tetano
Editor, Senior Moderator
Int J Epidemiol
. 2025 Jun 11;54(4):dyaf086.
doi: 10.1093/ije/dyaf086. The potential bias introduced into COVID-19 vaccine effectiveness studies at primary care level due to the availability of SARS-CoV-2 tests in the general population
Charlotte Lanièce Delaunay[SUP] 1 [/SUP], Baltazar Nunes[SUP] 1 [/SUP], Susana Monge[SUP] 2 [/SUP], Marit de Lange[SUP] 3 [/SUP], Gergő Túri[SUP] 4 [/SUP], Ausenda Machado[SUP] 5 [/SUP], Neus Latorre-Margalef[SUP] 6 [/SUP], Ivan Mlinarić[SUP] 7 [/SUP], Mihaela Lazar[SUP] 8 [/SUP], Paloma Botella Rocamora[SUP] 9 [/SUP], Annika Erdwiens[SUP] 10 [/SUP], Noémie Sève[SUP] 11 [/SUP], Lisa Domegan[SUP] 12 [/SUP], Iván Martínez-Baz[SUP] 13 14 [/SUP], Mariëtte Hooiveld[SUP] 15 [/SUP], Beatrix Oroszi[SUP] 4 [/SUP], Raquel Guiomar[SUP] 16 [/SUP], Maike Sperk[SUP] 6 [/SUP], Sanja Kurečić Filipović[SUP] 7 [/SUP], Catalina Pascu[SUP] 8 [/SUP], Juan Antonio Linares Dopido[SUP] 17 [/SUP], Ralf Dürrwald[SUP] 18 [/SUP], Marie-Anne Rameix-Welti[SUP] 19 20 21 [/SUP], Adele McKenna[SUP] 12 [/SUP], Jesús Castilla[SUP] 13 14 [/SUP], Cheyenne van Hagen[SUP] 3 [/SUP], Mirjam Knol[SUP] 3 [/SUP], Sabrina Bacci[SUP] 22 [/SUP], Marlena Kaczmarek[SUP] 22 [/SUP], Esther Kissling[SUP] 1 [/SUP]; VEBIS Primary Care Vaccine Effectiveness Group
Affiliations
Background: 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.
Keywords: COVID-19; SARS-CoV-2; bias; primary health care; self-testing; vaccine effectiveness.
. 2025 Jun 11;54(4):dyaf086.
doi: 10.1093/ije/dyaf086. The potential bias introduced into COVID-19 vaccine effectiveness studies at primary care level due to the availability of SARS-CoV-2 tests in the general population
Charlotte Lanièce Delaunay[SUP] 1 [/SUP], Baltazar Nunes[SUP] 1 [/SUP], Susana Monge[SUP] 2 [/SUP], Marit de Lange[SUP] 3 [/SUP], Gergő Túri[SUP] 4 [/SUP], Ausenda Machado[SUP] 5 [/SUP], Neus Latorre-Margalef[SUP] 6 [/SUP], Ivan Mlinarić[SUP] 7 [/SUP], Mihaela Lazar[SUP] 8 [/SUP], Paloma Botella Rocamora[SUP] 9 [/SUP], Annika Erdwiens[SUP] 10 [/SUP], Noémie Sève[SUP] 11 [/SUP], Lisa Domegan[SUP] 12 [/SUP], Iván Martínez-Baz[SUP] 13 14 [/SUP], Mariëtte Hooiveld[SUP] 15 [/SUP], Beatrix Oroszi[SUP] 4 [/SUP], Raquel Guiomar[SUP] 16 [/SUP], Maike Sperk[SUP] 6 [/SUP], Sanja Kurečić Filipović[SUP] 7 [/SUP], Catalina Pascu[SUP] 8 [/SUP], Juan Antonio Linares Dopido[SUP] 17 [/SUP], Ralf Dürrwald[SUP] 18 [/SUP], Marie-Anne Rameix-Welti[SUP] 19 20 21 [/SUP], Adele McKenna[SUP] 12 [/SUP], Jesús Castilla[SUP] 13 14 [/SUP], Cheyenne van Hagen[SUP] 3 [/SUP], Mirjam Knol[SUP] 3 [/SUP], Sabrina Bacci[SUP] 22 [/SUP], Marlena Kaczmarek[SUP] 22 [/SUP], Esther Kissling[SUP] 1 [/SUP]; VEBIS Primary Care Vaccine Effectiveness Group
Affiliations
- PMID: 40534212
- DOI: 10.1093/ije/dyaf086
Background: 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.
Keywords: COVID-19; SARS-CoV-2; bias; primary health care; self-testing; vaccine effectiveness.