Post-authorisation active surveillance of the Safety of COVID-19 Vaccine AstraZeneca (AZD-1222) in the UK: A consortium study

Study type

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

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Active surveillance of safety

Study drug and medical condition

• Medicinal product name, other:
  COVID-19 vaccine AstraZeneca (AZD-1222)
• Study drug International non-proprietary name (INN) or common name:
  COVID-19 VACCINE ASTRAZENECA (CHADOX1 NCOV-19)

Population studied

• Short description of the study population:
  Adults and children vaccinated with COVID-19 vaccine AstraZeneca (AZD1222) launched during the mass vaccination programme in the UK.
• Age groups:
  • Adolescents (12 to < 18 years)
  • 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:
  18000

Study design details

• Study design:
  Non-interventional post-authorisation active surveillance study to monitor the utilisation and safety of COVID-19 vaccine AstraZeneca (AZD1222) in the UK.
• Main study objective:
  To monitor the safety and utilisation of the COVID-19 Vaccine AstraZeneca (AZD-1222) administered to vaccinees under real-world use in the UK
• Setting:
  Vaccination sites including large vaccination hubs, GP practices, health clinics etc. in the UK were invited to participate. Vaccinees and/or their representatives (parent/guardian) were provided with study information explaining the surveillance by immunisation staff after vaccination. Sites were provided with supporting information. At least 10,000 adults and children vaccinated with COVID-19 vaccine AstraZeneca (AZD1222) would be recruited.
• Comparators:
  none
• Outcomes:
  • To examine the safety of COVID-19 vaccine AstraZeneca (AZD-1222) through active surveillance of all vaccinee reported adverse events and assessment of incidence. Description of: (i) serious adverse events following vaccination. (ii) adverse events of special interest (AESI) including AESI relevant to vaccinations in general and AESI for AZD-1222. (iii) utilisation of AZD-1222 in the cohort, including vaccination site, demographics of vaccinee and vaccine brand/batch. (iv) use and safety in pregnant, breastfeeding and immunodeficient vaccinees.
• Data analysis plan:
  Monthly summary reports will be produced. Interim reports will be produced at months 1 (or at the first 1,000 vaccinees, whichever comes first), 3 (or at the first 5,000 vaccinees), 6 (or at the first 10,000 vaccinees), 12, 18 and 24. Findings will also be summarised in a final report. Summary descriptive statistics including age, gender and specific co-morbidities/conditions (e.g. sub-populations of interest) reported on questionnaires will be presented, alongside event frequencies. Observed vs expected analysis will be performed for selected AESIs (where appropriate background rate information is available) at regular intervals throughout the study. For the final report, cumulative incidence risk and rates will be calculated with 95% confidence intervals. Time to onset analyses will be performed for AESI and serious adverse events where a sufficient number of events are reported. Descriptive statistics will be used for other outcome measures.
• Summary results:
  The first participant consented was 1st March 2021. Recruitment ended on the 31st August 2021.; The majority of participants were female (n=10845; 60.4%) and the median (interquartile range [IQR]) age was 50 (43, 62) years. Most participants were from White ethnic groups (English, Welsh, Scottish, Northern Irish, or British) (n=13112; 73.1%). ; For participants who reported adverse events, data were censored at two time points; time of receipt of the first non-AstraZeneca COVID-19 vaccine dose (Analysis Group 1) and time at which complete case level data was included for Analysis Group 1 (Analysis Group 2). The non-censored whole cohort data formed Analysis Group 3. Results for Analysis Group 2 were consistent with Analysis Group 1 with less than 20 additional adverse events to Analysis Group 1 being identified and therefore are not presented separately. ; Analysis Group 1 contained 19824 events (6591 participants); 399 events were serious (220 participants), 287 were adverse events of special interest (AESIs) (184 participants). Analysis Group 3 contained 22529 adverse events (6582 participants); 507 adverse events were serious (275 participants), 388 were AESIs (251 participants). In both analysis groups headache and fatigue had the highest cumulative risk and rate. The most frequently reported AESI in both analysis groups was anosmia and/or ageusia. Following stratification by age and gender an increased Observed vs Expected (O:E) ratio was seen for anosmia and/or ageusia (both analysis groups) and for anaphylaxis (Analysis Group 3 only). ; Data was obtained for special populations; 49 pregnancies were reported in 48 female participants, the outcome of pregnancy included spontaneous abortion (n=6) and four serious adverse events reported in the offspring were considered to be related to at least one dose of the AstraZeneca COVID-19 vaccine. ; During the study 11 deaths were reported, including 2 reports of multi organ failure and 2 reports of COVID-19 -related death.