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Questions remain over safety and effectiveness of oseltamivir

BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e467 (Published 17 January 2012) Cite this as: BMJ 2012;344:e467
  1. Deborah Cohen
  1. 1BMJ

Two years after the pharmaceutical giant Roche promised the BMJ that it would release key trial data on oseltamivir (Tamiflu) for independent scrutiny, the safety and effectiveness of this anti-influenza drug remain uncertain, a new meta-analysis by the Cochrane collaboration says.

Cochrane researchers set out to test Roche’s claim that the drug prevented complications and reduced the number of people needing hospital treatment. Their report says that Roche’s refusal to provide full access to all its data leaves critical questions about how well the drug works unresolved (BMJ 2012;344:d7898, doi:10.1136/bmj.d7898).

Roche maintains that it provided the Cochrane researchers with enough information to conduct their evaluation, but the Cochrane team says that this is not the case.

Peter Doshi of the Johns Hopkins University School of Medicine, Baltimore, said, “In the BMJ in December 2009 Roche promised full study reports to any legitimate investigators. They have not provided a single full study report to Cochrane, despite our repeated requests.”

Meanwhile GlaxoSmithKline—the manufacturer of the less popular antiviral zanamivir (Relenza)—has offered data on individual patients.

Rather than relying on the published academic literature, the Cochrane group pieced together information from over 16 000 pages of clinical trial data and documents used in the process of licensing oseltamivir (Tamiflu) by national drug authorities, obtained through freedom of information requests.

The latest Cochrane review poses new questions about the drug’s safety profile reported in the published literature and oseltamivir’s proposed mode of action.

The Cochrane team says that the drug’s ability to prevent the spread of flu has not been shown in trials. Yet this is one of the main reasons governments around the world spent billions of dollars stockpiling the drug in case of a pandemic.

The Cochrane team also compared published data with the more complete unpublished trial records and found inconsistencies in the published record of the trials. For example, while unpublished trial reports mentioned serious adverse events, some even classified as possibly related to oseltamivir, one of the two most cited publications makes no mention of such effects, and the other states, “There were no drug-related serious adverse events.”

A simultaneous investigation by the BMJ highlights concerns about how the medical community approaches scientific evidence (BMJ 2012;344:e458, doi:10.1136/bmj.e458).

It shows that the European Medicines Agency did not ask for all the data on the drug, despite having the authority to do so. It had about half of what the US Food and Drug Administration held on file and none of the individual patient data. The agency relied on the statistical summaries provided by the company and did not carry out trial site inspections.

The agency told the BMJ that it is discussing publishing full clinical study reports for all drugs submitted for approval as soon as it makes a decision on the drug.

The BMJ’s investigation also indicates that oseltamivir has become the mainstay of treatment of flu in the United Kingdom. The drug has also made it onto the World Health Organization’s list of essential medicines, and Roche’s claims continue to be supported by influential health agencies.

Notes

Cite this as: BMJ 2012;344:e467