title: Translating Pharmacometrics to a Pharmacoeconomic Model of COPD.
abstract: 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.
  
  
  OBJECTIVE
  To use a pharmacometric MBMA within a pharmacoeconomic model of chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  A Markov microsimulation model was developed to estimate monthly changes in the key disease severity metrics of COPD (forced expiratory volume in 1 second [FEV1] and exacerbations) to compare a hypothetical drug that increases FEV1to usual care. The MBMA was used to predict a baseline exacerbation rate in a group of actual trial patients, given their known baseline FEV1. The hypothetical drug increased FEV1, thereby decreasing individuals' predicted exacerbation rates. Individual patient simulations allowed stochastic changes in monthly FEV1decline.
  
  
  RESULTS
  In a sample of 1097 trial patients with a mean FEV1of 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 FEV1by 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 cost-effectiveness 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.
authors.affiliation: Pharmaceutical Health Services Research, University of Maryland School of Pharmacy, Baltimore, MD, USA. Electronic address: jslejko@rx.umaryland.edu.
authors.forename: Julia F
authors.initials: JF
authors.lastname: Slejko
authors.affiliation: International Society for Pharmacoeconomics and Outcomes Research, Lawrenceville, NJ, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Willke
authors.affiliation: Pharmetheus AB, Uppsala, Sweden.
authors.forename: Jakob
authors.initials: J
authors.lastname: Ribbing
authors.affiliation: Global Clinical Pharmacology, Pfizer, Sandwich, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Milligan
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000191:economics* / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D017850:Economics, Pharmaceutical; D005541:Forced Expiratory Volume; D006801:Humans; D008390:Markov Chains; D017059:Models, Econometric; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000191:economics*; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D012720:Severity of Illness Index; D013269:Stochastic Processes
chemical_list: D000305:Adrenal Cortex Hormones
keywords: COPD; Markov model; health economic methods; meta-analysis