Is Tamiflu actually helpful?

I had been reporting on the Tamiflu controversy for several years when the question of whether to take the drug became personal. For those who haven’t been nerding out on this fascinating scientific saga, the short summary is this: Tamiflu, a pill, is one of two first-line drugs approved to both prevent and treat influenza. (The other is an inhaler, Relenza.) About a decade ago, these flu medicines came under attack, as researchers began to dig into the evidence behind them and reveal holes, inconsistencies, and missing data. The antivirals, they argued, didn’t seem to be as effective as health officials around the world (and the manufacturers) had claimed, and Tamiflu became the poster-child for the open data movement in medicine. Stocks of Tamiflu in a UK warehouse. (Katie Collins/WPA Pool/Getty Images) I wrote a lot about the public-health and scientific debates: whether the $9 billion spent globally to stockpile antivirals was actually justified; whether researchers should have access to the raw data the regulators saw when they approved drugs (instead of just published data); and whether the public had been misled on what seemed to be an unimpressive therapy.And then my grandmother called from her old-age home this week. We hope that patients and doctors are much more likely this year to use Tamiflu”They’re giving out Tamiflu,” she said, explaining that entire floors at the home had been quarantined because of the severity of the flu this season. “I don’t know whether I should take it.” That same day, I heard Dr. Tom Frieden, the steward of American public health and director of the Centers for Disease Control and Prevention, on the radio heavily pushing antivirals. “We hope that patients and doctors are much more likely this year to use Tamiflu than the past because we know from past years, that the rates of use are very low,” Frieden said. In what is shaping up to be a very deadly flu season, he suggested Tamiflu could be taken by anyone at risk of influenza, and really should be given to the vulnerable and elderly, like my grandmother. On the face of it, there seemed to be two divergent narratives: the crusading researchers who have painstakingly documented the flaws and problems with evidence for these antivirals and the doctors and public-health officials who continue to endorse these medicines. The researchers argue the drugs work no better than Tylenol, that they aren’t value for money; the public-health officials say they can save lives. I told my grandmother to go ahead and talk to her doctor about getting Tamiflu. Here’s why. Who should take flu drugs? From a public-health perspective — when you’re considering the general population — antivirals like Tamiflu don’t look very good. These drugs were stockpiled by the US and many countries around the world to save lives and spare hospital beds, specifically to reduce hospital admissions and complications from influenza. But while early industry-funded trials showed that these drugs did just that, meta-researchers — like those in the Cochrane group, who look at all the evidence on clinical questions — found a less promising picture. In the most thorough analysis of the antivirals data to date, the Cochrane researchers revealed that there is no high-quality evidence that proves these drugs do what governments might have hoped: reduce the risk of influenza complications (like pneumonia) or hospitalizations among the general population. Public money may have been squandered here on national stockpiles. At the individual level, however, the data tell a different story.Even those critical Cochrane reviewers found that both Relenza and Tamiflu help minimize the spread of influenza when taken for prevention, particularly in households and institutions (such as my grandmother’s old-age home) where the virus is circulating. Still, according to the physicians’ bible, UpToDate, the drugs should only be considered as a preventive measure in adults who are around the flu and at a high risk of flu complications (such as residents of nursing homes or long-term care facilities, people 65 and older, and others with chronic medical conditions). So healthy people don’t need these drugs for prevention (and they don’t need to be stockpiled for entire populations). As for treatment, the story is the same: most studies have shown that antivirals can shorten the duration of flu symptoms by about a day. (To be effective, they need to be given to patients within 48 hours of the onset of flu.) Lessening flu symptoms for a day wouldn’t really do much if you’re young and robust. If you have a tidal wave coming at you and someone hands you a pair of water wings, you’ll probably take themBut there have been observational studies (considered lower quality evidence) on very sick or elderly patients, which show the drugs seemed to both shorten patients’ hospital stays and reduce the severity of the illness. So UpToDate suggests doctors consider prescribing antivirals in these patients — again, not healthy people — particularly since side effects are rare and mostly mild (i.e., nausea and vomiting). So you see the tension here: the proven benefits for healthy people aren’t very impressive, but there is some evidence that the drugs may help the otherwise sick or compromised. The best data on frail patients — in old-age homes or hospitals — is observational, and unlike experimental research on healthy adults, these types of studies can’t prove causation. In other words, there’s some low-quality evidence that these drugs might still help some people who could otherwise die from the flu. And right now, there are no alternatives. The antiviral dilemma Scott Gavura, a pharmacist who writes on the blog Science-Based Medicine, summed up the antiviral dilemma very nicely: “If you have a tidal wave coming at you and someone hands you a pair of water wings,” he told me, “you’ll probably take them because they might help you and they won’t do you harm.” When I talked to front-line clinicians, this is basically the position I heard echoed again and again. “People can get sick, and people can die from influenza,” said Dr. Paul Bunce, an internist and infectious diseases specialist who prescribes Tamiflu to treat compromised inpatients at his Toronto hospital. “We feel really helpless, and it’s easier to give something than nothing.” He couldn’t be sure that the drug saves lives or even improves health outcomes after the flu, but it appears to lessen symptoms and reduce the spread of the flu in people who could die from it. Eventually, we may see high-quality evidence that suggests these flu drugs are truly no better than Tylenol, even for people like my grandmother. But during a fierce flu season, with no viable alternatives, antivirals become appealing. “It’s a genius product,” noted Gavura. “And it got stockpiled because there really is nothing else.”


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