Lanièce Delaunay, CharlotteNunes, BaltazarMonge, Susanade Lange, MaritTúri, GergőMachado, AusendaLatorre-Margalef, NeusMlinarić, IvanLazar, MihaelaBotella Rocamora, PalomaErdwiens, AnnikaSève, NoémieDomegan, LisaMartínez-Baz, IvánHooiveld, MariëtteOroszi, BeatrixGuiomar, RaquelSperk, MaikeKurečić Filipović, SanjaPascu, CatalinaLinares Dopido, Juan AntonioDürrwald, RalfRameix-Welti, Marie-AnneMcKenna, AdeleCastilla, Jesúsvan Hagen, CheyenneKnol, MirjamBacci, SabrinaKaczmarek, MarlenaKissling, EstherVEBIS Primary Care Vaccine Effectiveness Group2026-02-192026-02-192025-06-11Int J Epidemiol. 2025 Jun 11;54(4):dyaf086. doi: 10.1093/ije/dyaf0860300-5771http://hdl.handle.net/10400.18/10955Background: With SARS-CoV-2 self-tests, persons with acute respiratory infections (ARI) can know their COVID-19 status. This may alter their decision to consult a general practitioner (GP), potentially biasing COVID-19 vaccine effectiveness (VE) studies. We explore bias mechanisms, simulate magnitude, and verify control methods. Methods: We used directed acyclic graphs (DAGs) to illustrate the bias mechanisms. Based on the European primary care VEBIS multicentre test-negative design (TND) study, we simulated populations with varying true VE (20%-60%), proportions of persons with ARI self-testing (10%-30%), effect of COVID-19 vaccination on self-testing (1.5-2.5), and effect of self-test result on GP consultation (0.5-2). We performed 5000 runs per scenario, estimating VE among those consulting a GP. We calculated bias as true VE minus mean simulated VE, unadjusted and adjusted for self-testing, using logistic regression. Results: DAGs suggested collider stratification bias if vaccination had an effect on self-testing and if self-test results affected GP consultation. Bias was -12% to 18% at 20% true VE, with the most extreme associations and 30% self-testing. With 60% true VE and 10%-20% self-testing, bias was lower. Bias was higher (-18% to 45%) if both positive and negative self-test results affected GP consultation. Adjusting for self-testing removed the bias. Conclusions: Self-testing may bias COVID-19 VE TND studies in primary care if self-testing is high, particularly with low VE. We recommend primary care TND VE studies collect self-testing information to eliminate potential bias. Observational studies are needed to understand the relationship between vaccination, self-testing, and GP consultation, in these studies' source population.Key Messages: - We investigated how the use of SARS-CoV-2 tests in the general population could bias COVID-19 vaccine effectiveness studies at the primary care level, and how to mitigate this bias. - Using directed acyclic graphs and data simulations, we showed that COVID-19 vaccine effectiveness could be biased due to self-test use, and that adjusting for self-testing removed this bias.- Our findings have major implications for the validity of test-negative, case–control vaccine effectiveness studies and suggest that straightforward analytical techniques can be used to correct for bias of a potentially large magnitude.enCOVID-19SARS-CoV-2BiasPrimary Health CareSelf-testingVaccine EffectivenessInfecções RespiratóriasEstados de Saúde e de Doençajournal article10.1093/ije/dyaf08640534212