Study type

Study topic

Human medicinal product

Study type

Non-interventional study

Scope of the study

Effectiveness study (incl. comparative)

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Name of medicine

BIMERVAX
COMIRNATY
JCOVDEN
NUVAXOVID
SPIKEVAX
VAXZEVRIA

Study drug International non-proprietary name (INN) or common name

COVID-19 MRNA VACCINE (NUCLEOSIDE-MODIFIED)
COVID-19 VACCINE (RECOMBINANT, ADJUVANTED)
DAVESOMERAN
ELASOMERAN
IMELASOMERAN
RAXTOZINAMERAN
TOZINAMERAN

Anatomical Therapeutic Chemical (ATC) code

(J07BN) Covid-19 vaccines
Covid-19 vaccines
(J07BN01) covid-19, RNA-based vaccine
covid-19, RNA-based vaccine
(J07BN02) covid-19, viral vector, non-replicating
covid-19, viral vector, non-replicating
(J07BN04) covid-19, protein subunit
covid-19, protein subunit

Medical condition to be studied

COVID-19
Population studied

Short description of the study population

The study population included individuals in the national vaccination plan and/or the reference population registries fulfilling the following criteria during each eight–week study period:

• Resident in any of the participating EU/EEA country at the beginning of each study period.
• Aged between 50 and 110 years at the beginning of each study period.
• Not living in nursing homes (if available, and according to last update of data).
• First vaccine dose received at a time when it was recommended for the corresponding age group (i.e., excluding individuals vaccinated before the start of the recommended period was in place for a target age group or, alternatively, for those countries with no clearly defined recommended start date by age, the first 5% of persons vaccinated within each age-group –for each five-year age category- as these first vaccinees may not be representative of their corresponding age group).
• Completed primary COVID-19 vaccination series ≥24 weeks ago.
• Do not have inconsistent or missing data on vaccination (vaccination status unknown, any vaccination date is unknown, any vaccine brand is unknown, number of doses is unknown, interval between first and second dose is shorter than 19 days, interval between complete vaccination and booster dose or between booster doses is shorter than 90 days, number of doses higher than recommended, receive any vaccine brand not approved by EMA, and the combination of vaccine brands is not a recommended schedule by national public health authorities may vary by age group).

Age groups

Adults (46 to < 65 years)
Elderly (≥ 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

14000000
Study design details

Study design

This is a retrospective cohort study using data collected routinely in EHR databases. A comparison of the risk of the severe outcomes (hospitalisation due to COVID-19 and COVID-19 related death), is done between individuals
with different vaccination status.

Main study objective

To measure VE of booster doses of COVID-19 vaccine, in resident populations living in the community aged ≥50 years in EU/EEA countries, against the following outcomes:
• Hospital admission due to COVID-19
• Death related to COVID-19.
The relative VE (rVE) of first, second or third booster was estimated compared to individuals with COVID-19 primary vaccination administered ≥ 24 weeks ago without a subsequent booster.

Setting

The study was carried out in six EU/EEA countries: Belgium, Denmark, Luxembourg, Spain (Navarre), Norway, Portugal, representing close to 14 million people ≥50 years.

Outcomes

Outcomes of interest are defined as:
Hospital admission due to COVID-19:
- Admission to hospital in which COVID-19 is the main diagnosis in the admission or discharge record (for example, based on International Classification of Diseases (ICD) coding or similar);
OR,
- Admission to hospital in which admission criteria are compatible with SARI (based on similar criteria as in SARI surveillance, ICD coding or similar) AND with a laboratory-confirmed SARS-CoV-2 infection ≤14 days before
admission or up to 24 hours after admission.
COVID-19 related death:
- death for which COVID-19 is recorded as the cause of death;
OR, if cause of death not available,
- laboratory-confirmed SARS-CoV-2 infection with death within 30 days after a positive test.
For each outcome, the censoring date of the outcome occurrence (date of the event of interest) was the earliest among the date of hospital admission or death, and the date of the laboratory diagnosis (i.e. the date of the first diagnosis of the infection episode that resulted in hospital admission or death).

Data analysis plan

Vaccination status was a time-changing variable defined at the beginning of the eight-week study period.
Individuals for which vaccination status changed during the follow-up period were censored without an event reported in the vaccination status group they left, and were recorded as a delayed entry into the new vaccination status group, on the date their vaccination status changed.

Individuals were then followed up until the earliest date of:
• Event of interest, with date of outcome as previously defined;
• Death from any cause (on the date of death);
• Discontinuation in the administrative database (i.e. emigration);
• Administrative censoring (eight weeks after the start of the observation period).
Cox regression with calendar time as the underlying time scale was used to estimate hazard ratios (HRs) of defined outcomes among the group with the vaccine status of interest compared to the reference vaccination status group.
Vaccine effectiveness was defined as VE = (1-HR) x 100. To estimate the rVE of booster doses compared to primary vaccination we used complete primary vaccination series ≥24 weeks ago without a subsequent booster as
the reference group.
Cox regression models were adjusted by age, sex geographical region (if applicable to the study site), previous infection, comorbidities, socioeconomic variables or others as available and relevant at each study site.

See protocol.
Documents
Study report
Interim analysis of COVID-19 vaccine effectiveness against hospitalisation and …