title: Generalized causal mediation analysis.
abstract: The goal of mediation analysis is to assess direct and indirect effects of a treatment or exposure on an outcome. More generally, we may be interested in the context of a causal model as characterized by a directed acyclic graph (DAG), where mediation via a specific path from exposure to outcome may involve an arbitrary number of links (or "stages"). Methods for estimating mediation (or pathway) effects are available for a continuous outcome and a continuous mediator related via a linear model, while for a categorical outcome or categorical mediator, methods are usually limited to two-stage mediation. We present a method applicable to multiple stages of mediation and mixed variable types using generalized linear models. We define pathway effects using a potential outcomes framework and present a general formula that provides the effect of exposure through any specified pathway. Some pathway effects are nonidentifiable and their estimation requires an assumption regarding the correlation between counterfactuals. We provide a sensitivity analysis to assess the impact of this assumption. Confidence intervals for pathway effect estimates are obtained via a bootstrap method. The method is applied to a cohort study of dental caries in very low birth weight adolescents. A simulation study demonstrates low bias of pathway effect estimators and close-to-nominal coverage rates of confidence intervals. We also find low sensitivity to the counterfactual correlation in most scenarios.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Medicine, WG-43, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA. jma13@case.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Albert
authors.forename: Suchitra
authors.initials: S
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D015984:Causality; D015331:Cohort Studies; D003731:Dental Caries; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008137:Longitudinal Studies; D060891:Root Cause Analysis / Q000379:methods*; D016896:Treatment Outcome