, Volume 35, Issue 2, pp 237–248 | Cite as

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

  • Lindsay ClaxtonEmail author
  • Robert Hodgson
  • Matthew Taylor
  • Bill Malcolm
  • Ruth Pulikottil Jacob
Original Research Article



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.


Ranibizumab Well Correct Visual Acuity Diabetic Macular Oedema Aflibercept Evidence Review Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The original regression analysis of the Czoski-Murray quality of life dataset was undertaken by David Trueman and Tim Reason at Abacus International, and was funded by Novartis.

The authors would like to thank the IVAN trial investigators for providing the dataset for modelling ranibizumab BCVA progression.

Author contributions

All authors were involved in the conceptualisation of the analysis. LC and RH developed the economic analysis. LC, RH and RPJ contributed equally towards the drafting of the manuscript. All authors provided feedback on each draft of the manuscript. LC will act as the overall guarantor.

Compliance with Ethical Standards

The study was funded and initiated by Novartis Pharmaceuticals UK Ltd. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Ruth Pulikottil-Jacob is an employee of Novartis and Bill Malcolm is an ex-employee of Novartis. Lindsay Claxton and Matthew Taylor are employees of York Health Economics Consortium, which was commissioned by Novartis to develop the study. Robert Hodgson is an ex-employee of York Health Economics Consortium.

Supplementary material

40273_2016_459_MOESM1_ESM.docx (103 kb)
Supplementary material 1 (DOCX 102 kb)


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Lindsay Claxton
    • 1
    Email author
  • Robert Hodgson
    • 1
  • Matthew Taylor
    • 1
  • Bill Malcolm
    • 2
  • Ruth Pulikottil Jacob
    • 2
  1. 1.York Health Economics ConsortiumUniversity of YorkYorkUK
  2. 2.Novartis Pharmaceuticals UK LimitedSurreyUK

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