Debiased inference for stochastic treatment interventions with survival outcomes

Abstract

Estimating the causal effect of a time-dependent treatment on time to death is challenging. In this paper, we formulate the problem using the illness-death model and focus on a stochastic intervention that modifies the hazard governing the transition from no treatment to treatment initiation. Such an intervention can only be implemented at the level of the observed data, whereas the causally valid intervention is defined at the level of the true data-generating process. We provide conditions under which the practically feasible intervention corresponds to the desired causal intervention in the specific setting. We first consider an intervention in which treatment is initiated at a fixed time point, which may subsequently be varied across the relevant time span. However, the resulting estimand is not pathwise differentiable, preventing the development of assumption-lean inference. To address this, we instead consider a smoothed intervention that assigns treatment within a time window around the target time point, thereby yielding a parameter amenable to semiparametric analysis. We derive the corresponding efficient influence function and propose a debiased one-step estimator with desirable robustness properties. We investigate its finite-sample performance in a simulation study and apply the method to the classical Stanford Heart Transplant data, as well as to data on treatment delay among couples with unexplained subfertility seeking intrauterine insemination.