© 2017 MA Healthcare Ltd. Introduction: Demonstration of cost-effectiveness is an established hurdle for new treatments and technologies. However, evidence synthesis, including simulation modelling, can be very difficult in the absence of good quality research that addresses pertinent questions, and people with rare conditions may have to forego the best available treatments. We illustrate this point with regard to the current choice between intravitreal ranibizumab, verteporfin photodynamic therapy (VPDT) or combinations of these (combination therapy) for polypoidal choroidal vasculopathy. Methods: We developed a Markov model to simulate equivalent cohorts of 65-year-old patients over a lifetime horizon. We obtained costs from the NHS national tariff, and utility values based on unilateral visual function deterioration. We carried out deterministic and probabilistic sensitivity analyses to investigate the sensitivity of the results to uncertainty in the model parameters. Results: Our model predicts that both VPDT and combination therapy offer cost savings but lower clinical efficacy over a lifetime horizon at δ81 165 and δ14 826 per quality-adjusted life year (QALY) respectively. VPDT monotherapy has a 99% chance of cost-effectiveness at a willingness to pay of δ30 000 per QALY gained. Combination therapy has a low (29%) probability of cost-effectiveness, however, this is heavily dependent on the modelled incidence of haemorrhagic adverse events. Conclusion: Based on the results of our model, VPDT might be commissioned according to a strict decision rule interpretation. The outcome regarding combination therapy is uncertain. These conclusions are dependent on the available evidence. There is considerable modelling and parameter uncertainty, which needs to be urgently addressed.

BACKGROUND: Keratoconus is a progressive degenerative corneal disorder of children and young adults that is traditionally managed by refractive error correction, with corneal transplantation reserved for the most severe cases. UVA collagen crosslinking is a novel procedure that aims to prevent disease progression, currently being considered for use in the UK NHS. We assess whether it might be a cost-effective alternative to standard management for patients with progressive keratoconus. METHODS: We constructed a Markov model in which we estimated disease progression from prospective follow-up studies, derived costs derived from the NHS National Tariff, and calculated utilities from linear regression models of visual acuity in the better-seeing eye. We performed deterministic and probabilistic sensitivity analyses to assess the impact of possible variations in the model parameters. RESULTS: Collagen crosslinking is cost effective compared with standard management at an incremental cost of £ 3174 per QALY in the base case. Deterministic sensitivity analysis shows that this could rise above £ 33,263 per QALY if the duration of treatment efficacy is limited to 5 years. Other model parameters are not decision significant. Collagen crosslinking is cost effective in 85% of simulations at a willingness-to-pay threshold of £ 30,000 per QALY. CONCLUSION: UVA collagen crosslinking is very likely to be cost effective, compared with standard management, for the treatment of progressive keratoconus. However, further research to explore its efficacy beyond 5 years is desirable.