A key plank of the international response to pandemic influenza — the stockpiling and widespread use of antiviral drugs such as Tamiflu — has been called into question by an important new review.

More broadly, the review and subsequent investigations jointly undertaken by the BMJ and Channel 4 News, have raised major concerns about the wider drug regulatory process.

A BMJ editorial, published online today, says the investigations “cast doubt not only on the effectiveness and safety of oseltamivir (Tamiflu) but on the system by which drugs are evaluated, regulated, and promoted”.

“This case exposes how much of the evidence on drug safety and effectiveness is taken on trust,” it said.

“The current system isn’t working. Worse than that, it gives a false sense of security. The system’s failures have left a legacy of drug evaluations for which, in the absence of better information, we must assume the same levels of confusion and uncertainty as for oseltamivir.”

The new review, updating a 2005 systematic review by the Cochrane Collaboration, concludes the antiviral drugs known as neuraminidase inhibitors have only “modest” effectiveness against influenza symptoms in otherwise healthy adults, reducing illness by about one day.

More significantly, the researchers identified major flaws in the evidence, which has been used to support claims of Tamiflu’s benefits against serious complications of influenza in otherwise healthy adults, and to justify governments’ billion dollar investments in stockpiling the drug.

They conclude there is insufficient evidence to support these claims and believe the drug should not be used in routine control of seasonal influenza. They also call for independent investigation of potential safety concerns surrounding Tamiflu.

Dr Fiona Godlee, editor-in-chief of the BMJ, said in a statement: “Governments around the world have spent billions of pounds on a drug that the scientific community now finds itself unable to judge.”

The review was funded in part by the NHMRC and will be presented at a workshop in Canberra tomorrow for H1N1 researchers. No doubt the implications will be hotly debated — especially as the Australian Health Management Plan for Pandemic Influenza stresses the role of antivirals and says their early use is likely to have significant impact in reducing complications and deaths.

The BMJ has given the review a huge splash. It is accompanied by several related articles, one of which traces the difficulties the Cochrane reviewers had in obtaining data from Tamiflu researchers and the manufacturer, Roche.

An Australian academic who helped conduct the review, Professor Chris Del Mar, dean of health sciences and medicine at Bond University, told Crikey that governments should review their policies around pandemic and seasonal influenza.

“We have to ask what the opportunity cost is of having warehouses full of drugs of modest effect,” he said. “My feeling is we probably ought to start tinkering with the policy; we should reserve oseltamivir  for people who are seriously ill or those in high-risk groups. I don’t think we should use it as a public health measure.”

He also said the review should prompt some critical reflection by drug regulators and governments, which needed to start investing in independent evaluation rather than relying on companies’ data. “We need to insist on looking at data more critically when we’re basing quite important policy decisions which cost billions,” he said.

The BMJ published lengthy responses from Roche and noted in its editorial: “In being less than forthcoming with the raw data, Roche has done nothing wrong by current standards and even less by standards of 10 years ago. It has done exactly what the current system allows.”

Crikey has sought response from the TGA and Federal Health Department.

Peter Fray

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