Time Magazine
February 20, 2005


A permanent director and a new safety panel may not be enough to
bring the agency back to health

By Christine Gorman

Like any government agency that has been around for almost a
century, the U.S. Food and Drug Administration (FDA) has
endured its share of rough patches. But "rough patch" hardly
begins to describe all the bad news that has battered the
agency over the past few months, from the possible suicide
risks with antidepressants like Prozac, Paxil and Zoloft to the
cardiac risks of pain-killers like Vioxx, Celebrex and Bextra.
Americans depend on the FDA to carefully weigh the benefits and
risks of all drugs before approving them, but the agency has
had trouble lately shaking the growing perception, justified or
not, that it has been working harder protecting the
pharmaceutical industry than the public it's supposed to serve.

The pressure for action grew so intense by last week that the
FDA was forced to take action. On the eve of an extraordinary
three-day hearing to air grievances resulting from the Vioxx
and Celebrex snafu, it announced plans to create a new safety
board to monitor drugs for unexpected side effects that show up
after the drugs have gone on sale. Meanwhile, the Bush
Administration finally moved to fill a one- year power vacuum
at the top of the organization by nominating its acting chief,
Dr. Lester Crawford, to be the FDA's permanent head.

Crawford wasted no time signaling a change in direction. "Our
culture is not to alarm the public," he told employees at a
department briefing, referring to the agency's practice of
keeping mum about apparent side effects until they have been
scientifically confirmed. "That era has passed. What the public
is demanding is to know as soon as we know."

So far, however, the flurry of activity has done little to
mollify critics both outside the agency and within. "I think
the FDA is beginning to admit, in sort of a halting and
hesitating fashion, that it hasn't done a good job with drug
safety," says Dr. David Graham, the associate director for
science and medicine in the agency's Office of Drug Safety and
its chief whistle-blower. Graham calls the latest changes
"cosmetic." An FDA official counters, saying they are
"significant" and promise to have "a profound impact."

Democrats in Congress argue that the latest dustups show that
the FDA needs more regulatory power and a bigger budget to
stand up to the pharmaceutical industry. But the most
aggressive attacks have come from a Republican, Iowa Senator
Chuck Grassley, 71, chairman of the Senate Finance Committee.
Normally the FDA would be the province of the Senate Health
Committee, which usually has to approve any changes at the
agency. But Grassley, whose state has many elderly
constituents, has focused on the FDA for a year -- ever since
he learned that the agency held close to its chest worrisome
data suggesting that certain antidepressant drugs might
increase a teenager's risk of suicide. Grassley plans to
introduce a bill next month that would create a new Office of
Drug Safety independent of the FDA department that approves

"We've seen some evidence over the last year that the agency
has been too cozy with drugmakers," Grassley says. An
independent safety board, he argues, would ensure that the
experts who are responsible for finding and publicizing
unexpected side effects are not the same ones who originally
gave the drug a clean bill of health.

It's a humiliating turn of events for an agency whose approval
was once considered the world's gold standard of drug safety,
especially after 1960, when it refused to approve thalidomide
for use in the U.S. until it had more data and thus spared
Americans the birth defects that plagued newborns in Europe and
South America. In some ways, the FDA's recent troubles can be
traced back to a pair of reforms that were made in the 1990s
and hailed at the time as great innovations. Responding to
complaints from AIDS activists and the pharmaceutical industry
that drug approval was taking too long, the agency in 1992
announced a "fast track" for vital medications to treat life-
threatening diseases. Although they would not be subjected to
lengthy safety trials, fast-tracked drugs were supposed to be
carefully monitored by their manufacturers after release to the
public for any unexpected side effects. It was a compromise
that made sense because problems are more likely to surface
when millions of patients are taking a drug as opposed to the
few thousand in a clinical trial. Over the years, however, as
the drug-approval part of the arrangement grew, manufacturers
became increasingly reluctant to undertake expensive
postapproval safety studies.

Then, in 1997, the FDA -- this time under pressure from drug
manufacturers and their friends in Congress -- loosened the
rules on direct-to-consumer advertising of prescription
medications. Soon the airwaves were saturated with
pharmaceutical messages, complete with big-budget videos and
catchy jingles. Side effects received scant play, and most
viewers assumed that if the drugs were FDA approved, the risks
were probably minimal. Patients bombarded their doctors with
requests for the new drugs. Harried physicians often acquiesced
so they could address what they thought were more pressing
needs. Demand for heavily promoted blockbuster drugs quickly

By late 1998, when the first of the cox-2 inhibitors won FDA
approval, the stage was set for a debacle. The easiest side
effects to detect, once a drug is used by large numbers of
people, turn out to be the rare ones. Most doctors don't see
very many cases of liver failure, for example. So they notice
right away if more and more of their patients get hospitalized
for it. The problem with cox-2 inhibitors like Vioxx is that
they increase the risk of two very common ailments: heart
attacks and strokes. It's much harder to tell, without careful
statistical analyses, when common events become more common.
"The [drug-approval] system was tested in ways it was never
tested before," says Dr. Eric Topol, chairman of cardiovascular
medicine at the Cleveland Clinic. "In an era of mass marketing,
where data may show uncertainty and where the FDA has no real
authority to take action, this class of drugs was set up to

Beefing up the FDA's safety portfolio or farming it out to
another agency are two ways to address that kind of failure.
Another would be for manufacturers to design their drug trials
so that more attention is paid to the effects on all patients
who take them, not just the relatively healthy ones usually
used in their studies. A fourth would be to force drug
companies to publish all their clinical data, not just the data
that show their product in the best light. Editors at several
prominent research journals are calling for measures that would
do just that.

In the meantime, the FDA keeps plugging along. It's a small
agency with a fine old tradition dwarfed in both budget and
political power by the pharmaceutical giants it is being asked
to police. It's going to take more than a three-day hearing to
straighten that out.

-- Reported by Perry Bacon Jr. and Mark Thompson/Washington and
Alice Park/New York

Copyright 2005 Time Inc.