Rethinking Statistical Approaches to Evaluating Drug Safety

PURPOSE: The current methods used to evaluate the efficacy of drug products are inadequate. We propose a non-inferiority approach to prove the safety of drugs. MATERIALS AND METHODS: Traditional hypotheses for the evaluation of the safety of drugs are based on proof of hazard, which have proven to be inadequate. Therefore, based on the concept of proof of safety, the non-inferiority hypothesis is employed to prove that the risk of new drugs does not exceed a pre-specified allowable safety margin, hence proving that a drug has no excessive risk. The results from papers published on Vioxx® and Avandia® are used to illustrate the difference between the traditional approach for proof of hazard and the non-inferiority approach for proof of safety. RESULTS: The p-values from traditional hypotheses were greater than 0.05, and failed to demonstrate that Vioxx® and Avandia® are of cardiovascular hazard. However, these results cannot prove that both Vioxx® and Avandia® are of no cardiovascular risk. On the other hand, the non-inferiority approach can prove that they are of excessive cardiovascular risk. CONCLUSION: The non-inferiority approach is appropriate to prove the safety of drugs.