Background Rates of 41 Adverse Events of Special Interest for COVID-19 Vaccines in 10 European Healthcare Databases - an ACCESS Cohort Study

25 Pages Posted: 12 Mar 2022

See all articles by Corinne Willame

Corinne Willame

affiliation not provided to SSRN

Durán Carlos

affiliation not provided to SSRN

Carlos Duran

affiliation not provided to SSRN

Elbers Roel

affiliation not provided to SSRN

Rosa Gini

affiliation not provided to SSRN

Claudia Bartolini

ARS Toscana

Olga Paoletti

affiliation not provided to SSRN

Lei Wang

affiliation not provided to SSRN

Vera Ehrenstein

affiliation not provided to SSRN

Johnny Kahlert

affiliation not provided to SSRN

Ulrike Haug

affiliation not provided to SSRN

Tania Schink

affiliation not provided to SSRN

Javier Diez-Domingo

affiliation not provided to SSRN

Ainara Mira-Iglesias

affiliation not provided to SSRN

Carlos Vergara-Hernández

affiliation not provided to SSRN

Carlo Giaquinto

University of Padua - Department of Women’s and Children’s Health

Elisa Barbieri

University of Padua - Division of Paediatric Infectious Diseases

Luca Stona

affiliation not provided to SSRN

Consuelo Huerta

affiliation not provided to SSRN

Patricia García-Poza

affiliation not provided to SSRN

Mar Martín-Pérez

Spanish Agency for Medicines and Medical Devices (AEMPS) - Division of Pharmacoepidemiology and Pharmacovigilance

Airam de Burgos González

affiliation not provided to SSRN

María Martínez-González

affiliation not provided to SSRN

Verónica Bryant

affiliation not provided to SSRN

Felipe Villalobos

affiliation not provided to SSRN

Meritxell Palleja-Millan

affiliation not provided to SSRN

Maria Aragón

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

Carreras Juan Jose

affiliation not provided to SSRN

Patrick Souverein

Utrecht University

Nicolas Thurin

Univ. Bordeaux - Bordeaux PharmacoEpi

Thurin Nicolas

affiliation not provided to SSRN

Klungel Olaf

Utrecht University

Sturkenboom Miriam

University Medical Center Utrecht - Department Datascience & Biostatistics

Multiple version iconThere are 2 versions of this paper

Abstract

Background: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines.

Methods: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events.

Findings: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively.

Interpretation: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates.

Funding: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Funding Information: The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharmacovigilance) Research Network which is a public academic partnership coordinated by the Utrecht University, The Netherlands. The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Conflict of Interests: Corinne Willame is conducting a PhD at the University Medical Center Utrecht, as part of which she coordinated this project from January 2021. She works full time for Janssen Pharmaceutica and allocated working-time to finalize this project, this should be considered an in-kind contribution. Janssen Pharmaceutica was not a member of the consortium or project. Rosa Gini, Claudia Bartolini and Olga Paoletti are employed by ARS Toscana, a public research center that conducts or participates in pharmacoepidemiology studies compliant with the ENCePP Code of Conduct. The budget of ARS is partially sustained by such studies Nicolas Thurin works for Bordeaux PharmacoEpi, an independent research platform of the Bordeaux University and its subsidiary the ADERA SAS, which performs financially supported studies for public and private partners, in line with the ENCePP Code of Conduct. Lei Wang, Vera Ehrenstein and Johnny Kahlert are salaried employees of their organization, which receives institutional research funding from pharmaceutical companies and regulatory agencies, administered by Aarhus University. Miriam Sturkenboom, Daniel Weibel, Carlos E. Durán, Roel Elbers, are salaried employees by University Medical Center Utrecht, which receives institutional research funding from pharmaceutical companies and regulatory agencies, administered by University Medical Center Utrecht. All these studies follow the ENCePP code of conduct. Miriam Sturkenboom is a consultant to the Task Force for Global Health for the Safety Platform for Emergency vACcines (SPEAC) project. Caitlin Dodd currently works for Panalgo. Felipe Villalobos, Meritxell Pallejà-Millán and María Aragón are salaried employees at Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), which receives institutional research funding from public and private partners, pharmaceutical companies and regulatory agencies, administered by IDIAPJGol. Mar Martín-Pérez, Patricia García-Poza, Airam de Burgos, Maria Martínez-González and Verónica Bryant are employees at the Spanish Agency for Medicines and Medical Devices which fully finance the BIFAP database, a non-profit database for performing independent pharmacoepidemiologic research in the public research Spanish setting. Consuelo Huerta was employee at the Spanish Agency for Medicines during the time in which this study was performed. She is currently assistant professor of the Public Health Department of the Faculty of Medicine in the Complutense University of Madrid. Ulrike Haug and Tania Schink are working at an independent, non-profit research institute, the Leibniz Institute for Prevention Research and Epidemiology – BIPS. Unrelated to this study, BIPS occasionally conducts studies financed by the pharmaceutical industry. Almost exclusively, these are post- authorization safety studies (PASS) requested by health authorities. The design and conduct of these studies as well as the interpretation and publication are not influenced by the pharmaceutical industry and performed in line with the ENCePP Code of Conduct. All other authors have no conflict of interest.

Ethical Approval: Access to databases was approved by local scientific and ethics committees. Use of CPRD data in this study was approved by the Independent Scientific Advisory Committee for MHRA database research (protocol 20_000177).

Keywords: Background rates, vaccine safety, Adverse events of special interest, COVID-19

Suggested Citation

Willame, Corinne and Carlos, Durán and Duran, Carlos and Roel, Elbers and Gini, Rosa and Bartolini, Claudia and Paoletti, Olga and Wang, Lei and Ehrenstein, Vera and Kahlert, Johnny and Haug, Ulrike and Schink, Tania and Diez-Domingo, Javier and Mira-Iglesias, Ainara and Vergara-Hernández, Carlos and Giaquinto, Carlo and Barbieri, Elisa and Stona, Luca and Huerta, Consuelo and García-Poza, Patricia and Martín-Pérez, Mar and de Burgos González, Airam and Martínez-González, María and Bryant, Verónica and Villalobos, Felipe and Palleja-Millan, Meritxell and Aragón, Maria and Juan Jose, Carreras and Souverein, Patrick and Thurin, Nicolas and Nicolas, Thurin and Olaf, Klungel and Miriam, Sturkenboom, Background Rates of 41 Adverse Events of Special Interest for COVID-19 Vaccines in 10 European Healthcare Databases - an ACCESS Cohort Study. Available at SSRN: https://ssrn.com/abstract=4055926 or http://dx.doi.org/10.2139/ssrn.4055926

Corinne Willame (Contact Author)

affiliation not provided to SSRN ( email )

No Address Available

Durán Carlos

affiliation not provided to SSRN ( email )

No Address Available

Carlos Duran

affiliation not provided to SSRN ( email )

No Address Available

Elbers Roel

affiliation not provided to SSRN ( email )

No Address Available

Rosa Gini

affiliation not provided to SSRN

Claudia Bartolini

ARS Toscana ( email )

Via pietro dazzi 1
Firenze, Fi 50141
Italy

HOME PAGE: http://https://www.ars.toscana.it/

Olga Paoletti

affiliation not provided to SSRN

Lei Wang

affiliation not provided to SSRN

Vera Ehrenstein

affiliation not provided to SSRN

Johnny Kahlert

affiliation not provided to SSRN

Ulrike Haug

affiliation not provided to SSRN

Tania Schink

affiliation not provided to SSRN

Javier Diez-Domingo

affiliation not provided to SSRN ( email )

No Address Available

Ainara Mira-Iglesias

affiliation not provided to SSRN ( email )

No Address Available

Carlos Vergara-Hernández

affiliation not provided to SSRN

Carlo Giaquinto

University of Padua - Department of Women’s and Children’s Health ( email )

Via Giustiniani
Padova, 3-35128
Italy

Elisa Barbieri

University of Padua - Division of Paediatric Infectious Diseases ( email )

Luca Stona

affiliation not provided to SSRN

Consuelo Huerta

affiliation not provided to SSRN

Patricia García-Poza

affiliation not provided to SSRN

Mar Martín-Pérez

Spanish Agency for Medicines and Medical Devices (AEMPS) - Division of Pharmacoepidemiology and Pharmacovigilance ( email )

Madrid
Spain

Airam De Burgos González

affiliation not provided to SSRN

María Martínez-González

affiliation not provided to SSRN

Verónica Bryant

affiliation not provided to SSRN

Felipe Villalobos

affiliation not provided to SSRN

Meritxell Palleja-Millan

affiliation not provided to SSRN ( email )

No Address Available

Maria Aragón

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

Barcelona
Spain

Carreras Juan Jose

affiliation not provided to SSRN ( email )

No Address Available

Patrick Souverein

Utrecht University ( email )

Nicolas Thurin

Univ. Bordeaux - Bordeaux PharmacoEpi ( email )

Thurin Nicolas

affiliation not provided to SSRN ( email )

No Address Available

Klungel Olaf

Utrecht University ( email )

Sturkenboom Miriam

University Medical Center Utrecht - Department Datascience & Biostatistics ( email )

Netherlands

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