A post-authorisation/post-marketing observational study to evaluate the association between exposure to AZD1222 and safety concerns using existing secondary health data sources (COVID-19)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Safety study (incl. comparative)

  Validation of study variables (exposure outcome covariate)
• Data collection methods:
  Secondary data collection

Non-interventional study

• Non-interventional study design:
  Case-only

  Cohort

Study drug and medical condition

• Name of medicine:
  Vaxzevria
• Name of medicine, other:
  COVID-19 Vaccine (ChAdOx1-S [recombinant])
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BN02) covid-19, viral vector, non-replicating

  (J07BX03) covid-19 vaccines
• Medical condition to be studied:
  COVID-19 immunisation

Population studied

• Short description of the study population:
  All individuals registered in each healthcare data source during the study period.;
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Immunocompromised

  Pregnant women
• Estimated number of subjects:
  5200000

Study design details

• Study design:
  Multinational, matched cohort design; self-controlled risk interval (SCRI) design for selected outcomes.
• Main study objective:
  To evaluate the incidence and relative risk of safety concerns and adverse events of special interest (AESIs) following the administration of at least one dose of the AZ COVID-19 vaccine in the real-world setting.
• Setting:
  The source population for each of the study designs will comprise all individuals registered in each healthcare data source during the study period. The study period will start on the date AZD1222 vaccination began in each country. The first vaccinations started approximately 1 week after approval date, which was 30 December 2020 in the UK and 29 January 2021 in the EU. The study period duration will be 24 months in each data source or until latest data available at the time of start of data collection. The all AZD1222 vaccinated population will include all subjects vaccinated with at least 1 dose of AZD1222 during the study period. ; For each AESI, subjects who had an event of a specific AESI during the clean look-back interval were excluded from the cohort included in the analysis for the specific AESI with which they had history, but not from the analysis cohorts for other AESIs. For each AESI to be evaluated using the SCRI design, the eligible population will include subjects from the AZD1222 cohort who experienced the AESI during the study period.
• Comparators:
  The AZD1222 cohort will be identified based on the first vaccination with AZD1222 (index date). A concurrent unvaccinated comparator cohort will be identified among subjects who have not received any vaccination for COVID-19 matched (to the extent possible) on the vaccinee’s index date, age, sex, prior diagnosis of COVID-19, and status according to each of the 5 special populations. The active comparator cohort will be initially identified based on the first vaccination with an mRNA vaccine (Comirnaty or Spikevax) matched (to the extent possible) on the vaccinee’s index date (first dose; a second matching will be done using second dose for the comparative analysis), age, sex, prior diagnosis of COVID-19, and status according to each of the 5 special populations. A historical comparator cohort will be identified among subjects who were enrolled in the study data sources at any time during 2017 and 2018 matched on age, sex, and status according to each of the 5 special populations.
• Outcomes:
  Adverse events of special interest (AESIs) and other safety concerns listed in Table 2 of the study protocol.
• Data analysis plan:
  Baseline characteristics will be described overall and in sequential periods overtime. For the cohort study, exposure propensity scores will be used to exclude noncomparable subjects and refine the balance between study cohorts, initially matched on calendar date of vaccination, age, and gender. Propensity scores will be used to control for confounding either by matching or by analytic methods involving stratification or weighting. For AESIs for which the risk interval is characterised, crude IRs and 95%CIs for the vaccinated population and for the comparator cohort will be estimated. Poisson regression models will be used to estimate crude and adjusted IRRs and IR differences with 95%CIs comparing vaccinated and comparator cohorts. Cox regression models will be used to estimate crude and adjusted hazard ratios and 95% CIs. For comparative analysis using the SCRI approach, conditional Poisson regression will be used to estimate IRRs and 95%CIs of specific AESIs, where appropriate.

Documents

Study report

AZD1222 PASS_Interim Report 1_Final_21Apr2022_Redacted