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. 2017 Jun 8:9:331-338.
doi: 10.2147/CLEP.S129728. eCollection 2017.

Effect modification, interaction and mediation: an overview of theoretical insights for clinical investigators

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Effect modification, interaction and mediation: an overview of theoretical insights for clinical investigators

Priscila Corraini et al. Clin Epidemiol. .

Erratum in

Abstract

We revisited the three interrelated epidemiological concepts of effect modification, interaction and mediation for clinical investigators and examined their applicability when using research databases. The standard methods that are available to assess interaction, effect modification and mediation are explained and exemplified. For each concept, we first give a simple "best-case" example from a randomized controlled trial, followed by a structurally similar example from an observational study using research databases. Our explanation of the examples is based on recent theoretical developments and insights in the context of large health care databases. Terminology is sometimes ambiguous for what constitutes effect modification and interaction. The strong assumptions underlying the assessment of interaction, and particularly mediation, require clinicians and epidemiologists to take extra care when conducting observational studies in the context of health care databases. These strong assumptions may limit the applicability of interaction and mediation assessments, at least until the biases and limitations of these assessments when using large research databases are clarified.

Keywords: effect modifiers; epidemiology; health care administrative claims; methods; stratified analyses.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Mean (95% CI) heavy drinking days per week by topiramate (green circle) or placebo (red square) intervention group. Notes: (A) Main analysis; (B) analysis in three different alleles of the rs2832407 genotype. Adapted from Kranzler et al with permission from the American Journal of Psychiatry (Copyright ©2014). American Psychiatric Association. All Rights Reserved.
Figure 2
Figure 2
Relation between the exposure – the intermediate or mediator – and the outcome.

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