Abstract
The use of extrapolation of efficacy in pediatric drug development programs is possible when disease progression and treatment response are similar in adult and pediatric populations. Historically, the exposure-response (E-R) similarity was assessed by visual inspection of 2 E-R curves to support pediatric extrapolation. The aim of this study was to develop a quantitative framework to describe the E-R relationship and the difference in E-R between pediatric and adult patients based on accumulated experience in pediatric drug development programs. Using clinical data for 8 drugs with either a linear or nonlinear E-R relationship, we adapted the methodology used in noninferiority testing to assess the E-R similarity between adult and pediatric patients at the targeted drug exposure. We implemented bootstrap-based and Bayesian-based methodologies to estimate the probability of concluding noninferiority of the E-R relationship. This approach provides objective criteria that can be applied to an assessment of E-R noninferiority in 2 populations to support extrapolation of efficacy in drug development programs from adults to pediatric populations.
Original language | English (US) |
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Pages (from-to) | S165-S174 |
Journal | Journal of clinical pharmacology |
Volume | 61 |
Issue number | S1 |
DOIs | |
State | Published - Jun 2021 |
Externally published | Yes |
Keywords
- exposure-response
- extrapolation
- pediatric drug development
- regulatory science
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)