A Mixed Approach for Proving Non‐Inferiority in Clinical Trials with Binary Endpoints

Abstract

When a new treatment is compared to an established one in a randomized clinical trial, it is standard practice to statistically test for non‐inferiority rather than for superiority. When the endpoint is binary, one usually compares two treatments using either an odds‐ratio or a difference of proportions. In this paper, we propose a mixed approach which uses both concepts. One first defines the non‐inferiority margin using an odds‐ratio and one ultimately proves non‐inferiority statistically using a difference of proportions. The mixed approach is shown to be more powerful than the conventional odds‐ratio approach when the efficacy of the established treatment is known (with good precision) and high (e.g. with more than 56% of success). The gain of power achieved may lead in turn to a substantial reduction in the sample size needed to prove non‐inferiority. The mixed approach can be generalized to ordinal endpoints.