Independent researchers are urging governments to re-evaluate policies to stockpile Tamiflu, citing strong evidence that the Roche antiviral drug does not reduce the risk of admittance to hospital or complications from the flu.
The Cochrane Collaboration, a global non-profit research network, analyzed 46 clinical trials of the antiviral drugs Tamiflu and Relenza in a review published Thursday in the British Medical Journal. Their findings challenge the assumption that antivirals are a first line of defence against flu pandemics.
Tamiflu shortens flu symptoms by half a day but is otherwise ineffective in treating the flu, said co-author Carl Heneghan, a professor of evidence-based medicine at the University of Oxford.
The minimal benefits “do not warrant large-scale use,” he said.
Canada maintains a national stockpile of antiviral drugs, despite debate about their efficacy. Canada’s National Emergency Stockpile System currently holds a total of 19.7 million doses of Tamiflu and Relenza, an antiviral that is inhaled instead of taken in capsule form.
Since 2004, the Public Health Agency of Canada has spent $67.5-million to stockpile Tamiflu and Relenza, including replacement costs due to use and drug expiry, according to a statement from the PHAC.
Media reports estimate global sales of Tamiflu at close to $10-billion in the years following the 2002 SARS outbreak, the avian flu scare of 2005 and H1N1 swine flu pandemic in 2009, as governments built emergency reserves of antiviral drugs on the advice of the World Health Organization.
But according to an accompanying editorial in BMJ, regulators, policy makers and the public were misled by pharmaceutical companies that marketed antivirals based on incomplete data not fully released until 2013.
“Important benefits have been overestimated and harms under-reported,” the authors wrote. The Cochrane review found that Tamiflu causes nausea and vomiting, and may also cause headaches, renal problems and psychiatric syndromes.
However, critics of the review argue that the findings apply only to healthy people. Patients with pre-existing medical conditions, such as cancer and Type 2 diabetes, were largely excluded from drug trials in the review, although they are the most likely to benefit from antiviral treatment, said Marek Smieja, an infectious diseases specialist at McMaster University.
“This is old data in the wrong populations,” Dr. Smieja said. When influenza makes the rounds in hospitals and nursing homes, “these drugs are highly effective in curtailing that outbreak,” he said.
Perry Kendall, provincial health officer at the B.C. Ministry of Health, noted that Cochrane reviewers excluded observational studies of antivirals in real-life pandemic conditions. He pointed to a review of 78 observational studies, published in March in the Lancet, which found a significant reduction in mortality among flu patients treated with antivirals during the H1N1 outbreak in 2009.
“Based on this, I would recommend that we continue to maintain our antiviral stockpiles,” Dr. Kendall said.
According to the PHAC, observational studies from the H1N1 pandemic “support the benefits and effectiveness of antivirals, particularly when used early (within 48 hours) and in people at high risk of complications from the flu.”
But evidence-based researchers such as Dr. Heneghan caution against putting faith in observational studies, which have a high risk for bias since healthy people tend to receive drug treatment while sick patients are sent to hospital.
Observational studies should not form the basis of treatment and policy decisions, Dr. Heneghan said. “We clearly know after 40 years of experience that that is a very dangerous thing to do.”