Proximal Path-Specific Inference

Causal mediation analysis has been extended to estimate path-specific effects with multiple intermediate variables, isolating treatment effects through a mediator of interest while excluding pathways through its ancestors. Such analyses address bias from recanting witnesses, i.e., treatment-induced mediator-outcome confounders. However, existing methods typically rely on stringent assumptions precluding general unmeasured confounding, which are often violated in practice. In this paper, we relax these restrictions by leveraging observed covariates as proxy variables to accommodate unmeasured confounding among the treatment, recanting witness, mediator, and outcome. Using proximal confounding bridge functions, we develop four nonparametric identification strategies for the path-specific effect. We further derive the efficient influence function and propose a quadruply robust, locally efficient estimator. To handle high-dimensional nuisance parameters, we propose a proximal debiased machine learning approach. We theoretically guarantee that our estimator achieves $\sqrt{n}$-consistency and asymptotic normality even when machine learning estimators for nuisance functions converge at slower rates. Our approaches are validated via semiparametric and nonparametric simulations and an application to the CDC WONDER Natality study, estimating the path-specific effect of prenatal care on preterm birth through preeclampsia, independent of maternal smoking during pregnancy.

Proximal Inference on Population Intervention Indirect Effect

The population intervention indirect effect (PIIE) is a novel mediation effect representing the indirect component of the population intervention effect. Unlike traditional mediation measures, such as the natural indirect effect, the PIIE holds particular relevance in observational studies involving unethical exposures, when hypothetical interventions that impose harmful exposures are inappropriate. Although prior research has identified PIIE under unmeasured confounders between exposure and outcome, it has not fully addressed the confounding that affects the mediator. This study extends the PIIE identification to settings where unmeasured confounders influence exposure-outcome, exposure-mediator, and mediator-outcome relationships. Specifically, we leverage observed covariates as proxy variables for unmeasured confounders, constructing three proximal identification frameworks. Additionally, we characterize the semiparametric efficiency bound and develop multiply robust and locally efficient estimators. To handle high-dimensional nuisance parameters, we propose a debiased machine learning approach that achieves $\sqrt{n}$-consistency and asymptotic normality to estimate the true PIIE values, even when the machine learning estimators for the nuisance functions do not converge at $\sqrt{n}$-rate. In simulations, our estimators demonstrate higher confidence interval coverage rates than conventional methods across various model misspecifications. In a real data application, our approaches reveal an indirect effect of alcohol consumption on depression risk mediated by depersonalization symptoms.