Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)

Adapt Out COVID is a master protocol to evaluate the safety and efficacy of investigationalagents for the treatment of symptomatic non-hospitalized adults with SARS-CoV-2infection. It includes a Phase II evaluation, with a seamless transition into a larger PhaseIII evaluation for promising agents.The trial is a randomized, controlled platform that allows agents to be added and droppedduring the course of the study for efficient testing of new agents against placebo within thesame trial infrastructure. When more than one new agent is being tested concurrently, thesame placebo will be used, when feasible.The primary outcome measures in the Phase II evaluation will be duration of symptoms,similar to the outcome used for outpatient influenza studies, detection of SARS-CoV-2RNA by nasopharyngeal (NP) swab, and safety. Determination of whether a Phase IIagent will continue to be evaluation in Phase III will be made after the last participantrandomized to that agent or placebo completes their day 28 Phase II visit. If continued,data collected from participants enrolled in Phase II will be included in the Phase IIIevaluation.The Phase III evaluation is a continuation of the Phase II trial, for those agents that meetcriteria for further evaluation and for which sufficient study product is available. Enrollmentof those agents advancing to Phase III will continue for a fully powered trial to determinethe efficacy of each investigational agent compared to placebo to prevent hospitalizationand death in non-hospitalized adults with COVID-19. 1. The ACTG Leadership and Operations Center (LOC). A newly restructured LOC is proposed to provide scientific leadership and fiscal and organizational management of the ACTG. The ACTG Executive Committee (AEC) will serve as the overarching governing body of the network. Transformative Science Groups will oversee the development and execution of the ACTG research agenda, which will be coordinated and prioritized by the Scientific Agenda Steering Committee (SASC). Protocol development, implementation, training and network evaluation will be facilitated by the Network Coordinating Center at Social & Scientific Systems, Inc. The LOC financial management group at Brigham and Women's Hospital (BWH) will oversee resource management and protocol fund distribution at the direction of the AEC. The LOC will assure the engagement of Community in all aspects of the ACTG, and will coordinate communication between all three components of the network. 2. The ACTG Laboratory Center (LC). The ACTG LC will comprise Specialty Laboratories in virology, immunology, pharmacology, mycobacteriology and genomics equipped to perform protocol-specified testing and to advance the state-of-the-art by developing novel assays to address innovative pathogenesis-based questions arising from ACTG clinical trials. The LC will also oversee the quality management of all laboratories performing testing for clinical monitoring and primary endpoint determination. The LC leadership will be fully integrated into the scientific committee and governance structure of the LOC, assuring close alignment of LC activities with the research agenda of the network as a whole. Particular emphasis will be placed on building network laboratory capacity at international sites in resource-limited settings. 3. The ACTG Statistics and Data Management Center (SDMC). The SDMC will comprise the Statistical and Data Analysis Center (SDAC) at the Center for Biostatistics and AIDS Research (CBAR) at Harvard School of Public Health (HSPH) and the Data Management Center (DMC) at Frontier Science & Technology Research Foundation (FSTRF) in Amherst, NY. The SDMC will provide innovative approaches to the design and biostatistical analysis of ACTG clinical trials and laboratory studies; leads accurate collection of protocol specific clinical and laboratory datathrough electronic data capture; ensure data integrity, security and quality; and provide training to sites and laboratories. The SDMC will prepare regular reports to support the work of data monitoring committees overseeing the safety of ACTG trials. The SDMC leadership will be fully integrated into the scientific committee and governance structure of the LOC, assuring close alignment of SDMC activities with the research agenda of the network as a whole. RELEVANCE: The expertise provided by the SDMC will help advance research concerning the treatment of HIV-infected people or of diseases such as tuberculosis and hepatitis affecting these people. It will achieve this by ensuring that ACTG clinical trials and other studies are efficiently designed and analyzed to the highest standards. This research will continue to make significant contributions in advancing optimal treatment of HIV-infected individuals both in the Unites States and internationally.