In re Rezulin Products Liability Litigation, 00 Civ. 2843(LAK).

• Decision Date: 26 July 2006
• Docket Number: No. 03 Civ. 2865.,No. 04 Civ. 8539.,No. 00 Civ. 9168.,No. 01 Civ. 11878.,MDL No. 1348.,No. 02 Civ. 1719.,No. 02 Civ. 8395.,No. 01 Civ. 6066.,No. 03 Civ. 2867.,No. 01 Civ. 8171.,No. 03 Civ. 2863.,No. 03 Civ. 2861.,No. 04 Civ. 8538.,No. 04 Civ. 4916.,No. 00 Civ. 2843(LAK).,No. 04 Civ. 7807.,No. 03 Civ. 2864.,00 Civ. 2843(LAK).,00 Civ. 9168.,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.
• Citation: 441 F.Supp.2d 567
• Parties: In re REZULIN PRODUCTS LIABILITY LITIGATION.
• Court: U.S. District Court — Southern District of New York

441 F.Supp.2d 567

In re REZULIN PRODUCTS LIABILITY LITIGATION.

No. 00 Civ. 2843(LAK).

No. 00 Civ. 9168.

No. 01 Civ. 6066.

No. 01 Civ. 8171.

No. 01 Civ. 11878.

No. 02 Civ. 1719.

No. 02 Civ. 8395.

No. 03 Civ. 2861.

No. 03 Civ. 2863.

No. 03 Civ. 2864.

No. 03 Civ. 2865.

No. 03 Civ. 2867.

No. 04 Civ. 4916.

No. 04 Civ. 7807.

No. 04 Civ. 8538.

No. 04 Civ. 8539.

MDL No. 1348.

United States District Court, S.D. New York.

July 26, 2006.

Stanley M. Chesley, Louise M. Roselle, Jean M. Geoppinger, Waite, Schneider, Bayless & Chesley Co., L.P.A., Cincinnati, OH, for Plaintiffs Hughes and Prince.

Robert J. Zavesky, Berger & Zavesky Co., L.P.A., Cleveland, OH, for Plaintiffs Anderson, Hughes, and Prince.

Zoe B. Littlepage, Joshua H. Brockman, Christopher L. Nichols, Natasha D. Hanberry, Littlepage Booth, Houston, TX, for Plaintiffs Borklund, Bowman, Brown, Buskey, Dyal, Elizono, Freel, Gable, Gandy, Glass, Green, Molina, Morris, Negron, Ormeland,,Perez, Salinas, Sanchez, Spivey, Vallery, Walker, Weaver, Webb, Weisser, and Winberg.

David Klingsberg, Steven Glickstein, Bert Slonim, Kaye Scholer LLP, for Defendants.

MEMORANDUM OPINION

KAPLAN, District Judge.

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 plaintiffs¹ 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 failure² 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.³

After extensive discovery, Pfizer moved pursuant to Federal Rule of Evidence 702 and Daubert v. Merrell Dow Pharmaceuticals, Inc.,⁴ 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.⁵ 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,⁶ 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."⁷

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.⁸ 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."⁹

B. Plaintiffs' Lone Pine Submissions

All 28 plaintiffs whose complaints are the subject of this motion subsequently submitted expert opinions.¹⁰ 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.¹¹ Most of the plaintiffs rely on opinions from the same handful of experts,¹² some of whom were already considered on the previous motion. Their opinions are summarized below.

1. Dr. Glenn Wilson, Ph.D.¹³

Dr. Wilson, a biomedical scientist¹⁴ 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.¹⁵ 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."¹⁶

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.¹⁷ He relies also on an in vitro study he performed on normal human hepatocytes exposed to Rezulin at concentrations of 5 and 50 µM, both with and without the presence of fetal bovine albumin.¹⁸ 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.¹⁹ 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."²⁰

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.²¹ It was prepared for this litigation and was funded at least in part by the Littlepage law firm.²² Nor does the study address the potential condentration 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.²³

Finally, Dr. Wilson does not state that Rezulin can cause silent injury to human hepatocytes, by apoptosis or otherwise.²⁴ 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."²⁵ But Dr. Wilson's report makes no such statement and provides no basis for drawing such a conclusion.²⁶ 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.²⁷

2. Dr. Herbert A. Rubin, M.D.²⁸

Dr. Rubin, a board-certified internist specializing in gastroenterology,²⁹ 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."³⁰ 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.³¹ 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."³² He does not, however, provide any support for this conclusion about silent liver injury.³³

3. Dr. Martyn Smith, Ph.D³⁴

Dr. Smith, a toxicologist, testified at length at the Silent Injury hearing as to his theory that Rezulin can cause apoptosis by either triggering "a cascade of chemical events in which the mitochondria cease functioning normally and release a protein into the cytoplasm that triggers apoptosis" or interfering with the functioning of the bile salt export pump, which leads "to the build-up of toxic bile salts in the cells [which] triggers apoptosis."³⁵ The Court analyzed his opinion and conclusions in the Silent Injury decision, eventually excluding the opinion as evidence...