aa Beran 2009b.

Methods	A randomised, double‐blind, placebo‐controlled study conducted during the 2006 to 2007 influenza season at 15 centres located in the Czech Republic and Finland. The protocols and study documents were approved by the ethics committee of each country. Participants were randomised to receive 1 dose of TIV (lot 1 or lot 2 of Fluarix) or placebo (normal saline solution) at the first study visit (day 0) by intramuscular injection. Each 0.5 mL dose of TIV contained 15 mg of each of the haemagglutinin antigens of strains A/New Caledonia/20/99(H1N1) IVR‐116, A/Wisconsin/67/2005(H3N2), and B/Malaysia/2506/2004 (from the Victoria lineage). From the day of vaccination, passive and active surveillance (biweekly contact) to detect ILI cases. For each case of suspected ILI, a nasal and throat swab specimen (composed of a swab of both nasal sinuses and a second swab of the throat) was collected for culture (as much as possible on the same day as the ILI report and, at the latest, 5 days after the ILI onset). Each participant was provided with a calibrated thermometer to measure temperature and a diary card to record temperatures and symptoms during the ILI episode. Blinded analysis was carried out at GSK Biologicals in Dresden, Germany. Blood samples for the evaluation of influenza vaccine immunogenicity were obtained from the randomly selected, planned subset of an estimated 500 participants just prior to vaccination and 21 to 28 days later. Frozen aliquots of culture supernatants from positive viral cultures were sent to J Treanor's laboratory (University of Rochester Vaccine Evaluation Unit Influenza Serology Laboratory, Rochester, NY, USA) for identification of virus‐matching isolates by conventional haemagglutination‐inhibition testing (using H1 and H3 antisera from the CDC and B/Malaysia antiserum from the WHO).
Participants	Eligible participants were self referred women or men who were between 18 and 64 years of age and had no significant clinical disease at the time of vaccination. WHO provided written informed consent.
Interventions	Intervention 1 dose of TIV (lot 1 or lot 2 of Fluarix), IM injection, at the first day of the study (day 0) Each 0.5 mL dose of TIV contained 15 mg of each of the haemagglutinin antigens of strains A/New/Caledonia/20/99(H1N1) IVR‐116, A/Wisconsin/67/2005(H3N2), and B/Malaysia/2506/2004 (from the Victoria lineage). Comparator placebo (normal saline solution), IM injection, at the first day of the study (day 0)
Outcomes	Serological (only carried out for the TIV group) Effectiveness  Evaluate efficacy of TIV versus placebo in the prevention of culture‐confirmed influenza A and/or B due to strains antigenically matched to the vaccine (their primary objective) Secondary objectives were evaluation of TIV in the prevention of: culture‐confirmed influenza due to strains antigenically matched to the vaccine for each of the 2 vaccine lots; culture‐confirmed influenza A and/or B attributable to any influenza A or B strain; ILI, which was less stringently defined as at least 1 systemic symptom (fever or myalgia, or both) and 1 respiratory symptom (cough or sore throat, or both). Safety vaccine reactogenicity and immunogenicity in a random subset of participants by obtaining blood samples prior to vaccination and 21 to 28 days later. However, no harms data were reported.
Notes	The authors concluded that TIV is efficacious against culture‐confirmed influenza in healthy adults. Industry funded
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details provided.
Allocation concealment (selection bias)	Unclear risk	No details provided.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	There is no mention of appearance of the injection content.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition reasons for the whole cohort are provided by the participant flow.
Summary assessment	Unclear risk	Unclear risk of bias