{"doi":"10.1016/j.epidem.2024.100768","title":"Estimating vaccine efficacy during open-label follow-up of COVID-19 vaccine trials based on population-level surveillance 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.","journal":"Epidemics","year":2024,"id":473266,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8483,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04516746"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":519126,"name":"Yifan Zhu","orcid":"0000-0001-7872-4533","position":1,"is_corresponding":false},{"id":553744,"name":"Ian Hirsch","orcid":"0000-0003-1232-9770","position":2,"is_corresponding":false},{"id":20365,"name":"Tom White","orcid":"0000-0001-8456-0803","position":3,"is_corresponding":false},{"id":48646,"name":"Robert C. Reiner","orcid":"0000-0003-1056-7919","position":4,"is_corresponding":false},{"id":613683,"name":"Ryan M Barber","orcid":null,"position":5,"is_corresponding":false},{"id":61320,"name":"David M. Pigott","orcid":"0000-0002-6731-4034","position":6,"is_corresponding":false},{"id":633081,"name":"James K. Collins","orcid":"0000-0001-7633-7804","position":7,"is_corresponding":false},{"id":1309014,"name":"Serena Santoni","orcid":"0000-0002-4964-3774","position":8,"is_corresponding":false},{"id":105379,"name":"Magdalena E. Sobieszczyk","orcid":"0000-0002-7112-3118","position":9,"is_corresponding":false},{"id":30696,"name":"Holly Janes","orcid":"0000-0002-3237-984X","position":10,"is_corresponding":false},{"id":425962,"name":"Mia Moore","orcid":"0000-0001-5055-7075","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:01.000126Z","pmid":"38643547","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}