Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) was an extraordinary example of a public-private partnership (PPP) that brought together over thirty organizations and hundreds of individuals to address one of the most pressing global health needs in recent decades. In particular, ACTIV provided a key avenue for testing numerous therapeutics for their potential benefit in treating the SARS-CoV-2 virus or the resulting symptoms of acute COVID-19 infection. Given the speed and scale at which ACTIV designed and implemented master protocols across global networks that it was simultaneously working to create, the PPP can provide valuable lessons for best practices and avoiding pitfalls the next time the world is faced with a global pandemic of a novel pathogen. This report provides a general overview of the ACTIV partnership to set the stage and context for the subsequent articles in this issue that will relay these lessons learned.