title: A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis.
abstract: OBJECTIVE
  To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS).
  
  
  METHODS
  Discrete event simulation paradigm was selected for model development. Drug efficacy was modelled as changes in disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis Functional Index (BASFI)), which were linked to costs and health utility using statistical models fitted based on an observational AS cohort. Published clinical data were used to estimate drug efficacy and time to events. Two strategies were compared: (1) five available non-steroidal anti-inflammatory drugs (strategy 1) and (2) same as strategy 1 plus two tumour necrosis factor α inhibitors (strategy 2). 13,000 patients were followed up individually until death. For probability sensitivity analysis, Monte Carlo simulations were performed with 1000 sets of parameters sampled from the appropriate probability distributions.
  
  
  RESULTS
  The models successfully generated valid data on treatments, BASDAI, BASFI, utility, quality-adjusted life years (QALYs) and costs at time points with intervals of 1-3 months during the simulation length of 70 years. Incremental cost per QALY gained in strategy 2 compared with strategy 1 was €35,186. At a willingness-to-pay threshold of €80,000, it was 99.9% certain that strategy 2 was cost-effective.
  
  
  CONCLUSIONS
  The modelling framework provides great flexibility to implement complex algorithms representing treatment selection, disease progression and changes in costs and utilities over time of patients with AS. Results obtained from the simulation are plausible.
authors.affiliation: Department of Health Services Research, Maastricht University, The Netherlands. a.tranduy@maastrichtuniversity.nl
authors.forename: An
authors.initials: A
authors.lastname: Tran-Duy
authors.forename: Annelies
authors.initials: A
authors.lastname: Boonen
authors.forename: Mart A F J
authors.initials: MA
authors.lastname: van de Laar
authors.forename: Angelinus C
authors.initials: AC
authors.lastname: Franke
authors.forename: Johan L
authors.initials: JL
authors.lastname: Severens
mesh_terms: D000328:Adult; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000191:economics / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000191:economics / Q000627:therapeutic use; D017281:Cost of Illness; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D017048:Health Care Costs / Q000706:statistics & numerical data; D006295:Health Resources / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D017059:Models, Econometric; D015233:Models, Statistical; D009426:Netherlands; D019057:Quality-Adjusted Life Years; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000188:drug therapy* / Q000191:economics; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha