Medical Journal Calls
for a New Drug Watchdog
The United States needs a better system to detect harmful effects
of drugs already on the market, and it should be independent of
the Food and Drug Administration and the drug industry, medical
researchers and journal editors said.
Arguing that it was unreasonable to expect the same agency that
approves drugs to "also be committed to actively seek evidence
to prove itself wrong," the editors of The Journal of the American
Medical Association recommended that the nation consider establishing
an "independent drug safety board" to track the safety of drugs
and medical devices after they were approved and in widespread
The idea has been proposed several times, usually after a spectacular
drug imbroglio like the recent withdrawal of the popular arthritis
drug and painkiller Vioxx after it was linked to heart attacks.
But the earlier proposals went nowhere.
This time around, as in the past, the industry and the drug agency
reacted by challenging the need for a new safety board.
"It is not at all clear that there is need for change," Jeff Trewhitt,
a spokesman for PhRMA, the trade group for drug makers, said.
Dr. Sandra Kweder, deputy director of the Office of New Drugs
at the F.D.A., said a safety board was not necessary because "we
consider our office of drug safety independent of the office of
But both also left open the possibility of change in the future,
depending on the findings of a study to be conducted by the Institute
of Medicine, a branch of the Congressionally chartered National
Academy of Sciences, which conducts scientific reviews for the
An act of Congress would most likely be needed to establish an
independent board to evaluate the safety of drugs after they reach
the market. The recommendation for a new safety board appeared
in an editorial and in one of several articles that were scheduled
for the Dec. 1 issue of the journal but were published online
yesterday at www.jama.com.
The articles were released early because of their relevance to
recent events: the Vioxx withdrawal and the addition of a strong
warning to antidepressants because of evidence that they may raise
the risk of suicidal thinking or suicide attempts in teenagers.
Those actions led to Congressional hearings last week and complaints
that the drug agency was not moving quickly enough to get dangerous
drugs off the market or to warn consumers about risks that emerged
after drugs were approved.
Senator Charles E. Grassley, the Iowa Republican who led the hearings,
favors an even stronger separation between the F.D.A.'s offices
of new drugs and drug safety, a spokeswoman said yesterday. Mr.
Grassley could not be reached for comment on the proposal for
a new safety board.
The nation's current system for tracking drug side effects, called
Medwatch, is rife with inadequacies, the editors of the journal
wrote. The major problem, they said, is that drug makers are the
ones who collect and evaluate most of the information on side
effects from their own products and then report it to the F.D.A.
The companies "may be tempted to conceal" unfavorable data, the
editors wrote, and they and the drug agency may be too slow to
order studies to follow up hints of trouble.
Another flaw the editors cited is the system's reliance on voluntary
reports from doctors, which means that most adverse effects probably
go unreported. In addition, they said, most of the reports are
of poor quality and cannot be used to determine how common side
effects are or whether particular problems resulted from medicines
or from the illnesses they were meant to treat.
The reports can be used as red flags, particularly if they concern
rare conditions that would be hard to explain as anything other
than a drug effect. But researchers say a passive system like
Medwatch cannot be expected to pick up a drug-related increase
in a disease that is already very common, like heart attacks or
stroke. Carefully controlled studies are required to detect such
problems - and they are not done often enough, researchers say.
The journal editors also noted that although drug companies have
agreed to conduct postmarketing studies as a condition of approval
for certain drugs, fewer than half the promised studies have been
completed and many have not even been started.
Dr. Kweder, of the F.D.A., said, "We have very little authority
to make sure those postmarketing commitments are carried out."
Legislation would be needed to give the agency that power, she
But she said she did not see the need for an independent safety
agency, given the separation between the Office of Drug Safety
and the Office of New Drugs.
"We believe there is a healthy tension between those offices and
there should be," Dr.. Kweder said. But, she added, "We are certainly
willing to consider what alternatives there might be or how to
facilitate that separation further."
That openness to change, she said, is why the drug agency asked
the Institute of Medicine to evaluate its ability to track drug
Mr. Trewhitt, the PhRMA spokesman, also said the F.D.A.'s Office
of Drug Safety was independent enough, and noted that it would
be doubling its staff by adding 106 officers over the next few
years. He said "it would be wise" to wait for the Institute of
Medicine's recommendations before making any changes in postmarket
Other articles in the journal included a contentious exchange
between doctors and a lawyer for Bayer over the company's drug
Baycol, a cholesterol-lowering statin drug that was taken off
the market in 2001 because it caused muscle breakdown in some
The doctors, who acted as expert witnesses for plaintiffs suing
Bayer, relied in part on company documents that became public
during the case to conclude that Bayer had withheld or delayed
releasing data that would have revealed the problems with Baycol
and might have led to an earlier withdrawal.
"My judgment is that pharmaceutical companies may have too high
a threshold for taking action in a timely fashion to protect the
health of the public," one of the experts, Dr. Bruce M. Psaty,
a professor of medicine and epidemiology at the University of
Washington, said in an interview.
In a published response in the journal, Bayer's lawyer, Joseph
D. Piorkowski Jr., denied that Bayer had acted too slowly, and
said that the company had acted responsibly by withdrawing the
Bayer also issued a statement that said, in part, "The company
believes the article is unscientific, lacking in fair balance
and objectivity," and questioned the doctors' objectivity because
they had worked for the plaintiffs suing the company.
Like the journal editors, Dr. Psaty recommended that an independent
safety board be formed, perhaps appointed by Congress, to decide
when drugs should be taken off the market.
Not all researchers agree. In another article in the journal,
Dr. Brian L. Strom of the University of Pennsylvania School of
Medicine said, "Our F.D.A. colleagues can be trusted to do the
job, given sufficient resources."
But Dr. Alastair Wood of Vanderbilt University, an expert on drug
research and regulation, who did not contribute to the journal,
said he thought an independent board was needed.
Dr. Wood said: "When we have a drug problem it's analogous to
a plane crashing off the coast of New York City, and being investigated
by the air traffic controllers who controlled the flight and the
airline flying the plane. They're not bad people, but it's not
the way we do things in this country."
Reference Source 117
November 25, 2004