Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience

Purpose: Applying standardized Brighton Collaboration (BC) case definitions retrospectively to heterogeneous real-world data (RWD) is challenging due to inconsistent clinical detail and data structures across settings. To address this, the Vaccine Monitoring Collaboration for Europe (VAC4EU) develop...

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Authors: Tarazjani, AD, Weibel, D, Aurelius, T, Zwiers, LC, Van den Berg, JM, Pérez-Breva, L, Gimeno-Miguel, A, Stona, L, Solórzano, M, Desalegn, AA, Poblador-Plou, B, Lysen, TS, Wheler, J, Zidan, M, Carreras, JJ, Villalobos, F, Ehrenstein, V, Morton, K, Rebordosa, C, Ahmadizar, F, Fortuny, J, Arana, A, Sturkenboom, M
Format: article
Status:Published version
Publication Date:2026
Country:España
Institution:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repository:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:dnet:r-fisabio___::619a8ae8995dff60fae0eb9934bb0827
Online Access:https://fisabio.portalinvestigacion.com/publicaciones/20390
Access Level:Open access
Keyword:validation
vaccine safety
real-world data
Brighton collaboration
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spelling Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU ExperienceTarazjani, ADWeibel, DAurelius, TZwiers, LCVan den Berg, JMPérez-Breva, LGimeno-Miguel, AStona, LSolórzano, MDesalegn, AAPoblador-Plou, BLysen, TSWheler, JZidan, MCarreras, JJVillalobos, FEhrenstein, VMorton, KRebordosa, CAhmadizar, FFortuny, JArana, ASturkenboom, Mvalidationvaccine safetyreal-world dataBrighton collaborationPurpose: Applying standardized Brighton Collaboration (BC) case definitions retrospectively to heterogeneous real-world data (RWD) is challenging due to inconsistent clinical detail and data structures across settings. To address this, the Vaccine Monitoring Collaboration for Europe (VAC4EU) developed a structured validation pipeline that operationalizes BC case definitions for vaccine safety outcomes in RWD in a harmonized, scalable, and reusable manner. Methods: VAC4EU developed a systematic, stepwise approach to validate vaccine safety outcomes. BC case definitions were utilized when available, adapted for RWD as needed, and newly developed for outcomes without an existing BC definition. The approach involves: 1) Critical review and adaptation of BC definition by clinical and RWD experts; 2) Creation of dummy cases based on published reports; 3) Creation of REDCap electronic data collection forms (eDCF) incorporating decision logic to assigned levels of certainty (LOC); 4) Iterative testing of decision logic; and 5) comprehensive training of abstractors with real-time feedback. A dedicated task force assigned reference LOCs for dummy cases. Inter-rater reliability was measured using Fleiss' kappa (kappa) by comparing abstractor LOCs to the reference standard. Results: The pipeline was applied to 16 COVID-19 vaccine safety outcomes, of which 13 had existing BC definition. In total, 78 dummy case descriptions were developed across the outcomes for training of abstractors, and 15 REDCap eDCFs were created. Myocarditis and pericarditis shared an eDCF. Across 33 abstractors, 747 dummy case abstractions were completed. Agreement analysis showed 93 discrepancies (12.4%) and moderate overall concordance (kappa = 0.55, across all outcomes), with the lowest for thrombosis with thrombocytopenia syndrome (kappa = -0.05). Conclusion: The VAC4EU validation pipeline provides a standardized framework for training and validating vaccine safety outcome in RWD. By adapting BC case definitions and dedicated training of abstractors, we will reduce variability in outcome validation in post-authorization safety studies.DOVE MEDICAL PRESS LTD2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/20390Clinical EpidemiologyISSN: 11791349reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:dnet:r-fisabio___::619a8ae8995dff60fae0eb9934bb08272026-06-11T12:45:17Z
dc.title.none.fl_str_mv Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
title Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
spellingShingle Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
Tarazjani, AD
validation
vaccine safety
real-world data
Brighton collaboration
title_short Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
title_full Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
title_fullStr Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
title_full_unstemmed Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
title_sort Harmonizing Case Validation for Vaccine Safety in Real-World Data: The VAC4EU Experience
dc.creator.none.fl_str_mv Tarazjani, AD
Weibel, D
Aurelius, T
Zwiers, LC
Van den Berg, JM
Pérez-Breva, L
Gimeno-Miguel, A
Stona, L
Solórzano, M
Desalegn, AA
Poblador-Plou, B
Lysen, TS
Wheler, J
Zidan, M
Carreras, JJ
Villalobos, F
Ehrenstein, V
Morton, K
Rebordosa, C
Ahmadizar, F
Fortuny, J
Arana, A
Sturkenboom, M
author Tarazjani, AD
author_facet Tarazjani, AD
Weibel, D
Aurelius, T
Zwiers, LC
Van den Berg, JM
Pérez-Breva, L
Gimeno-Miguel, A
Stona, L
Solórzano, M
Desalegn, AA
Poblador-Plou, B
Lysen, TS
Wheler, J
Zidan, M
Carreras, JJ
Villalobos, F
Ehrenstein, V
Morton, K
Rebordosa, C
Ahmadizar, F
Fortuny, J
Arana, A
Sturkenboom, M
author_role author
author2 Weibel, D
Aurelius, T
Zwiers, LC
Van den Berg, JM
Pérez-Breva, L
Gimeno-Miguel, A
Stona, L
Solórzano, M
Desalegn, AA
Poblador-Plou, B
Lysen, TS
Wheler, J
Zidan, M
Carreras, JJ
Villalobos, F
Ehrenstein, V
Morton, K
Rebordosa, C
Ahmadizar, F
Fortuny, J
Arana, A
Sturkenboom, M
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv validation
vaccine safety
real-world data
Brighton collaboration
topic validation
vaccine safety
real-world data
Brighton collaboration
description Purpose: Applying standardized Brighton Collaboration (BC) case definitions retrospectively to heterogeneous real-world data (RWD) is challenging due to inconsistent clinical detail and data structures across settings. To address this, the Vaccine Monitoring Collaboration for Europe (VAC4EU) developed a structured validation pipeline that operationalizes BC case definitions for vaccine safety outcomes in RWD in a harmonized, scalable, and reusable manner. Methods: VAC4EU developed a systematic, stepwise approach to validate vaccine safety outcomes. BC case definitions were utilized when available, adapted for RWD as needed, and newly developed for outcomes without an existing BC definition. The approach involves: 1) Critical review and adaptation of BC definition by clinical and RWD experts; 2) Creation of dummy cases based on published reports; 3) Creation of REDCap electronic data collection forms (eDCF) incorporating decision logic to assigned levels of certainty (LOC); 4) Iterative testing of decision logic; and 5) comprehensive training of abstractors with real-time feedback. A dedicated task force assigned reference LOCs for dummy cases. Inter-rater reliability was measured using Fleiss' kappa (kappa) by comparing abstractor LOCs to the reference standard. Results: The pipeline was applied to 16 COVID-19 vaccine safety outcomes, of which 13 had existing BC definition. In total, 78 dummy case descriptions were developed across the outcomes for training of abstractors, and 15 REDCap eDCFs were created. Myocarditis and pericarditis shared an eDCF. Across 33 abstractors, 747 dummy case abstractions were completed. Agreement analysis showed 93 discrepancies (12.4%) and moderate overall concordance (kappa = 0.55, across all outcomes), with the lowest for thrombosis with thrombocytopenia syndrome (kappa = -0.05). Conclusion: The VAC4EU validation pipeline provides a standardized framework for training and validating vaccine safety outcome in RWD. By adapting BC case definitions and dedicated training of abstractors, we will reduce variability in outcome validation in post-authorization safety studies.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/20390
url https://fisabio.portalinvestigacion.com/publicaciones/20390
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv DOVE MEDICAL PRESS LTD
publisher.none.fl_str_mv DOVE MEDICAL PRESS LTD
dc.source.none.fl_str_mv Clinical Epidemiology
ISSN: 11791349
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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