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

• 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
• 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

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.

项目摘要 在门诊环境中，对高风险共vid-19患者实施早期有效治疗是一种 重要的公共卫生工具，以防止医疗保健系统通过提早增强达到破裂点 恢复和减少住院。在早期临床试验中，两种中和单克隆抗体（NMAB） 治疗，bamlanivimab和casirivimab/imdevimab，大大降低了病毒负荷，症状和 住院，导致美国食品和药物管理局签发紧急使用授权 这些代理在高风险的Covid-19门诊患者中。不幸的是，只有一小部分（<5％）合格 由于许多后勤障碍和临床医生，门诊病人目前正在接受NMAB治疗 不知道或相信其治疗益处。医疗和公共卫生社区拼命 需要可扩展的解决方案，以快速和公平地使用门诊NMAB，同时提供现实 世界确认性证据表明其有效性。科罗拉多州实施了全州随机 NMAB分配给合格患者的分配系统，这是唯一具有这种系统的州。建立在强大的基础上 传播以增强NMAB治疗的摄取，这种随机分配系统将有助于快速 评估这些新型治疗方法对临床重要，以患者为中心的现实有效性 结局，通过时间敏感的自然实验。该项目使用2型混合实现 - 实现以下特定目的的有效性设计：1）评估使用NMAB的障碍和促进者 全州，基于创新理论的扩散； 2）制定，实施和评估全州策略 优化公平的NMAB访问； 3）确定NMAB的现实效力和安全性 在高风险的COVID-19医院中进行治疗。该方法将结合尖端的传播和 实施方法具有独特的自然实验，利用状态随机分配系统， 以及电子健康记录，患者调查和行政索赔数据。这个CTSA 行政补充剂将为NMAB提供急需的现实世界T4翻译证据 治疗并为当前和未来的门诊COVID-19疗法快速传播。这 可交付成果将推进“为传播”概念推进；解决紧迫的问题以帮助患者 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，以快速产生高 传染病大流行病和其他未来公共卫生紧急情况的质量现实证据。