that forces physicians to use therapeutic agents in essentially uncontrolled experiments every time that they write a prescription for a child. Furthermore, the Academy stated that it was imperative that new drugs intended for use in children be studied in children under controlled circumstances so that the benefits of therapeutic advances could become available to all who need them.

These principles made a powerful, yet simple statement: children deserve and should have the same standard as adults when it comes to therapeutics. If adequate and well-controlled studies are needed to determine the efficacy of products used for adults, then the same should be true for products used for children. This statement of principle shifted everyone's thinking about clinical testing of medical products in the pediatric population. No longer were the experts focused on the dogma of how unethical it was to study the effects of drugs in children. It became unethical not to conduct such studies.

In 1979, FDA confirmed the need to have information on how best to use a product in the pediatric population by issuing regulations. The position of the agency was that if statements were to be made regarding pediatric use of a drug for an indication approved for adults, such statements were required to be based on substantial evidence derived from adequate and well-controlled studies, unless the requirement was waived.

Unfortunately, this particular regulation did not generate the intended response. Few clinical trials with the pediatric population were initiated. The regulation did not provide incentives for companies to conduct such studies, nor were there repercussions for not doing so. Thus, for two-thirds to three-quarters of all drugs used by the pediatric population, directions for use by children that were based on data from clinical trials were not available.

More than a decade passed before the agency took a more assertive stance. In 1994, FDA issued a final rule requiring drug manufacturers to survey existing data and determine whether those data were sufficient to support the presentation of additional pediatric use information in a drug's labeling. The rule explicitly recognized that controlled clinical studies conducted to support pediatric use need not be carried out with a pediatric population if the course of the disease and the effects of the drug are sufficiently similar in children and adults. Extrapolation of adult effectiveness data to pediatric patients was permitted. In these cases, controlled clinical studies with adults, together with other information such as pharmacokinetics and adverse reaction data for pediatric patients, could be found to be sufficient to establish the safety and effectiveness of a drug in children.

Under the 1994 role, if a manufacturer determined that existing data permitted modification of the label's pediatric use information, the manufacturer had to submit a supplemental new drug application to FDA to seek approval of these labeling changes. It is important to recognize that this rule did not impose a general requirement that manufacturers carry out studies if existing informa-



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement