United States District Court, D. Massachusetts
IN RE ZOFRAN ONDANSETRON PRODUCTS LIABILITY LITIGATION This Document Relates To All Actions
MEMORANDUM AND ORDER ON MOTIONS TO EXCLUDE REGULATORY
DENNIS SAYLOR, IV UNITED STATES DISTRICT JUDGE.
a multi-district litigation (“MDL”) proceeding
arising out of product-liability claims that the use of the
drug Zofran (ondansetron) by pregnant women caused birth
defects in their children.
have moved to exclude certain portions of the testimony of
the regulatory expert of GlaxoSmithKline LLC
(“GSK”), Dr. Dena Hixon. GSK has moved to exclude
the testimony of plaintiffs' regulatory expert, Dr. Brian
Harvey. For the reasons set forth below, plaintiffs'
motion will be denied and GSK's motion will be granted in
part and denied in part.
Standard of Review
Rule of Evidence 702 provides as follows:
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. The adoption of Rule 702 in its present form codified
the standard of admissibility for expert testimony that was
set forth in Daubert v. Merrell Dow Pharmaceuticals,
Inc., 509 U.S. 579 (1993). United States v.
Diaz, 300 F.3d 66, 73 (1st Cir. 2002).
Rule 702, district courts considering the admissibility of
expert testimony must “act as gatekeepers, ensuring
that an expert's proffered testimony ‘both rests on
a reliable foundation and is relevant to the task at
hand.'” Samaan v. St. Joseph Hosp., 670
F.3d 21, 31 (1st Cir. 2012) (quoting Daubert, 509
U.S. at 597). That gatekeeping function requires that the
court consider three sets of issues: (1) whether the proposed
expert is qualified by “knowledge, skill, experience,
training or education”; (2) whether the subject matter
of the proposed testimony properly concerns
“scientific, technical, or other specialized
knowledge”; and (3) “whether the testimony [will
be] helpful to the trier of fact, i.e., whether it
rests on a reliable foundation and is relevant to the facts
of the case.” Bogosian v. Mercedes-Benz of N. Am.,
Inc., 104 F.3d 472, 476 (1st Cir. 1997) (quoting
Fed.R.Evid. 702) (internal quotation marks omitted).
“These two requirements-a reliable foundation and an
adequate fit-are separate and distinct.”
Samaan, 670 F.3d at 31.
requirement that an expert's testimony must be based on
reliable methods is often the “central focus of a
Daubert inquiry.” Ruiz-Troche v. Pepsi
Cola of P.R. Bottling Co., 161 F.3d 77, 81 (1st Cir.
1998). In Daubert, the Supreme Court enumerated a
non-exhaustive list of factors that a court may consider in
undertaking its reliability analysis: (1) whether the
scientific theory or technique can be (and has been) tested;
(2) whether it has been subjected to peer review and
publication; (3) whether it has a known rate of error; (4)
whether there are standards controlling its application or
operation; and (5) whether it is generally accepted in the
relevant scientific community. Daubert, 509 U.S. at
593-94; see also Samaan, 670 F.3d at 31-32.
centrally, but importantly, Rule 702 requires the court to
examine whether those methods have been reliably applied. In
other words, the court must “ensure that there is an
adequate fit between the expert's methods and his
conclusions.” Samaan, 670 F.3d at 32 (citing
Daubert, 509 U.S. at 591). “This prong of the
Daubert inquiry addresses the problem that arises
when an expert's methods, though impeccable, yield
results that bear a dubious relationship to the questions on
which he proposes to opine.” Id. (citing
Daubert, 509 U.S. at 591-92).
evaluating whether expert testimony will be helpful to the
trier of fact, the court must determine whether it is
relevant, “not only in the sense that all evidence must
be relevant, but also in the incremental sense that the
expert's proposed opinion, if admitted, likely would
assist the trier of fact to understand or determine a fact in
issue.” Ruiz-Troche, 161 F.3d at 81 (citations
omitted); see also Cipollone v. Yale Indus. Prods.,
Inc., 202 F.3d 376, 380 (1st Cir. 2000) (“The
ultimate purpose of the Daubert inquiry is to
determine whether the testimony of the expert would be
helpful to the jury in resolving a fact in issue.”).
focus of the inquiry is on the principles and methodology
employed by the expert, not the ultimate conclusions.
Daubert, 509 U.S. at 595. The court may not subvert
the role of the factfinder in assessing credibility or in
weighing conflicting expert opinions. Rather,
“[v]igorous cross-examination, presentation of contrary
evidence, and careful instruction on the burden of proof are
the traditional and appropriate means of attacking shaky but
admissible evidence.” Id. at 596; see also
Ruiz-Troche, 161 F.3d at 85 (admitting testimony
notwithstanding a lack of peer-reviewed publications because
the opinion rested upon good grounds generally and should be
tested by the “adversary process”).
testimony that is admissible under Rule 702 may nonetheless
be excluded under Rule 403 “if its probative value is
substantially outweighed by the danger of one or more of the
following: unfair prejudice, confusion of the issues,
misleading the jury, undue delay, wasting time, or needlessly
presenting cumulative evidence.” Fed.R.Evid. 403;
see also Daubert, 509 U.S. at 595. Thus, expert
testimony that is relevant and that passes muster from a
scientific or technical standpoint may nonetheless be
excluded if it is likely to be misinterpreted or misused by
Plaintiffs' Motion to Exclude Testimony of Dr.
seek to exclude certain portions of the testimony of
GSK's regulatory expert, Dr. Dena Hixon. They contend
that her opinions on two topics-determination of
teratogenicity (or pregnancy labeling) and
pharmacovigilance-should be excluded on the grounds that she
is not qualified to render the opinions and that the opinions
are based on unsound methodology.
Hixon is a medical doctor and a former board-certified
obstetrician/gynecologist with thirteen years of clinical
experience. She also worked at the Food and Drug
Administration (“FDA”) for thirteen years, first
as a medical officer within the Center for Drug Evaluation
and Research (“CDER”), and then as an advisor on
safety issues in the Office of Generic Drugs. For three of
those years, she was the primary reviewer of human clinical
studies submitted as part of Investigational New Drug
(“IND”) applications and New Drug Applications
(“NDAs”). She also served on the FDA's
Pregnancy Labeling Task Force. That task force assessed
pregnancy-related drug-labeling categories, developed the
Pregnancy and Lactation Labeling Rule (“PLLR”),
and developed FDA guidance documents concerning risk
assessment of drugs used in pregnancy. She now works as a
regulatory consultant, advising on drug development and
regulation for both new and generic drugs, from early
development through product approval and post-market
Hixon produced an expert report in this case on September 21,
2018. Among other things, the report concluded-in what
plaintiffs refer to as a “determination of
teratogenicity, ” or “pregnancy labeling, ”
opinion-that the FDA “appropriately assigned
ondansetron Pregnancy Category B in the labeling, based on
the data available to GSK and FDA and the applicable
regulations.” (Hixon Report at 4). It further
concluded-in what plaintiffs refer to as a
“pharmacovigilance” opinion-that GSK
“appropriately monitored the drug's safety in
pregnancy and complied with the regulations in collection,
analyzing[, ] and reporting pregnancy-related safety
information, ” and that GSK “performed several
thorough internal assessments of pregnancy exposure and
outcome data.” (Id.).
contend that both of those opinions should be excluded on the
grounds that they exceed her regulatory experience and lack
reliable scientific foundation.
Determination of Teratogenicity (or Pregnancy Labeling)
first object to Dr. Hixon's opinion that Zofran was
properly labeled as a pregnancy Category B Drug.
Specifically, they contend that (1) her methodology is flawed
because one of the Japanese animal studies (Study 424) was
never submitted to the FDA and she does not have the
expertise to opine on whether the FDA would have found
evidence of teratogenicity if that study had been taken into
consideration; and (2) her opinions are unreliable because
she is not qualified to opine on whether reproductive
toxicology animal studies provide evidence of teratogenicity.
undisputed that GSK has never provided a complete version of
Study 424 to the FDA. According to plaintiffs, the factfinder
will have to rely on expert-witness testimony to assess
whether the data from all of the animal studies at issue,
when considered in totality, demonstrated sufficient fetal
risk such that GSK should have requested a Pregnancy Category
C warning. They further contend that Dr. Hixon cannot offer
an opinion that the disclosure of Study 424, or any of the
other disputed Japanese animal studies, would not have
changed the pregnancy category for Zofran without also
opining that the study does not show evidence of
teratogenicity. Because, they contend, she is not qualified
to offer such an opinion, and did not consult with a
toxicologist, her opinions as to those topics are unreliable
and should be excluded.
identify four such “determination of teratogenicity,
” or “pregnancy labeling, ” opinions-that
is, “[o]pinions regarding whether the Japanese animal
studies provided evidence of teratogenicity and whether their
disclosure to FDA would have changed the pregnancy
categorization of Zofran”-that they seek to exclude:
(1) “FDA appropriately assigned ondansetron Pregnancy
Category B in the labeling, based on the data available to
GSK and FDA and the applicable regulations.” (Hixon
Report at 4).
(2) “Because data from the studies did not lead to
different conclusions regarding safety than the studies that
had already been provided to FDA in previous IND and NDA
submissions . . ., GSK appropriately determined that the data
in these studies did not constitute ‘new'
information relevant to safety.” (Id. at 36).
(3) “The evidence must provide a reasonable basis to
believe that there is a causal association between the risk
and the drug. At no time did such evidence exist, including
in reproductive toxicity studies, scientific literature, or
GSK's safety database.” (Id. at 36, 72).
(4) “GSK's scientists uniformly concluded that none
of the reproductive toxicology studies showed evidence of
teratogenicity in animals, and FDA's experts
agreed.” (Id. at 72).
the circumstances, the opinions will not be excluded. Dr.
Hixon does not claim to determine independently whether the
data from reproductive toxicity studies show that Zofran is
teratogenic. Instead, she is relying upon the conclusions of
GSK's scientists that those studies did not show that
Zofran is teratogenic. Starting with that assumption, Dr.
Hixon applied what she says are the relevant regulatory
standards, which she appears qualified to provide based on
her background and training.
that reason, the Court will construe Dr. Hixon's opinions
(2) and (4) as regulatory opinions conditioned on a specific
assumption: the assumption that GSK's experts correctly
interpreted the toxicity studies. Of course, if that
assumption is incorrect, that would likely undermine her
conclusions, if not vitiate them completely. Furthermore, any
opinion she expresses must be carefully couched to make clear
that she is not testifying (and cannot testify) as to whether
the toxicity studies were correctly interpreted.
opinions (1) and (3), GSK contends that they do not turn on a
toxicological determination of “non-teratogenicity,
” but are instead based on Dr. Hixon's regulatory
analysis of the study reports, FDA standards, and other
materials. She appears qualified to deliver those opinions
based on her thirteen years of clinical experience as a
practicing OB/GYN and her thirteen years of experience at the
FDA, including her work on the Pregnancy Labeling Task Force
and her role as a team leader in the Office of New Drugs. At
the FDA, she directly participated in redeveloping the
regulations setting forth the pregnancy categories; worked on
guidances concerning pregnancy-related risk assessment; and
reviewed NDAs, including the evaluations of
pharmacologist/toxicologist reviewers. (Hixon Report at
1). In short, Dr. Hixon is ...