A new study has cast aspersions over the effectiveness of Roche’s antiviral Tamiflu and the company stands accused of not making enough data available to evaluate its risks and benefits properly.

An expert review published by the BMJ says there is no clear evidence that the antiviral most commonly used against influenza – Tamiflu (oseltamivir) - prevents complications like pneumonia in healthy people. __The study, which updates a 2006 review published in The Cochrane Library, acknowledges that Tamiflu (and other neuraminidase inhibitors) have a modest effect in reducing flu symptoms and infectivity in otherwise healthy adults by about one day. However, it claims that there is insufficient published data to know if oseltamivir reduces complications in otherwise healthy adults.__

__The research team, led by Chris Del Mar of Bond University in Australia, analysed 20 published trials that focused on prevention, treatment and adverse reactions. __However they say their investigation was hampered by the “paucity of good data” available from authors and Roche itself.

The team therefore dropped “eight key trials which were never fully published” that were included in the earlier review because they were unable to independently verify the results. As a result, they conclude that they have no confidence in claims that Tamiflu reduces the risk of complications of influenza in otherwise healthy adults, and believe “it should not be used in routine control of seasonal influenza”. __

The drug has been in the headlines since swine flu started spreading earlier this year and before any vaccines were approved, Tamiflu and to a lesser extent GlaxoSmithKline/Biota’s Relenza (zanamivir) were seen as the answer to the pandemic.

__Nick Freemantle and Melanie Calvert from the University of Birmingham were asked by the BMJ and Channel 4 News to review observational studies based on a list provided to the Cochrane authors by Roche. They concluded that Tamiflu may reduce the risk of pneumonia in otherwise healthy people who contract flu but the “absolute benefit is small, and side effects and safety should also be considered.” __

__Prof Freemantle said that “we have remarkably few resources in this country to spend on pharmaceuticals on health and it’s surprising to see such widespread use of oseltamivir”. He went on to say: “I suppose that once you’ve gone and bought lots of doses then it’s a bit like the situation with gun control in the US. If you have a gun in the house it’s much easier to use it. But it does not mean it’s the right thing to do.” __

Fiona Godlee, editor-in-chief of the BMJ, noted that governments around the world “have spent billions of pounds on a drug that the scientific community now finds itself unable to judge”. She and
Mike Clarke, director of the UK Cochrane Centre, went on to say this updated review is important because it calls into question “not only the effectiveness of oseltamivir but the whole system by which drugs are evaluated, regulated and promoted”.

__ Roche responds
James Smith, international medical leader for Tamiflu responded to the BMJ’s claims in a letter that responses to all questions have been provided in full to the journal and Channel 4 “and should leave no doubt about the high integrity of the data, publications, and interactions between Roche and independent investigators”.

Regarding the lack of data complaint, he said that at the time the trials were conducted (1999-2003), “it was not standard practice for study protocols or reports to be automatically made public as it is now”. However, “for transparency and to facilitate disclosure”, Roche has posted study summaries, including data tables, for all the component trials online and full reports “will also shortly be available by password-protected access for all bona fide scientific investigation”.

Dr Smith went on to say that as well as providing reports to such regulatory bodies, Roche has, “through appropriate channels, willingly shared data and reports with numerous other eligible individuals and groups”, including the Cochrane review group”. However, the company is concerned that the later team, led by Tom Jefferson, “chose to follow-up their inquiries through a television company rather than by approaching the manufacturer directly and obtaining data under a standard agreement—a move that questioned whether the motives for inquiries were truly for clarity and scientific validation”.

The letter goes on to say “it is unclear to us why Dr Jefferson would adopt this approach, particularly given that he was a paid ad hoc consultant to Roche working on flu and oseltamivir between 1997 and 1999”. During that period he worked closely with Roche experts [and] would therefore not have had difficulty in contacting them directly to discuss his requirements”.

Dr Smith says that the role of Tamiflu in mitigating the serious threats from flu infections has been recognised in the recommendations from the World Health Organization. He concludes by saying that why Dr Jefferson and the BMJ “chose to pursue their scientific enquiries through commercial television remains to be clarified”.