Liu Jen-pei
Statistical Education Center, Division of Biometry, Graduate Institute of Agronomy, National Taiwan University, Taipei, Taiwan.
Yonsei Med J. 2007 Dec 31;48(6):895-900. doi: 10.3349/ymj.2007.48.6.895.
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.
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.
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.
The non-inferiority approach is appropriate to prove the safety of drugs.
当前用于评估药品疗效的方法并不充分。我们提出一种非劣效性方法来证明药物的安全性。
用于评估药物安全性的传统假设基于危害证明，事实证明这种方法并不充分。因此，基于安全性证明的概念，采用非劣效性假设来证明新药的风险不超过预先设定的可接受安全边际，从而证明一种药物没有过高风险。使用发表在关于万络（罗非昔布）和文迪雅（马来酸罗格列酮）的论文中的结果来说明危害证明的传统方法与安全性证明的非劣效性方法之间的差异。
传统假设的p值大于0.05，未能证明万络和文迪雅存在心血管危害。然而，这些结果并不能证明万络和文迪雅都没有心血管风险。另一方面，非劣效性方法可以证明它们存在过高的心血管风险。
非劣效性方法适用于证明药物的安全性。
