Tutorial: A nontechnical explanation of the counterfactual definition of effect modification and interaction

Martijn J. L. Bours*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Effect modification and interaction are important concepts for answering causal questions about interdependent effects of two (or more) exposures on some outcome of interest. Although conceptually alike and often mistakenly regarded as synonymous, effect modification and interaction actually refer to slightly different concepts when considered from a causal perspective. Their subtle yet relevant distinction lies in how the interplay between exposures is defined and the causal roles attributed to the exposures involved in the effect modification and interaction. To gain more insight into similarities and differences between the concepts of effect modification and interaction, the counterfactual theory of causation, albeit complicated, can be very helpful. Therefore, this article presents a nontechnical explanation of the counterfactual definition of effect modification and interaction. Essentially, effect modification and interaction are reflections of the reality and complexity of multicausality. The causal effect of an exposure of interest often depends on the levels of other exposures (effect modification) or causal effects of other exposures (interaction). Consequently, exposure effects should not be regarded in isolation but in combination. Understanding the underlying principles of effect modification and interaction on a conceptual level enables researchers to better anticipate, detect, and interpret these causal phenomena when setting up, analyzing, and reporting findings of (clinical) epidemiological studies. Effect modification and interaction are not biases to be avoided but properties of causal effects that ought to be unveiled. Hence, evidence for effect modification and interaction needs to be shown in order to delineate in whom and which instances causal effects occur. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Original languageEnglish
Pages (from-to)113-124
Number of pages12
JournalJournal of Clinical Epidemiology
Publication statusPublished - Jun 2021


  • Additive and multiplicative models
  • Causal effects
  • Counterfactual theory
  • Effect modification
  • Interaction
  • KRAS
  • WORD

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