medical literature as case series reports or codified in consensus guidelines. Although recent years have seen increasing emphasis on evidence-based practice guidelines, neither guideline developers nor practitioners can use evidence that does not exist or is not public. The use of medications by children without guidance from pediatric studies of safety and efficacy raises ethical issues that underscore the importance of such studies. In some cases, high-quality clinical trials sponsored by government agencies or nonprofit groups are available but are not reflected in product labeling.

In the years preceding the adoption of BPCA and PREA and their predecessor policies, several analyses documented the lack of information on the safety and efficacy of FDA-approved medications that are prescribed for children. Table 1-1 summarizes several of these.

The frustration of many clinicians with the lack of pediatric prescribing information was expressed decades ago in a 1968 editorial in the Journal of Pediatrics that referred to children as “therapeutic orphans” (Shirkey, 1968). This oft-used description of children appeared years later in the Senate report (Senate Report 105-43, 1997) that accompanied the Food and Drug Administration Modernization and Accountability Act of 1997 (FDAMA; PL 105-115). FDAMA first established the incentives for pediatric research, which were reauthorized in 2002 and 2007. The 1997 Senate report also stated that less than 20 percent of prescription medications available in the United States were labeled for pediatric use.

For drugs that may be used by children as well as adults, evidence from pediatric studies is important for several reasons (see, e.g., IOM, 2000,

TABLE 1-1 Historical Data on Drugs Without Adequate Labeling for Pediatric Use

Year     Extent of Pediatric Drug Labeling


78% of drugs listed in the Physicians’ Desk Reference (PDR) lacked sufficient pediatric drug labeling


80% of new molecular entities (NMEs) approved by FDA lacked pediatric drug labeling


81% of drugs in PDR had disclaimers or age restrictions


44% of NMEs with potential pediatric usefulness had no pediatric labeling when approved


79% of NMEs were not approved for potential pediatric use


71% of NMEs lacked pediatric drug labeling


37% of NMEs with potential pediatric usefulness had some pediatric labeling when approved

SOURCE: Adapted from Wilson (1999), with additional information from FDA (1998).

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