Nested g-computation: A causal approach to analysis of censored medical costs in the presence of time-varying treatment.

Rising medical costs are an emerging challenge in policy decisions and resource allocation planning. When cumulative medical cost is the outcome, right-censoring induces informative missingness due to heterogeneity in cost accumulation rates across subjects. Inverse-weighting approaches have been developed to address the challenge of informative cost trajectories in mean cost estimation, though these approaches generally ignore post-baseline treatment changes. In post-hysterectomy endometrial cancer patients, data from a linked database of Medicare records and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute reveal substantial within-subject variation in treatment over time. In such a setting, the utility of existing intent-to-treat approaches is generally limited. Estimates of population mean cost under a hypothetical time-varying treatment regime can better assist with resource allocation when planning for a treatment policy change; such estimates must inherently take time-dependent treatment and confounding into account. In this paper, we develop a nested g-computation approach to cost analysis to address this challenge, while accounting for censoring. We develop a procedure to evaluate sensitivity to departures from baseline treatment ignorability. We further conduct a variety of simulations and apply our nested g-computation procedure to two-year costs from endometrial cancer patients.