Rapid Safety Assessment of SARS-CoV-2 vaccines in 5 EU Member States using 10 electronic health care datasources

Date of Approval
Application Number
Technical Summary

The COVID-19 pandemic caused by SARS-CoV2 triggered the need for developing vaccines. This study will create readiness and allows for rapid assessment of the association of adverse events of special interest (AESI) following COVID-19 vaccination in 10 data sources in five countries, including UK CPRD.

Rapid assessment will be conducted using a retrospective observational study using electronic health care databases gone through the readiness phase. Eligible individuals will be included in the study from the start of vaccination campaignsand will end at the last date of data availability in each database. For specific events of concern, the study design will depend on whether the event is considered acute or non-acute and follow the decision framework described in the ACCESS template protocols (EUPAS 39361). The primary study design for acute events (events expected to occur within 60 days of vaccination) will be a self-controlled risk interval (SCRI) design and for non-acute events (events expected to occur or be diagnosed with delay, within 180 days) will be a cohort design with contemporary exposed comparators. Acute events may also be studied using the cohort design to address uncertainties around risk windows and limitations of the SCRI design. In the SCRI design, a non-exposed control window will be used.

Subjects start follow-up at time zero (time of vaccination or the start of the pre-vaccination control window for the SCRI) and end follow-up at the earliest of occurrence of latest data availability of the databank, subject exit, or the completion of the period, or death. At least one year of enrollment/ presence prior to time zero (cohort entry) will be required to determine whether individuals meet the study criteria and to define baseline characteristics.

Study results will be be followed-up by EMA, who will take regulatory action if needed to benefit public health for patients.

Health Outcomes to be Measured

The list of AESI (as per EMA June 8 communication) is listed below, this list may be updated if new issues occur.

Multisystem inflammatory syndrome;
Acute respiratory distress syndrome;
Acute cardiovascular injury (microangiopathy, Coronary Artery Disease, Arrhythmia, Myocarditis, Pericarditis);
Coagulation disorders, including deep vein thrombosis, pulmonary embolus, cerebrovascular stroke, limb ischaemia, haemorrhagic disease (VTE (DVT & PE & Splanchnic), Cerebral venous sinus thrombosis, Arterial thrombosis, Thrombosis with Thrombocytopenia Sundrome (VTE, arterial thrombosis, or Cerebral venous sinus thrombosis with thrombocytopenia in 10 days), Hemorrhagic stroke, Disseminated intravascular coagulation);
Generalised convulsion;
Guillain Barré Syndrome;
Diabetes (type 1 and unspecified type);
Acute kidney injury;
Acute liver injury;
Chilblain-like lesions;
Single organ cutaneous vasculitis;
Erythema multiforme;
Death (any cause)** (postvaccination control window);
Sudden death (by codes)** (postvaccination control window);
Acute disseminated encephalomyelitis (ADEM);
Transverse myelitis;
Bells’ palsy;
Haemophagocytic lymphohistiocytosis ;
Kawasaki's disease ;
Pancreatitis ;
Rhabdomyolysis ;
Sensorineural hearing loss;

Negative control events:
Otitis externa;
Trigeminal neuralgia;


Olaf Klungel - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Helga Gardarsdottir - Collaborator - Utrecht University
Romin Pajouheshnia - Collaborator - Utrecht University
Satu Johanna Siiskonen - Collaborator - Utrecht University
Svetlana Belitser - Collaborator - Utrecht University


HES Admitted Patient Care