학술논문
A comparison of four self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases.
Document Type
Academic Journal
Author
Schultze A; Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address: anna.schultze@lshtm.ac.uk.; Martin I; Department of Data Science and Biostatistics, University Medical Centre Utrecht, Utrecht, The Netherlands.; Messina D; Agenzia Regionale di Sanità (ARS), Florence, Toscana, Italy.; Bots S; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Belitser S; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; José Carreras-Martínez J; Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO - Public Health), Valencia, Spain; CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain.; Correcher-Martinez E; Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO - Public Health), Valencia, Spain; CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain.; Urchueguía-Fornes A; Vaccine Research Department, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO - Public Health), Valencia, Spain; CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid, Spain.; Martín-Pérez M; Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.; García-Poza P; Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.; Villalobos F; Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.; Pallejà-Millán M; Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.; Alberto Bissacco C; Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.; Segundo E; Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.; Souverein P; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Riefolo F; Teamit Institute, Partnerships, Barcelona Health Hub, Barcelona, Spain.; Durán CE; Department of Data Science and Biostatistics, University Medical Centre Utrecht, Utrecht, The Netherlands.; Gini R; Agenzia Regionale di Sanità (ARS), Florence, Toscana, Italy.; Sturkenboom M; Department of Data Science and Biostatistics, University Medical Centre Utrecht, Utrecht, The Netherlands.; Klungel O; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Douglas I; Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Source
Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 8406899 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2518 (Electronic) Linking ISSN: 0264410X NLM ISO Abbreviation: Vaccine Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse 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 a self-controlled risk interval study (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.
Results: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine.
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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: University Medical Center Utrecht in collaboration with the Vaccine Monitoring Collaboration for Europe network (VAC4EU). reports financial support was provided by European Medicines Agency. Anna Schultze reports a relationship with GSK that includes: funding grants. Ian Douglas reports a relationship with GSK that includes: equity or stocks and funding grants. Fabio Riefolo reports a relationship with TEAMIT Institute, a research management organisation that participates in financially supported studies for the European Medicines Agency and related healthcare authorities, pharmaceutical companies, and the European Union that includes: employment. Felipe Villalobos, Meritxell Palleja-Millan, Carlo Alberto Bissacco and Elena Segundo reports a relationship with IDIAPJGol, which receives institutional research funding from public and private partners, pharmaceutical companies and regulatory agencies that includes: employment. Miriam Sturkenboom reports a relationship with University Medical Center Utrecht, which conducts studies for the European Medicines Agency, the European Commission and medicine manufacturers, all according to the ENCePP code of conduct that includes: employment. Carlos E. Duran reports a relationship with University Medical Center Utrecht, which receives institutional research funding from pharmaceutical companies and regulatory agencies that includes: employment. Rosa Gini and Davide Messina reports a relationship with ARS Tuscany, which reports funding from the Innovative Medicines Initiative, RTI, PHARMO, University of Southern Denmark, University of Utrecht, Eli Lilly, Pfizer, Novartis, AstraZeneca, Galapagos, and LeoPharma that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)
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 a self-controlled risk interval study (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.
Results: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine.
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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: University Medical Center Utrecht in collaboration with the Vaccine Monitoring Collaboration for Europe network (VAC4EU). reports financial support was provided by European Medicines Agency. Anna Schultze reports a relationship with GSK that includes: funding grants. Ian Douglas reports a relationship with GSK that includes: equity or stocks and funding grants. Fabio Riefolo reports a relationship with TEAMIT Institute, a research management organisation that participates in financially supported studies for the European Medicines Agency and related healthcare authorities, pharmaceutical companies, and the European Union that includes: employment. Felipe Villalobos, Meritxell Palleja-Millan, Carlo Alberto Bissacco and Elena Segundo reports a relationship with IDIAPJGol, which receives institutional research funding from public and private partners, pharmaceutical companies and regulatory agencies that includes: employment. Miriam Sturkenboom reports a relationship with University Medical Center Utrecht, which conducts studies for the European Medicines Agency, the European Commission and medicine manufacturers, all according to the ENCePP code of conduct that includes: employment. Carlos E. Duran reports a relationship with University Medical Center Utrecht, which receives institutional research funding from pharmaceutical companies and regulatory agencies that includes: employment. Rosa Gini and Davide Messina reports a relationship with ARS Tuscany, which reports funding from the Innovative Medicines Initiative, RTI, PHARMO, University of Southern Denmark, University of Utrecht, Eli Lilly, Pfizer, Novartis, AstraZeneca, Galapagos, and LeoPharma that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier India Pvt Ltd. All rights reserved.)