Sample size calculations for combination drugs of 2 monotherapies with a single approved dose level: Binary endpoint cases

Background: In this article, we study the sample size calculations for the combination drugs of 2 monotherapies with a single approved dose level when the primary endpoints are binary. Methods: Two study cases are examined: In the first, each monotherapy has the same indication, while in the second, each monotherapy has a different indication. The sample sizes are calculated by using an asymptotic joint distribution of test statistics and employing unequal allocation for 3 popular measures of 2 proportions: the risk difference, the log relative risk, and the log odds ratio. Results: Results show that our proposed method produces smaller total sample sizes compared with the heuristic method. Conclusions: The total sample sizes can be reduced by incorporating unequal allocation and dependency between 2 test statistics.