By GINA KOLATA, Published: October 16, 2010
In the past month, the Food and Drug Administration has concluded that in some cases two types of drugs that were supposed to be preventing serious medical problems were, in fact, causing them.
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Prescriptions Blog: F.D.A. Warning on Bone Drugs (October 13, 2010)
One is bisphosphonates, which is widely used to prevent the fractures, especially of the hip and spine, that are common in people with osteoporosis. Those drugs, like Fosamax, Actonel and Boniva, will now have to carry labels saying they can lead to rare fractures of the thigh bone, a surprising new discovery that came after another surprise — that they can cause a rare degeneration of the jawbone.
The other is Avandia, which is widely prescribed for diabetics, whose disease puts them at risk for heart attacks and heart failure. Two-thirds of diabetics die of heart problems, and a main reason for taking drugs like Avandia is to protect them from that.
But now the F.D.A. and drug regulators in Europe are restricting Avandia’s use because it appears to increase heart risks.
In the case of bisphosphonates, the benefits for people with osteoporosis still outweigh the risk, bone experts say. And no one has restricted their use.
But the fact remains that with decades of using drugs to treat chronic diseases, the unexpected can occur.
Something new is happening, said Daniel Carpenter, a government professor at Harvard who is an expert on the drug agency. The population is aging, many have chronic diseases. And companies are going after giant markets, huge parts of the population, heavily advertising drugs that are to be taken for a lifetime.
And the way drugs are evaluated, with the emphasis on shorter-term studies before marketing, is not helping, Dr. Carpenter said.
“Here is a wide-scale institutional failure,” he said. “We have placed far more resources and requirements upon premarket assessment of drugs than on postmarket.”
Dr. Jason Karlawish, a University of Pennsylvania ethicist who studies the ways new treatments are developed and disseminated, expressed a similar concern.
“The point is not that the drugs are bad, but that drugs for these chronic diseases present a novel set of challenges about how to assess their safety,” he said.
But such discussions make Dr. Ethel Siris, an osteoporosis expert at Columbia-Presbyterian Medical Center, nervous. Bisphosphonates have been extensively studied, she said, and the thigh fractures from bisphosphonates — while surprising — are very rare. Dr. Siris’s fear is that people who really need the drugs will turn away from them.
It is not clear how the nation should respond to the new era of widespread drug use for chronic diseases.
“The basic underlying theme is that we don’t have good long-term safety indices for common chronic diseases that we are treating with major drugs,” said Dr. Clifford J. Rosen, director of the Maine Center for Osteoporosis Research. Dr. Rosen, in addition to studying osteoporosis, was on an advisory committee of the drug agency that examined the evidence that Avandia was linked to heart risks.
The difficulty is in figuring out how to assess the safety of drugs that will be taken for decades, when the clinical trials last at most a few years.
Today’s system, which largely consists of asking doctors to report adverse reactions and of researchers’ attempts to look at patient experiences in a variety of diverse databases, like records of large health plans, is ineffective, medical experts agree.
“There has to be a better system,” Dr. Rosen said.
Congress recently gave the drug agency the power to require studies after drug approval, but the agency has used it sparingly.
Some, like Dr. Rosen and Dr. Carpenter, would like large clinical trials after a drug is approved and continuing for years, even for drugs that met all the premarket requirements.
Dr. Karlawish questions whether this is practical. Once a drug is approved, it can be difficult to persuade doctors to assign their patients randomly to one approved treatment or another, and the sort of studies being suggested would go on for many years, making them difficult.
He favors something different — the development of a national electronic drug database that would reveal drug use and complications. In the meantime, Dr. Karlawish said, he could not help marveling at the paradox of drugs causing what they were supposed to prevent.
“This is priceless,” he said.