Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials
Alfredo J Mena Lora, Jessica E. Long, Yunda Huang, Lindsey R. Baden, Hana M. El Sahly, Dean Follmann, Paul Goepfert, Glenda Gray, Beatriz Grinsztejn, Karen L. Kotloff, Nadine Rouphael, Magdelena Sobieszczyk, Stephen R. Walsh, Jessica Andriesen, Karan A. Shah, Yuanyuan Zhang, Peter B. Gilbert, Holly Janes, Cynthia L. Gay, Ann R. Falsey, Rebecca L. Tripp, Richard L. Gorman, Tina Tong, Mary Marovich, Kathleen M. Neuzil, Lawrence Corey, James G. Kublin, COVID-19 Prevention Network, Daniel Reirden, Lilly Cheng Immergluck, Colleen F. Kelley, Anna P. Durbin, Milagritos Tapia, Megan Deming, Karen L. Kotloff, Jorge Pinto, Paul Goepfert, Zaheer Hoosain, Johan Lombaard, Kathryn E. Stephenson, Lindsey R. Baden, Stephen R. Walsh, Ken Mayer, Pedro Cahn, Marcelo Losso, Isabel Cassetti, Steven Innes, Linda‐Gail Bekker, Sheetal Kassim, Catherine Orrel, Graeme Meintjes, Amy Ward, Andreas Diacon, David A. Wohl, Cindy M. Gray, Chrinstine Turley, Temitope Oyedele, Babafemi Taiwo, Karen Krueger, Rick Novak, Beverly E. Sha, Laura Hammit, Carl J. Fichtenbaum, David I. Bernstein, Jeffrey M. Jacobson, Dima Dandachi, Hasan Raja Naqvi, Susan L. Koletar, Nadine Rouphael, Sri Edupuganti, Thomas Campbell, Elizabeth Secord, Samantha Siva, Nitesha Jeenarain, Logashvari Naidoo, Nigel Garrett, Nivashnee Naicker, Vimla Naicker, Jayganthie Naidoo, Anamikah Premrajh, Emmanuel B. Walter, Jeff Henderson, Hugo A. Tempelman, Abraham Siika, Evan J. Anderson, Brenda Okech, Richard Rupp, Hana M. El Sahly, Catherine M. Healy, Robert Arduino, Patricia Winokur, Martín Casapía, Gailen D. Marshall, Bhagyashri Navalkele, Sharla Badel-Faeson, Ian Sanne, Lee Fairlie, Adeodata Kekitiinwa, Patricia Ntege, Peter Elyanu
Abstract
Importance: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts. Observations: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus. Conclusions and Relevance: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness.