Sample size evaluation assumed that virological response was obtained in 70% of patients in the oseltamivir-zanamivir arm, compared to 55% in each of monotherapy arms on the basis of the extrapolation of the results of previous trials [2, 4] . Samples of 300 subjects per arm had 90% power to detect this difference, with a two-sided test and a type I error of 0.025 because of the two tests (factoring 20% lack of follow-up). Proportions of response at day 2 were compared between the combination therapy arm (OZ) and each monotherapy arm (O or Z) separately using two tests with a type I error of 0.025 because of the two tests. Patients without a day 2 sample were considered treatment failures. Mean decreases of log 10 viral load were compared using a t-test in patients who had both day 0 and day 2 samples assuming a value of 0.5 cgeq/ml when RT-PCR was negative. For clinical endpoints nonparametric tests were used. Times to resolution of illness and symptoms score at the end of treatment were compared using Wilcoxon tests. If time to symptom alleviation was missing it was imputed to be 14 d, i.e., the end of the trial; 95% confidence intervals (95% CIs) of median differences were estimated by bootstrap. Probability of symptoms alleviation versus day of treatment was estimated using the Kaplan Meier method and was compared between groups with the log-rank test. Proportions of clinical events and of patients with alleviation of symptoms were compared using Fisher's exact tests. As an exploratory analysis, 95% CIs for differences of response between the two monotherapies were also estimated. All analyses were performed using SAS software, version 9.1 (SAS Institute). 