title: Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials.
abstract: BACKGROUND
  Despite widespread use, questions remain about the efficacy of oseltamivir in the treatment of influenza. We aimed to do an individual patient data meta-analysis for all clinical trials comparing oseltamivir with placebo for treatment of seasonal influenza in adults regarding symptom alleviation, complications, and safety.
  
  
  METHODS
  We included all published and unpublished Roche-sponsored randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults. Trials of oseltamivir for treatment of naturally occurring influenza-like illness in adults reporting at least one of the study outcomes were eligible. We also searched Medline, PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov trials register for other relevant trials published before Jan 1, 2014 (search last updated on Nov 27, 2014). We analysed intention-to-treat infected, intention-to-treat, and safety populations. The primary outcome was time to alleviation of all symptoms analysed with accelerated failure time methods. We used risk ratios and Mantel-Haenszel methods to work out complications, admittances to hospital, and safety outcomes.
  
  
  RESULTS
  We included data from nine trials including 4328 patients. In the intention-to-treat infected population, we noted a 21% shorter time to alleviation of all symptoms for oseltamivir versus placebo recipients (time ratio 0·79, 95% CI 0·74-0·85; p<0·0001). The median times to alleviation were 97·5 h for oseltamivir and 122·7 h for placebo groups (difference -25·2 h, 95% CI -36·2 to -16·0). For the intention-to-treat population, the estimated treatment effect was attenuated (time ratio 0·85) but remained highly significant (median difference -17·8 h). In the intention-to-treat infected population, we noted fewer lower respiratory tract complications requiring antibiotics more than 48 h after randomisation (risk ratio [RR] 0·56, 95% CI 0·42-0·75; p=0·0001; 4·9% oseltamivir vs 8·7% placebo, risk difference -3·8%, 95% CI -5·0 to -2·2) and also fewer admittances to hospital for any cause (RR 0·37, 95% CI 0·17-0·81; p=0·013; 0·6% oseltamivir, 1·7% placebo, risk difference -1·1%, 95% CI -1·4 to -0·3). Regarding safety, oseltamivir increased the risk of nausea (RR 1·60, 95% CI 1·29-1·99; p<0·0001; 9·9% oseltamivir vs 6·2% placebo, risk difference 3·7%, 95% CI 1·8-6·1) and vomiting (RR 2·43, 95% CI 1·83-3·23; p<0·0001; 8·0% oseltamivir vs 3·3% placebo, risk difference 4·7%, 95% CI 2·7-7·3). We recorded no effect on neurological or psychiatric disorders or serious adverse events.
  
  
  CONCLUSIONS
  Our findings show that oseltamivir in adults with influenza accelerates time to clinical symptom alleviation, reduces risk of lower respiratory tract complications, and admittance to hospital, but increases the occurrence of nausea and vomiting.
  
  
  BACKGROUND
  Multiparty Group for Advice on Science (MUGAS) foundation.
authors: Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
authors: Joanna
authors: J
authors: Dobson
authors: Department of Pediatrics, Microbiology, Medicine and Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Richard J
authors: RJ
authors: Whitley
authors: Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
authors: Stuart
authors: S
authors: Pocock
authors: Department of Epidemiology, University of Michigan School of Public Health, MI, USA. Electronic address: asmonto@umich.edu.
authors: Arnold S
authors: AS
authors: Monto
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*; D008875:Middle Aged; D053139:Oseltamivir / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir