Seven RCTs (n=7,021 patients) were included in the review. Six trials used an intention-to-treat analysis. The mean Jadad score was 4 points; no trials were excluded on this basis. Adherence to at least 80% of medication doses ranged from 87.1% to 98.1%. Withdrawal rates ranged from 1 to 10%. Three RCTs assessed zanamivir chemoprophylaxis and four assessed oseltamivir.
Symptomatic influenza: Extended-duration neuraminidase inhibitor treatment decreased the risk of symptomatic influenza (RR 0.26, 95% CI: 0.18 to 0.37; RD -3.9%, 95% CI: -5.8% to -1.9%; six RCTs, n=6,335 patients). There was no evidence of statistically significant heterogeneity (I2 = 0%), and there was no statistically significant difference between zanamivir and oseltamivir.
Asymptomatic influenza virus infection: There was no statistically significant difference between intervention and control groups in asymptomatic influenza virus infection (six RCTs) or in serious adverse events or all adverse events (both seven RCTs). Again there was no evidence of statistically significant heterogeneity and no difference between zanamivir and oseltamivir.
Adverse events: Four trials of oseltamivir reported nausea and vomiting; there was an increased risk of this compared to control groups in these studies (RR 1.48, 95% CI: 1.86 to 2.33; four RCTs, n=1,867). None of the trials was powered to detect rare adverse events. Apart from an increased incidence of nausea and vomiting in a trial of higher dose oseltamivir, there were no significant differences found in any of the subgroup analyses. None of the sensitivity analyses significantly affected the findings.
There was evidence of publication bias on both the funnel plot analysis and the Begg test, although analysis was limited by the small trial numbers.