This review suggested that vaccination in healthy children over the age of 2 years is effective in the prevention of both clinical and laboratory-confirmed cases of influenza, as well as acute otitis media. However, the authors' pooled estimates may not be reliable given the apparent statistical and clinical variation between the studies.

To evaluate the efficacy of influenza vaccinations in healthy children.

MEDLINE, EMBASE and the Cochrane Library were searched up to May 2005; the search terms were reported. In addition, the reference lists of relevant articles including reviews and meta-analyses were checked. All languages were included.

Study designs of evaluations included in the review

Randomised controlled trials (RCTs) or quasi-RCTs were eligible for inclusion in the review.

Specific interventions included in the review

Studies comparing any influenza vaccine with placebo, a control vaccine or no intervention were eligible for inclusion. The majority of the included studies assessed parenteral inactivated vaccines and the rest assessed live aerosol vaccines; most vaccines complied with official recommendations and matched circulating influenza virus strains.

Participants included in the review

Studies where more than 70% of the participants were healthy children (aged 18 years or younger) were eligible for inclusion. The age of the included participants ranged from 6 months to 18 years. The majority of the trials were carried out in the USA, with the remainder mainly carried out in the former Soviet Union.

Outcomes assessed in the review

Eligible studies had to report the number of clinically-confirmed or laboratory-confirmed cases of influenza (CCCs or LCCs respectively) or the incidence of acute otitis media (AOM). The majority of the studies reported either CCCs or LCCs and less than half of the studies reported the incidence of AOM.

How were decisions on the relevance of primary studies made?

Two reviewers independently assessed the eligibility of the studies; both reviewers were blinded to the authors, institution and journal.

The studies were assessed using three published scales: Chalmers (assessing several items; scores ranging from 0 to 1), Jadad (assessing randomisation, masking and drop-outs and withdrawals; scores ranging from 0 to 5) and Schultz (assessing randomisation, allocation concealment and double-blinding). The authors did not state how many reviewers performed the assessment.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for each trial.

How were the studies combined?

The studies were grouped by outcome and pooled RRs with 95% CIs calculated using both random-effects and fixed-effect models; the reported results focused on the random-effects models. Publication bias was assessed using funnel plots, the Egger regression asymmetry test and the Begg adjusted rank correlation test.

How were differences between studies investigated?

Heterogeneity was assessed using the I-squared statistic. In addition, meta-regression was used to assess the effects of multiple covariates including elements of study quality; subgroup analyses and sensitivity analyses were used to investigate the effects of other study variables.

Twenty-one articles, which were split into 32 sub-studies (number of cases unclear) were eligible for inclusion in the review.

The mean quality score was 0.37 (range: 0.13 to 0.72) when using the Chalmers scale and 2.0 when using the Jadad scale. Overall, few trials reported adequate methods for randomisation and allocation concealment and few were truly double-blind according to the criteria of Chalmers and Jadad. Only 5 studies adequately considered the issue of withdrawals and drop-outs.

Incidence of LCCs of influenza (18 comparisons, n=8,574).

There were significantly fewer LCCs in children receiving vaccinations as compared with control groups (RR 0.33, 95% CI: 0.22, 0.49, p<0.00001; I-squared 87.2%).

Incidence of CCCs of influenza (19 comparisons, n=247,517).

There were significantly fewer CCCs in children receiving vaccinations as compared with control groups (RR 0.64, 95% CI: 0.60, 0.69, p=<0.00001; I-squared 88.9%).

Incidence of AOM (11 comparisons, n=11,349).

There were significantly fewer cases of AOM in children receiving vaccinations as compared with control groups (RR 0.49, 95% CI: 0.30, 0.79, p=0.004; I-squared 82.5%).

Subgroup and sensitivity analyses.

Factors that were found to affect the efficacy of vaccination included the participants' age, study quality (e.g. double-blinding, allocation concealment), and whether or not the study was carried out in the former Soviet Union. However, the effects varied across outcomes, and many of the subgroup and sensitivity analyses showed significant heterogeneity.

The funnel plot showed some evidence of potential publication bias for studies assessing CCCs and AOM, but the Begg and Egger tests for publication bias were not significant for trials that assessed CCCs. Only the Egger test found significant asymmetry for studies assessing AOM.

This review suggested that vaccination in healthy children over the age of two is effective in the prevention of both CCCs and LCCs, as well as AOM. There is insufficient evidence to determine the effects of vaccination in children aged 2 years or younger.

This review was based on a clearly defined review question. An adequate search appears to have been conducted for published literature in any language, but there appears to have been no specific attempt to locate unpublished studies, which may suggest a risk of publication bias. Attempts to investigate publication bias were inconclusive and, given the low number of included studies, the reviewers' statistical assessments of publication bias may be underpowered. Some attempt was made to reduce the risk of error and bias during the selection of the studies, but it is unclear whether similar attempts were made when assessing the quality of the studies and extracting the study data. Study quality was assessed using appropriate scales and the effects of varying quality was assessed in subgroup and sensitivity analyses. The effects of other study variables and potential sources of heterogeneity were also examined. Few individual study details were reported although additional information is available online (accessed 08/04/2008); a subscription may be required for access. Given the level of statistical heterogeneity between studies, the findings of the review should be interpreted with caution.

Practice: The authors stated that this review supports vaccination as a possible option for the prevention of influenza in healthy children.

Research: The authors did not state any implications for research; however, they did highlight in their conclusions a lack of evidence available for children aged 2 years and younger.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.