FDA Told U.S. Drug
System Is Broken
Expert Panel Calls For Major Changes
By Shankar Vedantam
Washington Post Staff
Writer
Saturday, September 23, 2006; A01
The federal system for approving and regulating drugs is in serious
disrepair, and a host of dramatic changes are needed to fix the problem, a
blue-ribbon panel of government advisers concluded yesterday in a long-awaited
report.
The analysis by the Institute of Medicine shined an unsparing spotlight on
the erosion of public confidence in the Food and Drug Administration, an agency
that holds sway over a quarter of the U.S. economy. The report, requested by the
FDA itself, found that Congress, agency officials and the pharmaceutical
industry share responsibility for the problems -- and bear the burden for
implementing solutions.
The report represents a watershed moment after two years of controversy over
the safety of such widely used drugs as pain relievers and antidepressants. The
Institute of Medicine is part of the National Academies, chartered by Congress
to advise the government on scientific and health policy issues. Its
recommendations traditionally carry great weight.
The 15 experts drawn from academic and professional organizations were
unanimous in endorsing the recommendations, which called for several major
policy changes. Several of these have long been urged by drug safety advocates
but have been resisted by the industry, Congress and the FDA itself. A number of
them would require congressional approval.
The panel called for a moratorium on consumer advertising of newly approved
classes of drugs until they have been on the market long enough for unrecognized
side effects and risks to emerge. Packaging for new types of medications should
also carry a special symbol, such as the black triangle required in Britain, to
alert patients that the drug's safety profile would not be fully known until it
had been more widely studied, the report said.
The FDA should reevaluate safety and effectiveness data of such new drugs
within five years after initial approval, the panel added, and the agency needs
new powers to impose fines and requirements on drugmakers. In addition, the
report called for the agency to have authority to place a wider range of
restrictions on drugs it deems risky.
Manufacturers should also be required to register all clinical trials they
sponsor in a government-run database to allow patients and physicians to see the
outcome of all studies, not just those published in medical journals, the report
said. Studies that show positive results for a drug are more likely to be
published by journals than negative ones.
The committee also took aim at FDA management, citing a history of
intra-agency squabbling and conflicts of interest on the expert advisory panels
appointed by the agency to review the scientific data on proposed new drugs and
devices. A substantial majority of advisory panel members should have no ties to
industry, it said.
"FDA's credibility is its most crucial asset, and recent concerns about the
independence of advisory committee members . . . have cast a shadow on the
trustworthiness of the scientific advice received by the agency," the report
said.
To reduce turnover and political interference, the institute said, the FDA
commissioner should be appointed to a fixed six-year term. Currently, the
commissioner serves at the pleasure of the president.
Agency officials said they will take the report seriously but added that
changes implemented over the past year meant that the report is somewhat out of
date. Acting FDA Commissioner Andrew C. von Eschenbach said the agency is
especially focused on improving its scientific, technological and communication
methods.
The pharmaceutical industry echoed the agency's response.
"Though there is always room for improvements, it would be a mistake to
accept the notion that the FDA drug safety system is seriously flawed," the
Pharmaceutical Research and Manufacturers of America said in a statement. "After
all, fewer than three percent of approved prescription drugs have been withdrawn
from the American market for safety reasons over the last 20 years."
But Sen. Charles E. Grassley (R-Iowa), who has led a number of investigations
into the workings of the FDA in recent years, said the agency's reaction to a
report it had commissioned speaks volumes.
"The FDA appears to be focused on damage control rather than addressing its
core problems," Grassley said in a statement. "As a science-based agency, the
FDA is remarkable for its lack of introspection, second-guessing, and failure to
assess its own performance and capabilities in a systematic way."
Much of the institute's report focused on a central gap in drug regulation:
While the FDA demands strict data on efficacy and safety from clinical trials
before approving a new drug, less attention is paid after the drug reaches the
market.
A safety problem that occurs once in every thousand patients, for example,
would be unlikely to show up in clinical studies of a few hundred people, but it
could result in thousands of serious side effects once the drug is approved and
being taken by millions. The current system for monitoring adverse effects is
nowhere near as systematic as the evidence collected before approval, the report
said.
Besides, said R. Alta Charo, a panel member and bioethicist at the University
of Wisconsin at Madison, patients who participate in drug trials are carefully
selected, and hardly typical of patients in the real world who usually suffer
from more complex problems.
"A drug tested in a few hundred or thousand people is very different when
used by millions, especially over long periods of time and in conjunction with
other supplements," she said.
While the agency can negotiate with companies to conduct long-term,
post-approval studies, there are glaring gaps in such information, the report
said. This is partly why the report also recommended limits on advertising new
drugs. The report's authors acknowledged, however, that limits on advertising
could run afoul of constitutional free-speech guarantees.
Charo also cited "a lack of collaboration among divisions, tensions [and]
inappropriate management" at the FDA, saying officials who focus on safety
issues are chronically underfunded compared with those who handle new-drug
approvals.
Part of the problem, the report said, is that the money paid by industry to
help fund FDA's regulators, under a 1992 law designed to speed up new drug
reviews, cannot under the law be diverted to FDA's safety division, which
suffers from chronic underfunding.
"What the report does not do very well is explain that the vast majority of
interactions at the center are successful," countered Steven Galson, who directs
the FDA division that evaluates new drugs. Still, he added, "I accept the
recommendation and see it as an opportunity to improve."
Scott Lassman, senior assistant general counsel for the drug industry group,
said it would study the report carefully. He said that the industry is open to
suggestions for greater transparency but that the FDA already has enough
authority to act after drugs are approved.
The trade group also opposes mandatory registration of clinical trials
because that would force companies to reveal trade secrets to competitors,
Lassman said. Manufacturers also oppose restrictions on advertising, he said,
adding that advertisements help educate patients about problems and
treatments.
? 2006 The
Washington Post Company