Robust Causal Inference for EHR-based Studies of Point Exposures with Missingness in Eligibility Criteria

Abstract: Missingness in variables that define study eligibility criteria is a seldom addressed challenge in electronic health record (EHR)-based settings. It is typically the case that patients with incomplete eligibility information are excluded from analysis without consideration of (implicit) assumptions that are being made, leaving study conclusions subject to potential selection bias. In an effort to ascertain eligibility for more patients, researchers may look back further in time prior to study baseline, and in using outdated values of eligibility-defining covariates may inappropriately be including individuals who, unbeknownst to the researcher, fail to meet eligibility at baseline. To the best of our knowledge, however, very little work has been done to mitigate these concerns. We propose a robust and efficient estimator of the causal average treatment effect on the treated, defined in the study eligible population, in cohort studies where eligibility-defining covariates are missing at random. The approach facilitates the use of flexible machine-learning strategies for component nuisance functions while maintaining appropriate convergence rates for valid asymptotic inference. EHR data from Kaiser Permanente are used as motivation as well as a basis for extensive simulations that verify robustness properties under various degrees of model misspecification. The data are also used to demonstrate the use of the method to analyze differences between two common bariatric surgical interventions for long-term weight and glycemic outcomes among a cohort of severely obese patients with type II diabetes mellitus.