Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study

C Willame; C Dodd; C E Durán; Rjhj Elbers; R Gini; C Bartolini; O Paoletti; L Wang; V Ehrenstein; J Kahlert; U Haug; T Schink; J Diez-Domingo; A Mira-Iglesias; J J Carreras; C Vergara-Hernández; C Giaquinto; E Barbieri; L Stona; C Huerta; M Martín-Pérez; P García-Poza; A de Burgos; M Martínez-González; V Bryant; F Villalobos; M Pallejà-Millán; M Aragón; J J Carreras; P Souverein; N H Thurin; D Weibel; O H Klungel; McJm Sturkenboom

doi:10.1016/j.vaccine.2022.11.031

Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study

C Willame, C Dodd, C E Durán, Rjhj Elbers, R Gini, C Bartolini, O Paoletti, L Wang, V Ehrenstein, J Kahlert, U Haug, T Schink, J Diez-Domingo, A Mira-Iglesias, J J Carreras, C Vergara-Hernández, C Giaquinto, E Barbieri, L Stona, C HuertaM Martín-Pérez, P García-Poza, A de Burgos, M Martínez-González, V Bryant, F Villalobos, M Pallejà-Millán, M Aragón, J J Carreras, P Souverein, N H Thurin, D Weibel, O H Klungel, McJm Sturkenboom

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	251-262
Number of pages	12
Journal	Vaccine
Volume	41
Issue number	1
Early online date	22 Nov 2022
DOIs	https://doi.org/10.1016/j.vaccine.2022.11.031
Publication status	Published - 4 Jan 2023

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

Funding

The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharma-covigilance) Research Network which is a public academic partnership coordinated by the Utrecht University, The Netherlands. EU PE&PV collaborated with the Vaccine Monitoring Collaboration for Europe (VAC4EU) association The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE. The content of this paper expresses the opinion of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the Euro-pean Medicines Agency or one of its committees or working parties.

Funders	Funder number
EU PE&PV
VAC4EU
European Medicines Agency	EMA/2018/28/PE

Keywords

Adverse events of special interest
Background rates
COVID-19
Vaccine safety

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2022.11.031Licence: CC BY

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Cite this

Willame, C., Dodd, C., Durán, C. E., Elbers, R., Gini, R., Bartolini, C., Paoletti, O., Wang, L., Ehrenstein, V., Kahlert, J., Haug, U., Schink, T., Diez-Domingo, J., Mira-Iglesias, A., Carreras, J. J., Vergara-Hernández, C., Giaquinto, C., Barbieri, E., Stona, L., ... Sturkenboom, M. (2023). Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study. Vaccine, 41(1), 251-262. https://doi.org/10.1016/j.vaccine.2022.11.031

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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.",

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Willame, C, Dodd, C, Durán, CE, Elbers, R, Gini, R, Bartolini, C, Paoletti, O, Wang, L, Ehrenstein, V, Kahlert, J, Haug, U, Schink, T, Diez-Domingo, J, Mira-Iglesias, A, Carreras, JJ, Vergara-Hernández, C, Giaquinto, C, Barbieri, E, Stona, L, Huerta, C, Martín-Pérez, M, García-Poza, P, de Burgos, A, Martínez-González, M, Bryant, V, Villalobos, F, Pallejà-Millán, M, Aragón, M, Carreras, JJ, Souverein, P, Thurin, NH, Weibel, D, Klungel, OH & Sturkenboom, M 2023, 'Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study', Vaccine, vol. 41, no. 1, pp. 251-262. https://doi.org/10.1016/j.vaccine.2022.11.031

TY - JOUR

T1 - Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study

AU - Willame, C

AU - Dodd, C

AU - Durán, C E

AU - Elbers, Rjhj

AU - Gini, R

AU - Bartolini, C

AU - Paoletti, O

AU - Wang, L

AU - Ehrenstein, V

AU - Kahlert, J

AU - Haug, U

AU - Schink, T

AU - Diez-Domingo, J

AU - Mira-Iglesias, A

AU - Carreras, J J

AU - Vergara-Hernández, C

AU - Giaquinto, C

AU - Barbieri, E

AU - Stona, L

AU - Huerta, C

AU - Martín-Pérez, M

AU - García-Poza, P

AU - de Burgos, A

AU - Martínez-González, M

AU - Bryant, V

AU - Villalobos, F

AU - Pallejà-Millán, M

AU - Aragón, M

AU - Carreras, J J

AU - Souverein, P

AU - Thurin, N H

AU - Weibel, D

AU - Klungel, O H

AU - Sturkenboom, McJm

PY - 2023/1/4

Y1 - 2023/1/4

N2 - 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.

AB - 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.

KW - Adverse events of special interest

KW - Background rates

KW - COVID-19

KW - Vaccine safety

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DO - 10.1016/j.vaccine.2022.11.031

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Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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