Craig A Garmendia1,2, Neera Bhansali3, Purnima Madhivanan2. 1. 1 Office of Regulatory Affairs, US Food and Drug Administration, Miami Lakes, FL, USA. 2. 2 Department of Epidemiology, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA. 3. 3 Department of Biostatistics, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA.
Abstract
BACKGROUND: The US Food and Drug Administration (FDA) ensures that clinical trials meet regulatory and ethical standards through inspections of researchers, also known as clinical investigators. Inspections with significant regulatory/ethical violations may result in regulatory actions, such as a warning letter or a Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE). Objectives included the standardization of regulatory violation themes cited by the FDA for novel analysis of published regulatory actions rate issued by study intervention type, violation theme by intervention type, and violation theme variation between regulatory action type. METHODS: Cross-sectional analysis of regulatory actions from October 1, 2006, to September 30, 2015, for inspections of researchers. For each FDA regulatory action, the main measure was the Code of Federal Regulations cited coded into a violation theme. Data were paired with FDA's published researcher inspection metrics to perform fiscal year analysis. RESULTS: The FDA conducted 6375 domestic inspections of researchers in 2007 to 2015: 360 had significant regulatory violations, and 194 received published regulatory actions. Since 2007, rates of significant deviations have decreased. Medical device researchers had higher rates of warning letter issuance than did biologic product researchers. In contrast, medical device researchers had lower rates of NIDPOE issuance as compared to rates of biologic or pharmaceutical researchers. Lack of researcher supervision and submission of false information were cited more frequently for NIDPOEs. CONCLUSIONS: Researcher compliance has significantly improved as evidenced by medical device researchers having the lowest rate of the most significant noncompliance. Disqualification is more likely to occur when researchers fail to supervise the trial or false information is submitted.
BACKGROUND: The US Food and Drug Administration (FDA) ensures that clinical trials meet regulatory and ethical standards through inspections of researchers, also known as clinical investigators. Inspections with significant regulatory/ethical violations may result in regulatory actions, such as a warning letter or a Notice of Initiation of Disqualification Proceedings and Opportunity to Explain (NIDPOE). Objectives included the standardization of regulatory violation themes cited by the FDA for novel analysis of published regulatory actions rate issued by study intervention type, violation theme by intervention type, and violation theme variation between regulatory action type. METHODS: Cross-sectional analysis of regulatory actions from October 1, 2006, to September 30, 2015, for inspections of researchers. For each FDA regulatory action, the main measure was the Code of Federal Regulations cited coded into a violation theme. Data were paired with FDA's published researcher inspection metrics to perform fiscal year analysis. RESULTS: The FDA conducted 6375 domestic inspections of researchers in 2007 to 2015: 360 had significant regulatory violations, and 194 received published regulatory actions. Since 2007, rates of significant deviations have decreased. Medical device researchers had higher rates of warning letter issuance than did biologic product researchers. In contrast, medical device researchers had lower rates of NIDPOE issuance as compared to rates of biologic or pharmaceutical researchers. Lack of researcher supervision and submission of false information were cited more frequently for NIDPOEs. CONCLUSIONS: Researcher compliance has significantly improved as evidenced by medical device researchers having the lowest rate of the most significant noncompliance. Disqualification is more likely to occur when researchers fail to supervise the trial or false information is submitted.
Keywords:
Code of Federal Regulations; clinical investigator; disqualification; inspection; regulatory action; warning letter