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Daniel K. Benjamin, Jr, MD, PhD; Philip Brian Smith, MD; M. Dianne Murphy, MD; Rosemary Roberts, MD; Lisa Mathis, MD; Debbie Avant, RPh; Robert M. Califf, MD; Jennifer S. Li, MD, MHS

JAMA. 2006;296:1266-1273.

Context  Much of pediatric drug use is off-label because appropriate pediatric studies have not been conducted and the drugs have not been labeled by the US Food and Drug Administration (FDA) for use in children. In 1997, Congress authorized the FDA to grant extensions of marketing rights known as "pediatric exclusivity" if FDA-requested pediatric trials were conducted. As a result, there have been over 100 product labeling changes. The publication status of studies completed for pediatric exclusivity has not been evaluated.

Objective  To quantify the dissemination of results of studies conducted for pediatric exclusivity into the peer-review literature.

Design  Cohort study of all trials conducted for pediatric exclusivity between 1998 and 2004 as determined by MEDLINE and EMBASE searches through 2005, the subsequent labeling changes, and the publication of those studies in peer-reviewed journals. We categorized any labeling changes resulting from the studies as positive or negative for the drug under study. We then evaluated aspects of the studies and product label changes that were associated with subsequent publication in peer-reviewed medical journals.

Main Outcome Measures  Publication of the trial data in peer-reviewed journals.

Results  Between 1998 and 2004, 253 studies were submitted to the FDA for pediatric exclusivity: 125 (50%) evaluated efficacy, 51 (20%) were multi-dose pharmacokinetic, 34 (13%) were single-dose pharmacokinetic, and 43 (17%) were safety studies. Labeling changes were positive for 127/253 (50%) of studies; only 113/253 (45%) were published. Efficacy studies and those with a positive labeling change were more likely to be published.

Conclusions  The pediatric exclusivity program has been successful in encouraging drug studies in children. However, the dissemination of these results in the peer-reviewed literature is limited. Mechanisms to more widely disperse this information through publication warrant further evaluation.

Author Affiliations: Office of Pediatric Therapeutics, Office of the Commissioner (Drs Benjamin, Murphy, and Li), Office of Counter-Terrorism and Pediatric Drug Development, Center for Drug Evaluation and Research (Drs Roberts, Mathis, and Avant), US Food and Drug Administration, Rockville, Md; Departments of Pediatrics and Medicine and the Duke Clinical Research Institute, Duke University, Durham, NC (Drs Benjamin, Smith, Califf, and Li).

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