Implementation and Real-World Effectiveness of Monoclonal Antibodies to Treat High-Risk Outpatients with COVID-19

单克隆抗体治疗高危门诊 COVID-19 患者的实施和实际有效性

基本信息

批准号：
10342493
负责人：
Adit A. Ginde
金额：
$ 544.95万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10342493
关键词：
2019-nCoV Address Administrative Supplement Adopted Antibody Therapy Awareness Bioethics Biometry COVID-19 COVID-19 morbidity COVID-19 mortality COVID-19 patient COVID-19 treatment Cessation of life Clinical Clinical Medicine Clinical Trials Colorado Communicable Diseases Community Health Data Diffusion of Innovation Disease Dissemination and Implementation Dose Early treatment Effectiveness Elderly Electronic Health Record Environment and Public Health Evaluation FDA Emergency Use Authorization Focus Groups Future Geography Health Healthcare Healthcare Systems Hospitalization Incidence Interview Intravenous Intravenous infusion procedures Lead Logistics Long COVID Medical Methods Modeling Monoclonal Antibodies Natural experiment Not Hispanic or Latino Outcome Outpatients Patient Outcomes Assessments Patient-Focused Outcomes Patients Phase Positioning Attribute Primary Health Care Protocols documentation Provider Public Health Quality of life Random Allocation Recovery Research Personnel Resistance Risk Rural SARS-CoV-2 variant Safety Severities Speed Subgroup Surveys Symptoms System Therapeutic Time Uncertainty United States Food and Drug Administration Vaccines Viral Viral Load result acute care acute symptom base biomedical informatics casirivimab and imdevimab comorbidity convalescent plasma design dissemination strategy early phase clinical trial effective therapy effectiveness implementation study experience high risk implementation science implementation strategy informant minority communities neutralizing monoclonal antibodies novel operation pandemic disease practice-based research network prevent primary outcome prototype public health emergency public-private partnership racial and ethnic remdesivir secondary outcome theories therapeutic development tool treatment as usual uptake vaccine distribution

项目摘要

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.

项目概要在门诊对高危 COVID-19 患者实施早期有效治疗是一项重要任务通过早期加强预防医疗保健系统达到崩溃点的重要公共卫生工具康复并减少住院治疗。在早期临床试验中，两种中和单克隆抗体（nMAb） bamlanivimab 和 casirivimab/imdevimab 治疗显着降低了病毒载量、症状和住院治疗，导致美国食品和药物管理局颁发紧急使用授权这些药物用于高危 COVID-19 门诊患者。不幸的是，只有一小部分（<5%）符合条件由于一些后勤障碍和临床医生的阻碍，门诊患者目前正在接受 nMAb 治疗不知道或不相信其治疗益处。医疗和公共卫生界迫切需要需要可扩展的解决方案来快速、公平地使用门诊 nMAb，同时提供真实的其有效性的世界确凿证据。科罗拉多州在全州范围内实施了随机向符合条件的患者分配 nMAb 的分配系统，这是唯一拥有此类系统的州。建立在稳健的基础上传播以提高 nMAb 治疗的吸收，这种随机分配系统将促进快速评估这些新疗法对临床重要的、以患者为中心的现实世界的有效性通过对时间敏感的自然实验获得结果。该项目使用类型 2 混合实现 - 有效性设计以实现以下具体目标： 1) 评估使用 nMAb 的障碍和促进因素基于创新扩散理论的全州范围； 2) 制定、实施和评估全州战略优化 nMAb 的公平获取； 3) 确定 nMAb 在现实世界中的有效性和安全性高危 COVID-19 门诊患者的治疗。该方法将结合前沿的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，以及电子健康记录、患者调查和行政索赔数据。本次CTSA 行政补充文件将为 nMAb 提供急需的现实世界 T4 转化证据治疗并为当前和未来门诊 COVID-19 疗法的快速传播提供信息。这可交付成果将推进“传播设计”概念；解决紧迫问题以帮助患者临床医生管理不确定性、风险和紧迫性问题；并创建一个快速生成高值的模型传染病大流行和其他未来公共卫生紧急情况的高质量真实证据。