Summary of findings for the main comparison. Live attenuated influenza vaccine compared to placebo or do nothing for preventing influenza in children.
| Influenza vaccine compared to placebo or do nothing for preventing influenza in children | ||||||
| Patient or population: healthy, community‐dwelling children younger than 16 years of age Setting: influenza seasons in the USA, Western Europe, Russia, and Bangladesh Intervention: live attenuated influenza vaccine Comparison: placebo or do nothing | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Risk with placebo or do nothing | Risk with influenza vaccine | |||||
| Influenza assessed by laboratory confirmation Follow‐up over 1 or 2 influenza seasons |
Low | RR 0.22 (0.11 to 0.41) | 7718 (7 RCTs) | ⊕⊕⊕⊝ MODERATE2 3 | ||
| 130 per 10001 | 29 per 1000 (14 to 53) | |||||
| Moderate | ||||||
| 180 per 1000 | 40 per 1000 (20 to 74) | |||||
| High | ||||||
| 480 per 1000 | 106 per 1000 (53 to 197) | |||||
| Influenza‐like illness assessed by subjective report Follow‐up over a single influenza season |
Low | RR 0.69 (0.60 to 0.80) | 124,606 (7 RCTs) | ⊕⊕⊝⊝ LOW4 5 | ||
| 121 per 10001 | 83 per 1000 (73 to 97) | |||||
| Moderate | ||||||
| 172 per 1000 | 119 per 1000 (103 to 138) | |||||
| High | ||||||
| 341 per 1000 | 235 per 1000 (205 to 273) | |||||
| Otitis media assessed by clinical confirmation (inspection of ear and symptoms) Follow‐up over a single influenza season |
915 per 1000 | 897 per 1000 (869 to 924) |
RR 0.98 (0.95 to 1.01) | 1784 (1 RCT) |
⊕⊕⊕⊝ MODERATE6 | |
| Number of children with time off from school during follow‐up Follow‐up over a single influenza season |
Study population | RR 0.51 (0.22 to 1.19) | 296 (1 RCT) | ⊕⊝⊝⊝ VERY LOW7 8 | ||
| 100 per 1000 | 51 per 1000 (22 to 119) | |||||
| Number of parents having to take off work during follow‐up Follow‐up over a single influenza season |
Study population | RR 0.69 (0.46 to 1.03) | 2874 (2 RCTs) | ⊕⊕⊝⊝ LOW9 1 0 | ||
| 262 per 1000 | 181 per 1000 (121 to 270) | |||||
| Hospitalisation ‐ not reported | ‐ | ‐ | ‐ | ‐ | ‐ | |
| Fever assessed as reported increase in temperature | Temperature rise as an outcome was presented in most of the RCTs, with large differences among trials. Considering only studies reporting raw data for this outcome, the proportion of vaccinated children with fever ranged from 0.16% to 15%, while the proportion of children in the placebo groups with fever ranged from 0.71% to 22%. | ‐ | 20,561 (4 RCTs) |
⊕⊝⊝⊝ VERY LOW11 12 | ||
| Nausea ‐ not reported | ‐ | ‐ | ‐ | ‐ | ‐ | |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
1Control group risks stratified for low‐, moderate‐, and high‐risk groups due to wide variation in event rates across the studies. 2Sensitivity analysis by risk of bias did not change the size or direction of effect. 3Downgraded one level due to serious inconsistency. Although direction of effect across the studies is consistent, there is variation in the magnitude of effect (I2 94%). Statistical variation could not be explained by age or dose. The reasons for wide variation in control group risk could be due to variable viral circulation, but this is uncertain. 4Downgraded one level due to serious risk of bias. Analysis dominated by studies at high or unclear risk of bias for multiple domains. We considered only one study as at low risk of bias. 5Downgraded one level due to serious inconsistency. Direction and magnitude of effect varies between the studies, and there is a high level of statistical heterogeneity (96%). 6Downgraded one level due to serious indirectness. Single study following children over a single influenza season with particularly high rates of otitis media. It is uncertain whether a rate of 92% would be expected over a similar time frame in other settings. 7Downgraded one level due to serious risk of bias. Single study at unclear or high risk of bias for most domains. 8Downgraded two levels due to serious imprecision. The number of events is low, and the confidence interval for the absolute effect is consistent with a small increase and small reduction in school absenteeism. 9Downgraded one level due to serious risk of bias. Of two data sets used from the eligible study, we judged one to be at high risk of bias. 10Downgraded due to serious inconsistency. Study results are discordant in terms of size of reduction in parental working days lost. 11Downgraded due to very serious inconsistency. Proportion of children with fever differed substantially between studies. 12Downgraded due to serious risk of bias. Studies at high or unclear risk of bias across several domains.