Project #64:
Short-term safety of COVID-19 vaccines in England 2020/21 - acute venous thromboembolic events

Safe and effective vaccination is vital for the public health response to the COVID-19 pandemic. The COVID-19 pandemic prompted rapid vaccine development and roll-out. Each vaccine demonstrated a reassuring safety profile in large clinical trials before licensing for use. However, post-licensing vaccine safety surveillance remains important for vaccine safety and public confidence. On March 11 2021, the Danish authorities temporarily paused delivery of COVID-19 vaccination while investigating a report of a fatal blood clot in a person who had received the AstraZeneca COVID-19 adenovirus vector vaccine. A new syndrome of thrombosis with thrombocytopaenia has been described, prompting further investigation of venous thromboembolism events following vaccination.

This study aims to investigate the associations of each of Pfizer BioNTech and AstraZeneca COVID-19 vaccines with any venous thromboembolism (VTE) in England. The study will also look at the specific outcomes of pulmonary embolism and cerebral venous thrombosis.

Primary analysis will use a self-controlled case series (SCCS) design, a case-only design which compares incidence of events within the same individual across different time periods. A separate analysis will be conducted for each vaccine brand. Vaccination status will be obtained from the primary care record. We will use primary care and hospital admission records to define episodes of venous thromboembolism.

A secondary objective is to investigate the extent to which self-controlled case series (SCCS) and cohort study designs differ in their estimations of any associations of COVID-19 vaccination with venous thromboembolic events, to aid interpretation of findings from other observational vaccine safety studies. A secondary analysis will use a cohort study design with both historical and concurrent comparator groups. A cohort study design can be a useful complement to investigate the robustness of findings from SCCS analysis in safety studies, since they have a different profile of biases. We will use this analysis to explore the effect of study design on estimates of vaccine safety.

This study is a partnership between the OpenSAFELY collaboration, the NIHR Health Protection Research Unit (HPRU) in Vaccines and Immunisation (a partnership between the London School of Hygiene and the UK Health Security Agency), the NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, and the Medicines and Healthcare products Regulatory Agency (MHRA).