Translating Pharmacometrics to a Pharmacoeconomic Model of COPD

摘要

Background: A model-based meta-analysis (MBMA) is a type of meta regression that uses nonlinear mixed-effects models estimated on trial-level data to relate patient and trial characteristics, dosing, biomarkers, and outcomes of treatment. Objectives: To use a pharmacometric MBMA within a pharmacoeconomic model of chronic obstructive pulmonary disease (COPD). Methods: A Markov micro simulation model was developed to estimate monthly changes in the key disease severity metrics of COPD (forced expiratory volume in 1 second FEVi and exacerbations) to compare a hypothetical drug that increases FEVi to usual care. The MBMA was used to predict a baseline exacerbation rate in a group of actual trial patients, given their known baseline FEVi. The hypothetical drug increased FEVi, thereby decreasing individuals' predicted exacerbation rates. Individual patient simulations allowed stochastic changes in monthly FEVi decline. Results: In a sample of 1097 trial patients with a mean FEVi of 50, the MBMA predicted 0.93 exacerbations per year on average. The exacerbation rate ranged from 0.52 to 1.3 per year across moderate and severe patient subgroups. A hypothetical anti-inflammatory drug that increased FEVi by 50 ml decreased exacerbations by 26. Given a simplified estimation of costs and quality-adjusted life-years (QALYs) associated with COPD, a drug with a 50-ml increase priced at 35/mo had an incremental costeffectiveness ratio ranging from 13,000/QALY to approximately 207,000/QALY across patient severity subgroups. Conclusions: The synergistic aspects of MBMA and pharmacoeconomic modeling are highlighted in this hypothetical example. Markov microsimulation modeling allows the finer predictions of MBMA to inform parameters. Such an approach has utility in both early-phase cost-effectiveness estimations and trial design.