Unmeasured confounding and misclassification in studies estimating vaccine effectiveness against hospitalisation and death using electronic health records (EHRs): an evaluation of a multi-country European retrospective cohort study
We observed some evidence of unmeasured confounding when using non-COVID-19 deaths as a negative outcome, though the specificity of our negative control must be considered. This result may suggest overestimation of VE, but also the need for further analysis with more specific negative control outcomes and confounding-adjustment techniques. Addressing such confounding using richer data sources and more refined approaches remains critical to ensure accurate, timely VE estimates based on retrospective cohorts constructed using registry data. Extending the delay between the end of observation and data extraction modestly improves the completeness of exposure and outcome data, with limited effect on pooled VE estimates.
Authors
- James Humphreys
- Toon Braeye (ORCID: https://orcid.org/0000-0002-5637-4613)
- Ida Rask Moustsen‐Helms (ORCID: https://orcid.org/0000-0002-1143-511X)
- Susana Monge (ORCID: https://orcid.org/0000-0003-1412-3012)
- Brechje de Gier (ORCID: https://orcid.org/0000-0002-9067-090X)
- Hinta Meijerink (ORCID: https://orcid.org/0000-0002-5898-2778)
- Carla Nunes (ORCID: https://orcid.org/0000-0003-4562-1057)
- Izaak Van Evercooren
- Alberto Mateo‐Urdiales (ORCID: https://orcid.org/0000-0002-0480-8723)
- Sabrina Bacci (ORCID: https://orcid.org/0000-0002-6575-3439)
- Ausenda Machado (ORCID: https://orcid.org/0000-0002-1849-1499)
- Nathalie Nicolay (ORCID: https://orcid.org/0000-0002-5916-7855)
- Chiara Sacco (ORCID: https://orcid.org/0000-0002-3958-8353)
- Christian Holm Hansen (ORCID: https://orcid.org/0000-0002-5949-0097)
- Patrícia Soares (ORCID: https://orcid.org/0000-0001-5033-9115)
- Iván Martínez‐Baz (ORCID: https://orcid.org/0000-0002-3405-2277)
Institutions
- Statens Serum Institut (DK)
- Norwegian Institute of Public Health (NO)
- Istituto Superiore di Sanità (IT)
- Instituto de Salud Carlos III (ES)
- Instituto de Salud Pública de Navarra (ES)
- National Institute for Public Health and the Environment (NL)
- Centre for Biomedical Network Research on Rare Diseases (ES)
- Instituto Nacional de Saúde (MZ)
- National Institute of Health Dr. Ricardo Jorge (PT)
- Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES)
- Vesticon (United States) (US)
- Institut Scientifique de Santé Publique (BE)
- European Centre for Disease Prevention and Control (SE)
Publication Details
- Journal
- BMC Medical Research Methodology
- Published
- 2025-12-17
- DOI
- https://doi.org/10.1186/s12874-025-02742-8
- Citations
- 2
- Primary Topic
- Advanced Causal Inference Techniques
- Type
- article
- Field-Weighted Citation Impact
- 5.26