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

BackgroundPreviously 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 bestcorrected 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. ObjectiveThis 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. MethodsA de novo economic model was built using a patient-level simulation, which compared ranibizumab to 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. ResultsThe 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. ConclusionsThis analysis suggests that patient-level simulation models may be well suited to representing the realworld 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. Key Points for Decision Makers Patient-level simulation modelling may be a technique well-suited to representing the patient pathway and disease progression in ophthalmology.  An analysis of two NICE-approved treatments for wAMD provides an example of the benefits of simulation modelling over cohort (Markov) modelling in this disease area.3

Real-World Effectiveness and Real-World Cost-Effectiveness of Intravitreal Aflibercept and Intravitreal Ranibizumab in Neovascular Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Real-World Studies

“…The cost-effectiveness of intravitreally administered aflibercept and RBZ to treat patients with nAMD in the European setting was established primarily on the basis of data from RCTs [18][19][20][21][22]. Both intravitreally administered aflibercept and RBZ have been shown to be cost-effective treatment options in different settings, but no analysis of the real-world costeffectiveness of these two treatments has been undertaken.…”

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration: A Novel Regression Analysis to Capture the Bilateral Nature of the Disease

“…The utility values derived using the different exchangeable regression models described here have been used in a recent economic evaluation of ranibizumab versus aflibercept for wet AMD [ 14 ]. This paper by Claxton et al demonstrates the practical use of this regression analysis and its importance to future economic evaluations for this disease [ 14 ].…”

“…The utility values derived using the different exchangeable regression models described here have been used in a recent economic evaluation of ranibizumab versus aflibercept for wet AMD [ 14 ]. This paper by Claxton et al demonstrates the practical use of this regression analysis and its importance to future economic evaluations for this disease [ 14 ]. The results of this cost-effectiveness analysis demonstrated that the scenario that incorporated utility values based on the BSE eye only (model 1) provided a substantially higher estimate of total QALY gains compared with the scenario based on the WSE only (model 2), providing evidence to support the use of a “two-eye” regression model (i.e., models 3–5).…”

“…When comparing the TTO-derived utilities with those derived via the Health Utilities Index-3 (HUI-3), EQ-5D, Short Form-6 Dimensions (SF-6D), and TTO by Espallargues et al [ 8 ], Czoski-Murray et al found a stronger significant correlation between VA in the BSE and the TTO-elicited utility values derived through the use of different contact lenses, than those derived by Espallargues et al for the HUI-3 and the EQ-5D, as well as those elicited directly via TTO from a population of wet AMD patients (i.e., without contact lenses) [ 8 ]. Whilst the opacity of the contact lenses has been criticized for simplifying the full effects of wet AMD on VA [ 13 , 14 ], the study by Czoski-Murray et al offers an interesting attempt to address the challenges associated with utility value elicitation in wet AMD and forms the basis of the de novo regression analysis presented in this publication.…”

“…In an attempt to address this limitation and the uncertainties raised by NICE regarding the estimation of utility values as a function of VA in both eyes, we present here a de novo regression analysis based on the dataset from Czoski-Murray et al that explores the estimation of utility as a function of VA in both the BSE and the WSE [ 19 ]. This analysis was briefly introduced in a recent paper by Claxton et al [ 14 ], and is presented in full in this publication.…”