Interaction and Effect Modification in Clinical and Epidemiological Studies: Part 38 of a Series on the Evaluation of Scientific Publications.

Abstract

A common objective of studies in clinical research is to investigate the effect of an individual factor on the course of a disease. Studying the combined effect of two or more factors on an outcome variable is more complex, as is the question whether an effect varies across subgroups (e.g., men vs. women). The concepts of interaction and effect modification are useful for analyses of this kind. This review is based on relevant publications retrieved by a selective search. The concepts of interaction and effect modification are illustrated using examples involving real and fictitious data. An interaction is present when, for example, taking two drugs reduces the risk of a disease by an amount that differs from the sum of the individual effects. In contrast, an effect modification is present when, for example, the effect of a drug on the risk of disease varies depending on the presence or absence of a particular genotype. In this article, the concepts of interaction, effect modification, synergism, and antagonism are explained. Interactions can occur on either an additive or a multiplicative scale. Moreover, quantitative measures of interactions on the additive scale are explained, and the potential for misinterpreting evaluations of interactions in regression analyses is discussed. The concepts of interaction and effect modification provide valuable insights for the prevention and treatment of disease.