October 20, 2010
In the past month, the Food and Drug
has concluded that in some cases two types of drugs that were
supposed to be preventing serious medical problems were, in fact,
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
The Mayo Clinic Proceedings published an
earlier blow to Avandia where
researchers found it caused heart failure and a buildup of fluid in
the lungs in men.
But now the FDA and drug regulators in Europe are restricting
Avandia’s use because it appears to increase heart risks.
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
Dr. Jason Karlawish, a University
of Pennsylvania ethicist who studies the ways new treatments are
developed and disseminated, expressed a similar concern.
Such discussions make Dr. Ethel Siris, an osteoporosis expert
at Columbia-Presbyterian Medical Center, nervous.
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
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 'me' 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
He favors something different - the development of a national
electronic drug database that would reveal drug use and
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.