COST-EFFECTIVENESS OF MODEL-INFORMED PRECISION DOSING VERSUS GUIDELINE DOSING FOR POLYMYXIN B: A SIMULATION-BASED ECONOMIC EVALUATION
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 evaluate the clinical and economic impact of MIPD compared with guideline-based polymyxin B dosing using an integrated population pharmacokinetic, exposure-toxicity, and decision-analytic simulation framework.
METHODS: A Monte Carlo simulation of 5,000 virtual critically ill adults was performed using a published two-compartment population pharmacokinetic model. Guideline dosing (2.0 mg/kg/day) was compared with Bayesian MIPD targeting a minimum effective exposure (AUCss,24h ≈58 mg·h/L). Efficacy was assessed using a pharmacodynamic target of AUC/MIC ≥50. A clinically calibrated exposure-toxicity model linked polymyxin B exposure to acute kidney injury (AKI). A decision-analytic model estimated healthcare costs, quality-adjusted life years (QALYs), incremental cost-effectiveness, and cost-effectiveness acceptability curves (CEACs) from an Indian private-ICU perspective. MIC-shift sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed.
RESULTS: MIPD increased therapeutic-window attainment (50-100 mg·h/L) from 61.7% to 84.3% and improved probability of target attainment at MIC 1 mg/L from 75.7% to 84.4%. Simulated AKI incidence decreased from 29.0% to 15.3%. Mean treatment costs decreased from ₹112,612 to ₹93,345 per patient, while mean QALYs increased from 3.538 to 3.667. MIPD was economically dominant, providing lower costs and greater effectiveness. MIC-shift analyses showed declining response with increasing resistance; however, MIC-adaptive MIPD improved coverage under high-MIC scenarios. PSA demonstrated a 93% probability that MIPD would remain dominant and a 99% probability of cost-effectiveness at a willingness-to-pay threshold of ₹200,000/QALY.
CONCLUSIONS: Model-informed precision dosing improved target attainment, reduced nephrotoxicity, and generated favorable economic outcomes compared with conventional dosing. These findings support pharmacometric-guided precision dosing as a clinically beneficial and cost-effective strategy for managing MDR Gram-negative infections in critically ill patients.
METHODS: A Monte Carlo simulation of 5,000 virtual critically ill adults was performed using a published two-compartment population pharmacokinetic model. Guideline dosing (2.0 mg/kg/day) was compared with Bayesian MIPD targeting a minimum effective exposure (AUCss,24h ≈58 mg·h/L). Efficacy was assessed using a pharmacodynamic target of AUC/MIC ≥50. A clinically calibrated exposure-toxicity model linked polymyxin B exposure to acute kidney injury (AKI). A decision-analytic model estimated healthcare costs, quality-adjusted life years (QALYs), incremental cost-effectiveness, and cost-effectiveness acceptability curves (CEACs) from an Indian private-ICU perspective. MIC-shift sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed.
RESULTS: MIPD increased therapeutic-window attainment (50-100 mg·h/L) from 61.7% to 84.3% and improved probability of target attainment at MIC 1 mg/L from 75.7% to 84.4%. Simulated AKI incidence decreased from 29.0% to 15.3%. Mean treatment costs decreased from ₹112,612 to ₹93,345 per patient, while mean QALYs increased from 3.538 to 3.667. MIPD was economically dominant, providing lower costs and greater effectiveness. MIC-shift analyses showed declining response with increasing resistance; however, MIC-adaptive MIPD improved coverage under high-MIC scenarios. PSA demonstrated a 93% probability that MIPD would remain dominant and a 99% probability of cost-effectiveness at a willingness-to-pay threshold of ₹200,000/QALY.
CONCLUSIONS: Model-informed precision dosing improved target attainment, reduced nephrotoxicity, and generated favorable economic outcomes compared with conventional dosing. These findings support pharmacometric-guided precision dosing as a clinically beneficial and cost-effective strategy for managing MDR Gram-negative infections in critically ill patients.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EE711
Topic
Economic Evaluation, Health Technology Assessment, Patient-Centered Research
Topic Subcategory
Budget Impact Analysis
Disease
Infectious Disease (non-vaccine), Personalized & Precision Medicine