Effect measure modification conceptualized using selection diagrams as mediation by mechanisms of varying...

We are often confronted in public health by associations that vary by population or subpopulation. Much effort has focused on the statistical and biological interpretation of such effect measure modification (EMM) because of the importance to public health. However, EMM remains difficult to conceptualize because it apparently violates everyday understanding of causes as usually acting consistently, making it difficult to predict when EMM may occur and raises questions about how to determine the external validity of interventions without extensive retesting by population or subpopulation.

Methods exposition.

We propose that EMM can be thought of as mediation of an intervention (or exposure) on outcome by mechanism(s) whose relevance differs between population groups, which can be illustrated in causal diagrams, that is, directed acyclic graphs and selection diagrams, meaning external validity can be formally considered as mediation according to "selection variables." EMM can then be represented graphically and its consequences predicted.

This new conceptualization of EMM transforms EMM from a concept that violates everyday understanding of causes into an insight generating means of thinking about interventions (or exposures) in terms of their mediating mechanism(s) and corresponding population- or subpopulation-specific attributes to help target interventions effectively.