                      FOR PUBLICATION

    UNITED STATES COURT OF APPEALS
         FOR THE NINTH CIRCUIT


 STEPHEN WENDELL; LISA                              No. 14-16321
 WENDELL, for themselves and as
 successors-in-interest to Maxx                      D.C. No.
 Wendell, deceased,                             4:09-cv-04124-CW
              Plaintiffs-Appellants,

                     v.                               OPINION

 GLAXOSMITHKLINE LLC; TEVA
 PHARMACEUTICALS USA, INC.,
          Defendants-Appellees.


         Appeal from the United States District Court
           for the Northern District of California
          Claudia Wilken, District Judge, Presiding

          Argued and Submitted September 16, 2016
                  San Francisco, California

                          Filed June 2, 2017

 Before: Ronald M. Gould and Marsha S. Berzon, Circuit
   Judges, and William K. Sessions III,* District Judge.

                     Opinion by Judge Gould

     *
       The Honorable William K. Sessions III, United States District Judge
for the District of Vermont, sitting by designation.
2               WENDELL V. GLAXOSMITHKLINE

                            SUMMARY**


               Expert Testimony / Duty to Warn

    The panel reversed the district court’s summary judgment
in favor of Teva Pharmaceuticals USA, Inc., and the
dismissal, as moot, of plaintiffs’ motion to reconsider, in an
action alleging negligence and strict liability concerning the
manufacture and distribution of drugs that were used to treat
plaintiffs’ deceased son, Maxx Wendell, for inflammatory
bowel disease.

    Plaintiffs alleged that the drugs caused Maxx Wendell to
develop Hepatosplenic T-cell lymphoma, and that the
manufacturers and distributors did not give adequate
warnings about the risks associated with the drugs. The
district court granted summary judgment for Teva because the
testimony of plaintiffs’ causation experts was not reliable and
not admissible under Fed. R. Evid. 702, and because plaintiffs
did not present evidence that Maxx’s prescribing physician
relied on Teva’s warning labels.

    The panel held that the district court erred by excluding
the experts’ testimony. The panel held that the district court
looked too narrowly at each individual consideration under
Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 589
(1993), without taking into account the broader picture of the
experts’ overall methodology. Specifically, the panel held
that the district court improperly ignored the experts’
experience, reliance on a variety of literature and studies, and

    **
       This summary constitutes no part of the opinion of the court. It has
been prepared by court staff for the convenience of the reader.
              WENDELL V. GLAXOSMITHKLINE                      3

review of Maxx’s medical records and history, as well as the
fundamental importance of differential diagnosis by
experienced doctors treating troubled patients. The panel
further held that the district court overemphasized certain
facts; and taken together, these mistakes warranted reversal.
The panel concluded that the proposed testimony was
sufficiently reliable, and plaintiffs’ experts should have been
allowed to testify under Daubert, and admitted as expert
testimony under Fed. R. Evid. 702.

    The panel reversed the district court’s summary judgment
to Teva on the duty to warn claim. The panel held that under
California law, viewing the evidence in the light most
favorable to plaintiffs, there was a genuine dispute of material
fact as to whether the prescribing physician’s conduct would
have changed with warnings from Teva, and its predecessor
GlaxoSmithKline LLC.

    The panel declined to affirm the district court’s judgment
on alternative grounds, and held that Teva may raise the
issues with the district court on remand.

    Finally, the panel reversed the district court’s denial of
plaintiffs’ motion for reconsideration, and remanded.
4                WENDELL V. GLAXOSMITHKLINE

                              COUNSEL

Michael J. Quirk (argued), Williams Cuker Berezofsky LLC,
Philadelphia, Pennsylvania; Kevin Haverty, Williams Cuker
Berezofsky LLC, Cherry Hill, New Jersey; for Plaintiffs-
Appellants.

Alan J. Lazarus (argued) and William A. Hanssen, Drinker
Biddle & Reath LLP, San Francisco, California, for
Defendant-Appellee GlaxoSmithKline, LLC.

Jeffrey F. Peck (argued) and Prentiss W. Hallenback, Jr.,
Ulmer & Berne LLP, Cincinnati, Ohio, for Defendant-
Appellee Teva Pharmaceuticals USA, Inc.


                              OPINION

GOULD, Circuit Judge:

     Maxx Wendell1 tragically died at the age of 21 of
Hepatosplenic T-cell lymphoma (HSTCL), an exceedingly
rare and aggressive form of cancer. For many years before
his development of HSTCL, Maxx was treated with a
combination of drugs for inflammatory bowel disease. After
his death, his parents, Stephen and Lisa Wendell (Plaintiffs),
sued the manufacturers and distributors of these drugs,
asserting claims under California law for negligence and
strict liability. Plaintiffs alleged that the drugs caused Maxx
to develop HSTCL and that the manufacturers and



    1
        We refer to Maxx Wendell by his first name to avoid confusion.
                 WENDELL V. GLAXOSMITHKLINE                                5

distributors did not give adequate warnings about the risks
associated with the drugs.

     The district court granted summary judgment to Teva
Pharmaceuticals USA, Inc. (Teva), concluding that the
Plaintiffs did not present admissible expert testimony of
causation and did not show that Maxx’s prescribing physician
relied on the warning labels. For the same reasons, the
district court dismissed as moot Plaintiffs’ motion for leave
to file a motion for reconsideration of the district court’s prior
order granting summary judgment to GlaxoSmithKline LLC
(GSK). We reverse and remand.

                                     I

    In 1998, at the age of twelve, Maxx was diagnosed with
a form of inflammatory bowel disease (IBD) called ulcerative
colitis. IBD is an autoimmune disease characterized by
chronic inflammation. Maxx began treatment with Dr.
Edward Rich, a pediatric gastroenterologist at Kaiser
Permanente in San Francisco. Relevant here, in June 1999,
Dr. Rich prescribed mercaptopurine (6-MP), an
immunosuppressant, and one of a class of drugs known as
thiopurines. At the time, 6-MP was manufactured by GSK
and marketed as Purinethol. Although it has been widely
used off-label since 1980 to treat IBD,2 Purinethol has never
received approval for this use.

   In July 2002, Dr. Rich prescribed an additional drug, the
tumor necrosis factor alfa antagonist (anti-TNF) drug


    2
      Off-label use of a drug is legal, and is “generally based on published
scientific reports purporting to show a beneficial effect of the drug in such
indications or patient populations.”
6            WENDELL V. GLAXOSMITHKLINE

infliximab, marketed as Remicade. Anti-TNF drugs are
approved to treat various autoimmune disorders, such as
Crohn’s disease and rheumatoid arthritis.

    Maxx received his last dose of Remicade in March 2006,
after which his IBD went into remission. Two months later,
the Food and Drug Administration approved a new label for
the drug.      The label included a warning reporting
postmarketing cases of HSTCL in young male patients with
Crohn’s disease treated with both Remicade and a thiopurine
such as 6-MP or azathioprine. Centocor, the maker of
Remicade, also issued a “Dear Health Care Provider” letter
alerting prescribers to the labeling change and giving more
details on the cases of HSTCL. When Maxx’s symptoms
returned, Dr. Rich prescribed another anti-TNF drug, Humira,
which Maxx took until June 2007. At the time Dr. Rich
prescribed Humira, its label did not warn of the risk of
HSTCL.

    Maxx remained continuously on 6-MP from June 1999
until about March or April 2007. GSK stopped marketing
Purinethol on July 1, 2003, and transferred ownership rights
for the drug to Teva. Maxx continued on Teva’s Purinethol
until July 2004, when Dr. Rich switched him to a generic 6-
MP. According to Maxx’s mother, Maxx decided to stop
taking 6-MP in 2007 after reading in Men’s Health that
young men on a combination of Remicade and other
immunosupressive medication had developed HSTCL.

    In July 2007, Maxx checked into the emergency room
with fevers, fatigue, and malaise. Several days later he was
diagnosed with HSTCL—a non-Hodgkin’s lymphoma that is
exceedingly rare and aggressive. It has “low responses to
chemotherapy, frequent relapses after contemporary
             WENDELL V. GLAXOSMITHKLINE                      7

treatments and the inability of the majority of the patients to
undergo bone marrow transplantation.” Most patients die
within the first year of diagnosis; only a very small fraction
achieve long-term survival. Maxx died from HSTCL on
December 6, 2007, at the age of 21.

    In July 2009, Plaintiffs, Maxx’s parents, sued multiple
drug companies in Superior Court in California. The case
was removed to federal court in September 2009. Plaintiffs
filed the operative fourth amended complaint in April 2011.
Several defendants, including GSK and Teva, then moved for
summary judgment. The district court granted the motion,
but subsequently withdrew its summary judgment order in
light of Plaintiffs’ need for further discovery. In July 2012,
after reviewing new evidence, the district court denied the
motion for summary judgment as to Teva and two other drug
companies, Par Pharmaceutical, Inc. and Abbott Laboratories.
The court granted summary judgment to GSK because it
determined that Plaintiffs had not presented sufficient
evidence that a reasonable jury could find GSK had a duty to
warn of the risk of HSTCL before July 1, 2003, when GSK
stopped distributing Purinethol. A year later, the district
court granted summary judgment to Par Pharmaceuticals.

    In January 2014, the remaining defendants—including
Teva—filed another motion for summary judgment.
Plaintiffs settled their claims against the remaining
defendants, except for Teva, before the district court ruled on
the motion for summary judgment.

    On June 30, 2014, the district court granted Teva’s
motion for summary judgment because the testimony of
Plaintiffs’ causation experts, Dr. Andrei Shustov and Dr.
Dennis Weisenburger, was not reliable and therefore not
8             WENDELL V. GLAXOSMITHKLINE

admissible under Federal Rule of Evidence 702, and because
Plaintiffs did not present evidence that Maxx’s prescribing
physician relied on Teva’s warning labels. It also denied
Plaintiffs’ motion for leave to file a motion for
reconsideration of the Court’s July 2012 order granting
summary judgment to GSK. Plaintiffs filed a timely notice
of appeal, challenging the district court’s grant of summary
judgment to Teva and its denial of their motion for leave to
file a motion for reconsideration.

                              II

    We review the district court’s ruling on the admissibility
of expert testimony for an abuse of discretion. Messick v.
Novartis Pharm. Corp., 747 F.3d 1193, 1196 (9th Cir. 2014).
However, we “review de novo the ‘construction or
interpretation of . . . the Federal Rules of Evidence, including
whether particular evidence falls within the scope of a given
rule.’” Id. (alteration in original) (quoting United States v.
Durham, 464 F.3d 976, 981 (9th Cir. 2006)). We also review
de novo the district court’s grant of summary judgment. Id.
at 1199.

                              III

    The issues presented in this appeal arise under the Federal
Rules of Evidence and California substantive law. See Motus
v. Pfizer Inc. (Roerig Div.), 358 F.3d 659, 660 (9th Cir. 2004)
(explaining that in diversity actions the court applies state
substantive law and the federal rules of procedure). We begin
with the rules of evidence.
             WENDELL V. GLAXOSMITHKLINE                     9

                              A

    Federal Rule of Evidence 702 governs expert testimony.
It provides:

       A witness who is qualified as an expert by
       knowledge, skill, experience, training, or
       education may testify in the form of an
       opinion or otherwise if:

           (a) the expert’s scientific, technical, or
           other specialized knowledge will help the
           trier of fact to understand the evidence or
           to determine a fact in issue;

           (b) the testimony is based on sufficient
           facts or data;

           (c) the testimony is the product of reliable
           principles and methods; and

           (d) the expert has reliably applied the
           principles and methods to the facts of the
           case.

Fed. R. Evid. 702.

    Pursuant to the Federal Rules of Evidence, the district
court judge must ensure that all admitted expert testimony is
both relevant and reliable. See Daubert v. Merrell Dow
Pharm., Inc., 509 U.S. 579, 589 (1993). Defendants do not
contest that the opinions of Dr. Weisenburger and Dr.
Shustov are relevant; the only question, therefore, is whether
they are reliable.
10            WENDELL V. GLAXOSMITHKLINE

    Scientific evidence is reliable “if the principles and
methodology used by an expert are grounded in the methods
of science.” Clausen v. M/V New Carissa, 339 F.3d 1049,
1056 (9th Cir. 2003). The focus of the district court’s
analysis “must be solely on principles and methodology, not
on the conclusions that they generate.” Daubert, 509 U.S. at
595. As we explained in Daubert v. Merrell Dow
Pharmaceuticals, Inc., the court’s “task . . . is to analyze not
what the experts say, but what basis they have for saying it.”
43 F.3d 1311, 1316 (9th Cir. 1995) (hereinafter Daubert II).

     To assist courts with this task, the Supreme Court has
listed several non-exclusive factors that judges can consider
when determining whether to admit expert testimony under
Rule 702. See Daubert, 509 U.S. at 593–95. These include:
“whether the theory or technique employed by the expert is
generally accepted in the scientific community; whether it’s
been subjected to peer review and publication; whether it can
be and has been tested; and whether the known or potential
rate of error is acceptable.” Daubert II, 43 F.3d at 1316. We
also consider whether experts are testifying “about matters
growing naturally” out of their own independent research, or
if “they have developed their opinions expressly for purposes
of testifying.” Id. at 1317. These factors are illustrative, and
they are not all applicable in each case. Id. The inquiry is
“flexible,” Daubert, 509 U.S. at 594, and “Rule 702 should be
applied with a ‘liberal thrust’ favoring admission,” Messick,
747 F.3d at 1196 (quoting Daubert, 509 U.S. at 588).

     The district court concluded that the expert testimony of
Dr. Shustov and Dr. Weisenburger did not meet the Daubert
standard of reliability. The district court first focused on the
fact that the experts developed their opinions specifically for
litigation, and had never conducted independent research on
                WENDELL V. GLAXOSMITHKLINE                            11

the relationship between 6-MP and anti-TNF drugs and the
development of HSTCL. The court also noted that both
doctors conceded that although their opinions were based on
a reasonable degree of medical certainty, they “would not
satisfy the standards required for publication in peer-reviewed
medical journals.” It concluded that the lack of independent
research combined with the doctors’ reluctance to publish,
“casts doubt [on] the reliability of their methodologies under
Rule 702.”

    Second, the district court determined that the lack of
animal or epidemiological studies showing a causal link
between HSTCL and the combination of 6MP and anti-TNF
drugs also undermined the experts’ methodology. The court
concluded that although it might be difficult to conduct such
studies, given the rarity of HSTCL, that type of causal
evidence was “especially important here in light of the fact
that more than seventy percent of observed HSTCL cases are
idiopathic.”3 “[W]ithout some reliable evidence of a positive
link between the drugs at issue and the disease,” the district
court concluded that the experts “cannot reasonably eliminate
other potential causes of Maxx’s HSTCL.”

    Finally, the district court found that the studies Drs.
Weisenburger and Shustov cited did not “purport[] to show
that the specific combination of drugs prescribed to Maxx
actually causes HSTCL.” Although these studies contained
statistics about the incidence of HSTCL in different patient
populations, the court found that the experts did not show
“that all of the observed differences in these incidence rates
are statistically significant or that they account for plausible

   3
     A disease that is idiopathic, or de novo, is one that does not have a
known cause.
12            WENDELL V. GLAXOSMITHKLINE

alternative causes of HSTCL, such as IBD itself.” Further,
the doctors did not present scientific evidence to support their
opinion that IBD is not a risk factor for HSTCL.

    Although we think it a close question, we conclude that
the district court erred by excluding the experts’ testimony.
The district court looked too narrowly at each individual
consideration, without taking into account the broader picture
of the experts’ overall methodology. It improperly ignored
the experts’ experience, reliance on a variety of literature and
studies, and review of Maxx’s medical records and history, as
well as the fundamental importance of differential diagnosis
by experienced doctors treating troubled patients. The district
court also overemphasized the facts that (1) the experts did
not develop their opinions based on independent research and
(2) the experts did not cite epidemiological studies. We hold
that all together, these mistakes warrant reversal. Cf.
Kennedy v. Collagen Corp., 161 F.3d 1226, 1228–30 (9th Cir.
1998) (concluding that the expert’s reliance on studies that
showed a connection between collagen and autoimmune
disorders combined with the expert’s observations of the
patient and review of her medical history was a sufficiently
reliable methodology even though the cause-effect
relationship between the collagen and the disease was not
conclusively established).

    To begin, the experts were highly qualified doctors. Dr.
Shustov is a licensed, board-certified physician and an
Associate Professor of Medicine at the University of
Washington Medical Center. He specializes in the diagnosis
and treatment of lymphomas, with a clinical research focus on
T-cell leukemia and lymphomas. He has treated “hundreds
of patients with T-cell lymphomas,” and “thousands of
patients with lymphomas,” including seven patients with
             WENDELL V. GLAXOSMITHKLINE                    13

HSTCL. Two of those patients were treated with the
combination of drugs at issue here. Given the rarity of
HSTCL, Dr. Shustov estimated that he has seen more cases
of the disease than 99% of oncologists in the country. Dr.
Weisenburger is an expert hematopathologist—a physician
trained in the study and diagnosis of diseases of the bone
marrow and the immune system—with more than 30 years of
experience diagnosing non-Hodgkin lymphoma. He is the
professor and Chair of the Department of Pathology at City
of Hope Medical Center. Although he has not written
specifically on HSTCL, he has written hundreds of papers on
the subject of non-Hodgkin’s lymphoma, including some on
the potential causes of non-Hodgkin’s lymphoma.

     The doctors employed sound methodologies to reach their
conclusions. Dr. Shustov based his opinions “on medical
records as well as [his] education, training and experience,
knowledge of the pertinent medical literature and [his]
knowledge of the epidemiology, diagnosis and natural history
of HSTCL.” He explained: “I reviewed the literature, I
pulled the facts out of the literature.” He found that the
literature shows there is an increased risk of HSTCL in
patients taking 6-MP over the general population. After
reviewing the literature, he “compiled the numbers about
frequency of diseases, about frequency of inflammatory
bowel disease and [he] looked at the biological causation of
lymphoma pertaining to this case.”

    Dr. Shustov stated that he performs differential diagnosis
in attempting to diagnose every patient, and that he has
applied the same technique to determine the cause of a
disease. When performing a differential diagnosis, he first
assumes the pertinence of all potential causes, then rules out
the ones as to which there is no plausible evidence of
14           WENDELL V. GLAXOSMITHKLINE

causation, and then determines the most likely cause among
those that cannot be excluded. We have recognized that this
method of conducting a differential diagnosis is scientifically
sound. See Clausen, 339 F.3d at 1057–58. For cases of
HSTCL in patients that have taken 6-MP, like Maxx, Dr.
Shustov recognized:

       that 6-MP is a well-known mutagen and
       carcinogen and puts every person who takes it
       at risk.     And given the frequency of
       hepatosplenic lymphoma in [the] general
       population as . . . [compared to] those who
       take 6-MP, it makes it plausible or
       biologically plausible that that’s [an] etiologic
       factor.    You construct your differential
       diagnosis . . . [of] what might have caused
       lymphoma. You come up with the strongest
       probability that patient was taking carcinogen
       and developed lymphoma and you start
       thinking again what can cause his lymphoma,
       you can’t identify anything else in the
       patient’s history or his medical records.

    Regarding Maxx specifically, Dr. Shustov stated that
there was a one in six million chance that Maxx would have
developed HSTCL without being exposed to 6-MP. In light
of those odds, Dr. Shustov stated that “based on [his]
experience in T-cell lymphomas, knowledge of the literature
and being involved in T-cell lymphoma research in the past
ten years” he determined “that it’s much more likely that
exposure to mutagen and immunosuppressants caused the
lymphoma.” Dr. Shustov did not need to eliminate all
potential causes; “[i]t is enough that a [proposed cause] be a
substantial causative factor.” Messick, 747 F.3d at 1199.
               WENDELL V. GLAXOSMITHKLINE                            15

    Dr. Weisenburger described his methodology for reaching
his opinions as follows:

         I reviewed the medical records. I reviewed
         the pathology slides and confirmed the
         diagnosis. I reviewed all of the pathology
         records. I reviewed the literature on the
         disease, hepatosplenic lymphoma. And I
         reviewed all the literature I could find on
         causes of hepatopathic T-cell lymphoma,
         including literature on inflammatory bowel
         disease and treatments for inflammatory
         bowel disease. And then I used the Bradford
         Hill methodology to come to the conclusion
         that I did.[4, 5]

    Regarding Maxx specifically, Dr. Weisenburger based his
opinion on “a summary of the medical records of [Maxx] as
well as copies of the pathology reports, and the original slides
of the diagnostic bone marrow,” which he evaluated with
over 30 years of experience diagnosing non-Hodgkin
lymphoma. He stated that he considered that Maxx’s HSTCL
might have been idiopathic, and that although he was not
entirely able to rule that possibility out, “[w]hen you have a
patient with obvious and known risk factors, you tend to
assume that those risk factors were the cause.” He did not
base that assumption on pure conjecture. As he discussed
throughout his deposition testimony and in his expert report,


    4
      The Bradford Hill methodology refers to a set of criteria that are
well accepted in the medical field for making causal judgments.
     5
       Dr. Weisenburger also identified at least one paper that showed
there was no risk of lymphoma in IBD patients.
16            WENDELL V. GLAXOSMITHKLINE

the literature shows that patients exposed to 6-MP and anti-
TNF drugs are at an increased risk for HSTCL. Dr.
Weisenburger also weighed other risk factors, including
Maxx’s sex and age, and determined that those were “weak
risk factors; whereas, the disease he had, particularly in the
setting of the drugs he received would be considered very
strong risk factors.”

    The proposed testimony was sufficiently reliable that the
Plaintiffs’ experts should have been allowed to testify under
Daubert. The district court improperly required more. The
Supreme Court in Daubert aimed at screening out unreliable
or bogus expert testimony. Nothing in Daubert, or its
progeny, properly understood, suggests that the most
experienced and credentialed doctors in a given field should
be barred from testifying based on a differential diagnosis.

     First, the district court was wrong to put so much weight
on the fact that the experts’ opinions were not developed
independently of litigation and had not been published.
While independent research into the topic at issue is helpful
to establish reliability, its absence does not mean the experts’
methods were unreliable. Where “the proffered expert
testimony is not based on independent research,” the experts
can instead present “other objective, verifiable evidence that
the testimony is based on ‘scientifically valid principles.’”
Daubert II, 43 F.3d at 1317–18. To be sure, “[o]ne means of
showing [that the testimony is based on scientifically valid
principles] is by proof that the research and analysis
supporting the proffered conclusions have been subjected to
normal scientific scrutiny through peer review and
publication.” Id. at 1318. However, expert testimony may
still be reliable and admissible without peer review and
publication. See Clausen, 339 F.3d at 1056. That is
             WENDELL V. GLAXOSMITHKLINE                     17

especially true when dealing with rare diseases that do not
impel published studies. See Milward v. Acuity Specialty
Prods. Grp., Inc., 639 F.3d 11, 24 (1st Cir. 2011)
(recognizing that the “rarity” of a particular form of leukemia
was one reason that it would be “very difficult to perform an
epidemiological study of the causes of [the disease] that
would yield statistically significant results.”).

    The district court also wrongly conflated the standards for
publication in a peer-reviewed journal with the standards for
admitting expert testimony in a courtroom. Dr. Weisenburger
stated on cross-examination that to publish his opinion he
would use a “more rigorous” standard than the one he used to
come up with his expert opinion. Dr. Shustov stated that he
would not be comfortable publishing his opinion because he
did not have any new data, and any meta-analysis or review
of the literature could only be published upon invitation. The
district court viewed these statements regarding the experts’
willingness to publish as evidence that their methods were not
up to snuff. But this analysis misses that while an expert
must “employ[] in the courtroom the same level of
intellectual rigor that characterizes the practice of an expert
in the relevant field,” Kumho Tire Co., Ltd. v. Carmichael,
526 U.S. 137, 152 (1999), the standards for courtroom
testimony do not necessarily parallel those of the professional
publications, see Ambrosini v. Labarraque, 101 F.3d 129, 138
(D.C. Cir. 1996) (“[T]he fact ‘that science would require
more evidence before conclusively considering the causation
question resolved is irrelevant [to the admissibility of expert
testimony].’”) (quoting Ferebee v. Chevron Chem. Co.,
736 F.2d 1529, 1536 (D.C. Cir. 1984)). For example, Dr.
Shustov explained that, “[o]pinions are not publishable. Data
is publishable. What I’m reporting here is my opinion.”
Although unwillingness to publish weighs against
18           WENDELL V. GLAXOSMITHKLINE

admissibility, it alone is not determinative. See Daubert II,
43 F.3d at 1318 n.9 (“That plaintiffs’ experts have been
unable or unwilling to publish their work undermines
plaintiffs’ claim that the findings these experts proffer are
‘ground[ed] in the methods and procedures of science’ and
‘derived by the scientific method.’” (alteration in original)
(quoting Daubert, 509 U.S. at 590)). We have previously
held expert opinions to be reliable that were not subject to
peer review through publication. See Clausen, 339 F.3d at
1056, 1061.

    The district court also wrongfully required that the
experts’ opinions rely on animal or epidemiological studies.
Neither are necessary for an expert’s testimony to be found
reliable and admissible. See Kennedy, 161 F.3d at 1229. We
have long recognized that it may not always be possible to
conduct certain types of studies. See, e.g., Daubert II,
43 F.3d at 1318 n.9 (“There may well be good reasons why
a scientific study has not been published. For example, it
may be too recent or of insufficiently broad interest.”).
HSTCL is an exceedingly rare cancer, with only 100 to 200
cases reported since it was first recognized. It is not
surprising that the scientific community has not invested
substantial time or resources into investigating the causes of
such a rare disease.

    Although they did not rely on animal or epidemiological
studies, the experts here did rely on other published studies
and articles. The district court only addressed a few of these,
quickly dismissing them because they are case reports and do
not control or account for alternative causes of HSTCL.
Although case studies alone generally do not prove causation,
they “may support other proof of causation.” Rider v. Sandoz
Pharm. Corp., 295 F.3d 1194, 1199 (11th Cir. 2002). Here,
                WENDELL V. GLAXOSMITHKLINE                            19

the experts relied not just on these studies—which not only
examined reported cases but also used statistical analysis to
come up with risk rates—but also on their own wealth of
experience and additional literature.6

    We also note that “[n]ot knowing the mechanism whereby
a particular agent causes a particular effect is not always fatal
to a plaintiff’s claim. Causation can be proved even when we
don’t know precisely how the damage occurred, if there is
sufficiently compelling proof that the agent must have caused
the damage somehow.” Daubert II, 43 F.3d at 1314
(emphasis in original). That there is no study that definitively
states HSTCL is caused by the ingestion of 6-MP and anti-
TNF drugs does not prevent the admission of Plaintiffs’
experts’ testimony. See Kennedy, 161 F.3d at 1230.

    Finally, the district court erred when it excluded
Plaintiffs’ experts’ opinion testimony because of the high rate
of idiopathic HSTCL and the alleged inability of the experts
to rule out an idiopathic origin or IBD itself. We do not
require experts to eliminate all other possible causes of a
condition for the expert’s testimony to be reliable. Messick,
747 F.3d at 1199. It is enough that the proposed cause “be a
substantial causative factor.” Id. This is true in patients with
multiple risk factors, and analogously, in cases where there is
a high rate of idiopathy. See id. (holding that the district
court abused its discretion when it excluded expert testimony
as unreliable because the expert could not determine which of


    6
       Teva argues that its own experts highlight the dearth of scientific
evidence to support Plaintiffs’ claims and undermine any assertion that
Drs. Shustov and Weisenburger employed sound scientific methodology.
The district court did not consider this evidence, and we decline to do so
in the first instance.
20           WENDELL V. GLAXOSMITHKLINE

multiple risk factors caused plaintiff’s disease). Moreover,
when an expert establishes causation based on a differential
diagnosis, the expert may rely on his or her extensive clinical
experience as a basis for ruling out a potential cause of the
disease. See id. at 1198. The district court abused its
discretion by excluding Dr. Shustov’s and Dr.
Weisenburger’s testimony because they could not completely
rule out the possibility that Maxx’s HSTCL was idiopathic.

    Perhaps in some cases there will be a plethora of peer
reviewed evidence that specifically shows causation.
However, such literature is not required in each and every
case. “The first several victims of a new toxic tort should not
be barred from having their day in court simply because the
medical literature, which will eventually show the connection
between the victims’ condition and the toxic substance, has
not yet been completed.” Clausen, 339 F.3d at 1060 (quoting
Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1209 (8th
Cir. 2000)). In the case of a rare disease like HSTCL, the
Supreme Court’s mandate that in determining the
admissibility of expert testimony, the focus “must be solely
on principles and methodology, not on the conclusions that
they generate,” is especially important. Daubert, 509 U.S. at
595.

    Where, as here, the experts’ opinions are not the “junk
science” Rule 702 was meant to exclude, see Estate of
Barabin v. AstenJohnson, Inc., 740 F.3d 457, 463 (9th Cir.
2014), the interests of justice favor leaving difficult issues
in the hands of the jury and relying on the safeguards of
the adversary system—“[v]igorous cross-examination,
presentation of contrary evidence, and careful instruction on
the burden of proof”—to “attack[] shaky but admissible
evidence,” Daubert, 509 U.S. at 596. Because we conclude
              WENDELL V. GLAXOSMITHKLINE                     21

that the district court erred in excluding the testimony of Dr.
Shustov and Dr. Weisenburger, we reverse the district court’s
grant of summary judgment. See Messick, 747 F.3d at 1199.
As explained in Messick, “[m]edicine partakes of art as well
as science.” Id. at 1198. Where, as here, two doctors who
stand at or near the top of their field and have extensive
clinical experience with the rare disease or class of disease at
issue, are prepared to give expert opinions supporting
causation, we conclude that Daubert poses no bar based on
their principles and methodology. That defendants may be
able to offer other equally qualified medical opinion opposing
causation also does not support the idea that Daubert should
bar the admission of the testimony of the doctors offered as
experts by Plaintiffs. Instead, the testimony of Dr.
Weisenburger and of Dr. Shustov should have been admitted
as expert testimony under Federal Rules of Evidence 702.
The defendants’ expert testimony could have been offered in
opposition. Then, the jury, as the trier of fact, would be
empowered to decide, based on the law given in proper jury
instructions and the facts as determined by the jury.

                               B

    The district court granted summary judgment to Teva on
the duty to warn claim for two reasons. First, the district
court held that the lack of admissible causation evidence
precluded Plaintiffs from prevailing on their duty to warn
claims. Second, Plaintiffs did not produce “any evidence to
suggest that Dr. Rich actually relied on Teva’s warning labels
before prescribing Purinethol to Maxx.” For the reasons
discussed above, we reverse on the district court’s first
ground. For the reasons discussed below, we reverse on the
district court’s second ground.
22              WENDELL V. GLAXOSMITHKLINE

    Under California law, drug manufacturers have a duty to
warn physicians of risks that are known or scientifically
knowable at the time of the drug’s distribution. See Carlin v.
Superior Court, 920 P.2d 1347, 1349–54 (Cal. 1996). “A
plaintiff asserting causes of action based on a failure to warn
must prove not only that no warning was provided or the
warning was inadequate, but also that the inadequacy or
absence of the warning caused the plaintiff’s injury.” Motus
v. Pfizer Inc., 196 F. Supp. 2d 984, 991 (C.D. Cal. 2001),
aff’d, 358 F.3d 659. “[A] product defect claim based on
insufficient warnings cannot survive summary judgment if
stronger warnings would not have altered the conduct of the
prescribing physician.” Motus, 358 F.3d at 661.

    In this case, viewing the evidence in the light most
favorable to Plaintiffs, there is a genuine dispute of material
fact as to whether Dr. Rich’s conduct would have changed
with warnings from Teva and GSK. Summary judgment was
improper.

    Although Dr. Rich testified that it is not his “regular
practice to look at drug labeling,” when he does read them it
is “one of the things that is part of [his] decision-making
process.” He also testified that “a black box warning means
there is a significant side effect that I need to be aware of.”7
Indeed, this type of warning did influence Dr. Rich’s
prescribing decisions for Maxx. Centocor began circulating
warnings—both a black box warning and a Dear Health Care


     7
       A black box warning is a warning that is placed in a box in a drug’s
labeling information. According to Plaintiffs’ pharmacovigilance expert,
a black box warning may only be used with FDA authorization, and it is
“the strongest possible warning that can be given short of restricting
distribution of a drug or completely withdrawing it from the market.”
                WENDELL V. GLAXOSMITHKLINE                            23

Provider letter—about HSTCL for Remicade in May 2006,
just a few months after Maxx stopped taking Remicade.
When Maxx’s IBD relapsed in November 2006, Dr. Rich
prescribed Humira—which did not have a warning about
HSTCL—in place of Remicade. Dr. Rich testified that he
prescribed Humira because he believed it had a better safety
profile, noting that at that point there were no reports of
HSTCL developing in patients who took Humira. This
change in prescribing practices which can, at least in part,
reasonably be attributed to the lack of a warning for Humira
creates a question of material fact as to whether the presence
of a warning on Teva’s Purinethol would have changed Dr.
Rich’s prescribing practices as to Maxx.

    There is also evidence that Dr. Rich changed his
prescribing practices generally after he learned of incidents of
HSTCL in patients taking both 6-MP and anti-TNF agents.
As the information came out, his prescribing practices
evolved. He now no longer prescribes combination therapy
but uses only monotherapy. Viewing the facts in the light
most favorable to the Plaintiffs, there are questions of
material fact as to whether warnings would have changed Dr.
Rich’s prescribing practice. See Stanley v. Novartis Pharm.
Corp., 11 F. Supp. 3d 987, 1003 (C.D. Cal. 2014)
(“[C]hanges to treatment and prescription procedures
create[d] a triable question of fact on specific causation.”).
We reverse the district court’s grant of summary judgment in
favor of Teva.8


    8
      GSK asserts that Plaintiffs’ warning expert’s testimony shows that
Purinethol’s label should have been changed in 2006, approximately three
years after GSK stopped distributing the drug. It argues that there can be
no causal connection between the alleged failure to warn and the harm.
The district court did not address this argument, and we decline to do so.
24              WENDELL V. GLAXOSMITHKLINE

                                   C

    Teva urges us to affirm the district court on four
alternative grounds.9 Although we may affirm on any ground
raised below and supported by the record, see Proctor v.
Vishay Intertechnology Inc., 584 F.3d 1208, 1226 (9th Cir.
2009), the issues that Teva raises would require extensive fact
finding, and are matters on which the district court did not
rule. It would be inappropriate for us to reach these issues,
and we decline to do so. See Greater L.A. Council on
Deafness, Inc. v. Zolin, 812 F.2d 1103, 1107 & n.5 (9th Cir.
1987), superceded by statute on other grounds. They may be
raised with the district court on remand.

                                   D

    Finally, Plaintiffs challenge the district court’s order
denying Plaintiffs’ motion for leave to file a motion for
reconsideration of the district court’s July 2012 order
granting summary judgment to GSK. GSK asserts that, as
Plaintiffs’ opening brief does not challenge the district court’s
underlying grant of summary judgment to GSK, Plaintiffs


See Greater L.A. Council on Deafness, Inc. v. Zolin, 812 F.2d 1103, 1107
& n.5 (9th Cir. 1987), superceded by statute on other grounds.
     9
       Briefly, Teva argues that we should affirm on each of the following
four bases: (1) it had no duty to warn about the alleged risk of HSTCL
arising from an off-label use of Purinethol; (2) it had no duty to warn
about alleged risks from use of a competitor’s product; (3) Plaintiffs
cannot maintain a failure to warn claim because Dr. Rich had already
received the information; and (4) because Plaintiffs cannot prove that
Maxx developed HSTCL after May 2006, they cannot prove that an
alleged failure to warn by Teva was the proximate cause of Maxx’s
injuries.
             WENDELL V. GLAXOSMITHKLINE                     25

abandoned their argument that the district court erroneously
granted summary judgment to GSK.

    GSK’s argument is unpersuasive. As to GSK, Plaintiffs
are challenging only the district court’s denial of its motion
for leave to file a motion for reconsideration. A challenge to
a denial of a motion for leave to file a motion for
reconsideration brings up just the denial of that motion, not
the underlying merits. Cf. Molloy v. Wilson, 878 F.2d 313,
315 (9th Cir. 1989) (“An appeal from a denial of a Rule 60(b)
motion brings up only the denial of the motion for review, not
the merits of the underlying judgment.”). Plaintiffs did raise
this argument in their Opening Brief, asserting that because
the district court’s rulings regarding the admissibility of
expert testimony and causation were erroneous, “the ruling on
Plaintiffs’ motion likewise should be vacated so that it can be
decided on its merits on remand.”

    We agree with Plaintiffs. The district court denied their
motion “as moot” because “Plaintiffs cannot prevail on their
claims against [GSK] for the same reasons they cannot
prevail on their claims against Teva”: lack of admissible
causation evidence, and lack of evidence showing Dr. Rich’s
reliance on warnings. Because we reverse the district court
on those issues, we also reverse the district court’s denial of
Plaintiffs’ motion for reconsideration.

   REVERSED AND REMANDED.
