An FDA Analysis of Inspected Entities After Receiving Official Action Indicated Letters for Good Clinical Practice Violations

BACKGROUND: Limited research has been conducted to examine whether clinical investigators (CIs), sponsors (SPs), contract research organizations (CROs), and sponsor-investigators (SIs) continue conducting clinical trials following issuance of FDA Official Action Indicated (OAI) letters. FDA issues OAI letters for significant regulatory violations. The objective of this study was to evaluate the status of inspected entities who received OAI letters in the conduct of Center for Drug Evaluation and Research (CDER)-regulated clinical trials (CRCTs). METHODS: This cross-sectional study included an analysis of inspectional data from CDER’s Good Clinical Practice (GCP) inspections for OAI letters issued from October 1, 2010, to September 30, 2015, with an in-depth analysis of post-OAI status of inspected entities, including OAI follow-up inspections. RESULTS: Of the 2248 GCP letters issued during this period, 104 (4.6%) OAI letters were sent: 95 (4.2%) to CIs (91% of OAIs), 7 (0.3%) to SPs (7% of OAIs), and 2 (0.08%) to SIs (2% of OAIs). Majority of OAI letters were issued as a result of a for-cause inspection. Five CIs were excluded from analysis. No OAI letters were sent to CROs. Only 30% of CIs (27 out of 90) continued to conduct CRCTs. OAI follow-up inspections were completed for these CIs resulting in 16 No Action Indicated (NAI), 11 Voluntary Action Indicated (VAI), and no OAI letters. Majority (64%) of the VAI letters noted repeated but not significant violations. CONCLUSIONS: Majority (70%) of CIs who received an OAI letter were no longer conducting CRCTs at the time of follow-up. Of the 27 CIs continuing CRCTs, 16 (59%) OAI follow-up inspections resulted in NAI classifications and 11 (41%) in VAI.