Practical guidance for conducting mediation analysis with multiple mediators using inverse odds ratio weighting

Quynh C. Nguyen, Theresa L. Osypuk, Nicole M. Schmidt, M. Maria Glymour, Eric J Tchetgen Tchetgen

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97 Scopus citations


Despite the recent flourishing of mediation analysis techniques, many modern approaches are difficult to implement or applicable to only a restricted range of regression models. This report provides practical guidance for implementing a new technique utilizing inverse odds ratio weighting (IORW) to estimate natural direct and indirect effects for mediation analyses. IORW takes advantage of the odds ratio's invariance property and condenses information on the odds ratio for the relationship between the exposure (treatment) and multiple mediators, conditional on covariates, by regressing exposure on mediators and covariates. The inverse of the covariate-adjusted exposure-mediator odds ratio association is used to weight the primary analytical regression of the outcome on treatment. The treatment coefficient in such a weighted regression estimates the natural direct effect of treatment on the outcome, and indirect effects are identified by subtracting direct effects from total effects. Weighting renders treatment and mediators independent, thereby deactivating indirect pathways of the mediators. This new mediation technique accommodates multiple discrete or continuous mediators. IORW is easily implemented and is appropriate for any standard regression model, including quantile regression and survival analysis. An empirical example is given using data from the Moving to Opportunity (1994-2002) experiment, testing whether neighborhood context mediated the effects of a housing voucher program on obesity. Relevant Stata code (StataCorp LP, College Station, Texas) is provided.

Original languageEnglish (US)
Pages (from-to)349-356
Number of pages8
JournalAmerican journal of epidemiology
Issue number5
StatePublished - Mar 1 2015

Bibliographical note

Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.


  • direct effects
  • effect decomposition
  • indirect effects
  • mediation
  • weighted regression


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