Burden and Treatment of Achondroplasia: A Systematic Literature Review.

BACKGROUND: Achondroplasia is the most common form of skeletal dysplasia. Recent advances in therapeutic options have highlighted the need for understanding the burden and treatment landscape of the condition. This systematic literature review (SLR) aimed to identify health-related quality of life (HRQoL)/utilities, healthcare resource use (HCRU), costs, efficacy, safety and economic evaluation data in achondroplasia and to identify gaps in the research. METHODS: Searches of MEDLINE, Embase, the University of York Centre for Reviews and Dissemination (CRD), the Cochrane Library and grey literature were performed. Articles were screened against pre-specified eligibility criteria by two individuals and study quality was assessed using published checklists. Additional targeted searches were conducted to identify management guidelines. RESULTS: Fifty-nine unique studies were included. Results demonstrated a substantial HRQoL and HCRU/cost-related burden of achondroplasia on affected individuals and their families throughout their lifetimes, particularly in emotional wellbeing and hospitalisation costs and resource use. Vosoritide, growth hormone (GH) and limb lengthening all conferred benefits for height or growth velocity; however, the long-term effects of GH therapy were unclear, data for vosoritide were from a limited number of studies, and limb lengthening was associated with complications. Included management guidelines varied widely in their scope, with the first global effort to standardise achondroplasia management represented by the International Achondroplasia Consensus Statement published at the end of 2021. Current evidence gaps include a lack of utility and cost-effectiveness data for achondroplasia and its treatments. CONCLUSIONS: This SLR provides a comprehensive overview of the current burden and treatment landscape for achondroplasia, along with areas where evidence is lacking. This review should be updated as new evidence becomes available on emerging therapies.

Disease-specific assessment of Vision Impairment in Low Luminance in age-related macular degeneration - a MACUSTAR study report.

BACKGROUND/AIMS: To further validate the Vision Impairment in Low Luminance (VILL) questionnaire, which captures visual functioning and vision-related quality of life (VRQoL) under low luminance, low-contrast conditions relevant to age-related macular degeneration (AMD). METHODS: The VILL was translated from German into English (UK), Danish, Dutch, French, Italian and Portuguese. Rasch analysis was used to assess psychometric characteristics of 716 participants (65% female, mean age 72±7 years, 82% intermediate AMD) from the baseline visit of the MACUSTAR study. In a subset of participants (n=301), test-retest reliability (intraclass correlation coefficient (ICC) and coefficient of repeatability (CoR)) and construct validity were assessed. RESULTS: Four items were removed from the VILL with 37 items due to misfit. The resulting Vision Impairment in Low Luminance with 33 items (VILL-33) has three subscales with no disordered thresholds and no misfitting items. No differential item functioning and no multidimensionality were observed. Person reliability and person separation index were 0.91 and 3.27 for the Vision Impairment in Low Luminance Reading Subscale (VILL-R), 0.87 and 2.58 for the Vision Impairment in Low Luminance Mobility Subscale (VILL-M), and 0.78 and 1.90 for the Vision Impairment in Low Luminance Emotional Subscale (VILL-E). ICC and CoR were 0.92 and 1.9 for VILL-R, 0.93 and 1.8 for VILL-M and 0.82 and 5.0 for VILL-E. Reported VRQoL decreased with advanced AMD stage (p<0.0001) and was lower in the intermediate AMD group than in the no AMD group (p≤0.0053). CONCLUSION: The VILL is a psychometrically sound patient-reported outcome instrument, and the results further support its reliability and validity across all AMD stages. We recommend the shortened version of the questionnaire with three subscales (VILL-33) for future use. TRIAL REGISTRATION NUMBER: NCT03349801.

The economics of vision impairment and its leading causes: A systematic review.

Vision impairment (VI) can have wide ranging economic impact on individuals, households, and health systems. The aim of this systematic review was to describe and summarise the costs associated with VI and its major causes. We searched MEDLINE (16 November 2019), National Health Service Economic Evaluation Database, the Database of Abstracts of Reviews of Effects and the Health Technology Assessment database (12 December 2019) for partial or full economic evaluation studies, published between 1 January 2000 and the search dates, reporting cost data for participants with VI due to an unspecified cause or one of the seven leading causes globally: cataract, uncorrected refractive error, diabetic retinopathy, glaucoma, age-related macular degeneration, corneal opacity, trachoma. The search was repeated on 20 January 2022 to identify studies published since our initial search. Included studies were quality appraised using the British Medical Journal Checklist for economic submissions adapted for cost of illness studies. Results were synthesized in a structured narrative. Of the 138 included studies, 38 reported cost estimates for VI due to an unspecified cause and 100 reported costs for one of the leading causes. These 138 studies provided 155 regional cost estimates. Fourteen studies reported global data; 103/155 (66%) regional estimates were from high-income countries. Costs were most commonly reported using a societal (n = 48) or healthcare system perspective (n = 25). Most studies included only a limited number of cost components. Large variations in methodology and reporting across studies meant cost estimates varied considerably. The average quality assessment score was 78% (range 35-100%); the most common weaknesses were the lack of sensitivity analysis and insufficient disaggregation of costs. There was substantial variation across studies in average treatment costs per patient for most conditions, including refractive error correction (range $12-$201 ppp), cataract surgery (range $54-$3654 ppp), glaucoma (range $351-$1354 ppp) and AMD (range $2209-$7524 ppp). Future cost estimates of the economic burden of VI and its major causes will be improved by the development and adoption of a reference case for eye health. This could then be used in regular studies, particularly in countries with data gaps, including low- and middle-income countries in Asia, Eastern Europe, Oceania, Latin America and sub-Saharan Africa.

Evaluating discrete choice experiment willingness to pay [DCE-WTP] analysis and relative social willingness to pay [RS-WTP] analysis in a health technology assessment of a treatment for an ultra-rare childhood disease [CLN2].

BACKGROUND: Conventional cost-effectiveness analysis [CEA] using cost per QALY thresholds may counteract other incentives introduced to foster development of treatments for rare and ultra-rare diseases. Therefore, alternative economic evaluation methods were explored, namely Discrete Choice Experiment Willingness to Pay (DCE-WTP) and Relative Social Willingness to Pay (RS-WTP), to value interventions for an ultra-rare childhood disease, Neuronal Ceroid Lipofuscinosis type 2 (CLN2). RESEARCH DESIGN AND METHODS: Treatment for CLN2 was valued from a citizen's ('social') perspective using DCE-WTP and RS-WTP in a survey of 4,009 United Kingdom [UK] adults. Three attributes (initial quality of life, treatment effect, and life expectancy) were used in both analyses. For DCE-WTP, a cost attribute (marginal income tax increase) was also included. Optimal econometric models were identified. RESULTS: DCE-WTP indicated that UK adults are willing to pay incremental increases through taxation for improvements in CLN2 attributes. RS-WTP identified a willingness to allocate >40% of a pre-assigned healthcare budget to prevent child mortality and approximately 15% for improved health status. CONCLUSIONS: Both techniques illustrate substantive social WTP for CLN2 interventions, despite the small number of children benefitting. This highlights a gap between UK citizens' willingness to spend on rare disease interventions and current funding policies.

Investigating health-related quality of life in rare diseases: a case study in utility value determination for patients with CLN2 disease (neuronal ceroid lipofuscinosis type 2).

BACKGROUND: Utility studies enable preference-based quantification of a disease's impact on patients' health-related quality of life (HRQoL). It is often difficult to obtain utility values for rare, neurodegenerative conditions due to cognitive burden of direct elicitation methods, and the limited size of patient/caregiver populations. CLN2 disease (neuronal ceroid lipofuscinosis type 2) is an ultra-rare, progressive condition, for which there are no published utility data fully capturing all disease stages. This case study demonstrates how utility values can be estimated for ultra-rare paediatric diseases by asking clinicians to complete EQ-5D-5L questionnaires based on vignettes describing the stages of CLN2 disease. METHODS: An indirect elicitation method using proxy-reporting by clinical experts was adopted. Eighteen vignettes were developed, describing nine progressive disease stages as defined by motor and language domain scores of the CLN2 Clinical Rating Scale, in individuals treated with cerliponase alfa or standard care. Eight clinical experts with experience of treating CLN2 disease with cerliponase alfa and current standard care completed the proxy version 2 EQ-5D-5L online after reading these vignettes. Resulting scores were converted to EQ-5D-5L utility values for each disease stage, using UK, German and Spanish value sets. RESULTS: Utility values, which are typically anchored by 0 (equivalent to death) and 1 (full health), decreased with CLN2 disease progression (results spanned the maximum range of the utility scale). Assigned utility values were consistently higher for patients receiving cerliponase alfa than standard care; differences were statistically significant for the 6 most severe disease stages (p < 0.05). Analysis of the individual dimensions of the EQ-5D-5L showed that greatest differences between patients treated with cerliponase alfa and standard care occurred in the pain dimension (differences in mean scores ranged between no difference and 1.8), with notable differences also observed in the anxiety/depression dimension (differences in mean scores ranged between 0.1 and 1.0). CONCLUSIONS: This study demonstrates a feasible methodology for eliciting utility values in CLN2 disease, indicating HRQoL declines with disease progression. Vignettes describing patients receiving cerliponase alfa were consistently assigned higher utility values for the same disease state, suggesting this treatment improves HRQoL compared with standard care. Trial registration NCT01907087, NCT02485899.

Global economic productivity losses from vision impairment and blindness.

BACKGROUND: In the absence of accessible, good quality eye health services and inclusive environments, vision loss can impact individuals, households and communities in many ways, including through increased poverty, reduced quality of life and reduced employment. We aimed to estimate the annual potential productivity losses associated with reduced employment due to blindness and moderate and severe vision impairment (MSVI) at a regional and global level. METHODS: We constructed a model using the most recent economic, demographic (2018) and prevalence (2020) data. Calculations were limited to the working age population (15-64 years) and presented in 2018 US Dollars purchasing power parity (ppp). Two separate models, using Gross Domestic Product (GDP) and Gross National Income (GNI), were calculated to maximise comparability with previous estimates. FINDINGS: We found that 160.7 million people with MSVI or blindness were within the working age and estimated that the overall relative reduction in employment by people with vision loss was 30.2%. Globally, using GDP we estimated that the annual cost of potential productivity losses of MSVI and blindness was $410.7 billion ppp (range $322.1 - $518.7 billion), or 0.3% of GDP. Using GNI, overall productivity losses were estimated at $408.5 billion ppp (range $320.4 - $515.9 billion), 0.5% lower than estimates using GDP. INTERPRETATION: These findings support the view that blindness and MSVI are associated with a large economic impact worldwide. Reducing and preventing vision loss and developing and implementing strategies to help visually impaired people to find and keep employment may result in significant productivity gains. FUNDING: MJB is supported by the Wellcome Trust (207472/Z/17/Z). JR's appointment at the University of Auckland is funded by the Buchanan Charitable Foundation, New Zealand. The Lancet Global Health Commission on Global Eye Health was supported by grants from The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity (GR001061), NIHR Moorfields Biomedical Research Centre, The Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The SEVA Foundation, The British Council for the Prevention of Blindness and Christian Blind Mission. The funders had no role in the design, conduct, data analysis of the study, or writing of the manuscript.

Estimating the global cost of vision impairment and its major causes: protocol for a systematic review.

INTRODUCTION: Vision impairment (VI) places a burden on individuals, health systems and society in general. In order to support the case for investing in eye health services, an updated cost of illness study that measures the global impact of VI is necessary. To perform such a study, a systematic review of the literature is needed. Here we outline the protocol for a systematic review to describe and summarise the costs associated with VI and its major causes. METHODS AND ANALYSIS: We will systematically search in Medline (Ovid) and the Centre for Reviews and Dissemination database which includes the National Health Service Economics Evaluation Database. No language or geographical restriction will be applied. Additional literature will be identified by reviewing the references in the included studies and by contacting field experts. Grey literature will be considered. The review will include any study published from 1 January 2000 to November 2019 that provides information about costs of illness, burden of disease and/or loss of well-being in participants with VI due to an unspecified cause or due to one of the seven leading causes globally.Two reviewers will independently screen studies and extract relevant data from included studies. Methodological quality of economic studies will be assessed based on the British Medical Journal checklist for economic submissions adapted to costs of illness studies. This protocol has been prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocols and has been published prospectively in Open Science Framework. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as primary data will not be collected in this review. The findings of this study will be disseminated through peer-reviewed publications, stakeholder meetings and inclusion in the ongoing Lancet Global Health Commission on Global Eye Health. REGISTRATION DETAILS: https://osf.io/9au3w (DOI 10.17605/OSF.IO/6F8VM).

Characteristics and health burden of the undiagnosed population at risk of chronic obstructive pulmonary disease in China.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in China. However, identifying patients has proved challenging, resulting in widespread under-diagnosis of the condition. We examined the prevalence of COPD diagnosis and COPD risk among adults in urban mainland China, the factors associated with having a COPD diagnosis or COPD risk, and the healthcare resource use and health outcomes of these groups compared with controls. METHODS: Respondents to the 2017 National Health and Wellness Survey in China (n = 19,994) were classified into three groups: 'COPD Diagnosed', 'COPD Risk (undiagnosed)', and Control (unaffected), based on their self-reported diagnosis and Lung Function Questionnaire (LFQ) score. The groups were characterised by sociodemographic, health-related quality of life (HRQoL), productivity impairment, and healthcare resource use. Pairwise comparisons (t tests and chi-squared tests) and multivariable regression analyses were used to investigate factors associated with being at risk of, or diagnosed with, COPD. RESULTS: 3320 (16.6%) respondents had a suspected risk of COPD but did not report receiving a diagnosis. This was projected to 105.3 million people, or 16.9% of adult urban Chinese. Of these respondents with an identified risk, only 554 (16.7%) were aware of COPD by name. Relative to those without COPD, those with a risk of COPD (undiagnosed) had significantly greater healthcare resource use, lower productivity and lower HRQoL not only compared to those without COPD, but also compared to people with a COPD diagnosis. Factors associated with increased odds of being at risk of COPD were older age, smoking, alcohol consumption, overweight BMI, occasional exercise, higher comorbidities, asthma diagnosis, being female, lower education, not being employed, and living in a high pollution province (p < 0.05). CONCLUSIONS: There is a substantial group of individuals, undiagnosed, but living with a risk of COPD, who have impaired HRQoL, lower productivity and elevated healthcare resource use patterns. Case-detection tools such as the LFQ may prove a quick and cost-effective approach for identifying these at-risk individuals for further definitive testing and appropriate treatment in China.

Productivity Losses and Their Explanatory Factors Amongst People with Impaired Vision.

Purpose: To estimate productivity losses amongst people with impaired vision in Portugal and to investigate explanatory factors associated with non-participation in the labour market.Methods: A total of 546 visually impaired individuals participated in face-to-face interviews. Participants were asked about their workforce participation to determine productivity (employment status questionnaire), their health-related quality of life - HRQoL (EQ-5D) and their visual acuity and visual ability (Activity Inventory). Productivity losses included absenteeism and reduction in workforce participation. Logistic regression was used to determine independent factors associated with participation in the labour market.Results: From the 546 participants, 50% were retired, 47% were of working age and 3% were students. The employment rate was 28%, and the unemployment rate was 21% for the working age sample. For those of working age, productivity losses were estimated at €1.51 million per year, mean of €5496 per participant. The largest contributor to productivity losses was reduced workforce participation, estimated from 159 early retired or unemployed participants. After controlling for visual acuity and ability, younger individuals, with more years of education, without comorbidities and high HRQoL had a higher probability of being employed.Conclusions: Our findings show a high unemployment rate and high productivity losses amongst people with impaired vision. The probability of being employed was associated with education, HRQoL and comorbidities. We speculate that promoting education and health through effective visual rehabilitation programs may help to increase participation in the labour market. These findings can inform decisions to intervene to reduce the burden of vision loss.

Taking stock of cost-effectiveness analysis of healthcare in China.

INTRODUCTION: Cost-effectiveness analysis (CEA) is playing an increasingly important role in informing healthcare decision-making in China. This study aims to review the published literature on CEA in mainland China and describe its characteristics and evolution. We provide recommendations on the future direction of CEA as a methodology and as a tool to support healthcare decision-making in China. METHODS: English-language cost-per-quality-adjusted life-year (QALY) and cost-per-disability-adjusted life-year (DALY) publications relating to mainland China were reviewed using the Tufts Medical Center Cost-Effectiveness Analysis Registry and Global Health Cost-Effectiveness Analysis Registry through 2017. Study features were summarised using descriptive statistics. Changes in study methodology over time were analysed by trend test, and study characteristics influencing the incremental cost-effectiveness ratio (ICER) of cost-per-QALY studies were investigated using logistic regression. RESULTS: 170 studies were identified reporting CEA for mainland China (cost/QALY=125, cost/DALY=45) since 1998. The number and quality of studies has increased over the past two decades, with significantly more cost-per-QALY studies compared with cost-per-DALY studies (p<0.0001) and more studies with authors affiliated with Chinese institutions (p=0.0002). The average quality score was 5.04 out of 7 for cost-per-QALY and 4.70 for cost-per-DALY studies based on Registry reviewers' subjective assessment of overall quality (methods, assumptions and reporting practices). The median ICER reported for interventions for oncology patients was higher (US$26 694 per QALY) than the median ICER reported for all interventions (US$11 503 per QALY). Oncology interventions were associated with the likelihood of reporting higher ICERs than the median ICER (p=0.003). CONCLUSION: The number of English-language published CEA studies relating to China has grown rapidly over the past 20 years. In terms of quality, the China studies compare favourably with international studies, although they remain a small proportion of studies globally.

Measuring the Benefits of Decision Aids for Economic Evaluation.

Decision aids, sometimes known as decision-support tools, are increasingly used to help patients to understand treatment options and to reach an informed decision consistent with their own values, yet methods for their economic evaluation have received limited attention. This is at odds with the increasingly rigorous methods being applied to assess the cost effectiveness of other health technologies. This paper reviews current approaches to evaluating decision aids and proposes a new method for assessing their benefits relative to other interventions in a resource-constrained health system that seeks to improve health, equity and patient satisfaction. Current evaluation frameworks are found to be unsuitable for the economic evaluation of decision aids since their objectives are broader than health maximisation. Decision aids may generate significant non-health benefits such as improved patient knowledge and satisfaction, which cannot be assessed using cost-utility analysis. A stated-preference consultation time trade-off (CTTO) is proposed in which a proportion of hypothetical physician consultation is traded for use of the decision aid. A decision aid provides information for a patient to make an informed choice and therefore may be considered to be a substitute for physician time. The CTTO can be reported in consultation minutes or converted to monetary units using the cost of physician time. These values may be used, alongside the implementation cost, for economic evaluation.

Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data.

AIMS: To evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related macular degeneration AMD (nAMD), AREDS category 4. METHODS: A patient-level health state transition model based on levels of visual acuity in the better-seeing eye was constructed to simulate the costs and consequences of patients taking AREDS vitamin supplements. SETTING: UK National Health Service (NHS). The model was populated with data from AREDS and real-world outcomes and resource use from a prospective multicentre national nAMD database study containing 92 976 ranibizumab treatment episodes. INTERVENTIONS: Two treatment approaches were compared: immediate intervention with AREDS supplements or no supplements. MAIN OUTCOME MEASURES: quality-adjusted life years (QALYs) and healthcare costs were accrued for each strategy, and incremental costs and QALYs were calculated for the lifetime of the patient. One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model. RESULTS: For AREDS category 3, the incremental cost-effectiveness ratio was £30 197. For AREDS category 4 compared with no intervention, AREDS supplements are more effective (10.59 vs 10.43 QALYs) and less costly (£52 074 vs 54 900) over the lifetime of the patient. CONCLUSIONS: The recommendation to publicly fund AREDS supplements to category 3 patients would depend on the healthcare system willingness to pay. In contrast, initiating AREDS supplements in AREDS category 4 patients is both cost saving and more effective than no supplement use and should therefore be considered in public health policy.

Comparing Generic and Condition-Specific Preference-Based Measures in Epilepsy: EQ-5D-3L and NEWQOL-6D.

BACKGROUND: There is debate about the psychometric characteristics of the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) for use in epilepsy. In response to the concerns, an epilepsy-specific preference-based measure (NEWQOL-6D) was developed. The psychometric characteristics of the NEWQOL-6D, however, have not been assessed. OBJECTIVES: To investigate the validity and responsiveness of the EQ-5D-3L and the Quality of Life in Newly Diagnosed Epilepsy Instrument-six dimensions (NEWQOL-6D) for use in the assessment of treatments for newly diagnosed focal epilepsy. METHODS: The analysis used data from the Standard And New Antiepileptic Drugs trial including patients with focal epilepsy. We assessed convergent validity using correlations, and known-group validity across different epilepsy and general health severity indicators using analysis of variance and effect sizes. The responsiveness of the measures to change over time was assessed using standardized response means. We also assessed agreement between the measures. RESULTS: There was some level of convergence and agreement between the measures in terms of utility score but divergence in the concepts measured by the descriptive systems. Both instruments displayed known-group validity, with significant differences between severity groups, and generally slightly larger effect sizes for the NEWQOL-6D across the epilepsy-specific indicators. Evidence for responsiveness was less clear, with small to moderate standardized response means demonstrating different levels of change across different indicators. CONCLUSIONS: There was an overall tendency for the NEWQOL-6D to better reflect differences across groups, but this does not translate into large absolute utility differences. Both the EQ-5D-3L and the NEWQOL-6D show some evidence of validity for providing utility values for economic evaluations in newly diagnosed focal epilepsy.

Health State Utility Values for Age-Related Macular Degeneration: Review and Advice.

Health state utility values are a major source of uncertainty in economic evaluations of interventions for age-related macular degeneration (AMD). This review identifies and critiques published utility values and methods for eliciting de novo utility values in AMD. We describe how utility values have been used in healthcare decision making and provide guidance on the choice of utility values for future economic evaluations for AMD. Literature was searched using PubMed, and health technology assessments (HTA) were searched using HTA agency websites to identify articles reporting utility values or approaches to derive utility values in AMD and articles applying utilities for use in healthcare decision making relating to treatments for AMD. A total of 70 studies qualified for data extraction, 22 of which were classified as containing utility values and/or elicitation methods, and 48 were classified as using utility values in decision making. A large number of studies have elicited utility values for AMD, although those applied to decision making have focused on a few of these. There is an appreciation of the challenges in the measurement and valuation of health states, with recent studies addressing challenges such as the insensitivity of generic health-related quality of life (HRQoL) questionnaires and utility in the worse-seeing eye. We would encourage careful consideration when choosing utility values in decision making and an explicit critique of their applicability to the decision problem.

The cost-effectiveness of initiating ranibizumab therapy in eyes with neovascular AMD with good vision: an economic model using real-world outcomes.

OBJECTIVES: To evaluate the cost-effectiveness of immediate treatment with ranibizumab in patients with neovascular age-related macular degeneration (nAMD) with good (better than 6/12) starting visual acuity compared with current UK clinical guidance of waiting until vision falls below 6/12 to begin treatment, using real-world outcomes data. DESIGN: A patient-level health economic state transition model based on levels of visual acuity in the better seeing eye was constructed to simulate the costs and consequences of treating patients with nAMD with ranibizumab. SETTING: The model took the perspective of the UK National Health Service (NHS). PARTICIPANTS: The model was populated with real-world outcomes and resource use from a prospective multicentre national nAMD database study containing 92,976 ranibizumab treatment episodes. INTERVENTIONS: Two treatment approaches were compared: immediate intervention with 0.5 mg ranibizumab pro re nata, PRN (on detection of nAMD) or delayed intervention (waiting until vision fell to 6/12 before beginning treatment). MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) for health states and healthcare costs were accrued for each strategy, and an incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model. RESULTS: Over a 2-year time horizon, based on 10,000 Monte Carlo simulations, the early treatment arm accumulated 1.59 QALYs and £8469.79 cost. The delayed treatment arm accumulated 1.35 QALYs and £7460.21 cost. The central ICER estimate was £4251.60. CONCLUSIONS: A model based on real-world data is likely to be a realistic reflection of the health gains and resource use of ranibizumab for nAMD in the UK NHS. Initiating treatment immediately with ranibizumab PRN regimen is a cost-effective strategy compared with current guidance of initiating treatment at a level of 6/12 or worse vision.

An educational review of the statistical issues in analysing utility data for cost-utility analysis.

The aim of cost-utility analysis is to support decision making in healthcare by providing a standardised mechanism for comparing resource use and health outcomes across programmes of work. The focus of this paper is the denominator of the cost-utility analysis, specifically the methodology and statistical challenges associated with calculating QALYs from patient-level data collected as part of a trial. We provide a brief description of the most common questionnaire used to calculate patient level utility scores, the EQ-5D, followed by a discussion of other ways to calculate patient level utility scores alongside a trial including other generic measures of health-related quality of life and condition- and population-specific questionnaires. Detail is provided on how to calculate the mean QALYs per patient, including discounting, adjusting for baseline differences in utility scores and a discussion of the implications of different methods for handling missing data. The methods are demonstrated using data from a trial. As the methods chosen can systematically change the results of the analysis, it is important that standardised methods such as patient-level analysis are adhered to as best as possible. Regardless, researchers need to ensure that they are sufficiently transparent about the methods they use so as to provide the best possible information to aid in healthcare decision making.

Modelling cost effectiveness in neovascular age-related macular degeneration: the impact of using contrast sensitivity vs. visual acuity.

BACKGROUND: The cost utility of treatments of age-related macular degeneration (AMD) is commonly assessed using health state transition models defined by levels of visual acuity. However, there is evidence that another measure of visual function, contrast sensitivity, may be better associated with utility than visual acuity. This paper investigates the difference in cost effectiveness resulting from models based on visual acuity and contrast sensitivity using the example of bevacizumab (Avastin) for neovascular AMD. The implications of the choice of outcome on structural uncertainty in the model are investigated. METHOD: Health state transition Markov models based on levels of visual acuity and contrast sensitivity are used to represent the costs, health utilities and outcomes of the Avastin for choroidal neovascular age-related macular degeneration (ABC) trial. Health states are associated with costs and utilities based on literature values. Treatment outcomes from the ABC trial are used to predict transitions between states in both models. Total costs and quality-adjusted life-years (QALYs) are calculated for a cohort of patients treated over a defined number of model cycles. RESULTS: Over a 5-year time horizon, a contrast sensitivity model predicts a statistically significant (p < 0.05) 25% greater QALY gain than the visual acuity model based on 10,000 Monte Carlo simulations. Bevacizumab is more effective and less costly than the comparator in the contrast sensitivity model and the visual acuity model. CONCLUSION: There is considerable structural uncertainty associated with the choice of outcome for modelling the cost effectiveness of AMD treatments. Bevacizumab has a higher incremental QALY gain and more favourable incremental cost-effectiveness ratio when cost effectiveness is assessed using contrast sensitivity outcomes compared with using visual acuity outcomes. Previous cost-effectiveness analyses may have underestimated the cost effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapy.