Exact power and sample size in clinical trials with two co-primary binary endpoints

Music City Center 

Although clinical trials in many therapeutic areas evaluate a single binary endpoint as the primary endpoint, clinical trials in certain therapeutic areas require the use of two co-primary binary endpoints to evaluate treatment benefit multi-dimensionally. When designing clinical trials with two co-primary binary endpoints, considering the correlation between the two endpoints can increase the power of the trial and can consequently reduce the required sample size, leading to improved trial efficiency. For this study, we derive formulae for calculating the exact power and sample size in clinical trials with two co-primary binary endpoints. The proposed formulae are useful for any statistical test for binary endpoints. Numerical investigation under various scenarios showed that our proposed formulae can incorporate consideration of the correlation between two co-primary binary endpoints in the sample size calculation, thereby allowing the required sample size to be reduced. We also demonstrate that the exact power for the required sample size calculated using our proposed formula is approximately equal to a target power.

binary endpoint

co-primary endpoints

correlation

exact

power

sample size 

Biopharmaceutical Section