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In re Rezulin Products Liability Litigation

July 26, 2006

IN RE: REZULIN PRODUCTS LIABILITY LITIGATION,


The opinion of the court was delivered by: Lewis A. Kaplan, District Judge

(MDL No. 1348)

MASTER FILE

This Document Relates to: 00 Civ. 9168, 00 Civ. 3098, 01 Civ. 6066, 01 Civ. 8171, 01 Civ. 11878, 02 Civ. 1719, 02 Civ. 8395, 03 Civ. 2861, 03 Civ. 2863, 03 Civ. 2864, 03 Civ. 2865, 03 Civ. 2867, 04 Civ. 4916, 04 Civ. 7807, 04 Civ. 8538, 04 Civ. 8539, 04 Civ. 8940, 04 Civ. 8941, 04 Civ. 8942.

MEMORANDUM OPINION

Defendants Pfizer, Inc., Warner-Lambert Company, and Parke-Davis (collectively, "Pfizer") move for an order excluding the proposed opinion testimony of experts in reports submitted by 28 plaintiffs*fn1 and granting summary judgment dismissing those plaintiffs' claims. Pfizer argues that the expert reports are not admissible.

I. Background and Undisputed Facts

A. Procedural History

These actions arise from the use of the prescription diabetes medication Rezulin, formerly manufactured by defendants Warner-Lambert Co. and its Parke-Davis division. The drug was approved by the Food and Drug Administration in 1997 but was withdrawn from the market in 2000 after reports that some patients taking it experienced liver failure*fn2 Thousands of lawsuits for alleged personal injuries ensued. The federal actions, including those at issue here, were consolidated before this Court for pre-trial proceedings by the Judicial Panel on Multidistrict Litigation.*fn3

After extensive discovery, Pfizer moved pursuant to Federal Rule of Evidence 702 and Daubert v. Merrell Dow Pharmaceuticals, Inc.,*fn4 to exclude proposed expert testimony proffered by the Plaintiffs' Steering Committee ("PSC") to the effect that Rezulin can cause so-called silent injury to the liver -- that is, that Rezulin can cause liver injury in the absence of marked elevation of specific liver enzymes while the patient was taking the drug.*fn5 In the Silent Injury opinion, familiarity with which is assumed, the Court analyzed the proposed expert testimony, which was intended to provide a basis for finding general causation,*fn6 and concluded that plaintiffs had not established the reliability of the silent injury theory:

"The theory never has been tested or peer-reviewed, has not been published except by [one proposed expert] after the commencement of this litigation and only then in speculative terms and suspicious circumstances, and has no acceptance outside this litigation. The plaintiffs' experts have ignored information that appears to call crucial aspects of their theory into question. The theory rests on a series of empirically unbridgeable analytical gaps. Most importantly, the experts have not established a sound basis for concluding that Rezulin-induced apoptosis can occur at clinically significant levels and remain silent. Similarly, the experts have failed to show that any mitochondrial changes attributable to Rezulin themselves can cause apoptosis or that any cholestatic injury due to Rezulin's effect on the BSEP would be silent. ". . . The plaintiffs attempt to deal with all of these problems by arguing that the testimony in question could factor into the diagnosis of an individual patient. The plaintiffs' position is that a physician, faced with a patient who took Rezulin and had symptoms of liver disease but no elevated enzymes, could use the opinions of [plaintiffs' experts] and the research they cite to conclude that the patient's injury was caused by Rezulin. The flaw, however, is that a physician must have some reliable basis for believing that a particular substance is capable of causing the injury in question in relevant circumstances before concluding that the substance caused that injury in a particular case. Here, there is no such basis."*fn7

The Court accordingly granted Pfizer's motion to exclude the proposed expert testimony on Rezulin's ability to cause silent liver injury.

The Court later issued a so-called Lone Pine order, which required each plaintiff to consider whether good grounds existed to continue prosecuting his or her claim in light of the Silent Injury and other decisions.*fn8 If a plaintiff concluded that good cause to continue existed, he or she was required to provide an expert report reflecting, among other things, "[w]hether the plaintiff's medical records report that the plaintiff had [specific liver enzyme] levels more than two times the upper limit of normal range while the plaintiff was on Rezulin therapy or within 30 days after the last use of Rezulin" and an "expert's opinion on causation of each claimed injury."*fn9

B. Plaintiffs' Lone Pine Submissions

All 28 plaintiffs whose complaints are the subject of this motion subsequently submitted expert opinions.*fn10 Although each opinion states that the given plaintiff sustained a liver injury attributable to Rezulin, no plaintiff has provided evidence that his or her liver enzyme levels were more than two times the upper limit of normal range while he or she was on Rezulin or within 30 days of ceasing the therapy.*fn11 Most of the plaintiffs rely on opinions from the same handful of experts,*fn12 some of whom were already considered on the previous motion. Their opinions are summarized below.

1. Dr. Glenn Wilson, Ph.D.*fn13

Dr. Wilson, a biomedical scientist*fn14 and professor at the University of South Alabama College of Medicine, opines that Rezulin can injure the mitochondria of cells with which it comes into contact.*fn15 He states that Rezulin reduces blood sugar levels by damaging mitochondria, which then results in "organ toxicity, dysfunction, and failure through apoptosis, necrosis, and impaired ATP (energy) production within the organ."*fn16

In reaching this conclusion, Dr. Wilson relies on a variety of data, including drug class effect information, in vitro cell testing, in vivo animal testing, human clinical trials, and case reports.*fn17 He relies also on an in vitro study he performed on normal human hepatocytes exposed to Rezulin at concentrations of 5 and 50 uM, both with and without the presence of fetal bovine albumin.*fn18 This study found that Rezulin causes cell death in normal human hepatocytes in vitro, even in the presence of albumin, "at [Rezulin] concentrations comparable to those [allegedly] found in vivo in the patients taking Rezulin."*fn19 The mechanism for this toxicity, Dr. Wilson states, is damage to the mitochondria, manifested "as a significant reduction in cellular ATP [] at lower doses and cell death at higher doses."*fn20

This study -- which has not been published, subjected to peer review, or independently validated or duplicated -- did not measure liver enzyme levels or the effect of Rezulin in living humans or animals.*fn21 It was prepared for this litigation and was funded at least in part by the Littlepage law firm.*fn22 Nor does the study address the potential concentration discrepancies discussed in the Silent Injury decision -- whether the concentrations of troglitazone used in this and other studies match the concentrations of the drug to which the outside of the cells in patients actually were exposed -- or the question of how troglitazone is distributed in the liver.*fn23

Finally, Dr. Wilson does not state that Rezulin can cause silent injury to human hepatocytes, by apoptosis or otherwise.*fn24 The Littlepage plaintiffs' lawyers incorrectly suggest that he concludes that "[m]ost importantly, because Rezulin's mechanism of injury is directed at the cell's mitochondria and it causes apoptosis, most of this damage occurs without any easy diagnostic means of detection."*fn25 But Dr. Wilson's report makes no such statement and provides no basis for drawing such a conclusion.*fn26 Rather, he confines his conclusions to the medication's toxicity and mechanism of harming the cell and does not opine on what happens after the cell is harmed.*fn27

2. Dr. Herbert A. Rubin, M.D.*fn28

Dr. Rubin, a board-certified internist specializing in gastroenterology,*fn29 states that Rezulin is a known hepatotoxin causing "a multitude of hepatocellular injuries including, but not limited to, cytolytic hepatitis, steatosis, microvesicular steatosis, apoptosis, and cholestatis."*fn30 He bases his conclusions on internal Pfizer documents, the testimony of Pfizer employees and experts, other experts' testimony, his own experience as a clinician, and the published medical literature.*fn31

In analyzing the cause of the Littlepage plaintiffs' alleged symptoms, he states that the "damage Rezulin causes to liver cells leads to liver cell death via apoptosis. Cell death by apoptosis does not result in the release of [liver enzymes] into the blood stream unless there has been massive liver cell death."*fn32 He does ...


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