Experts call for tests on use of flu drugs in pandemic

New trials are urgently needed to establish whether the anti-flu drug Tamiflu would help save lives in a pandemic, experts have said.

Flu pandemics are highly dangerous, with the potential to kill millions around the world. Each winter in the UK, hundreds die of flu. Yet the drugs available to treat people, of which the best known and most widely used is Tamiflu, appear to have only a modest effect and have only been tested on seasonal flu, according to a report by the Academy of Medical Sciences and the Wellcome Trust.

The senior doctors on the review panel urge that plans should be put in place to test whether the drugs would work in a pandemic. That could involve people who go to their GP with flu symptoms being randomly assigned either Tamiflu, nothing at all, or an alternative such as paracetamol to deal with the symptoms.

The panel concluded that there was sufficient evidence that Tamiflu helps those who are hospitalised with severe flu to recover, as long as it is given within 48 hours of their symptoms developing. Trials in hospitals are still needed because doctors have only limited data, but nobody taking part would be denied Tamiflu. The study might, for example, compare two groups of patients given different doses.

“Of all the infectious diseases, influenza is the one I would worry about the most,” said Jeremy Farrar, director of the Wellcome Trust. A flu virus that causes a pandemic will have crossed from animals, such as chickens and pigs, with a capacity to spread among humans. The last outbreak of bird flu killed 60% of those who caught it.

Farrar said he did not think it would be ethical for hospitals to compare randomly chosen patients with severe flu given Tamiflu with others given a placebo, because of the evidence that it can shorten a bout of illness. But there was an absence of good data to show how well Tamiflu works in the community. “I think it would be unethical not to conduct these studies, given the uncertainties,” he said.

Tamiflu was stockpiled by the UK government and others around the world in readiness for the swine flu epidemic on the basis of evidence from trials conducted by Roche, the manufacturer. But there has been controversy since then as investigators have reanalysed the trials and successfully fought for access to the detailed data from them.

In April 2014, the Cochrane collaboration published the results of an extensive review of the trials of Tamiflu and a similar drug, Relenza, made by GlaxoSmithKline, carried out during seasonal flu outbreaks. They found that the drugs reduced flu symptoms if given within 48 hours, but did not help keep people out of hospital.

An opportunity was lost during the 2009 swine flu pandemic, when many people were told to stay at home and take Tamiflu. Trials could have been conducted to find out whether the drugs help reduce the toll of the disease, but they were not. Launching trials in a pandemic is fraught with difficulty because of the bureaucratic hurdles that have to be crossed. But against all the odds, drugs trials were launched for the first time in an epidemic when Ebola was ravaging west Africa, encouraging scientists to attempt it in flu.

“We don’t know whether we did the right thing or not [during the swine flu outbreak],” said Chris Butler, professor of primary care at Oxford University, who was on the panel. “At the moment it takes years to set up a trial. The population of Britain is suffering from a lack of evidence because we can’t set up trials quickly enough when you need them. It is a huge pity that we haven’t made the most of our opportunity to generate evidence.”

He is now involved in trying to set up an EU-funded trial of Tamiflu in 20 separate sites across Europe, with the aspiration to modify the trial as it goes along if the winter’s seasonal flu takes an epidemic turn. He hopes it will be “a platform for moving seamlessly into a pandemic, should one emerge”.

Carl Heneghan, professor of evidence-based medicine at Oxford University and one of the Cochrane investigators, said: “The misinterpretation of the evidence to date has wasted scarce resources and led to widespread confusion. Use of antivirals in a pandemic would not be based on the best available evidence, but principally on poor-quality evidence and opinion. This is primarily due to the failure to undertake trials in the last outbreak.”

Antiviral drugs such as Tamiflu are not beneficial in seasonal flu, he said. “There is an urgent need to know whether antivirals work in hospitalised patients. To ensure we best serve patients, and to reduce any further uncertainties, trials in hospitalised patients should be done independently and results [be] published in full.”