A Post-authorisation/Post-marketing Observational Study to Evaluate the Association Between Exposure to AZD1222 and Safety Concerns Using Existing Secondary Health Data Sources

This retrospective study based on electronic heath records will evaluate the incidence and relative risk of safety concerns and adverse events of special interest (AESIs) following immunisation by AZD1222 in the real-world setting. The primary study objectives are to (1) describe baseline characteristics of all individuals in the matched population over the study period; (2) describe, among subjects who receive a first dose of AZD1222, the timing and type of second dose of any COVID-19 vaccine over the study period; (3) describe the incidence of prespecified AESIs in subjects who have received at least one dose of AZD1222 in the matched population and unvaccinated subjects; and (4) estimate any increased risk of prespecified AESIs following vaccination with AZD1222 using study retrospective cohort and self-controlled risk interval designs. Secondary objectives are identical to the primary, although focused on specific populations considered to have missing information, specifically (a) women who are pregnant or breastfeeding, (b) immunocompromised patients, (b) frail patients with certain comorbidities, (c) patients with autoimmune or inflammatory disorders, and (d) patients who, at cohort entry, had recently received a number of selected vaccines to prevent diseases other than COVID-19. A cohort and a self-controlled case series designs will be used.

Exploratory objectives: 1) To describe the IRs of prespecified AESIs in subjects who received an mRNA vaccine against COVID-19 (either Comirnaty or Spikevax) (active comparators) and in subjects from the pre-pandemic period (2017-2018) (historical comparators) in the matched population; 2) To estimate the relative and absolute risk of prespecified AESIs in subjects who received at least 1 dose of AZD1222 in the matched population compared with historical comparators in the matched population; and 3) To estimate the relative and absolute risk of prespecified AESIs in subjects who received 2 doses of AZD1222 in the matched population compared with subjects who received 2 doses of active comparator (Comirnaty or Spikevax as per homologous vaccination regimen) in the matched population*

*Feasibility of the active comparator analysis will be assessed prior to conducting the analysis to ensure comparability between groups.