| Methods |
Randomised controlled trial, double‐blind, conducted in the USA during the 1988 to 1989 influenza season. Follow‐up lasted the whole epidemic period. The epidemic period in any study year started on the day that the first influenza A virus isolate was obtained in Nashville and ended on the day that the last isolate was obtained and lasted 11 weeks. Participants were recruited from 7 organisations and assigned to 1 of the study groups using a permuted block randomisation scheme that was stratified by treatment centre and age group. Sealed randomisation envelopes contained vaccine codes. Pharyngeal swab and paired sera were collected from ill people. |
| Participants |
1676 healthy children and adults of metropolitan Nashville: 1114 treated and 562 placebo. Age of participants was 1 to 65. 85% of participants were older than 16. |
| Interventions |
Bivalent, live, cold‐adapted, aerosol‐administered influenza A vaccine and the commercial inactivated intramuscularly administered influenza vaccine. Schedule and dose were: single dose; cold‐adapted 107 to 107.6 pfu/mL; inactivated 15 µg each strain. Vaccine composition was: cold‐adapted: Kawasaki/9/86 H1N1 and Los Angeles/2/87 H3N2; inactivated: Taiwan/1/86 H1N1 and Sichuan/2/87 H3N2. Placebo was allantoic fluid. Vaccine was recommended and matched circulating strain. |
| Outcomes |
Influenza‐like illness, influenza. They were defined as follows: fever of abrupt onset with at least 1 of the following: chills, headache, malaise, myalgia, cough, pharyngitis, or other respiratory complaints (ILI symptoms retrospectively reported were considered); 4‐fold antibody rise between postvaccination and spring sera. Surveillance was passive. |
| Notes |
Influenza B strain contained in the commercial and monovalent vaccines was not described. Strains used yearly to develop cold‐adapted and inactivated vaccines were antigenically comparable. Since cold‐adapted influenza B vaccines were not sufficiently characterised to include in the study, the authors used monovalent inactivated influenza B vaccine in all participants in the cold‐adapted arm and as placebo in the control group inactivated arm. Only the cold‐adapted comparison was included in the analysis. The circulating strain was Taiwan/1/86 (H1N1) and B/Yamata/16/88. Effectiveness data only were extracted. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
Insufficient description: "permutated block randomization scheme that was stratified by treatment centre and age group" |
| Allocation concealment (selection bias) |
Low risk |
Adequate: participants and clinical staff were kept unaware of the assigned vaccine group through the use of sealed randomisation envelopes that contained vaccines codes. |
| Blinding (performance bias and detection bias)
All outcomes |
Low risk |
Adequate |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
Insufficient description |
| Summary assessment |
Unclear risk |
Unclear |
