The adjustment of the type I error rate in noninferiority trials with λ-margin approach: each of two different new drugs is approved with two independent trials with the same active control.

A regulatory agency usually requires two independent positive trials of the same new drug for approval. If two different new drugs are approved with the λ-margin approach by using the same active control, it implies that four noninferiority trials share the same active control. Sharing the same active control generates dependencies among trials. In this paper we investigate how much such dependencies inflate the unconditional and conditional across-trial type I error rates, and we propose a new procedure to adjust the inflated unconditional across-trial type I error rates.