| Title: |
Applying two approaches to detect unmeasured confounding due to time-varying variables in a self-controlled risk interval design evaluating COVID-19 vaccine safety signals, using myocarditis as a case example |
| Authors: |
Bots,Sophie H; Belitser,Svetlana; Groenwold,Rolf H H; Durán, Carlos E; Riera-Arnau, Judit; Schultze,Anna; Messina,Davide; Segundo,Elena; Douglas,Ian; Carreras,Juan José; Garcia-Poza,Patricia; Gini,Rosa; Huerta,Consuelo; Martín-Pérez,Mar; Martin, Ivonne; Paoletti,Olga; Bissacco,Carlo Alberto; Correcher-Martínez,Elisa; Souverein,Patrick; Urchuequía,Arantxa; Villalobos,Felipe; Sturkenboom, Miriam C J M; Klungel, Olaf H; RWE/Causal inference; Datascience; Data Science & Biostatistiek; Child Health; Infection & Immunity |
| Publication Year: |
2025 |
| Subject Terms: |
COVID-19 vaccine safety; negative controls; pharmacoepidemiology; quantitative bias analysis; self-controlled risk interval design; General Medicine |
| Description: |
We test the robustness of the self-controlled risk interval (SCRI) design in a setting where time between doses may introduce time-varying confounding, using both negative control outcomes (NCOs) and quantitative bias analysis (QBA). All vaccinated cases identified from 5 European databases between September 1, 2020, and end of data availability were included. Exposures were doses 1-3 of the Pfizer, Moderna, AstraZeneca, and Janssen COVID-19 vaccines; outcomes were myocarditis and, as the NCO, otitis externa. The SCRI used a 60-day control window and dose-specific 28-day risk windows, stratified by vaccine brand and adjusted for calendar time. The QBA included two scenarios: (1) baseline probability of the confounder was higher in the control window and (2) vice versa. The NCO was not associated with any of the COVID-19 vaccine types or doses except Moderna dose 1 (IRR = 1.09; 95% CI 1.01-1.09). The QBA suggested that even the strongest literature-reported confounder (COVID-19; RR for myocarditis = 18.3) could only explain away part of the observed effect, from IRR = 3 to IRR = 1.40. The SCRI seems robust to unmeasured confounding in the COVID-19 setting, although a strong unmeasured confounder could bias the observed effect upward. Replication of our findings for other safety signals would strengthen this conclusion. This article is part of a Special Collection on Pharmacoepidemiology. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/plain |
| Language: |
English |
| ISSN: |
0002-9262 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/458261 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/458261 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.16C48883 |
| Database: |
BASE |