Dose Extrapolation

Evaluating Conditional Exchangeability Assumptions for Bayesian Borrowing, With Application to Pediatric Extrapolation

Presented at the Graybill Conference 2024. Dr. Jim Rogers from MetrumRG as he demonstrates the application of causal selection diagrams as a statistical consulting tool for Bayesian prior elicitation. Bayesian dynamic borrowing is an increasingly important methodology in pediatric extrapolation, and its successful application requires quantitative scientists who can bridge the gap between qualitative notions of “similarity” and formal statistical notions of “exchangeability.”

Adaptive Buprenorphine Dose Simulations In Infants with NOWS (Neonatal Opioid Withdrawal Syndrome).

Presented by Dr. Rena Byrne at the 13th Annual Indiana CTSI Disease and Therapeutic Response Modeling Symposium, February 2024.
View presentation recording.

MIDD for dose confirmation in special populations: full covariate modeling meets intersection-union testing

Presented at the International Symposium on Biopharmaceutical Statistics, March 2024. From basic dose adjustments to more ambitious programs for personalized medicine, pharmacometrics has a long tradition of informing tailored treatment strategies. Many of the modeling strategies are well-precedented, but formal decision frameworks are needed to address the question: how much data is enough to support a decision?

Population Pharmacokinetic (PK) and Exposure-Response (ER) Analysis of Empagliflozin in Pediatric Patients with Type 2 Diabetes Mellitus (T2DM)

Presented at ACoP14. Empagliflozin, effective for type 2 diabetes in adults and children, underwent Study 1218.91 to assess its safety and efficacy over 26 weeks (with potential extension to 52 weeks) in children and adolescents. Using pediatric data from this study, researchers re-evaluated empagliflozin’s models in a Bayesian framework. Results showed similar drug exposure between children and adults at a 10 mg dose. At week 26, pediatric patients displayed a slightly larger but variable decrease in A1c compared to adults. This Bayesian method allowed insights into empagliflozin’s effects in children, drawing from knowledge gained in adult studies.

Choice of Hyperparameters for Spike And Slab Prior, with Application to Dose Optimization in Oncology

This poster highlights the use of population pharmacokinetic and exposure-response models with regularized regression using spike and slab priors to optimize dosing for specific patient subpopulations, particularly focusing on the context of valemetostat treatment for Adult T-cell Leukemia / Lymphoma (ATTLL) and Non-Hodgkin’s lymphoma (NHL).

A physiologically-based pharmacokinetic modeling approach to support candidate and first in human dose selection for bamlanivimab

Tim Knab, Ahmed Elmokadem, Emmanuel Chigutsa, Eric Jordie, Matthew Riggs, Patricia Brown-Augsburger, Christopher Wiethoff, Ajay Nirula, Jenny Y Chien, Lisa O’Brien.  Poster presented at Population Approach Group Europe Annual Meeting; 2-3 and 6-7 September 2021.  Poster I-64.

Animal-to-human dose translation of obiltoxaximab for treatment of inhalational anthrax under the US FDA animal rule.

Nagy CF, Mondick J, Serbina N, Casey LS, Carpenter SE, French J, Guttendorf R.  Clinical And Translational Science, 2016 Dec; 10: 12–19.

Efficacy projection of obiltoxaximab for treatment of inhalational anthrax across a range of disease severity

Yamamoto BJ, Shadiack AM, Carpenter S, Sanford D, Henning LN, O’Connor E, Gonzales N, Mondick J, French J, Stark GV, Fisher AC, Casey LS, Serbina NV. Antimicrob Agents Chemother 60:5787–5795. doi:10.1128/AAC.00972-16

The role of simulation in assessing extrapolation assumptions

Gastonguay MR.  Presented at the Quantitative Assessment of Assumptions to Support Extrapolation of Efficacy in Pediatrics: FDA – U Maryland CERSI Cosponsored Workshop.  FDA. June 1, 2016.

Population pharmacokinetic (PPK) modeling and simulation to support pediatric dose selection of ceftaroline fosamil (CPT-F) in children aged 28 days to 12 years

Khariton T, Riccobene T, Knebel W, O’Neal T, Ghahramani P. Presented at the 5th American Conference on Pharmacometrics (ACoP), Las Vegas, NV, October 2014.