RCTs with Time-to-Event Outcomes

Abstract

RCTs are often designed with the goal of investigating a causal effect of a new treatment drug vs. the standard of care on a time-to-event outcome. Possible outcomes are time to death, time to virologic failure, and time to recurrence of cancer. The data collected on a subject accumulates over time until the minimum of the time of analysis (end of study), the time the subject drops out of the study, or until the event of interest is observed. Typically, for a large proportion of the subjects recruited into the trial, the subject is right censored before the event of interest is observed, i.e., the time of analysis or the time the subject drops out of the study occurs before the time until the event of interest. The dropout time of the subject can be related to the actual time to failure one would have observed if the person had not dropped out prematurely. In this case, the standard unadjusted estimator of a causal effect of treatment on a survival time, such as the difference of the treatment-specific Kaplan–Meier survival curves at a particular point in time, is not only inefficient by not utilizing the available covariate information, but it is also biased due to informative dropout.