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Evaluation

Oral Presentation

Session: CV Risk Post-Vaccine Exposure

A comparison of self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases

Monday, August 26, 2024
5:15 PM – 5:30 PM CEST
Location: Conv Hall I C

    Presenting Author(s)

  • Anna Schultze, PhD, MSc

    Assistant Professor
    London School of Hygiene and Tropical Medicine
    London, United Kingdom

    • Co-Author(s)

  • IM

    Ivonne Martin

    2. Department Data Science & Biostatistics, University Medical Centre Utrecht, the Netherlands, Netherlands

  • DM

    Davide Messina

    Programmer
    ARS Toscana, Florence, Italy, Italy

  • Sophie H. Bots, PhD (she/her/hers)

    Assistant Professor
    Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University
    Utrecht University
    Utrecht, Netherlands

  • SB

    Svetlana V. Belitser

    4. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands, Netherlands

  • JC

    Juan José Carreras, PhD, PharmD

    Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO - Public Health), Avenida Cataluña, 21, 46020 Valencia, Spain.
    Valencia, Spain

  • EC

    Elisa Correcher-Martinez

    5. Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO - Public Health), Spain

  • AU

    Arantxa Urchueguía-Fornes, PhD

    Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO - Public Health)
    Valencia, Spain

  • MM

    Mar Martín-Pérez, PharmD, PhD

    Pharmacoepidemiologist
    Spanish Agency of Medicines and Medical Devices (AEMPS)
    Madrid, Spain

  • PG

    Patricia Garcia

    Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency of Medicines and Medical Devices (AEMPS), Madrid, Spain, Spain

  • Felipe Villalobos, MD, PhD

    Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)
    Barcelona, Spain

  • MP

    Meritxell Pallejà-Millán

    8. Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Spain

  • Carlo Alberto Bissacco

    Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Spain

  • ES

    Elena Segundo, n/a

    Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Spain

  • Patrick C. Souverein, PhD (he/him/his)

    Assistent professor
    Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University
    Utrecht, Netherlands

  • FR

    Fabio Riefolo, PhD

    Medical Writer
    Teamit Institute, Partnership, Barcelona Health Hub, Barcelona, Spain.
    Barcelona, Spain

  • CD

    Carlos E. Durán, MD, PhD

    Assistant Professor
    Department of Data Science and Biostatistics, University Medical Center Utrecht
    Utrecht, Netherlands

  • Rosa Gini, PhD (she/her/hers)

    Head of Unit at ARS Toscana, Florence, Italy
    ARS Toscana, Florence, Italy
    Florence, Italy

  • Miriam C.J.M. Sturkenboom, PhD

    Professor
    Department of Data Science & Biostatistics, Julius Global Health, University Medical Center Utrecht (UMCU), Utrecht, the Netherlands
    Utrecht, Netherlands

  • Olaf H. Klungel, PharmD, PhD

    Head of Division
    Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University
    Utrecht, Netherlands

  • ID

    Ian Douglas, PhD, MSc, BSc

    Professor
    London School of Hygiene & Tropical Medicine, United Kingdom

Background: Self-controlled case series (SCCS) and self-controlled risk interval (SCRI) designs are often used to evaluate vaccine safety signals, as there is no need to identify an unvaccinated control group, and unmeasured time stable confounding is automatically controlled for. Although they typically lead to comparable findings, their sensitivity to bias when the assumption of event-dependent exposures is violated might differ.

Objectives: The aim of this study was to compare SCCS and SCRI designs in an analysis of the association between COVID-19 vaccines and myocarditis.

Methods: We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared an SCRI using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. We fit conditional Poisson regression models to calculate incidence rate ratios for the association between the first and second vaccine dose and myocarditis, stratified by DAP and vaccine brand. Finally, we added a random-effect meta-analysis across the data sources.

Results: We included 1,757 cases of myocarditis across all five databases. Agreement between study designs varied by vaccine brand. In analysis of the first dose, there was good agreement between all designs AstraZeneca and Pfizer vaccines, but for Moderna vaccine we found harmful incidence rate ratios (IRR) using the standard and extended SCCS (standard SCCS: IRR = 3.12, 95%CI = 1.53 – 6.40; extended SCCS: IRR = 2.43, 95%CI = 1.11 – 5.33) compared with no association with the SCRIs (SCRI-pre: IRR = 0.60, 95%CI = 0.27 – 1.33; SCRI-post: IRR = 0.86, 95%CI = 0.34 – 2.19), although confidence intervals were wide. There was very good agreement between all designs for the second dose, confirming the known harmful association between the second dose of Moderna and Pfizer vaccines and myocarditis.

Conclusions: In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.