Thirteen RCTs (13,515 patients) were included in the review. Seven trials were undertaken in adults aged 18 to 60 years, four trials were undertaken in adults aged more than 60 years, one trial did separate analyses for older and younger participants (≤60 years and >60 years) and one trial did a separate analysis for older adults only (>60 years). Nine trials had an overall Jadad score of 3 and four trials had an overall Jadad score of 1. No trials were double blinded.
Efficacy in patients 18 to 60 years old: In seven out of eight studies, geometric mean titre ratio, seroconversion rates and seroprotection rates were comparable between groups. In one study, patients with intramuscular vaccines had significantly higher geometric mean titre ratio, seroconversion rates and seroprotection rates than patients with intradermal vaccines; this was except for seroconversion rates for H1N1 and H3N2 strains in those with a pre-vaccination titre less than 10 and seroprotection rate for H1N1.
Efficacy in patients more than 60 years of age: In four out of six studies, geometric mean titre ratio, seroconversion rates and seroprotection rates were comparable between groups. In two studies, compared to the intramuscular group the intradermal group had significantly higher geometric mean titre ratio, seroconversion and protection rates.
Safety: In all studies, rates of adverse events in the first three days were generally comparable between intradermal and intramuscular vaccine administration. In 13 studies, some local adverse events that occurred within the first seven days, such as erythema, swelling, induration and pruritis, were significantly more frequent in the intradermal group when compared to the intramuscular group. There was no evidence of a difference in the rates of ecchymosis or pain at the injection site between groups.