Planning the size of survival time clinical trials with allowance for stratification

Abstract

Approximate allocation designs for comparing two survival distributions are considered and compared with the exact solution. The influence of incorporating covariates by stratification, accrual and follow-up duration on trial size and power is investigated. The Bernstein and Lagakos design is suited for exponential survival due to its generality and allowance for stratification while the Freedman design is convenient for distribution-free survival in view of its simplicity. With other specifications fixed, the saving in sample size becomes minimal as the accrual period or post-accrual follow-up time units expand above three. Required sample size also increases dramatically when the number of strata exceeds three.