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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

Title: 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
Authors: Lanièce Delaunay, Charlotte; Nunes, Baltazar; Monge, Susana; de Lange, Marit; Túri, Gergő; Machado, Ausenda; Latorre-Margalef, Neus; Mlinarić, Ivan; Lazar, Mihaela; Botella Rocamora, Paloma; Erdwiens, Annika; Sève, Noémie; Domegan, Lisa; Martínez-Baz, Iván; Hooiveld, Mariëtte; Oroszi, Beatrix; Guiomar, Raquel; Sperk, Maike; Kurečić Filipović, Sanja; Pascu, Catalina; Linares Dopido, Juan Antonio; Dürrwald, Ralf; Rameix-Welti, Marie-Anne; Mckenna, Adele; Castilla, Jesús; van Hagen, Cheyenne; Knol, Mirjam; Bacci, Sabrina; Kaczmarek, Marlena; Kissling, Esther
Contributors: EpiConcept Paris; Institute of Health Carlos III; Centre for Infectious Disease Control Netherlands; National Institute for Public Health and the Environment Bilthoven (RIVM); Semmelweis University Budapest; National Institute of Health Doctor Ricardo Jorge (INSA) (INSA); Public Health Agency of Sweden; Croatian Institute of Public Health Zagreb (CIPH); Cantacuzino National Medico-Military Institute for Research Development = Institutul Național de Cercetare Dezvoltare Medico-Militară "Cantacuzino" Bucharest, Romania; General Directorate of Public Health Valencia, Spain; Robert Koch Institute Berlin (RKI); Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Health Service Executive Dublin (HSE); Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA); Universidad Pública de Navarra Espagne = Public University of Navarra (UPNA)-Universidad de Navarra Pamplona (UNAV)-Clínica Universidad de Navarra Pamplona; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health (CIBERESP); Netherlands Institute for Health Services Research Utrecht (NIVEL); Servicio Extremeño de Salud; Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae Paris (CNR - laboratoire coordonnateur); Institut Pasteur Paris (IP)-Université Paris Cité (UPCité); Mécanismes moléculaires de la multiplication des Pneumovirus / Molecular mechanisms of multiplication of Pneumoviruses (M3P); Hôpital Ambroise Paré AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Health Service Executive (HSE); European Centre for Disease Prevention and Control Solna, Sweden (ECDC); Union Européenne = European Union (UE); This study received funding from the European Centre for Disease Prevention and Control (ECDC), through the framework contract Vaccine Effectiveness, Burden and Impact Studies (VEBIS) of COVID-19 and Influenza ECDC/2021/019.; We acknowledge the contribution by the VEBIS Primary Care Vaccine Effectiveness Group: Croatia—Ivana Ferenčak, Bernard Kaić, Maja Ilić, Vesna Višekruna Vučina, Croatian Institute of Public Health, Zagreb; Katica Čusek Adamić, Institute of Public Health, Varaždin County, Varaždin; Mirjana Lana Kosanović Ličina, ‘Dr Andrija Štampar’ Teaching Institute of Public Health, Zagreb; Danijela Lakošeljac, Teaching Institute of Public Health, Primorje-Gorski kotar County, Rijeka; Ivana Mihin Huskić, Teaching Institute of Public Health, Osijek-Baranja County, Osijek; Diana Nonković, Teaching Institute for Public Health, Split-Dalmatia County, Split. France—Thierry Blanchon, Caroline Guerrisi, Titouan Launay, Aubane Renard, Sorbonne Université, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136); Marie Chazelle, Alessandra Falchi, Shirley Masse, Laboratoire de Virologie, Université de Corse-Inserm; Vincent Enouf, Sylvie van der Werf, Centre National de Référence Virus des Infections Respiratoire (CNR VIR), Institut Pasteur. Germany—Luise Goerlitz, Silke Buda, Ute Preuss, Kristin Tolksdorf, Carolin Hackmann, Department for Infectious Disease Epidemiology, Respiratory Infections Unit, Robert Koch Institute; Barbara Biere, Djin-Ye Oh, Janine Reiche, Marianne Wedde, National Reference Centre for Influenza, Robert Koch Institute. Hungary—Judit Krisztina Horváth, Krisztina Mucsányiné Juhász, Katalin Krisztalovics, Csaba Luca, National Laboratory for Health Security, Epidemiology and Surveillance Centre, Semmelweis University, Budapest; Katalin Kristóf, Institute of Laboratory Medicine, Semmelweis University, Budapest. The Hungarian study team works as part of the National Laboratory for Health Security Hungary (RRF-2.3.1-21-2022-00006) supported by the National Research, Development and Innovation Office (NKFIH). Ireland—Joan O’Donnell, HSE Health Protection Surveillance Centre, Dublin; Jeff Connell, National Virus Reference Laboratory, Dublin; Michael Joyce, Olga Levis and the Irish sentinel GP network, Irish College of General Practitioners, Dublin; The Netherlands Lynn Aarts, Mariam Bagheri, Danytza Berry, Sanne Bos, Sharon van den Brink, Dirk Eggink, Rianne van Gageldonk-Lafeber, Gabriel Goderski, Liz Jenniskens, Femke Jongenotter, Adam Meijer, Tara Sprong, Anne Teirlinck, molecular pool technicians, National Institute for Public Health and the Environment (RIVM), Bilthoven; Nivel Primary Care Database—Sentinel Practices team, Ruud van den Broek, Safira Wortel, Ruben van der Burgh, Cathrien Kager, Mayra Klinkhamer, Bart Knottnerus, Marloes Riethof, Nienke Veldhuijzen, participating general practices and their patients, Nivel, Utrecht. Portugal—Vitor Borges, Licínia Gomes, Camila Henriques, Ana Paula Rodrigues, Daniela Dias, Débora Pereira, Pais de Lacerda, Susana Maia Silva, Paula Pinto, Cristina Bárbara, Epidemiology Department, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon. Romania—Maria Elena Mihai, Alina Ivanciuc, Catalina Pascu, Iulia Bistriceanu, Sorin Dinu, Mihaela Oprea, Olivia Timnea, Adrian Jidovu, ‘Cantacuzino’ National Military-Medical Institute for Research and Development, Bucharest; Rodica Popescu, National Institute of Public Health, Bucharest. Spain, national—SiVIRA surveillance and vaccine effectiveness group. Spain, Navarre—Itziar Casado, Aitziber Echeverria, Camino Trobajo-Sanmartín, Manuel García Cenoz, Guillermo Ezpeleta, Instituto de Salud Pública de Navarra—IdiSNA, CIBERESP, Pamplona; Ana Navascués, Miguel Fernández-Huerta, Carmen Ezpeleta, Hospital Universitario de Navarra—IdiSNA, Pamplona. Sweden—Annasara Carnahan (epidemiology team), Emmi Andersson, Eva Hansson-Pihlainen, Elin Arvesen, Nora Nid, Anna-Lena Hansen and Lena Dillner (influenza virus surveillance team) and the NGS platform, Public Health Agency of Sweden, Stockholm, Sweden. All study teams are very grateful to all patients, general practitioners, paediatricians, laboratory teams, and regional epidemiologists who have contributed to the studies. We would like to acknowledge Gilles Desvé for his contribution to and validation of the simulation study methods and programming, and Ruoran Li for her contribution to the development of directed acyclic graphs.; European Project: 26300,ECDC
Source: ISSN: 0300-5771.
Publisher Information: CCSD; Oxford University Press (OUP)
Publication Year: 2025
Subject Terms: primary health care; self-testing; vaccine effectiveness; bias; SARS-CoV-2; COVID-19; [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Description: International audience ; 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.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40534212; info:eu-repo/grantAgreement//26300/EU/European Centre for Disease Prevention and Control/ECDC; PUBMED: 40534212; PUBMEDCENTRAL: PMC12204317
DOI: 10.1093/ije/dyaf086
Availability: https://pasteur.hal.science/pasteur-05489123; https://pasteur.hal.science/pasteur-05489123v1/document; https://pasteur.hal.science/pasteur-05489123v1/file/dyaf086.pdf; https://doi.org/10.1093/ije/dyaf086
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.849FDDC3
Database: BASE