Finding a Needle in a Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection

Abstract Background Rapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test’s performance in asymptomatic individuals when used serially. Objective To describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Design Prospective cohort study using a decentralized approach. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Setting Participants throughout the mainland United States were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Ag-RDTs were completed at home, and molecular comparators were shipped to a central laboratory. Participants Individuals over 2 years old from across the U.S. with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Measurements Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results A total of 7,361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Limitations New, complex workflows required significant operational and data team support. Conclusions: The digital site-less approach employed in the ‘Test Us At Home’ study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.