Population Health Research Institute, Hamilton, ON, Canada.
Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
Clin Trials. 2023 Apr;20(2):166-175. doi: 10.1177/17407745221149222. Epub 2023 Feb 3.
In clinical trials, event adjudication is a process to review and confirm the accuracy of outcomes reported by site investigators. Despite efforts to automate the communication between a clinical-data-and-coordination center and an event adjudication committee, the review and confirmation of outcomes, as the core function of the process, still fully rely on human labor. To address this issue, we present an automated event adjudication system and its application in two randomized controlled trials.
Centrally executed by a clinical-data-and-coordination center, the automated event adjudication system automatedly assessed and classified outcomes in a clinical data management system. By checking clinically predefined criteria, the automated event adjudication system either confirmed or unconfirmed an outcome and automatedly updated its status in the database. It also served as a management tool to assist staff to oversee the process of event adjudication. The system has been applied in: (1) the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial and (2) the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial. The automated event adjudication system first screened outcomes reported on a case report form and confirmed those with data matched to preset definitions. For selected primary efficacy, secondary, and safety outcomes, the unconfirmed cases were referred to a human event adjudication committee for a final decision. In the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial, human adjudicators were given priority to review cases, while the automated event adjudication system took the lead in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial.
Outcomes that were adjudicated in a hybrid model are discussed here. The COMPASS automated event adjudication system adjudicated 3283 primary efficacy outcomes and confirmed 1652 (50.3%): 132 (21.1%) strokes, 522 (53%) myocardial infarctions, and 998 (59.7%) causes of deaths. The NAVIGATE ESUS one adjudicated 737 cases of selected outcomes and confirmed 383 (52%): 219 (51.5%) strokes, 34 (42.5%) myocardial infarctions, 73 (54.9%) causes of deaths, and 57 (57.6%) major bleedings. After one deducts the time needed for migrating the system to a new study, the automated event adjudication system helped to reduce the time required for human review from approximately 1303 to 716.5 h for the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial and from 387 to 196 h for the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source trial.
The automated event adjudication system in combination with human adjudicators provides a streamlined and efficient approach to event adjudication in clinical trials. To immediately apply automated event adjudication, one can first consider the automated event adjudication system and involve human assistance for cases unconfirmed by the former.
在临床试验中，事件裁定是一个审查和确认站点研究者报告的结果准确性的过程。尽管努力使临床数据和协调中心与事件裁定委员会之间的沟通自动化，但作为该过程核心功能的结果审查和确认仍然完全依赖于人工劳动。为了解决这个问题，我们提出了一个自动化的事件裁定系统及其在两项随机对照试验中的应用。
由临床数据和协调中心集中执行，自动化事件裁定系统自动评估和分类临床数据管理系统中的结果。通过检查临床预定义标准，自动化事件裁定系统确认或不确认结果，并自动更新数据库中的状态。它还作为一种管理工具，协助工作人员监督事件裁定过程。该系统已应用于：（1）使用抗凝策略的人群心血管结局（COMPASS）试验和（2）新型利伐沙班抑制全球因子 Xa 与阿司匹林预防不明来源栓塞性卒中的栓塞事件（NAVIGATE ESUS）试验。自动化事件裁定系统首先筛选病例报告表上报告的结果，并确认与预设定义匹配的数据的结果。对于选定的主要疗效、次要疗效和安全性结局，未确认的病例将提交给人类事件裁定委员会做出最终决定。在新型利伐沙班抑制全球因子 Xa 与阿司匹林预防不明来源栓塞性卒中的栓塞事件（NAVIGATE ESUS）试验中，人类裁判被优先安排审查病例，而自动化事件裁定系统在使用抗凝策略的人群心血管结局（COMPASS）试验中处于领先地位。
在此讨论了混合模型裁定的结果。COMPASS 自动化事件裁定系统裁定了 3283 项主要疗效结局，并确认了 1652 项（50.3%）：132 例（21.1%）中风、522 例（53%）心肌梗死和 998 例（59.7%）死亡原因。NAVIGATE ESUS 裁定了 737 例选定结局，并确认了 383 例（52%）：219 例（51.5%）中风、34 例（42.5%）心肌梗死、73 例（54.9%）死亡原因和 57 例（57.6%）大出血。扣除将系统迁移到新项目所需的时间后，自动化事件裁定系统帮助减少了人类审查所需的时间，对于使用抗凝策略的人群心血管结局试验，从大约 1303 小时减少到 716.5 小时，对于新型利伐沙班抑制全球因子 Xa 与阿司匹林预防不明来源栓塞性卒中的栓塞事件（NAVIGATE ESUS）试验，从 387 小时减少到 196 小时。
自动化事件裁定系统与人类裁判相结合，为临床试验中的事件裁定提供了一种简化和高效的方法。要立即应用自动化事件裁定，可以首先考虑自动化事件裁定系统，并在前者未确认的情况下，由人工协助。
