To paraphrase Freud, "What does the FDA want?" For a couple of
days in early March, the answer was unclear as the U.S. Food and Drug
Administration (FDA) tried to sort out its message on the best ways to ensure
David Fassler, M.D. (left), Sen. Michael Enzi (R-Wyo.), and William B.
Schultz, J.D., a former FDA deputy commissioner, talk during a break of a
Senate hearing last month on the future of the FDA and what steps are
necessary to ensure drug safety in the United States.
Photo: David Hathcox
In testimony before a Senate committee delivered two days apart, two FDA
officials offered contradictory statements on the approach to drug-safety
First, Sandra L. Kweder, M.D., deputy director of the Office of New Drugs
at the FDA, told the panel that the FDA needed additional powers to require
new clinical trials and to order label changes for drugs when safety questions
arise following approval.
"Stronger authority to change labeling would be helpful," she
said, addressing the Senate Committee on Health, Education, Labor, and
Pensions on March 1.
But 48 hours later, Janet Woodcock, M.D., acting director for operations at
the FDA, addressing the same committee, said that new legislation granting
such authority was unneeded. The FDA will not have an official position on
these issues until the Institute of Medicine completes its study of
postapproval drug-safety monitoring, she said. Woodcock outranks Kweder at the
FDA so her statement was taken as superseding Kweder's earlier remarks.
Woodcock also placed greater emphasis on the FDA's proposed "Drug
Watch" Web page, which would get "information directly out to
people who need it in a timely
Sandra L. Kweder, M.D.: "You can't anticipate how a drug will be
marketed or used."
Photo: David Hathcox
Other witnesses supported the FDA's February announcement of the formation
of an independent Drug Safety Oversight Board, saying it was an important
first step, but they also called for greater transparency in clinical-trials
data and controls on direct-to-consumer advertising.
"This is a time for re-evaluation of the FDA," said committee
chair Sen. Michael Enzi (R-Wyo.), referring to controversies like the Vioxx
recall and warning labeling for SSRIs. "It's appropriate to react to
recent events, but not to overreact."
The hearings, held on two days, served as the opening of a fact-finding
process intended to guide a congressional response to concerns about drug
safety, according to a joint statement by Enzi and ranking minority member
Sen. Edward Kennedy (D-Mass.).
"Since 1992, more funds have been available to speed approval, but
drug safety checks have not kept pace," added Kennedy at the hearing."
The FDA needs clear authority to assess risk and change labeling,
conflicts of interest must be addressed in advance, and patients need
information in understandable language."
The FDA's approval process is still the "gold standard" for
evaluating drugs, Kweder said, adding that no one could identify in advance
all risk from a drug. "You can't anticipate how a drug will be marketed
The agency cannot evaluate a drug in terms of only risks or only benefits,
she said. A drug whose side effects included itching would have to be
considered in a different light from one that caused liver failure, for
instance. Even if a drug carried serious risks, the FDA might recommend
continued sale if there were also major benefits to some patient groups.
Currently, the FDA can only persuade, not force, drug companies to change
label content or take a drug off the market, said Kweder. Labeling changes
often require lengthy back-and-forth negotiations between the companies and
the agency, leading to long delays in remedial action, as occurred in the
A separate, outside safety panel is not needed because postmarketing drug
safety analysis would benefit from in-house expertise, and
conflict-of-interest issues would be fewer, she said.
"The data safety board will include FDA staff not involved in the
original review of the drug, as well as medical experts from other agencies
like the National Institutes of Health and the Department of Veterans
Affairs," she said. "Our goal is to create a source of
consumer-friendly information for health professionals and patients on
emerging health risks."
Representing APA, Vermont psychiatrist and APA Trustee David Fassler, M.D.,
put forth three proposals for improved safety.
In the light of recent concerns about SSRIs and suicidal ideation, the FDA
should create a new drug advisory committee focusing only on central nervous
system drugs for children and adolescents, he said. In addition, registration
of clinical trials is essential to allow physicians and patients access all to
data from both published and unpublished studies. Congress should also enact
new educational incentives and federal support for mental health training
programs to increase the number of health professionals available to treat
Calls for a drug-safety board do not mean that the FDA is broken, said
Thomas Fleming, Ph.D., a professor of biostatistics at the University of
Washington who has served on several FDA drug advisory committees. There is no
need for a separate outside group to monitor safety once a drug is on the
"The FDA staff is familiar with the regulatory process, serious
conflict-of-interest issues would arise with an outside board, and there would
be problems incorporating outside recommendations into the workings of the
agency," he said.
Not every product would require randomized controlled trials to test
safety, said Fleming. A surveillance system based on adverse-event reports by
clinicians and data from large, linked databases could signal safety issues,
he said. That safety signal would trigger the FDA's authority to require new
trials from manufacturers.
Another panelist, William B. Schultz, J.D., agreed that recent recalls and
labeling changes do not require a wholesale overhaul of the FDA.
"The fact that a drug has serious safety problems doesn't mean that
the FDA made a mistake [in the approval stage]," said Schultz, a former
FDA deputy commissioner for policy, now in private practice. Because of the
limited number of patients recruited, clinical trials conducted as part of the
premarket approval process were unlikely to detect either rare or common
adverse reactions, he said. Thousands of patients were included in those
clinical trials, but millions might take a new drug in its first years on the
market. The FDA should educate patients about the inherent risks of all
prescription drugs, he added.
"The FDA should remind physicians and patients about the additional
risks of newly approved drugs, and it should advise caution in taking drugs to
which large numbers of patients have not yet been exposed," he said.
The agency also needs sufficient money and staff to monitor drugs following
approval and should have authority to order changes in labeling or to require
postmarketing clinical trials to gauge safety. The FDA already can require
postmarket surveillance for medical devices but not for drugs.
Better disclosure about the safety of new drugs and a ban on
direct-to-consumer advertising for one or two years following approval could
reduce the pressure to prescribe new drugs before their risks are well known.
Finally, said Schultz, the the FDA should have the power to restrict
physicians' use of drugs to their stated indications or to limit distribution
of some drugs to certain specialists. Traditionally, the FDA has drawn a line
between approving drugs and regulating the practice of medicine.