Sample Size Calculations for Combination Drugs of Two Monotherapies With One Approved Dose Level

In this article, we consider sample size calculations for combination drugs of two monotherapies that each has only one approved dose level. We modify the method of Laska and Meiner by employing the asymptotic joint distribution of test statistics to derive the power function and using unequal allocation to minimize the total sample sizes. Two cases are investigated. In the first case, each monotherapy has the same indication. A heuristic method, the method of Laska and Meiner, and the proposed method are compared in terms of the total sample sizes. We show that the proposed method produces the smallest total sample sizes. In the second case, each monotherapy has a different indication. While the method of Laska and Meiner cannot be applied in this case, we show that the proposed method can be employed and that it produces smaller total sample sizes than a heuristic method.