Monitoring of COVID-19 medicines

The European Medicines Agency (EMA) makes use of real-world data to monitor the safety and effectiveness of authorised COVID-19 treatments and vaccines and other medicines used in patients with COVID-19 in the European Union (EU).

EMA published the information on this page for use during the COVID-19 public health emergency. EMA is no longer updating this page.

COVID-19 vaccines: pharmacovigilance plan

The pharmacovigilance plan for COVID-19 vaccines sets out how EMA and the national competent authorities in the EU Member States identify and evaluate any new information that arises promptly, including any safety signals that are relevant for the benefit-risk balance of these vaccines:

Pharmacovigilance plan of the EU Regulatory Network for COVID-19 vaccines

Reference Number: EMA/333964/2020

For more information, see:

• Safety of COVID-19 vaccines
• COVID-19 vaccines: Monitoring vaccine safety and use in real life
• COVID-19 guidance: post-authorisation
• Pharmacovigilance: Overview

Observational research

EMA is taking steps to use real-world data from clinical practice to monitor the safety and effectiveness of COVID-19 treatments and vaccines and other medicines used in patients with COVID-19.

Real-world monitoring complements EMA's regular safety-monitoring activities, including spontaneous reporting of suspected side effects by patients and healthcare professionals.

Information on ongoing COVID-19-related observational studies in the EU is available in the European Union electronic register of post-authorisation studies (EU PAS Register). Users can find these studies by entering 'COVID-19' in the 'Title of Study' search filter.

EMA and the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) are encouraging all researchers to register their pharmacoepidemiological studies related to COVID-19 in the EU PAS Register.

They should also upload and make their study protocols public, with a description of the data collected, and include ‘COVID-19’ in the study title.

EMA has contracted institutions specialising in observational research to conduct several research projects detailed below.

Click on the research areas to read more about each project.

Safety monitoring of COVID-19 vaccines in the EU

Project title	Safety monitoring of COVID-19 vaccines in the EU (Covid-Vaccine-Monitor)
Objectives	Cohort-event monitoring to generate prospective data on the incidence of suspected adverse reactions following vaccination in the general population and in special populations (e.g. pregnant women, immunocompromised) in a large number of EU Member States Readiness and rapid signal assessment of emerging safety concerns in at least 10 electronic healthcare data sources from VAC4EU and the EU Pharmacoepidemiology and Pharmacovigilance (PE & PV) research network at Utrecht University, using common protocols, common data models and distributed analytics. Contributing EU Member States include The Netherlands, Denmark, Norway, Spain, Italy, France and Germany; and in addition, the United Kingdom.
Timelines	Start of project:  April 2021 Start of study: mid-2021 Final study report: April 2023
Contractor	EU PE&PV Research Network, coordinated by Utrecht University: Pharmacoepidemiology and Clinical Pharmacology - Universiteit Utrecht (uu.nl)
Related information	EMA infrastructure for real-world monitoring of COVID-19 treatments and vaccines VAC4EU (collaboration with University of Utrecht to deliver the study) University Medical Center Utrecht: Department of Datascience and Biostatistics: Julius Centre (scientific coordination)

Natural history of coagulopathy and use of anti-thrombotic agents in COVID-19 patients and COVID-19 vaccine recipients

Project title	Natural history of coagulopathy and use of anti-thrombotic agents in COVID-19 patients and people vaccinated against SARS-CoV-2
Objectives	Determine the incidence of arterial and venous thromboembolic events and their consequences among groups of patients diagnosed with COVID-19 infection, and groups of persons vaccinated against SARS-CoV-2 with a first dose and a second dose In these patients, evaluate how arterial and venous thromboembolic events are associated with patient characteristics that promote stasis of circulation, vascular endothelial injury and hypercoagulability, taking into account factors such as treatments
Deliverables	Study protocol
Timelines	Start of project: November 2020 First deliverables: January 2021 Final delivery: September 2021
Contractor	Erasmus MC Rotterdam

Early safety monitoring of COVID-19 vaccines

Project title	Early safety monitoring of COVID-19 vaccines in EU Member States (Early-Covid-Vaccine-Monitor)
Objectives	The study complements routine pharmacovigilance and other EU-level safety monitoring activities by: Generating prospective data on the incidence of suspected adverse reactions following vaccination of different population groups in 2021, in seven EU Member States (the Netherlands, Belgium, Luxembourg, Italy, France, Germany, Croatia) and the United Kingdom. The study uses a web-based application to collect self-reported information from vaccinated individuals. Conducting cohort monitoring of exposure, adverse events of special interest (including coagulation disorders) in vaccinated cohorts (by brand) and COVID-19 diagnoses using 4 electronic healthcare databases (the Netherlands, Italy, Spain and the United Kingdom) prior to and after COVID-19 vaccination Test systems and tools to enable larger studies aimed at further monitoring the safety of COVID-19 vaccines, as vaccination campaigns continue to be rolled out
Deliverables	Study protocol: Cohort event monitoring of safety of COVID-19 vaccines (Early-Covid-Vaccine-Monitor)  Study protocol: cohort monitoring of adverse events of special interest and COVID-19 diagnoses prior to and after COVID-19 vaccination
Timelines	Start of project: December 2020 Start of study: February 2021 Final study report: December 2021
Contractor	EU PE&PV Research Network, coordinated by Utrecht University: Pharmacoepidemiology and Clinical Pharmacology - Universiteit Utrecht (uu.nl)
Related information	EMA infrastructure for real-world monitoring of COVID-19 treatments and vaccines VAC4EU (collaboration with Utrecht University to deliver the study) University Medical Center Utrecht: Department of Datascience and Biostatistics: Julius Centre (scientific coordination)

Impact of COVID-19 infection and medicines in pregnancy

Project title	CONSIGN (COVID-19 infectiOn aNd medicineS In preGNancy)
Objectives	Establish a multinational research network using existing data sources and cohorts of pregnant women Estimate the prevalence of medicines used in pregnant women with COVID-19 Describe the severity and clinical outcomes of COVID-19 according to treatments received during pregnancy Assess and compare the rate of pregnancy and neonatal outcomes of different treatments for COVID-19 in pregnant women
Timelines	Start of project: July 2020 First deliverables: October 2020 Final delivery: July 2021
Contractor	Utrecht University
Related information	COVID-19: EMA sets up infrastructure for real-world monitoring of treatments and vaccines (21/07/2020) Information on ongoing observational studies in the EU International Coalition of Medicines Regulatory Authorities (ICMRA): Supporting the development of COVID-19 vaccines and treatments

Building a framework for the conduct of multicentre cohort studies on the use of medicines in COVID-19 patients

Project title	Multicentre collaboration for COVID-19 observational studies
Objectives	Identify large national cohorts of COVID-19 patients and appropriate comparator groups Develop a study protocol template for multinational studies Establish a collaborative framework for researchers together with the European Health Data & Evidence Network (EHDEN) consortium established under the EU's Innovative Medicines Initiative Conduct a multinational pilot study on a research question to be agreed with EMA
Timelines	Start of project: June 2020 First deliverables: September 2020 Final delivery: June 2021
Contractor	IQVIA Ltd.
Results	Study protocol for proof-of-concept on use and adverse reactions of systemic glucocorticoids in the treatment of COVID-19 in the primary and secondary care settings.
Related information	Information on ongoing observational studies in the EU International Coalition of Medicines Regulatory Authorities (ICMRA): Supporting the development of COVID-19 vaccines and treatments

Preparing an infrastructure for the monitoring of the coverage, safety and effectiveness of COVID-19 vaccines

Project title	ACCESS (vACcine Covid-19 monitoring readinESS)
Objectives	Generate background incidence rates of adverse events of special interest Identify a Europe-wide network of healthcare databases for monitoring the coverage, safety and effectiveness of COVID-19 vaccines, to enable pharmacoepidemiological studies Develop template protocols for COVID-19 vaccine coverage, effectiveness and safety studies
Deliverables	Background incidence rates of adverse events of special interest (AESIs) Study protocols (EU PAS register) Datasets (ENCePP website) Vaccine safety studies Study protocols (EU PAS register). These cover: Prospective cohort-event monitoring Rapid assessment of safety concerns using electronic health records Signal evaluation in electronic healthcare databases Hospital case-based signal evaluation  Vaccine effectiveness studies Study protocols (EU PAS register). These cover: Cohort study in electronic healthcare databases Hospital-based test-negative case-control study Coverage of COVID-19 vaccines in electronic healthcare databases Study protocol (EU PAS register) Feasibility analysis of an EU infrastructure for COVID-19 vaccine monitoring Report (EU PAS register - under 'Documents' tab) These deliverables are also available on the website of the Vaccine monitoring Collaboration for Europe, VAC4EU.
Timelines	Start of project: May 2020 First deliverables: August 2020 Final delivery: first quarter of 2021
Contractor	Utrecht University
Related information	EMA commissions independent research to prepare for real-world monitoring of COVID-19 vaccines (27/05/2020) Information on ongoing observational studies in the EU

For more information, see:

Report on pharmacovigilance tasks from EU Member States and the European Medicines Agency (EMA) 2019-2022

Reference Number: EMA/142695/2023