Blinded sample size recalculation in clinical trials with binary composite endpoints.
We consider clinical trials with a binary composite endpoint where the trial is successful when a significant result is achieved for the composite or one prespecified main component. Appropriate sample size planning is challenging in this situation, as in addition to the Type I error rate, power, and target difference the overall event rates and the correlation between the test statistics have to be defined. Reliable estimates of these quantities, however, are usually hard to obtain and therefore there is a high risk to not achieve the intended power in a fixed sample size design. In this article, we propose an internal pilot study design where the nuisance parameters are estimated in a blinded way at an interim stage and where the sample size is then revised accordingly. We investigate the characteristics of the proposed design with respect to the actual Type I error rate, power, and sample size. The application of this design is illustrated by a clinical trial example.
a Institute of Medical Biometry and Informatics , University of Heidelberg , Heidelberg , Germany.
Anja
A
Sander
a Institute of Medical Biometry and Informatics , University of Heidelberg , Heidelberg , Germany.
Geraldine
G
Rauch
a Institute of Medical Biometry and Informatics , University of Heidelberg , Heidelberg , Germany.
Meinhard
M
Kieser
D002986:Clinical Trials as Topic; D006801:Humans; D010865:Pilot Projects; D012107:Research Design; D018401:Sample Size
Clinical trials; composite endpoints; internal pilot study design; multiple testing; sample size recalculation