The most thorough analysis of oseltamivir (marketed as Tamiflu) data to date, including all available published and unpublished randomised treatment trials of adults, suggests that the antiviral drug shortens the duration of flu symptoms by about a day, compared to placebo, in adults with laboratory-confirmed influenza.

The results, published in The Lancet, also indicate that oseltamivir significantly reduces the risk of influenza complications requiring antibiotics (such as pneumonia) and hospitalisations in adults infected with influenza.

For the first time, the meta-analysis includes individual patient data from all published and unpublished trials (made available by the manufacturer Roche). The study was conducted by an independent research group led by Arnold Monto, Professor of Epidemiology at the University of Michigan School of Public Health, USA, and Stuart Pocock, Professor of Medical Statistics at the London School of Hygiene & Tropical Medicine, UK.

Monto, Pocock, and colleagues analysed data from nine trials comparing the licensed 75mg dose of oseltamivir with placebo for the treatment of seasonal influenza in 4328 adults between 1997 and 2001.

They found that treating adults with laboratory-confirmed influenza with oseltamivir reduced the duration of symptoms by 21% compared with placebo (from 123 hours to 98 hours). However, no benefit was noted in adults without influenza virus infection.

The analysis confirmed that oseltamivir treatment results in a significantly increased risk of nausea (absolute increase 3.7%) and vomiting (4.7%) compared with placebo. The authors noted no difference between the groups in neurological and psychological disorders in this setting, which have previously been linked with the drug.

Although rates of complications were low, oseltamivir reduced the risk of lower respiratory tract infections requiring antibiotics more than 48 hours after study entry by 44% compared with placebo (4.9% vs 8.7%), and hospital admission for any cause by 63% (0.6% vs 1.7%) in adults with laboratory-confirmed influenza.

According to Monto, "The safety and effectiveness of oseltamivir has been hotly debated, with some researchers claiming there is little evidence that oseltamivir works. Our meta-analysis provides compelling evidence that oseltamivir therapy reduces by one day the typical length of illness in adults infected with influenza and also prevents complications and reduces the number of people needing hospital treatment. Whether the magnitude of these benefits outweigh the harms of nausea and vomiting needs careful consideration."*

Writing in a linked Comment, Heath Kelly from the Australian National University in Canberra and Benjamin Cowling from The University of Hong Kong say, "The rational use of oseltamivir is becoming clear…Because benefits accrue only to patients with laboratory-confirmed influenza, but the risk of adverse events is increased in all patients, rapid diagnostic testing, if available, is advisable before oseltamivir administration in routine clinical practice…In a pandemic or severe epidemic, oseltamivir can be used presumptively when there is a high probability that influenza-like illness is caused by influenza virus infection and when the outcome of infection is likely to be severe, but a proven strategy for rapid distribution needs to accompany any plan that proposes widespread use of oseltamivir."

In a pandemic or severe epidemic, oseltamivir can be used presumptively when there is a high probability that influenza-like illness is caused by influenza virus infection and when the outcome of infection is likely to be severe, but a proven strategy for rapid distribution needs to accompany any plan that proposes widespread use of oseltamivir."