Evidence of cardiovascular risks associated with taking Vioxx, the popular, nonsteroidal anti-inflammatory drug (rofecoxib), could have been identified nearly four years before its manufacturer, Merck, voluntarily pulled the drug from the market, based on data made available through litigation and published in the Nov. 23 issue of Archives of Internal Medicine.
Joseph Ross, MD, assistant professor of geriatrics and palliative medicine at Mount Sinai School of Medicine in New York City, and a team of six investigators analyzed 30 randomized, placebo-controlled trials of Vioxx. Under new FDA disclosure requirements, the analysis may also serve as a blueprint for other independent post-market pharmaceutical safety studies, according to the authors.
The trials enrolled a combined 20,152 individuals, lasted from four weeks to four years and assigned a range of 17 to 2,586 participants to take doses of Vioxx ranging from 12.5 g to 50 mg. The authors pooled the data from these studies and analyzed the results cumulatively, as information from each newly completed clinical trial became available.
The authors found that safety concerns arose almost four years before the drug was withdrawn from the market.
Ross and his colleagues revealed that as of December 2000—when 21 of the 30 studies had been completed—there was a strong concern that patients taking Vioxx were at a greater risk for adverse events or death from cardiovascular conditions or blood clots. Thereafter, collected data through June 2001 showed Vioxx to be associated with a 35 percent increase in risk of a cardiovascular events or death. According to the authors, the association with cardiovascular risk strengthened as more data became available. As of April 2002, the pooled analysis showed a 39 percent increased risk, and as of September 2004, a 43 percent increased risk.
Whitehouse Station, N.J.-based Merck introduced Vioxx to the market in May 1999 and the drug quickly became a commercial success, with sales reaching $2 billion annually.
The authors concluded that due to the requirements of the recently enacted FDA Amendments Act, “public disclosure of trial results within the ClinicalTrials.gov database within 12-24 months of study completion, including both efficacy and safety outcomes, clinical trial data should be available to conduct iterative meta-analyses independent of the FDA and manufacturers."
They concluded: "Physicians and the public deserve to be in a position to make informed choices about risk and benefits [of pharmaceutical products]. And the early disclosure and dissemination of information about potential risk after its recognition must be required."