Eight studies were included: 6 RCTs (n=190,288) and 2 quasi-RCTs (n=175,080). In total 185,138 children received the Hib vaccine and 180,230 remained unvaccinated. Two of the RCTs were cluster randomised by either district or health centre. The authors also found two unpublished abstracts, which were not included in the analysis but are mentioned in the discussion.
Four trials were carried out in the USA and one each in Finland, the UK, Chile and Gambia. The overall mean protective efficacy of the vaccine against invasive Hib (8 trials) was 84% (OR 0.16, 95% CI: 0.08, 0.31). However, there was significant heterogeneity (chi-squared 23.03, P=0.0008, I-squared 73.9%) due to one study carried out in Alaska. When this study was removed, the protective efficacy against invasive Hib was 86% (OR 0.14, 95% CI: 0.09, 0.20; chi-squared 7.31, P=0.20).
Against meningitis (4 trials) the protective efficacy was 75% (OR 0.25, 95% CI: 0.08, 0.84), and against bacterial pneumonia (4 trials) it was 69% (OR 0.31, 95% CI: 0.10, 0.97). Only 2 trials reported all-cause mortality, and the overall protective efficacy in these trials was 6% (OR 0.94, 95% CI: 0.74, 1.19). None of the trials reported data on Hib-specific mortality.
Adverse events were reported in 6 studies, but were mainly mild and transient with similar event rates being reported in both the vaccine and control groups. In general, serious adverse events were rare.
Subgroup analyses showed differences in the overall protective effect against invasive Hib which was dependent on: the number of doses used (one versus two doses); when the first dose was administered (2 months old versus 3 months old); baseline risk for Hib; and type of conjugate vaccine administered. With the exception of age at first dose, the differences were usually small. There were no differences in the overall efficacy between developing and developed countries, and none of the studies reported the HIV status of the children.
The only factor included in the sensitivity analysis that changed the overall protective efficacy against Hib was the presence or absence of double-blinding.