Pragmatic Approaches to Capture and Ascertainment of Clinical Trial Endpoints

背景和意义： 进行临床试验的务实方法将显著减轻患者和 临床研究生态系统。集中捕获和查明事件是一种主要的务实方法 取代地方事件捕获和由独立委员会进行事件裁决。正在进行的4期临床 由国家心肺血液研究所主办的流感疫苗试验有效停止 心胸事件和失代偿性心力衰竭(投资)，退伍军人事务部(VA) 由34个站点组成的网络PI正在参与其中，提供了一个理想的机会来开发合适的 改进基于电子病历(EMR)的终端捕获集中策略的方法 并比较中央事件捕获方法和传统事件捕获方法。 我们的目标是测试这样一种假设，即集中式端点捕获策略与传统的 利用以下具体目标确定事件的方法： 具体目标1.开发捕获主要临床试验终点的算法。 我们将开发从国家VA数据库中获取以下临床试验终点的方法：ALL- 死因死亡、心血管(CV)死亡、心肺住院(CV-心力衰竭、 脑血管事件、心肌梗死/急性冠脉综合征、心律失常；以及 肺炎、慢性阻塞性肺疾病/慢性支气管炎、肺栓塞、哮喘、急性 呼吸衰竭)和疫苗的不良反应(格林-巴利综合征，贝尔麻痹， 脑炎/脊髓炎、视神经炎、史蒂文-约翰逊综合征、中毒性表皮坏死松解症) 退伍军人通过中央方法。对于事件捕获，我们将从多个VA和非VA数据中识别终端 源代码，并使用迭代的方法来求精算法，并将独立测试算法的有效性 医生对病历的审查和裁决。 具体目标2.比较中央和传统端点方法的事件捕获率 抓捕和查明。 结果(预计)和预期影响： 我们将比较每个主要临床试验的中心方法和传统方法的事件捕获率 在每个连续的流感季节及以后，在事件一级的具体目标1所述的终点 整个试用期。 我们将开发使用易于实现的算法来准确捕获主要临床试验终点的方法 适用于任何电子病历系统。我们还希望发现，基于电子病历的事件捕获策略不是 比传统方法差。该项目还将提供有关如何简化流程的重要新数据 在临床试验中实现实时捕获和确定终点的中央方法。这个项目是 非常重要，因为它将开发集中式事件捕获方法，从而降低 进行临床试验，以及患者、研究人员和临床研究生态系统的负担， 并使退伍军人管理局成为临床试验创新方法的世界领先者。

Background and Significance: Pragmatic approaches to the conduct of clinical trials would markedly reduce the burden on patients and the clinical research ecosystem. Centralized capture and ascertainment of events is a major pragmatic approach to replace local event capture and event adjudication by independent committees. An ongoing phase 4 clinical trial sponsored by the National Heart, Lung, and Blood Institute, INfluenza Vaccine to Effectively Stop CardioThoracic Events and Decompensated heart failure (INVESTED), in which the Veterans Affairs (VA) Network of 34 sites led by the PI is participating, offers an ideal opportunity to develop appropriate methodology to improve electronic medical record (EMR)-based centralized strategies for endpoint capture and to compare central versus traditional event capture methodology. We aim to test the hypothesis that centralized endpoint capture strategies are comparable to traditional methods of event ascertainment utilizing the following specific aims: Specific Aim 1. Develop algorithms for capture of major clinical trial endpoints. We will develop methodology to capture following clinical trial endpoints from the national VA databases: all- cause mortality, cardiovascular (CV) death, cardiopulmonary hospitalizations (CV -heart failure, cerebrovascular events, myocardial infarction/acute coronary syndrome, arrhythmias; and pulmonary - pneumonia, chronic obstructive pulmonary disease/chronic bronchitis, pulmonary embolism, asthma, acute respiratory failure), and adverse reaction to vaccine (Guillain-Barre syndrome, Bell's palsy, encephalitis/myelitis, optic neuritis, Steven-Johnson syndrome, toxic epidermal necrolysis), of enrolled veterans by central methods. For event capture, we will identify endpoints from multiple VA and non-VA data sources and use an iterative method to refine algorithms and will test validity of algorithms by independent physician review and adjudication of medical records. Specific Aim 2. Compare the event capture rate between central and traditional methods of endpoint capture and ascertainment. Outcomes (projected) and Anticipated impact: We will compare event capture rates of central and traditional methods for each of the major clinical trial endpoints described in Specific Aim 1 at the event level during each consecutive influenza season and over the entire trial period. We will develop methods to accurately capture major clinical trial endpoints using algorithms that will be easily applicable to any EMR system. We also expect to find that EMR based event capture strategies are non- inferior to traditional methods. This project will also provide significant new data about how to streamline central approaches to achieve real-time capture and ascertainment of endpoints in clinical trials. This project is highly significant since it will develop centralized event capture methods that will reduce the costs of conducting clinical trials as well as the burden on patients, investigators, and the clinical research ecosystem, and make the VA a world leader in innovative approaches to clinical trials.