Dissection of non-inferiority clinical trials to establish effectiveness
Although non-inferiority trials have been practiced for decades,they continue to be a subject of ongoing debate,especially due to the misunderstanding and misuse of international guidelines,necessitating a reevaluation.Generally,current non-inferiority testing methods can only determine whether a test drug is superior to a placebo,confirming its efficacy,but they struggle to provide comparative conclusions with positive control drugs.That is to say,non-inferiority trials do not produce genuine non-inferiority conclusions unless a clinical threshold for efficacy difference is additionally set.Furthermore,the non-inferiority margin represents a statistical limit in the confidence interval of the efficacy difference.However,the choice of its size boils down to clinical judgment,correlating to the clinically acceptable sample size.Therefore,the non-inferiority margin should be neither equated with an efficacy difference,nor considered the maximum clinically acceptable loss of efficacy when comparing the test drug with a positive control drug.Moreover,the use of non-inferiority trials for evaluating generic drugs in China has historical reasons.Since these trials cannot produce comparative conclusions,they should be discarded in favor of bioequivalence trials with clinical endpoints.This article,starting from basic principles and relying on international guidelines,uses examples to clarify the above key issues and attempts to propose some solutions,providing a reference for the proper conduct of non-inferiority trials in China.
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