A Deferred-Vaccination Design to Assess Durability of COVID-19 Vaccine Effect After the Placebo Group Is Vaccinated
Author
Follmann, DeanFintzi, Jonathan
Fay, Michael P
Janes, Holly E
Baden, Lindsey R
El Sahly, Hana M
Fleming, Thomas R
Mehrotra, Devan V
Carpp, Lindsay N
Juraska, Michal
Benkeser, David
Donnell, Deborah
Fong, Youyi
Han, Shu
Hirsch, Ian
Huang, Ying
Huang, Yunda
Hyrien, Ollivier
Luedtke, Alex
Carone, Marco
Nason, Martha
Vandebosch, An
Zhou, Honghong
Cho, Iksung
Gabriel, Erin
Kublin, James G
Cohen, Myron S
Corey, Lawrence
Gilbert, Peter B
Neuzil, Kathleen M
Date
2021-04-13Journal
Annals of Internal MedicinePublisher
American College of PhysiciansType
Article
Metadata
Show full item recordAbstract
Multiple candidate vaccines to prevent COVID-19 have entered large-scale phase 3 placebo-controlled randomized clinical trials, and several have demonstrated substantial short-term efficacy. At some point after demonstration of substantial efficacy, placebo recipients should be offered the efficacious vaccine from their trial, which will occur before longer-term efficacy and safety are known. The absence of a placebo group could compromise assessment of longer-term vaccine effects. However, by continuing follow-up after vaccination of the placebo group, this study shows that placebo-controlled vaccine efficacy can be mathematically derived by assuming that the benefit of vaccination over time has the same profile for the original vaccine recipients and the original placebo recipients after their vaccination. Although this derivation provides less precise estimates than would be obtained by a standard trial where the placebo group remains unvaccinated, this proposed approach allows estimation of longer-term effect, including durability of vaccine efficacy and whether the vaccine eventually becomes harmful for some. Deferred vaccination, if done open-label, may lead to riskier behavior in the unblinded original vaccine group, confounding estimates of long-term vaccine efficacy. Hence, deferred vaccination via blinded crossover, where the vaccine group receives placebo and vice versa, would be the preferred way to assess vaccine durability and potential delayed harm. Deferred vaccination allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain them on placebo, yet still allows important insights about immunologic and clinical effectiveness over time.Identifier to cite or link to this item
http://hdl.handle.net/10713/15459ae974a485f413a2113503eed53cd6c53
10.7326/M20-8149
Scopus Count
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