Statistical inference for time-to-event data in non-randomized cohorts with selective attrition.

Abstract

In multi-season clinical trials with a randomize-once strategy, patients enrolled from previous seasons who stay alive and remain in the study will be treated according to the initial randomization in subsequent seasons. To address the potentially selective attrition from earlier seasons for the non-randomized cohorts, we develop an inverse probability of treatment weighting method using season-specific propensity scores to produce unbiased estimates of survival functions or hazard ratios. Bootstrap variance estimators are used to account for the randomness in the estimated weights and the potential correlations in repeated events within each patient from season to season. Simulation studies show that the weighting procedure and bootstrap variance estimator provide unbiased estimates and valid inferences in Kaplan-Meier estimates and Cox proportional hazard models. Finally, data from the INVESTED trial are analyzed to illustrate the proposed method.