Bias in progression‐free survival analysis due to intermittent assessment of progression

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. Copyright © 2015 John Wiley & Sons, Ltd.