Sample size correction for treatment crossovers in randomized clinical trials with a survival endpoint.

摘要

Sample size determination in randomized clinical trials usually relies on the determination of survival rates at the time of analysis in both groups, under the null and the alternative hypotheses, the type I and II error rates and on other assumptions, such as proportional hazards in most cases. However, in numerous clinical trials for malignant chronic diseases, it is currently common that a patient allocated to the conventional treatment group would receive the experimental treatment in case of disease progression or relapse. Such crossovers are usually not taken into account when computing the sample size of the trial, but generally result in a decreased power of the trial. In this work, we aimed to correct the sample size of such trials to control the power, under an exponential survival assumption.