ab Swierkosz 1994

Methods	Randomised, double‐blinded, placebo‐controlled trial to assess safety of adding a third dose of a live attenuated, cold‐recombinant, trivalent influenza vaccine
Participants	22 healthy infants and children aged 2 to 22 months were recruited. 17 were seronegative to all three hemagglutinin types, while 2 were seronegative to H3 and B and 2 were seronegative to H1 and B
Interventions	Subjects were randomised to receive 3 doses of 0.5 ml vaccine or placebo intranasally in a double‐blinded way. 17 healthy infants and children received vaccine and 5 received placebo. Vaccine was administered at day 0, day 60 and day 120. Vaccine contained three strains: A/Kawasaki/9/86 (H1N1), A/Los Angeles/2/87 (H3N2) and B/Yamagata/16/88. The vaccine lots contained 108.0, 108.0 and 107.6 TCDI50/ml H1N1, H3N2 and B. 106 TCDI50 of each strains was present in 0.5 ml of trivalent vaccine
Outcomes	Serological "HAI titres against H1, H3, B and all types (H1, H3 and B) after first dose at day 0, second dose at day 60 and third dose at day 120 ELISA response to H1, H3, B and to all types (H1, H3 and B) after dose first dose at day 0, after second dose at day 60 and third dose at day 120" Effectiveness N/A Safety Adverse reactions were defined as fever (rectal temperature > 38.3°C, or > 37.2°C axillary); cough (2 or more episodes during examination on 2 consecutive days); otitis media (red immovable ear drum diagnosed by pneumotoscopy); and lower respiratory tract infection as indicated by wheezing (sustained musical sound during expiration) or pneumonia (a new alveolar consolidation seen radiographically). Clinical observations were recorded daily for 11 days
Funding Source	Government
Notes	The authors conclude that trivalent, cold adapted intranasal influenza vaccine is safe and immunogenic, when administered in a three dose regime. A tiny schedule‐ranging trial. Only 4 participants were aged less than 6 months
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not described
Summary assessments	Unclear risk	Insufficient information to assess study design