According to a review conducted by The Cochrane Collaboration and published Thursday in the BMJ, although Roche's Tamiflu (oseltamivir) can shorten the symptoms of influenza by half a day, the analysis found "no good evidence" to support claims that it reduces admissions to hospital or complications of the condition. The analysis also indicated that treatment with Tamiflu increased the risk of suffering from nausea and vomiting, while use of the drug as a preventative was linked to an increased risk of headaches, psychiatric disturbances and renal events.
The review found that when used as a preventative treatment, Tamiflu can reduce the risk of people suffering symptomatic influenza, however, the researchers said "it is unproven that it can stop people carrying the influenza virus and spreading it to others." The Cochrane Collaboration's analysis of neuraminidase inhibitors included 20 studies of Tamiflu, and 26 trials of GlaxoSmithKline's Relenza (zanamivir), consisting of more than 24 000 people. The Cochrane Collaboration has lobbied since 2009 for Roche to hand over all its data from clinical trials of Tamiflu, with the company agreeing last year to do so.
Results of the review showed that compared with placebo, Tamiflu led to a quicker alleviation of influenza-like symptoms from 7 days to 6.3 days in adults, although the effect was "more uncertain" in children. The analysis suggested that Roche's drug increased the risk of nausea and vomiting in adults by around 4 percent and in children by 5 percent, while there was a reported increased risk of psychiatric events of around 1 percent when Tamiflu was used to prevent influenza.
The review of data on Relenza found that the agent can shorten the symptoms of influenza in adults by just over half a day, from 6.6 days to 6 days. However, there was no evidence that the drug reduces the risk of complications of the infection, particularly pneumonia, or the risk of hospital admission or death. Study author Carl Heneghan remarked "there’s no credible way these drugs could prevent a pandemic," adding that money spent by governments on stockpiling the medicines "has been thrown down the drain."
According to The Cochrane Collaboration, the US has spent more than $1.3 billion on stockpiling antivirals, while the UK government has spent almost 424 million pounds ($711 million) buying around 40 million doses of the drugs. Sales of Tamiflu reached 3.2 billion Swiss francs ($3.7 billion) in 2009, as demand was boosted by the influenza A (H1N1) outbreak. Study author Tom Jefferson questioned "why did they stockpile? What was the rationale? The evidence doesn't support it." He added that given the side effects, neuraminidase inhibitors might cause more harm than good.
In response to the findings, Roche said it "fundamentally disagrees" with the conclusions of the review, adding "we firmly stand by the quality and integrity of our data." The company suggested that The Cochrane Collaboration's analysis included only 20 out of 77 clinical trials available, and excluded real-world data from observational trials, as well as patient-level data. Roche highlighted a recent study of patient-level data from nearly 30 000 subjects in a pandemic setting, which showed that treatment with neuraminidase inhibitors reduced the risk of death by 19 percent when compared with no treatment.
Barry Clinch, Roche’s global development leader for Tamiflu, added "we stand behind our label" for the product, which he noted details all the possible side effects. "We haven’t changed it on the basis of any previous Cochrane review and we won’t change it on the basis of this one," Clinch remarked. GlaxoSmithKline said the data show Relenza is effective "and when used appropriately, in the right patient, it can reduce duration of flu symptoms."
BMJ editor Fiona Godlee noted that policy makers need better information to make decisions about buying medicines, and they can’t depend on manufacturers for unbiased data. She suggested that much of the responsibility falls on the regulators, such as the European Medicines Agency, and the politicians who authorised the stockpiling. "It was a system-wide failure," Godlee commented, adding "the current system is clearly broken."
However, Enrica Alteri, head of the EMA's Human Medicines Evaluation Division, said the regulator had seen and reviewed 43 studies in its approval of Tamiflu, 18 of which were included in the latest analysis. "The review, we believe, supports our benefits-risk assessment and does not raise any new concerns that would not be already addressed in the product information," Alteri noted.