ab King 1998

Methods	Randomised, placebo‐controlled, multicentre trial
Participants	Children aged 18 to 71 months in good health. 238 were altogether enrolled at Baylor College of Medicine Houston, Cincinnati Children Hospital, Saint Louis University and University of Maryland at Baltimore in three steps. 118 were enrolled from one ambulatory clinic in the northern area of Santiago (Chile)
Interventions	Cold adapted trivalent flu vaccine containing the strains A/Johannesburg/33/94 (H3N2), B/Panama/45/90 and A/Texas/36/91 (H1N1) in different titre (104, 105, 106 or 107 TCID50 of each strain) versus placebo Vaccine and placebo (allantoic fluid) were assigned in double‐blind manner using a randomisation table provided by the manufacturer (Avion). Enrollment took place in 3 steps : 115 children in the USA and 60 in Chile were randomised to receiver either 104 or 105 TCID50 of vaccine or placebo at a ratio of 1:1:1 59 children in the USA and 30 in Chile were randomised to receive 106 TCID50 of vaccine or placebo at 2:1 ratio 64 children in the USA and 28 in Chile were randomised to107 TCID50 of vaccine or placebo in a 2:1 ratio In the USA the randomisation was designed so that 50% of the participants received vaccine or placebo as drops and the remaining 50% by spray
Outcomes	Serological Antibody titres Effectiveness N/A Safety Temperature was recorded each evening within 10 days after vaccination on a diary card. Other daily recorded symptoms were: cough, wheezing, rhinorrhoea, sore throat, or irritability. Children were examined by clinicians if an axillary, oral or rectal temperature > 38°C was observed
Funding Source	Government/Industry
Notes	The authors conclude that the vaccine was safe and immunogenic in 2 of the 3 strains. Small denominator
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient descriptions
Allocation concealment (selection bias)	Unclear risk	No description
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Insufficient descriptions
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow‐up
Summary assessments	Unclear risk	Insufficient information about study design