Second study raises questions over the benefits of Tamiflu

http://www.theguardian.com/society/2015/jan/30/tamiflu-study-questions-drugs-usefulness-roche-lancet

Version 0 of 1.

The drug Tamiflu shortens the symptoms of flu by about a day and reduces the numbers who end up in hospital, but it causes nausea and vomiting which may outweigh any benefit, according to a major new analysis of the data.

Tamiflu has been the subject of huge controversy. Researchers from the Cochrane Collaboration fought for four years to extract the full patient data from drug trials by the manufacturer, Roche. They eventually succeeded with the backing of the British Medical Journal and published their review which concluded that the British government’s £424m stockpile of Tamiflu against a pandemic was a waste of money.

The new review of Tamiflu for seasonal flu – not in pandemics – is by another team of independent researchers and includes Roche data. It is published by the BMJ’s rival, the Lancet.

Where the BMJ study found Tamiflu shortened a flu bout by about half a day, the Lancet analysis suggests the reduction is a whole day. The Lancet paper says Tamiflu reduced the risk of a patient needing antibiotics for a respiratory tract infection by 44% and cut the risk of hospital admission for any cause by 63%. In all cases, these were patients whose flu had been confirmed by lab tests. Tamiflu had no effect on people who were ill for other reasons.

But the independent research group led by Arnold Monto, professor of epidemiology at the University of Michigan School of Public Health in the US, and Stuart Pocock, professor of medical statistics at the London School of Hygiene and Tropical Medicine, found Tamiflu had problematic side effects. The drug increase the risk of nausea by 3.7% and vomiting by 4.7%. They conclude that this raises questions about its usefulness.

“Whether the magnitude of these benefits outweigh the harms attributed to nausea and vomiting needs to be carefully considered,” they write.

Kevin McConway, professor of applied statistics at the Open University, said the conclusions from both studies were much the same – that the drug reduces the length of a flu bout.

“But is a reduction of this size worthwhile, particularly given that the new review confirmed that Tamiflu has side effects? Tamiflu increases the risk of nausea and vomiting.

“A study like this can’t on its own say whether it is worthwhile to trade off the reduction in the length of symptoms against the risk of nausea and vomiting,” he said.

“That is particularly true in relation to the possible use of Tamiflu in a future severe flu epidemic, where it would not be feasible to confirm all diagnoses in a laboratory. Making such a decision requires some complicated value judgements.”

Professor Peter Openshaw, director of the centre for respiratory infection at Imperial College London, said: “The important thing about this study is that it shows that Roche were not hiding skeletons in its cupboards. As a full review of the published and unpublished data, it leaves the conclusion unaltered that oseltamivir [Tamiflu is the trade name] reduces symptom duration by about a day while causing nausea and vomiting in a minority of recipients.”

But Dr Tom Jefferson, an epidemiologist and one of the authors of the Cochrane review of Tamiflu, pointed out that the funding for the study came – albeit indirectly – from Roche, which funded the multiparty group for advice on science (Mugas) which paid for the analysis.

However, he said, “on the science side, there are no new data presented here on complications or hospitalisations that we did not already know of and present and make public in April last year in our Cochrane review. The reasons the conclusions are different is because they have differing interpretation of the same data.

“They for example are apparently happy to trust that what was recorded as ‘pneumonia’ really was pneumonia when patients got antibiotics. I would challenge that assumption.

“Our interpretations are in line with FDA [Food and Drug Administration which licences drugs in the US] which does not allow Roche to claim Tamiflu reduces the risk of complications. Our interpretations were driven by our access to over 100,000 pages of Tamiflu clinical study reports, something these authors did not access according to their methods section, but something the FDA did.”