title: Bias in progression-free survival analysis due to intermittent assessment of progression.
abstract: 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.
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, ON N2L 3G1, Waterloo, Canada.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, ON N2L 3G1, Waterloo, Canada.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cook
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, ON N2L 3G1, Waterloo, Canada.
authors.forename: Lan
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Statistics and Actuarial Science, University of Waterloo, ON N2L 3G1, Waterloo, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Boruvka
mesh_terms: D015982:Bias; D015331:Cohort Studies; D003198:Computer Simulation; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008390:Markov Chains; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms; D016032:Randomized Controlled Trials as Topic
keywords: illness-death process; intermittent observation; model misspecification; multistate model; progression-free survival