TOUGH RULES FOR KID DRUGS

FDA: Improve Safety Testing

WASHINGTON - The government Friday issued new rules that require drug
companies to conduct much wider testing of drugs in children, so the
companies can write labels that provide detailed information to doctors and
parents about the proper use of medications by children.

The final rules, issued by the Food and Drug Administration, were a top
priority for President Clinton and Hillary Rodham Clinton but met with
strenuous objections from many drug companies, which said they were
impractical and burdensome.

Pediatricians and patients' groups praised the rules.

``This is a good thing. Children are not just little grown-ups,'' said Dr.
Lucy S. Crain, chairwoman of the California Division of the American
Academy of Pediatrics.

Because children have immature kidneys and livers, they metabolize
medicines differently than adults, Crain said. It is inappropriate, and
potentially dangerous, to calculate doses by simply downsizing adult doses,
she said.

``The correct dosages of many life-saving drugs, like anti-cancer
chemotherapeutic agents, have not been calculated for use in children,''
she said. The new FDA regulations will also guide parents in the use of
common over-the-counter drugs like adult Tylenol and cold medications,
Crain said.

For children under the age of 2, almost all medicines lack important dosage
information, said Crain, a San Francisco pediatrician who practices at
UC-San Francisco Medical Center.

The White House said drug companies rarely did the studies needed to assess
the safety and proper dosage of drugs widely used to treat childhood
illnesses. Instead, many drugs prescribed for children were tested only in
adults, with an assumption that the drugs' effects on children would be
very similar. About 20 percent of the drugs marketed in the United States
have been tested and labeled specifically for children.

Shared Goal

Drug companies said they shared Clinton's goal of discovering better
medicines for children. But they said the new tests would be costly and
could be unethical, because they might put thousands of children at risk.

Under the rules issued Friday, pharmaceutical companies must generally
study the safety and effectiveness of drugs and vaccines in children ``if
the product is likely to be used in a substantial number of pediatric
patients,'' or if it provides a ``meaningful therapeutic benefit'' over
existing treatments for children in the same age group.

To gain FDA approval for their products, drug companies will ordinarily
have to submit data showing their ``safety and effectiveness and benefits
and risks'' in children.

Despite commitments by drug companies to do more studies in children, ``the
percentage of new products entering the marketplace with adequate pediatric
safety and effectiveness information has not increased in the last
decade,'' the agency said.

``It is not profitable for pharmaceutical companies to do testing of
medicines in kids,'' said pediatrician Dr. Dean Didech of San Jose Medical
Group.

The final rules are, in some ways, more flexible than the proposals issued
by the Clinton administration in August 1997. Under the final rules, for
example, the FDA may allow a company to defer testing in children until
clinical trials suggest that a new drug is safe and effective in adults.
Indeed, the agency said, in some cases, pediatric testing will occur after
a new drug has been approved for use by adults.

Various Factors

Rather than impose a rigid, uniform rule for all new drugs, the government
said that the timing of pediatric studies would depend on various factors.

If, for example, a new drug is urgently needed to treat a life-threatening
disease in children and if there is no adequate therapy on the market, the
government may insist that the manufacturer immediately begin tests in
children, before full data on adults are available. But pediatric studies
could begin later if similar medications were already available for children.

Judith Bello, executive vice president of the Pharmaceutical Research and
Manufacturers of America, a trade association for the industry, said
Friday, ``We haven't seen the final rules and won't be able to comment
today.''

In written comments on the proposed rules, drug companies including Merck,
Glaxo Wellcome, Novartis and Wyeth-Ayerst said they wanted to discover
better medicines for children, but found the details of Clinton's proposal
extremely impractical and burdensome.

Moreover, the companies said that children injured in drug tests might file
lawsuits years later, after they grow up, even though parents gave consent
for the tests. The companies said they could not obtain informed consent
from children as they do from adults.

In response, the Clinton administration said that children need not be
exposed to ``inappropriate risks'' because drug companies could defer
pediatric testing until new drugs were shown to be safe and effective for
adults.

The rules will be published next week in the Federal Register and will take
effect, with the force of law, on April 1.

Checked-by: derek rea