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Increased
Conservatism at FDA: Number of New Drugs Approved in First Half
of 2005 Decreases by Nearly 50%
By Gardiner Harris
Reprinted with permission
from The New York Times
Stung by a series
of drug safety scandals, the US Food and Drug Administration (FDA)
has in recent months issued a blizzard of drug-safety warnings and
approval times for new drugs are slower.
The
agency is issuing twice the number of public advisories about drug
risks as it did a year ago and adding five times as many black box
warnings - its most serious alert - to drug labels. And drugs approved
in the first half of this year took almost twice as long to get
that approval as drugs approved in the same period last year.
This new conservatism,
a response to fierce recent criticism from Congress that the FDA
has failed to protect the public against drug dangers, has upset
some doctors and drug makers.
Doctors say that
the agency's vague warnings and confusing advice mean that doctors
are not getting the information they need to avoid problems but
will get blamed for them anyway. Drug makers say the warnings are
scaring patients and reducing sales.
The apparent changes
have done little to mollify the FDA's many critics, who say that
the agency is either not doing enough, doing too much or failing
to be consistent.
"The FDA
should not be slowing things down or speeding them up depending
on how the wind blows," said Senator Charles E. Grassley, a
powerful Iowa Republican who has become one of the agency's toughest
critics. "Instead, the agency should be a rock of stability."
FDA officials
dismissed the notion that the agency has changed the way it regulates
drugs. "Maybe we're not being overly cautious but instead trying
to be responsive," said Dr. Scott Gottlieb, the agency's deputy
commissioner.
But Dr. Gottlieb
said that the agency's advisory committees - crucial arbiters of
drug risks - are vulnerable to a growing chorus of criticism. If
the advisory committees become more cautious, he said, the FDA might
follow their lead.
The agency once
avoided issuing disturbing warnings about drugs unless studies proved
that a risk was certain. Agency officials had worried that issuing
warnings about suspected problems would cause undue alarm and lead
patients to stop taking needed therapies.
But two episodes
over the last year - one involving antidepressants and suicide risk
and the other the withdrawal of the pain pill Vioxx - have led the
agency to become more cautious.
Now, instead of
waiting for proof, the agency has promised to issue public health
alerts about drug risks even when problems are only suspected. And
over the last year, it has demanded that pharmaceutical companies
add tough warnings for drugs as diverse as the antidepressant Zoloft,
because it might lead a small number of teenagers to become suicidal,
and the popular pain pill Advil, because it might in rare cases
cause heart attacks.
In each case, according to disclosures at open hearings, the
agency has acted with little or no evidence that the risks are real.
But it has demanded that warnings be placed on them anyway. In many
cases, patients have stopped taking the medicines in the wake of
the warnings. [emphasis added-Ed]
"Drug reviewers
have seen that the environment has changed, and they've become more
cautious because they don't want to be the next person hauled before
Congress," said Dr. Kenneth I. Kaitin, director of the Tufts
Center for Study of Drug Development.
Agency officials
say that they are simply trying to do a better job of communicating
drug risks directly to doctors, pharmacists and patients after years
of letting drug makers do most of the talking. The agency will soon
issue instructions to drug companies about how to send information
by e-mail directly to physicians about drug risks, Dr. Gottlieb
said.
Dr. Lester Crawford,
who last month was confirmed by the Senate to become the Food and
Drug Administration commissioner, has said that the agency can no
longer wait until risk information is proved but must communicate
its uncertainty to the public. This has left many physicians uneasy.
"They're just passing the blame onto the physician if
something goes wrong," said Dr. Phillip Kennedy, a family-practice
physician in Augusta, Ga. "They're just trying to say that
they warned us." Vague warnings about uncertain risks are difficult
for doctors to interpret, Dr. Kennedy said.[emphasis added-Ed]
Dr. William Schreiber,
an internist from Louisville, Ky., said that the agency's murky
and sometimes contradictory messages have hurt its credibility.
Many of us depend
on that agency to tell us that a drug is O.K.," Dr. Schreiber
said. "And when they miss the risks for a whole category of
significant drugs - and I'm still not sure whether they're right
- it makes you question the linchpins of the system."
The problem is
that the FDA is often uncertain about how important a potential
problem with a drug might be, Dr. Kaiten said.
"So, more
often than not, they just don't know what to tell physicians and
patients," Dr. Kaiten said.
When it is unsure,
the agency often advises patients to speak with their doctors, Dr.
Kaiten said, "but the physicians don't know what to tell patients,
either."
Dr. Jeremy A.
Lazarus, vice speaker of the House of Delegates of the American
Medical Association, said that there is a solution. "We think
there have to be better studies done that are adequately designed
and long enough to answer these questions," he said.
So
far this year, the FDA has issued 11 public health advisories about
drug risks compared with five in all of last year and two in 2003.
In the first half of 2005, the agency placed black-box warnings
- its most serious alert - on the labels of 45 drugs compared to
just 9 during a similar period last year.”
The agency is also taking more time to review new drug applications.
For drugs approved in the first half of 2005, the average time
from application to approval was 29 months, compared with an average
of 16 months for drugs approved in the first half of 2004. And
the FDA is more often asking that drug makers study the safety of
their medicines after they are approved. [emphasis added-Ed]
Dr. Gottlieb explained
that much of the recent increase in the number of black-box warnings
is due to the agency's decisions to place the warnings on 33 antidepressants.
He said that because the agency processes so few new drug applications,
average approval times can change substantially from year to year
because of a single difficult application.
The agency's growing
caution has drawn muted praise and scorn from critics. Dr. Sidney
Wolfe of Public Citizen said that the agency still is not cautious
enough. Dr. Jerry Avorn, a professor of medicine at Harvard Medical
School who for years criticized what he saw as a lack of caution
at the FDA, said that the agency has overreacted.
"They went
from comatose to spastic without any rational period in the middle,"
Dr. Avorn said.
Jack Calfee, a
resident scholar at the American Enterprise Institute who has long
criticized the agency for being overly cautious, said that its latest
actions are an unfortunate but understandable reaction to fierce
public criticism.
"It would
be amazing if they did not become more cautious in the wake of the
Vioxx episode," Mr. Calfee said.
Merck, the maker
of the painkiller Vioxx, withdrew the drug from the market in September
after a study found that it doubled the risks of heart attack and
stroke.
The Vioxx withdrawal
has been a driving force for some of the changes at the agency.
Critics in Congress pointed out in hearings that the FDA negotiated
with Merck for 14 months in 2001 and 2002 before any substantial
mention of Vioxx's heart risks appeared on the drug's label.
"When FDA
goes through a 14-month-long period to get a labeling change that
both it and its panel of experts agrees is necessary, that shows
us that something is wrong," Representative Maurice D. Hinchey,
Democrat of New York, said in a hearing last week.
Dr. Steven Galson,
director of the agency's center for drugs, answered Mr. Hinchey,
"We're not proud of how long that took, let me just be clear
about that."
The FDA does not own a drug's label, drug makers do. Short
of threatening to seize a drug if a label is not changed, the agency
must negotiate with drug makers over any changes. This can lead
to delays. Some in Congress have proposed giving the agency the
power to mandate label changes, but Dr. Crawford said that the Bush
administration has no position on these proposals. [emphasis added]
Even without legislation,
the agency is trying to fix the problem of delayed label changes
by moving away from its almost complete reliance on drug labels
to communicate with physicians and patients. Instead, the agency
is increasingly using the Internet, news releases and public health
advisories.
Two weeks ago,
the agency issued a news release about the recall of 206,000 intravenous
pumps made by Baxter International, a first for such a recall. In
the past, the FDA had asked companies to publicize such recalls.
The agency recently created a Drug Safety Oversight Board that will
likely encourage more such communiqués.
But public warnings
issued by the agency garner far more attention and create more alarm
than those made by drug makers.
Some experts worry
that physicians and patients will stop paying attention if the FDA
issues too many warnings. Agency officials say that they are aware
of this problem.
Still, FDA observers
are predicting that the agency will remain cautious for some time
to come.
"The FDA
came under a lot of criticism, and it's reacting as regulators do,"
said Dr. Alastair Wood, an associate dean at Vanderbilt University
Medical Center. "Now the pendulum is swinging a bit too far
the other way."
08/08/05
Source
G
Harris. FDA Responds to Criticism with New Caution. The New York
Times. August 6, 2005.
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