Most drugs never tested for safety in
Children seen facing risks from medicines
Pediatricians are forced to engage in risky "trial-and-error"
medicine when they give drugs to children because two-thirds of
all drugs they routinely prescribe have never been adequately
studied on kids, according to a study by Food and Drug
Administration researchers to be published today in the Journal
of the American Medical Association.
What's more, when certain drugs developed for adults were
methodically tested in children, researchers found previously
unknown safety risks, including higher incidences of death,
seizures, and suicidal thoughts, according to new data contained
in the study.
"Most people don't have any idea that such a low
proportion of prescription medicines have never been approved as
safe and effective for kids," said Dr. Peter P. Budetti, a
professor at the University of Oklahoma College of Public Health
who wrote an editorial accompanying the study.
"You can't treat children merely as small adults," he said.
"Just because a child weighs one-tenth the amount of an adult,
it doesn't mean they can take one-tenth of that drug. They may
not be able to take that drug at all."
The lack of trials is a growing concern in Washington, where
the Senate last month unanimously approved a bill that would
give the FDA authority to require drug companies to test new
drugs for safety, efficacy, and dosing information in children.
The measure is pending in the House.
It's both legal and common for doctors to prescribe drugs for
children that haven't been fully tested on them, as long as the
drugs have shown to be effective in limited studies. But with
major differences in physiology between adults and children,
doctors have long worried that relying on these so-called
"off-label" indications is inadequate.
The study bolstered those concerns with drugs doctors had
been using for years. After full trials were performed on
children given an anesthesia drug called Diprivan in intensive
care units, for example, researchers found a statistically
higher risk of deaths than for children given different forms of
anesthesia. Another anesthetic, Ultane, triggered rare cases of
seizures in young adults and children with no history of
seizures. An antiviral therapy called Rebetron was associated
with suicidal thoughts in 2.4 percent of children, compared with
1 percent for adults given the drug, according to the FDA.
In an interview, Dr. Richard Gorman, a Baltimore pediatrician
and chairman of the American Academy of Pediatrics' committee on
drugs, said an epilepsy medication called Neurontin prescribed
to control pain in some children was ineffective because the
dose was too small. Once clinical trials were performed, it
turned out that the dosing schedule had been improperly
recalculated for children. The original dosing was based on
children's weight alone, without taking into account their
"We were giving it to kids in good faith to help their pain,
and it didn't work," he said. "You have kids who suffered
needlessly because the data wasn't there."
Dr. Richard Parad, a specialist in neonatal intensive care at
Brigham and Women's Hospital in Boston, said none of the drugs
he uses to treat premature infants for potentially deadly
pulmonary disorders has FDA approval for pediatric uses. He said
he has picked up expertise in off-label dosing for these drugs
by reading medical journals.
"Most of the tools we use as pediatricians are kind of
hand-me-downs that have been tested and tried in adults," he
The pace of trials did not pick up significantly until
Congress approved the Food and Drug Administration Modernization
Act of 1997. That gave drug companies an additional six months
of market exclusivity, with no generic competition, if they
voluntarily performed pediatric clinical trials. There have been
risks associated with the accelerated trials, including deaths
and lawsuits relating to alleged ethical lapses.
The FDA researchers who wrote the study published today did
not discuss those concerns. They pointed to the benefits of the
government's incentive: 53 drugs have won the exclusivity
provision and 49 drugs have new labels updated with pediatric
information. Thirteen of the findings or labeling changes were
considered "significant" by the FDA, meaning they revealed
improper recommendations for dosage that affected safety or
In 1998, the FDA imposed a requirement that all drugs with
possible pediatric indications be tested on children, but that
was thrown out by a US District Court judge in Washington last
year after a legal challenge by several groups that lobby for
fewer regulations, including the Competitive Enterprise
Institute and the Association of American Physicians and
Surgeons. The bill passed by the Senate in July would restore
the rule legislatively.
Opponents say requiring pediatric clinical trials will slow
down new drug approvals and make it more difficult for companies
to bring drugs to market. Sam Kazman, general counsel of the
Competitive Enterprise Institute, said the measure would
discourage drug companies from researching new uses for drugs if
they believed off-label pediatric uses might trigger FDA
requirements for expensive, full-blown clinical trials.
The drug-industry trade group, the Pharmaceutical Research
and Manufacturers of America, backs the voluntary provisions of
the 1997 law.
Budetti, who wrote the journal editorial, said the FDA needs
to wield a regulatory stick because drug companies on their own
aren't performing enough trials, in part because there are fewer
child patients than adults. "Just in terms of the financial
incentive, there is not the same kind of gain for pharmaceutical
companies to be spending the money that it costs to run the
tests in children, because the market isn't going to be there,"
he said. Until the climate improves for pediatric clinical
trials, he added, parents must be advocates for their children.
"It is fair to ask questions like, `How widely is this drug
used in children,' and `Is it approved or not by the FDA,' " he
Christopher Rowland can be reached at
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