Colorado Clinical and Transational Sciences Institute

项目摘要 在门诊环境中对高风险COVID-19患者实施早期有效治疗是一项 一个重要的公共卫生工具，以防止医疗保健系统达到突破点，加强早期 康复和减少住院治疗。在早期临床试验中，两种中和性单克隆抗体（nMAb） 治疗，bamlanivimab和casirivimab/imdevimab，显著降低病毒载量，症状， 住院治疗，导致美国食品和药物管理局发布紧急使用授权， 在高风险的COVID-19门诊患者中使用这些药物。不幸的是，只有一小部分（<5%）符合条件的 由于存在一些后勤障碍，门诊患者目前正在接受nMAb治疗， 不知道或不相信它的治疗效果。医学界和公共卫生界 需要可扩展的解决方案，以快速和公平地使用门诊nMAb，同时提供真实的- 证明其有效性的世界性证据。科罗拉多州实施了全州范围的随机 用于向合格患者分配nMAb的分配系统，这是唯一具有这种系统的州。基于鲁棒性 为了提高nMAb治疗的接受率，这种随机分配系统将促进快速 评价这些新型治疗在临床上重要的、以患者为中心的 通过一个时间敏感的自然实验。该项目使用类型2混合实现- 有效性设计旨在实现以下具体目标：1）评估使用nMAb的障碍和促进因素 全州范围内，基于创新理论的扩散; 2）制定，实施和评估全州范围内的战略 优化nMAb的公平获取;以及3）确定nMAb的真实有效性和安全性 高危COVID-19门诊患者的治疗。该方法将结合联合收割机的尖端传播和 利用状态随机分配系统的独特自然实验的实现方法， 沿着电子健康记录、患者调查和行政索赔数据。这个CTSA 管理补充将提供nMAb急需的真实世界T4转化证据 治疗和通知当前和未来门诊COVID-19治疗的快速传播。的 可交付成果将推进“为传播而设计”的概念;解决紧迫问题，以帮助患者 和临床医生管理不确定性，风险和紧迫性的问题;并创建一个模型，快速产生高 传染病大流行和其他未来突发公共卫生事件中的高质量真实世界证据。

PROJECT SUMMARY Implementation of early and effective treatment for high-risk COVID-19 patients in the outpatient setting is an important public health tool to prevent healthcare systems from reaching a breaking point by enhancing early recovery and reducing hospitalizations. In early clinical trials, two neutralizing monoclonal antibody (nMAb) treatments, bamlanivimab and casirivimab/imdevimab, significantly reduced viral load, symptoms, and hospitalizations, leading the U.S. Food and Drug Administration to issue Emergency Use Authorizations for these agents in high-risk COVID-19 outpatients. Unfortunately, only a small fraction (<5%) of eligible outpatients are currently accessing nMAb treatment due to a number of logistical barriers and clinicians who are not aware or convinced of its therapeutic benefit. The medical and public health communities desperately need scalable solutions for rapid and equitable use of outpatient nMAbs, while simultaneously providing real- world confirmatory evidence of their effectiveness. The State of Colorado implemented a statewide random allocation system for nMAb allocation to eligible patients, the only state with such a system. Building on robust dissemination to enhance uptake of nMAb treatment, this random allocation system will facilitate rapid evaluation of real-world effectiveness of these novel treatments on clinically important, patient-centered outcomes, through a time-sensitive natural experiment. This project uses a type 2 hybrid implementation- effectiveness design to achieve the following specific aims: 1) Assess barriers and facilitators to use of nMAbs statewide, based on diffusion of innovations theory; 2) Develop, implement, and evaluate statewide strategies to optimize equitable nMAb access; and 3) Determine the real-world effectiveness and safety of nMAb treatment in high-risk COVID-19 outpatients. The approach will combine cutting-edge dissemination and implementation methods with a unique natural experiment leveraging the state random allocation system, along with with electronic health record, patient survey, and administrative claims data. This CTSA Administrative Supplement will provide urgently needed real-world T4 translational evidence for nMAb treatment and inform rapid dissemination of current and future outpatient COVID-19 therapies. The deliverables will advance `designing for dissemination' concepts; address pressing concerns to help patients and clinicians manage issues of uncertainty, risk, and urgency; and create a model for rapidly generating high quality real-world evidence in infectious disease pandemics and other future public health emergencies.