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

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.