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Original Investigation
November 2018

Labeling Changes and Costs for Clinical Trials Performed Under the US Food and Drug Administration Pediatric Exclusivity Extension, 2007 to 2012

Author Affiliations
  • 1Program on Regulation, Therapeutics, and Law (PORTAL), Brigham and Women’s Hospital, Boston, Massachusetts
  • 2Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  • 3MPP/MPH student, University of California, Berkeley
  • 4Knowledge Ecology International (KEI), Washington, DC
JAMA Intern Med. 2018;178(11):1458-1466. doi:10.1001/jamainternmed.2018.3933
Key Points

Question  What have been the benefits of the US Food and Drug Administration’s pediatric exclusivity program in terms of new safety and efficacy data in pediatric populations, and what have been the costs to all consumers of extending market exclusivity by 6 months?

Findings  In this study of 54 drugs receiving pediatric exclusivity under the Best Pharmaceuticals for Children Act from September 27, 2007, to December 31, 2012, 31 (57%) demonstrated safety and efficacy in children. Pediatric exclusivity provided pharmaceutical manufacturers with a median net return of $176.0 million and a median ratio of net return to cost of investment of 680%.

Meaning  Meaningful knowledge of pediatric uses of pharmaceuticals has come from the pediatric exclusivity program, but at a high cost; other approaches to pediatric research, such as direct funding of such studies, may be more economically efficient.


Importance  Pharmaceutical manufacturers can receive 6 additional months of market exclusivity for performing pediatric clinical trials of brand-name drugs widely used in adults. Congress created this incentive in 1997 because these drugs were being used off-label in children without such trials.

Objective  To review updates to drug labeling and the cost to consumers of extending market exclusivity related to the pediatric exclusivity program.

Design  From government records, we identified 54 drugs that earned the pediatric exclusivity incentive between 2007 and 2012. We evaluated labeling changes from the pediatric studies. We then extracted trial details from clinical review documents and used industry estimates of trial costs on a per-patient basis to estimate cost of investment for trials (with a 10% cost of capital). To calculate the net return and cost to consumers during the 6-month exclusivity period, we estimated additional revenue for the 48 drugs with available information.

Main Outcomes and Measures  For each drug, we evaluated labeling changes and costs associated with pediatric trials under the Best Pharmaceuticals for Children Act and the cost to consumers of 6-month market exclusivity extensions.

Results  The 141 trials in our sample enrolled 20 240 children (interquartile range [IQR], 2-3 trials and 127-556 patients per drug). These trials led to 29 extended indications and 3 new indications, as well as new safety information for 16 drugs. Median cost of investment for trials was $36.4 million (IQR, $16.6 to $100.6 million). Among 48 drugs with available financial information, median net return was $176.0 million (IQR, $47.0 million to $404.1 million), with a median ratio of net return to cost of investment of 680% (IQR, 80% to 1270%).

Conclusions and Relevance  Clinical trials conducted under the US Food and Drug Administration’s pediatric exclusivity program have provided important information about the effectiveness and safety of drugs used in children. The costs to consumers have been high, exceeding the estimated costs of investment for conducting the trials. As an alternative, policymakers should consider direct funding of such studies.

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