Framing time-to-event estimands and censoring mechanisms in oncology in light of the estimands framework

In oncology clinical trials with time-to-event endpoints, censoring rules have traditionally been defined and applied following standard approaches based on longstanding regulatory guidelines. The estimand framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest and requires predefining the handling of intercurrent events that occur after treatment initiation and either preclude the observation of an event of interest or impact the interpretation of the treatment effect. In the context of time to event endpoints, this requires a careful discussion on how censoring rules are applied. We discuss a practical problem in clinical trial design and execution, i.e. in some clinical contexts it is not feasible to systematically follow patients to an event of interest. We discuss what censoring means in such contexts and alternative strategies available to address it. We introduce terminology to distinguish types of censoring. We provide recommendations for trial design, stressing the need for close alignment of the clinical question of interest and study design, impact on data collection and other practical implications. We discuss the use of sensitivity and supplementary analyses to examine such censoring assumptions.