By Lisa Seachrist

Washington Editor

WASHINGTON — Noting that less than half the drugs commonly prescribed to children have been tested in pediatric populations, President Clinton announced in a White House ceremony a proposed FDA regulation requiring that all new drugs and biologics detail pediatric dosages on their labels.

The proposed rule is designed to aid physicians and parents in making decisions about medications they give to children. This comes on the heels of a 33 percent decline in testing drugs in children since 1991 despite agency efforts to encourage drug sponsors to perform such studies.

"The executive action I take today simply is designed to ensure that parents and pediatricians have the safety information they need," Clinton said. "Doctors have known for a long time that children respond differently to many drugs. Without clear guidance, pediatricians sometimes decide not to prescribe for children drugs used successfully by adults, and this means that children may very well be denied the very best treatment available."

Developing a drug for children can take an enormous amount of effort. Manufacturers must be certain that the drug has merit before exposing children to potentially unnecessary risks. In addition, developing chewable and syrup formulations of medications can prove difficult. As a result, many manufacturers have chosen to forgo testing in children.

The result, however, is that a large number of drugs commonly used to treat childhood diseases like ear infections and asthma have never been tested in children.

"When it comes to prescribing children's medication, information about how much and how often to give it to them is sorely lacking," said Joseph Zanga, vice president of the American Academy of Pediatrics. "For example, asthma is the leading cause of hospitalization of children in the U.S., and commonly affects children younger than age five. Despite that, there is only one asthma drug labeled for use in children under the age of six."

In order to motivate manufacturers to test their products in children, the FDA simplified the required pediatric data in 1994 and encouraged manufacturers to voluntarily submit the data for review.

"We did not get the kind of progress that we had hoped," said Donna Shalala, secretary of the Department of Health and Human Services. "Kids deserve the same kind of access to newly developed drugs that their parents get."

Shalala and the president noted that this regulation as well as provisions in congressional FDA reform efforts should encourage manufacturers to test their products in children. In the Senate, Sen. Michael DeWine (R-Ohio) and Sen. Christopher Dodd (D-Conn.) have sponsored the Better Pharmaceuticals for Children Act, which provides six months additional market exclusivity for drugs tested in children. Their provision was incorporated into the FDA reform bill, S. 830. Rep. Jim Greenwood (R-Pa.) and Rep. Henry Waxman (D-Calif.) are spearheading efforts in the House.

"[The Congressional] approach is compatible with the rule we're announcing today," Clinton said. "And I look forward to working with them on this issue as Congress continues our bipartisan effort to pass comprehensive FDA reform this fall."

Rather than demanding full pivotal trials in pediatric populations, the regulation would require that drug manufacturers submit pediatric pharmacokinetic data that details dosages and side effects specific to children with all new drug applications (NDA) .

"We are taking a rational and flexible approach," said Michael Friedman, FDA lead deputy commissioner. "All we need is to test a small number of children to be sure that they are getting an effective dose in their bloodstreams."

Friedman noted that the agency expected to see such data when an NDA was filed but that submissions after filing would be acceptable as well. The proposed rule also allows companies to forgo such testing should the product be unlikely to be used in children, if the necessary studies prove impossible because the number of patients is too small or too geographically diverse, or if there is evidence that the product would be unsafe or ineffective in children.

In a statement, President of the Pharmaceutical Research and Manufacturers of America Alan Holmer questioned whether such a rule was necessary, but noted, "We are committed to working with the president and others in the administration on a collaborative and constructive basis regarding their proposed regulation to advance the goal of better medicine for children — a goal we all share."

This proposed regulation must go through the formal rules process before it can be adopted by the agency. The FDA currently is accepting comments from industry and the public. *