Why the CDC and the FDA Offer Different Advice About Flu Drugs

According to the best data scientists can get their hands on, antiviral drugs like Tamiflu can shorten your bout with the flu by maybe a day; maybe by only a few hours. So why does the Centers for Disease Control and Prevention (CDC) recommend people with flu symptoms get a prescription for these expensive drugs?

Promoting a drug that comes with the risk of side effects in exchange for a fairly modest benefit seems nutty, especially when it’s against FDA regulations for manufacturers of flu antivirals to claim that they reduce complications or deaths due to flu, because of the lack of good evidence that they do that.

This curiously contrary message from the federal government recently was examined by the numbers-crunching journalist site FiveThirtyEight.com to find out why such authoritative agencies take such opposite approaches to a common health issue.

Given that this year’s flu vaccine has been estimated to be only about 23% effective, more people than usual are expected to fall victim to the nasty respiratory infection, and of all them want relief from the coughing, congestion, fever, head and body aches.

The CDC is encouraging doctors to write more prescriptions for influenza drugs (Tamiflu, Relenza and Rapivab), and patients to ask for them. In early January, CDC Director Tom Frieden said, “Antiviral flu medicines are underutilized. If you get them early, they could keep you out of the hospital and might even save your life.”

Frieden says the three flu medications can prevent “serious complications,” but FDA spokeswoman Stephanie Yao told FiveThirtyEight, “Please note that neither [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.” Instead, she said, the drugs have demonstrated “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,” said FiveThirtyEight, “comes down to how they weigh the evidence.”

The FDA is more demanding, scientifically, than is the CDC. In order for manufacturers to make health claims about their products, they must present results from randomized clinical trials.

Those are the most rigorous, in terms of science. But the CDC makes recommendations based as well on nonrandomized reports. You might have heard of “observational studies,” which might show associations between things, but can’t be defined as “proof.”

Such studies, one CDC spokesperson told FiveThirtyEight, have consistently found that treating flu early with oseltamivir (Tamiflu) reduces the duration of hospitalization and risk of more serious problems including admission to an intensive care unit, or even death.

Hold your horses, said Dr. Tom Jefferson of the Cochrane Collaboration. That outfit assesses medical evidence wherever it can find it, often publishing the combined results of many studies, known as “meta-analysis.” Jefferson called the studies the CDC uses to support its position on antivirals poorly designed and unreliable. He noted that they’re funded by the drugs’ maker and led by researchers associated with the manufacturers. That’s known as a potential conflict of interest.

Jefferson said that higher-quality trials don’t support those the CDC points to. One study published late last year that randomly assigned 400 hospitalized patients to receive either the newly approved peramivir (Rapivab) or a placebo (fake, or inert medicine) was halted early because it was clear that patients receiving the drug weren’t benefiting.

All three antiviral meds are aimed at an enzyme influenza viruses need to release viral particles from infected cells. “If the drugs can prevent the replication of these viruses,” explained FiveThirtyEight, “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 is that happening? Jefferson is dubious. In studies where people with influenza-like illnesses were assigned to a drug with either the ability to inhibit replication of the virus or a placebo, the drugs worked for people with influenza as well as those who ultimately tested negative for the flu. (The drugs work best when given early on, and it takes a few days for test results to determine if someone really had the flu or not.)

Other viruses can cause flu-like symptoms, but the specific flu enzyme isn’t found in other respiratory viruses, Jefferson said. So if the drug works for both groups of patients, it must be doing so for some other reason. And if the drugs make you feel better because of that other reason, “it’s possible they’re nothing more than expensive alternatives to acetaminophen and ibuprofen, which alleviate aches and reduce fevers,” according to FiveThirtyEight.

Acetaminophen is the active ingredient in Tylenol, and ibuprofen is the active ingredient in Advil. They sell over the counter for a few dollars, but Tamiflu retails for about $130, Relenza for about $67 and Rapivab for about $1,000.

There’s just not enough evidence to draw firm conclusions about how the antiviral drugs work, and Jefferson’s team at Cochrane, as well as editors of the British medical journal (BMJ) have been trying for years to get complete clinical trials data from the maker of Tamiflu. If it’s such a slam-dunk flu treatment, why is this so difficult? (See our post of a couple years ago, “The Trouble with Tamiflu.”

Last spring, Cochrane published its latest meta-analysis of all the evidence it could get on Tamiflu. The researchers concluded that the drug can reduce the duration of flu symptoms by a little less than a day in adults, and similar results were seen for the other antiviral drugs.

But to get even that modest effect you must take the drugs in the first 48 hours from the onset of symptoms. Not many people spring into the doctor’s office after only a couple days of feeling punk. That’s the point of the CDC’s promotion: Don’t wait until it’s too late (to get the maximum benefit).

But, all things considered, that maximum is pretty minimal.

Dr. Brian Alper is founder of DynaMed, a company that monitors and assesses the latest medical evidence to inform doctors. He believes that deciding whether the drugs are right for you means considering the hassle of getting a doctor’s appointment and picking up the prescription at the pharmacy for what could be a hefty price, never mind the potential side effects. They include vomiting, dizziness and delirium.

The picture might be different for people whose underlying health problems such as asthma or immune disorders, would make a bout with the flu worse than for an otherwise healthy individual, who might shorten the agony by a day but in the meantime spread the virus around the doctor’s office and the pharmacy.

As FiveThirtyEight concluded, “[I] f you’re generally healthy, it may be that the best thing you can do for yourself, and your community, is stay home and practice some self-care.”

Patrick Malone & Associates, P.C. listed in Best Lawyers Rated by Super Lawyers Patrick A. Malone
Washingtonian Top Lawyer 2011
Avvo Rating 10.0 Superb Top Attorney Best Lawyers Firm
Contact Information