The latest—and possibly last—salvo in a long-running debate over the merits of the influenza-fighting drug Tamiflu was fired off today, but it seems unlikely to quell skeptics or nurture unanimity around the drug’s effects.
For years, members of the Cochrane Collaboration, an international network of scientists who review medical evidence, have charged that Tamiflu’s benefits are overstated. They agree that if taken soon after symptoms surface, the drug reduces by about a day the length of time someone feels sick. But they dispute that the evidence—including 12 randomized trials conducted by Roche, which makes Tamiflu, known generically as oseltamivir—shows that it cuts down on serious complications, hospitalizations, and deaths. The Cochrane group has also put a focus on transparency in science: It argued that publication bias had left Tamiflu looking better than it really was.
The dispute prompted Roche and some influenza researchers to pledge to reanalyze the data—and that’s what’s being released online today. Writing in The Lancet, four flu experts describe blending data from nine clinical trials of more than 4000 patients to assess Tamiflu. Pooling data makes it easier to discern the drug’s effect on rarer outcomes, such as pneumonia. And, the authors report, Tamiflu makes a meaningful difference, reducing the risk of hospital admission by 63%. The actual numbers are small: Nine of 1591 participants who took Tamiflu were admitted to the hospital, and 22 of 1302 those not taking the drug ended up there. The drug was also associated with fewer cases of lower respiratory tract infections that called for antibiotics, the authors say, such as bronchitis or bacterial pneumonia. Patients on the drug had a 4.9% risk compared with an 8.7% risk if not on the drug. “Significant risk reductions were detected,” the authors note, acknowledging that Tamiflu also had side effects, particularly nausea and vomiting, which must be balanced against its benefits.
The Lancet paper may be unlikely to compel many people to switch sides, however. “There are no new data presented here on complications or hospitalizations that we did not already know of,” says epidemiologist Peter Doshi of the University of Maryland School of Pharmacy in Baltimore, a critic of Roche and part of the Cochrane group that reviewed Tamiflu studies. The differences, he says, stem from how complications are interpreted: For example, were all those cases recorded as pneumonia really pneumonia? Clinical study reports, examined by Cochrane reviewers such as Doshi, suggest they weren’t always, he believes.
More troubling, Doshi says, is that the new analysis was funded by Roche through a foundation called MUGAS that it helps support. That detail was not shared in The Lancet’s press release—which Doshi says is “disappointing”—though it does appear at the end of the paper. “This is not independent science,” Doshi asserts.
Others suggest that the new report doesn’t change much about our understanding of Tamiflu, though they praise Roche for supporting it and agree with its finding that the drug reduces hospitalizations. “The important thing about this study is that it shows that Roche [was] not hiding skeletons in its cupboards,” said Peter Openshaw, director of the Centre for Respiratory Infection at Imperial College London, in a prepared statement. “Oseltamivir is not a perfect drug, but it does what you might expect,” especially when given after the flu has taken hold and is harder to beat back.