• Amanda MacPherson, Nora Hutchinson, Oliver Schneider, Elisabeth Oliviero, Emma Feldhake, Charlotte Ouimet, Jacky Sheng, Fareed Awan, Catherine Wang, Jesse Papenburg, Nicole E Basta, and Jonathan Kimmelman.
• Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada (A.M., N.H., O.S., E.O., E.F., C.O., J.S., F.A., C.W., J.K.).
• Ann. Intern. Med. 2021 Mar 1; 174 (3): 326-334.

BackgroundAnticipated success rates and timelines for COVID-19 vaccine development vary. Recent experience with developing and testing viral vaccine candidates can inform expectations regarding the development of safe and effective vaccines.ObjectiveTo estimate timelines and probabilities of success for recent vaccine candidates.DesignClinicalTrials.gov was searched to identify trials testing viral vaccines that had not advanced to phase 2 before 2005, and the progress of each vaccine from phase 1 through to U.S. Food and Drug Administration (FDA) licensure was tracked. Trial characteristics were double-coded. (Registration: Open Science Framework [https://osf.io/dmuzx/]).SettingTrials launched between January 2005 and March 2020.ParticipantsPreventive viral vaccine candidates for 23 emerging or reemerged viral infectious diseases.MeasurementsThe primary end point was the probability of vaccines advancing from launch of phase 2 to FDA licensure within 10 years.ResultsIn total, 606 clinical trials forming 220 distinct development trajectories (267 343 enrolled participants) were identified. The probability of vaccines progressing from phase 2 to licensure within 10 years was 10.0% (95% CI, 2.6% to 16.9%), with most approvals representing H1N1 or H5N1 vaccines. The average timeline from phase 2 to approval was 4.4 years (range, 6.4 weeks to 13.9 years). The probabilities of advancing from phase 1 to 2, phase 2 to 3, and phase 3 to licensure within the total available follow-up time were 38.2% (CI, 30.7% to 45.0%), 38.3% (CI, 23.1% to 50.5%), and 61.1% (CI, 3.7% to 84.3%), respectively.LimitationsThe study did not account for preclinical development and relied primarily on ClinicalTrials.gov and FDA resources. Success probabilities do not capture the varied reasons why vaccines fail to advance to regulatory approval.ConclusionSuccess probabilities and timelines varied widely across different vaccine types and diseases. If a SARS-CoV-2 vaccine is licensed within 18 months of the start of the pandemic, it will mark an unprecedented achievement for noninfluenza viral vaccine development.Primary Funding SourceMcGill Interdisciplinary Initiative in Infection and Immunity (MI4) Emergency COVID-19 Research Funding program.

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