1. Estimating vaccine efficacy during open-label follow-up of COVID-19 vaccine trials based on population-level surveillance data.
- Author
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Moore M, Zhu Y, Hirsch I, White T, Reiner RC, Barber RM, Pigott D, Collins JK, Santoni S, Sobieszczyk ME, and Janes H
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Follow-Up Studies, Incidence, Population Surveillance methods, United States epidemiology, COVID-19 prevention & control, COVID-19 epidemiology, COVID-19 Vaccines administration & dosage, COVID-19 Vaccines therapeutic use, SARS-CoV-2 immunology, Vaccine Efficacy statistics & numerical data
- Abstract
While rapid development and roll out of COVID-19 vaccines is necessary in a pandemic, the process limits the ability of clinical trials to assess longer-term vaccine efficacy. We leveraged COVID-19 surveillance data in the U.S. to evaluate vaccine efficacy in U.S. Government-funded COVID-19 vaccine efficacy trials with a three-step estimation process. First, we used a compartmental epidemiological model informed by county-level surveillance data, a "population model", to estimate SARS-CoV-2 incidence among the unvaccinated. Second, a "cohort model" was used to adjust the population SARS-CoV-2 incidence to the vaccine trial cohort, taking into account individual participant characteristics and the difference between SARS-CoV-2 infection and COVID-19 disease. Third, we fit a regression model estimating the offset between the cohort-model-based COVID-19 incidence in the unvaccinated with the placebo-group COVID-19 incidence in the trial during blinded follow-up. Counterfactual placebo COVID-19 incidence was estimated during open-label follow-up by adjusting the cohort-model-based incidence rate by the estimated offset. Vaccine efficacy during open-label follow-up was estimated by contrasting the vaccine group COVID-19 incidence with the counterfactual placebo COVID-19 incidence. We documented good performance of the methodology in a simulation study. We also applied the methodology to estimate vaccine efficacy for the two-dose AZD1222 COVID-19 vaccine using data from the phase 3 U.S. trial (ClinicalTrials.gov # NCT04516746). We estimated AZD1222 vaccine efficacy of 59.1% (95% uncertainty interval (UI): 40.4%-74.3%) in April, 2021 (mean 106 days post-second dose), which reduced to 35.7% (95% UI: 15.0%-51.7%) in July, 2021 (mean 198 days post-second-dose). We developed and evaluated a methodology for estimating longer-term vaccine efficacy. This methodology could be applied to estimating counterfactual placebo incidence for future placebo-controlled vaccine efficacy trials of emerging pathogens with early termination of blinded follow-up, to active-controlled or uncontrolled COVID-19 vaccine efficacy trials, and to other clinical endpoints influenced by vaccination., Competing Interests: Declaration of competing interest Ian Hirsch is an employee of and own shares in AstraZeneca. Tom White is an employee of AstraZeneca and owns shares in AstraZeneca. Holly Janes, Mia Moore, Yifan Zhu, Robert C. Reiner, Serena Santoni, Ryan M. Barber, David Pigott, James K. Collins have no competing interests. Magdalena E. Sobieszczyk declares grants from the NIH and NIAID during the conduct of the study and grants from NIH/NIAID and the Gates Foundation outside the submitted work; she has received grants to her institution from Merck Sharpe and Dohme, Sanofi, and Gilead outside of submitted work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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