Abstract

We consider a clinical trial in which two versions of a new treatment are compared against control with the primary endpoint of overall survival. At an interim analysis, mid-way through the trial, one of the two treatments is selected, based on the short term response of progression-free survival. For such an adaptive design the familywise type I error rate can be protected by use of a closed testing procedure to deal with the two null hypotheses and combination tests to combine data from before and after the interim analysis. However, with the primary endpoint of overall survival, there is still a danger of inflating the type I error rate: we present a way of applying the combination test that solves this problem simply and effectively. With the methodology in place, we then assess the potential benefits of treatment selection in this adaptive trial design.