Table 1. Summary of methods for the six European interim influenza vaccine effectiveness studies, influenza season 2022/23.
| Study characteristics | Study | |||||
|---|---|---|---|---|---|---|
| DK-PC | EU-PC | EN-EC | DK-H | EU-H | SC-H | |
| Study period | 1 Nov 2022 to 29 Jan 2023 | 3 Oct 2022 to 31 Jan 2023 | 9 Oct 2022 to 8 Jan 2023 | 1 Nov 2022 to 29 Jan 2023 | 10 Oct 2022 to 30 Jan 2023 | 3 Oct 2022 to 22 Jan 2023 |
| Setting | Non-hospitalised patientsa | Primary care | Emergency care | Hospital | Hospital | Hospital |
| Location | DK | HR, FR, DE, HU, IE, NL, PT, RO, ES (Navarra region), ES (11 regions combined, excluding Navarra) and SE | EN | DK | 29 hospitals in BE, HR, DE, LT, MT, RO, ES (Navarra region) and ES (12 regions combined, excluding Navarra) | SC |
| Study design | TND | TND | TND | TND | TND | TND |
| Data source | Data linkage of Danish Microbiology Database, the Danish Vaccination Register and the Danish National Patient Register | Physicians and laboratory, in some sites data linkage to electronic health records | Data linkage of sentinel laboratory surveillance (Respiratory DataMart), the National Immunisations Management System (NIMS), and the Emergency Care DataSet (ECDS) | Data linkage of Danish Microbiology Database, the Danish Vaccination Register and the Danish National Patient Register | Hospital charts, vaccine registers, interviews with patients, laboratory records | EAVE-II national patient-level dataset, Electronic Communication of Surveillance in SC (ECOSS; all virology testing national database), Rapid Preliminary Inpatient Data (RAPID; Scottish hospital admissions data), National Records of Scotland (NRS; death certification), National Clinical Data Store (NCDS; vaccination events in SC) |
| Age groups of study population | All ages | All agesb | All ages | All ages | All agesb | Adults ≥ 18 years old |
| Case definition for patient recruitment | Sudden onset of symptoms with feverc, myalgia and respiratory symptomsd | EU ARIe
or EU ILI (sudden onset of symptoms AND ≥ 1 of: feverc or feverishness, malaise, headache, myalgia AND ≥ 1 of cough, sore throat, shortness of breath) |
Patients with an influenza swab test 14 days before to 7 days after an emergency care visit compatible with influenza infection or its complications | Sudden onset of symptoms with feverc, myalgia and respiratory symptoms among patients admitted to hospital for at least 12 hours | EU SARI (hospitalised person with ≥ 1 of feverc/feverishness, malaise, headache, myalgia, deterioration of general condition (asthenia, weight loss, anorexia, confusion/dizziness) AND ≥ 1 respiratory symptom (cough, sore throat or shortness of breath) at admission or within 48 hours after admission) | Patients with EU ARIe symptoms and clinician’s judgement that there is an infectionf and limited to emergency care where the influenza test occurs 14 days before admission or within 48 hours after admission |
| Selection of patients | At practitioner's/ clinician's judgement | Systematic | At practitioner's/ clinician's judgement | At practitioner's/ clinician's judgement | Exhaustive (DE, HR, LT, MT, NA, RO) Systematic (BE, ES; some hospitals in BE: exhaustive on either 1 or 2 days per week, depending on workload) |
At practitioner's/ clinician's judgement |
| Vaccine types used nationally or in the studyg,h | 100% QIV (children 2–6 years of age are offered a LAIV as nasal spray) |
In the study among controls: among the seven study sites providing information on influenza vaccine brand, the brand was unknown in 19% of vaccinated controls; among the rest, 8% used a QIVc, 2% a LAIV, 12% an egg-propagated trivalent and 78% a QIVe | In the study among controls: ages 2–17 years (90% LAIV, 7% QIVc, 1% QIVe, 2% unknown); ages 18–64 years (74% QIVc, 14% QIVe, 2% QIVr, 5% aQIV, 5% unknown); ages ≥ 65 years (4% QIVc, 1% QIVr, 91% aQIV, 5% unknown) | 100% QIV (children 2–6 years of age are offered a LAIV as nasal spray) |
In the study among controls: in the only site providing influenza vaccine brand information, 77% were QIV; the remaining 23% unknown (all countries participating use QIV nationally) | 22% QIVc; 78% aQIV |
| Variables of adjustment | Age group, sexi, presence of chronic conditions, calendar time as month (Nov–Jan) (if possible, week) | Age (modelled as RCS, age group or linear term depending on analysis), sexi, presence of chronic conditions, onset date (RCS) and study site | Age group, region, clinically extremely vulnerable, COVID-19 vaccination status, calendar time as week (spline) | Age group, sexi, presence of chronic conditions, calendar time as month (Nov–Jan) (if possible, week) | Age (modelled as RCS, age group or linear term depending on analysis), sexi, presence of chronic conditions, time (onset date as RCS or month of swab as categorical term) and study site | Age (spline), sexi, number of QCOVIDj clinical risk groups (0,1,2,3,4, ≥ 5)j, time (days, spline), setting (community or hospital) and deprivation quintile (SIMD) |
ARI: acute respiratory infection; aQIV: adjuvanted QIV; BE: Belgium; DE: Germany; DK: Denmark; DK-H: DK hospital study; DK-PC: DK primary care study; EN: England; EN-EC: EN emergency care study; ES: Spain; EU: European Union; EU-H: EU hospital multicentre VEBIS study; EU-PC: EU primary care multicentre VEBIS study; FR: France; GP: general practitioner; HR: Croatia; HU: Hungary; IE: Ireland; ILI: influenza-like illness; LAIV4: quadrivalent live attenuated influenza vaccine; LT: Lithuania; LRI: lower respiratory infection; MT: Malta; NL: Netherlands; PT: Portugal; QIV: quadrivalent inactivated influenza vaccine; QIVc: cell-grown QIV; QIVe: egg-grown QIV; QIVr: recombinant QIV; RCS: restricted cubic spline; RO: Romania; SARI: severe acute respiratory infection; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SC: Scotland; SC-H: SC hospital study; SIMD: Scottish Index of Multiple Deprivation; SE: Sweden; TIV: trivalent inactivated influenza vaccine; TND: test-negative design; VE: vaccine effectiveness; VEBIS: VE, Burden and Impact Studies.
a Patients are seen by the GP, but also in emergency care.
b Patients < 6 months of age should have been excluded from the study, however the age group is specified as ‘all ages’ as age in months could not be verified from the data.
c For EU-PC and EU-H, there is no temperature threshold reported for fever, which can be measured or self-reported. For DK-PC and DK-H there is no temperature threshold for fever given in the guidance to practitioners.
d This is the case definition for patient recruitment for all GPs within DK-PC. Sentinel GPs within DK-PC follow the EU-ILI case definition (sudden onset of symptoms, AND ≥1 of: fever >38°C, feverishness, malaise, headache, myalgia AND ≥1 of: cough, sore throat, shortness of breath).
e The EU-ARI definition is sudden onset of symptoms AND ≥ 1 of cough, sore throat, shortness of breath or coryza AND a clinician’s judgement that the illness is due to an infection.
f Varies according to SARS-CoV-2/influenza testing practices by Health Board.
g Vaccines were prepared from egg-propagated vaccine viruses, non-adjuvanted and administered intramuscularly unless otherwise specified.
h Where indicated, vaccine coverage among controls were used as representative of the source population from which the cases arose.
i For all studies ‘sex’ is used in the statistical model for estimating VE as a binary variable: male/female.
j The QCOVID risk groups are defined as the number of generic comorbidity conditions of a patient, and are used as a measure of comorbidity. The list of conditions is found in the study of Clift et al [26].