Toxicology Litigation Support

Vioxx

VIOXX (rofecoxib) is a non-steroidal anti-inflammatory drug recommended for use as a analgesic and anti-inflammatory medication in cases of arthritis and menstrual pain, among other conditions. It was launched in 1999 and has been heavily marketed in the US and in over 80 other countries. VIOXX is a diphenlyfuranone sulfone and is in a class of drugs called “COX-2 inhibitors”. It is thought to provide its therapeutic effects by inhibition of prostaglandin synthesis via inhibition of cyclooxygenase-2(COX-2). Recommended doses of VIOXX begin at 12.5mg upt to 50mg and attains peak plasma concentrations in about 2-3 hours but this peak can be delayed from 1-2 hours by food. Other drugs in this class include Celebrex and Bextra.

Although the extent of knowledge by Merck relative to this drug’s potential for initiating cardiovascular and thrombotic events awaits discovery, a clinical trial called “VIGOR” was reported in the New England Journal of Medicine in November of 2000. Included in those findings was the observation of 18 non-fatal cases of myocardial infarction in the VIOXX treated group versus only four cases in the naproxen group. In addition, they reported six peripheral thrombotic events versus only one in the naproxen group. It would appear that this was an advanced warning of the potential for this drug to produce cardiovascular deaths and thrombotic strokes, as has been recently reported in the APPROVe Trial of VIOXX leading to withdrawal of the drug from the market.

While the VIOXX litigation is in its infancy, it becomes important to develop an approach to these cases that can withstand challenges of the Federal Court System relative to causation. What then is the role of the Toxicologist in this litigation? The answer is in the establishment of Causation that will survive the Federal Court System requirements, that is, Daubert.

It is obvious that review of the studies in both animals and man that resulted in the FDA’s approval of the drug, that is, the documents which make up the IND[Investigative New Drug Application] and the NDA[ New Drug Application] will be important. Timing and the number of Adverse Effect Reports to Merck and their disclosures to the FDA will also be of interest . What is less obvious, is the need to review pathological findings related to the upstream animal studies that were carried out in support of the establishment of clinical trials to determine if there was any evidence of any cardiovascular or thrombotic effects in test animals. In other words, what did Merck scientists know about this drug prior to administering it to people in clinical trials, and when did they know it?

The task ahead is daunting and will require an appropriate team of experts to address the various issues at hand. Clearly, a Toxicologist should be a key person on that team.

Richard A Parent, PhD, DABT, FATS, RAC, ERT
Consulting Toxicologist and President
Consultox Limited

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