title: Justification of exclusion criteria was underreported in a review of cardiovascular trials.
abstract: OBJECTIVE
  Ethical guidelines for human subject research require that the burdens and benefits of participation be equally distributed. This study aimed to provide empirical data on exclusion of trial participants and reasons for this exclusion. As a secondary objective, we assessed to what extent exclusion affects generalizability of study results.
  
  
  METHODS
  Review of trials on secondary prevention of cardiovascular events.
  
  
  RESULTS
  One hundred thirteen trials were identified, of which 112 reported exclusion criteria. One study justified the exclusion criteria applied. Ambiguous exclusion criteria due to the opinion of the physician (28 of 112 = 25%) or physical disability (12 of 112 = 11%) were reported. Within groups of trials that studied similar treatments (ie, beta-blocker, clopidogrel, or statin therapy), baseline characteristics differed among trials. For example, the proportion of women ranged between 23.1-47.4%, 2.1-38.9%, and 10.6-50.6% for the clopidogrel, beta-blocker, and statin trials, respectively. Nevertheless, no evidence was found for heterogeneity of treatment effects.
  
  
  CONCLUSIONS
  Almost none of the articles justified the applied exclusion criteria. No evidence was found that inclusion of dissimilar participants affected generalizability. To allow for a normative discussion on equitable selection of study populations, researchers should not only report exclusion criteria but also the reasons for using these criteria.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, P.O. Box 80082, 3508 TB Utrecht, The Netherlands; Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 107, Utrecht 3584 CL, The Netherlands. Electronic address: a.f.schmidt@umcutrecht.nl.
authors.forename: Amand F
authors.initials: AF
authors.lastname: Schmidt
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Johannes J M
authors.initials: JJ
authors.lastname: van Delden
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Department of Emergency Medicine, Erasmus University Medical Center, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Yuri
authors.initials: Y
authors.lastname: van der Does
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands; Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Kit C B
authors.initials: KC
authors.lastname: Roes
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Arno W
authors.initials: AW
authors.lastname: Hoes
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Stratenum 6.131, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
authors.forename: Rieke
authors.initials: R
authors.lastname: van der Graaf
mesh_terms: D002318:Cardiovascular Diseases / Q000628:therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012107:Research Design / Q000592:standards*
keywords: Ethics; Exclusion criteria; Generalizability; Human experimentation; Medical; Randomized controlled trials; Research