Tamiflu and Relenza are drugs commonly used for the prevention and treatment of influenza in adults and children. Past research has hailed the drugs for reducing hospital admissions and complications as a result of the virus. But in the latest Cochrane Review, recently published in the BMJ, researchers say there is no solid evidence to support such claims.
Tamiflu (oseltamivir) and Relenza (zanamivir) are classes of drugs known as neuraminidase inhibitors. Both drugs are thought to prevent and reduce symptoms of flu by stopping the influenza virus from spreading inside the body.
At present, Tamiflu is used to combat flu in patients 2 weeks of age and older whose symptoms have not lasted longer than 2 days. It can be used to prevent flu in patients aged 1 year and older. Relenza is used to tackle flu in patients aged 7 years and older and can be used for flu prevention in those aged 5 years and older.
According to the researchers involved in this latest review, including Dr. Carl Heneghan of the University of Oxford in the UK and Dr. Peter Doshi of the University of Maryland School of Pharmacy in the US, both drugs are stockpiled for use against seasonal and pandemic influenza. For example, the US has spent over $1.3 billion on reserves of influenza antivirals.
This stockpiling has been based on international and national recommendations from bodies such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). But what are their recommendations based on?
The team says that for the European CDC, neuraminidase inhibitor recommendations were based on a summary of benefits and harms carried out by the European Medicines Agency (EMA), while other recommendations have been based on findings of trials from drug manufacturers, such as GlaxoSmithKline (GSK).
In 2009, Cochrane researchers looked to verify the safety and effectiveness of neuraminidase inhibitors. However, drug manufacturers refused to provide full access to clinical trial data of the drugs, which hindered their efforts.
This raised questions as to whether the risks and benefits of influenza antivirals have been accurately reported, and whether they should be stockpiled for the treatment of seasonal and pandemic flu in children and adults.
In 2012, Medical News Today reported on a story detailing how the BMJ were putting pressure on Roche – the manufacturers of Tamiflu – to release trial data for the drug.
Having now gained access to original clinical trial data, the researchers were able to analyze 20 full internal reports on the effects of Tamiflu and 26 reports on the effects of Relenza. In total, the reports included more than 24,000 people.
On reviewing the benefits of Tamiflu, the researchers found that the drug led to faster relief of flu symptoms by only half a day (from 7 days to 6.3 days), compared with a placebo drug.
The researchers found that the drug increased nausea and vomiting in adults and children by 4% and 5%, respectively. When Tamiflu was used for prevention of influenza, there was a 1% increase in risk of psychiatric events. These effects were not reported in the initial clinical trial publications.
Furthermore, the team found that Tamiflu stopped some people from producing enough of their own antibodies to fight flu infection.
Commenting on these findings, Dr. David Tovey, editor in chief at Cochrane, says:
“Initially thought to reduce hospitalizations and serious complications from influenza, the review highlights that Tamiflu is not proven to do this, and it also seems to lead to harmful effects that were not fully reported in the original publications. This shows the importance of ensuring that trial data are transparent and accessible.”
Results were similar for Relenza. The drug was found to reduce the duration of flu symptoms from 6.6 days to 6 days in adults – the equivalent of 14.4 hours – compared with a placebo drug. No significant effect was found in children.
The team found no evidence that Relenza reduces the risk of flu complications or risk of hospitalization.
Based on their findings, the researchers say that recommendations on the use of both Tamiflu and Relenza for the prevention or treatment of influenza should be revised.
“Drug approval and use cannot be based on biased or missing information any longer. We risk too much in our population’s health and economy,” the authors say.
They point out that this updated Cochrane Review is the first to be based only on clinical studies and regulator’s comments, meaning the findings are “much richer.”
“We urge people not to trust in published trials alone or on comment from conflicted health decision makers, but to view the information for themselves,” they add.
In an editorial linked to the reviews, Dr. Tovey, alongside BMJ Editor-in-Chief Fiona Godlee and clinical editor Elizabeth Loder, note that the findings of this review emphasize the need for all data to be made available from clinical trials for drugs currently in use so that all information can be closely assessed.
“The Cochrane reviewers’ exceptional efforts have achieved what should have been a matter of routine – the independent scrutiny of clinical trial data,” they add.
“They have shown with greater clarity than ever that the current system is broken. There are substantial battles still to fight before we have a system of drug evaluation and emulation that truly serves patients and the public interest.”