Over- and under-estimation of vaccine effectiveness

Abstract Background The effectiveness of SARS-CoV-2 vaccines against infection has been a subject of debate, with varying results reported in different studies, ranging from 60–95% vaccine effectiveness (VE). This range is striking when comparing two studies conducted in Israel at the same time, as...

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Main Authors: Hilla De-Leon, Dvir Aran
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Medical Research Methodology
Subjects:
Online Access:https://doi.org/10.1186/s12874-025-02611-4
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author Hilla De-Leon
Dvir Aran
author_facet Hilla De-Leon
Dvir Aran
author_sort Hilla De-Leon
collection DOAJ
description Abstract Background The effectiveness of SARS-CoV-2 vaccines against infection has been a subject of debate, with varying results reported in different studies, ranging from 60–95% vaccine effectiveness (VE). This range is striking when comparing two studies conducted in Israel at the same time, as one study reported VE of 90–95%, while the other study reported only ~ 80%. We argue that this variability is due to inadequate accounting for indirect protection provided by vaccines, which can block further transmission of the virus. Materials and methods We developed a novel analytic heterogenous infection model and extended our agent-based model of disease spread to allow for heterogenous interactions between vaccinated and unvaccinated across close-contacts and regions. We applied these models on real-world regional data from Israel from early 2021 to estimate VE using two common study designs: population-based and secondary infections. Results Our results show that the estimated VE of a vaccine with efficacy of 85% can range from 70–95% depending on the interactions between vaccinated and unvaccinated individuals. Since different study designs capture different levels of interactions, we suggest that this interference explains the variability across studies. Finally, we propose a methodology for more accurate estimation without knowledge of interactions. Discussions and conclusions Our study highlights the importance of considering indirect protection when estimating vaccine effectiveness, explains how different study designs may report biased estimations, and propose a method to overcome this bias. We hope that our models will lead to more accurate understanding of the impact of vaccinations and inform public health policy. Clinical trial number Not applicable.
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spelling doaj-art-61690e7b9d3e4b64848e7f91f5ba3a792025-08-20T04:01:35ZengBMCBMC Medical Research Methodology1471-22882025-07-0125111010.1186/s12874-025-02611-4Over- and under-estimation of vaccine effectivenessHilla De-Leon0Dvir Aran1Faculty of Biology, Technion-Israel Institute of Technology, Technion-Israel Institute of TechnologyFaculty of Biology, Technion-Israel Institute of Technology, Technion-Israel Institute of TechnologyAbstract Background The effectiveness of SARS-CoV-2 vaccines against infection has been a subject of debate, with varying results reported in different studies, ranging from 60–95% vaccine effectiveness (VE). This range is striking when comparing two studies conducted in Israel at the same time, as one study reported VE of 90–95%, while the other study reported only ~ 80%. We argue that this variability is due to inadequate accounting for indirect protection provided by vaccines, which can block further transmission of the virus. Materials and methods We developed a novel analytic heterogenous infection model and extended our agent-based model of disease spread to allow for heterogenous interactions between vaccinated and unvaccinated across close-contacts and regions. We applied these models on real-world regional data from Israel from early 2021 to estimate VE using two common study designs: population-based and secondary infections. Results Our results show that the estimated VE of a vaccine with efficacy of 85% can range from 70–95% depending on the interactions between vaccinated and unvaccinated individuals. Since different study designs capture different levels of interactions, we suggest that this interference explains the variability across studies. Finally, we propose a methodology for more accurate estimation without knowledge of interactions. Discussions and conclusions Our study highlights the importance of considering indirect protection when estimating vaccine effectiveness, explains how different study designs may report biased estimations, and propose a method to overcome this bias. We hope that our models will lead to more accurate understanding of the impact of vaccinations and inform public health policy. Clinical trial number Not applicable.https://doi.org/10.1186/s12874-025-02611-4Vaccine effectivenessCOVID-19InterferencePopulation-based studiesAgent-based modelingIndirect protection
spellingShingle Hilla De-Leon
Dvir Aran
Over- and under-estimation of vaccine effectiveness
BMC Medical Research Methodology
Vaccine effectiveness
COVID-19
Interference
Population-based studies
Agent-based modeling
Indirect protection
title Over- and under-estimation of vaccine effectiveness
title_full Over- and under-estimation of vaccine effectiveness
title_fullStr Over- and under-estimation of vaccine effectiveness
title_full_unstemmed Over- and under-estimation of vaccine effectiveness
title_short Over- and under-estimation of vaccine effectiveness
title_sort over and under estimation of vaccine effectiveness
topic Vaccine effectiveness
COVID-19
Interference
Population-based studies
Agent-based modeling
Indirect protection
url https://doi.org/10.1186/s12874-025-02611-4
work_keys_str_mv AT hilladeleon overandunderestimationofvaccineeffectiveness
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