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

Author

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  • Zheng Wenjing

    (Division of Biostatistics, University of California, 101 Havilland Hall, Berkeley, CA 94720, USA)

  • van der Laan Mark

    (Department of School of Public Health, University of California, 101 Havilland Hall, Berkeley, CA 94720, USA)

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.

Suggested Citation

  • Zheng Wenjing & van der Laan Mark, 2017. "Longitudinal Mediation Analysis with Time-varying Mediators and Exposures, with Application to Survival Outcomes," Journal of Causal Inference, De Gruyter, vol. 5(2), pages 1-24, September.
    • Handle: RePEc:bpj:causin:v:5:y:2017:i:2:p:24:n:4
    DOI: 10.1515/jci-2016-0006
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    References listed on IDEAS

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    1. Tyler J. VanderWeele & Eric J. Tchetgen Tchetgen, 2017. "Mediation analysis with time varying exposures and mediators," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 79(3), pages 917-938, June.
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    Cited by:

    1. Cheng Zheng & Lei Liu, 2022. "Quantifying direct and indirect effect for longitudinal mediator and survival outcome using joint modeling approach," Biometrics, The International Biometric Society, vol. 78(3), pages 1233-1243, September.
    2. Iván Díaz & Nima S. Hejazi, 2020. "Causal mediation analysis for stochastic interventions," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 82(3), pages 661-683, July.
    3. Zhichao Jiang & Shu Yang & Peng Ding, 2022. "Multiply robust estimation of causal effects under principal ignorability," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 84(4), pages 1423-1445, September.
    4. Kara E. Rudolph & Jonathan Levy & Mark J. van der Laan, 2021. "Transporting stochastic direct and indirect effects to new populations," Biometrics, The International Biometric Society, vol. 77(1), pages 197-211, March.
    5. Park Soojin & Kang Suyeon & Lee Chioun & Ma Shujie, 2023. "Sensitivity analysis for causal decomposition analysis: Assessing robustness toward omitted variable bias," Journal of Causal Inference, De Gruyter, vol. 11(1), pages 1-23, January.
    6. Vanessa Didelez, 2019. "Defining causal mediation with a longitudinal mediator and a survival outcome," Lifetime Data Analysis: An International Journal Devoted to Statistical Methods and Applications for Time-to-Event Data, Springer, vol. 25(4), pages 593-610, October.
    7. Shuxi Zeng & Elizabeth C. Lange & Elizabeth A. Archie & Fernando A. Campos & Susan C. Alberts & Fan Li, 2023. "A Causal Mediation Model for Longitudinal Mediators and Survival Outcomes with an Application to Animal Behavior," Journal of Agricultural, Biological and Environmental Statistics, Springer;The International Biometric Society;American Statistical Association, vol. 28(2), pages 197-218, June.
    8. Tat-Thang Vo & Hilary Davies-Kershaw & Ruth Hackett & Stijn Vansteelandt, 2022. "Longitudinal mediation analysis of time-to-event endpoints in the presence of competing risks," Lifetime Data Analysis: An International Journal Devoted to Statistical Methods and Applications for Time-to-Event Data, Springer, vol. 28(3), pages 380-400, July.

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