Identification and estimation of mediational effects of longitudinal modified treatment policies

We demonstrate a comprehensive semiparametric approach to causal mediation analysis, addressing the complexities inherent in settings with longitudinal and continuous treatments, confounders, and mediators. Our methodology utilizes a nonparametric structural equation model and a cross-fitted sequential regression technique based on doubly robust pseudo-outcomes, yielding an efficient, asymptotically normal estimator without relying on restrictive parametric modeling assumptions. We are motivated by a recent scientific controversy regarding the effects of invasive mechanical ventilation (IMV) on the survival of COVID-19 patients, considering acute kidney injury (AKI) as a mediating factor. We highlight the possibility of "inconsistent mediation," in which the direct and indirect effects of the exposure operate in opposite directions. We discuss the significance of mediation analysis for scientific understanding and its potential utility in treatment decisions.