Effect Modification

  • Bryan Kestenbaum


  1. 11.1

    Effect modification is defined as a differential impact of a treatment or exposure on the disease process.

  2. 11.2
    Differences in the size of associations observed in studies may or may not represent a true differential impact of a treatment or exposure.
    1. 11.2.1
      Observed differences in the size of an association are more likely to represent an actual differential effect of an exposure or treatment on the disease if:

        The amount of difference in the association across subgroups is large.


        The subgroups contain sufficient numbers of people and outcomes.


        There is plausibility for the differential size of the association.


        The differential size of the association is replicated in other studies.

    2. 11.2.2

      Statistical measures estimate whether the differential size of an association likely exceeds chance but require careful interpretation in the context of multiple testing.

  3. 11.3

    Effect modification addresses a fundamentally different concept than confounding.

  4. 11.4

    The presence of effect modification on the additive scale suggests target populations that would receive the greatest benefits or harms from treatment .



  1. 1.
    James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377(4):338–51.CrossRefGoogle Scholar
  2. 2.
    Kent DM, Price LL, Ringleb P, Hill MD, Selker HP. Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials. Stroke. 2005;36(1):62–5.CrossRefGoogle Scholar
  3. 3.
    Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006;354(8):795–808.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bryan Kestenbaum
    • 1
  1. 1.Division of Nephrology, Department of MedicineUniversity of WashingtonSeattleUSA

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