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Causal Mediation Analysis with Multiple Mediators: A Simulation Approach

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  • Jesse Zhou
  • Geoffrey T. Wodtke

Abstract

Analyses of causal mediation often involve exposure-induced confounders or, relatedly, multiple mediators. In such applications, researchers aim to estimate a variety of different quantities, including interventional direct and indirect effects, multivariate natural direct and indirect effects, and/or path-specific effects. This study introduces a general approach to estimating all these quantities by simulating potential outcomes from a series of distribution models for each mediator and the outcome. Building on similar methods developed for analyses with only a single mediator (Imai et al. 2010), we first outline how to implement this approach with parametric models. The parametric implementation can accommodate linear and nonlinear relationships, both continuous and discrete mediators, and many different types of outcomes. However, it depends on correct specification of each model used to simulate the potential outcomes. To address the risk of misspecification, we also introduce an alternative implementation using a novel class of nonparametric models, which leverage deep neural networks to approximate the relevant distributions without relying on strict assumptions about functional form. We illustrate both methods by reanalyzing the effects of media framing on attitudes toward immigration (Brader et al. 2008) and the effects of prenatal care on preterm birth (VanderWeele et al. 2014).

Suggested Citation

  • Jesse Zhou & Geoffrey T. Wodtke, 2025. "Causal Mediation Analysis with Multiple Mediators: A Simulation Approach," Papers 2506.14019, arXiv.org.
  • Handle: RePEc:arx:papers:2506.14019
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    References listed on IDEAS

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    1. Sara Geneletti, 2007. "Identifying direct and indirect effects in a non‐counterfactual framework," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 69(2), pages 199-215, April.
    2. Imai, Kosuke & Keele, Luke & Tingley, Dustin & Yamamoto, Teppei, 2011. "Unpacking the Black Box of Causality: Learning about Causal Mechanisms from Experimental and Observational Studies," American Political Science Review, Cambridge University Press, vol. 105(4), pages 765-789, November.
    3. Imai, Kosuke & Yamamoto, Teppei, 2013. "Identification and Sensitivity Analysis for Multiple Causal Mechanisms: Revisiting Evidence from Framing Experiments," Political Analysis, Cambridge University Press, vol. 21(2), pages 141-171, April.
    4. Zhou, Xiang & Wodtke, Geoffrey T., 2020. "Residual Balancing: A Method of Constructing Weights for Marginal Structural Models," Political Analysis, Cambridge University Press, vol. 28(4), pages 487-506, October.
    5. Ted Brader & Nicholas A. Valentino & Elizabeth Suhay, 2008. "What Triggers Public Opposition to Immigration? Anxiety, Group Cues, and Immigration Threat," American Journal of Political Science, John Wiley & Sons, vol. 52(4), pages 959-978, October.
    6. Kotelchuck, M., 1994. "An evaluation of the Kessner Adequacy of Prenatal Care Index and a proposed Adequacy of Prenatal Care Utilization Index," American Journal of Public Health, American Public Health Association, vol. 84(9), pages 1414-1420.
    7. Xiang Zhou, 2022. "Semiparametric estimation for causal mediation analysis with multiple causally ordered mediators," Journal of the Royal Statistical Society Series B, Royal Statistical Society, vol. 84(3), pages 794-821, July.
    8. Zhou, Xiang & Wodtke, Geoffrey T., 2019. "A Regression-with-Residuals Method for Estimating Controlled Direct Effects," Political Analysis, Cambridge University Press, vol. 27(3), pages 360-369, July.
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