Pragmatic Approaches to Capture and Ascertainment of Clinical Trial Endpoints

背景和意义： 采取务实的方法进行临床试验将显著减轻患者的负担， 临床研究生态系统。集中捕获和确定事件是一种主要的实用方法 取代由独立委员会进行的当地事件采集和事件裁定。正在进行的4期临床试验 由国家心肺血液研究所赞助的一项试验，流感疫苗有效阻止 胸事件和失代偿性心力衰竭（INVESTED），其中退伍军人事务部（VA） 由PI领导的34个研究中心组成的网络正在参与，为制定适当的 改进基于电子病历（EMR）的集中式端点捕获策略的方法 并比较中心事件捕获方法与传统事件捕获方法。 我们的目标是测试集中式端点捕获策略与传统端点捕获策略相比的假设。 利用以下具体目标的事件查明方法： 具体目标1。开发用于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：所有- 原因死亡率、心血管（CV）死亡、心肺住院（CV-心力衰竭， 脑血管事件、心肌梗死/急性冠状动脉综合征、心律失常;以及肺- 肺炎、慢性阻塞性肺病/慢性支气管炎、肺栓塞、哮喘、急性 呼吸衰竭）和对疫苗的不良反应（格林-巴利综合征，贝尔麻痹， 脑炎/肌炎、视神经炎、Steven-Johnson综合征、中毒性表皮坏死松解症）， 退伍军人通过中央方法。对于事件采集，我们将从多个VA和非VA数据中识别终点 来源，并使用迭代方法来完善算法，并将通过独立的 医生对医疗记录的审查和裁定。 具体目标2。比较中心和传统终点方法的事件捕获率 捕获和确认。 成果（预计）和预期影响： 我们将比较每项主要临床试验的中心方法和传统方法的事件捕获率 在每个连续流感季节及以上的事件水平上，具体目标1中描述的终点 整个审判期间。 我们将开发使用算法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EMR的事件捕获策略是非 比传统方法差。该项目还将提供有关如何简化 在临床试验中实现实时捕获和确定终点的中心方法。这个项目是 非常重要，因为它将开发集中的事件捕获方法， 开展临床试验以及患者、研究者和临床研究生态系统的负担， 并使VA成为临床试验创新方法的世界领导者。

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.