Cancer clinical trials are routinely designed to assess the effect of treatment on disease progression and death, often in terms of a composite endpoint called progression-free survival. When progression status is known only at periodic assessment times, the progression time is interval censored, and complications arise in the analysis of progression-free survival. Despite the advances in methods for dealing with interval-censored data, naive methods such as right-endpoint imputation are widely adopted in this setting. We examine the asymptotic and empirical properties of estimators of the marginal progression-free survival functions and associated treatment effects under this scheme. Specifically, we explore the determinants of the asymptotic bias and point out that there is typically a loss in power of tests for treatment effects.
Keywords: illness-death process; intermittent observation; model misspecification; multistate model; progression-free survival.
© 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.