To evaluate the post-inspectional status of inspected entities who received Official Action Indicated (OAI) letters (i.e., post-OAI status) for significant regulatory violations during the conduct of Center for Drug Evaluation and Research (CDER)-regulated clinical trials (CRCTs).
Method
In this cross-sectional study, we analyzed post-inspectional GCP letters that the FDA issued to sponsors (SPs), clinical investigators (CIs), and sponsor-investigators (SIs) from fiscal years 2011 to 2015 (FY11-15) and conducted a descriptive analysis to examine post-OAI status.
Results
Of the 2248 GCP letters issued during FY11-15, 104 OAI letters were sent to CIs (n=95, 91%), SPs (n=7, 7%), and SIs (n=2, 2%). OAI letters to CIs included 47 OAI-Untitled Letters (OAI-ULs), 38 Warning Letter (WLs), and 10 Notice of Initiation of Disqualification Proceedings and Opportunity to Explain Letters (NIDPOEs). SPs received two OAI-ULs and five WLs; and SIs, one OAI-UL and one NIDPOE.
Our OAI follow-up evaluation found that only 31 of 95 CIs continued to conduct CRCTs. OAI follow-up inspections were completed for 27 CIs which resulted in 16 NAIs and 11 VAIs. Of the 11 CI VAI letters, 7 were issued due to repeated regulatory violations (i.e., new infractions of previously cited violations), 2 due to new violations not cited in the original OAI letter, and 2 due to both repeated and new violations.
Among SPs and SIs who had OAI follow-up inspections, two SPs each received an NAI and one SI received a VAI due to a new violation.
Conclusion
To our knowledge, limited research has been conducted to examine whether CIs, SPs, and SIs continue conducting CRCTs following issuance of an FDA OAI letter. Most CIs were no longer conducting CRCTs after receiving an OAI letter. Most OAI follow-up inspections resulted in NAI.
For those resulting in VAI, repeated and new regulatory violations were noted.
Our findings may guide future research on whether the type of regulatory action influences the inspected entity’s decision to continue participation in clinical trials. Our findings emphasize the importance of implementing corrective and preventive actions to improve compliance with GCP regulations.
