United States District Court, D. South Carolina, Charleston Division
IN RE: LIPITOR (ATORVASTATIN CALCIUM) MARKETING, SALES PRACTICES AND PRODUCTS LIABILITY LITIGATION
Lipitor (Atorvastatin Calcium) Marketing Sales Practices and
Products Liability Litigation, In Re: H Blair Hahn, LEAD
ATTORNEY, Richardson Patrick Westbrook and Brickman, Mt
Plaintiffs' Lead Counsel, Plaintiff: H Blair Hahn, LEAD
ATTORNEY, Christiaan A Marcum, Elizabeth Middleton Burke,
Richardson Patrick Westbrook and Brickman, Mt Pleasant, SC.
Plaintiffs' Liason Counsel, Plaintiff: Mark Charles
Tanenbaum, LEAD ATTORNEY, Mark C Tanenbaum Law Office,
Pfizer Inc, Defendant: Amanda S Kitts, David Eidson Dukes,
John Mark Jones, LEAD ATTORNEYS, Nelson Mullins Riley and
Scarborough, Columbia, SC; Karin Kramer, LEAD ATTORNEY, Quinn
Emanuel Urquhart and Sullivan, San Francisco, CA; Kelly A
Evans, LEAD ATTORNEY, Snell and Wilmer, Las Vegas, NV; Lee A
Mickus, LEAD ATTORNEY, PRO HAC VICE, Snell and Wilmer,
Denver, CO; Lyn Peeples Pruitt, LEAD ATTORNEY, Mitchell
Williams Selig Gages and Woodyard, Little Rock, AK; Mara C
Cusker Gonzalez, Mark Steven Cheffo, LEAD ATTORNEYS, Lincoln
D Wilson, Sheila L Birnbaum, Quinn Emanuel Urquhart and
Sullivan, New York, NY; Michael Tucker Cole, LEAD ATTORNEY,
Nelson Mullins Riley and Scarborough (Ch), Charleston, SC;
Rachel B Passaretti-Wu, LEAD ATTORNEY, PRO HAC VICE, Quinn
Emanuel Urquhart and Sullivan, New York, NY; Amy Chung, Lucas
Przymusinski, DLA Piper U.S. LLP, New York, NY; Brett M
Collings, Theodore VH Mayer, Hughes Hubbard and Reed, New
McKesson Corporation, Defendant: Emma E Garrison, Habib
Nasrullah, Jeremy A Moseley, LEAD ATTORNEYS, Wheeler Trigg
O'Donnell LLP, Denver, CO.
Greenstone LLC, Defendant: Carole W Nimaroff, George A
Tsougarakis, LEAD ATTORNEYS, Brett M Collings, Theodore VH
Mayer, Hughes Hubbard and Reed, New York, NY; Mark Steven
Cheffo, LEAD ATTORNEY, Quinn Emanuel Urquhart and Sullivan,
New York, NY.
Pfizer International LLC, Defendant: Carole W Nimaroff,
George A Tsougarakis, LEAD ATTORNEYS, Brett M Collings,
Theodore VH Mayer, Hughes Hubbard and Reed, New York, NY;
Loren H Brown, LEAD ATTORNEY, DLA Piper U.S. LLP, New York,
Laura McCammon, Interested Party: John T Lay, LEAD ATTORNEY,
Gallivan White and Boyd, Columbia, SC; Joseph D Cohen, LEAD
ATTORNEY, PRO HAC VICE, Porter Hedges, Houston, TX.
Mark Gergel, United States District Judge.
MANAGEMENT ORDER NO. 54
Order relates to all cases.
MDL, Plaintiffs allege that Lipitor caused them to develop
Type 2 diabetes. To carry their burden, Plaintiffs must prove
both general and specific causation. Westberry v.
Gislaved Gummi AB, 178 F.3d 257, 263 (4th Cir. 1999).
Defendant has moved to exclude the testimony of
Plaintiffs' general causation experts. (Dkt. No. 972). In
its motion, Defendant also moves to exclude the testimony of
Dr. Nicholas Jewell. Dr. Jewell is a statistician. He does
not opine on whether Lipitor causes diabetes but offers
opinions related to whether particular data show a
statistical association between Lipitor and new-onset
diabetes. All of Plaintiffs' general
causation experts have relied on Dr. Jewell's analysis to
some extent in their initial expert reports.
Jewell's initial report, he analyzes (1) data submitted
with Lipitor's FDA New Drug Application (NDA), (2) data
from the SPARCL trial, and (3) data from the IDEAL and TNT
trials. (Dkt. Nos. 972-10, 1247-9, 1247-10). From the outset,
Plaintiffs' counsel provided Dr. Jewell with data from
the ASCOT trial, but Dr. Jewell did not consider or discuss
the ASCOT trial in his initial report. (Dkt. No. 972-7 at
121-22; Dkt. No. 972-10). In his deposition, he testified
that " chose not to study the data in ASCOT." (Dkt.
No. 972-7 at 120, 123).
experts criticized Dr. Jewell's statistical methodologies
and specifically attacked Dr. Jewell's analysis on the
fact that he did not consider the ASCOT trial data. Plaintiff
then sought leave from the Court for Dr. Jewell to submit a
supplemental and/or rebuttal report addressing
Defendant's experts' criticisms and allowing Dr.
Jewell to consider and analyze the ASCOT data. " In an
abundance of caution, and to ensure this Court ha[d] the best
information possible when addressing Daubert
motions," the Court allowed Dr. Jewell to submit a
supplemental report. (CMO 34, Dkt. No. 869 at 2). In this
supplemental report, Dr. Jewell analyzes the ASCOT data,
performs additional analysis on the NDA data, and performs
some additional analysis of the SPARCL data. (Dkt. Nos.
specifically attacks Dr. Jewell's analyses of the NDA
data and ASCOT data as unreliable. ( See Dkt. No.
972 at 14-15, 34-38, 44-46, 51; Dkt. No. 1247-2 at 27-35;
Dkt. No. 1247-5 at 7-8, 12-15, 2; Dkt. No. 1247-6 at 18-19).
In briefing, Defendant does not specifically attack Dr.
Jewell's statistical analyses of the SPARCL, TNT and
IDEAL data but argues that Dr. Jewell has cherry-picked these
studies and that such cherry-picking cannot be the basis of a
general causation opinion. ( See Dkt. No. 972 at
12-15, 38-43, 53). The Court takes each issue in turn.
Rule 104(a) and 702, " the trial judge must ensure that
any and all scientific testimony or evidence admitted is not
only relevant, but reliable." Daubert v. Merrell Dow
Pharms., 509 U.S. 579, 589, 113 S.Ct. 2786, 125 L.Ed.2d
469 (1993). Thus, the trial court must ensure that (1) "
the testimony is the product of reliable principles and
methods," that (2) " the expert has reliably
applied the principles and methods to the facts of the
case," and (3) that the " testimony is based on
sufficient facts or data." Fed.R.Evid. 702(b), (c), (d).
" This entails a preliminary assessment of whether the
reasoning or methodology underlying the testimony is
scientifically valid," Daubert, 509 U.S. at
592-93, and whether the expert has " faithfully
appl[ied] the methodology to facts." Roche v.
Lincoln Prop. Co., 175 Fed.Appx. 597, 602 (4th Cir.
Factors to be considered include " whether a theory or
technique . . . can be (and has been) tested," "
whether the theory or technique has been subjected to peer
review and publication," the " known or potential
rate of error," the " existence and maintenance of
standards controlling the technique's operation,"
and whether the theory or technique has garnered "
general acceptance." Daubert, 509 U.S. at
593-94; accord United States v. Hassan, 742
F.3d 104, 130 (4th Cir. 2014). However, these factors are
neither definitive nor exhaustive, United States v.
Fultz, 591 Fed.Appx. 226, 227 (4th Cir. 2015), cert.
denied, 135 S.Ct. 2370, 192 L.Ed.2d 159 (2015), and
" merely illustrate the types of factors that will
bear on the inquiry." Hassan, 742 F.3d at 130.
Courts have also considered whether the " expert
developed his opinions expressly for the purposes of
testifying," Wehling v. Sandoz Pharms. Corp.,
162 F.3d 1158 (4th Cir. 1998), or through " research
they have conducted independent of the litigation,"
Daubert v. Merrell Dow Pharm., Inc., 43 F.3d 1311,
1317 (9th Cir. 1995) (on remand), and whether experts have
" failed to meaningfully account for . . . literature at
odds with their testimony." McEwen v. Baltimore
Washington Med. Ctr. Inc., 404 Fed.Appx. 789, 791-92
(4th Cir. 2010).
702 also requires courts " to verify that expert
testimony is 'based on sufficient facts or
data.'" E.E.O.C. v. Freeman, 778 F.3d 463,
472 (4th Cir. 2015) (quoting Fed.R.Evid. 702(b)). Thus,
judges may evaluate the data offered to support an
expert's bottom-line opinions to determine if that data
provides adequate support to mark the expert's testimony
as reliable." Id. The court may exclude an
opinion if " there is simply too great an analytical gap
between the data and the opinion offered." Id.
" The proponent of the [expert] testimony must establish
its admissibility by a preponderance of proof."
Cooper v. Smith & Nephew, Inc., 259 F.3d 194, 199
(4th Cir. 2001).
Court is mindful that the Daubert inquiry involves
" two guiding, and sometimes competing,
principles." Westberry v. Gislaved Gummi AB,
178 F.3d 257, 261 (4th Cir. 1999). " On the one hand, .
. . Rule 702 was intended to liberalize the introduction of
relevant expert evidence," id., and " the
trial court's role as a gatekeeper is not intended to
serve as a replacement for the adversary system."
United States v. Stanley, 533 Fed.Appx. 325, 327
(4th Cir. 2013) cert. denied, 134 S.Ct. 1002, 187
L.Ed.2d 852 (2014). On the other, " [b]ecause expert
witnesses have the potential to be both powerful and quite
misleading, it is crucial that the district court conduct a
careful analysis into the reliability of the expert's
proposed opinion." United States v. Fultz, 591
Fed.Appx. 226, 227 (4th Cir.) cert. denied, 135
S.Ct. 2370, 192 L.Ed.2d 159 (2015); accord
Westberry, 178 F.3d at 261.
Dr. Jewell's Analysis of the NDA Data
Background on the NDA Data
Jewell's first opinion concerns data that Defendant
submitted with Lipitor's FDA New Drug Application (NDA).
(Dkt. No. 1247-9 at ¶ 6). With its application to the
FDA, Defendant submitted an Integrated Summary of Safety
(ISS) that summarizes data from 31 completed clinical
pharmacology studies and 21 completed clinical studies. (Dkt.
No. 1063-8 at 6). Section 5.2.1 and Table 42 group all of the
data from the placebo-controlled clinical trials. (
Id. at 118-19). There were seven such
placebo-clinical trials, excluding one placebo-controlled
trial where all participants had pre-existing Type 2
diabetes. ( See id. at 120; Dkt. No. 1247-9
at ¶ 13). These seven trials included a total of 1,122
participants given various doses of Lipitor and 270
participants given placebo. (Dkt. No. 1063-8 at 119; Dkt. No.
1247-9 at ¶ 13). Dr. Jewell was provided with the data
from these seven clinical trials, including patient-level
other things not relevant here, Table 42 reports how many
participants in these seven clinical trials had an elevated
blood glucose reading during the trials, with elevated
glucose defined as > 1.25 ULN [the upper limit of normal].
(Dkt. No. 1063-8 at 119). For most trials, the upper limit of
normal was defined as 100 mg/dL such that 1.25 ULN = 1.25
mg/dL. However, there was one trial where ULN
was defined as 104 mg/dL such that 1.25 ULN was 130 mg/dL.
(Dkt. No. 1063-8 at ¶ 18). Table 42 reports that three
(3) of the 270 participants on placebo had an elevated
glucose reading " on treatment," i.e. during the
trial, and that 37 of the 1,122 participants on Lipitor had
an elevated glucose reading on treatment. (Dkt. No. 1063-8 at
on the data from these seven clinical trials in the NDA data,
Dr. Jewell opined that this data " provide less than
optimum information about [Lipitor's] effect on glucose
metabolism or new-onset diabetes, because of their short
duration, relatively small sample sizes, and the unusual
imbalance between the number of participants allocated to
placebo and atorvastatin treatment." (Dkt. No. 1247-9 at
¶ 6). Yet, Dr. Jewell mined the data and, after some
effort, concluded that " [t]he placebo-controlled data
[from the NDA trials] show a statistically significant
three-fold higher incidence of clinically meaningful abnormal
increases in blood glucose measurement greater than 1.25
times the upper limit of normal, a level that, if persistent,
is diagnostic for diabetes" and that this glucose data
" should have alerted Parke-Davis and Defendant to the
possibility of increased risk of new-onset diabetes
associated with atorvastatin treatment." (Dkt. No.
1247-9 at ¶ 6). To reach this conclusion, Dr. Jewell
improperly engaged in a results-driven methodology,
performing, in his words, a " whole lot" of
analyses of the data, excluding from his report analyses that
he " didn't believe . . . supported . . . being the
basis of the kinds of opinions I wanted to put in my
summary,"  (Dkt. No. 1247-8 at 230-31), and
conducting multiple statistical tests when the first test did
not produce the results that he wanted.
Jewell first looked at adverse event data from these seven
clinical trials but could not reach any conclusions from it.
Of the 1,392 participants in these trials, only five reported
adverse events of diabetes and five others noted an event
such as " elevated glucose."  (Dkt. No. 1247-9 at
¶ 14). None of these incidents were reported by
participants in the placebo group but " it's not a
shock . . . given th[e] distribution of participants."
(Dkt. No. 1247-8 at 206-07). There are " very few
participants" reporting an adverse event of diabetes, so
Dr. Jewell " basically lay[s] to rest the hope that one
might glean too much from the adverse event [data]."
(Dkt. No. 1247-8 at 206).
Jewell then turns to glucose measurements. Dr. Jewell "
count[ed] the number of individuals who had elevated glucose
measurements at any point after baseline"
(i.e., during the trial), and compared this number in the
groups on Lipitor and the groups on placebo. (Dkt. No.
1247-9 at ¶ 17 (emphasis in original)). Dr. Jewell took
the count from Table 42 of the ISS. ( Id. ).
Use of a Single Glucose Measurement
initial matter, whether a single elevated glucose measurement
can be used as a proxy for new-onset diabetes
(Plaintiffs' alleged injury in this lawsuit) is suspect.
Dr. Jewell himself was unwilling to testify about the role or
use of blood glucose as a surrogate marker for diabetes
because he was not a clinician. (Dkt. No.
972-7 at 128). Furthermore, when he used fasting glucose
levels as diagnostic of diabetes in other analyses, he
defined diabetes as two post-baseline fasting
glucose measurements > 125 mg/dL, not one. (
E.g., Dkt. No. 1247-9 at ¶ 146). Indeed,
Plaintiffs argue in another context that participants with an
elevated glucose reading at baseline are not necessarily
diabetic " because a diagnosis of diabetes requires more
than a single elevated plasma glucose level." (Dkt. No.
1159 at 12).
Dr. Jewell used a single glucose measurement in his NDA
analysis because, at least for some participants, there is
only one post-baseline glucose measurement during the
controlled trial. ( See Dkt. No. 1247-12 at 59-63).
However, when Dr. Jewell examined the IDEAL data and realized
that a number of participants would have to be excluded from
the analysis because they lacked two post-baseline glucose
values, Dr. Jewell chose not to look at glucose measurements
at all and chose not to run any statistical
analyses using glucose values. (Dkt. No. 1247-9 at ¶
¶ 95-110). Instead, he only used adverse event
reporting. ( Id. ). Nevertheless, with this NDA
data, Dr. Jewell not only performed statistical tests based
on a single elevated glucose measurement but opined that data
based on a single glucose measurement is sufficient to
suggest an increased risk of new-onset diabetes. (
See Dkt. No. 1247-9 at ¶ 6 (opining that this
glucose data " should have alerted Parke-Davis and
Defendant to the possibility of increased risk of new-onset
diabetes associated with atorvastatin treatment" )).
deposition testimony, Dr. Jewell lacks the clinical expertise
to make any inferences about new-onset diabetes from data
regarding a single elevated glucose reading. (Dkt. No. 972-7
at 128). And Plaintiffs state a single elevated glucose
measurement is insufficient to infer diabetes. (Dkt. No. 1159
at 12). Therefore, even if the methodological flaws discussed
below were not present, the Court would exclude Dr.
Jewell's opinion that this data " should have
alerted Parke-Davis and Defendant to the possibility of
increased risk of new-onset diabetes associated with
atorvastatin treatment." (Dkt. No. 1247-9 at ¶ 6).
Including Participants with Elevated Glucose at
Jewell's second methodological flaw in his analysis of
the NDA data is that he chose to include participants that
had glucose measures above 125 mg/dL at baseline
when the study began. ( See Dkt. No. 1247-9 at
¶ 19); see also Reference Manual on Scientific
Evidence 216 (3d ed. 2011) (" [F]laws in the data can
undermine any statistical analysis." ). Dr. Jewell's
analysis starts with the count that three (3) of the 270
placebo participants had " abnormal glucose levels"
during the trial and 37 of the 1,122 Lipitor participants had
" abnormal glucose levels" during the trial. (
Id. at ¶ ¶ 13, 20). However, 2 of the 3
placebo participants with elevated glucose readings during
the trial had baseline glucose levels over 125
mg/dL, and 25 of the 37 Lipitor participants had
baseline glucose levels over 125 mg/dL. (Dkt. No.
1247-12 at ¶ 140; Dkt. No. 974-11 at 131). Seven of the
37 with elevated glucose in the Lipitor group had a
documented history of diabetes before the trial
began. (Dkt. No. 974-11 at 131). Thus, in the
NDA Medical Review, the FDA states the following:
The increased incidence of glucose elevations in the
atorvastatin-treated participants bears comment. In the
placebo-controlled data grouping, of the 37 atorvastatin
participants with glucose elevations, 36/37 had elevated
glucose at baseline, and in 25 of those 36, elevations were
> 1.25 X ULN. In addition, 7/37 had a history of diabetes
and 2/37 had a history of glucose intolerance.
Similarly, in the all-completed studies grouping, of 185
atorvastatin participants with glucose elevations, 115/185
had a history of NIDDM. 174/185 had baseline values > ULN.
In sum, there is little evidence for an effect of
atorvastatin on glucose metabolism.
(Dkt. No. 974-11 at 131) (footnote added).
are two ways that failing to exclude participants with
elevated baseline glucose is problematic for Dr. Jewell's
analysis. First, there is the potential for
confounding. In the NDA trials, 5.3% of all
participants on Lipitor had at least one glucose measurement
above 125 mg/dL before the trial, while only 1.9% of
the placebo participants had at least one glucose reading
above 125 mg/dL before the trial, and this difference between
the two groups was statistically significant. (Dkt. No.
972-36 at ¶ 140). Looking only at the very first
pre-trial glucose measurement for each participant, as
opposed to all pre-trial glucose measurements, 3.83% of the
Lipitor group had an elevated glucose value at this first
measurement and only 1.85% of the placebo group had an
elevated glucose value at this first measurement, though this
difference was not statistically significant. (Dkt. No.
1247-11 at ¶ ¶ 37, 39). This difference has the
potential to confound Dr. Jewell's data.
because Dr. Jewell's analysis includes those with
elevated glucose at baseline, it does not compare
new cases of elevated glucose, i.e., those
participants with elevated glucose due to Lipitor. In
other words, the analysis does not test for new-onset
diabetes, the subject of Dr. Jewell's opinion, or even
new-onset elevated glucose. Dr. Jewell claims that he was
only concerned with " clinically meaningful abnormal
deviations in glucose" or " assessing whether
atorvastatin had a potentially deleterious effect on glucose
levels" regardless of baseline characteristics. (Dkt.
No. 1247-8 at 235.; Dkt. No. 1247-9 at ¶ 19). He argues
that " [w]hether the patient had diabetes, was
prediabetic, had elevated blood glucose before the trial is
irrelevant to me," (Dkt. No. 1247-8 at 235), because all
of these groups could still experience significant increases
in their glucose levels. (Dkt. No. 1247-9 at ¶ 19).
claims are belied by Dr. Jewell use of this data to support
opinions about " the possibility of increased risk of
new-onset diabetes," (Dkt. No. 1247-9 at ¶
6 (emphasis added)), and Plaintiffs argument that this NDA
data supports the opinion that 10 mg of Lipitor causes
new-onset diabetes. (Dkt. No. 1159 at 11-13). However, even
assuming that he did want to assess significant changes in
glucose levels, regardless of baseline characteristics, this
is not what he assessed. He included 100% of the participants
that had an elevated glucose measurement during a trial,
regardless of whether they actually experienced any
significant increase in glucose from baseline. For example,
Patient #1 had a baseline glucose measurement of 131 mg/dL
and an on-treatment glucose measurement of 133 mg/dL, (Dkt.
No. 1247-12 at 59), a change of 2 mg/dL, a change that