aa Clover 1991.
| Methods | Multicentre, cluster‐randomised, placebo‐controlled clinical trial in which the efficacy of bivalent cold‐adapted and trivalent inactivated influenza vaccines were compared. 70% of the study population had already been immunised in the previous aa Gruber 1990, whose participants were enrolled at the same centres and which was carried out during the previous year. Design and methods of enrolment are similar to those adopted in that study. | |
| Participants | 103 families were enrolled from Houston Family Study, Baylor Family Practice Clinic (Houston), and Family Medicine Clinic (University of Oklahoma). They were randomly assigned to receive placebo (40%) or 1 of the 2 vaccines (each 30%). About 70% of the families were enrolled and randomised the previous year and received the same preparation. The entire study population consisted of 166 adults and 225 children. 98 families with 157 adults and 192 children aged almost 3 years and 20 children younger than 3 years completed the study. | |
| Interventions | Bivalent cold recombinant influenza A vaccine containing 107 TCID50 of CR – 90 (A/Bethesda/1/85 H3N2) and 10 7 TCID 50 of CR – 98 (A/Texas/1/85 H1N1) in 0.5 mL. 1 dose intranasally administered.
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| Outcomes |
Serological
Children receiving vaccine or placebo were brought in 3 to 4 weeks after vaccination to obtain a second blood specimen to determine antibody responses to vaccine antigens. However, paired sera were taken from 112 children, with no explanation as to why. Effectiveness
When ongoing community surveillance at the Influenza Research Center indicated that influenza virus was spreading in the community (influenza A/Taiwan/86), weekly telephone contacts to families were made to evaluate respiratory illnesses. Home or clinic visits were scheduled for physical examination and collection of nasal washes or swab specimens for viral isolation. An illness was attributed to influenza A infection if influenza virus was isolated during the illness or, for a person with a postseason antibody rise only, if no other virus was detected in the illness specimen and if the illness occurred within 10 days of an isolate in household contact or during the period of most intense influenza activity in the community. Illnesses were characterised by review of records, which included date of onset, symptoms, physical signs diagnosis of each contact. Safety N/A |
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| Funding Source | Unclear | |
| Notes | The authors conclude that TIV provided better protection against detectable infection in older children (P > 0.1 TIV versus placebo) than CR vaccine, which instead was more protective in younger children (however, based on a denominator of 27, 35, and 51 CR, TIV, and placebo recipients). There were no statistical differences in infection rates for family contacts of children receiving TI or CR or placebo. Analysis seems to have been done at individual level, whereas randomisation was at cluster level. The authors report that the vaccines were ineffective in preventing transmission. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No description |
| Allocation concealment (selection bias) | Unclear risk | Not used |
| 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 | Unclear risk | Plausible bias that raises some doubt about the results |