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2,000 people across 16 countries have signed up to the world's largest clinical trial on oseltamivir in primary care, led in the UK by the Primary Care Clinical Trials Unit. © Shutterstock
By providing evidence through a study of this scale, the results will be of great interest to governments, policy makers, companies, practitioners, and members of the public.
- Professor Chris Butler, University of Oxford

2,000 people have been recruited into the world’s largest clinical trial to test the clinical and cost effectiveness of the controversial flu drug oseltamivir (Tamiflu) in primary care. The trial aims to clear up the widespread uncertainty over whether people with flu symptoms should be treated with antiviral drugs in the community.

Led in the UK by researchers in Oxford University’s Nuffield Department of Primary Care Health Sciences, the ALIC4E trial investigates whether oseltamivir is cost effective and beneficial to patients consulting their General Practitioner with flu symptoms. In particular, it will understand if older people, infants, people with other health conditions, those treated early, or those with particularly severe flu can benefit from the treatment.

ALIC4E is the first publically funded randomised controlled trial of its kind to assess antiviral treatment for influenza in primary care. It is a collaboration between researchers in the UK, The Netherlands and Belgium and aims to recruit a total of 4,500 participants across 16 countries.

Since launching in 2015, 324 participants have been recruited across England and Wales - 138 in Oxford, 86 in Southampton and 100 in Cardiff, with the trial as a whole reaching the milestone of 2000 participants this week.

The trial is an initiative of the Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium. Funded by the European Commission's FP7 Programme, PREPARE was set up to support research organisations to respond rapidly to pandemics with clinical studies that can provide real-time evidence to inform the public health response.

The antiviral oseltamivir is a member of a class of drugs called neuraminidase inhibitors. These drugs are stockpiled and recommended by public health agencies worldwide for treating and preventing severe outbreaks of seasonal and pandemic influenza, yet some experts suggest the evidence supporting their use is lacking. The drug was widely used during the ‘swine ‘flu’ pandemic, for example, but no trial was done of its clinical and cost effectiveness.

Lead investigator Professor Chris Butler, a salaried GP in the Cwm Taf University Health Board in Wales and Professor of Primary Care at the University of Oxford’s Nuffield Department of Primary Care Health Science, said:

“We are celebrating an incredible international achievement of having recruited over 2,000 patients into the critically important ALIC4E study.  Especially when there seems to be a particularly widespread flu outbreak, it’s a real shame that we don’t confidently know which people with symptoms of the flu should be prescribed antiviral drugs, and the cost-effectiveness of this treatment in terms of helping people return to their usual activities. 

“The resource implications for the health service and implications for patient well-being are considerable, especially given the debate around the effectiveness of antiviral treatment for influenza. By providing evidence through a study of this scale, the results will be of great interest to governments, policy makers, companies, practitioners, and members of the public.

“We urgently need rapid response studies like ALIC4E embedded in everyday general practice to guide care for common and potential serious conditions, and address the questions that matter most to patients. The European Union has shown tremendous foresight in funding the Europe-wide PREPARE consortium to generate this unique evidence and ensure primary care is better equipped to respond to a flu outbreak.”

Professor Theo Verheij, of the Department of General Practice at the University Medical Center Utrecht, The Netherlands, ALIC4E’s co-lead investigator, said:

“General Practitioners and patients in 16 countries are contributing to this critically important study that is unique in many ways: it is the biggest randomised trial so far of oseltamivir for influenza-like illness in primary care, so will give us much needed, real-world evidence about the cost effectiveness of using it overall and especially in patients with certain characteristics. The result will hugely reduce uncertainty about drug treatment for flu.”

Professor Herman Goossens, Professor of Microbiology at the University of Antwerp, Belgium and Coordinator of the PREPARE Consortium said:

“Not only will ALIC4E fill huge gaps in the evidence base that supports the treatment of influenza, ALIC4E; and the PREPARE Consortium are developing the infrastructure and methods for delivering studies during both infectious epidemics and pandemics. Europe is leading the way in being able to implement research more quickly and efficiently, to give us answers about treatment that will help patients far more quickly than before. 

“Our aim is to be able to offer people the opportunity to participate in clinical trials within two weeks of a pandemic emerging, so that evidence from such trials can inform care during the pandemic itself. Until now, we only figure out what was best care once the pandemic is over, if at all.”

In the UK, people with influenza-like illness are eligible to participate in the trial if they have experienced flu symptoms for less than 72 hours and are being cared for by a general practice that is part of the study in Oxfordshire, Hampshire or South Wales. 

Across Europe, ALIC4E is recruiting patients in Belgium, the Czech Republic, Denmark, France, Greece, Hungary, Republic of Ireland, Lithuania, The Netherlands, Norway, Poland, Spain, Sweden, Switzerland, England, and Wales.  The study is managed in the UK by Oxford University's Primary Care Clinical Trials Unit.

PREPARE is funded by the European Commission's FP7 Programme under grant number 602525.

Read more:

Blog: Should flu symptoms be treated with antivirals in primary care?
Professor Chris Butler blogs about the ALIC4E study on the University of Oxford Science Blog.


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