Drug Safety 2005; 28 (8): 651-658

In major medical journals, as well as in the public 1. Postmarketing Studies Confirmed the Early Signals media, it has been said that regulators have not managed the risk issues of rofecoxib (Vioxx®)1 A review of the discussions in the WHO email well. The Canadian Medical Association is even conference system (Vigimed) and discussions at calling for a new body to be set up to monitor drug subsequent annual meetings of the WHO Prosafety in that country. They are reported as saying gramme in 2001 and 2002 reveals continuous monithat North America’s regulatory agencies have toring of the selective cyclo-oxygenase (COX)-2 “failed miserably”.[1] In another article, the authors inhibitor situation, particularly of rofecoxib, by regsay: “our findings indicate that rofecoxib should ulators. In several countries, regulatory authorities have been withdrawn several years earlier. The readid warn both health professionals and the public about the latest developments reported in the literasons why manufacturer and drug licensing authoriture on a regular basis via official newsletters and ties did not continuously monitor and summarise the websites. Even in February 2000 there were recomaccumulating evidence need to be clarified”.[2] mendations to add information about cardiovascular These are but two examples of the criticism of events to the labelling of rofecoxib in the US[3] and pharmacovigilance as it relates to rofecoxib and elsewhere. these reflect broader drug safety concerns. More information came from the VIGOR (Vioxx In fact, pharmacovigilance detected the early sigGI Outcomes Research) study,[4] which received nals of an increased risk of cardiovascular disorders wide publicity. The main criticism of this trial was with rofecoxib. At the annual meeting of the nationthat the comparator in VIGOR, naproxen, may have reduced the MI rate and many further studies, using al centres participating in the WHO Programme for a number of COX-2 selective drugs, were performed International Drug Monitoring in Tunis (October by the pharmaceutical industry with the MI rate in 2000) the Netherlands Monitoring Centre (Lareb) mind. presented new evidence of cardiovascular disorders The Merck polyp trial, APPROVe (Adenomatous related to rofecoxib, with reporting of a high odds Polyp Prevention on VIOXX), is but one study that ratio for adverse cardiovascular effects, with some included a well designed safety evaluation and safefatalities and occurring early in treatment. The afty concerns led to the premature closure of this study fected patients were elderly and in addition, the dose at 34 months when the MI rate with rofecoxib at 18 of rofecoxib was often high. This prompted a remonths was found to be significantly higher than sponse from many countries where myocardial inthat in the control group. Two odd features of this farction (MI) had been seen in association with study were the relatively low MI rate in the controls rofecoxib use. So what happened after that, why did and the non-linear increase in MI in the rofecoxib it happen and what can we do better? group following long-term use (this could be inter-