Background of the Act

Federal legislation and regulations of the U.S. Food and Drug Administration (FDA) require that drugs be tested for safety and efficacy for use in a specific population, at a specific dosage, and for a specific time period, before the drugs can be approved for clinical use. Use in situations not included in this testing is considered to be "off-label" uses.

Over the years, several practical problems and difficulties have discouraged the testing of drugs in pediatric populations due to:

• A range of ethical issues, including parental permission and the child's assent
• Lack of necessary technology to monitor patients and assay very small amounts of blood
• Lack of incentives for pharmaceutical companies to study drugs in neonates, infants, and children
• Unforeseeable nature of some clinical responses in immature individuals
• Possibility of catastrophic unanticipated reactions
• Threat of effect on growth or health long after the drug's administration
• Difficulty in predicting dose-response or concentration-response relationships by extrapolation of data obtained from adults
• Ethical considerations for conducting non-therapeutic research in children
• Lack of suitable infrastructure for conducting pediatric pharmacology research

As a result, the majority of medications used in children today are done so off label, in most cases, without adequate understanding of appropriate dose, safety, or efficacy.

The Pediatric Rule of 1994, issued by FDA, allowed the labeling of drugs for pediatric use based on extrapolation of efficacy in adults and additional pharmacokinetics, pharmacodynamics, and safety studies in pediatric patients, if the course of the disease and the response to the drug are similar in children as in adults. Although designed to improve pediatric labeling, only a small number of well-designed and well-conducted studies resulted from this rule.

Additional legislation passed in1997 as part of the FDA Modernization Act (FDAMA) provided extra incentive to pharmaceutical companies for pediatric testing, namely an additional six-month exclusivity period for marketing. As a result of this program, many drugs have and continue to receive pediatric labeling under this provision.