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Cochrane and BMJ inquiry Tamiflu and Relenza effectiveness

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There is no good evidence about the effectiveness of Tamiflu (oseltamivir) and Relenza (zanamivir) for influenza prevention and treatment. This is the though claim made by Cochrane Collaboration and the British Medical Journal (BMJ), based on the extended systematic review they just published about the use of neuraminidase inhibitors against influenza.

Their study is entirely based on complete clinical study reports, trial registries, electronic databases, regulatory archives and correspondence with manufacturers, which correspond to more than 150,000 pages of documents; more specifically, the researchers focused on 20 (Tamiflu) and 26 (Relenza) randomized placebo controlled trials testing the effects of the drugs for treatment, prophylaxis, and post-exposure prophylaxis of influenza. Taken together, the trials analyzed involved more than 24,000 adults and children who had confirmed or suspected exposure to natural influenza.

What they found is that, when used for prophylaxis, both drugs reduce the proportion of symptomatic influenza (but not in children, for zanamivir). In spite of such a reduction, their effectiveness in preventing infected people to spread the disease to others remains unproven. Both drugs showed modest effects in terms of alleviation of influenza-like symptoms, but oseltamivir also increased the risk of nausea, vomiting, headaches, and renal and psychiatric syndromes. Whilst zanamivir reduces the proportion of patients with laboratory confirmed symptomatic influenza, no evidence has been found that the two drugs may decrease the risk of complications of influenza, particularly pneumonia, or the risk of hospital admission or death. Evidence also suggests that Tamiflu prevented some people from producing sufficient numbers of their own antibodies to fight infection.

Such a massive review was not possible in 2009, due to a lack of access to available trial data, and this prevented researchers from verifying the claims about the effectiveness of neuraminidase inhibitors against influenza complications, which in turns led to governments’ decision to stockpile these drugs in case of a pandemic. A decision that cost a huge amount of money and that raised many controversies.

The authors of the study concluded that their findings do not support the mode of action of zanamivir proposed by the manufacturers, and raise question about the global stockpiling of oseltamivir and its inclusion on the WHO list of essential drugs as an anti-influenza drug. According to authors, governments took such decisions “on the basis of a published evidence base that has been affected by reporting bias, ghost authorship, and poor methods”.

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