GCoVS was established to examine potential associations between COVID‑19 vaccines and specific adverse events of special interest, including rare neurological outcomes such as GBS. GBS is an acute autoimmune neuropathy characterised by progressive weakness, often requiring hospitalisation, and is therefore typically diagnosed in secondary or tertiary care. Because clinical presentation and diagnostic pathways vary across healthcare settings, harmonised case definitions are essential for ensuring that GBS cases can be compared reliably across countries. For this reason, the study applied the Brighton Collaboration case definitions, which classify cases according to levels of diagnostic certainty based on available clinical, electrophysiological, and cerebrospinal fluid information. The authors also estimated the PPV, which reflects the proportion of cases identified by diagnostic codes that are confirmed through clinical validation. The objective of this sub‑study was to assess how accurately GBS cases can be identified in three European real‑world data sources and to understand how differences in data availability influence classification.
The study validated 180 GBS cases across participating sites and found substantial variation in levels of diagnostic certainty, reflecting differences in underlying data completeness. Most cases were classified as Level of Certainty 4, particularly in settings with more limited access to in‑hospital clinical information, while higher-certainty cases (Levels 1 and 2) were concentrated in sites with comprehensive hospital records. These differences were mirrored in PPV estimates, which ranged widely from low values in primary-care–dominated systems to values of around 90% in hospital-based settings. The findings underscore that access to hospital data, especially neurophysiology and cerebrospinal fluid results, is essential for achieving high levels of certainty in GBS case validation and for reducing the likelihood of misclassification.
The publication represents the outcome of a major collaborative effort within the GCoVS consortium. GCoVS is coordinated globally by GVDN, an international partnership of research institutions committed to improving global vaccine safety monitoring through harmonised methods. VAC4EU participated as the European coordinator, enabling several DEAPs from within our network to contribute data according to shared protocols and quality standards. Vall d’Hebron University Hospital, Fisabio, Drug Safety Research Unit and IDIAP JGol participated in this study. The work benefitted greatly from the extensive expertise available within these DEAPs, who carried out the clinical validation work and ensured consistent application of the Brighton criteria across heterogeneous data sources. We extend our sincere thanks to all contributing teams and partners for their commitment and collaboration: Mònica Sabaté, Judit Riera-Arnau, Elena Ballarín, Oleguer Parés-Badell, Xavier Martínez, Juan José Carreras, Felipe Villalobos, Alison Yeomans, Kathryn Morton, Arantxa Urchueguía Fornes, Martín Solórzano, Debabrata Roy, Elisa Correcher-Martinez, Carlo Alberto Bissacco, Taylor Aurelius, Gianmarco Di Mauro, Hazel Clothier, Jennifer Griffin, Yannan Jiang, Jeffrey C Kwong, Miriam Sturkenboom.
The findings illustrate the importance of incorporating diverse data sources into international vaccine safety studies. Because GBS is almost exclusively diagnosed in hospital settings, the inclusion of in‑hospital medical records was critical for accurate validation. This work highlights the strengths and limitations of different European routine data systems and demonstrates the value of using harmonised validation frameworks when conducting large-scale, comparative real‑world evidence research. As part of the broader GCoVS programme, this study contributes to improving the reliability of multinational safety assessments and supports the development of stronger methodological standards for future research relying on real‑world data.