Physical Sciences and Mathematics Commons^™

Adaptive Non-Inferiority Margins Under Observable Non-Constancy, Brett S. Hanscom, Deborah J. Donnell, Brian D. Williamson, Jim Hughes

UW Biostatistics Working Paper Series

A central assumption in the design and conduct of non-inferiority trials is that the active-control therapy will have the same degree of effectiveness in the planned non-inferiority trial as it had in the prior placebo-controlled trials used to define the non-inferiority margin. This is referred to as the `constancy' assumption. If the constancy assumption fails, the chosen non-inferiority margin is not valid and the study runs the risk of approving an inferior product or failing to approve a beneficial product. The constancy assumption cannot be validated in a trial without a placebo arm, and it is unlikely ever to be …