Supplementary Confirmatory Analyses of the Components

Abstract

As discussed above, clinical trials using a composite endpoint as primary outcome are often difficult to interpret as the single components may show varying or even opposite treatment effects. Although a descriptive analysis of the single components is the current standard and can reveal those problems, this approach does not provide any confirmatory evidence and thus gives no guidance for a definite conclusion on the treatment efficacy. Methods for a confirmatory analysis of a composite endpoint and one main component have been presented in Part III of this book. In there, the focus was to define an efficacy claim based on a multiple test problem and to calculate the sample size such that there is sufficient power to reach this claim. However, a confirmatory analysis of the components can still be of interest, even if the underlying multiple test problem does not correspond to the formal efficacy claim for which the trial is powered. In this chapter, the focus lies on simple confirmatory multiple test strategies for the components which provide a reasonable chance to get additional confirmatory evidence without the need to increase sample size.