Analysis of warning letters issued by the US Food and Drug Administration to clinical investigators, institutional review boards and sponsors: a retrospective study

• Published in: Journal of medical ethics Vol. 41; no. 5; pp. 398 - 403
• Main Authors: Shetty, Yashashri C, Saiyed, Aafreen A
• Format: Journal Article
• Language: English
• Published: England Institute of Medical Ethics and BMJ Publishing Group Ltd 01.05.2015; BMJ Publishing Group Ltd; BMJ Publishing Group LTD
• Subjects: Clinical medicine; Clinical trials; Compliance; Corporate sponsorship; Correspondence as Topic; Ethics; Ethics Committees, Research - ethics; Ethics Committees, Research - standards; Humans; Inspection; Inspections; Institutional review boards (Research ethics); Laboratories; Letters; Medical research; Pharmaceutical industry; Public health; Quality; Regulatory agencies; Research ethics; Research Personnel - ethics; Research Support as Topic - ethics; Researchers; Retrospective Studies; Review boards; Studies; United States; United States Food and Drug Administration; Violations; United States; Legal Aspects; Informed Consent; Ethics Committees/Consultation; Research Ethics; Clinical Trials
• ISSN: 0306-6800; 1473-4257; 1473-4257
• DOI: 10.1136/medethics-2013-101829

The US Food and Drug Administration (FDA) issues warning letters to all research stakeholders if unacceptable deficiencies are found during site visits. Warning letters issued by the FDA between January 2011 and December 2012 to clinical investigators and institutional review boards (IRBs) were reviewed for various violation themes and compared to similar studies in the past. Warning letters issued to sponsors between January 2005 and December 2012 were analysed for the first time for a specific set of violations using descriptive statistics. Failure to protect subject safety and to report adverse events to IRBs was found to be significant compared to prior studies for clinical investigators, while failure to follow standard operating procedures and maintain documentation was noted as significant in warning letters to IRBs. Failure to maintain minutes of meeting and to follow written procedures for continuing review were new substantial violations in warning letters issued to IRBs. Forty-six warning letters were issued to sponsors, the most common violations being failure to follow a monitoring schedule (58.69%), failure to obtain investigator agreement (34.78%), failure to secure investigators’ compliance (30.43%), and failure to maintain data records and ship documents to investigators (30.43%). Appropriate methods for handling clinical trial procedural violations should be developed and implemented worldwide.