title: Simulation Modelling in Ophthalmology: Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom.
abstract: Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions.
  
  
  
  This study aimed to explore the appropriateness of simulation modelling in ophthalmology, using the disease area of wet age-related macular degeneration (wAMD) as an example.
  
  
  
  A de novo economic model was built using a patient-level simulation, which compared ranibizumab with aflibercept in wAMD. Disease progression was measured using BCVA. Health-related quality of life (HRQoL) was estimated using a regression analysis linking BCVA in each eye to utility. The analysis was from the perspective of the National Health Service in the UK. Five different regression models were explored and were based on BCVA in either one eye or both eyes.
  
  
  
  The model outputs provide some evidence to support the hypothesis that the analyses using the two-eye models for estimating HRQoL generate a more accurate estimation of incremental quality-adjusted life-years (QALYs) associated with the positive treatment effect for ranibizumab versus aflibercept. Second-order analysis broadly supported these findings, and showed that the variation in incremental costs was slightly lower than in incremental QALYs. The second-order analysis estimated similar incremental costs and a greater overall variation in incremental QALYs than the first-order analysis, suggesting important non-linearities within the model.
  
  
  
  This analysis suggests that patient-level simulation models may be well suited to representing the real-world patient pathway in wAMD, particularly when aspects of disease progression cannot be adequately captured using a Markov structure. The benefits of a simulation approach can be demonstrated in the modelling of HRQoL as a function of BCVA in both eyes.
authors: York Health Economics Consortium, University of York, York, UK. lindsay.claxton@york.ac.uk.
authors: Lindsay
authors: L
authors: Claxton
authors: York Health Economics Consortium, University of York, York, UK.
authors: Robert
authors: R
authors: Hodgson
authors: York Health Economics Consortium, University of York, York, UK.
authors: Matthew
authors: M
authors: Taylor
authors: Novartis Pharmaceuticals UK Limited, Frimley Business Park, Surrey, UK.
authors: Bill
authors: B
authors: Malcolm
authors: Novartis Pharmaceuticals UK Limited, Frimley Business Park, Surrey, UK.
authors: Ruth
authors: R
authors: Pulikottil Jacob
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000191:economics; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D006801:Humans; D008390:Markov Chains; D018803:Models, Economic; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D000069579:Ranibizumab / Q000008:administration & dosage* / Q000191:economics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000191:economics; D012044:Regression Analysis; D006113:United Kingdom; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab