title: A study of warning letters issued to clinical investigators and institutional review boards by the United States Food and Drug Administration.
abstract: BACKGROUND
  Warning letters (WLs) issued by the US FDA (United States Food and Drug Administration) mention the nature of violations by clinical investigators and institutional review boards (IRBS) and can help as training tools.
  
  
  METHODS
  WLs issued by the US FDA between January 2005 and December 2010 to clinical investigators and IRBs were reviewed for various violation themes.
  
  
  RESULTS
  A total of 129 WLs were issued to investigators and 40 to IRBs. Among the WLs issued to investigators, 67 (51.95%) were issued for drug-related research and 62 (48.06%) were for device-related research. For investigators, deviation from the investigational plan was the most common violation (81%) followed by failure to maintain accurate and adequate case histories (58.1%) and then informed consent issues (48.06%). Among WLs issued to IRBs, failure to have and follow standard operating procedures (SOPs) was seen in 93.89% followed by issues pertaining to membership (59.4%). When compared to a similar study published in 2004, for clinical investigators, no improvement was seen with respect to deviation from the investigational plan and study supervision. However, a significant improvement was seen in reporting of adverse events to IRBs, and some improvement was seen in the area of informed consent. For IRBs, no improvement was seen in most areas which included maintaining and following SOPs, membership, quorum requirements, misuse of expedited review and informed consent.
  
  
  CONCLUSIONS
  WLs serve as indicators of an active regulatory agency which should translate into greater safety for participants in clinical trials. For developing countries with weak regulatory systems, these can serve as useful learning tools to help improve systems and put in patient safeguards.
authors: Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai 400 012, India. njgogtay@hotmail.com
authors: N J
authors: NJ
authors: Gogtay
authors: B M
authors: BM
authors: Doshi
authors: S
authors: S
authors: Kannan
authors: U
authors: U
authors: Thatte
mesh_terms: D002986:Clinical Trials as Topic / Q000941:ethics*; D003906:Developing Countries; D018795:Device Approval; D017277:Drug Approval; D028744:Ethics Committees, Research / Q000941:ethics / Q000592:standards*; D019983:Guideline Adherence; D006801:Humans; D058996:Quality Improvement; D014481:United States; D014486:United States Food and Drug Administration