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.

Cost-effectiveness of olaparib versus routine surveillance in the maintenance setting for patients with BRCA-mutated advanced ovarian cancer after response to first-line platinum-based chemotherapy in Singapore.

OBJECTIVE: To evaluate the cost-effectiveness of olaparib as a maintenance treatment versus routine surveillance (RS) in patients with BRCA mutated (BRCAm) advanced ovarian cancer (OC) following response to first-line platinum-based chemotherapy in Singapore. METHODS: A 4-health state partitioned survival model was developed to simulate the lifetime (50 years) incremental cost-effectiveness ratio (ICER) of olaparib versus RS from a healthcare payer perspective. Progression-free survival, time to second disease progression, and overall survival were estimated using SOLO-1 data and extrapolated beyond the trial period using parametric survival models. Any patient who remained progression-free at year 7 was assumed to be no longer at risk of progression. Mortality rates were based on all-cause mortality, adjusted based on BRCA1/2 mutation. Health state utilities and adverse event frequencies were from SOLO-1. Drug costs were from local public healthcare institutions. Healthcare resource usage and costs were from local clinician input and publications. A 3% discount rate was applied to costs and outcomes. Deterministic and probabilistic sensitivity analyses (PSA) were performed to assess the robustness of results. RESULTS: The base-case analysis of olaparib maintenance therapy versus RS resulted in an ICER of Singapore dollar (SGD) 19,822 per quality-adjusted life-year (QALY) gained. The ICER was most sensitive to variations in the discount rate. PSA demonstrated that olaparib had an 87% probability of being cost-effective versus RS at a willingness-to-pay of SGD 60,000 per QALY gained. CONCLUSION: Olaparib has a high potential of being a cost-effective maintenance treatment versus RS for patients with BRCA1/2m advanced OC after response to first-line chemotherapy in Singapore.

Perspective on the Budgetary Impact of FP/FORM pMDI on Treatment and Management of Exacerbation in Moderate-to-Severe Asthma Patients in Singapore.

PURPOSE: Reducing the risk of exacerbation is a long-term goal of managing moderate-to-severe asthma. The use of fluticasone propionate/formoterol fumarate dihydrate (FP/FORM) pressurized metered-dose (pMDI, Flutiform®), a type of inhaled corticosteroid (ICS) and long-acting ß2 agonist (LABA) fixed-dose combination, has been associated with lower oral corticosteroid-requiring exacerbation rates than other ICS/LABA fixed-dose combinations, fluticasone propionate/salmeterol xinafoate (FP/SAL) and budesonide/formoterol fumarate (BUD/FORM). This study presents the first budget impact analysis of drug and exacerbation management cost savings associated with the increased access to FP/FORM compared to the currently available ICS/LABAs for treating moderate-to-severe asthma in Singapore. PATIENTS AND METHODS: A budget impact model showed changes to annual drug and exacerbation costs over 5 years for patients with moderate-to-severe asthma in Singapore, following the inclusion of FP/FORM on a government subsidy list. The eligible patient population was identified based on national statistics data. Different treatment costs pertaining to the population were applied according to the usage data (IQVIA Singapore National Sales Data) for different scenarios. Drug costs were obtained from public-sector hospitals. Exacerbation management costs were obtained from literature searches. RESULTS: The analysis showed that increased access to FP/FORM as a result of switching from FP/SAL could help achieve drug (S$1,042,289) and exacerbation management (S$223,550) cost savings over 5 years. In the scenario where patients switched from BUD/FORM, greater drug (S$2,572,797) and exacerbation management (S$256,781) cost savings were observed over 5 years. CONCLUSION: The analysis provides a perspective that the increased access to FP/FORM could help achieve drug and exacerbation cost savings for the treatment of moderate-to-severe asthma.

A cost of illness study evaluating the burden of Wolfram syndrome in the United Kingdom.

BACKGROUND: Wolfram syndrome is a rare genetic, progressive, neurodegenerative disorder characterised by childhood-onset diabetes mellitus, diabetes insipidus, optic atrophy and deafness. To date, the economic burden of Wolfram syndrome has not been well-studied or reported. The aim of this study was to evaluate the cost of illness (COI) of all people with Wolfram syndrome in the UK and to identify major determinants of cost from a service provider perspective (National Health Service, NHS). METHODS: A prevalence-based approach was used to model the UK Wolfram syndrome specialist service. Model inputs were informed by a pragmatic literature review and UK reference costs, in conjunction with patient interviews and expert opinion. A deterministic sensitivity analysis (DSA) was run at 10% to identify major cost drivers. RESULTS: The total COI of all people with Wolfram syndrome to the NHS was £1,055,899 per year, with an average annual cost per person with Wolfram syndrome of £16,498. Costs associated with diabetes mellitus care, late-stage diabetes mellitus complications and hearing impairment contributed most to the COI (18.9, 21.4 and 15.8% of the COI, respectively). The DSA identified costs associated with hearing impairment, diabetes mellitus care and end-stage renal disease (a diabetes mellitus complication) as major model drivers. CONCLUSIONS: The annual cost of Wolfram syndrome to the NHS was found to be substantial, with areas of potential cost savings identified, such as diabetes mellitus management. This model provides crucial information to facilitate economic evaluation of prospective therapies for this disease.

The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus Aflibercept in the UK.

INTRODUCTION: Wet age-related macular degeneration (AMD) is a chronic eye condition that causes severe deterioration of vision and even blindness. Current wet AMD treatment in the UK involves the vascular endothelial growth factor inhibitors ranibizumab and aflibercept. Patients with wet AMD require frequent and long-term monitoring for treatment to be effective, contributing to a substantial resource burden at wet AMD centers. The European license for ranibizumab was recently updated with an individualized 'treat and extend' (T&E) regimen, comprising a structured monitoring and treatment protocol. This study evaluated the cost-effectiveness of ranibizumab T&E versus aflibercept within a UK setting. METHODS: An individual patient-level simulation model was developed utilizing treatment effects from a network meta-analysis of randomized controlled trials. The model was conducted from a UK National Health Service (NHS) perspective over a lifetime horizon and the base case utilized probabilistic sensitivity analysis to assess uncertainty in the model. Additional scenario analyses were conducted to assess the impact of changes to the model inputs. RESULTS: Ranibizumab T&E was found to be more effective and less costly than aflibercept, providing, on average, an additional 1.058 quality-adjusted life years (QALYs) and a cost-saving of £19,604 over a lifetime horizon. At list price, ranibizumab T&E was found to be cost-effective versus aflibercept in 100% of simulations at a willingness-to-pay threshold of £20,000 per QALY. The robustness of the results was tested in several scenario analyses; ranibizumab T&E was found to be more effective, and less costly, than aflibercept in the vast majority of cases. CONCLUSION: This evaluation suggests that treating patients with ranibizumab according to the T&E regimen could be a better use of NHS resources than aflibercept, and could, therefore, be considered as a first-line regimen for patients with wet AMD in the UK. FUNDING: Novartis Pharmaceuticals UK Limited.