children (Gilman and Gal, 1992, cited in AAP, 1995). Based on data from 1991 to 1997 involving new molecular entities with potential pediatric uses, a Food and Drug Administration (FDA) report found that 62 percent lacked labeling information for pediatric use at the time that they were initially approved for marketing (Steinbrook, 2002). The committee did not locate similar information about medical devices and biological agents.1

When drug labels lack pediatric prescribing information, physicians can still legally prescribe drugs for children on an “off-label” basis—and they do. According to Choonara and Conroy (2002), European studies suggest that at least one-third of hospitalized children and up to 90 percent of neonates in intensive care receive such prescriptions. A study in the United States, which used 1994 data on outpatient prescriptions, reported more than 1,600,000 off-label prescriptions of nebulized albuterol for children under age 12 years, nearly 350,000 prescriptions of the anti-depression drug fluoxetine (Prozac) for children under age 16 years, and more than 200,000 off-label prescriptions of methylphenidate (Ritalin, which is used to treat attention deficit disorder) for children under age 6 years (Pina, 1997; see also Turner et al., 1999 and Conroy et al., 2000). Altogether, the 10 identified drugs were prescribed more than five million times for children in age groups for which the drug label either had a disclaimer or lacked information for children. Since 1994, the FDA has reviewed supporting studies and approved pediatric labeling for several of these drugs (e.g., Prozac for ages 7 to 17 years, Ritalin for ages 6 to 12 years, leval-buterol down to age 7 years) (FDA, 2004).

The American Academy of Pediatrics has argued that the shortage of pediatric research creates an ethical dilemma for physicians, who “must frequently either not treat children with potentially beneficial medications or treat them with medications based on adult studies or anecdotal empirical experience in children” (AAP, 1995, p. 286). Many children undoubtedly benefit when physicians follow the second course. On occasion, however, some children will experience harm, either because the dose used was ineffective or because it was toxic. Even those children who receive some


One provision of the Medical Device User Fee and Modernization Act of 2002 (P.L. 107-250) calls for an assessment of whether clinical studies of implanted devices continue long enough to assess the impact of children’s growth and development in relation to the time that children are expected to have different kinds of implants. Another provision calls for an assessment of the adequacy of FDA’s monitoring of commitments for further clinical studies of pediatric medical devices that are made by manufacturers at the time they obtain approval to market a device. The Act also directs the FDA to provide guidance on the kinds of information needed to provide reasonable assurance that medical devices intended for use in pediatric populations are safe and effective.

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