Researchers who have fought for years to get full data on Roche's flu medicine Tamiflu said on Thursday that governments who stockpile it are wasting billions of dollars on a drug whose effectiveness is in doubt.
In a review of trial data on Tamiflu, and on GlaxoSmithKline's flu drug Relenza, scientists from the respected research network the Cochrane Review said that while the medicines can shorten flu symptoms by around half a day, there is no good evidence behind claims they cut hospital admissions or lessen complications of the disease.
"There is no credible way these drugs could prevent a pandemic," said Carl Heneghan, one of the lead investigators of the review and a professor of evidence-based medicine at Britain's Oxford University.
The review's main findings were that the medicines had few if any beneficial effects, but did have adverse side effects that were previously dismissed or overlooked.
"Remember, the idea of a drug is that the benefits should exceed the harms," Heneghan said. "So if you can't find any benefits, that accentuates the harms."
Yet Roche, which has been under fire for several years over its refusal to allow the Cochrane team unrestricted access to Tamiflu data, rejected the findings, saying it "fundamentally disagrees with the overall conclusions" of their study.
"We firmly stand by the quality and integrity of our data ... and subsequent real-world evidence demonstrating that Tamiflu is an effective medicine in the treatment and prevention of influenza," it said in a statement.
Tamiflu sales hit almost $3 billion in 2009 - mostly due to its use in the H1N1 flu pandemic - but they have since declined.
The drug, one of a class of medicines known as neuraminidase inhibitors, is approved by regulators worldwide and is stockpiled in preparation for a potential global flu outbreak. It is also on the World Health Organization's "essential medicines" list.
The United States has spent more than $1.3 billion buying a strategic reserve of antivirals including Tamiflu, while the British government has spent almost $703 million (424 million pounds) on a stockpile of some 40 million Tamiflu doses.
"Down the drain"
Heneghan's team say their analysis is the first based on full data - from 20 trials of Tamiflu, known generically as oseltamivir, and 26 trials of Relenza, also known as zanamivir.
At a briefing in London about their findings, Heneghan said the money spent on stockpiles "has been thrown down the drain" because, until now, the full data had not been seen by regulators, governments, doctors or patients.
"The original evidence presented to government agencies around the world was incomplete," said Fiona Godlee, editor of the British Medical Journal which has spearheaded a four-year campaign to force Roche to reveal all its Tamiflu data.
"And when they (the Cochrane review team) eventually received the full information on these drugs, the complete evidence gives a very much less positive picture."
But the European Medicines Agency (EMA) - which approved the drug for sale in Europe - disputed the claim they had not seen all the Tamiflu data.
Enrica Alteri, head of medicines evaluation, said EMA had seen and reviewed all 20 studies referred to in the review, and this new analysis did not raise any fresh concerns or alter the agency's assessment that Tamiflu's benefits outweigh its risks.
Wendy Barclay, a flu expert at Imperial College London with no links to the Cochrane Review or the drugs, said she still felt the benefits were worthwhile, particularly in a pandemic.
"If another pandemic came tomorrow, and the government had no drug with which to treat thousands of influenza infected patients, I imagine there would be a public outcry," she said.
The Cochrane review found that compared with a placebo, or dummy pill, Tamiflu led to a quicker alleviation of flu-like symptoms of around half a day (down from 7 days to 6.3 days) in adults, but the effect in children was more uncertain.
There was no evidence of a reduction in hospitalisations or in flu complications like pneumonia, bronchitis, sinusitis or ear infections in either adults or children, Heneghan's team said, and Tamiflu also increased the risk of nausea and vomiting in adults by around 4 percent and in children by 5 percent.
Godlee described the battle with Roche as a "really lengthy cat and mouse, Alice in Wonderland, bizarre experience of trying to get data on a drug which governments around the world were busy buying, stockpiling and spending billions of dollars on".
"Why did no-one else demand this level of scrutiny before spending such huge sums on one drug?" she said. "The whole story gives an extraordinary picture of the entrenched flaws in the current system of drug regulation and drug evaluation."