Analytical approach:
A Markov model was developed to assess the costs and benefits of the three sequences, over 10 years. The authors hypothesised that cost-effectiveness could be optimised by minimising therapy switches. The model was based on three triggers for therapy change: intolerance to treatment; intraocular pressure not below target level; and progression in visual field defect. The average age of patients at baseline was assumed to be 65 years. The authors stated that the perspective was that of the UK NHS.
Effectiveness data:
The key effectiveness inputs were the expected rates of therapy switching, for each treatment, due to the three triggers. Treatments differed in tolerance and the achievement of intraocular pressure targets. The rate of disease progression did not differ by treatment, but differed by whether the intraocular pressure targets were met. For intolerance, the rates of hyperaemia were used as a proxy, and switch rates were from a mixed-treatment comparison with 72 studies, identified by a systematic review. Switches due to non-compliance were based on expert opinion. The relative difference in intraocular pressure (after three months), for each treatment, was from a mixed-treatment comparison of 18 studies from the systematic review; the absolute on-treatment intraocular pressure over time was predicted using a meta-regression of data from 73 studies. Disease progression was from three clinical trials. The main analysis assumed a 50:50 mix of low- to high-risk patients.
Monetary benefit and utility valuations:
The utility values were applied to the four glaucoma health states. The ocular hypertension state was assumed to have the same utility as the UK population norm, as it had no symptoms. Age-specific, UK population norm utility values were from a 1999 published UK study, in which utility was measured using the EQ-5D. The other health states were based on a 2003 published study, which used visual acuity scores to predict the ocular utility values.
Measure of benefit:
The measures of benefit were the reduction in glaucoma progression, reduction in low vision, and improvement in quality-adjusted life-years (QALYs). Future QALYs were discounted at an annual rate of 3.5%.
Cost data:
The direct costs of glaucoma treatment were considered. The cost items included drug acquisition, out-patient visits, additional consultation time, surgery, and the annual cost of low vision (non-treatment and care costs). Monthly UK list prices were used to calculate the total cost of medical therapy. The frequency of out-patient visits was based on the NHS Do Once and Share treatment pathway. The cost per hour of addition consultant or nurse time was from the Personal Social Services Research Unit. The cost of extra optometrist time was from a published paper. The annual cost of low vision was from a published paper and the Personal Social Services Research Unit. All costs were reported in 2008 to 2009 prices. Future costs were discounted at an annual rate of 3.5%.
Analysis of uncertainty:
A sensitivity analysis was conducted on the rate of switching, due to intolerance, using estimates from an expert consultant ophthalmologist. The model was run separately for low- and high-risk patients.