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. Children were excluded if they had received any vaccine within 3 weeks before vaccination with influenza or placebo. | |
| Interventions | Enrolled children 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 intranasally administered. |
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| Outcomes |
Serological
Haemagglutination antibody inhibition 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 Parent kept a diary card for 7 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. |
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| Funding Source | Government/industry | |
| Notes | The authors conclude that CR vaccine is well tolerated and immunogenic but less so in very young children. The number of children 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 children 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 |