An expert group in the United Kingdom that was asked to review neuraminidase inhibitor use for flu in the wake of research and pandemic stockpiling controversies unveiled its report today, finding a modest benefit for seasonal flu but a greater impact for hospitalized patients.
The two leading neuraminidase inhibitors for flu—oseltamivir (Tamiflu) and zanamivir (Relenza)—have been controversial in the UK, with the journal BMJ spearheading a campaign to persuade Roche to release unpublished clinical trial data on oseltamivir and criticism from some that European Union governments overreacted with their 2009 pandemic responses, which included purchases for drug and vaccine stockpiles.
The UK's Department of Health asked the expert group for an evidence-based report to help guide its future policy decisions. The experts, who published a 47-page report, are from the Academy of Medical Sciences (AMS) and the Wellcome Trust.
The AMS said in a press release that the evidence base for antiviral treatment in flu epidemics, compared with seasonal flu, has some weaknesses, and said researchers missed an opportunity to study the impact of the drugs during the 2009 H1N1 pandemic. The academy noted that the lack of evidence has helped fuel controversies about the drugs' effectiveness and whether the UK government is justified in stockpiling them.
Sifting evidence for policy guidance
When the scientists looked at evidence for use in seasonal flu, they concluded that neuraminidase inhibitors can cut symptom duration by 14 to 17 hours. Unless the flu strain is severe or patients have severe infections, they didn't support the routine use of the drugs for seasonal flu. They said that for routine use the benefits didn't outweigh the risk of side effects.
The group did find, however, that the drugs significantly cut deaths in hospitalized patients, especially when the medications are given within 48 hours of symptom onset. They added that that role for neuraminidase inhibitors could be critical in an epidemic setting and that the evidence supports antivirals for hospitalized patients.
The public may be more likely to benefit from the drugs when outbreaks are especially severe, with strains that carry greater complications and death, the experts said. In those settings, expanding the scope of people who are treated may be justified, they concluded.
The team didn't make a recommendation on whether governments should stockpile the drugs. Instead they urged policymakers to consider the scientific evidence along with economic, political, and ethical considerations.
Research gaps, future steps
The group recommended that plans be put in place to study the use of the drugs in future outbreaks, prioritizing randomized controlled trials in hospitalized patients and high-risk groups.
Sir Patrick Sissons, MD, former clinical vice president of the AMS who chaired the report's steering group, said in the AMS release that it can be difficult to apply evidence collected in one outbreak to another, because factors affecting each can vary so much. He added that it's very important to learn as much as possible from any new outbreak.
Jeremy Farrar, MD, director of the Wellcome Trust and steering group member, said, "The research protocols and infrastructure need to be put in place now—in 'peace time'—so we can start collecting new evidence immediately at the start of a new epidemic or pandemic. An assessment of the ability to do this research must be included in any scenario planning exercises for future pandemics."
Oct 8 full report
Oct 8 AMS press release
Oct 8 Wellcome Trust news release
Nov 2, 2012, CIDRAP News story "BMJ renews pressure on Roche to release all Tamiflu trial data"