The opinion of the court was delivered by: J. Phil Gilbert, U.S. District Judge
MEMORANDUM OPINION AND ORDER
Before this Court is Sandoz' motion in limine to exclude the testimony
of the plaintiffs' experts, Drs. Kulig and Petro. (Doc. 212).
On September 12, 2001, following a two-day Daubert hearing, this Court
issued a preliminary order granting Sandoz' motion to exclude the
plaintiffs' experts' causation testimony. [Doc. 316]. Upon a full
consideration of the testimony, exhibits and arguments of the parties,
the Court hereby issues its final order. For the reasons discussed
below, the defendant's motion to exclude the plaintiffs' expert causation
testimony is granted.
This is a products liability case that involves the drug Parlodel.
Parlodel is manufactured by Defendant Sandoz Pharmaceutical Corporation
— now known as Novartis Pharmaceutical Corporation and Sandoz A.G.
The active ingredient of Parlodel is bromocriptine mesylate
("bromocriptine"). Bromocriptine is derived from ergot, a
naturally-occurring fungus that grows on the rye plant. Drugs derived
from ergot are known as ergot alkaloids. Bromocriptine differs
structurally and physically from the other ergot alkaloids in that a
bromine atom has also been added. Bromocriptine prevents lactation from
occurring by blocking the secretion of the hormone prolactin, which acts
on the breasts to induce the secretion of milk.
In 1980, the Food and Drug Administration ("FDA") approved Parlodel to
be used to prevent postpartum lactation in women who could not or elected
not to breast-feed. Fourteen years later, on August 18, 1994, the
defendant withdrew the Parlodel indication for prevention of physiologic
lactation after receiving notice that the FDA would be filing a notice of
opportunity and hearing to withdraw Parlodel for that indication. Parlodel
remains approved for various other indications (e.g., Parkinson's
Disease, amenorrhea, and acromegaly). For the prevention of physiologic
lactation ("PPL"), Parlodel was typically prescribed for fourteen days
with a prescribed dosage of 5 mg per day, taken in two 2.5 mg. doses.*fn1
On the evening of May 9, 1988, after an uneventful pregnancy,
24-year-old Alisa Caraker delivered her infant via a normal and
uneventful cesarean section. The next day, May 10, Mrs. Caraker began
taking Parlodel, prescribed at 2.5 mg. twice per day for 14 days because
she had elected not to breast feed. On May 11, while still in the
hospital, Mrs. Caraker reported developing headaches. During her
hospitalization, she also experienced some transient (temporary, passing
away with time) elevated blood pressure. On May 13, Mrs. Caraker was
discharged in good health, but, after returning home, Mrs. Caraker's
headaches progressively became much worse.
On May 15, six days postpartum, still on Parlodel, Mrs. Caraker
returned to the Carbondale Hospital with a severe headache,
hypertension, and neurologic symptoms. That day, a CT scan (a method of
examining the body's soft tissues using X-rays) revealed a large,
left-sided intracerebral hematoma ("ICH") due to intracerebral
hemorrhaging. On May 16, 1998, Mrs. Caraker was transferred to St.
Francis Medical Center where she underwent brain surgery to remove the
hematoma blood clot and stop the bleeding.
The plaintiffs filed their complaint on March, 25, 1996, claiming that
Parlodel is an unreasonably dangerous and defective product.
Specifically, they allege that (1) in May of 1988, Ms. Caraker took
Parlodel PPL; (2) after taking Parlodel, Ms. Caraker suffered an ICH; and
(3) Ms. Caraker's ingestion of Parlodel caused her stroke. The Carakers
claim damages for their resulting injuries.*fn2
To show that Parlodel caused Mrs. Caraker's stroke, the plaintiffs rely
on the testimony of Toxicologist Kenneth Kulig and Neurologist Denis
Petro. Together, they testify that a causal relationship exists between
Mrs. Caraker's ingestion of Parlodel and her stroke.
The defendants moved to exclude the testimony of Drs. Kulig and Petro
on the grounds that it is not sufficiently reliable. This Court ordered
the parties to file briefs, detailed witness affidavits and all the
relevant exhibits. After reviewing this extensive amount of information,
this Court conducted a two-day Daubert hearing, at which both sides had
the opportunity to present their best streamlined case for or against
admissibility. See Siharath v. Sandoz Pharmaceuticals Corp.,
131 F. Supp.2d 1347, 1350 n. 4 (N.D. Ga. 2001).
The admissibility of plaintiffs' expert evidence is governed by, inter
alia, Federal Rule of Evidence 702 — as interpreted by Daubert v.
Merrell Dow Pharmaceuticals, 509 U.S. 579 (1993), and its progeny.*fn3
The plaintiffs had the burden of showing two things. First, they had
the burden of showing that their experts' opinions were reliable. The
hallmark of this reliability prong is the scientific method, i.e., the
generation of testable hypotheses that are then subjected to the real
world crucible of experimentation, falsification/validation, and
replication. See Daubert v. Merrell Dow Pharmaceuticals, 509 U.S. 579,
593 (1993). Second, they must show that their experts' opinions "fit"
(i.e., have a valid scientific connection to) the issues in this lawsuit
so as to assist the fact-finder in understanding the evidence. See
Daubert, 509 U.S. at 590-92 & n. 9. This requirement is not satisfied when
there is "simply too great an analytical gap between the data and the
opinion proffered." General Elec. Co. v. Joiner, 522 U.S. 136, 138
The district court is not required to simply "tak[e] the expert's word
for it." Advisory Committee Notes to 2000 Amendments to Rule 702 (citing
Daubert v. Merrell Dow Pharmaceuticals, Inc., 43 F.3d 1311, 1319 (9th
Cir. 1995)). Instead, district courts must rigorously scrutinize (1) the
sufficiency of the data upon which the expert relies, (2) the reliability
of the principles and methods the expert employs, and (3) the reliability
of the expert's application of the principles and methods to the facts of
the case. See Fed. R. Evid. 702.
Focusing on the three items enumerated in Rule 702, district courts
must determine whether the expert's opinion "is genuinely scientific [or]
unscientific speculation offered by a genuine scientist." Rosen v.
Ciba-Geigy Corp., 78 F.3d 316, 318 (7th Cir. 1996) (noting that "an
insightful, even an inspired, hunch" is insufficient). This so-called
"gatekeeper" function requires that the district court separate "expert
opinion evidence based on `good grounds' from subjective speculation that
masquerades as scientific knowledge." Glastetter v. Novartis
Pharmaceuticals Corp., 252 F.3d 986, 989 (8th Cir. 2001).
In this case, Drs. Kulig and Petro testified that (1) Parlodel can
cause ICH in general; and (2) Parlodel caused Ms. Caraker's ICH
specifically. To reach their opinions, they each rely on a differential
diagnosis methodology, a methodology that involves "ruling in" potential
causes to develop a potential-cause checklist and then "ruling out"
potential causes one by one based on objective data and criteria.
Causation is attributed to the last potential cause left on the list, or
at least the most probable one if there are two left. The methodology, in
the abstract, has been considered sound, see Glastetter, 252 F.3d at
989; cf. Cooper v. Carl A. Nelson & Co., 211 F.3d 1008, 1019 (7th Cir.
2000), but when it is used in the practice of science (as opposed to its
use by treating physicians in the practice of medicine out of necessity)
it must reliably "rule in" a potential cause. See Glastetter, 252 F.3d at
989. Thus, if the "ruling in" step is based on too great an analytical
leap (or several such leaps), the whole opinion is questionable. See
Advisory Committee Notes to 2000 Amendments to Rule 702 ("any step that
renders the analysis unreliable . . . renders the expert's testimony
In support of their premise that Parlodel causes vasoconstriction, the
plaintiffs' experts point to several kinds of evidence: (1)
epidemiological data, (2) case reports, (2) human dechallenge/rechallenge
data, (3) animal studies, (4) an ergot-alkaloid inference, (5) medical
texts, (6) Sandoz documents, and (7) FDA actions. While admitting most of
this data, individually, would not show that Parlodel causes ICH, they
insist on being 90% certain that Parlodel can cause ICH after putting the
pieces of the puzzle together.*fn4
Generally, the problem with the opinions of Drs. Kulig and Petro is
that their "ruling in" decision requires too many extrapolations from
dissimilar data, too many analytical leaps and involves a loose
application of purportedly objective scientific causation standards. For
these and other reasons, the data these experts used to extrapolate their
conclusions is suspect, and their opinions are more like personal
opinions than products of any scientific methodology rigorously applied.
A. EPIDEMIOLOGICAL STUDIES
Epidemiology is the study of disease patterns and risks in human
populations. "Epidemiology focuses on the question of general causation
(i.e., is the agent capable of causing the disease?) rather than that of
specific causation (i.e., did the agent cause the disease in this
particular individual?)." Reference on Scientific Evidence 335 (Fed.
Judicial Ctr. 2000).
In a typical epidemiologic study, an epidemiologist compares the health
of people exposed to a substance to that of persons not so exposed to
determine whether the exposure to the substance is associated with an
increased rate of disease. There are essentially three types of study
designs used by epidemiologists in attempting to determine whether there
is an association between exposure to an agent and development of a
disease: (1) randomized trial or randomized clinical trial, (2) cohort
studies, and (3) case-control studies.
In any epidemiological study, the first question is whether an
association exists; the second is whether that association is actually a
true association and not an association due to some error. Reference on
Scientific Evidence 387 (Fed. Judicial Ctr. 2000). The second step is
important, because, while a causal relationship is one possible
explanation for an association, an association does not necessarily mean
that there is a cause-effect relationship. See generally, id. at 348.
Epidemiology cannot objectively prove causation; rather, causation is a
judgment for epidemiologists and others interpreting the epidemiological
If an epidemiologist finds any association (either positive or
negative), he then scrutinizes the results in his particular study to
determine whether that association indicates a causal relationship or is
due to chance, error or bias. Similarly, a study that does not find an
association may be erroneous on the same grounds.
In this case, the plaintiffs' experts generally state that the
potentially relevant epidemiological studies that do exist are
"fundamentally flawed" and, therefore, do not show conclusively that
Parlodel either does or does not cause stroke or that the postpartum
period is a risk factor for ICH by itself. Nevertheless, Drs. Kulig and