ab Gruber 1997

Methods	RCT, double‐blind, multicentre to assess reactogenicity and safety of a cold adapted bivalent influenza vaccine containing the strains A/Kawasaki/9/86 (H1N1) virus and ca A/Beijing/352/89 (H3N2)
Participants	1126 children aged 2 to 36 months enrolled from 13 participating institutes in autumn 1993. Subjects were excluded if they had received any vaccine within 3 weeks before vaccination with influenza or placebo
Interventions	Enrolled participants were randomised to receive 1 0.5 ml dose of cold adapted bivalent flu vaccine containing 104, 106 or 107 TCDI50 ca A/Kawasaki/9/86 (H1N1) virus and ca A/Beijing/352/89 (H3N2) virus per 0.5 ml dose or placebo, consisting of egg allantoic fluid Vaccines and placebo were intranasal administered
Outcomes	Serological HAI titre against A/Kawasaki/9/86 and A/Beijing/352/89 were determined. Serum specimens were collected before vaccination and 35 days after by finger stick or venipuncture Effectiveness Not assessed Safety A diary card was kept by parent for seven days after immunisation. Temperature (recorded axillary, rectal or orally) and other symptoms were reported. Fever was considered as temperature 38.6°C rectal; 38.1°C orally or 37.5°C axillary
Funding Source	Government/Industry
Notes	The authors conclude that CA vaccine is well tolerated and immunogenic but less so in very young children: The number of individuals in each study arm, is not clearly reported. Data from the table of respiratory symptoms (table 2 of this paper) do not agree with those reported in table 1 (fever). A total of 1126 study participants were enrolled but they resulted in 1249 from table 1 (and 1123 from table 2)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No description
Allocation concealment (selection bias)	Unclear risk	No description
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	Few losses to follow‐up, unlikely to be related to true outcome
Summary assessments	High risk	Follow‐up very short (7 days after each dose). Major denominator discrepancies between text and tables