ab Gruber 1996

Methods	Multicentre, randomised, double‐blind, placebo‐controlled clinical trial to assess the efficacy and safety of live attenuated, cold adapted influenza vaccine in children aged 6 to 18 months. Vaccine was administered either as monovalent or bivalent preparation in a randomised, double‐blind manner (any description, author contact is needed)
Participants	Children aged 6 to 18 months who were enrolled at some vaccination units: Baylor College of Medicine, St. Louis University, University of Rochester, Vanderbilt University, University of Maryland. 182 participants were vaccinated, all were born after the last influenza A epidemic and had little opportunity for H3N2 exposure
Interventions	Monovalent live attenuated, cold adapted influenza vaccine A/Kawasaki/9/86 (H1N1) CR – 125, lot BDS 911501, 106.2 TCID50 per 0.5 ml in egg allantoic fluid Monovalent live attenuated, cold adapted influenza vaccine A/Los Angeles/2/87 (H3N2) CR – 149, lot BDS 915301, 106.2 TCID50 per 0.5 ml in egg allantoic fluid Bivalent live attenuated, cold adapted influenza vaccine A/Kawasaki/9/86 and A/Los Angeles/2/87 , lot BDS 915501, containing 106.2 TCID50 of each strains in 0.5 ml of egg allantoic fluid Placebo consisting in egg allantoic fluid Vaccines were prepared by Wyeth‐Ayerst (Philadelphia) Vaccine and placebo were administered as nose drops as 0.5 ml dose in the autumn of 1991
Outcomes	Serological HAI and ELISA were determined against H1N1 and H3N2 Effectiveness Subjects were monitored during the winter 1991–92 to evaluate the protection against influenza A H3N2 (A/Beijing/89) epidemic. Once influenza was detected by community surveillance, all participants were followed closely by weekly phone calls. A home visit was done if a subject had symptoms of respiratory illnesses or any household contacts had fever > 37.8°C and upper respiratory symptoms. In these cases a nasal wash for viral culture was obtained. Respiratory illnesses were classified as febrile or afebrile. Individual doing examination remained blinded to the treatment group. OM was coded separately. A total of 128 illnesses among 181 participants were identified. More than 50% of children with respiratory illnesses had viruses other than influenza. Influenza A/Beijing/89 was isolated from 23 children with respiratory illnesses Safety During the 10 days after vaccination, parents and guardians recorded the subject’s temperature twice a day (morning and evening) and symptoms including cough, rhinorrhoea, diarrhoea (evening) once a day. Fever was considered any temperature > 37.8°C. For the other symptoms were considered at least 3 stools in 24 hours. Parents had to contact the study site if a subject had more than 1 symptom on a given day or had fever > 37.8°C. These were clinically evaluated. Diary information was unavailable for 2 children"
Funding Source	Government/industry
Notes	The authors conclude that live attenuated vaccines were significantly more effective than inactivated vaccines. Data about epidemic strain isolation in the 4 arms were pooled based on whether participants received a H3N2‐containing vaccine or not. It is not possible to go back to the isolation in the single 4 arms
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	Unclear risk	No description
Summary assessments	Unclear risk	Plausible bias that raises some doubt about the results