Longitudinal Mediation Analysis with Time-varying Mediators and Exposures, with Application to Survival Outcomes

Zheng Wenjing () and Mark van der Laan ()
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Zheng Wenjing: Division of Biostatistics, University of California, 101 Havilland Hall, Berkeley, CA 94720, USA
Mark van der Laan: Department of School of Public Health, University of California, 101 Havilland Hall, Berkeley, CA 94720, USA

Journal of Causal Inference, 2017, vol. 5, issue 2, 24

Abstract: 1 In this paper, we study the effect of a time-varying exposure mediated by a time-varying intermediate variable. We consider general longitudinal settings, including survival outcomes. At a given time point, the exposure and mediator of interest are influenced by past covariates, mediators and exposures, and affect future covariates, mediators and exposures. Right censoring, if present, occurs in response to past history. To address the challenges in mediation analysis that are unique to these settings, we propose a formulation in terms of random interventions based on conditional distributions for the mediator. This formulation, in particular, allows for well-defined natural direct and indirect effects in the survival setting, and natural decomposition of the standard total effect. Upon establishing identifiability and the corresponding statistical estimands, we derive the efficient influence curves and establish their robustness properties. Applying Targeted Maximum Likelihood Estimation, we use these efficient influence curves to construct multiply robust and efficient estimators. We also present an inverse probability weighted estimator and a nested non-targeted substitution estimator for these parameters.

Keywords: natural direct effects; natural indirect effects; mediation analysis; mediation formula; survival; time-varying; targeted maximum likelihood estimator; IPTW; G-computation (search for similar items in EconPapers)
Date: 2017
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Citations: View citations in EconPapers (8)

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Persistent link: https://EconPapers.repec.org/RePEc:bpj:causin:v:5:y:2017:i:2:p:24:n:4

DOI: 10.1515/jci-2016-0006

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