The impact of heterogeneity on the comparison of survival times.

We consider several sources of heterogeneity in a clinical trial with patients' survival time as the main response criterion: differences in prognosis which can be attributed to a latent or ignored prognostic factor; differences in treatment efficacy in subgroups of patients, and differences in treatment combinations received by the patients. The impact of these types of heterogeneity on the treatment comparison is studied assuming a proportional hazards model. It is measured by the size and power of the logrank and proportional hazards score tests and by the bias of the estimated treatment effect. We show that heterogeneity can seriously affect the treatment comparison and has to be considered during the planning stage as well as at the analysis of a clinical trial.