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ICMRA meeting: COVID-19 Real-World Evidence and Observational studies

25 January 2021


Chairs: Kelly Robinson (Health Canada) and Peter Arlett (European Medicines Agency)


1. Welcome and introduction

Emer Cooke, EMA Executive Director and Chair of ICMRA, opened the meeting by welcoming all the participants. Emer emphasised the challenges we have been facing over the last year and reminded colleagues that this unprecedented situation provides an opportunity to collaborate and share expertise globally on important Covid-19-related aspects.

As vaccines are being authorised and rolled-out across the world, regulators must ensure post-authorisation monitoring of the safety and effectiveness of these products, including on special populations such as pregnant women, children, immunosuppressed patients. The creation in 2020 of three ICMRA technical work streams on vaccine surveillance, pregnancy research and international cohorts have strongly intensified the interactions between regulatory agencies and will help us combat the pandemic all together.

2. ICMRA members to share information on any initiatives on observational studies including sharing:

Kelly introduced the topic by thanking all colleagues who provided a response to the survey sent on the 21st January to all ICMRA members seeking information on ongoing initiatives regulators are working on that may be of interest to ICMRA and highlight opportunities for international collaboration.

  • National Agency for Food and Drug Administration and Control (NAFDC: Nigeria): Moji Adeyeye reported that Nigeria is part of a group of African countries with Ghana, Ethiopia and South Africa implementing a 3S program focusing on conducting smart safety surveillance for COVID-19 vaccines. This group allows Nigeria to have an opportunity to have a strong coordinated approach to safety monitoring. A track and trace system is being deployed and piloted using the COVID-19 vaccine to operationalize the system. NAFDAC is working with MHRA to generate a database to collect and leverage high quality information. Joint efforts from WHO and MHRA are underway including training to NAFDC and primary health care staff and develop effective monitoring systems. Key learnings have been identified, and there will be opportunities for data and information from these initiatives to be leveraged by other ICMRA authorities.
  • Denmark: Danish colleagues informed in writing about the DAC COVID, a cohort of all Danish COVID-19 patients that is continuously updated and linked to the existing Danish health and administrative registries. This has allowed analyses of how drugs, demographic factors and diseases affect the course of COVID-19. Steering group and expert groups containing multiple stakeholders from academia, government agencies, healthcare and patients. A total of sixteen project proposals have been handled since late February 2020. Results from eight projects have been published (of which two are method papers), further 6 are submitted and under review or revision and two are in development.
  • Japan: Several observational studies on vaccines are under discussion and protocols can be shared once agreed.

3. Update on the three technical workstreams initiated at the 19 May 2020 ICMRA meeting:

Peter Arlett introduced the topic by inviting presenters from the three technical workstreams to update members on the progress and next steps of each project. Peter also invited questions and discussions following each of the presentations.

a) Vaccine surveillance and vigilance (MHRA + TGA)

Patrick Batty (MHRA) provided an update on the Covid-19 Vaccine Pharmacovigilance Network on behalf of MHRA and its workstream co-chair TGA.

The group is currently composed of eighteen active members and aims at sharing experience and communications on vaccines pharmacovigilance activities, and emerging benefit / risk profiles. The group is however not intended to develop designs of epidemiological studies to evaluate outcomes of AESI or emerging safety signals or develop pharmacovigilance guidance.

Discussions include countries’ approaches to vaccines pharmacovigilance (e.g. active / passive surveillance, epi studies), RMP activities, lists of AESI, and more recently since vaccines have been authorised, the group is considered to provide a relevant forum to share and discuss live and real pharmacovigilance issues during its bi-monthly meetings. Ad-hoc meetings can also be organised as required. It is important to note that normal communication channels will still apply. 

Guest presentations have been provided the Global Vaccine Data Network (GVDN), ACCESS consortium and FDA/CDC on their plans for monitoring Covid-19 vaccines.

A simulation exercise is planned to test processes in place and assess collaborative actions. The exact technical aspects and timelines are to be clarified. Patrick Batty will inform ICMRA on the results of the simulation exercise.

Additional ICMRA members are invited to take part in this workstream. Expressions of interest can be sent to ICMRA secretariat (

b) Pregnancy observational research (EMA)

Corinne de Vries (EMA) presented an update on the CONSIGN project and on the international collaboration currently ongoing, which is key to collecting meaningful exposure data and increasing the power of evidence to study the impact of Covid-19 treatments on pregnancy and newborns.

Since the ICMRA meeting in October 2020, EMA accepted the CONSIGN protocol for the retrospective study in nine population based electronic health and medical birth registers in eight EEA countries, as well as a description of EHR data sources in EU and a document outlining practical steps for international collaboration on meta-analyses. These have all been shared with ICMRA technical WG and other organisations, as well as code books of variables used by COVI-PREG and INOSS.

The first report on near-real-time utilisation data from COVI-PREG and INOSS is expected Friday, 29 January.
Work in Progress:

  1. Retrospective studies on electronic health records: discussion with various partners to ensure that the protocol has been designed in such way that it can be implemented in other regions (e.g. in the US through Sentinel).
  2. COVI-PREG and INOSS: level of details collected on treatments varies across countries/regions/centres. Work is ongoing with the CDC and GWU to map the codes list with those used in ongoing data collection initiatives and meta-analyses and see how such information can be collected in a more structured way.

The door is open for collaboration with any interested countries which have electronic health records that could participate in meta-analysis within CONSIGN project 1, or which are not yet part of COVI-PREG or INOSS for meta-analyses on primary data.

Manufacturers have the responsibility to monitor their vaccines. They have their own initiatives included in their risk management plans for which we are waiting for the protocols. Applicants and MAH are talking with COVI-PREG and INOSS networks to see how these can be leveraged to increase numbers. However, MAA/MAH are free to decide if they wish to use these networks.

WHO also has ongoing work on pregnancy: development of a guidance on the monitoring of pregnant women infected by Covid-19, including 2 master protocols, both looking at Covid-19 vaccines.

WHO Global Advisory Committee on Vaccine Safety (GACVS) sub-committee: reviews reports related to Covid-19 vaccines including 23 cases of death with Pfizer vaccine reported in Norway. Great collaboration including a joint ICMRA statement that took into account the background rate for weekly death in this frail population (N=300) for contextualisation: WHO to share the link to the report.

There was discussion on the importance of the vaccine surveillance work stream to consider background rates when sharing data on emerging safety signals for the sake of contextualisation.

ICMRA Workshop on Pregnancy and Lactation scheduled on Tuesday 9th February – open to all ICMRA members.

c) Building international cohorts (HC)

Craig Simon presented the workstream on building international cohorts that aims at sharing expertise and increase study power and data quality to meet regulatory requirements and address knowledge gaps. There are 3 topics areas:

  • Proof of concept study on steroids use led by EMA (results in April 2021). This protocol is published: US FDA and HC projects currently under development
  • The FDA provided an overview of their protocol for their study of coagulopathy, which addresses the reports of abnormalities in blood coagulation resulting from COVID-19. The study has three aims: 1. Determine the incidence rates of thrombotic events in those with COVID-19 and risk of death; 2. Evaluate patient as risk factors for thrombotic events; and 3. Compare risk of thrombotic events between those with COVID 19 and those with influenza.  The study protocol has been developed and posted online (, and the analytic plan is current under development.  Final results are anticipated for August 2021. There is a replicate study under development by the EMA, and a query has been submitted to DSEN by HC
  • COVID-19 case definitions led by HC and is currently being developed.

4. Summary and next steps

Kelly Robinson closed the meeting by thanking the co-chair Peter Arlett, the presenters and participants and noting the importance of this work and that the discussions demonstrate the need and value of these meetings to share experience and opportunities to collaborate. Thanks were also extended to the ICMRA team for organising and to all colleagues for their involvement.

The next meeting will be scheduled for April 2021.