ECONOMIC OPTIMIZATION OF POLYMYXIN B EXPOSURE TARGETS USING AN INTEGRATED PHARMACOMETRIC-PHARMACOECONOMIC SIMULATION FRAMEWORK
Author(s)
Jesmitha J. M, PharmD1, Ganesan Rajalekshmi Saraswathy, PhD2.
1Student, M S Ramaiah University Of Applied Sciences, Bengaluru, India, 2M S Ramaiah University Of Applied Sciences, Bangalore, India.
1Student, M S Ramaiah University Of Applied Sciences, Bengaluru, India, 2M S Ramaiah University Of Applied Sciences, Bangalore, India.
OBJECTIVES: To identify the polymyxin B steady-state exposure (AUCss,24h) that maximizes net monetary benefit (NMB) using an integrated pharmacometric and pharmacoeconomic simulation framework.
METHODS: A Monte Carlo simulation of 5,000 virtual critically ill adults was performed using a published two-compartment population pharmacokinetic model for polymyxin B. Candidate AUCss,24h targets ranging from 40 to 120 mg·h/L were evaluated. Clinical efficacy was described using a continuous Emax exposure-response model, while nephrotoxicity was modelled using a continuous logistic exposure-AKI relationship. A decision-analytic model estimated direct medical costs, quality-adjusted life years (QALYs), and NMB from the perspective of an Indian private intensive care unit. Candidate exposure targets were compared according to probability of target attainment (PTA), therapeutic-window attainment, acute kidney injury (AKI), mortality, costs, QALYs, and NMB. Parameter uncertainty was explored using probabilistic sensitivity analysis (300 iterations), and an economic therapeutic window was defined as exposure targets within 1% of the maximum NMB.
RESULTS: Increasing AUC targets from 40 to approximately 70 mg·h/L substantially improved PTA (2.8% to 94.7%) and clinical response (62.5% to 76.5%) while maintaining acceptable nephrotoxicity. Beyond this range, incremental improvements in efficacy were offset by progressively increasing AKI risk. Mean NMB reached a plateau between approximately 70 and 90 mg·h/L, with the highest mean NMB observed near 90 mg·h/L (₹534,370 per patient). However, probabilistic sensitivity analysis demonstrated considerable decision uncertainty, with AUC targets between 70 and 85 mg·h/L consistently exhibiting the highest probability of economic optimality. Exposure targets exceeding 100 mg·h/L were rarely economically preferred because increased nephrotoxicity outweighed marginal clinical benefit.
CONCLUSIONS: Integrating pharmacometric and pharmacoeconomic modelling identified an economically favorable polymyxin B exposure range of approximately 70-90 mg·h/L, rather than a single optimal target. These findings suggest that Bayesian model-informed precision dosing should aim for an economic therapeutic window that balances efficacy, toxicity, and healthcare value.
METHODS: A Monte Carlo simulation of 5,000 virtual critically ill adults was performed using a published two-compartment population pharmacokinetic model for polymyxin B. Candidate AUCss,24h targets ranging from 40 to 120 mg·h/L were evaluated. Clinical efficacy was described using a continuous Emax exposure-response model, while nephrotoxicity was modelled using a continuous logistic exposure-AKI relationship. A decision-analytic model estimated direct medical costs, quality-adjusted life years (QALYs), and NMB from the perspective of an Indian private intensive care unit. Candidate exposure targets were compared according to probability of target attainment (PTA), therapeutic-window attainment, acute kidney injury (AKI), mortality, costs, QALYs, and NMB. Parameter uncertainty was explored using probabilistic sensitivity analysis (300 iterations), and an economic therapeutic window was defined as exposure targets within 1% of the maximum NMB.
RESULTS: Increasing AUC targets from 40 to approximately 70 mg·h/L substantially improved PTA (2.8% to 94.7%) and clinical response (62.5% to 76.5%) while maintaining acceptable nephrotoxicity. Beyond this range, incremental improvements in efficacy were offset by progressively increasing AKI risk. Mean NMB reached a plateau between approximately 70 and 90 mg·h/L, with the highest mean NMB observed near 90 mg·h/L (₹534,370 per patient). However, probabilistic sensitivity analysis demonstrated considerable decision uncertainty, with AUC targets between 70 and 85 mg·h/L consistently exhibiting the highest probability of economic optimality. Exposure targets exceeding 100 mg·h/L were rarely economically preferred because increased nephrotoxicity outweighed marginal clinical benefit.
CONCLUSIONS: Integrating pharmacometric and pharmacoeconomic modelling identified an economically favorable polymyxin B exposure range of approximately 70-90 mg·h/L, rather than a single optimal target. These findings suggest that Bayesian model-informed precision dosing should aim for an economic therapeutic window that balances efficacy, toxicity, and healthcare value.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
MSR267
Topic
Clinical Outcomes, Economic Evaluation, Methodological & Statistical Research
Disease
Infectious Disease (non-vaccine), Personalized & Precision Medicine