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CARAKER v. SANDOZ PHARMACEUTICALS CORP.

November 21, 2001

ALISA ANN CARAKER AND KEITH ALLEN CARAKER, PLAINTIFFS,
v.
SANDOZ PHARMACEUTICALS CORP. AND SANDOZ AG, DEFENDANTS.



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.

BACKGROUND

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. ("Sandoz").

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).

DISCUSSION

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 (1997).

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 inadmissible").

To "rule in" Parlodel on their differential diagnoses, the plaintiffs' experts postulate their theory: (1) Parlodel causes arteries to constrict (i.e., vasoconstriction) either in general or when the patient has a low vascular tone specifically; (2) vasoconstriction can elevate blood pressure; (3) high blood pressure is a recognized risk factor for ICHs, (4) Parlodel causes (or can cause) ICH, especially in postpartum women who would expect to normally have low vascular tone immediately after delivery. Cf. Glastetter, 252 F.3d at 989 (outlining methodology of Drs. Kulig and Petro); Siharath v. Sandoz Pharmaceuticals Corp., 131 F. Supp.2d 1347, 1354-55 (N.D. Ga. 2001) (outlining methodology of plaintiffs' experts including Drs. Kulig and Petro).

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 data.

Epidemiologic studies typically provide an estimate of "relative risk" ("RR"),*fn5 which is the strength of an association between exposure and disease. Relative risk is the ration of the incidence of a disease in exposed individuals to the incidence in unexposed individuals. A relative risk of 1.0 means that the incidence in the groups is the same; that is, the exposure has no association with the disease. If the study is properly performed, a relative risk below 1.0 means that the exposure is associated with the absence of the disease (a negative association), whereas a relative risk significantly above 1.0 means that exposure is associated with an increased risk of the disease (positive association).*fn6

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 Petro ...


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