title: Tailoring treatments using treatment effect modification.
abstract: OBJECTIVE
  Applying results from clinical studies to individual patients can be a difficult process. Using the concept of treatment effect modification (also referred to as interaction), defined as a difference in treatment response between patient groups, we discuss whether and how treatment effects can be tailored to better meet patients' needs.
  
  
  RESULTS
  First we argue that contrary to how most studies are designed, treatment effect modification should be expected. Second, given this expected heterogeneity, a small number of clinically relevant subgroups should be a priori selected, depending on the expected magnitude of effect modification, and prevalence of the patient type. Third, by defining generalizability as the absence of treatment effect modification we show that generalizability can be evaluated within the usual statistical framework of equivalence testing. Fourth, when equivalence cannot be confirmed, we address the need for further analyses and studies tailoring treatment towards groups of patients with similar response to treatment. Fifth, we argue that to properly frame, the entire body of evidence on effect modification should be quantified in a prior probability.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.|Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.|Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.|Institute of Cardiovascular Science, Faculty of Population Health, University College London, London, UK.
authors.forename: A F
authors.initials: AF
authors.lastname: Schmidt
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.|Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
authors.forename: O H
authors.initials: OH
authors.lastname: Klungel
authors.affiliation: Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Nielen
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.|Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
authors.forename: R H H
authors.initials: RH
authors.lastname: Groenwold
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: A W
authors.initials: AW
authors.lastname: Hoes
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D006301:Health Services Needs and Demand; D006801:Humans; D057285:Precision Medicine / Q000379:methods*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012107:Research Design
keywords: effect modification; generalizability; interaction; nonrandomized study design; observational study design; pharmacoepidemiology; randomized controlled trial; statistics