United States District Court, D. South Carolina, Charleston Division
IN RE: LIPITOR (ATORVASTATIN CALCIUM) MARKETING, SALES PRACTICES AND PRODUCTS LIABILITY LITIGATION
the Matter of Lipitor (Atorvastatin Calcium) Marketing Sales
Practices and Products Liability Litigation: H Blair Hahn,
LEAD ATTORNEY, Richardson Patrick Westbrook and Brickman, Mt
Plaintiffs' Lead H Blair Hahn, LEAD ATTORNEY, Christiaan
A Marcum, Elizabeth Middleton Burke, Richardson Patrick
Westbrook and Brickman, Mt Pleasant, SC.
Plaintiffs' Liason Mark Charles Tanenbaum, LEAD ATTORNEY,
Mark C Tanenbaum Law Office, Charleston, SC.
Pfizer Inc., Defendant: Amanda S Kitts, John Mark Jones,
David Eidson Dukes, 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, Rachel B
Passaretti-Wu, LEAD ATTORNEYS, PRO HAC VICE, Nelson Mullins
Riley and Scarborough, Charleston, SC; 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 ATTORNEY, Hughes Hubbard and Reed, New
York, NY; Mark Steven Cheffo, LEAD ATTORNEY, Quinn Emanuel
Urquhart and Sullivan, New York, NY; Brett M Collings,
Theodore VH Mayer, Hughes Hubbard and Reed, New York, NY.
Pfizer International LLC, Defendant: Carole W Nimaroff,
George A Tsougarakis, LEAD ATTORNEYS, Hughes Hubbard and
Reed, New York, NY; Loren H Brown, LEAD ATTORNEY, DLA Piper
U.S. LLP, New York, NY; Brett M Collings, Theodore VH Mayer,
Hughes Hubbard and Reed, New York, NY.
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.
MANAGEMENT ORDER NO. 55
Richard Mark Gergel, United States District Judge.
Order relates to:
Hempstead v. Pfizer, Inc., 2:14-cv-1879
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).
The Court will address Plaintiffs' general causation
testimony by separate order. The Court makes no finding here
as to whether the testimony of Plaintiffs' general
causation experts is admissible or whether Plaintiffs can
survive summary judgment on the issue of general causation in
this particular case. For the purposes of this motion, the
Court assumes that general causation can be established in
this case and turns to Plaintiffs' specific causation
has disclosed two case-specific expert witnesses in this
bellwether case, Dr. Daniel Handshoe and Dr. Elizabeth
Murphy. Both experts opine that Lipitor caused, or was a
substantial contributing factor of, Ms. Hempstead's Type
2 diabetes. Pfizer has moved to exclude the testimony of both
experts. (Dkt. Nos. 1004, 1006). Here, the Court addresses
Pfizer's motion to exclude the testimony of Dr. Elizabeth
Murphy. (Dkt. No. 1006).
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., Inc., 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.
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,
" trial 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.
Ms. Hempstead's Medical History and Diagnosis of
Hempstead began seeing primary care physician Dr. Lou Sabih
in January of 1998. (Dkt. No. 1275-1 at 9). In March of 1998,
Dr. Sabih ordered a lipid panel, which showed that Ms.
Hempstead had total cholesterol of 243 mg/dL, LDL of 151
mg/dL, HDL of 41 mg/dL, and triglycerides of 255
mg/dL. ( Id. ). In response to these
labs, Dr. Sabih prescribed 20 mg of Lipitor daily. (
Id. ). Because of apparent concerns about possible
liver toxicity, Ms. Hempstead did not start taking Lipitor at
that time. ( Id. ).
year later in June of 1999 (and after adjustments to her
blood pressure medication), Ms. Hempstead had another lipid
panel, which showed Ms. Hempstead had a total cholesterol of
250 mg/dL, LDL of 175 mg/dL, HDL of 46 mg/dL, and
triglycerides of 142 mg/dL. ( Id. at 10). Ms.
Hempstead weighed 176 lbs at the time and had a body mass
index (BMI) of 26.37. ( Id. ). Her glucose
measurement at the time was 97 mg/dL. ( Id. ).
Ms. Hempstead was again prescribed 20 mg of Lipitor daily. (
Id. ). Ms. Hempstead took Lipitor inconsistently
over the next year. ( Id. ). Pharmacy records
indicate that she did not refill the prescription at all
between January and July of 2000. ( Id. ).
of 2000, Ms. Hempstead began taking Lipitor regularly. (
Id. at 11). In the fall of 2000, Dr. Michael Ausmus
became Ms. Hempstead's primary care physician. (
Id. at 10-11). Two years later, in September of
2002, a lipid panel showed Ms. Hempstead had total
cholesterol of 179 md/dL, LDL of 111 mg/dL, HDL of 40 mg/dL,
and triglycerides of 139 mg/dL. ( Id. at 10). She
had an abnormal glucose reading of 114 mg/dL. ( Id.
). She had gained a total of 13 pounds since starting Lipitor
in 1999, resulting in a total weight of 184 and a BMI of
27.57. ( Id. ).
fall of 2003, Ms. Hempstead stopped taking Lipitor for three
weeks due to abdominal pain. ( Id. at 11). A lipid
panel taken after being off Lipitor for approximately three
weeks showed Ms. Hempstead's blood lipid levels had
risen. She had total cholesterol of 258 mg/dL, LDL of 173
mg/dL, HDL of 46 mg/dL, and triglycerides of 194 mg/dL. (
Id. at 10). Her glucose reading after three weeks
off Lipitor was 122 mg/dL. ( Id. ). Three months
later, after resuming Lipitor, her lipid levels came back
down, with total cholesterol of 176 mg/dL, LDL of 103 mg/dL,
HDL of 37 mg/dL, and triglycerides of 179 mg/dL. (
Id. at 10, 11).
February of 2004, Ms. Hempstead was seen in the emergency
room and diagnosed with colitis. ( Id. at 11). She
had a random blood glucose reading of 214 mg/dL, but there
was no diagnosis of diabetes. ( Id. ). On May 14,
2004, Ms. Hempstead was admitted to the hospital with a blood
glucose level of 613 mg/dL and diagnosed with new-onset
diabetes. ( Id. ). She was two weeks shy of her
sixtieth birthday. (Dkt. No. 1094 at 8). Ms. Hempstead's
weight was not properly recorded during her hospital stay.
However, her weight a couple of weeks prior to the hospital
stay was 191 pounds, with a BMI of 28.6, and her weight at
her first follow-up appointment after the hospital stay was
180 pounds, with a BMI of 27. (Dkt. No. 1275-1 at 10, 11).
The Role of Relative Risk in General and Specific
addressing Dr. Murphy's opinion, it is helpful to review
the difference between general and specific causation and how
each is proven. " [I]n order to carry the burden of
proving a plaintiff's injury was caused by exposure to a
specified substance," a plaintiff must demonstrate
general and specific causation. Westberry v. Gislaved
Gummi AB, 178 F.3d 257, 263 (4th Cir. 1999); Zellers
v. NexTech Ne., LLC, 533 Fed.Appx. 192, 196 n.6 (4th
Cir. 2013) cert. denied, 134 S.Ct. 911, 187 L.Ed.2d
780 (2014). " General causation is whether a substance
is capable of causing a particular injury or condition in the
general population and specific causation is whether a
substance caused a particular individual's injury."
Norris v. Baxter Healthcare Corp., 397 F.3d 878, 881
(10th Cir. 2005). " Plaintiff must first demonstrate
general causation because without general causation, there
can be no specific causation." Id. ; accord
Knight v. Kirby Inland Marine Inc., 482 F.3d 347,
351-52 (5th Cir. 2007).
parties agree that epidemiologists use a two-step process for
establishing general causation. (Dkt. No. 972 at 27-28; Dkt.
No. 1053 at 13); see also Ambrosini v.
Labarraque, 101 F.3d 129, 136, 322 U.S.App.D.C. 19 (D.C.
Cir. 1996). First, studies must establish an association or
correlation between two variables, here, Lipitor and
diabetes. If two variables correlate, the incidence of one
variable (diabetes) changes with the incidence of another
(Lipitor). In other words, one variable (Lipitor) increases
the risk of the other (diabetes). Once an association is
established, epidemiologists apply the " Hill
factors" to evaluate whether an association is causal.
Reference Manual on Scientific Evidence 600 (3d ed. 2011);
In re Zoloft (Sertraline Hydrochloride) Products Liab.
Litig., 26 F.Supp.3d 449, 454-55 (E.D. Pa. 2014),
recon. denied, 2015 WL 314149 (E.D. Pa. Jan. 23,
even if Plaintiffs establish that there is an association
between Lipitor and diabetes (i.e., that Lipitor increases
the risk of diabetes) and that Lipitor is capable of causing
diabetes, it does not necessarily follow the Lipitor caused
the development of diabetes in a particular plaintiff. For
specific causation, the plaintiff must " demonstrate
that the substance actually caused injury in her particular
case." Guinn v. AstraZeneca Pharms. LP, 602
F.3d 1245, 1249 n.1 (11th Cir. 2010). Under a
preponderance-of-evidence burden, a plaintiff must show, more
likely than not, the substance caused, or was a substantial
contributing factor to, her particular injury.
courts have held that one way that a plaintiff can meet her
burden of production on specific causation is to have an
expert witness testify to specific causation based on
epidemiologic studies that find a relative risk of injury of
2.0 or higher and what is referred to as " the logic of
the effect of doubling of the risk." Reference Manual on
Scientific Evidence 612 (3d ed. 2011); see also
Marder v. G.D. Searle & Co., 630 F.Supp. 1087, 1092
(D. Md. 1986) (" In epidemiological terms, a two-fold
increased risk is an important showing for plaintiffs to make
because it is the equivalent of the required legal burden of
proof--a showing of causation by the preponderance of the
evidence or, in other words, a probability of greater than
relative risk ratio is the risk of disease or injury among
people exposed to an allegedly harmful substance divided by
the risk of the disease among those not exposed to the
substance. Reference Manual on Scientific Evidence at 627.
For instance, if the risk of developing diabetes while on
Lipitor is 6% and the risk of developing diabetes not on
Lipitor (i.e., in a placebo group) is 4%, then the relative
risk of developing diabetes for Lipitor is 6/4 or
1.5. A relative risk of 1.0 indicates no
difference between the two groups in risk. The risk in the
two groups is the same (e.g., 5% divided by 5% or 20% divided
no confounding factors, bias, etc., a statistically
significant relative risk ratio between 1.0 and 2.0 can be
used, in conjunction with the " Hill factors," to
establish general causation but cannot be used, by itself, to
establish specific causation. A relative risk ratio in this
range suggests that while some people exposed to the
substance developed the disease due to exposure (i.e., there
is the potential for the substance to cause the disease),
most would have developed the disease anyway. Take the
example above with a relative risk ratio of
1.5, where 4% of the placebo group and 6%
of the Lipitor group develop diabetes. In a group of 100
people all taking Lipitor, six of them will develop diabetes.
Four of these people (4% of 100) would have developed
diabetes regardless, as in the placebo group. The other two
diabetics (2% of 100) would not have developed diabetes but
for Lipitor. In other words, two-thirds of the people who
take Lipitor and develop diabetes would have done so
regardless, and one-third of people who take Lipitor and
develop diabetes would not have developed diabetes but for
the Lipitor. For this minority (the one-third), Lipitor is a
substantial contributing factor to their diabetes. Thus, to
establish specific causation with a relative risk between 1.0
and 2.0, an expert--utilizing a valid methodology, applying
it reasonably and relying on sufficient data to support her
opinions--must opine to a reasonable degree of medical
certainty that the particular plaintiff is in the minority of
those that developed the disease due to exposure to a
particular drug or substance rather than in the majority that
would have developed the disease regardless.
relative risk ratio greater than 2.0, however, suggests that
of the people exposed to a substance who developed the
disease, most of them developed the disease due to
the exposure. For example, if the relative risk of diabetes
due to Lipitor were 3.0, then two-thirds of those on Lipitor
who develop diabetes would not have developed diabetes but
for the drug. An example of this would be if, in a randomized
study, 6% of the Lipitor group developed diabetes and 2% of
the placebo group developed diabetes. In this example, six
out of a hundred people on Lipitor would develop diabetes. Of
these six, two would have done so regardless and four would
develop diabetes only because they took Lipitor.
for a relative risk ratio above 2.0, there is a "
probability of greater than 50%" that the substance at
issue caused the disease or injury. Marder, 630
F.Supp. at 1092 . In other words, it is more likely than not
that the substance caused the injury or disease. This logic
does have its limitations. It relies on studies "
identifying a genuine causal relationship and a reasonably
reliable measure of the increased risk." Reference
Manual on Scientific Evidence at 612. If confounding factors,
bias or random error is the source of the association, rather
than a true causal relationship, the logic falls apart.
Id. at 612-13. Thus, a finding of statistical
significance is very important, and observational studies
with the potential for confounding and bias may not be
sufficient for this theory of specific causation. Randomized
controlled trials may be required to show an actual doubling
of the risk exists (i.e., to show a valid relative risk
ratio). Even with randomized controlled trials, this logic is
based on the assumption that the plaintiff at issue is
similar to the study subjects and has the same amount of
exposure to the substance as the study subjects. Id.
to the actual case at hand, Dr. Murphy determined that "
the most reliable data suggests the [relative] risk ratio is
somewhere around 1.6."  (Dkt. No. 1006-3 at 49).
Thus, using her estimate of relative risk, most of the people
who develop diabetes while on Lipitor would have done so
anyway, and she cannot use the logic of " doubling the
risk" to provide a specific causation opinion. Using her
estimate, 63% of the people who take Lipitor and develop
diabetes would have done so in the absence of
Lipitor, whereas 37% of the people who take Lipitor and
develop diabetes did so only because they took
Lipitor. The question then becomes ...