Burden of chronic skin disease from an Asian perspective: Assessment of health state utilities and quality of life in a Singapore cohort.

Background: Understanding health state utilities of skin diseases is essential for health economic evaluations in an era of rising health care costs. Objective: To create a catalog of utility values of chronic skin diseases among Asians. Methods: This is a cross-sectional study of adults attending a dermatology outpatient clinic from February 2019 to March 2023 with one of the following skin diseases: (1) eczema, (2) psoriasis, (3) acne vulgaris, (4) chronic urticaria, (5) pigmentary disorders, (6) hair loss, (7) viral warts, (8) fungal infections, and (9) keloids. Demographic and socioeconomic information was collected. Health status and utilities (Dermatology Life Quality Index, Skindex-16, EuroQol-5 Dimension, visual analog scale, time-trade-off, and willingness-to-pay) were measured. Results: A total of 183 patients with a median age of 35.5 (21-77 years) years were included. Majority (76.9%) were Chinese, followed by Malays (11.5%). The time-trade-off utilities were lower than EuroQol-5 Dimension utilities across all disease severity and most skin diseases. Patients were willing to pay $740 USD or more for a hypothetical drug to cure conditions such as psoriasis, acne, hair loss, and keloids. Limitations: Limited sample size and ethnic representation. Conclusions: This study provides a catalog of utilities in skin diseases and highlights the strengths and challenges of different measures.

Valuing quality of life for economic evaluations in cancer: navigating multiple methods.

INTRODUCTION: Utility values offer a quantitative means to evaluate the impact of novel cancer treatments on patients' quality of life (QoL). However, the multiple methods available for valuing QoL present challenges in selecting the most appropriate method across different contexts. AREAS COVERED: This review provides cancer clinicians and researchers with an overview of methods to value QoL for economic evaluations, including standalone and derived preference-based measures (PBMs) and direct preference elicitation methods. Recent developments are described, including the comparative performance of cancer-specific PBMs versus generic PBMs, measurement of outcomes beyond health-related QoL, and increased use of discrete choice experiments to elicit preferences. Recommendations and considerations are provided to guide the choice of method for cancer research. EXPERT OPINION: We foresee continued adoption of the QLU-C10D and FACT-8D in cancer clinical trials given the extensive use of the EORTC QLQ-C30 and FACT-G in cancer research. While these cancer-specific PBMs offer the convenience of eliciting utility values without needing a standalone PBM, researchers should consider potential limitations if they intend to substitute them for generic PBMs. As the field advances, there is a greater need for consensus on the approach to selection and integration of various methods in cancer clinical trials.

A Systematic Literature Review and Meta-Analysis of Primary Evidence Reporting Health-State Preference Values in Chronic Hepatitis B, C, and D.

OBJECTIVES: Chronic viral hepatitis is associated with severe impairment and reduction in patient health-related quality of life because of the substantial morbidity associated with advanced liver disease. The aim of this study was to identify and synthesize utilities for chronic hepatitis B (cHBV), C (cHCV), and D (cHDV) through a systematic literature review (SLR) and meta-analyses. METHODS: Electronic databases were searched from inception to May 2023 to identify primary studies reporting health-state utilities in English in patients aged 18 years and over, with cHBV, cHCV, or cHDV in the United States, the United Kingdom, Europe, Canada, Australia, or New Zealand. Meta-analyses were conducted for studies reporting a measure of uncertainty; model selection (fixed and random) was based on the observed levels of heterogeneity among studies. RESULTS: A total of 24 studies met the inclusion criteria and were included in the meta-analyses. More studies meeting the inclusion criteria reported utilities for cHCV (n = 20) than for cHBV (n = 8); no studies reported utility values for cHDV. Although mean utilities were higher for cHBV compared with cHCV for any given health state, utilities decreased with disease progression toward cirrhosis health states. Meta-analyses in cHCV found a utility decline of 0.1 and 0.03, based on progression from noncirrhosis to compensated cirrhosis and for decompensation in established cirrhosis, respectively. CONCLUSIONS: Chronic viral hepatitis is associated with a considerable impairment in health-related quality of life. Despite our findings, there is a need for more evidence on the lived experience in patients living with chronic hepatitis, notably in cHBV and cHDV.

A Feasible Estimation of a "Corrected" EQ-5D Social Tariff.

OBJECTIVES: To demonstrate the feasibility of estimating a social tariff free of utility curvature and probability weighting biases and to test transferability between riskless and risky contexts. METHODS: Valuations for a selection of EQ-5D-3L health states were collected from a large and representative sample (N = 1676) of the Spanish general population through computer-assisted personal interviewing. Two elicitation methods were used: the traditional time trade-off (TTO) and a novel risky-TTO procedure. Both methods are equivalent for better than death states, which allowed us to test transferability of utilities across riskless and risky contexts. Corrective procedures applied are based on rank-dependent utility theory, identifying parameter estimates at the individual level. All corrections are health-state specific, which is a unique feature of our corrective approach. RESULTS: Two corrected value sets for the EQ-5D-3L system are estimated, highlighting the feasibility of developing national tariffs under nonexpected utility theories, such as rank-dependent utility. Furthermore, transferability was not supported for at least half of the health states valued by our sample. CONCLUSIONS: It is feasible to estimate a social tariff by using interviewing techniques, sample sizes, and sample representativeness equivalent to prior studies designed to generate national value sets for the EQ-5D. Utilities obtained in distinct contexts may not be interchangeable. Our findings caution against routinely taking transferability of utility for granted.

Quantitative Benefit-Risk Evaluation of Rivaroxaban in Patients After Peripheral Arterial Revascularization: The VOYAGER PAD Trial.

BACKGROUND: The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit-risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit-risk analyses with formal weighting approaches. METHODS AND RESULTS: Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi-criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent-to-treat and on-treatment analyses were conducted. For unweighted intent-to-treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, -208 to -32) fewer events of the primary composite end point (per 10 000 patient-years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8-72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, -85.3 to 52.6) and 68.1 (95% CI, 7.9-135.7) fewer deaths per 10 000 patient-years (intent-to-treat and on-treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation. CONCLUSIONS: These analyses show a favorable benefit-risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.

Health-related quality of life in Thai patients with chronic hepatitis B.

Background: Chronic hepatitis B (CHB) significantly impacts the health-related quality of life (HRQoL), but remains underexplored in the Thai population. Health state utilities (HSU) are indicators reflecting HRQoL which serve as fundamental inputs for economic evaluation analyses. This study aimed at assessing differences in HRQoL across five CHB stages in Thai patients, including non-cirrhotic CHB, compensated cirrhosis, decompensated cirrhosis, early-/intermediate-stage hepatocellular carcinoma (HCC) and advanced-/terminal-stage HCC. Methods: We conducted a cross-sectional study to collect HRQoL data from patients with CHB at five stages. The study included patients with CHB who were followed up at a super-tertiary care centre between March 2021 and February 2022. The participants completed the EQ-5D-5L questionnaire and provided demographic data. Disease stage and relevant data were obtained from medical records. HSU and Euroqol-visual analogue scale (EQ-VAS) scores, calculated using Thai-specific conversion coefficients, were assessed. Results: Among 422 patients, 236 did not have cirrhosis, 92 had compensated cirrhosis, 13 had decompensated cirrhosis, 55 had early-/intermediate-stage HCC, and 26 had advanced-/terminal-stage HCC. The HSU scores for non-cirrhotic, compensated cirrhosis, decompensated cirrhosis, early-/intermediate-stage HCC and advanced-/terminal-stage HCC were 0.95 ± 0.08, 0.89 ± 0.16, 0.79 ± 0.19, 0.89 ± 0.12 and 0.52 ± 0.39, respectively. Similarly, the EQ-VAS scores for various CHB stages were 83.56 ± 12.90, 80.48 ± 13.03, 68.76 ± 17.40, 79.00 ± 14.38 and 62.92 ± 20.62, respectively. A significant correlation (r = 0.469, P < 0.001) was observed between the HSU and EQ-VAS scores. The disease progression led to a notable HSU decline, particularly in the advanced-/terminal-stage HCC group (regression coefficient: -0.436, P < 0.001). The EQ-VAS scores indicated reduced quality of life in advanced liver disease. Conclusions: Later CHB stages compromise the HRQoL. Decompensated cirrhosis and advanced-/terminal-stage HCC profoundly affect physical health and quality of life, whereas patients with compensated cirrhosis and early-/intermediate-stage HCC report better HRQoL.

Health state utilities associated with weight loss: preferences of people with type 2 diabetes and obesity in Japan.

AIMS: Health state utilities associated with weight change are needed for cost-utility analyses (CUAs) examining the value of treatments for type 2 diabetes and obesity. Previous studies have estimated the utility benefits associated with various amounts of weight reduction in the US and Europe, but preferences for weight change in Asian cultures may differ from these published values. The purpose of this study was to estimate utilities associated with reductions in body weight based on preferences of individuals with type 2 diabetes and obesity in Japan. METHODS: Health state vignettes represented type 2 diabetes with respondents' own current weight and weight reductions of 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, and 20%. Utilities were elicited in time trade-off interviews with a sample of respondents in Japan with type 2 diabetes and body mass index (BMI) ≥25 kg/m2 (the cutoff for obesity in Japan). RESULTS: Analyses were conducted with data from 138 respondents (84.8% male; mean age = 58.0 years; mean BMI = 29.4 kg/m2) from all eight regions of Japan. Utility gains gradually increased with rising percentage of weight reductions ranging from 2.5% to 15%. Weight reductions of 2.5% to 15% resulted in utility increases of 0.013 to 0.048. The health state representing a 20% weight reduction yielded a wide range of preferences (mean utility increase of 0.044). Equations are recommended for estimating utility change based on any percentage of weight reduction (up to 20%) in Japanese people with type 2 diabetes and obesity. LIMITATIONS: This study was conducted in a sample with limited representation of patients with BMI >35 kg/m2 (n = 13) and relatively few women (n = 21). CONCLUSION: Results may be used to provide inputs for CUAs examining the value of treatments that are associated with weight loss in patients with type 2 diabetes and obesity in Japan.

Association of body mass index from childhood to mid-adulthood with health-related quality of life in mid-adulthood.

PURPOSE: Most studies regarding the association of obesity with health-related quality of life (HRQoL) have assessed obesity at only one or two time points. We aimed to examine the associations of life course body mass index (BMI) from childhood with health-related quality of life (HRQoL) in mid-adulthood. METHODS: Data were from a cohort study of Australian children (n = 2254, mean baseline age 12.0 (2.0) years in 1985, 46.8% male). Weight and height were measured at baseline and measured or self-reported on average 20, 25, and 30 years later. Age and sex-standardised BMI-z score was calculated at each time point. Physical and mental HRQoL and health state utilities (HSUs) were measured by SF-12 and SF-6D at the last adult follow-up. Linear regression was used to examine the associations adjusting for age, sex, and childhood health status. RESULTS: Higher BMI-z score in childhood (ßadjusted - 1.39, 95% CI - 1.73 to - 1.05) and increasing BMI-z score from childhood to young adulthood (ßadjusted - 1.82, 95% CI - 2.17 to - 1.46) and from young to mid-adulthood (ßadjusted - 1.77, 95% CI - 2.28 to - 1.26) were associated with lower physical HRQoL in mid-adulthood. Similar results were found for mid-adulthood HSUs (ßadjusted ranged - 0.006 to - 0.014, all P < 0.05). Only increasing BMI-z score from young to mid-adulthood significantly related to poorer mental HRQoL (ßadjusted - 0.74, 95% CI - 1.29 to - 0.19) in mid-adulthood. CONCLUSION: High BMI from childhood to mid-adulthood had only modest associations with HRQoL and HSUs, with effects on physical HRQoL most apparent.

Health state utilities associated with hyperphagia: Data for use in cost-utility models.

Objective: Rare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost-utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels. Methods: Four health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade-off elicitation study in a UK general population sample. Results: In total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were -0.08 (0.10) for mild, -0.28 (0.30) for moderate, and -0.77 (0.58) for severe hyperphagia. Conclusions: These data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost-utility models of treatments for rare genetic diseases of obesity.

Estimation of Health State Utility Values in Fabry Disease Using Vignette Development and Valuation.

Background: Health state utilities are measures of health-related quality of life that reflect the value placed on improvements in patients' health status and are necessary for estimation of quality-adjusted life-years. Health state utility data on Fabry disease (FD) are limited. In this study we used vignette (scenario) construction and valuation to develop health state utilities. Objectives: The aim of this study was to use vignette construction and valuation to estimate health state utility values suitable for inclusion in economic models of FD treatments. Methods: Health state vignettes were developed from semistructured qualitative telephone interviews with patients with FD and informed by published literature and input from an expert. Each vignette was valued in an online survey by members of the United Kingdom (UK) general population using the composite time trade-off (TTO) method, which aims to determine the time the respondent would trade to live in full health compared with each impaired health state. Results: Eight adults (50% women) with FD from the UK were interviewed. They were recruited via various approaches, including patient organizations and social media. The interviewees' responses, evidence from published literature, and input from a clinical expert informed the development of 6 health state vignettes (pain, moderate clinically evident FD [CEFD], severe CEFD, end-stage renal disease [ESRD], stroke, and cardiovascular disease [CVD]) and 3 combined health states (severe CEFD + ESRD, severe CEFD + CVD, and severe CEFD + stroke). A vignette valuation survey was administered to 1222 participants from the UK general population who were members of an external surveying organization and agreed to participate in this study; 1175 surveys were successfully completed and included in the analysis. Responses to TTO questions were converted into utility values for each health state. Pain was the highest valued health state (0.465), and severe CEFD + ESRD was the lowest (0.033). Discussion: Overall, mean utility values declined as the severity of the vignettes increased, indicating that respondents were more willing to trade life-years to avoid a severe health state. Conclusions: Health state vignettes reflect the effects of FD on all major health-related quality-of-life domains and may help to support economic modeling for treatment of FD.

Evaluating process utilities for the treatment burden of chemotherapy in multiple myeloma in Japan: a time trade-off valuation study.

AIMS: This study estimated the "process utilities" of treatment options for patients with relapsed/refractory multiple myeloma (RRMM) in Japan using the time trade-off (TTO) method. Chimeric antigen receptor (CAR) T cell immunotherapy is available for patients with RRMM who are triple-class exposed (TCE) after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies. However, the impact of available treatment options on health state utilities has not been well characterized, particularly in relation to process utilities. METHODS: Eight vignettes of health states and daily activity restrictions related to each of the following RRMM therapies were prepared: no treatment, CAR T cell therapy with idecabtagene vicleucel (ide-cel), regular intravenous infusion, and oral administration. A face-to-face survey of healthy Japanese adults who were representative of the general population was conducted. The TTO method was used to evaluate each vignette and to generate utility scores for each treatment regimen. RESULTS: Three hundred and nineteen respondents participated in the survey (mean age: 44 years [range: 20-64]; female: 50%). Utility scores for no treatment, ide-cel, oral pomalidomide, and dexamethasone (Pd) therapy ranged from ∼0.7 to 0.8. Utility scores for regular intravenous infusion regimens ranged from 0.50 to 0.56. There was a difference of ∼0.2 between the utility scores for no treatment/ide-cel/oral administration and regular intravenous infusions. CONCLUSIONS: Differences in treatment administration across RRMM therapies showed a substantial impact on health state utilities. When quantifying the value of treatments, process utility gains should be considered as an independent factor in health technology assessments.

Loss of Health State Utilities Attributable to Obesity.

OBJECTIVES: This study aimed to quantify the association between the loss of health state utilities (LHSU) and obesity, considering different obesity categories. This is relevant to interventions economic evaluations and for public policy decision planning. METHODS: Using data from the Chilean National Health Survey, this study uses linear regression models and counterfactual scenarios to calculate the prevalent burden, population averages, and total sum of LHSU attributable to obesity for the Chilean national level on people older than 15 years, year 2017. Adjustments for socioeconomic status and associated noncommunicable diseases (NCDs) are considered. Calculating the LHSU using these methods enables the approximation of loss of prevalent quality-adjusted life-years (QALYs). RESULTS: The raw obesity LHSU burden was 9.1% (95% uncertainty interval [UI] 5.1-13). When adjustment is considered, the LHSU attributable to obesity reaches 4.6% (95% UI 0.6-8.5) being responsible for 121 045 prevalent QALYs. Socioeconomic status adjusted analysis of higher body mass index (BMI, in kg/m2) categories of obesity shows a dose-response effect for LHSU, being the BMI ≥ 40 category with the highest population average of attributable LHSU (10.1; 95% UI 5.5-14.5, scale 0 [full health] to 100 [dead]). Burden for BMI ≥ 35 categories showed the biggest change after NCD adjustment. CONCLUSIONS: Obesity carries a significant burden of QALY loss. Policy decision-making addressing obesity should focus specially on the BMI ≥ 40 group. NCD comorbidity should be considered for policies addressing the BMI ≥ 35 group.

Health-state utilities in long-term advanced melanoma survivors comparable with the general population.

BACKGROUND: Checkpoint inhibitors have been shown to substantially improve the survival of patients with advanced melanoma. With this growing group of survivors treated with immunotherapies, assessing their health-state utilities is essential and can be used for the calculation of quality-adjusted life years and for cost-effectiveness analyses. Therefore, we evaluated the health-state utilities in long-term advanced melanoma survivors. METHODS: Health-state utilities were evaluated in a cohort of advanced melanoma survivors 24-36 months (N = 37) and 36-plus months (N = 47) post-ipilimumab monotherapy. In addition, the health-state utilities of the 24-36 months survivor group were assessed longitudinally, and utilities of the combined survival groups (N = 84) were compared with a matched control population (N = 168). The EQ-5D was used to generate health-state utility values, and quality-of-life questionnaires were used to establish correlations and influencing factors of utility scores. RESULTS: Health-state utility scores were similar between the 24-36 months'- and the 36-plus months' survival group (0.81 vs 0.86; p = .22). In survivors, lower utility scores were associated with symptoms of depression (ß = - .82, p = .022) and fatigue burden (ß = - .29, p = .007). Utility scores did not significantly change after 24-36 months of survival, and the utilities of survivors were comparable to the matched control population (0.84 vs 0.87; p = .07). DISCUSSION: Our results show that long-term advanced melanoma survivors treated with ipilimumab monotherapy experience relatively stable and high health-state utility scores.

Health Utility Analysis of Tepotinib in Patients With Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping.

OBJECTIVES: The VISION trial showed durable activity of tepotinib in MET exon 14 (METex14) skipping non-small cell lung cancer. We analyzed health state utilities using patient-reported outcomes from VISION. METHODS: 5-level version of EQ-5D (EQ-5D-5L) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 responses were collected at baseline, every 6 to 12 weeks during treatment, and at the end of treatment and safety follow-up. EQ-5D-5L and European Organisation for Research and Treatment of Cancer Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D) utilities were derived using United States, Canada, United Kingdom, and Taiwan value sets, where available. Utilities were analyzed with linear mixed models including covariates for progression or time-to-death (TTD). RESULTS: Utilities were derived for 273/291 patients (EQ-5D-5L, 1545 observations; QLU-C10D, 1546 observations). Mean (± SD) US EQ-5D-5L utilities increased after tepotinib initiation, from 0.687 ± 0.287 at baseline to 0.754 ± 0.250 before independently assessed progression, and decreased post progression (0.704 ± 0.288). US QLU-C10D utilities showed similar trends (0.705 ± 0.215, 0.753 ± 0.195, and 0.708 ± 0.209, respectively). Progression-based models demonstrated a statistically significant impact of progression on utilities and predicted higher utilities pre versus post progression. TTD-based models showed statistically significant associations of TTD with utilities and predicted declining utilities as TTD decreased. Prior treatment (yes/no) did not significantly predict utilities in progression- or TTD-based models. Utilities for Canada, United Kingdom, and Taiwan showed comparable trends. CONCLUSIONS: In this first analysis of health state utilities in patients with METex14 skipping non-small cell lung cancer, who received tepotinib, utilities were significantly associated with progression and TTD, but not prior treatment.

Exploring Health-Related Quality of Life Burden in Peanut Allergy and the Potential Benefit of Oral Immunotherapy: Estimation of Health State Utility Values for Children and Adolescents and Their Caregivers.

Purpose: This study aimed to estimate utility values for health states relating to oral immunotherapy (OIT) for peanut allergy (PA), for children with PA and their caregivers. Patients and Methods: Two methods were used: an online survey and structured interviews. Both methods assessed current utility/untreated PA (health-related quality of life, HRQoL) and HRQoL in different health states: "up-dosing phase of treatment", "maintenance phase" and "able to tolerate 6-8 peanuts if accidentally ingested". The survey was conducted in individuals with and without experience of OIT; data collected included the EQ-5D-Y (child states) and EQ-5D-5L (caregiver states). Results: In total, 100 caregivers and 38 adolescents completed the treatment-naïve survey, a separate sample of 50 caregivers participated in structured interviews. Seven caregivers and two adolescents with experience of OIT for PA completed the survey. Data from the three samples were pooled, the mean utility values were untreated PA: 0.796 (child), 0.855 (caregiver); up-dosing: 0.711 (child), 0.806 (caregiver); maintenance: 0.821 (child), 0.849 (caregiver), tolerate 6-8 peanuts: 0.859 (child), 0.884 (caregiver). The results show a gain in utility of 0.063 for children and 0.029 for caregivers between the untreated and tolerate 6-8 peanuts health states. Conclusion: This study is the first to assess utilities relating to OIT for PA. The results show the potential benefit of OIT for individuals with PA and their caregivers and provide values for use in cost-effectiveness evaluation.

A Discrete Choice Experiment to Derive Health Utilities for Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency in France.

PURPOSE: Cost-effectiveness evaluations of interventions require health utility data. However, in medical conditions, such as aromatic L-amino acid decarboxylase (AADC) deficiency, this presents problems due to the rarity of the disease. The study aim therefore was to employ a discrete choice experiment (DCE) to generate health utilities for AADC deficiency. METHODS: A previous literature review, clinician and parent interviews had identified six key AADC deficiency attributes: mobility, muscle weakness, oculogyric crises (OCG), feeding ability, cognitive impairment and screaming. A representative sample of the French general population was recruited. Participants rated 5 health state vignettes describing AADC deficiency using time-trade-off (TTO) and standard gamble (SG). Additionally, participants rated the worst health state using the Health Utility Index version 3 (HUI3). Subsequently, participants completed DCE 11 choice sets. Indirect DCE part-worth utilities were converted to health utilities using the anchors from the TTO, SG and HUI3. RESULTS: The DCE was completed online by 1001 participants (50.9% female; mean age 45.7 years). Most participants (596, 59.5%) provided consistent responses to the repeated choice task. Five models were evaluated, and one preference reversal ("head control"/"sitting unaided") was identified in all models. The rescaled utilities ranged from 0.3891 to 0.5577 (difference of 0.17 utilities) for TTO anchors corresponding to the worst (633233) and best (111111) health states. Health utilities ranged from 0.5534 to 0.7093 for the SG anchors. The disutility associated with a transition from "no problems walking" to "bedridden" was -0.0533, whereas disutility of moving from "constant screaming" relative to "no screaming" was -0.0248. The disutility associated with daily OCG was -0.0167. Disutilities for the other attributes were small although there were exceptions. CONCLUSION: A DCE was used to derive health utilities for AADC deficiency. These health utilities will subsequently be used in an economic model evaluating an AADC deficiency intervention.

Health state utilities associated with weight loss in type 2 diabetes and obesity.

INTRODUCTION: Health state utilities associated with weight change are needed as inputs for cost-utility analyses (CUAs) examining the value of treatments for obesity and type 2 diabetes (T2D). Although some pharmaceutical treatments currently in development are associated with substantial weight loss, little is known about the utility impact of weight decreases greater than 10%. The purpose of this study was to estimate utilities associated with body weight decreases up to 20% based on preferences of individuals with obesity, with and without T2D. METHODS: Health state vignettes were developed to represent respondents' own current weight and weight decreases of 2.5, 5, 10, 15, and 20%. Health state utilities were elicited in time trade-off interviews in two UK locations (Edinburgh and London) with a sample of participants with obesity, with and without T2D. Mean utility increases associated with each amount of weight decrease were calculated. Regression analyses were performed to derive a method for estimating utility change associated with weight decreases. RESULTS: Analyses were conducted with data from 405 individuals with obesity (202 with T2D, 203 without T2D). Utility increases associated with various levels of weight decrease ranged from 0.011 to 0.060 in the subgroup with T2D and 0.015 to 0.077 in the subgroup without T2D. All regression models found that the percentage of weight decrease was a highly significant predictor of change in utility (p < .0001). The relationship between weight change and utility change did not appear to be linear. Equations are recommended for estimating utility change based on the natural logarithm of percentage of weight decrease. DISCUSSION: Results of this study may be used to provide inputs for CUAs examining and comparing the value of treatments that are associated with substantial amounts of weight loss in patients with obesity, with or without T2D.

The impact of acute pneumococcal disease on health state utility values: a systematic review.

PURPOSE: Streptococcus pneumoniae infections remain a significant source of morbidity and mortality worldwide. The purpose of this review was to summarize the impact of pneumococcal disease on health state utilities (HSU) in the acute phase of illness. METHODS: We searched MEDLINE, EMBASE, EconLit, the Health Technology Assessment Database, the National Health Economic Evaluation Database, and Tufts Cost-Effectiveness Registry (up to January 2020) for primary studies. Eligible studies elicited HSU estimates using preference-based instruments for the acute phase of infection of pneumococcal syndromes including acute otitis media, pneumonia/lower respiratory tract infections, bacteremia/sepsis, and meningitis. Two reviewers independently conducted screening, data extraction and quality appraisal. RESULTS: We screened 10,178 studies, of which 26 met our inclusion criteria. Cohort sizes ranged from 8 to 2060 respondents. The most frequently studied syndrome was pneumonia (n = 17), followed by acute otitis media (n = 9), meningitis (n = 7) and bacteremia/sepsis (n = 4). Overall, each syndrome was associated with a substantial impact on HSU. Bacteremia/sepsis (range: - 0.331 to 0.992) and meningitis (range: - 0.330 to 0.977) were generally associated with the lowest HSU, followed by pneumonia (range: - 0.054 to 0.998) and acute otitis media (range: 0.064 to 0.970). HSU estimates varied considerably by treatment setting, elicitation method and type of respondent. The only study to compare pneumococcal infections to non-pneumococcal infections in the same population revealed significantly lower HSU estimates among pneumococcal infections. CONCLUSIONS: Pneumococcal syndromes are associated with decreased HSU estimates. Given the considerable heterogeneity in methods and source populations as well as study quality, care should be taken to select the most appropriate estimates.

Patient and Caregiver Health State Utilities in Lennox-Gastaut Syndrome and Dravet Syndrome.

PURPOSE: Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) are rare, treatment-resistant forms of epilepsy characterized by childhood onset of seizures. Cost-effectiveness analysis for new antiseizure medications typically requires health state utilities (HSUs) that reflect the patient and caregiver burden of the relevant conditions. This study aimed to estimate HSUs for LGS and DS. Focus was placed on valuing the impact of seizure frequency and seizure-free days on health-related quality of life (HRQL) for patients and caregivers. METHODS: Health state vignettes that described the experience of living with and caring for a child with LGS or DS were developed based on a targeted literature review and feedback from interviews with LGS and DS clinical experts and DS caregivers. Vignettes varied by the number of seizures and seizure-free days per month. Twenty-four vignettes were developed that described patient HRQL (6 per condition) and caregiver HRQL (6 per condition) for LGS or DS. Vignettes were evaluated via interviews from the general population in the United Kingdom and Sweden using a visual analog scale and time trade-off (TTO) method. Participants were recruited by interviewers based in different regions of the United Kingdom and Sweden using convenience sampling. FINDINGS: Two hundred interviews were conducted by video call from March to April 2020. One hundred participants evaluated each of the 6 patient and 6 caregiver vignettes for LGS; a different 100 participants evaluated each of the DS vignettes. The estimated utility values vary consistently according to seizure frequency and number of seizure-free days. Patient TTO utility values range from -0.186 (highest seizure frequency and fewest seizure-free days) to 0.754 (seizure-free state) for LGS and from 0.171 to 0.778 for DS. The caregiver TTO utility values range from 0.032 to 0.810 and 0.510 to 0.881 for LGS and DS, respectively. Fewer seizures and additional seizure-free days are associated with better patient and caregiver HRQL. IMPLICATIONS: This study estimated utility values for patients with LGS or DS and their caregivers using visual analog scale and TTO valuation among a general public sample. These utility values can be used in cost-effectiveness assessments of new antiseizure medications. The findings indicate the importance of seizure-free days as well as seizure frequency in patient and caregiver HRQL, which may inform the design of future clinical trials.

Estimation of the Quality-of-Life Impact of X-Linked Myotubular Myopathy.

X-linked myotubular myopathy (XLMTM) is a rare, severe, neuromuscular disorder for which novel treatments are under investigation. This study estimated quality-of-life weights (or utilities) for children with XLMTM. The state that was rated the worst described a child unable to sit and requiring invasive ventilation for≥16 hours a day (utility = -0.07 or -0.27 depending on method used). The state describing a child who can stand and walk and does not require invasive ventilation was the most highly rated state and had a utility of 0.91 or 0.77 (depending on method used).Nine health state vignettes were developed for XLMTM defined in terms of respiratory and motor function based on clinical trial data from parents completing the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) Domain 1 scale assessing mobility, transfers, sitting, playing, eating, grooming and dressing. These data were supplemented with qualitative data from parent interviews on the daily impact of XLMTM, especially in terms of psychological wellbeing, pain and discomfort, and communication. Seven clinical experts reviewed the draft vignettes for accuracy. Vignettes were rated by members of the UK general public using a time trade-off (TTO) interview and an EQ-5D-5L assessment. This study demonstrated a substantial impact of XLMTM on utility weights.