Drugs Cause Problems They Are Supposed to Prevent
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.
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.
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
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.
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.
is a wide-scale institutional failure,” he said. “We have placed
far more resources and requirements upon premarket assessment of drugs than
Jason Karlawish, a University of Pennsylvania ethicist who studies the ways
new treatments are developed and disseminated, expressed a similar concern.
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.
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.
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.
has to be a better system,” Dr. Rosen said.
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.
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.
is priceless,” he said.