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Applying the Noninferiority Paradigm to Assess Exposure‐Response Similarity and Dose Between Pediatric and Adult Patients
Author(s) -
Zhang Qunshu,
Travis James,
Rothwell Rebecca,
Jay Christopher E.,
Jahidur Rashid,
Zhang Yifei,
Crentsil Victor,
Altepeter Tara,
Lee Jessica J.,
Burckart Gilbert J.,
Ganley Charles,
Wang Jian
Publication year - 2021
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1885
Subject(s) - bayesian probability , extrapolation , medicine , similarity (geometry) , drug development , drug , statistics , computer science , pharmacology , mathematics , artificial intelligence , image (mathematics)
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.