Applying the Noninferiority Paradigm to Assess Exposure‐Response Similarity and Dose Between Pediatric and Adult Patients. (29th June 2021)

• Record Type: Journal Article
• Authors: 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
• Other Names: Burckart Gilbert J. guestEditor.; van den Anker John N. guestEditor.
• Is Part Of: Journal of clinical pharmacology. Volume 61(2021)Supplement 1
• Page Start: S165
• Page End: S174
• Publication Date: 2021-06-29
• Subjects: pediatric drug development -- extrapolation -- exposure‐response -- regulatory science; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.1885
• Languages: English
• ISSNs: 0091-2700

Abstract

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.