Methodology of therapeutic trials: lessons from the late evidence of the cardiovascular toxicity of some coxibs.
The removal of rofecoxib after several years on the market has caused deep concern among patients, physicians, researchers, editors, and regulatory agencies. Similar situations have occurred in the recent past. They illustrate the serious limitations of preregistration trials. Approved drugs should be subjected to close postmarketing surveillance. A number of methodological issues regarding the evaluation of drug safety are discussed in this article. The advantages and drawbacks of observational studies and randomized trials are reviewed. Emphasis is put on the usefulness of independent steering committees for therapeutic trials and on the value of cumulative meta-analyses.
Ravaud
Philippe
P
Inserm U738, Département d'épidémiologie, de biostatistique et de recherche clinique, groupe hospitalier Bichat - Claude Bernard, faculté Xavier Bichat, université Paris-7, Paris cedex 18, France. philippe.ravaud@bch.ap-hop-paris.fr
Tubach
Florence
F
D026661:Clinical Trials Data Monitoring Committees / Q000458:organization & administration; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D017277:Drug Approval; D004341:Drug Evaluation; D006801:Humans; D007783:Lactones / Q000009:adverse effects* / Q000627:therapeutic use; D015201:Meta-Analysis as Topic; D019370:Observation; D011358:Product Surveillance, Postmarketing; D016032:Randomized Controlled Trials as Topic; D013450:Sulfones / Q000009:adverse effects* / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib