Effectiveness of oseltamivir in adults: a meta-analysis of published and unpublished clinical trials

Oseltamivir is widely used for the treatment of influenza. Previous systematic reviews suggest that they reduce complications, but had significant methodologic limitations. To assess the effect of oseltamivir on duration of symptoms, complications and hospitalizations in adults. We searched Medline without time or language restrictions, and trial registries maintained by the manufacturer. We included published and unpublished randomized double-blinded, placebo-controlled trials of oseltamivir in adults with suspected influenza that reported duration of symptoms, complications or hospitalizations. We abstracted data regarding study quality, the duration of symptoms and rates of complications and hospitalization. Three published and eight unpublished studies met our inclusion criteria. For the intention-to-treat (ITT) population, the mean reduction in the duration of symptoms was 20.7 hours [95% confidence interval (CI) 13.3 to 28.0 hours]. Two large unpublished studies in the elderly and in adults with chronic disease did not find a significant reduction in the symptom duration. There was no difference in the likelihood of hospitalization in the ITT population (33/2633 patients for oseltamivir versus 20/1694 for placebo). The rate of complications in the intention-to-treat infected (ITTI) population was reduced when acute bronchitis was included (2.8%, 95% CI 0.6 to 4.9), but not when it was excluded. The risk of pneumonia was reduced in the ITTI population (0.9%, 95% CI 0.1 to 1.7) but not in the ITT population. There is no evidence that oseltamivir reduces the likelihood of hospitalization, pneumonia or the combined outcome of pneumonia, otitis media and sinusitis in the ITT population.