Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, Bansback N, Beverley C, Bird A, Harding S, Chisholm I, Yang YC.

OBJECTIVES: To estimate the cost-effectiveness of screening for age-related macular degeneration (AMD) by developing a decision analytic model that incorporated and assessed all of the National Screening Committee criteria. A further objective was to identify the major areas of uncertainty in the model, and so inform future research priorities in this disease area. DATA SOURCES: Major databases were searched in March 2004 and updated in January 2005. REVIEW METHODS: Systematic literature reviews covered the epidemiology and natural history of AMD, the screening and treatment effectiveness and health-related quality of life relating to AMD. A hybrid cohort-individual sampling model was implemented to describe the range of pathways between the incidence of age-related maculopathy (ARM) and death via clinical presentation and treatment at different stages of the disease. As significant shortfalls in the data available from the literature were apparent, so a range of primary data sources were also used to populate the model. To obtain estimates for the value of parameters deemed to be within an expert’s remit, data describing some parameters were elicited from relevant experts. The data identified informed probability distributions describing the uncertainty around the model parameters. To incorporate joint parameter uncertainty (i.e. correlations between parameters), the AMD natural history model was calibrated probabilistically. Randomly sampled sets of input parameters were assigned weights representing the accuracy of their predictions of a set of observed model outputs. The analysis of the AMD screening model estimated the costs, numbers of quality-adjusted life-years (QALYs) and cases of blindness in a general population sample of 50-year-olds over the remainder of their lifetime, for 16 alternative screening options (including no screening). The reference case analysis incorporated current treatment options of laser photocoagulation and photodynamic therapy. Sensitivity analyses describing six alternative sets of intervention strategies, based on horizon scanning of potential future treatments for AMD, were also undertaken. RESULTS: There remains significant uncertainty about whether any form of screening for AMD is cost-effective. However, annual screening from age 60 years seems to provide the highest mean net benefits, but this is based on a cost-effectiveness estimate that has very poor precision (high levels of uncertainty). The probabilistic sensitivity analysis shows that the 95% credible interval for annual screening from age 60 years ranges from this option dominating the previous option to an incremental cost per QALY of over 0.5 million pounds sterling. Plotting a cost-effectiveness acceptability frontier shows that although annual screening from age 60 years has the highest net benefits at a value of QALY of 30,000 pounds sterling, the associated probability of this option being the most cost-effective option is only around 20%. The sensitivity analyses around potential future treatment options indicate that screening may become more cost-effective with the new treatments. CONCLUSIONS: The conclusions focus on the interpretation of the results from the perspective of defining the major areas of uncertainty, which were defined as disease progression, rates of clinical presentation, screening test and optician effectiveness, treatment effectiveness, and costs of blindness. Future research may be best targeted at assessing how routine data may be used to describe clinical presentation rates of ARM. Other potential studies include a pilot study of the effectiveness of screening and opticians’ referral patterns for AMD and a costing study of blindness as a continuum of association with deterioration in vision.

Health Technol Assess. 2008 Jun;12(27):iii-iv, ix-124

Karnon J, Czoski-Murray C, Smith K, Brand C, Chakravarthy U, Davis S, Bansback N, Beverley C, Bird A, Harding S, Chisholm I, Yang YC

OBJECTIVES: To estimate the cost-effectiveness of screening for age-related macular degeneration (AMD) by developing a decision analytic model that incorporated and assessed all of the National Screening Committee criteria. A further objective was to identify the major areas of uncertainty in the model, and so inform future research priorities in this disease area. DATA SOURCES: Major databases were searched in March 2004 and updated in January 2005. REVIEW METHODS: Systematic literature reviews covered the epidemiology and natural history of AMD, the screening and treatment effectiveness and health-related quality of life relating to AMD. A hybrid cohort-individual sampling model was implemented to describe the range of pathways between the incidence of age-related maculopathy (ARM) and death via clinical presentation and treatment at different stages of the disease. As significant shortfalls in the data available from the literature were apparent, so a range of primary data sources were also used to populate the model. To obtain estimates for the value of parameters deemed to be within an expert’s remit, data describing some parameters were elicited from relevant experts. The data identified informed probability distributions describing the uncertainty around the model parameters. To incorporate joint parameter uncertainty (i.e. correlations between parameters), the AMD natural history model was calibrated probabilistically. Randomly sampled sets of input parameters were assigned weights representing the accuracy of their predictions of a set of observed model outputs. The analysis of the AMD screening model estimated the costs, numbers of quality-adjusted life-years (QALYs) and cases of blindness in a general population sample of 50-year-olds over the remainder of their lifetime, for 16 alternative screening options (including no screening). The reference case analysis incorporated current treatment options of laser photocoagulation and photodynamic therapy. Sensitivity analyses describing six alternative sets of intervention strategies, based on horizon scanning of potential future treatments for AMD, were also undertaken. RESULTS: There remains significant uncertainty about whether any form of screening for AMD is cost-effective. However, annual screening from age 60 years seems to provide the highest mean net benefits, but this is based on a cost-effectiveness estimate that has very poor precision (high levels of uncertainty). The probabilistic sensitivity analysis shows that the 95% credible interval for annual screening from age 60 years ranges from this option dominating the previous option to an incremental cost per QALY of over 0.5 million pounds sterling. Plotting a cost-effectiveness acceptability frontier shows that although annual screening from age 60 years has the highest net benefits at a value of QALY of 30,000 pounds sterling, the associated probability of this option being the most cost-effective option is only around 20%. The sensitivity analyses around potential future treatment options indicate that screening may become more cost-effective with the new treatments. CONCLUSIONS: The conclusions focus on the interpretation of the results from the perspective of defining the major areas of uncertainty, which were defined as disease progression, rates of clinical presentation, screening test and optician effectiveness, treatment effectiveness, and costs of blindness. Future research may be best targeted at assessing how routine data may be used to describe clinical presentation rates of ARM. Other potential studies include a pilot study of the effectiveness of screening and opticians’ referral patterns for AMD and a costing study of blindness as a continuum of association with deterioration in vision.

Health Technol Assess. 2008 Jun;12(27):iii-iv, ix-124

Bansback N, Davis S, Brazier J

AIMS: To re-evaluate the cost-effectiveness of photodynamic therapy with verteporfin (Visudyne, Novartis AG, Switzerland) in patients with predominantly classic and classic choroidal neovascularization (CNV) owing to age-related macular degeneration (AMD), using new evidence on the impact of contrast sensitivity on health status. METHOD: A health economic model is used to synthesise the evidence on contrast sensitivity and treatment rates from the TAP Investigation with health state utilities and costs. Impairment of visual function is estimated using a Markov model to predict transitions between states of contrast sensitivity. Each state is associated with costs and a health state utility. Total expected costs and benefits for a cohort of patients over a defined number of cycles are calculated. The expected health state utility for each disease state was estimated using results from a study of 209 patients with AMD in Sheffield. The model includes the costs associated with treatment and monitoring in the verteporfin treatment arm and costs offset by delaying the deterioration of visual function. RESULTS: Beyond 3 years, the annual costs of the verteporfin arm are estimated to be less than the annual costs of the control arm, owing to the cost associated with higher blindness prevalence in the control arm. Over time, the results show that both the incremental utility and cost decreases. By 10 years, the estimated incremental cost-effectiveness is approximately pound20 996 per Quality-Adjusted Life Years. CONCLUSION: The results of this study suggest that the verteporfin therapy in the treatment for patients with predominantly classic and classic CNV owing to AMD is encouraging.

Eye (Lond). 2007 Dec;21(12):1455-63

Bansback N, Czoski-Murray C, Carlton J, Lewis G, Hughes L, Espallargues M, Brand C, Brazier J

BACKGROUND: There has been increasing interest in the use of measures of health related quality of life (HRQoL) and health state utility values in Age Related Macular Degeneration (ARMD). Visual acuity has been found to be an important determinant of such measures in previous studies. More recently, another measure of visual impairment, contrast sensitivity has received considerable attention. We designed a study to examine whether the contribution of contrast sensitivity in explaining HRQoL and health utilities over and above that of visual acuity. METHODS: 209 patients with unilateral or bilateral ARMD were recruited into a cross-sectional study of patients from a large teaching hospital. Patients underwent visual tests (near and distant visual acuity, contrast sensitivity) and completed a vision function questionnaire, the VF-14, HUI3, and time trade-off. RESULTS: Using multivariate regression analysis, the study revealed that contrast sensitivity remained a statistically significant predictor of all outcome measures even when visual acuity was included. This result was supported by the correlation coefficients between measures. CONCLUSIONS: The measurement of contrast sensitivity appears to be better related to a person’s HRQoL and health utility. Future studies should consider incorporating contrast sensitivity in addition to visual acuity. Studies, in particular economic evaluations, may underestimate the effect of treatment unless contrast sensitivity is considered.

Qual Life Res. 2007 Apr;16(3):533-43

Espallargues M, Czoski-Murray CJ, Bansback NJ, Carlton J, Lewis GM, Hughes LA, Brand CS, Brazier JE

PURPOSE: To estimate health status utility values in patients with age-related macular degeneration (ARMD) associated with visual impairments, by using preference-based measures of health. METHOD: This was a cross-sectional study involving patients with unilateral or bilateral ARMD who attended a large teaching hospital. Patients underwent visual tests (near and distant visual acuity [VA] and contrast sensitivity [CS]) and completed health status questionnaires including the Index of Visual Function (VF)-14 and three preference-based measures (the Health Utilities Index Mark III [HUI-3], the EuroQoL Health Questionnaire [EQ-5D], and the Short Form 6D Health Status Questionnaire [SF-6D]) and the time tradeoff (TTO). The mean health status is presented for five groups, defined according to the VA in the better-seeing eye and for four CS groups. RESULTS: Two hundred nine patients were recruited with substantial loss of visual function as obtained by visual tests (mean decimal VA in the better-seeing eye: 0.2) and self-report (mean VF-14 score: 41.5). The mean (+/-SD) utilities were 0.34 +/- 0.28 for HUI-3, 0.66 +/- 0.14 for SF-6D, 0.72 +/- 0.22 for EQ-5D, and 0.64 +/- 0.31 for TTO. The HUI-3 had the highest correlation with VA and CS (0.40 and -0.34), followed by TTO (0.25 and -0.21). Across the VA and CS groups, only HUI3 and TTO had a significant linear trend (P < 0.05). In a regression model with CS and VA as explanatory variables, only the coefficient on CS was statistically significant. CONCLUSIONS: ARMD is associated with a substantial impact on patients’ health status, but this was not reflected in two of the generic preference-based measures used. The HUI-3 seems to be the instrument of choice for use in economic evaluations in which community data are needed. It may be more appropriate to base economic models on CS or some combination of CS and VA rather than on VA alone.

Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4016-23