Why The CDC And FDA Are Telling You Two Different Things About Flu Drugs
First, just an anecdote about what we did this year. Both my wife and I got the shot, and our kids got two. Supposedly it's more effective if you get two, spaced a few weeks apart.
Unfortunately, she came down with a nasty cold after getting her shot. While I don't believe getting the shot can make you sick, you usually have to go to a doctor's office to get the shot, and there's a high likelihood that there will be people in the waiting room there who are sick. Although we can't be certain, the timing suggests that maybe that's where she caught it. That's why she hates going to the doctor, because she often catches something from the other people who are there to see the doctor. What can you do? I've heard some people say that getting the shot gives them the flu. It's probably just the immune reaction they are feeling, but it could also be that they actually caught something at the doctor's office or somewhere else at the same time.
But, knock on wood, none of us has got the flu yet this year, unless what she had was the flu. I think it was just a nasty cold though.
Anyway, the article:
The CDC released figures Thursday showing that this season’s influenza vaccine is only about 23 percent effective, and the federal agency recently sent a letter to doctors, urging them to write more prescriptions for influenza drugs.
“Antiviral flu medicines are underutilized. If you get them early, they could keep you out of the hospital and might even save your life,” CDC Director Tom Frieden told reporters Jan. 9. Flu season lasts, on average, about 13 weeks. We’re about midway through a particularly bad one.
According to Frieden, three flu medications (Tamiflu, Relenza and Rapivab) can prevent “serious complications” and help people avoid hospitalization. But the Food and Drug Administration explicitly prohibits drug companies from making the claims that he and the CDC are making. Two different agencies, two different recommendations.
FDA spokeswoman Stephanie Yao told FiveThirtyEight in a statement: “Please note that neither product” — Rapivab nor Tamiflu — “is allowed to claim that they reduce complications or mortality due to flu. The data we’ve reviewed do not support this claim.” What the drugs have demonstrated, she said, is, “an ability to reduce the severity or duration of flu symptoms.”
The discrepancy between the CDC’s assertion that the flu drugs can prevent complications, hospitalizations and perhaps deaths, and the FDA’s insistence that the drugs have only been shown to cut the amount of time that symptoms persist comes down to how they weigh the evidence. The FDA requires randomized clinical trials, the gold standard of evidence in medicine, while the CDC also relies on non-randomized reports. “Observational studies from many countries have consistently found that early oseltamivir [Tamiflu] treatment of influenza patients reduces the duration of hospitalization and risk of severe outcomes such as intensive care unit admission or death,” CDC spokeswoman H. Amy Rowland told FiveThirtyEight in a statement.
But physician Tom Jefferson of the Cochrane Collaboration, an international organization that assesses medical evidence, calls the studies that the CDC is using to tout the drugs poorly designed and unreliable, pointing out that they’re funded by the drugs’ maker and led by researchers tied to the manufacturers. More rigorously designed trials do not back them up. For example, a study published last month that randomly assigned 400 hospitalized patients to receive either the newly approved peramivir (Rapivab) or a placebo was halted early for “futility” when it became clear that patients receiving the drug weren’t benefitting.
All three antiviral medications are designed to inhibit neuraminidase, an enzyme that influenza viruses need to release viral particles from infected cells. If the drugs can prevent the replication of these viruses, that’s a big deal, because they could stem the spread of the flu, making them vital tools for controlling epidemics. (This is why the U.S. has reportedly spent about $1.5 billion stockpiling Tamiflu.)
But Jefferson said clinical trials hint that the drugs may not work as advertised. In studies where people with influenza-like illnesses were assigned to either a neuraminidase inhibitor or a placebo, the drugs worked for people with influenza and for those who tested negative for the flu. (Because it takes a few days for test results and the drugs work best when given soon, patients were started on the drugs before the results were in.) Although other viruses can cause flulike symptoms, neurominadase isn’t found in other respiratory viruses, Jefferson said. So, he said, if the drug works for both groups of patients, it must be acting via a different mechanism.
And if the drugs are simply reducing fevers and making people feel better via some other mechanism, then it’s possible they’re nothing more than expensive alternatives to acetaminophen and ibuprofen, which alleviate aches and reduce fevers. (Tamiflu retails for about $130, Relenza goes for about $67, and Rapivab costs about $1,000.) Right now, there’s not enough evidence to draw firm conclusions on the drug’s actual mechanism of action, and Jefferson, his colleagues at Cochrane and editors at the British medical journal BMJ are embroiled in a years-long effort to obtain complete clinical trials data from the maker of Tamiflu.
Last April, Jefferson’s group published its latest meta-analysis of all the evidence it could get on Tamiflu, including thousands of pages of regulatory documents describing the various clinical trials. The researchers concluded that the drug can reduce the duration of flu symptoms by a little less than a day in adults. (The results are similar for the other antiviral drugs.) A typical case of influenza lasts about one to two weeks, and when you’re in the throes of it, something that can make your misery vanish a day sooner might seem very appealing.
Here’s the rub: For the drugs to work, you need to take them in the first 48 hours from the onset of symptoms.
So, is the director of the CDC overstating the benefits? Is is just that if you take them in the first 48 hours, your symptoms may be reduced by about 1 day? (Meh) or can you reduce the risk of complications or death? These are rather expensive and you have to go see a doctor to get them too (pain in the ass, expensive, you might catch something else there and you might make someone else sick because you are contagious). And how do "observational studies" work anyway? How do they control for, say, people who get the flu but don't report it to anyone, or at least not to someone who would be collecting the data used in these studies?