From the Albert Einstein College of Medicine, Bronx, New York.
Department of Anesthesiology, Montefiore Medical Center, Bronx, New York.
Anesth Analg. 2018 Mar;126(3):976-982. doi: 10.1213/ANE.0000000000002694.
The US Food and Drug Administration (FDA) conducts inspections of clinical investigation sites as a component of clinical trial regulation. The FDA describes the results of these inspections in the Clinical Investigator Inspection List (CLIIL). More serious violations are followed up in FDA warning letters issued to investigators. The primary objective of the current study is to qualitatively and quantitatively describe the CLIIL data and contents of FDA-issued warning letters from 2010 to 2014.
We retrospectively analyzed the CLIIL and FDA warning letters. For the CLIIL, we quantified the frequency of each violation among other data points. We compared recent data (2010-2014) to the previous 5 years (2005-2009). To analyze FDA warning letters, we developed a coding system to quantify the frequency of violations found.
We analyzed 3637 inspections in the CLIIL database and 60 warning letters. Overall, there was a decrease or no change in all violations in the CLIIL database. The largest violation code reported was "failure to follow investigational plan" in both the 2005-2009 and 2010-2014 timeframes. Coding of FDA warning letters shows that the most common violations reported were failing to maintain accurate case histories (10.82%), enrolling ineligible subjects (8.85%), and failing to perform required tests (8.52%).
The overall decrease in violations is encouraging. But, the high proportion of violations related to failure to follow the investigational plan is concerning as the complexity of trials increases. We conclude that more detailed information is necessary to accurately evaluate these violations. The current study provides a model for creating more granular data of violations to better inform clinical investigators and improve clinical trials.
美国食品和药物管理局（FDA）将临床调查场所的检查作为临床试验监管的一个组成部分。FDA 在临床研究者检查清单（CLIIL）中描述了这些检查的结果。更严重的违规行为会在 FDA 向研究者发出的警告信中得到跟进。本研究的主要目的是定性和定量描述 2010 年至 2014 年期间 FDA 发布的 CLIIL 数据和内容。
我们对 CLIIL 和 FDA 警告信进行了回顾性分析。对于 CLIIL，我们量化了每个违规行为在其他数据点中的频率。我们将最近的数据（2010-2014 年）与前 5 年（2005-2009 年）进行了比较。为了分析 FDA 警告信，我们开发了一个编码系统来量化发现的违规行为的频率。
我们分析了 CLIIL 数据库中的 3637 次检查和 60 封警告信。总体而言，CLIIL 数据库中的所有违规行为都有所减少或没有变化。报告的最大违规代码是“未按研究计划进行”，无论是在 2005-2009 年还是 2010-2014 年期间。FDA 警告信的编码显示，报告的最常见违规行为是未能维护准确的病历（10.82%）、招募不合格的受试者（8.85%）以及未能进行必需的测试（8.52%）。
违规行为的总体减少令人鼓舞。但是，与未按研究计划进行相关的违规行为比例较高令人担忧，因为试验的复杂性增加。我们得出结论，需要更详细的信息才能准确评估这些违规行为。本研究为创建更详细的违规行为数据提供了一个模型，以便更好地为临床研究者提供信息，并改进临床试验。
