Methods for one-sided testing of the difference between proportions and sample size considerations related to non-inferiority clinical trials

Assessment of non-inferiority is often performed using a one-sided statistical test through an analogous one-sided confidence limit. When the focus of attention is the difference in success rates between test and active control proportions, the lower confidence limit is computed, and many methods exist in the literature to address this objective. This paper considers methods which have been shown to be popular in the literature and have surfaced in this research as having good performance with respect to controlling type 1 error at the specified level. Performance of these methods is assessed with respect to power and type 1 error through simulations. Sample size considerations are also included to aid in the planning stages of non-inferiority trials focusing on the difference in proportions. Results suggest that the appropriate method to use depends on the sample size allocation of subjects in the test and active control groups. Copyright (C) 2007 John Wiley & Sons, Ltd.