Noninferiority testing in crossover trials with correlated binary outcomes and small event proportions with...

Regulatory agencies may require demonstrating a new therapy or device as noninferior to an existing method. For example, a new condom type must demonstrate noninferiority to existing latex condoms before consideration as an equivalent method of pregnancy prevention. Studies designed to assess condom effectiveness typically measure experimental and standard condom failure in a crossover trial, resulting in unbalanced correlated binary outcomes with low event proportions. We used simulations to evaluate the test size of a simple population average approach to noninferiority testing with the small event proportions, intracluster correlations, and sample sizes frequently found in condom studies. Results emphasize the importance of considering test accuracy when designing any study.