Onglyza Product Cases ( 2023 )

Filed 4/19/23
CERTIFIED FOR PUBLICATION
IN THE COURT OF APPEAL OF THE STATE OF CALIFORNIA
FIRST APPELLATE DISTRICT
DIVISION FOUR
A165387
ONGLYZA PRODUCT CASES
(City & County of San Francisco
Super. Ct. No. CJC16004909,
JCCP No. 4909)
Plaintiffs Theodore Crites, Gary Gilmore, Ronald White, Yvonne Lyall,
Lisa Hall, Mario Jimenez, Donald Leedy, Curtis Madden, Terry Miles, Paul
Moore, John Okoye, Jose Ramos, Robert Rosencranse, and Barbara
Thompson (collectively plaintiffs) appeal after the trial court granted the
motion for summary judgment by defendants Bristol-Myers Squibb Company,
AstraZeneca Pharmaceuticals LP (AstraZeneca), and McKesson Corporation
(collectively defendants). Plaintiffs alleged injuries from saxagliptin, the
main ingredient found in two medications manufactured and distributed by
defendants to treat type 2 diabetes. The trial court first granted defendants’
motion to exclude plaintiffs’ general causation expert, who opined that
saxagliptin can cause heart failure. Defendants then moved for summary
judgment on the ground that, without expert testimony, plaintiffs could not
show a triable issue of material fact as to general causation. The trial court
agreed, and in the same order denied plaintiffs’ request to enlarge discovery
deadlines to allow them to identify a new causation expert. We affirm.
BACKGROUND
A. SAVOR Study
In 2008, as part of defendants’ application for approval of Onglyza and
Kombiglyze XR, two diabetes drugs with saxagliptin as the active ingredient,
the Endocrinologic and Metabolic Drugs Advisory Committee of the Food and
Drug Administration (FDA) required that defendant AstraZeneca perform a
cardiovascular outcomes study to evaluate saxagliptin treatment in high-
cardiovascular risk patients with type 2 diabetes. Known as SAVOR, it was a
randomized, double-blind, placebo-controlled study that consisted of
16,492 patients with type 2 diabetes who were at high risk of cardiovascular
disease.
SAVOR’s “primary end point was a composite of cardiovascular death,
myocardial infarction, or ischemic stroke.” The study concluded that
saxagliptin did not increase or decrease the risk of these occurrences. In
addition, SAVOR examined various secondary end points that included
hospitalization for heart failure, coronary revascularization, or unstable
angina. Of the 10 secondary end points studied, the only statistically
significant finding was for hospitalization for heart failure. The study
concluded that “[m]ore patients in the saxagliptin group than in the placebo
group were hospitalized for heart failure (3.5% vs. 2.8% . . .).” The study’s
authors, however, noted that this finding “was unexpected and should be
considered within the context of multiple testing that may have resulted in a
false positive result.” The authors further cautioned that the finding “merits
further investigation and needs to be confirmed in other ongoing studies, and
a class effect should not be presumed.”
Following SAVOR, the FDA required that the labels for medications
containing saxagliptin be updated to include a warning for the potential
2
increased risk of heart failure. The warning label for Onglyza was updated to
include text that SAVOR subjects “with a prior history of heart failure and
subjects with renal impairment had a higher risk for hospitalization for heart
failure, irrespective of treatment assignment.” The label then stated,
“[c]onsider the risks and benefits of ONGLYZA prior to initiating treatment
in patients at a higher risk for heart failure.” After the SAVOR finding,
researchers conducted a number of observational studies of large groups of
patients around the world to examine the risk of hospitalization for heart
failure in users of saxagliptin as well as of other similar diabetes
medications.1 They did not find an association between saxagliptin and an
increased risk of hospitalization for heart failure.
Defendants’ scientists also conducted a post hoc analysis of pooled data
from 20 randomized controlled clinical trials of saxagliptin, and concluded
that saxagliptin was not associated with an increased cardiovascular risk,
including heart failure. As a possible explanation for SAVOR’s different
result, they noted that “SAVOR was an event-driven trial in a highly defined
population (prior CV disease or multiple CV risk factors), whereas the
20 clinical trials analyzed in this study had defined treatment periods
ranging from 4 to 206 weeks and included diverse patient populations with
[type 2 diabetes] . . . .”
B. Lawsuits
Patients who took drugs with saxagliptin filed approximately
250 related cases in federal and state courts. Most of these cases were filed
in federal court and consolidated into a federal multidistrict litigation (MDL)
before the United States District Court for the Eastern District of Kentucky,
1Saxagliptin is part of a class of diabetes medications known as DPP-4
inhibitors.
3
with the rest filed in state courts in California and New York. The MDL
court established a discovery plan in which the first phase would consist of
discovery on general causation, including expert discovery and any Daubert2
motions, and ordered the parties to coordinate discovery and other pretrial
proceedings with the related state court cases to avoid duplication and
inconsistency.
A Judicial Council coordination proceeding (JCCP) was established for
the six state court cases filed in California, which later grew to include
13 cases. To conform as much as possible to the MDL’s schedule, the court in
the JCCP followed the MDL’s discovery plan and ordered that the parties
first conduct discovery on the issue of general causation, noting that
litigation would proceed as to other issues only if plaintiffs were able to show
general causation.3
During this first phase of discovery, plaintiffs designated two experts to
support general causation, Dr. Parag Goyal and Dr. Martin Wells. Dr. Goyal
is a cardiologist who was asked to opine whether saxagliptin was capable of
causing heart failure. Answering the question affirmatively, Dr. Goyal relied
on SAVOR’s finding of an increased risk of hospitalization for heart failure.
He also supported his conclusion with a Bradford Hill analysis, a widely-used
methodology to evaluate whether a causal inference can be drawn from
epidemiological studies. The analysis examines nine factors: strength,
consistency, specificity, temporality, biologic gradient, plausibility, coherence,
2 Daubert v. Merrell Dow Pharmaceuticals, Inc. (1993) 509 U.S. 579.
3 “General causation” means that a product is capable of causing the
disease at issue in anyone, as distinguished from “specific causation,” which
means that the product was a substantial factor in bringing about the
plaintiff’s injury. (See Johnson & Johnson Talcum Powder Cases (2019)
37 Cal.App.5th 292, 323–332.)
4
experiment, and analogy. (Green et al., Reference Guide on Epidemiology, in
Reference Manual on Scientific Evidence (3d ed. 2011) 549, 600 (Reference
Guide).)
Dr. Wells is a biostatistician who performed an analysis of SAVOR data
as well as meta-analyses applying SAVOR data. He concluded that the
SAVOR data showed “a significant increase in the risk of hospitalization for
heart failure in the saxagliptin arm in SAVOR at various time points
throughout duration of the study.” He further concluded that the meta-
analyses “strongly support that saxagliptin has a distinct risk for
hospitalization for heart failure profile than the other DPP-4 inhibitor drugs
compared.” Dr. Goyal relied in part on Dr. Wells’ statistical analyses in
forming his opinions.
Defendants designated five experts who all opined that there was
insufficient evidence to demonstrate a causal relationship between
saxagliptin and heart failure.
C. Motion to Exclude Dr. Goyal’s Testimony
Following expert discovery, defendants moved to exclude Dr. Goyal’s
testimony. They argued that Dr. Goyal (1) unreliably found causation based
on the SAVOR study alone while disregarding other human data, including
other clinical trials and the observational studies; (2) analyzed animal data
even though he was unqualified to do so; and (3) misapplied each of the nine
factors of the Bradford Hill analysis. A joint Daubert/Sargon4 hearing took
place in the JCCP and MDL. Dr. Goyal and Dr. Wells both testified at the
hearing regarding their backgrounds, methodologies used, and the opinions
4Sargon Enterprises, Inc. v. University of Southern California (2012)
55 Cal.4th 747 (Sargon).
5
they formed. The court also heard the testimony of three of defendants’ five
causation experts.
Following the hearing, the trial court granted defendants’ motion.5
First, the court held that any “opinions regarding the inferences relevant to
the Bradford Hill analysis that may be drawn from the animal studies went
beyond [Dr. Goyal’s] expertise and were not supported by a reliable
methodology.” Second, the court found unreliable Dr. Goyal’s opinion that
the SAVOR finding alone supports causation, as “epidemiological studies can
demonstrate only association, not causation.” The court also explained why
Dr. Goyal’s application of most of the nine Bradford Hill factors was
unreliable and inadmissible. For example, the “consistency” factor looks at
whether similar findings are generated across multiple epidemiological
studies. In analyzing this factor, Dr. Goyal dismissed certain human studies
and testified that this factor could be established through SAVOR alone since
SAVOR included multiple groups of patients in different settings. In sum,
the court concluded that “Dr. Goyal’s opinion does not contain a reliable
methodology for weighing the evidence but a shifting results-based
methodology that fails to logically and consistently weigh all relevant
evidence.”
D. Motion for Summary Judgment
Defendants then moved for summary judgment on the ground that,
without any expert testimony on general causation, plaintiffs were unable to
show a triable issue of material fact on that issue. In their opposition,
plaintiffs argued that even without Dr. Goyal’s opinion, there was sufficient
5 In this same order, the trial court denied plaintiffs’ motions to exclude
two of defendants’ experts, Dr. Suneil Koliwad and Dr. Eric Adler, and
granted in part plaintiffs’ motion to exclude defendants’ expert, Dr. Todd Lee.
6
evidence to create a triable issue of fact as to whether saxagliptin can cause
heart failure. They pointed to the expert report of Dr. Wells, defendants’
updated saxagliptin label that included a heart failure warning, and a
warning issued by the American Heart Association (AHA) that saxagliptin
could cause heart failure. In the alternative, plaintiffs requested that the
court allow more time for plaintiffs to substitute another expert in place of
Dr. Goyal.
The trial court granted defendants’ motion and denied plaintiffs’
request to designate a new expert. The court held that summary judgment
was proper “because Plaintiffs’ claims rely on general causation, general
causation requires expert testimony, and Plaintiffs are unable to present
expert testimony on general causation.” The court held that Dr. Wells’
testimony was insufficient to support a finding of general causation because
he was unqualified to provide an ultimate opinion that saxagliptin can cause
heart failure.
Plaintiffs now appeal.6
DISCUSSION
A. Standard of Review
Summary judgment is proper “if all the papers submitted show that
there is no triable issue as to any material fact and that the moving party is
entitled to a judgment as a matter of law.” (Code Civ. Proc., § 437c,
subd. (c).) A defendant seeking summary judgment “bears the burden of
persuasion that there is no triable issue of material fact and that he is
entitled to judgment as a matter of law.” (Aguilar v. Atlantic Richfield Co.
6 Plaintiffs initially appealed from the order granting the motion for
summary judgment, which is not appealable. A judgment rendered on the
order however, was entered nunc pro tunc and was filed on January 27, 2023.
7
(2001) 25 Cal.4th 826, 850.) A defendant meets this burden by showing that
the plaintiff “has not established, and cannot reasonably expect to establish”
an essential element of his claim. (Saelzler v. Advanced Group 400 (2001)
25 Cal.4th 763, 768.)
We review a grant of summary judgment de novo, which means we
“decide independently whether the facts not subject to triable dispute
warrant judgment for the moving party as a matter of law.” (Intel Corp. v.
Hamidi (2003) 30 Cal.4th 1342, 1348.) In deciding whether a material issue
of fact exists for trial, we “consider all of the evidence set forth in the papers,
except the evidence to which objections have been made and sustained by
the court, and all inferences reasonably deducible from the evidence.” (Code
Civ. Proc., § 437c, subd. (c).) We view the evidence in the light most
favorable to the plaintiff, as the nonmoving party. (Saelzler v. Advanced
Group 400, supra, 25 Cal.4th at p. 768.)
On the other hand, a trial court’s ruling excluding or admitting expert
testimony is generally reviewed for abuse of discretion. (Sargon, supra,55 Cal.4th at p. 773.) “A ruling that constitutes an abuse of discretion has
been described as one that is ‘so irrational or arbitrary that no reasonable
person could agree with it.’ [Citation.] But the court’s discretion is not
unlimited. . . . Rather, it must be exercised within the confines of the
applicable legal principles.” (Ibid.)
B. Applicable Legal Principles
Trial courts have a “substantial ‘gatekeeping’ responsibility” in
excluding unreliable expert testimony. (Sargon, supra, 55 Cal.4th at p. 769.)
This is to “ensure that an expert’s opinion is based on both reliable material
and sound reasoning.” (Bader v. Johnson & Johnson (2022) 86 Cal.App.5th
1094, 1104.)
8
Evidence Code7 section 801 limits expert testimony to opinions that are
“[r]elated to a subject that is sufficiently beyond common experience that the
opinion of an expert would assist the trier of fact” and “[b]ased on matter . . .
that is of a type that reasonably may be relied upon by an expert in forming
an opinion upon the subject to which his testimony relates.” (§ 801, subds. (a)
& (b).) Section 802 states that a witness, including an expert, may “state on
direct examination the reasons for his opinion and the matter . . . upon which
it is based, unless he is precluded by law from using such reasons or matter
as a basis for his opinion.” In sum, “Evidence Code section 801 governs
judicial review of the type of matter; Evidence Code section 802 governs
judicial review of the reasons for the opinion.” (Sargon, supra, 55 Cal.4th at
p. 771.)
However, “whether the expert opinion is founded on sound logic is not a
decision on its persuasiveness. The court must not weigh an opinion’s
probative value or substitute its own opinion for the expert’s opinion. Rather,
the court must simply determine whether the matter relied on can provide a
reasonable basis for the opinion or whether that opinion is based on a leap of
logic or conjecture. The court does not resolve scientific controversies.
Rather, it conducts a ‘circumscribed inquiry’ to ‘determine whether, as a
matter of logic, the studies and other information cited by experts adequately
support the conclusion that the expert’s general theory or technique is valid.’
[Citation.] The goal of trial court gatekeeping is simply to exclude ‘clearly
invalid and unreliable’ expert opinion.” (Sargon, supra, 55 Cal.4th at p. 772.)
As the high court noted, the focus of the trial court’s inquiry “must be solely
7All further statutory references are to the Evidence Code unless
otherwise specified.
9
on principles and methodology, not on the conclusions that they generate.”
(Daubert v. Merrell Dow Pharmaceuticals, Inc., supra, 509 U.S. at p. 595.)
C. The Trial Court Did Not Abuse its Discretion in Excluding
Dr. Goyal’s Testimony
With those general principles in mind, we now turn to the merits.
Plaintiffs contend that the trial court exceeded its gatekeeping responsibility
in excluding Dr. Goyal’s opinions. Plaintiffs’ primary argument is that, under
the principles set forth in Sargon, supra, 55 Cal.4th 747, Dr. Goyal was
permitted to place more weight on certain evidence, like SAVOR, and less
weight on other evidence, like the human observational studies. They
contend that the trial court could not properly exclude Dr. Goyal’s testimony
on this basis.
While we agree that the trial court may not weigh an expert opinion’s
probative value or persuasiveness, it must still consider whether the opinion
is logically sound. (Sargon, supra, 55 Cal.4th at p. 772.) Here, the trial court
explained in its detailed exclusion order that “Dr. Goyal’s opinion does not
contain a reliable methodology for weighing the evidence but a shifting
results-based methodology that fails to logically and consistently weigh all
relevant evidence.” We find no abuse of discretion.
First, with respect to SAVOR, plaintiffs argue that Dr. Goyal was
permitted to place the most weight on this study because randomized
controlled trials “are the gold standard of evidence-based medicine . . .”
However, in his expert report, Dr. Goyal went one step further and concluded
that the finding from SAVOR alone showed a causal link between saxagliptin
and heart failure. The trial court noted that “epidemiological studies can
demonstrate only association, not causation.” Indeed, “[r]arely, if ever, does a
single study persuasively demonstrate a cause-effect relationship. It is
important that a study be replicated in different populations and by different
10
investigators before a causal relationship is accepted by epidemiologists and
other scientists.” (Reference Guide, supra, at p. 604.) This does not go to the
weight of the evidence, but rather to the reliability of Dr. Goyal’s
methodology in basing his opinion on a type of matter that, by itself, does not
show causation.
Plaintiffs argue that “the law is clear that an expert does not have to
base their opinion upon any specific type of epidemiological evidence to
reliably opine that a drug caused an injury.” They cite Davis v. Honeywell
Internat. Inc. (2016) 245 Cal.App.4th 477, but that case merely held that, in
addition to epidemiological studies, which the court agreed provided the best
evidence of causation in most instances, an expert may also rely on other
evidence such as case series reports, especially if the subject medical
condition or health outcome is very rare. (Id. at p. 491.) The court in any
case found that the plaintiff’s expert reviewed at least three epidemiological
studies to support his opinion that the plaintiff’s exposure to asbestos
contributed to his development of mesothelioma. (Id. at pp. 489-490.)
A trial court does not abuse its discretion in excluding expert testimony
on general causation when the expert’s opinion is based on a single study
that provides no reasonable basis for the opinion offered. (Lockheed
Litigation Cases (2004) 115 Cal.App.4th 558, 564–565.) Here, SAVOR’s own
authors stated that the finding of increased hospitalization for heart failure
among saxagliptin users “was unexpected and should be considered in the
context of multiple testing that may have resulted in a false positive result”
and “needs to be confirmed in other ongoing studies . . . .” They therefore
11
rejected the notion that the SAVOR study alone established a causal link.8 In
his rebuttal report, Dr. Goyal agreed that reproducibility of SAVOR’s finding
was important for determining causation and that replication of the finding
was “urgently needed,” but stated that there has been “no additional peer-
reviewed data on this” since SAVOR. At the hearing, Dr. Goyal agreed that
consistency in findings was an important factor in determining causation,
that any experimental finding should not be relied upon until it has been
independently replicated, and that SAVOR’s finding of increased heart
failure could have been chance. We do not hold that one randomized
controlled trial is never sufficient to establish general causation, but on this
record, the trial court did not abuse its discretion in finding that Dr. Goyal’s
reliance on SAVOR alone to establish general causation was logically
unsound, especially given Dr. Goyal’s own agreement that SAVOR’s finding
needed to be replicated in order to determine causation.
Second, plaintiffs argue that Dr. Goyal reliably performed the Bradford
Hill analysis, an accepted methodology that was also used by defendants’ own
experts. They again argue that the trial court improperly excluded
Dr. Goyal’s opinions based on the weight he placed on certain evidence under
this analysis. The court’s order, however, explained that its decision was
based on various methodological defects it found in Dr. Goyal’s application of
8 At oral argument, plaintiffs’ counsel argued that in a subsequent 2014
publication, these same authors noted there was a “statistically significant
difference between the 2 [SAVOR] groups after post hoc adjustment for
multiple comparisons.” However, this same article also reaffirmed the risk of
a “ ‘false positive’ result” and that the observation of increased heart failure
in saxagliptin users “was unexpected and requires confirmation with several
ongoing cardiovascular outcomes trials.” Therefore, the publication does not
change the calculus about whether the SAVOR study establishes that
saxagliptin can cause heart failure.
12
six of the nine Bradford Hill factors, and that because he failed to weigh them
together, it could not identify any predicate opinion on a specific factor that
was not essential to his ultimate opinion. As a result, it concluded that
methodological defects in any of the factors would upset the ultimate opinion
on causation. This was a proper exercise of the court’s gatekeeping
responsibility. We discuss Dr. Goyal’s application of some of these factors
below.
“Strength of association” examines how strong the association is
between the exposure and the disease. “The higher the relative risk, the
greater the likelihood that the relationship is causal. For cigarette smoking,
for example, the estimated relative risk for lung cancer is very high, about
ten.” (Reference Guide, supra, at p. 602.) Here, SAVOR found the hazard
ratio for hospitalization for increased heart failure to be 1.27. Although
Dr. Goyal opined that SAVOR was a reliable study for assessing strength, his
report did not conclude whether a 1.27 hazard ratio reflected a strong or
weak association. When asked about this factor at his deposition, Dr. Goyal
could not say whether 1.27 was a strong association and testified that the
word “strong” was too subjective for him to interpret. The trial court
therefore found that Dr. Goyal had not actually given an opinion as to
strength and that he was “refusing to engage with a factor of the Bradford
Hill analysis on its terms.”
“Consistency,” as Dr. Goyal’s own report explains, “is upheld when the
same finding is shown in multiple studies across different populations and
settings.”9 On this factor, Dr. Goyal disregarded inconsistent data from other
9Plaintiffs criticize the trial court for interpreting consistency to
require replication despite Dr. Goyal’s own admission that replication of the
same finding is required in order to find consistency.
13
human studies and relied on data from preclinical animal studies, opining
that this was “the best approach” for evaluating consistency. The trial court
noted, however, that Dr. Goyal conceded that he was not qualified to
interpret animal data, and that the animal studies had the same defect
Dr. Goyal cited to justify disregarding the human studies—namely, that
cardiovascular safety was not a primary focus. Moreover, at the
Daubert/Sargon hearing, Dr. Goyal offered a new and different opinion from
the one in his report, contending that consistency was met through the
SAVOR study alone since SAVOR looked at different populations across
16,000 patients. The trial court again concluded that Dr. Goyal did not apply
the “consistency” factor on its own terms, since it requires the same finding
across different studies with different researchers using different
methodologies. This conclusion was not based on the weight Dr. Goyal
assigned to different evidence, but the unreliability of his shifting, results-
based methodology.
“Specificity” is met “if the exposure is associated only with a single
disease or type of disease.” (Reference Guide, supra, at p. 604.) Or, as
Dr. Goyal explained, “only one cause should be leading to a single effect.” His
report stated this factor was supported because SAVOR was “a large,
prospective, ‘gold standard’ RCT, designed in part to assess an association
between saxagliptin and hospitalization for heart failure.” At his deposition,
when asked whether the specificity criterion was met, Dr. Goyal responded
no. At the hearing, Dr. Goyal testified that “as much as we now know about
science and medicine, you know, there’s very few things where one cause
actually only has a single effect.” He then testified that specificity was
nonetheless met through SAVOR because “the randomized controlled trial
allows you to fulfill that criterion.” Similar to his “strength of association”
14
analysis, the trial court criticized Dr. Goyal’s redefinition of this factor and
his analysis as “another example of Dr. Goyal refusing to engage with a factor
of the Bradford Hill analysis on its terms.”
As stated in Dr. Goyal’s report, “[b]iological gradient refers to a dose-
response relationship between the exposure and outcome,” or in other words,
whether greater amounts of the putative cause are associated with increases
in the occurrence of the disease or harm. The report cited data from the pre-
clinical animal studies to support this factor, but the trial court held that
Dr. Goyal could not offer this opinion because, as discussed above, he was
unqualified to interpret animal data. At the Daubert/Sargon hearing, he
instead testified that there was an absence of data as to this factor and that it
was “hard to say in either direction.” The trial court observed that the
change in Dr. Goyal’s opinions between the time of his report and the hearing
underscored its concerns about their reliability, but it found admissible his
opinion that there was insufficient human data to evaluate this factor.
Biological plausibility refers to whether there is a plausible biological
mechanism to explain a cause and effect relationship between exposure and
disease. The report stated there were “multiple published, proposed
biological mechanisms.” The trial court noted that the strongest mechanism
Dr. Goyal could identify was only “a proposed hypothesis.” Plaintiffs contend
that “the trial court improperly held him to a higher standard than Sargon
requires because he does not have to prove the mechanism with certainty to
opine as to biological plausibility.” But the court did not exclude Dr. Goyal’s
opinions due to a lack of certainty; it found that he did “not undertake an
analysis of whether the data that exists supports or undermines his opinion
that the proposed mechanisms are plausible,” and conceded that data from
cardiovascular outcome trials weighed against his underlying premise that
15
hospitalization for heart failure was “a class-wide effect” across all DPP-4
inhibitors. As a result, the trial court found Dr. Goyal’s opinion to be
unreliable.
“Analogy” considers whether there have been associations found
between a related or similar substance to the one at issue and the disease or
outcome. With respect to saxagliptin and heart failure, Dr. Goyal contended
it was most relevant to examine “known links between other anti-diabetes
drugs and heart failure.” A number of human observational studies
conducted after SAVOR found no association between increased
hospitalization for heart failure and DPP-4 inhibitors. Dr. Goyal, however,
stated that it would not suffice to use other DPP-4 inhibitors as an analogy
because “saxagliptin differs from other agents in the DPP-4 inhibitor class.”
Instead, Dr. Goyal analogized saxagliptin to thiazolidinediones (TZDs), a
different class of diabetes medications that has been linked to an increased
risk of heart failure. However, he conceded that, while they have some
similarities, TZDs and DPP-4 inhibitors differ in many ways and do not
address or treat diabetes in the same way. The trial court reasonably
concluded that this opinion was not reliable because the only reason for
Dr. Goyal to analogize saxagliptin to TZDs rather than to other DPP-4
inhibitors was that the former supported his ultimate conclusion on causation
and the latter did not.
The trial court did not exceed its gatekeeping authority in concluding
that Dr. Goyal’s opinions were unreliable and inadmissible. Again, it was not
the weight afforded to certain evidence that the trial court found problematic,
but the shifting and unsound methodology Dr. Goyal utilized in weighing the
evidence. For example, in order to opine that “strength” and “specificity”
were satisfied, Dr. Goyal did not engage with these factors on their own
16
terms, but redefined their meanings so that SAVOR’s finding could support
his conclusions. As already discussed, SAVOR’s finding alone does not
support general causation.
In Lockheed Litigation Cases, supra, 115 Cal.App.4th 558, the court
explained that though the expert relied on an epidemiological study, the
study itself “must provide a reasonable basis for the particular opinion
offered, and . . . an expert opinion based on speculation or conjecture is
inadmissible.” (Id. at p. 564.) There, the plaintiffs alleged that their
occupational exposure to five chemicals manufactured and supplied by the
defendants caused personal injuries. (Id. at pp. 561, 565.) Plaintiffs’ expert
relied on a single study to find causation, but the study itself reviewed the
association between painters’ exposure to more than 130 different chemicals
and the increased risk of cancer. (Id. at p. 564.) Because the study provided
no reasonable basis for the expert opinion that the five specific chemicals to
which the plaintiffs were exposed caused an increased risk of cancer, the
court found that the trial court’s exclusion of the plaintiffs’ expert was not an
abuse of discretion. (Id. at p. 565.) Here, for different reasons, the trial court
also found Dr. Goyal’s reliance on the SAVOR study to be unsound and his
application of the Bradford Hill factors to be unreliable.
In San Francisco Print Media Co. v. The Hearst Corp. (2020)
44 Cal.App.5th 952, our colleagues in Division Three emphasized that, when
exercising its gatekeeping role, the trial court does not weigh an expert
opinion’s persuasiveness but instead “must focus on principles and
methodology to determine whether the opinion is founded on sound
logic . . . .” (Id. at p. 962.) There, the court found no abuse of discretion in the
trial court’s exclusion of the plaintiff’s expert because his analysis and
methodology “suffered from a clear foundational problem” and was “not the
17
mark of an opinion rooted in sound logic.” (Id. at p. 963.) Likewise, here, the
trial court found serious flaws in Dr. Goyal’s methodology where he “failed to
engage in a candid weighing of the evidence, choosing instead to avoid
mentioning facts or entertaining conclusions that weighed against an
ultimate conclusion of general causation.” This methodology resulted in an
unsound and unreliable opinion.
In sum, we conclude that, in evaluating Dr. Goyal’s application of the
Bradford Hill criteria, the trial court did not impermissibly weigh the
evidence but considered whether Dr. Goyal’s methodology was reliable.
D. Summary Judgment Was Properly Granted
1. Dr. Wells’ Expert Testimony is Insufficient to Create a Triable
Issue
Plaintiffs next argue that, even without Dr. Goyal’s testimony, the
unchallenged testimony of their second expert, Dr. Wells, was sufficient to
raise a triable issue of fact as to general causation. Dr. Wells is a
biostatistician who performed an analysis of SAVOR data and meta-analyses
applying SAVOR data that Dr. Goyal relied on in part in forming his opinions
as to general causation. Though Dr. Wells concluded that data from SAVOR
showed an association between saxagliptin and “a significant increase in the
risk of hospitalization for heart failure,” he testified that he was not asked to
provide an opinion as to medical causation because “[h]eart failure is
complicated” and doctors are the ones who have the training and expertise to
make that assessment, not him. Dr. Wells later reiterated that he was not
qualified to provide an opinion as to general causation.
As a heart failure cardiologist, whether saxagliptin was capable of
causing heart failure was within Dr. Goyal’s area of expertise, and plaintiffs
tasked him with examining all the evidence, including Dr. Wells’ statistical
analyses, to determine whether the association between saxagliptin and
18
increased heart failure reflected causation under the Bradford Hill factors.
We therefore find that Dr. Wells’ testimony alone does not create a triable
issue of fact as to general causation.
2. Plaintiffs’ Non-Expert Evidence is Insufficient to Create a
Triable Issue
In addition to Dr. Wells’ testimony, plaintiffs contend that there is
other non-expert evidence showing saxagliptin is capable of causing heart
failure that is sufficient to withstand a motion for summary judgment. We
disagree.
First, “[t]he law is well settled that in a personal injury action
causation must be proven within a reasonable medical probability based upon
competent expert testimony.” (Jones v. Ortho Pharmaceutical Corp. (1985)
163 Cal.App.3d 396, 402 (Jones).) This is especially true when the cause of a
disease or harm “is beyond the experience of laymen and can only be
explained through expert testimony.” (Id. at p. 403.) Summary judgment
may be proper in such a case where a plaintiff’s causation expert has been
excluded. (Lowery v. Kindred Healthcare Operating, Inc. (2020)
49 Cal.App.5th 119, 121.)
In Jones, supra, 163 Cal.App.3d 396, 403, the court held that “ ‘the
unknown and mysterious etiology of cancer’ is beyond the experience of
laymen and can only be explained through expert testimony.” (Id. at p. 403.)
Plaintiffs attempt to distinguish Jones by arguing that the issue in that case
was specific causation—whether the plaintiff’s ingestion of an oral
contraceptive caused her to develop cancer. (Id. at p. 401.) The court’s
reasoning, however, applies equally to the necessity of expert testimony to
explain the causes of heart failure—which, as Dr. Goyal himself testified, is
complicated to figure out even for a heart failure doctor. Indeed, admissible
expert testimony must first be provided to show “that defendants’ products
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were capable of causing the disease at issue, in anyone. Without any
evidence demonstrating the [product] was even capable of causing disease,
the experts could not reliably conclude the [product] caused the plaintiff’s
disease, even if other known causes were ruled out.” (Johnson & Johnson
Talcum Powder Cases, supra, 37 Cal.App.5th at p. 330.) In general, expert
testimony is required to establish general causation in products liability
cases. (In re Mirena IUD Prods. Liab. Litig. (S.D.N.Y. 2016) 202 F.Supp.3d
304, 310.)
“In contrast, if causation presents a question that is within the common
knowledge of persons of ordinary education, then expert testimony is not
required.” (Kaney v. Custance (2022) 74 Cal.App.5th 201, 217.) For example,
whether the absence of a handrail in a stairway and/or the size of the risers
caused plaintiff to fall down the stairs was within common knowledge and
therefore did not require expert testimony to establish causation. (Ibid.)
Likewise, “the question whether the absence of seat belt restraint . . .
constituted proximate cause of plaintiff’s claimed injuries, was one of such
common knowledge that persons of ordinary education could reach an
intelligent answer.” (McNeil v. Yellow Cab Co. (1978) 85 Cal.App.3d 116,
118.) Here, however, whether a diabetes medication like saxagliptin is
capable of causing heart failure in anyone is beyond the common knowledge
of persons of ordinary education. It is a highly complicated issue, as
plaintiffs’ own experts recognized.
Plaintiffs cite various cases in support of their argument that non-
expert evidence can create a triable issue of material fact as to general
causation. These cases, however, do not in fact support plaintiffs’
proposition. In Cooper v. Takeda Pharmaceuticals America, Inc. (2015)
239 Cal.App.4th 555, 577–578, for example, the court confirmed the holding
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in Jones, supra, 163 Cal.App.3d 396, that expert testimony is required to
establish causation in cases involving cancer. Moreover, while the court
there held that the trial court erred in finding that the epidemiological
studies relied on by the expert did not provide reasonable bases for his
causation opinion (Cooper, at p. 587), it is readily distinguishable. The court
found that “the trial court’s rejection of these studies was too simplistic,
because it did not take into account the varied scientific principles involved in
determining the validity of the studies.” (Id. at p. 588.) The court further
emphasized the importance of considering a body of studies as a whole,
because “any one study can be criticized, but if most studies consistently
reach a similar answer, that gives confidence to an epidemiologist that the
answer is correct.” 10 (Id. at p. 590.) As discussed above, here there have
been no subsequent studies done after SAVOR that confirmed the association
found between saxagliptin and increased heart failure.
In Monroe v. Zimmer U.S. Inc. (E.D.Cal. 2011) 766 F.Supp.2d 1012,
1029–1031, the court held that the plaintiff established a material issue of
fact regarding general causation based on admissible testimony from
plaintiffs’ two causation experts. In Sellers v. Bayer Healthcare Pharms. Inc.
(W.D.Mo., Feb. 9, 2017, No. 4:14-cv-00954-SRB) 2017 U.S. Dist.
Lexis 144168, the court, as plaintiffs highlight, found that warning labels on
similar drugs created “a genuine issue of material fact concerning Bayer’s
knowledge of a known or knowable risk in connection with Plaintiff’s failure
to warn claim.” (Id. at p. *14.) A failure to warn is not the subject of this
appeal. With respect to the relevant issue of causation, the court held that
10 This consideration further supports the importance of replicating the
result of a study before a causal relationship can be established or accepted in
the scientific community, as noted in the Reference Guide. (Reference Guide,
supra, at p. 604.)
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the testimony of the plaintiff’s expert “demonstrat[ed] a significant connection
between the conduct that occurred and the injury alleged by plaintiff.” (Id.
at p. *10.)
Because expert testimony is required to show general causation in this
case, we need not consider plaintiffs’ argument that there is substantial non-
expert evidence to support general causation.11 Even if we did consider such
evidence, it does not support the claim that saxagliptin can cause heart
failure. For example, plaintiffs argue that defendants’ updated saxagliptin
label admits that saxagliptin is capable of causing heart failure. However,
the updated label summarizes the findings from SAVOR and then states:
“Consider the risks and benefits of ONGLYZA prior to initiating treatment in
patients at a higher risk for heart failure.” Likewise, the statements made by
SAVOR’s authors, which plaintiffs also argue is an admission of causation,
cautioned that the unexpected finding of increased heart failure may be a
“false positive result” that needs to be further investigated and confirmed in
other studies.
Finally, plaintiffs point to statements issued by the AHA and FDA
following SAVOR which indicate that saxagliptin may cause or increase the
risk of heart failure. These are insufficient to create a triable issue as to
11 Plaintiffs have requested that we take judicial notice of the 2022
“Guideline for the Management of Heart Failure” published by the AHA,
American College of Cardiology, and Heart Failure Society of America
(Guideline). Defendants oppose the request. We deny the request. Plaintiffs
acknowledge that we could not properly take judicial notice of the material
for the truth of its contents, but fail to articulate in what other way it is
relevant to the issues on appeal. Moreover, the Guideline is duplicative of a
2016 statement by the AHA already in the record that noted SAVOR’s finding
of increased hospitalization for heart failure among saxagliptin users and
listed saxagliptin as one of the medications “that may cause or exacerbate
HF” based on this finding. The Guideline merely repeats this statement.
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general causation. First, neither the AHA nor FDA explicitly stated that
saxagliptin was capable of causing heart failure. Second, the AHA and FDA’s
statements regarding saxagliptin and heart failure were both based on
SAVOR’s finding alone which, as discussed above, does not support
causation. Logically, any warnings based only on SAVOR also cannot
support causation, and plaintiffs cannot attempt to circumvent the
shortcomings of SAVOR by pointing to other evidence that merely relies on
SAVOR’s finding. Again, any opinion as to causation requires expert
testimony, which has been excluded here.
3. The Trial Court Did Not Abuse Its Discretion in Denying
Plaintiffs’ Request for Continuance
Lastly, we review for abuse of discretion the trial court’s denial of
plaintiffs’ request to enlarge discovery deadlines in order to designate a new
expert. (Johnson v. Alameda County Medical Center (2012) 205 Cal.App.4th
521, 531.) We find none here, as plaintiffs were afforded ample time during
the first phase of discovery to designate general causation experts and to
conduct expert discovery. Plaintiffs designated Dr. Goyal as their only expert
to opine that saxagliptin can cause heart failure, and sought to identify a new
expert only after Dr. Goyal was excluded. Although the court’s decision to
exclude Dr. Goyal may have been unexpected to plaintiffs, they made the
strategic decision to identify only one expert in this area, despite knowing
how crucial it was to prevail on the issue of general causation. The trial court
did not abuse its discretion in concluding that allowing plaintiffs to designate
a new expert would prejudice defendants given the amount of time and
resources needed to conduct additional expert discovery and likely another
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round of Daubert/Sargon briefing and hearings.12
DISPOSITION
The judgment is affirmed. Defendants shall recover their costs on
appeal.
GOLDMAN, J.
WE CONCUR:
BROWN, P. J.
WHITMAN, J.*
12 Plaintiffs’ reliance on Oliveros v. County of Los Angeles (2004)
120 Cal.App.4th 1389 is inapposite, as that case involved a motion to
continue trial by a few weeks due to an unexpected trial conflict that had
arisen for the defendant’s counsel. (Id. at p. 1393.) The trial court denied the
motion despite this showing of good cause and despite having received no
objection to this brief continuance from opposing counsel. (Ibid.)
*Judge of the Superior Court of California, County of Alameda, assigned by
the Chief Justice pursuant to article VI, section 6 of the California
Constitution.
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Trial Court: City and County of San Francisco
Superior Court
Trial Judge: Honorable Anne-Christine Massullo
Counsel for Plaintiffs and MOORE LAW GROUP, Jennifer A.
Appellants: Moore, Ashton Rose Smith
TOSI LAW, Timothy M. Clark
MILBERG COLEMAN, BRYSON
PHILLIPS GROSSMAN, Lauren A.
Welling
Counsel for Defendants and COVINGTON & BURLING, Jeffrey M.
Respondents: Davidson, Paul W. Schmidt, Phyllis A.
Jones, Emily Ullman
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