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.
The proportion of subjects with NAR in an adolescent and adult population with rhinitis is around one-fourth. Women have NAR twice as often as men. In general, subjects with NAR have more persistent but equally severe symptoms compared to subjects with AR. However, subjects with AR have more sneezing and itchy eyes within their particular season of allergy compared to subjects with NAR.
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