Adaptive Superiority and Noninferiority Trial Design with Paired Binary Data

Abstract

Non-inferiority of a diagnostic test to the standard is a common issue in medical research. For instance, we may be interested in determining if a new diagnostic test is noninferior to the standard reference test because the new test might be inexpensive to the extent that some small inferior margin in sensitivity or specificity may be acceptable. Noninferiority trials are also found to be useful in clinical trials, such as image studies, where the data are collected in pairs. Conventional noninferiority trials for paired binary data are designed with a fixed sample size and no interim analysis is allowed. Adaptive design which allows for interim modifications of the trial becomes very popular in recent years and are widely used in clinical trials because of its efficiency. However, to our knowledge there is no adaptive design method available for noninferiority trial with paired binary data. In this study, we developed an adaptive design method for non-inferiority trials with paired binary data, which can also be used for superiority trials when the noninferiority margin is set to zero. We included a trial example and provided the SAS program for the design simulations.