title: Challenges in the research ethics review of cluster randomized trials: international survey of investigators.
abstract: BACKGROUND
  Cluster randomized trials (CRTs) complicate the interpretation of standard research ethics guidelines for several reasons. For one, the units of allocation, intervention, and observation often may differ within a single trial. In the absence of tailored and internationally accepted ethics guidelines for CRTs, researchers and research ethics committees have no common standard by which to judge ethically appropriate practices in CRTs. Moreover, lack of familiarity with and consideration of the unique features of the CRT design by research ethics committees may cause difficulties in the research ethics review process, and amplify problems such as variability in the requirements and decisions reached by different research ethics committees.
  
  
  OBJECTIVE
  We aimed to characterize research ethics review of CRTs, examine investigator experiences with the ethics review process, and assess the need for ethics guidelines for CRTs.
  
  
  METHODS
  An electronic search strategy implemented in MEDLINE was used to identify and randomly sample 300 CRTs published in English language journals from 2000 to 2008. A web-based survey with closed- and open-ended questions was administered to corresponding authors in a series of six contacts.
  
  
  RESULTS
  The survey response rate was 64%. Among 182 of 285 eligible respondents, 91% indicated that they had sought research ethics approval for the identified CRT, although only 70% respondents reported research ethics approval in the published article. Nearly one-third (31%) indicated that they have had to meet with ethics committees to explain aspects of their trials, nearly half (46%) experienced variability in the ethics review process in multijurisdictional trials, and 38% experienced negative impacts of the ethics review process on their trials, including delays in trial initiation (28%), increased costs (10%), compromised ability to recruit participants (16%), and compromised methodological quality (9%). Most respondents (74%; 95% confidence interval (CI): 67%-80%) agreed or strongly agreed that there is a need to develop ethics guidelines for CRTs, and (70%; 95% CI: 63%-77%) that ethics committees could be better informed about distinct ethical issues surrounding CRTs.
  
  
  CONCLUSIONS
  Thirty-six percent of authors did not respond to the survey. Due to the absence of comparable results from a representative sample of authors of individually randomized trials, it is unclear to what extent the reported challenges result from the CRT design.
  
  
  CONCLUSIONS
  CRT investigators are experiencing challenges in the research ethics review of their trials, including excessive delays, variability in process and outcome, and imposed requirements that can have negative consequences for study conduct. Investigators identified a clear need for ethics guidelines for CRTs and education of research ethics committees about distinct ethical issues in CRTs.
authors.affiliation: Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Shazia H
authors.initials: SH
authors.lastname: Chaudhry
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Brehaut
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Grimshaw
authors.forename: Charles
authors.initials: C
authors.lastname: Weijer
authors.forename: Robert
authors.initials: R
authors.lastname: Boruch
authors.forename: Allan
authors.initials: A
authors.lastname: Donner
authors.forename: Martin P
authors.initials: MP
authors.lastname: Eccles
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McRae
authors.forename: Raphael
authors.initials: R
authors.lastname: Saginur
authors.forename: Zoë C
authors.initials: ZC
authors.lastname: Skea
authors.forename: Merrick
authors.initials: M
authors.lastname: Zwarenstein
authors.forename: Monica
authors.initials: M
authors.lastname: Taljaard
mesh_terms: D028744:Ethics Committees, Research / Q000941:ethics; D032984:Ethics, Research; D006801:Humans; D007391:International Cooperation; D018579:Patient Selection / Q000941:ethics; D016032:Randomized Controlled Trials as Topic / Q000941:ethics* / Q000379:methods*; D012107:Research Design / Q000592:standards; D013997:Time Factors