Estimation of treatment effect among treatment responders with a time-to-event endpoint

Abstract

In a placebo-controlled clinical study one may calculate the average treatment effect to convey the effect of the active treatment on some outcome. However, if it is speculated that the treatment only has an effect if the patient responds to the treatment defined by a certain biomarker response, then it is arguably more relevant to estimate the treatment effect among such responders. We present such a causal parameter that is based on principal stratification and is identified under the exclusion of a treatment effect among the non-responders. We focus on time-;to-event outcomes allowing for right censoring, and construct a doubly robust and efficient estimator based on the associated efficient influence function. The properties of the estimator are showcased in a simulation study and the methodology is applied to the Leader trial investigating the effect of liraglutide on the occurrence of cardiovascular events.