We have also rewritten the objective twice, tightening up the text to bring it in line with our initial intentions and clarifying its meaning. comments TBA-354 (regulatory information). Design Systematic review of regulatory information. Data sources Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers. Eligibility criteria for selecting studies Randomised placebo controlled trials on adults and children who had confirmed or suspected exposure to natural influenza. Main outcome measures Time to first alleviation of symptoms, influenza outcomes, complications, admissions to hospital, and adverse events in the intention to treat population. Results From the European Medicines Agency and Roche, we obtained clinical study reports for 83 trials. We included 23 trials in stage 1 (reliability and completeness screen) and 20 in stage 2 (formal analysis). In treatment trials on adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval 8.4 to 25.1 hours, P 0.001). There was no effect in children with asthma, but there was an effect in TBA-354 otherwise healthy children (mean difference 29 hours, 95% confidence interval 12 to 47 hours, P=0.001). In treatment trials there was no difference in admissions to hospital in adults (risk difference 0.15%, 95% confidence interval ?0.91% to 0.78%, P=0.84) and sparse data in children TBA-354 and for prophylaxis. In adult treatment trials, oseltamivir reduced investigator mediated unverified pneumonia (risk difference 1.00%, 0.22% to 1 1.49%; number needed to treat to benefit (NNTB) 100, 95% confidence interval 67 to 451). The effect was not statistically significant in the five trials that used a more detailed diagnostic form for pneumonia, and no clinical study reports reported laboratory or diagnostic confirmation of pneumonia. The effect on unverified pneumonia in children and for prophylaxis was not significant. There was no significant reduction in risk of unverified bronchitis, otitis media, sinusitis, or any complication classified as serious or that led to study withdrawal. 14 of 20 trials prompted participants to self report all secondary illnesses to an investigator. Oseltamivir in the treatment of adults increased the risk of nausea (risk difference 3.66%, 0.90% to 7.39%; number needed to treat to harm (NNTH) 28, 95% confidence interval 14 to 112) and vomiting (4.56%, 2.39% to 7.58%; 22, 14 to 42). In treatment of children, oseltamivir induced vomiting (5.34%, 1.75% to 10.29%; 19, 10 to 57). In prophylaxis trials, oseltamivir reduced symptomatic influenza in participants by 55% (3.05%, 1.83% to 3.88%; NNTB 33, 26 to 55) and households (13.6%, 9.52% to 15.47%; NNTB 7, 6 to 11) based on one study, but there was no significant effect on asymptomatic influenza and no evidence of a reduction in transmission. In prophylaxis studies, oseltamivir increased the risk of psychiatric adverse events during the combined on-treatment and TBA-354 off-treatment periods (risk difference 1.06%, 0.07% to 2.76%; NNTH 94, 36 to 1538) and there was a dose-response effect on psychiatric events in two pivotal treatment trials of oseltamivir, at 75 mg (standard dose) and 150 mg (high dose) twice daily (P=0.038). In prophylaxis studies, oseltamivir increased the risk of headaches on-treatment (risk difference 3.15%, 0.88% to 5.78%; NNTH 32, 18 TBA-354 to 115), renal events with treatment (0.67%, ?0.01% to 2.93%), and nausea while receiving treatment (4.15%, 0.86% to 9.51%; NNTH 25, 11 to 116). Conclusions In prophylactic studies oseltamivir reduces the proportion of symptomatic influenza. In treatment studies it also modestly reduces the time to first alleviation of symptoms, but it causes nausea and vomiting and increases the risk of headaches and renal and psychiatric syndromes. The evidence of clinically significant effects on complications and viral transmission is limited because of rarity of such events and problems with study design. The trade-off between benefits and harms should be borne in mind when Igfbp1 making decisions to use oseltamivir for treatment, prophylaxis, or stockpiling. Introduction Influenza antivirals (oseltamivir and zanamivir of the neuraminidase inhibitor class) are commonly used and stockpiled drugs employed against seasonal and pandemic influenza on the basis of international and national recommendations; these recommendations partly justified by the claimed and assumed ability of oseltamivir to reduce complications and transmission of influenza.1 2 3 In theory, containing the spread of influenza allows time for an organised response with longer term interventions (such as vaccines), which take time to produce.3.