Extrapolation of adult data and other data in pediatric drug-development programs.
OBJECTIVE
In 1994, the US Food and Drug Administration (FDA) proposed an approach, based on extrapolation of efficacy findings from adults to the pediatric population, to maximize the use of adult data and other data when designing pediatric drug-development programs. We examined the experience of the FDA in using extrapolation to evaluate how and when it was used and any changes in scientific assumptions over time.


METHODS
We reviewed 370 pediatric studies submitted to the FDA between 1998 and 2008 in response to 159 written requests (166 products) issued under the Pediatric Exclusivity Provision. We identified cases in which efficacy was extrapolated from adult data or other data, we categorized the type of pediatric data required to support extrapolation, and we determined whether the data resulted in new pediatric labeling.


RESULTS
Extrapolation of efficacy from adult data occurred for 82.5% of the drug products (137 of 166). Extrapolation was defined as complete for 14.5% of the products (24 of 166) and partial for 68% of them (113 of 166). Approaches to extrapolation changed over time for 19% of the therapeutic indications studied (13 of 67). When extrapolation was used, 61% of the drug products (84 of 137) obtained a new pediatric indication or extension into a new age group; this number decreased to 34% (10 of 29) when there was no extrapolation.


CONCLUSIONS
Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals for pediatric use.
Office of Pediatric Therapeutics, Office of the Commissioner, Food and Drug Administration, Silver Spring, Maryland, USA. julia.dunne@fda.hhs.gov
Julia
J
Dunne
William J
WJ
Rodriguez
M Dianne
MD
Murphy
B Nhi
BN
Beasley
Gilbert J
GJ
Burckart
Jane D
JD
Filie
Linda L
LL
Lewis
Hari C
HC
Sachs
Philip H
PH
Sheridan
Peter
P
Starke
Lynne P
LP
Yao
D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D015195:Drug Design; D054796:Drug Dosage Calculations; D004358:Drug Therapy / Q000379:methods / Q000592:standards*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010372:Pediatrics; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D016730:Program Development; D011786:Quality Control; D012189:Retrospective Studies; D014481:United States; D014486:United States Food and Drug Administration / Q000458:organization & administration
D004364:Pharmaceutical Preparations