Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials
Authors: Mena Lora Alfredo J. , Long Jessica E. , Huang Yunda , Baden Lindsey R. , El Sahly Hana M. , Follmann Dean , Goepfert Paul , Gray Glenda , Grinsztejn Beatriz , Kotloff Karen , Rouphael Nadine , Sobieszczyk Magdelena , Walsh Stephen R. , Andriesen Jessica , Shah Karan A. , Zhang Yuanyuan , Gilbert Peter , Janes Holly , Gay Cynthia L. , Falsey Ann R. , Tripp Rebecca L. , Gorman Richard L. , Tong Tina , Marovich Mary , Neuzil Kathleen , Corey Lawrence , Kublin James G. ,   COVID-19 Prevention Network, Reirden Daniel , Immergluck Lilly , Kelley Colleen , Durbin Anna , Tapia Milagritos , Deming Megan , Kotloff Karen , Pinto Jorge , Goepfert Paul , Hoosain Zaheer , Lombaard Johan , Stephenson Kathryn , Baden Lindsey , Walsh Stephen , Mayer Ken , Cahn Pedro , Losso Marcelo , Cassetti Isabel , Innes Steven , Bekker Linda-Gail , Kassim Sheetal , Orrel Catherine , Meintjes Graeme , Ward Amy , Diacon Andreas , Wohl David , Gray Cindy , Turley Chrinstine , Oyedele Temitope , Taiwo Babafemi O. , Krueger Karen , Novak Rick , Sha Beverly E. , Hammit Laura , Fichtenbaum Carl , Bernstein David , Jacobson Jeffrey , Dandachi Dima , Naqvi Hasan , Koletar Susan , Rouphael Nadine , Edupuganti Sri , Campbell Thomas , Secord Elizabeth , Siva Samantha , Jeenarain Nitesha , Naidoo Logashvari , Garrett Nigel , Naicker Nivashnee , Naicker Vimla , Naidoo Jayganthie , Premrajh Anamikah , Walter Emmanuel , Henderson Jeff , Tempelman Hugo , Siika Abraham , Anderson Evan , Okech Brenda , Rupp Richard , El Sahly Hana , Healy Catherine M. , Arduino Robert , Winokur Patricia , Casapia Martin , Marshall Gailen , Navalkele Bhagyashri D. , Badel-Faeson Sharla , Sanne Ian , Fairlie Lee , Kekitiinwa Adeodata , Ntege Patricia , Elyanu Peter J. , Mutuluuza Cissy K. , Rwambuya Sandra , Musoke Philippa , Wabwire Deo , Pahud Barbara , Castro Mario , Sawe Fredrick , Ouma Samuel G. , Samandari Taraz , Mboya Grace , Innes Craig , Kotze Philip , Lama Javier , Sanchez Jorge , Gallardo Jorge , Gonzales Pedro , Cabello Robinson , Landovitz Raphael , Dube Michael P. , Gould-Porter Tamela , Shoptaw Steve , Clark Jesse , Kotze Sheena , Kasselman Olivia , Gill Katherine , Nchabeleng Maphoshane , Gaur Aditya , Cabrera Carlos , Doblecki-Lewis Susanne , Kline Susan , McClelland Scott , Kishorchandra Mandaliya , Mda Pamela , Dubula Thozama , Jaoko Walter , Kalams Spyros , Haas David , Berthaud Vladimir , Creech Clarence , Abdalian Sue Ellen , Justman Jessica , Delafontaine  , Marks Kristen , Mannheimer Sharon , Van Tieu Hong , Sobieszczyk Magda , Mulligan Mark , Raabe Vanessa , Olson Mary , Erb Juanita , Swaminathan Shobha , Pilotto Jose , Hall Christopher , Florescu Diana , de Jesus Edwin , Frank Ian , Barr Katie , McMahon Deborah , Riddler Sharon , Martin Judith M. , Barranco Elizabeth , Santos Breno , Tashima Karen , Grinsztejn Beatriz , Filho Esau J. , Keefer Mike , Falsey Ann , Brumskine William , Cohen Stuart , Okulicz Jason , Taylor Barbara , Patterson Thomas , Maves Ryan , Little Susan , Buchbinder Susan , Luetkemeyer Annie , Zorrilla Carmen , Kallas Esper , Silva Vivian A. , Newman Tamara , Valdez Madruga Jose , McElrath Julie , Jackson Lisa , Wald Anna , Malahleha Mookho , Laher Fatima , Lazarus Erica , Nana Anusha , Hoft Daniel , Frey Sharon , Presti Rachel , Nachman Sharon , Luft Benjamin , Rodriguez Carina , Mngadi Kathy , Daar Eric , Barnabas Shaun , Cotton Mark , Spector Stephen , Servilla Karen , Linder Kathleen A. , Moana Abeer , Kauffman Carol , Bessesen Mary , Talwani Rohit , Dell'Italia Louis , Alonto Augusto , Liebman Daniel , Bedimo Roger , Woods Christopher , Sriram Peruvemba , Padala Kalpana , Holt Gregory , Swialto Edwin , Jay Melanie , Felson Sabrina , Henderson Nora , Brown Sheldon , Aguayo Saumuel , Riddle Mark , Tien Phyllis , Toney John , Dawood Halima , Makhaza Disebo , Mighty Hugh , Mahgoub Siham , Campbell Wes , Diemert David , Schwasinger-Schmidt Tiffany , Morse Caryn G. , Sanders John W. , Williamson John , Luabeya Angelique , Bukusi Elizabeth , Mugo Nelly , Kibuuka Hannah , Mwesigwe Betty , Kambugu Andrew , Balyegisawa Apolo P. , Mullane Kathleen , Andagalu Ben , Tina Lucas , Copeland Nathaniel , Hutter Jack , de las Casas Claudio L. , Ruiz-Palacios Guillermo , Eron Joseph J. , Currier Judith S. , Cohen Myron S. , Kim Kami , Greenberg Richard N. , Kasaro Margaret , Delaney-Moretlwe Sinead , Dawson Rodney , Paez Carmen , Grunenberg Nicole , Hahn William O. , Gelderbloom Huub C. , Andrasik Michele P. , Wallace Stephaun E. 
Published: January 2023

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.