Regulations being introduced by the US Food and Drug Administration (FDA) should take the guesswork out of prescribing medicines for children.

All medicines will soon carry pediatric information.

From 2 December this year, all new drug applications submitted to the agency must include pediatric study reports—assessment of the safety and efficacy of the new product in neonates, infants and children under the age of 17—whether or not the medicine is intended for use in these subjects. In addition, the FDA may require a drug sponsor to make similar assessments for a drug already marketed, in certain circumstances. The agency estimates that it will require studies of two marketed drugs per year.

At present, 80% of all marketed drug products in the US do not carry FDA-approved labeling for use in neonates, infants or children. As a result, pediatricians who prescribe drugs often rely on their medical judgement to extrapolate the appropriate dose and schedule of administration. “Every time I give a child a drug that has not been tested in children I perform an uncontrolled experiment, and this is unacceptable,” says Philip Walson, director of clinical trials at Children Hospital Medical Center, University of Cincinnati.

The Pediatric Rule is the second measure adopted by the FDA in recent years to increase information on use of medicines in children. The 1997 FDA Modernization Act (FDAMA) contained economic incentives for pediatric trials of approved drugs. These included the six-month extension of existing market exclusivity, or patent protection, on a drug even if the data submitted is inconclusive or does not support a labeling change.

Contrary to what many view as major barriers to the collection of pediatric information, such as the cost of undertaking additional clinical studies in this age group for which the financial (market) return could be small, and the ethical and practical difficulties in enrolling children in experimental drug trials, the FDAMA pediatric exclusivity provisions have proven an effective incentive to the pharmaceutical industry. According to Senator Mike DeWine (R-OH), who along with Christopher Dodd (D-CT) introduced legislation that became part of the FDAMA, “Since the incentives program was brought into effect, 300 pediatric drug studies of 127 products have been initiated, compared to only 11 pediatric clinical trials in the prior 5 years.”

DeWine and Dodd also introduced the Children's Research Protection Act this June, which aims to provide fellowships for pediatric pharmacology training, as well as stronger safeguards to protect children participating in clinical drug trials. And DeWine is the author of the Pediatric Research Initiative, which calls for an ambitious $50 million to be given every year for five years to the Office of the Director at the National Institutes of Health to support pediatric research, and for $45 million over the next three years to be distributed through the National Institutes of Child Health and Human Development (NICHD), for pediatric research training grants. That proposal is now making its way through Congress as part of the Children's Public Health Act of 2000.

But the Pediatric Rule contains ‘get-out’ clauses. The requirement for studies will be waived if the manufacturer provides a convincing argument that the drug will not provide a meaningful therapeutic benefit or if it is not used in substantial numbers of pediatric patients or that pediatric studies are impossible or highly impractical.

In addition, drug manufacturers may try to contest the regulation. “Come November, they could file that the new rule is unworkable,” says Walson. Such action would not be unprecedented. In 1997, the FDA faced a court challenge from the generic drug industry to halt implementation of the FDAMA pediatric studies provision. This was ultimately dismissed.