Research in context
Evidence before this study
At the conception of this trial on Jan 15, 2015, we searched PubMed for systematic reviews in any language using the following MEDLINE subject heading keywords: “neuraminidase inhibitors” and “influenza”. A systematic review of placebo-controlled randomised trials found that oseltamivir reduced the median time to alleviation of symptoms over placebo by 17·8 h (95% CI 27·1 to 9·3), and a Cochrane systematic review found oseltamivir reduced time to first alleviation of symptoms by 16·8 h (95% CI 21·8 to 8·4), both in intention-to-treat populations with influenza-like illness. A systematic review and meta-analysis of published and unpublished placebo-controlled trials in adults with suspected or confirmed influenza found a mean reduction in duration of symptoms from oseltamivir of 20·7 h (95% CI 13·3–28·0) in five studies that included 3833 participants in an intention-to-treat population, and a mean reduction of 25·4 h (95% CI 17·2–33·5) in the intention-to-treat infected population (7 studies, 2690 patients), a difference of about 5 h. Trials have found relatively greater benefits in individuals treated within 24 h of symptom onset, and guidelines recommend initiating oseltamivir within 48 h of symptom onset. Some of the trials included in the systematic reviews have been criticised for under-recruiting, selective reporting of outcomes, not including sufficient children or older people, and recruiting in a single season. Additionally, the effects of antiviral treatment on return to daily activities, quality of life, and care-seeking in key subgroups is largely unknown.
Added value of this study
In an open-label, pragmatic, randomised controlled trial that included 3266 adults and children presenting in primary care with influenza-like illness, patients treated with oseltamivir recovered sooner, irrespective of influenza virus test results. Older, sicker, patients with comorbidities and longer previous symptom duration showed greater absolute benefit. Our overall estimate of benefit is similar to effects found in placebo-controlled trials, but we identified additional benefit in those with certain risk factors. Previous trials have found relatively greater benefit in those treated within 24 h of symptom onset, but additional benefit from earlier treatment was not apparent in our trial. Similarly, unlike some trials, benefit in our trial was similar regardless of influenza test results.
Implications of all the available evidence
Adding oseltamivir to usual primary care for patients with influenza-like illness accelerates recovery by a mean of about one day, and slightly longer in individuals with risk factors, irrespective of influenza status. Initiating oseltamivir 48–72 h after illness onset appears to give similar benefit to earlier initiation. Clinicians might consider treatment in patients who are sicker or older, who have comorbidities, and who have been unwell for longer, because oseltamivir might reduce their illness by as much as 2–3 days.