Journal
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
Volume 42, Issue 5, Pages 1511-1519Publisher
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyt127
Keywords
Mediation analysis; direct effects; indirect effects
Categories
Funding
- Compagnia SanPaolo Foundation
- Italian Association for Cancer Research
- Italian Ministry of University and Research (MIUR), PRIN X8YCBN
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In epidemiological studies it is often necessary to disentangle the pathways that link an exposure to an outcome. Typically the aim is to identify the total effect of the exposure on the outcome, the effect of the exposure that acts through a given set of mediators of interest (indirect effect) and the effect of the exposure unexplained by those same mediators (direct effect). The traditional approach to mediation analysis is based on adjusting for the mediator in standard regression models to estimate the direct effect. However, several methodological papers have shown that under a number of circumstances this traditional approach may produce flawed conclusions. Through a better understanding of the causal structure of the variables involved in the analysis, with a formal definition of direct and indirect effects in a counterfactual framework, alternative analytical methods have been introduced to improve the validity and interpretation of mediation analysis. In this paper, we review and discuss the impact of the three main sources of potential bias in the traditional approach to mediation analyses: (i) mediator-outcome confounding;(ii) exposure-mediator interaction and (iii) mediator-outcome confounding affected by the exposure. We provide examples and discuss the impact these sources have in terms of bias.
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