart failure after drug
exposure and that the SAVOR authors found no clear biological mechanism by which
saxagliptin could cause heart failure.
Thus, Dr. Adler opined that SAVOR should be interpreted to generate a hypothesis
that "saxagliptin and heart failure may be associated in some way," but that it should not
be interpreted to demonstrate a causal relationship. (DE 635-10, Adler Report at 19.) These
critiques of the SAVOR study apply whether a six-point multiplicity adjustment is applied
to the hospitalization finding or an 11-point adjustment. In fact, the SAVOR authors
themselves offered a similar critique. As discussed, they cautioned that hospitalization-forheart failure finding was "unexpected and should be considered within the context of
multiple testing that may have resulted in a false positive result." (DE 646-11, Scirica 2013
at 1324.) The authors advised, "This finding merits further investigation and needs to be
19 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 20 of 38 - Page ID#: 7117

confirmed in other ongoing studies, and a class effect should not be presumed." (DE 646-11,
Scirica 2013 at 1324; DE 626-10, Scirica 2014 at 1585.)
In their post-hearing briefing, plaintiffs argue that Dr. Adler's opinion should be
excluded because it "lacks reliability." (DE 718, Post-Hr'g Bf. at 5.) Plaintiffs argue that Dr.
Adler's opinion largely hinges on studies that were funded by the defendants. Again, Dr.
Adler's opinion relies on multiple studies. Based on the record, it appears that he
considered all the studies related to saxagliptin and heart failure. Plaintiffs do not point to
any studies that Dr. Adler should have considered that he did not. Nor do they point to any
evidence that would allow the Court to conclude that any of the studies considered by Dr.
Adler are unreliable.
Plaintiffs argue that Dr. Adler did not consider the statement of Dr. John Monyak, a
biostatistician employed by the defendants, who seems to discount the need to adjust for
multiplicity, stating in an e-mail, "Safety analyses usually downplay the role of multiplicity
or don't consider it rigorously . . . . If you adjusted everything for multiplicity, you'd never
find anything." (DE 718-5, e-mail.) Plaintiffs also argue that Dr. Adler did not consider
statements at a meeting of the FDA's Endocrinologic and Metabolic Drugs Advisory
Committeee (EMDAC). At that meeting, an FDA pharmacist stated that, although the
SAVOR study published in 2013 did not contain a multiplicity adjustment for the
hospitalization-for-heart-failure endpoint, "the validity of this finding is supported by the
large number of hospitalizations for heart failure events used for the estimation of risk, the
fact that hospitalization for heart failure was a prespecified endpoint using a standardized
definition and events were prospectively collected at end of trial and adjudicated by an
independent, blinded adjudication committee." (DE 718-6, EMDAC minutes at 127.)
For his report, Dr. Adler applied the Bradford Hill analysis and considered the
relevant scientific studies and literature. Plaintiffs cite to no authority indicating that
20 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 21 of 38 - Page ID#: 7118

reliable scientific methodology requires him to also consider particular e-mails or
statements at a meeting. Further, as to the statement at EMDAC meeting regarding the
validity of the hospitalization-for-heart failure finding in SAVOR, Dr. Adler agreed with the
statement, testifying that no one disputes SAVOR's finding that the patients went to the
hospital with heart failure. (DE 712, Adler Test. at 27-28.) The issue remains as to whether
saxagliptin can cause heart failure. The motion to exclude Dr. Adler's testimony on that
issue will be denied.
C.

Plaintiffs' motion to exclude Dr. Todd Lee's testimony (DE 635)

Plaintiffs move to exclude the testimony of Todd Lee, PhD, who is a
pharmacoepidemiologist and professor at the University of Illinois Chicago with experience
in researching the safety of medications, including significant work regarding diabetesrelated medications. (DE 631-3, Lee Report at 1-2.) Dr. Lee has been involved in research
examining the safety of medications including observational studies, clinical trial analyses,
and meta-analyses. Id.at 1.
In his report, Dr. Lee explains that clinical pharmacoepidemiology applies
"epidemiological methods to study the effects of medication in patient populations" to
"predict the effects of administering a medication to a patient." (DE 631-3, Lee Report at 3.)
He testified that pharmacoepidemiology is a subdiscipline, or specialty, of epidemiology.
(DE 712, Lee Test. at 91.) Dr. Lee opines that "the evidence does not support a clear-cut
association between saxagliptin and an increased risk for hospitalizations for heart failure,
let alone meet the much higher burden for establishing a causal association." (DE 109-3,
Lee Report at 1.)
Plaintiffs argue that Dr. Lee's testimony should be excluded because he does not
have a degree in pharmacoepidemiology. He has a Pharm D pharmacy degree and a Ph.D.
in pharmaceutical outcomes research and pharmacoeconomics. (DE 631-4, Lee CV at CM21 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 22 of 38 - Page ID#: 7119

ECF p. 2.) Regardless, Dr. Lee has extensive experience in pharmacoepidemiology. He
teaches both undergraduate and graduate courses in the field and has published articles
and given presentations on the topic. (DE 631-4, Lee CV; DE 712, Lee Test. at 94.) He
testified that he has worked in the field for more than 20 years. (DE 712, Lee Test. at 9192.) As part of that work, he has published observational studies and meta-analyses and
interpreted clinical trial. (DE 712, Lee Test. at 93.) In addition, he has been recognized as a
"best reviewer" by the Journal of Pharmacoepidemiology and Drug Safety, which Dr. Lee
testified is the premier journal of the International Society for Pharmacoepidemiologists.
(DE 712, Lee Test. at 95.)
In reaching his opinion as to whether the evidence supports an association or
causation relationship between saxagliptin and heart failure, Dr. Lee employed the
Bradford Hill framework and considered the SAVOR study, the CVOTs for other DPP-4
inhibitors, meta-analyses of saxagliptin and of other DPP-4 inhibitors, and observational
studies. (DE 631-3, Lee Report at 11-26.) This is precisely the kind of analysis Dr. Lee
performs as part of his regular work. In his report, Dr. Lee asserts that
"[p]harmacoepidemiologists scrutinize all phases of clinical trials . . . , observational
studies, and other evidence in evaluating the effects of medications." (DE 631-3, Report at
3.) Dr. Lee testified that the "primary focus" of pharmacoepidemiology is determining
whether drugs are associated with adverse effects on the human body. (DE 712, Lee Test. at
91.) He testified that causation analysis is part of his day-to-day work. Id. at 89. Further,
Dr. Lee's graduate and undergraduate pharmacoepidemiology courses include instruction
in the Bradford Hill analysis. (DE 712, Lee Test. at 94, 130.)
Dr. Lee is qualified to review the published literature to determine whether it
supports a causal connection between saxagliptin and heart failure. The plaintiffs also
argue that Dr. Lee is not qualified to render this opinion because he is not a cardiologist.
22 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 23 of 38 - Page ID#: 7120

For his analysis, however, Dr. Lee was not required to diagnose heart failure. Instead, as
Dr. Lee explained at the hearing, he reviewed the literature that studied the relationship
between 1) saxagliptin and other DPP-4 inhibitors and 2) events that the studies' authors
had identified as heart-failure events. (DE 712, Lee Test. at 170.) Dr. Lee did not himself
determine if the patients involved in the study experienced heart failure.
Plaintiffs argue that Dr. Lee's testimony should be excluded because he did not
employ a reliable methodology. Plaintiffs argue that Dr. Lee did not "undertake any of his
own analysis" of the raw data underlying the studies included in his analysis and, instead,
conducted a "literature review" of studies selected by defense counsel. (DE 635-1, Mem. at
8-9, 17.) Plaintiffs argue that Dr. Lee was required to perform his own "statistical analysis"
to validate the statistical findings of the SAVOR trial, the observational studies, and the
meta-analyses. (DE 729, Post-Hr'g Reply Br. at 3.) Plaintiffs cite no authority for the
argument that a reliable Bradford Hill analysis requires that the expert analyze the raw
data underlying the relevant studies. None of the experts in this case did so, including the
plaintiffs' expert Dr. Goyal. As to whether Dr. Lee chose the studies to include in his
analysis or defense counsel did, Dr. Lee testified that, while he primarily relied on the
literature provided by defense counsel, he also conducted his own searches on PubMed to
ensure that he had all the relevant literature. (DE 642-5, Lee Dep. at 29-30, 54-57; DE 712,
Lee Test. at 167.)
In their post-hearing brief, plaintiffs argue that Dr. Lee is not "qualified to opine
regarding a biologically plausible mechanism." (DE 719, Post-Hr'g Br. at 2.) As part of his
Bradford Hill analysis, Dr. Lee appropriately considered whether evidence existed of some
biological mechanism by which it would "make[] sense" that saxagliptin could cause heart
failure. (DE 631-1, Lee Report at 32.) In assessing biologic plausibility, Dr. Lee focused on
clinical trial and epidemiological evidence. (DE 631-3, Lee Report at 32.) He noted that the
23 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 24 of 38 - Page ID#: 7121

SAVOR authors reported that there were "no known mechanisms by which DPPP-4
inhibition could precipitate heart failure." (DE 631-3, Lee Report at 32; DE 626-10, Scirica
2014 at 1585.) Dr. Lee made clear at the hearing that he is not opining himself on whether
there is a biological reason that saxagliptin could cause heart failure, he is simply opining
that the studies involving human data have not found one. (DE 712, Lee Test. at 148.) Even
though Dr. Lee is not a cardiologist, he is qualified to review the relevant scientific
literature and determine whether any has theorized a biologically plausible mechanism by
which saxagliptin could cause heart failure.
Plaintiffs argue that Dr. Lee did not consider evidence that did not support the
defendants' position. (DE 719, Post-Hr'g Br. at 5.) But Dr. Lee testified that he reviewed the
reports of the plaintiffs' experts, and that they did not identify any materials that he had
not reviewed. (DE 712, Hr'g Tr. at 101-02.) In his report, Dr. Lee explains the kinds of
studies that he considered for his report. He considered the relevant CVOTs, observational
studies (including those involving saxagliptin users and those involving users of other DPP4 inhibitors), and meta-analysis (including saxagliptin-specific meta-analyses and metaanalysis of the DPP-4 inhibitor class.) Plaintiffs argue that Dr. Lee's reliance on pool
analyses and observational studies was improper, but they cite no authority for that
argument. (DE 719, Post-Hr'g Br. at 5.)
Plaintiffs argue that Dr. Lee failed to account for the limitations of observational
studies. But Dr. Lee recognizes in his report that observational studies present issues with
"bias and confounding . . . because the treatment is not randomly assigned, and neither the
patients nor the researchers are blinded to treatment." (DE 631-3, Lee Report at 4.) Dr. Lee
noted, however, that "researchers can take steps to minimize bias and confounding both
during the design of the study and during the analysis of the study data." (DE 631-3, Lee
Report at 4.) He further explains that the observational studies he considered follow a
24 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 25 of 38 - Page ID#: 7122

"cohort study design," which is "conceptually similar to a randomized controlled trial . . . ."
(DE 631-3, Lee Report at 4.) Plaintiffs do not argue that any of the observational studies
Dr. Lee relied upon were flawed in some way. His consideration of them in his Bradford
Hill analysis was not improper.
Plaintiffs argue that Dr. Lee relied only on class-wide observational studies for DPP4 inhibitors that support his opinion. (DE 719, Post-Hr'g Br. at 5.) However, Dr. Lee
testified that he considered all such studies but did not focus on them, choosing to focus
instead on the observational studies pertaining specifically to saxagliptin. (DE 712, Lee
Test. at 123.) Plaintiffs may cross examine Dr. Lee on that choice, but it is not a reason to
exclude his opinion.
Plaintiffs also argue that Dr. Lee ignored the "Wu article," which is a 2014 metaanalysis by Wu et al. (DE 719, Post-Hr'g Br. at 5.) But Dr. Lee testified that he did review
the Wu article. (DE 712, Lee Test. at 142.) The article is listed in Dr. Lee's report among
the literature he considered. (DE 631-3, Materials Considered at CM-ECF p. 53.) Dr. Lee
testified that his report did not focus on the 2014 Wu article because it does not consider
any saxagliptin-specific studies and because he focused on more recent meta-analyses,
which "would have been the most comprehensive collection of data." (DE 712, Lee Test. at
186-87.)
Dr. Lee explained that the early meta-analyses, like the Wu article, that found a
weak association between increased risk of heart failure and the DPP-4 inhibitor class were
dominated by SAVOR data. (DE 631-3, Report at 19-20.) He explains that this association
disappeared in later studies that included CVOTs other than SAVOR. (DE 631-3, Report at
20.) The Wu article itself explains that its result was "dominated" by the SAVOR trial. (Pfs.'
Ex. 21, Wu 2014 at 152.) Dr. Lee explained that SAVOR contributed about two-thirds of the
data for the Wu study, meaning "most of the effect estimate that is measured in the
25 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 26 of 38 - Page ID#: 7123

summary is due to SAVOR." (DE 712, Lee Test. at 187-88.) Plaintiffs may cross examine
Dr. Lee about his discounting of the 2014 Wu article, but he gives a sound rationale for
doing so. His treatment of the article does not render his opinion unreliable.
Plaintiffs argue that Dr. Lee's methodology is unreliable because he did not consider
a 2018 article by Dr. Milton Packer that identified a biologically plausible mechanism by
which saxagliptin and DPP-4 inhibitors could cause heart failure. (DE 710, Post Hr'g Br. at
6.) In his report, Dr. Lee concludes, "Clinal trial evidence does not support any biologically
plausible relationship between saxagliptin and heart failure." (DE 631-3, Lee Report at 32.)
Dr. Lee notes that, in analyzing plausibility, plaintiffs' expert Dr. Goyal relies on Packer's
article. Dr. Lee discounts Packer's article because it "suggests theoretical mechanisms, but
it does not provide original experimental findings." (DE 631-3, Lee Report at 32.) Further,
Dr. Lee discounts Dr. Packer's proposed mechanism because it is not specific to saxagliptin.
Instead, the proposed mechanism would purport to explain how the entire class of DPP-4
inhibitors pose a risk of heart failure. Dr. Lee noted that the most updated studies,
however, have not even shown an association between DPP-4 inhibitors as a class and heart
failure. (DE 631-3, Lee Report at 32-33; DE 712, Lee Test. at 188-89.) Dr. Lee gives sound
reasons for discounting the Packer article. His treatment of the article may be a subject for
cross examination, but it is not a reason to exclude his opinion.
Plaintiffs argue that Dr. Lee's methodology is unreliable because his analysis of the
"biological gradient" factor of the Bradford Hill criteria is unreliable. (DE 719, Past-Hr'g Br.
at 6.) Dr. Lee explains in his report that this factor looks at whether a "dose response"
exists. "If the exposure is truly causing the event, it is anticipated that bigger doses of the
exposure would lead to higher event rates. If this is demonstrated, then there is a 'doseresponse' between the exposure and the event." (DE 631-3, Lee Report at 31-32.) Dr. Lee
states, "In none of the available trials or observational studies is there clear evidence of a
26 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 27 of 38 - Page ID#: 7124

dose response relationship where heart failure risk increased, or increased more, in
patients using larger doses as compared to smaller doses." Id.at 32. Thus, in forming his
opinion regarding the biological gradient factor, Dr. Lee considered available scientific
evidence. This is a reliable methodology. His opinion on this issue is consistent with
plaintiffs' expert Dr. Goyal, who also testified that, based on all the data, he could not find
that this factor is met. (DE 710, Goyal Test. at 6, 125, 143.)
Plaintiffs argue that Dr. Lee's methodology is unsound because, in opining on the
Bonferroni correction, he did not undertake his own statistical analysis of the data
underlying the SAVOR study. (DE 635-1, Mem. at 10) As Dr. Lee explained, SAVOR tested
for multiple endpoints and found that "hospitalization for heart failure was the only event
associated with a nominally statistically significant increase." (DE 631-3, Lee Report at 12.)
As has been discussed, Dr. Lee, like the other experts, testified that one problem with
testing for multiple endpoints is that "the more statistical tests conducted, the greater
likelihood of having at least one false positive where the result is statistically significant by
chance." (DE 631-3, Lee Report at 13.)
Again, the SAVOR authors applied a six-point Bonferroni adjustment and still found
a statistically significant association between saxagliptin use and hospitalization for heart
failure even though the risk of a false positive remained. Like Dr. Adler, Dr. Lee opines that
SAVOR pre-specified 11 endpoints. (DE 631-3, Lee Report at 13.) Dr. Lee opines that, if an
11-point adjustment is applied, the difference in heart failure for hospitalization among
SAVOR's saxagliptin and placebo groups would not be statistically significant. Id. Thus,
like Dr. Adler, Dr. Lee opines that there is no "clear cut" association between saxagliptin
and an increased risk of hospitalization for heart failure. Id. at 27.
Plaintiffs have not demonstrated that it is necessary to review the raw data
underlying a study to determine the appropriate Bonferroni correction to apply. According
27 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 28 of 38 - Page ID#: 7125

to the testimony of Dr. Lee and Dr. Adler, the appropriate correction depends upon the
number of endpoints that were the object of the study. In his report, Dr. Lee identifies 11
endpoints. Id. at 13. There is no need to review the underlying data to determine the
number of endpoints. Dr. Lee states that several researchers have agreed with the 11-point
correction since SAVOR's publication. He cites Pocock 2015 and Cebrian-Cuenca 2016. Id.
Plaintiffs may present evidence that disputes the appropriateness of the 11-point
correction, but they have not shown that a reliable opinion on this issue requires an
analysis of the raw data underlying the study.
The Court notes, however, that, as was the case with Dr. Adler, Dr. Lee's Bradford
Hill analysis is not affected by which Bonferroni correction is applied. Again, the
application of the 11-point adjustment affects only whether the Bradford Hill analysis
should be undertaken at all. Dr. Lee and Dr. Adler agreed that, with the 11-point
correction, there is not even a statistically significant association between saxagliptin and
hospitalization for heart-failure, making a causation analysis unnecessary. Like Dr. Adler,
however, Dr. Lee did undertake a Bradford Hill causation analysis, which is a totally
separate analysis than the Bonferroni correction. (DE 712, Lee Test. at 100.)
Finally, Plaintiffs argue that Dr. Lee "inappropriately devalues the SAVOR
causation findings." (DE 729, Post-Hr'g Reply Br. at 5). The SAVOR study, however, did not
make causation findings. As noted multiple times in this opinion, the SAVOR authors
cautioned that the higher rate of hospitalization for heart failure "should be considered
within the context of multiple testing that may have resulted in a false positive result." (DE
646-11, Scirica 2013 at 1324.) The authors cautioned that the "finding merits further
investigation and needs to be confirmed in other ongoing studies." (DE 646-11, Scirica
1324.) Plaintiffs have not shown that Dr. Lee's conclusion that the SAVOR study presents a

28 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 29 of 38 - Page ID#: 7126

risk of a false positive is contrary to reliable scientific methodology or even to the findings
of the SAVOR authors themselves.
The motion to exclude Dr. Lee's testimony will be denied.
D.

Defendants' motion to exclude Dr. Parag Goyal's Testimony
(DE 626)

Defendants move to exclude the testimony of the plaintiffs' expert, Dr. Parag Goyal,
who is a board-certified cardiologist and assistant professor at Weill Cornell Medicine. He is
a member of both the heart-failure faculty and of the core-research faculty. Dr. Goyal's
clinical interests and expertise are focused on heart failure and his research interest and
expertise are focused on "the safety of medication prescribing patterns in heart failure."
(DE 628-3, Goyal Report at 1.)
He opines that "it is more likely than not that saxagliptin is capable of causing heart
failure." (DE 628-3, Goyal Report at 14.) Neither Dr. Goyal nor the plaintiffs have been able
to identify any other expert who has reached this opinion. (DE 710, Goyal Test. at 68.) Like
the defense experts, Dr. Goyal arrives at his opinion after applying the Bradford Hill
criteria. "When a scientist claims to rely on a method practiced by most scientists, yet
presents conclusions that are shared by no other scientist, the district court should be wary
that the method has not been faithfully applied." Lust By & Through Lust v. Merrell Dow
Pharms., Inc., 89 F.3d 594, 598 (9th Cir. 1996). "It is the proponent of the expert who has
the burden of proving admissibility. To enforce this burden, the district court can exclude
the opinion if the expert fails to identify and defend the reasons that his conclusions are
anomalous." Id.
Dr. Goyal has never published an article applying the Bradford Hill criteria. (DE
710, Goyal Test. at 124.) Nor has he ever written any paper applying the criteria except for
his report in this case. (DE 710, Goyal Test. at 124.) He agreed that no published paper had
29 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 30 of 38 - Page ID#: 7127

applied the Bradford Hill criteria and found that saxagliptin caused an increased risk of
hospitalization for heart failure. Id. at 124-25.
The defendants argue that Dr. Goyal's methodology is unreliable because his
Bradford Hill analysis considers only the SAVOR study and certain animal studies and
disregards all the other human data, which consists of the CVOTs, observational studies
and meta-analyses discussed above. Defendants further argue that Dr. Goyal is not
qualified to interpret the data from animal studies.
As to Dr. Goyal's reliance on the SAVOR study to the exclusion of all other studies
involving human data, Dr. Goyal testified that he was not aware of any clinical study other
than SAVOR that showed an increased risk of heart failure with saxagliptin. (DE 710,
Goyal Test. at 87.) In his report, he recognizes that no CVOT or randomized control trial of
DPP-4 inhibitors other than SAVOR found a statistically significant association between
exposure to the drug and hospitalization for heart failure. (DE 628-3, Goyal Report at 10;
DE 710, Goyal Test. at 107.) Nevertheless, he stated in his report and testified that
SAVOR's finding of a statistically significant increase in hospitalizations for heart failure
after exposure to saxagliptin "should be interpreted as cause and effect unless there is
compelling evidence to prove otherwise." (DE 628-3, Goyal Report at 8; DE 710, Goyal Test.
at 67.)
This is contrary to reliable scientific method. First, "[r]arely, if ever, does a single
study persuasively demonstrate a cause-effect relationship." Reference Manual on Scientific
Evidence at 604. It is important that a study be replicated in different populations and by
different investigators before a causal relationship is accepted by epidemiologists and other
scientists. Id. "A good general rule of thumb in science is never to rely on any experimental

30 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 31 of 38 - Page ID#: 7128

finding until it has been independently replicated." Id. at 777. Dr. Goyal agreed with all
this at the hearing. (DE 710, Goyal Test. at 76-79.)3
Second, drawing "unauthorized conclusions from limited data – conclusions the
authors of the study do not make" demonstrates a "lack of scientific rigor." McClain v.
Metabolife Int'l, Inc., 401 F.3d 1233, 1248 (11th Cir. 2005); see also In re Nexium
Esomeprazole, 662 F. App'x 528, 530 (9th Cir. 2016) (holding that expert was properly
excluded when doctor "did not adequately explain how he inferred a causal relationship
from epidemiological studies that did not come to such a conclusion themselves.") As
discussed, the SAVOR authors themselves noted that "[t]here are presently no known
mechanisms by which DPP-4 inhibition could precipitate heart failure." (DE 626-10, Scirica
2014 at 1585.) They cautioned that their observation of a higher incidence of hospitalization
for heart failure among patients treated with saxagliptin "should be considered within the
context of multiple testing that may have resulted in a false positive result." (DE 646-11,
Scirica 2013 at 1324.) The authors specifically stated, "[t]his finding merits further
investigation and needs to be confirmed in other ongoing studies, and a class effect should
not be presumed." Id. In his rebuttal report, Dr. Goyal states that he "completely agree[s]
with these points; and I would moreover argue that this [further investigation] is urgently
needed." (DE 646-3, Goyal Rebuttal at 2.)

 In their post-hearing briefing, plaintiffs point out that, in a footnote, the Reference Manual on Scientific Evidence
qualified that the requirement that a study be replicated before a causal relationship is established "may not be the
legal standard." Reference Manual on Scientific Evidence at 604, n. 163. The single case cited for this proposition is
a Western District of North Carolina district court case in which the court stated, in a footnote, that, consistency for
purposes of the Bradford Hill analysis was difficult to establish because only one epidemiological study existed in
that case. Smith v. Wyeth-Ayerst Lab'ys Co., 278 F. Supp. 2d 684, 710 (W.D.N.C. 2003). The court further noted that
finding consistency was less important in that case because there was no real question as to general causation. Here,
there are multiple studies on the issue of whether saxagliptin can cause heart failure and general causation is an
issue. Thus, for a causation analysis, it is important to consider whether consistency among the various studies
exists.

3

31 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 32 of 38 - Page ID#: 7129

In his report, Dr. Goyal recognizes that multiple observational studies conducted
after SAVOR have examined the association between saxagliptin and hospitalizations for
heart failure. He does not consider them, however, in his analysis of whether an association
between saxagliptin exposure and heart failure has been consistently reported in studies.
He states that inferences from such studies "are generally limited due to issues related to
confounding by indication and other residual unmeasured confounding issues." (DE 628-3,
Goyal Report at 9.) Dr. Goyal never explains what specific confounding issues exist in each
of the observational studies that he rejected or even explicitly states that the observational
studies present any such issues. At the hearing, Dr. Goyal conceded that the observational
studies were "reasonably designed." (DE 710, Tr. at 90.) He agreed that the observational
studies collectively evaluated over 180,000 patients and that the number of patients was a
strength of the studies. Id. at 91. Neither in his report nor at the hearing was Dr. Goyal
able to identify any defects in any of the individual observational studies. Id. at 106.
Dr. Goyal conceded that no human study had ever confirmed the hospitalization-forheart-failure finding in SAVOR. Id. at 44. He testified that he was aware that no other
clinical trial or observational study confirmed the finding. Id. at 87, 91. Yet he failed to
consider any of these studies in his causation analysis, and he provides no sound rationale
for failing to do so. Failing "to adequately account for contrary evidence is not reliable or
scientifically sound." In re Lipitor (Atorvastatin Calcium) Mktg., Sales Pracs. & Prod. Liab.
Litig., 174 F. Supp. 3d 911, 932 (D.S.C. 2016).
Instead of considering any of the human data contained in the CVOTs other than
SAVOR, the observational studies, or the meta-analyses, Dr. Goyal asserts in his report
that "the best approach" to evaluate consistency is to review "pre-clinical studies to
understand whether there were indicators of heart failure prior to SAVOR." (DE 628-3,

32 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 33 of 38 - Page ID#: 7130

Goyal Report at 9.) The pre-clinical studies he discusses in his report involve only animal
data. (DE 628-3, Goyal Report at 9-10.)
As discussed, however, according to the experts' testimony regarding the evidence
"pyramid," animal studies are inferior evidence compared to observational studies. (Pfs.' Ex.
10.) Dr. Goyal agreed that, in analyzing studies, "the application of the evidence pyramid
needs to be applied." (DE 710, Goyal Test. at 106.) He further agreed that animal studies
are at the very bottom of the pyramid. (DE 710, Goyal Test. at 136.) He testified that he
was not aware of any Bradford Hill analysis that had ever ignored available human data to
determine consistency and had instead looked to animal data. (DE 710, Goyal Test. at 139.)
By failing to consider any of the relevant human data other than SAVOR without
providing any sound rationale for failing to do so, Dr. Goyal violates Rule 702's requirement
that his opinion be based on "sufficient facts or data." Fed. R. Evid. 702. Further, Dr. Goyal
did not know if any of the animal studies he relied on were peer reviewed. (DE 710, Goyal
Test. at 153.) And he conceded that he did not consider peer-reviewed animal studies that
had findings inconsistent with a causal link between saxagliptin and heart failure. (DE 710,
Goyal Test. at 153-56.)
As to the defendants' objections to Dr. Goyal's qualifications to interpret the animal
data, it does not appear that, in any of the studies Dr. Goyal relies on, any animal was
diagnosed with heart failure. Instead, Dr. Goyal undertook to determine himself whether
any animals involved in the studies showed symptoms of heart failure. Dr. Goyal conceded
at the hearing that none of the animal studies specified heart failure as an outcome or
object of the study. (DE 710, Goyal Test. at 140-41.) Dr. Goyal relies on only certain isolated
findings regarding the physical status of the animals and opines that these findings could
be consistent with heart failure in the animals exposed to saxagliptin. For example, he
states that, in one study, anemia and low albium were noted in an unspecified number of
33 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 34 of 38 - Page ID#: 7131

both rodents and monkeys," which "could be suggestive of hemodilution, which is a marker
of heart failure" and that, in another study, an unspecified number of rodents gained
weight in the liver, spleen, and kidney which "could represent congestion . . . which is a
hallmark of heart failure." (DE 628-3, Goyal Report at 9-10) (emphasis added). He finds
"two overt cases of apparent cariogenic shock in monkeys." (DE 628-3, Goyal Report at 10)
(emphasis added). One of the monkeys was determined by the researchers to have died of
ileus, but Dr. Goyal finds that the monkey's symptoms "are highly suggestive of
hypoperfusion that could be seen from a cardiac process." (DE 628-3, Goyal Report at 10)
(emphasis added). As to the other monkey, Dr. Goyal determines that the monkey's
symptoms indicate that "it is highly likely that a cardiac process was a major contributor in
this case." (DE 628-3, Goyal Report at 10.)
Dr. Goyal conceded, however, that he has no expertise in diagnosing heart failure in
animals. (DE 710, Goyal Test. at 141, 147.) He has never studied heart failure in animals.
(DE 710, Goyal Test. at 147.) He conceded that he is not qualified to determine whether the
animals in the studies he considered actually had heart failure. (DE 710, Goyal Test. at
148, 152.) Further, Dr. Goyal agreed that the animal studies regularly use "very large
doses" and, thus, generate findings never seen in humans administered human doses. (DE
710, Goyal Test. at 162-63.) He testified that he did not know how to convert animal dosing
to human dosing. (DE 710, Goyal Test. at 163.)
"Opinions based on animal studies have been rejected because of reservations about
extrapolating from animals to humans or because the plaintiff's extrapolated dose was
lower than the animals' – which is invariably the case because one would have to study
unmanageable, gigantic numbers of animals to see results if animals were not given high
doses." Reference Manual on Scientific Evidence at 23. Animal study results "must be
extrapolated to another species – human beings – and differences in absorption,
34 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 35 of 38 - Page ID#: 7132

metabolism, and other factors may result in interspecies variation in responses." Id. at 563.
Another problem with animal studies is that "the high doses customarily used in animal
studies require consideration of the dose-response relationship and whether a threshold noeffect dose exists. These matters are almost always fraught with considerable, and
currently unresolvable, uncertainty." Id. Dr. Goyal has no expertise in these matters, which
renders his findings from the animal studies unreliable.
Plaintiffs have attempted to downplay Dr. Goyal's reliance on the animal studies. In
response to the motion to exclude, plaintiffs state that defendants "wholly overstate" the
amount that Dr. Goyal relies on animal data for his analysis. They argue that "Dr. Goyal
simply noted relevant preclinical data in his Bradford Hill analysis as potentially being
supportive of the relevant factor." (DE 647, Response at 33.) At the hearing, Dr. Goyal
testified that he simply thought "there were some interesting findings" in the animal
studies and so he included those findings in his report. (DE 707, Goyal Test. at 196.)
Plaintiffs argue in their post-hearing brief that Dr. Goyal did not "assign the animal studies
much weight." (DE 721, Post-Hr'g Br. at 9.)
With the exception of studies regarding TZDs, however, the animal studies are the
only studies other than SAVOR that Dr. Goyal mentions in his Bradford Hill analysis. As to
the studies involving TZDs, Dr. Goyal considers studies involving this class of drugs for his
analogy analysis but not studies involving DPP-4 inhibitors, the drug class to which
saxagliptin belongs. He asserts that "saxagliptin differs from other agents in the DPP4
inhibitor class; so using other DPP4 inhibitors as an analogy would not suffice." (DE 628-3,
Goyal Report at 14.) TZDs, however, are an entirely different class of diabetes drugs than
saxagliptin and other DPP4 inhibitors.
For the analogy analysis, researchers look at analogous drugs to determine whether
those drugs cause the same outcome. Dr Goyal chose TZDs as the analogous drug, not
35 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 36 of 38 - Page ID#: 7133

because of any similarities between saxagliptin and TZDs, but because TZDs "can worsen
heart failure; and thus provide[] an appropriate analogy." (DE 628-3, Goyal Report at 14.)
In other words, Dr. Goyal cherry picked TZDs as a comparison only because they have been
shown to cause the outcome at issue: worsened heart failure. "Result-driven analysis, or
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). “[C]ourts have consistently excluded expert testimony
that ‘cherry-picks’ relevant data." Id. (quoting EEOC v. Freeman, 778 F.3d 463, 469 (4th
Cir. 2015)). This is because such an approach “does not reflect scientific knowledge, is not
derived by the scientific method, and is not ‘good science.'” Id. (quoting In re Bextra &
Celebrex Mktg. Sales Practices & Prods. Liab. Litig., 524 F.Supp.2d 1166, 1176 (N.D. Cal.
2007)).
Another indication that Dr. Goyal's Bradford Hill analysis is not reliable is that he
altered his opinion on several of the factors after writing his report. Regarding the
specificity factor of the analysis, in his report, Dr. Goyal opined that the SAVOR
hospitalization-for-heart-failure finding "provides some reasonable specificity for the causal
link between saxagliptin and heart failure." (DE 628-3, Goyal Report at 11.) In his
deposition, however, he testified that specificity was not met. (DE 710, Goyal Test. at 185.)
And later, at the hearing, he testified that specificity is met if looking only to the "essence
or the spirit of what specificity is about," but that the factor is not met under the "original
1965 Bradford Hill verbiage." (DE 710, Goyal Test. at 5, 125.) As to the biological-gradient
factor, in his report, Dr. Goyal opined that the data "support a biological gradient." (DE
628-3, Goyal Report at 11.) But at the hearing, he testified that this factor is not met. (DE
710, Goyal Test. at 125.) And as to consistency, as discussed, Dr. Goyal opined in his report
36 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 37 of 38 - Page ID#: 7134

that the "best approach remaining to evaluate consistency would be to review pre-clinical
[animal] studies." (DE 628-3, Goyal Report at 9.) At the hearing, however, he analyzed
consistency by looking at findings among various "subgroups" within the SAVOR study
itself. (DE 710, Goyal Test. at 134-35.) In fact, as discussed, the plaintiffs now argue that
Dr. Goyal did not really consider the animal studies at all.
Plaintiffs have not met their burden of showing by a preponderance of the evidence
that 1) Dr. Goyal is qualified by knowledge, skill, experience, training, or education to
interpret animal data in the manner he purports to or 2) that his testimony is reliable.
Accordingly, the motion to exclude Dr. Goyal's testimony will be granted.
III.

Objections under Federal Rule of Evidence 403

Plaintiffs also argue that each of the defendants' experts should be excluded as
cumulative under Federal Rule of Evidence 403. The plaintiffs made clear after the hearing,
however, that they will pursue these arguments closer to trial. Accordingly, the Court does
not address those arguments here.
IV.

Conclusion

For all these reasons, the Court hereby ORDERS as follows:
1) the defendants' motion to exclude the testimony of Dr. Parag Goyal (DE 626) is
GRANTED;
2) the plaintiffs' motion to exclude the testimony of Dr. Suneil Koliwad (DE 630) is
DENIED;
3) the plaintiffs' motion to exclude the testimony of Dr. Eric Adler (DE 633) is
DENIED; and
4) the plaintiffs' motion to exclude the testimony of Dr. Todd Lee (DE 635) is
DENIED.

37 

Case: 5:18-cv-00053-KKC Doc #: 332 Filed: 01/05/22 Page: 38 of 38 - Page ID#: 7135

This 5th day of January, 2022.

38