aa Alexandrova 1986.
| Methods | C‐RCT possibly followed by 2 cohort studies | |
| Participants | Nearly 30,000 schoolchildren (aged 7 to 15) and preschool children (aged 3 to 6). The units sampled were schools and kindergartens. The samples were performed using random sampling numbers and stratified sampling in schools with different numbers of children. Initially reactogenicity of the vaccine was studied on a limited group of schoolchildren (190) and children between 3 and 6 years (267). After the low reactogenicity of the vaccine was assessed, vaccination of large groups of children was undertaken. The trial was extended to 45 schools (in 26 the bivaccine was administered, in 19 placebo) and to 142 community preschools (children from 76 preschools received vaccine, those from the other 66 received placebo). For each child a special form was completed in which data about immunisation and diseases were registered. No influenza was registered before the vaccination was carried out. | |
| Interventions | A reactogenicity study was carried out separately on a limited study population (those vaccinated in October 1982). This group consisted of 457 pupils and children who were divided into 2 groups. One group was given vaccine, the other received placebo. Cases of mild, moderate, or febrile reaction within 5 days of administration of vaccine or placebo were reported in consideration of the initial anti‐HA antibody level. These data were not considered because it is likely that the treatments were not randomly assigned. | |
| Outcomes | Incidence of influenza and acute respiratory disease during influenza epidemic 15 March to end of April 1983 Serological Antibody titres carried out on a non‐random section of the study population Effectiveness The prophylactic effectiveness of the bivaccine was estimated during an influenza epidemic caused by viruses A/Brazil/11/78 H1N1 and A/Bangkok/1/79 H3N2 (similar to the strains employed in the vaccine), which started in the middle of March 1983 and lasted for 6 weeks. The comparison of the influenza morbidity rates among vaccines and control groups of children were based on clinical diagnosis during the epidemic period. Safety
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| Funding Source | Government | |
| Notes | 3 studies are reported in this paper. The first is a phase ll, 5‐day reactogenicity and safety trial carried out in 284 placebo recipients and 173 vaccine recipients. Although randomisation is claimed, it is unclear why the imbalance in numbers and due to unclear text we classified it as a C‐RCT. There appears to be an extension of the safety data to 14,228 placebo and 15,727 vaccine recipients. The second study (1 October 1982 to 14 March 1983) appears to be an extension of the first study, assessing effectiveness in 3538 bivalent vaccine recipients and 3271 placebo recipients. However, in the absence of influenza viral circulation, the vaccine appears to be highly effective against ILI, bronchitis, pneumonia, OM, and tonsillitis. A third study is the extension by 6 weeks (from 14 March 1983 of the second study) during the influenza epidemic. As the denominators are different in all 3 studies and the text is unclear, it is very difficult to classify study design. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Cluster‐randomisation: random sampling numbers and stratified sampling were used |
| Allocation concealment (selection bias) | Low risk | Both vaccine and placebo batches were coded. |
| Blinding (performance bias and detection bias) All outcomes | Low risk | Double‐blinding |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Number lost to follow‐up is unknown. |
| Summary assessments | Low risk | Plausible bias unlikely to seriously alter the results. |