Compliance Enforcement Branch, Division of Enforcement and Postmarketing Safety, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Ther Innov Regul Sci. 2021 Sep;55(5):907-917. doi: 10.1007/s43441-021-00267-y. Epub 2021 Jun 8.
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).
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.
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.
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.
目前，仅有少量研究调查了临床研究者（CIs）、申办者（SPs）、合同研究组织（CROs）和申办研究者（SIs）在收到 FDA 官方行动指示（OAI）信后是否继续开展临床试验。FDA 发布 OAI 信是为了对重大监管违规行为进行处罚。本研究旨在评估收到 OAI 信的受检实体在开展中心药物评价与研究（CDER）监管临床试验（CRCTs）的情况。
本研究采用回顾性分析方法，对 2010 年 10 月 1 日至 2015 年 9 月 30 日期间 FDA 的药物评价与研究中心（CDER）药物临床试验质量管理规范（GCP）检查中 OAI 信的检查数据进行分析，同时对受检实体的 OAI 后状态进行深入分析，包括 OAI 随访检查。
在这期间，共发放 2248 份 GCP 信，其中 104 份（4.6%）为 OAI 信：95 份（4.2%）发给 CIs（91%的 OAI 信），7 份（0.3%）发给 SPs（7%的 OAI 信），2 份（0.08%）发给 SIs（2%的 OAI 信）。大部分 OAI 信是由于有因检查而发出的。5 名 CIs 被排除在分析之外。没有 OAI 信发给 CROs。只有 30%的 CIs（90 名中的 27 名）继续开展 CRCTs。对这些 CIs 进行了 OAI 随访检查，结果有 16 份无行动指示（NAI）、11 份自愿行动指示（VAI），没有 OAI 信。大多数（64%）的 VAI 信指出存在重复但非重大违规行为。
在随访时，收到 OAI 信的 CIs 中，有 70%（67 名中的 47 名）不再开展 CRCTs。在继续开展 CRCTs 的 27 名 CIs 中，有 16 名（59%）的 OAI 随访检查结果为 NAI 分类，11 名（41%）为 VAI。
