title: A study of warning letters issued to institutional review boards by the United States Food and Drug Administration.
abstract: OBJECTIVE
  This study explores the ethical issues contained in warning letters (WLs) issued to institutional review boards (IRBs) by the United States Food and Drug Administration (FDA).
  
  
  METHODS
  The online FDA Warning Letter Index was reviewed for letters issued to IRBs in the United States under the violation categories "Institutional Review Board" and "IRB" for the period January 1997 through July 2004. The resultant letters were evaluated for violations in 4 regulatory themes: having and following written procedures for research review; documentation of research review; IRB membership and conflict of interest; and informed consent.
  
  
  RESULTS
  Fifty-two (52) FDA WLs were issued to IRBs during this period. Hospital/medical centre IRBs received the most letters (n = 34), followed by university IRBs (n = 9) and private IRBs (n = 9). The most common regulatory violations were failure to have and follow adequate written procedures about how the review of research is conducted (50 WLs); failure to prepare and maintain adequate documentation of IRB activities (47 WLs); and failure to provide adequate continuing review of approved studies (36 WLs). Nineteen WLs were issued for consent form issues.
  
  
  CONCLUSIONS
  Warning letters are informative with regard to clinical research regulations and research subject protection. The content of these letters consistently indicates weaknesses in review and documentation activities of audited IRBs, potentially signalling similar issues among IRBs across the United States. Our findings, in a setting of overburdened IRBs who, in general, passively monitor studies, raise concerns about study oversight and optimal protection of research subjects.
authors.affiliation: Research Subject Advocacy Program, General Clinical Research Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. bioethics@go.com
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Bramstedt
authors.forename: Katy
authors.initials: K
authors.lastname: Kassimatis
mesh_terms: D035843:Biomedical Research / Q000592:standards*; D002985:Clinical Protocols / Q000592:standards; D002986:Clinical Trials as Topic / Q000592:standards; D015709:Correspondence as Topic; D028744:Ethics Committees, Research; D032984:Ethics, Research; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration