Sample size determination using an interim analysis.

Abstract

Interim analyses are often employed to terminate comparative clinical trials for ethical or economic reasons when the evidence indicates that one treatment is superior to the other. Here an interim analysis is proposed for the situation where a one-sided test is to be performed. The proposed interim analysis consists of a one-sided test to terminate the clinical trial if it appears that the null hypothesis of interest is true. By noting that incorporation of a single interim analysis is similar to the two-stage procedure used for constructing a test procedure with power independent of the unknown variance, it also includes estimation of the variance, which can be used to control the power of the test if the trial is not terminated. Various properties of this two-stage procedure and derivation of the constants needed for its implementation are presented.