The Pfizer-BioNTech COVID-19 vaccine received conditional approval in Europe for preventing COVID-19. Sometimes vaccine use is associated with side effects known as adverse events. As COVID-19 vaccines have been developed urgently, they require ongoing safety monitoring to examine these side effects. Therefore, the safety of the vaccine must be observed as it is given to people worldwide.
This UK study, part of several studies in Europe, will use information from UK primary care electronic health records (EHR) to determine the safety of the Pfizer-BioNTech COVID-19 vaccine among the UK population receiving the vaccine. It will investigate trends of Pfizer-BioNTech COVID-19 vaccine use in the UK, such as time between doses, characteristics of vaccinated people, and other sub-groups of interest.
Information on Adverse Events of Special Interest (AESI) in vaccinated people will be compared with AESI in unvaccinated people. AESI include side effects commonly associated with the use of various vaccines. This study will determine whether vaccinated people with specific medical conditions (e.g., immune system problems, frailty, prior COVID-19 infection, pregnancy) have different risk of AESI than unvaccinated people with these conditions.
A sub-study will examine and describe the clinical course and possible risk factors for two specific AESI, myocarditis and pericarditis. These conditions are known side effects of the Pfizer-BioNTech COVID-19 vaccine, and involve inflammation of the heart muscle or lining. It is important to understand the severity of myocarditis or pericarditis following vaccination, and determine whether any characteristics might increase a person’s risk of developing these side effects.
The Pfizer-BioNTech COVID-19 vaccine, tozinameran (Comirnaty®) a novel mRNA-based vaccine, has been authorised in the European Union (EU), for prevention of COVID-19. Due to the shortened pre-authorisation development period and the limited clinical trials for COVID-19 vaccines, post-authorisation safety studies (PASS) are required to continue monitoring safety. This CPRD study, conducted in GOLD and Aurum databases, forms the UK component of this multi-database multi-country study conducted in Europe, fulfilling European Medicines Agency (EMA) requirements.
The study aims to determine whether there is an increased risk of selected adverse events of special interest (AESI) after vaccination with the Pfizer-BioNTech COVID-19 vaccine. A retrospective cohort design, comparing risk in vaccinated and non-vaccinated individuals and a self-controlled risk interval (SCRI) design will be used to determine whether an increased risk of prespecified AESI exists following the administration of at least one dose the Pfizer-BioNTech COVID 19 vaccine. The cohort study design will be used to estimate incidence rates of prespecified AESI among individuals who receive at least one dose of the Pfizer-BioNTech COVID-19 vaccine.
A cohort and/or SCRI design will be used to describe incidence rates and determine whether an increased risk of prespecified AESI exists following at least one dose of the Pfizer-BioNTech COVID 19 vaccine compared with a matched comparator group with no COVID 19 vaccination, within sub-cohorts of interest. The cohort study will determine whether an increased risk of prespecified AESI exists following at least one dose of the Pfizer-BioNTech COVID-19 vaccine compared with no COVID-19 vaccination, in pregnant people and their neonates.
In addition, the study will characterise utilisation patterns of Pfizer-BioNTech COVID-19 vaccine by estimating the proportion of individuals receiving vaccine; two-dose vaccine completion rate and distribution of time gaps between the first and second dose; demographics and clinical characteristics of recipients, overall and among sub-cohorts of interest.
Safety outcomes:
Outcomes will be defined homogeneously across the data sources to the fullest extent possible. Selected AESI currently planned for inclusion in the study are listed below and are based on those proposed by the ACCESS project (vACcine COVID-19 monitoring readinESS), which has been funded by the EMA to ensure that a European infrastructure will be in place to effectively monitor COVID-19 vaccines in the real world, once the vaccines are authorised in the EU (http://www.encepp.eu/encepp/viewResource.htm?id=37274.).
The Adverse Events of Special Interest (AESI) to be analysed in the study are:
Autoimmune diseases to include: Guillain-Barré syndrome; acute disseminated encephalomyelitis; narcolepsy; acute aseptic arthritis; diabetes mellitus type 1; (idiopathic) thrombocytopenia; thrombotic thrombocytopenia syndrome (TTS), myositis. Cardiovascular system outcomes to include: acute cardiovascular injury, arrhythmia, heart failure, stress cardiomyopathy, coronary artery disease, myocarditis, pericarditis, myocarditis and pericarditis. Circulatory system outcomes to include: coagulation disorders (thromboembolism; haemorrhage); single organ cutaneous vasculitis; cerebral venous sinus thrombosis. Hepato-gastrointestinal and renal system outcomes to include: acute liver injury; acute kidney injury; acute pancreatitis; rhabdomyolysis, glomerulonephritis. Nerves and central nervous system outcomes to include: generalised convulsion; meningoencephalitis; transverse myelitis; Bell’s palsy. Respiratory system outcomes to include: acute respiratory distress syndrome. Skin and mucous membrane, bone and joints system outcomes to include: erythema multiforme; chilblain-like lesions. Reproductive system outcomes include: secondary amenorrhoea, hypermenorrhoea. Other system outcomes to include: anosmia, ageusia; anaphylaxis; multisystem inflammatory syndrome; death (any cause); subacute thyroiditis; sudden death. Maternal pregnancy outcomes to include: gestational diabetes; preeclampsia; maternal death. Neonatal pregnancy outcomes to include: foetal growth restriction; spontaneous abortions; stillbirth; preterm birth; major congenital anomalies; microcephaly; neonatal death; termination of pregnancy for foetal anomaly. Other outcomes to include: severe COVID-19 (defined as COVID-19 hospitalisation or death) .
First in period (possible recurrent) events will be assessed and case definition algorithms will be based on codes for diagnoses, procedures, and treatments. Definitions, codes, and proposed algorithms for all AESI will incorporate definitions developed by the ACCESS project (http://www.encepp.eu/encepp/viewResource.htm?id=37274)(https://drive.go…).
Myocarditis and pericarditis sub-study
Myocarditis and pericarditis cases identified using CPRD Aurum will undergo case validation. Validated cases will serve as eligibility criteria for the cohort to study the primary objective, and as study outcomes for the cohort to examine the secondary objective. To assess if a patient underwent procedures related to the myocarditis and/or pericarditis diagnosis and recovered, additional data will be collected using the CPRD PROVE Plus service ( 00130879). Potential outcomes for myocarditis that will be evaluated are recovery, survival, hospitalisations, sudden cardiac death, heart failure, cardiogenic shock, fulminant myocarditis, inflammatory cardiomyopathy, heart transplant, and arrhythmia. Potential outcomes for pericarditis that will be evaluated are recovery, survival, hospitalisations, and chronic, restrictive, and recurrent pericarditis. Furthermore, treatments for myocarditis or pericarditis will be examined.
Saad Shakir - Chief Investigator - Drug Safety Research Unit
Debabrata Roy - Corresponding Applicant - Drug Safety Research Unit
Catherine Fry - Collaborator - Drug Safety Research Unit
Denise Morris - Collaborator - Drug Safety Research Unit
Kathryn Morton - Collaborator - Drug Safety Research Unit
Miranda Davies - Collaborator - Drug Safety Research Unit
Samantha Lane - Collaborator - Drug Safety Research Unit
Sandeep Dhanda - Collaborator - Drug Safety Research Unit
Taylor Aurelius - Collaborator - Drug Safety Research Unit
Hai Nguyen - Collaborator - Drug Safety Research Unit
Kenneth Anujuo - Collaborator - Drug Safety Research Unit
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Mother-Baby Link;CPRD Aurum Pregnancy Register