Health State Descriptions Research Articles

Health state utility assessment for low-grade glioma.

e14039 Background: Low-grade gliomas (LGGs, WHO Grade II gliomas) undergo malignant transformation, portending a median survival of 5-15 years. Though resection and adjuvant therapies have significantly improved survival, there are increased risks of long-term neurological decline and treatment-related side effects. As a result, not only quantity but also quality of life (QoL) must be considered when appraising therapeutic paradigms. Health state utility assessments can quantify society’s perceptions of given health states, supporting quality-adjusted life years (QALYs) and cost-effectiveness analyses. The primary and secondary objectives were to calculate LGG health states utility values (UVs) and interpret differences between health states, respectively. Methods: Health state descriptions were developed from a comprehensive literature review, expert input, and focus groups involving neuro-oncology providers and patient advocates. Healthy, adult participants were surveyed through an online REDCap form. Two preference elicitation techniques, visual analog scale (VAS) and time trade-off (TTO), were used to derive UVs of ten LGG health states. UVs are anchored at 0 representing death and 1 for perfect health. Mann-Whitney U tests compared UVs across health states. Results: Ninety-eight participants were included. Most participants were male (52%), aged 18-29 (81.6%), and White or Asian (78%). Stable LGG had the highest UVs (Mean [SD]: VAS- 0.64 [0.21]; TTO- 0.54 [0.42]) compared to Progressive LGG (VAS- 0.44 [0.26], p<0.0001; TTO- 0.36 [0.37], p<0.0001), Stable LGG with Chemoradiation (VAS- 0.43 [0.23], p<0.0001; TTO- 0.32 [0.34], p<0.0001), and Stable LGG with Motor (VAS- 0.45 [0.23], p<0.0001; TTO- 0.23 [0.32], p<0.0001) and Language (VAS- 0.52 [0.22], p<0.0001; TTO- 0.43 [0.40], p=0.04) Deficits. Progressive LGG UVs were not statistically different from those in Progressive LGG with Motor (VAS- 0.43 [0.23], p=0.69; TTO- 0.32 [0.34], p=0.73), Language (VAS- 0.43 [0.23], p=0.62; TTO- 0.32 [0.34], p=0.60), or Visual (VAS- 0.43 [0.23], p=0.78; TTO- 0.32 [0.34], p=0.60) Deficits. Radiation negatively impacted UVs, as UVs of Stable LGG with Chemoradiation (VAS- 0.43 [0.23]; TTO- 0.32 [0.34]) were significantly lower than UVs of Stable LGG with Chemotherapy alone (VAS- 0.43 [0.23], p=0.018; TTO- 0.32 [0.34], p=0.28) on VAS. Conclusions: These are the first-ever reported LGG health state UVs. These data will enable future QALY and cost-effective analyses, which have increasing importance as new investigational therapies become available for LGG.

Estimation of health utility values for alopecia areata

PurposeAlopecia areata (AA) is an autoimmune-mediated inflammatory dermatological disease characterised by non-scarring hair loss affecting the scalp and sometimes other hair-bearing sites. This study aimed to elicit health state utility values (HSUVs) from the UK general population for AA using time trade off (TTO) interviews.MethodsVignette descriptions of health states defined by the extent of hair loss were developed (as well as one describing caregiver burden). These were developed using data from standardised patient reported outcome (PRO) measures, a literature review and qualitative interviews. Health states were defined based on the severity of alopecia tool (SALT), which assesses extensiveness of scalp hair loss. HSUVs were then elicited for each health state in TTO interviews with the UK public.ResultsOne caregiver and five patient health states were developed based on the literature review findings, clinical trial PRO (Hospital Anxiety and Depression Scale and Alopecia Areata Patient Priority Outcomes Questionnaire) data and qualitative interviews with patients (N = 11), clinical experts (N = 4) and caregivers of adolescents with AA (N = 10). These data showed a more severe impact among patients with more extensive hair loss. One hundred and twenty participants evaluated the vignettes in TTO interviews. Patient HSUVs ranged from 0.502 for the most extensive hair loss health state (SALT 50–100 + eyebrow and eyelash loss) to 0.919 (SALT 0–10) for the mildest health state. The caregiver HSUV was 0.882.ConclusionQuantitative and qualitative data sources were used to develop and validate vignettes describing different AA health states. Patient and caregiver HSUVs demonstrate a large impact associated with AA, especially for states defined by more extensive hair loss.

A Method for Satellite Component Health Assessment Based on Multiparametric Data Distribution Characteristics

This research presents a novel data-based multi-parameter health assessment method to meet the growing need for the in-orbit health assessment of satellite components. This method analyzed changes in component health status by calculating distribution deviations and variation similarities in real-time operational data. Firstly, a single-parameter health state description method based on data distribution characteristics was presented. Secondly, the main health characteristic parameters were selected by mechanistic analysis and expert experience. The CRITIC method and the entropy weighting method were fused to assign reasonable weights and establish a multi-parameter component health assessment model. Then, the feasibility of a component health assessment algorithm based on data distribution characteristics was verified using real telemetry data from satellites. Finally, to verify the rationality of the presented health assessment algorithm, the results were compared with the pre-processed original data using empirical mode decomposition. The experimental results show that the method can accurately describe the change trend of the health status of the components. It proves that the method can be effectively used for the real-time health condition assessment and monitoring of satellite components.

Elicitation of Health State Utility Values in Retinitis Pigmentosa by Time Trade-off in the United Kingdom.

Retinitis pigmentosa (RP) is an inherited retinal pathology associated with "night blindness" and progressive loss of peripheral vision, in some cases leading to complete blindness. Health state utility values are required for activities such as modelling disease burden or the cost-effectiveness of new interventions. The current study aimed to generate utility values for health states of varying levels of functional vision in RP, with members of the general public in the UK. Five health states were defined according to standard clinical measures of visual ability. Health state descriptions were developed following interviews with patients with RP in the UK (n=5). Further interviews were conducted for confirmation with healthcare professionals with specific experience of managing patients with RP in the UK (n=2). Interviews with members of the general public in the UK were conducted to value health states. A time trade-off (TTO) process based on the established Measurement and Valuation of Health (MVH) protocol was used. Due to the ongoing COVID-19 pandemic, all interviews were web-enabled and conducted 1:1 by a trained moderator. In total, n=110 TTO interviews were conducted with members of the UK general public. Mean TTO utility values followed the logical and expected order, with increasing visual impairment leading to decreased utility. Mean values varied between 0.78 ± 0.20 ("moderate impairment"), and 0.33 ± 0.26 ("hand motion" to "no light perception"). Supplementary visual analogue scale (VAS) scores also followed the logical and expected order: mean VAS values varied between 47.95 ± 15.38 ("moderate impairment") and 17.22 ± 12.49 in ("hand motion" to "no light perception"). These data suggest that individuals living with RP have substantially impaired quality of life. Utility values for RP have been elicited here using a method and sample that is suitable for economic modelling and health technology assessment purposes.

Utility Assessment of Moderate to Severe Thyroid Eye Disease Health States

Thyroid eye disease (TED) results in varying degrees of proptosis and diplopia negatively affecting quality of life (QoL), producing possibly substantial visual changes, disfigurement, and disability. To determine the association of varying TED severities with QoL in a non-TED population by assessing health state utility scores. This qualitative study, conducted from April 20, 2020, to April 29, 2021, assessed health states for active, moderate-severe TED, and values were elicited using time trade-off methods. Six health states of varying severity were determined from 2 placebo-controlled clinical trials (171 patients with TED and clinical activity score ≥4, ±diplopia/proptosis) and refined using interviews with US patients with TED (n = 6). Each health state description was validated by interviews with additional TED patient advocates (n = 3) and physician experts (n = 3). Health state descriptions and a QOL questionnaire were piloted and administered to a general population. Visual analog scales (VASs) were also administered to detect concurrence of the findings. TED health state utility scores and whether they differ from one another were assessed using Shapiro-Wilk, Kruskal-Wallis, pairwise Wilcoxon rank sum, and paired t tests. A total of 111 participants completed time trade-off interviews. The mean (SD) utility value was 0.44 (0.34). The lowest (worse) mean utility value was observed in the most severe disease state (constant diplopia/large proptosis) with 0.30 (95% CI, 0.24-0.36), followed by constant diplopia/small proptosis (0.34; 95% CI, 0.29-0.40), intermittent or inconstant diplopia/large proptosis (0.43; 95% CI, 0.36-0.49), no diplopia/large proptosis (0.46; 95% CI, 0.40-0.52), and intermittent or inconstant diplopia/small proptosis (0.52; 95% CI, 0.45-0.58). The highest (best) mean value, 0.60 (95% CI, 0.54-0.67), was observed for the least severe disease state (no diplopia/small proptosis). These findings suggest that patients with active, moderate-severe TED may have substantial disutility, with increasing severity of proptosis/diplopia more likely to have detrimental associations with QoL. These health state scores may provide a baseline for determining QoL improvement in these TED health states (utility gains) treated with new therapies.

Constructing Health State Descriptions for Low-Risk Thyroid Cancer: Stakeholder Engagement and Formative Qualitative Research.

This paper describes stakeholder involvement and formative qualitative research in the creation of health state descriptions (HSDs) or vignettes for low-risk thyroid cancer. The aim of this project was to engage stakeholders in the contribution of a novel set of HSDs, an important first step in the process of assessing value in thyroid cancer health states. We draw upon formative, descriptive qualitative methods, following a multi-stage framework of data collection. We conducted individual semi-structured interviews, cognitive interviews, and focus groups with thyroid cancer patients, community providers, academic subspecialists, and participants with no thyroid cancer diagnosis (N = 31). The HSDs went through several iterations over the course of a year, in collaboration with a highly engaged community advisory board, laying the groundwork for HSDs that are comprehensible, comparable, and appropriate for stated-preference research. Thyroid cancer survivors compared their experiences with those described in the HSDs. Feedback included concern for the emotional well-being of study participants who would be reading them. Providers were attuned to the need for clinical accuracy and made suggestions to reflect their clinical experience, including for patients with complications or disease progression. The pilot participants with no thyroid cancer were particularly valuable in promoting the need to simplify language and maximize readability. Stakeholder engagement was critical to being responsive to feedback as the iterations were refined and presented. Continuous engagement and consultation with multiple sources strengthened the HSDs. A secondary outcome from this project is that stakeholders expressed interest in adapting the HSDs into decision aids for people newly diagnosed with low-risk thyroid cancer.

EE379 Cataloguing Health State Utilities for Lower Extremity Peripheral Artery Disease

Health state utilities (HSUs) are a key parameter in cost effectiveness analyses (CEAs), yet heterogeneity in valuation methods, patient populations, and health state descriptions makes identification of appropriate HSUs challenging. We catalogued HSUs associated with lower extremity peripheral artery disease (PAD) and examined their application in published CEAs.

Rehabilitation Through Physical Activity and Sport in Light of the International Classification of Functioning, Disability, and Health-Current Research Perspectives.

The implementation of functioning by the World Health Organization (WHO) as the third global health indicator, along with mortality and morbidity, represents a promising advancement for a comprehensive assessment of international health systems and health strategies. The description of a person's health state operationalized by both biological and lived health via functioning provides a holistic picture of an individual's life situation and proved to be successful in building a framework for formulating therapy goals, achievable activities, and participational aspects against the background of an individual's life situation. Furthermore, improving an individual's functional ability and wellbeing could potentially affect the health indicators of morbidity and mortality and will be codable beyond the ICF in ICD-11. This methodological perspective emphasizes the use of ICF applications on the wider and narrower level of international rehabilitation systems and highlights the incorporation of the term functioning in rehabilitation through physical activity and sport. Current research perspectives in applying the ICF and functioning in clinical and rehabilitation practices are discussed and a current explorative study is presented, which applies the holistic orientation of functioning and the biopsychosocial model to the specific case by an individualized sports coaching intervention in rehabilitation. Subsequently, a unifying ICF- oriented language in rehabilitation is considered as a powerful foundation for a consistent international research strategy concerning increased international collaborations and future research perspectives.

Health state utilities for beta-thalassemia: a time trade-off study

BackgroundBeta-thalassemia (BT) is an inherited blood disorder characterized by reduced levels of functional hemoglobin resulting in phenotypes ranging from clinically asymptomatic to severely anemic. Patients with BT may require lifelong regular blood transfusions supported by appropriate iron chelation therapy (ICT). This study aimed to determine how the UK general population values BT health states associated with differing transfusion burden and ICT.MethodsComposite time trade-off (cTTO) methodology was employed to elicit health state utilities in BT. Relevant BT literature related to symptom and quality-of-life impact, including physical, functional, and emotional well-being, and safety profiles of BT treatments were considered when drafting health state descriptions. Eleven health state descriptions were developed and validated by hematologists and patient advocates for clinical accuracy and completeness. 200 individuals from the UK general population participated in the cTTO interviews.ResultsThe mean age of participants was 41.50 years (SD 16.01, range 18–81); 88 (46.8%) were female. Utility values ranged from 0.78 (SD 0.34) for non-transfusion dependent BT with oral ICT to 0.37 (SD 0.50) for high transfusion burden with subcutaneous ICT in transfusion-dependent BT.ConclusionsThis study provides health utilities for a range of BT health states from the UK general population perspective. Importantly, lower transfusion burden and lower burden of anemia were associated with higher utilities. To a lesser extent, differential modes of ICT were found to impact utility valuations in patients with BT. The utilities obtained in this study can be employed as inputs in cost-effectiveness analyses of BT therapies.

Defining utility values for patients with tardive dyskinesia

Objective To measure health state preferences and estimate utility values for tardive dyskinesia (TD) from the perspective of the US general population, accounting for factors affecting quality of life (QOL). Methods Participants from the general population were recruited and asked to watch and assess videos of professional actors simulating nine health states, including psychiatric disorders with/without TD and moderate-to-severe TD without any underlying disease. Time tradeoff (TTO) methods were used to elicit utility values, which ranged from −1 (worse than death) to +1 (perfect health) and represented individual preferences for avoiding specific health states associated with TD. Lower TTO utility values indicated individuals’ willingness to give up more years of life to avoid living in each health state. Results Based on TTO responses (n = 157), mean ± standard deviation utility for TD alone was 0.59 ± 0.38. Mean utilities for schizophrenia with negative symptoms (without TD: 0.43; with TD: 0.29) and positive symptoms (without TD: 0.44; with TD: 0.30) were generally lower than those for bipolar disorder (without TD: 0.59; with TD: 0.46) and major depressive disorder (without TD: 0.60; with TD: 0.44). According to utility decrements associated with TD (0.13–0.16), respondents were willing to give up 1.3 to 1.6 years during a 10-year lifespan to avoid living with TD. Conclusions Utility decrements for TD in this study were slightly larger than previously reported values, potentially due to incorporation of QOL and social consequences in TD health state descriptions. An important limitation of this analysis is that participants’ willingness to trade future years of healthy life may not indicate actual willingness to accept the life decrement. These findings can be leveraged to improve cost-effectiveness analyses used to assess the value of treatments for TD.

Ontological modeling of the International Classification of Functioning, Disabilities and Health (ICF): Activities&Participation and Environmental Factors components

BackgroundThe International Classification of Functioning, Disability and Health (ICF) is a classification of health and health-related states developed by the World Health Organization (WHO) to provide a standard and unified language to be used as a reference model for the description of health and health-related states. The concept of functioning on which ICF is based is that of a “dynamic interaction between a person’s health condition, environmental factors and personal factors”. This overall model has been translated into a classification covering all the main components of functioning. However, the practical use of ICF has highlighted some formal problems, mainly concerning conceptual clarity and ontological coherence.MethodsIn the present work, we propose an initial ontological formalization of ICF beyond its current status, focusing specifically on the interaction between activities and participation and environmental factors. The formalization has been based on ontology engineering methods to drive goal and scope definition, knowledge acquisition, selection of an upper ontology for mapping, conceptual model definition and evaluation, and finally representation using the Ontology Web Language (OWL).ResultsA conceptual model has been defined in a graphical language that included 202 entities, when possible mapped to the SUMO upper ontology. The conceptual model has been validated against 60 case studies from the literature, plus 6 ad-hoc case studies. The model has been then represented using OWL.ConclusionsThis formalization might provide the basis for a revision of the ICF classification in line with current efforts made by WHO on the International Classification of Diseases and on the International Classification of Health Interventions.

Psychometric Evaluation of the Health State Description Questionnaire in Chile: A Proposal for a Latent Variable Approach for Valuating Health States

BackgroundA few instruments that identify and valuate health states are based on the International Classification of Functioning, Disability and Health States of the World Health Organization. One of them is the Health State Description (HSD) questionnaire first used in the World Health Survey (WHS) initiative (HSD-WHS), whose psychometric properties have not been evaluated in Chile. Additionally, the use of latent variables for the valuation process of health states has been scarcely investigated in the context of population health metrics. We aim to evaluate the psychometric properties and factorial structure of the HSD-WHS for Chile and describe a latent variable method for valuating health states associated with diseases. MethodsWe used data from the second Chilean National Health population-based survey from 2009 to 2010 (N = 5293). We explored the factorial structure of the HSD-WHS through exploratory and confirmatory factor analyses, the reliability, and the discriminant validity of the latent variable of disability. Disability weights for diseases were calculated using a linear regression model. ResultsWe found an adequate goodness of fit for a second-order model with 9 factors corresponding to disability domains (Tucker–Lewis index = 0.99, comparative fit index = 0.99, root mean square error of approximation = 0.060), and good reliability estimates (standardized α = 0.91). The rescaled (between 0 and 100) latent variable of disability showed significant difference according to the explored variables. We estimated disability weights for the following: (1) depressive episode, 13.6 (12.1-15.2), (2) hypertension, 1.6 (0.0-3.3), and (3) diabetes, 5.0 (2.5-7.4). ConclusionsThis study supports the use of the HSD-WHS questionnaire in the Chilean population and a latent variable approach for valuating health states associated with diseases.

A Review of Utility Measurement Methods Used in Pharmacoeconomic Submissions to HIRA in South Korea: Methodological Consistency and Areas for Improvement.

Pharmacoeconomic (PE) guidelines, first published in 2006 and later updated in 2011, were developed to guide the preparation and submission of PE data to the Health Insurance Review and Assessment Service (HIRA) for drug reimbursement decision making in South Korea. This study, which was conducted as part of a project for revision of the PE guideline, reviewed utility values used in the PE submissions processed at HIRA during 2014-2018 to identify aspects of the current guidelines that may need to be revisited. A total of 50 PE submissions were processed at HIRA over the 5 years. Of these, 47 submissions that used quality-adjusted life-years as an outcome measure were included in this review. Data were extracted from full copies of the manufacturer's initial submissions and committee documents provided by HIRA. Of the 47 submissions, nearly half (n=23, 48.9%) used published sources to obtain health state utility values, followed by direct methods using time trade-off (n=7) or standard gamble (n=2) and indirect methods with patient-level data using the EQ-5D-3L (n=4) or the EQ-5D-5L (n=2). Mapping, using the EQ-5D-3L as a target measure, was also adopted in six submissions, although it was somewhat unfavourably described in the guideline. Notably, 52.2% of the submissions with published sources took utility values from different sources for different health states defined in a single model. In addition, details of utility measurement methods or mapping functions taken from published sources were relatively poorly reported. Moreover, the preferences of the Korean general public, preferred by the guideline, were rarely reflected in the utility values used in submissions relying on published sources (95.7% for foreign values only/mixed) and mapping (66.7%). While most submissions with direct and indirect methods used domestic preference values, the former was occasionally criticised by assessment committees because of health state descriptions. This review highlights a considerable amount of inconsistency in the measurement of utility values used in the PE submissions during 2014-2018, indicating a strong need for methodological standardisation.

Towards Transparency in the Selection of Published Health Utility Inputs in Cost-Utility Analyses: The Health Utility Application Tool (HAT).

Evaluating the relevance of published health utilities to the context of a cost-utility analysis (CUA) remains an essential, yet often overlooked, task. The objective of this study was to provide guidance on this process through the development of the Health utility Application Tool (HAT). We conducted semi-structured telephone interviews with Canadian stakeholders from reimbursement bodies, academia, and the pharmaceutical industry to identify current practices and perspectives of the application of the health utility literature to CUAs. An online survey with international members of the general health economics and outcomes research community was also conducted to gather opinions on key concepts. Based on the themes emerging from the interviews and online questionnaire, the HAT includes questions prompting investigators to consider the following constructs: similarity of the clinical condition in the health utility study and the CUA; similarity of health utility study participant demographics and the demographics of the CUA's target population; similarity of the health state descriptions in the health utility study and the CUA; and the method of assigning utility weights. Considerations of transparency prompted additional items, including: means by which the health utility study was identified; type of respondents; study design; and measure used to collect health utility estimates. The HAT is intended to guide the evaluation of the applicability of published health utilities for a CUA, thus promoting transparency and accountability in the selection of model inputs.

Vignette-Based Utilities: Usefulness, Limitations, and Methodological Recommendations

Health technology assessment agencies often prefer that utilities used to calculate quality-adjusted life years in cost-utility analyses (CUAs) are derived using standardized methods, such as generic preference-based measures completed by patients in clinical trials. However, there are situations when no standardized approach is feasible or appropriate for a specific medical condition or treatment that must be represented in a CUA. When this occurs, vignette-based methods are often used to estimate utilities. A vignette (sometimes called a “scenario,” “health state description,” “health state vignette,” or “health state”) is a description of a health state that is valued in a preference elicitation task to obtain a utility estimate. This method is sometimes the only feasible way to estimate utilities representing a concept that is important for a CUA. Consequently, vignette-based studies continue to be conducted and published, with the resulting utilities used in economic models to inform decision making about healthcare resource allocation. Despite the potential impact of vignette-based utilities on medical decision making, there is no published guidance or review of this methodology. This article provides recommendations for researchers, health technology assessment reviewers, and policymakers who may be deciding whether to use vignette-based methods, designing a vignette study, using vignette-based utilities in a CUA, or evaluating a CUA that includes vignette-based utilities. Recommendations are provided on: (A) when to use vignette-based utilities, (B) methods for developing vignettes, (C) valuing vignettes, (D) use of vignette-based utilities in models, and (E) limitations of vignette methods.

Evaluating the conduct and application of health utility studies: a review of critical appraisal tools and reporting checklists.

Published health utility studies are increasingly cited in cost-utility analyses to inform reimbursement decision-making. However, there is limited guidance for investigators looking to systematically evaluate the methodological quality of health utility studies or their applicability to decision contexts. To describe how health utility concepts are reflected in tools intended for use with the health economic literature, particularly with respect to the evaluation of methodological quality and context applicability. We reviewed the critical appraisal and reporting tools described in a 2012 report published by the Agency for Healthcare Research and Quality (AHRQ), supplemented with a keyword search of MEDLINE and EMBASE, to identify existing tools which include health utility constructs. From these tools, a list of relevant items was compiled and grouped into domain categories based on the methodological or applicability aspect they were directed toward. Of the 24 tools we identified, 12 contained items relevant to the evaluation of health utilities. Sixty-five items were considered relevant to the evaluation of quality, while 44 were relevant to the evaluation of applicability. Items were arranged into four domains: health state descriptions; selection and description of respondents; elicitation and measurement methods; and other considerations. As key inputs to cost-utility analyses, health utilities have the potential to significantly impact estimates of cost-effectiveness. Existing tools contain only general items related to the conduct or use of health utility studies. There is a need to develop tools that systematically evaluate the methodological quality and applicability of health utility studies.

Different Alternatives to Assess the Burden of Disease Using Attributable Fraction on a Disability Variable: The Case of Pain and Chronic Musculoskeletal Disorders in Chile

ObjectivesTo estimate the burden of disease through 4 complementary procedures to years lived with disability (YLDs) using the concept of attributable fraction and including analysis of subdomains of disability. MethodsWe explored the burden on disability for 7 common musculoskeletal disorders (CMD) using the 2009 to 2010 Chilean National Health Survey, which included the Community Oriented Programme for the Control of Rheumatic Disease Core Questionnaire to identify cases with CMD, and an 8-domain questionnaire for health state descriptions. We calculated the proportion of disability attributable to pain in the general population and people with CMD. We also estimated the burden of CMD expressed as YLD and as the proportion of the disability in the general population attributable to people with CMD, with a particular focus in the pain domain of disability. Second order of uncertainty around point estimations was also characterized. ResultsPain domain of disability accounted for 23.4% of the total disability in the general population, and between 20% (fibromyalgia) to 27.1% (osteoarthritis of the hip) in people with some of the selected CMD. People with chronic musculoskeletal pain accounted for 21.2% of total disability from general population, which generated 1.2 million of YLD (6679 YLD/100 000 inhabitants). Chronic low back pain and osteoarthritis of the knee were in the top position of specific CMDs, explaining the highest national burden. ConclusionPain is an essential component of disability in people with CMD and also in the general population. The approach used can be easily applied to other health conditions and other domains of disability.

Differences in the Selection of Health State Utility Values by Sponsorship in Published Cost-Effectiveness Analyses.

Health state utility values (HSUVs) are among the most influential attributes of cost-effectiveness analyses (CEAs). Our objective was to evaluate whether industry-funded studies select systematically different HSUVs as compared with studies without industry funding. Among 10 diseases with high disease burden in the United States, we further identified 31 progressive health states. We then searched the Tufts Medical Center's CEA Registry to identify studies that included HSUVs and were submitted to the registry between 2002 and 2019. Two reviewers mapped the free-text descriptions of health states onto the 31 predefined health states. We analyzed the effect of industry funding on the point estimates of these HSUVs with a beta regression. We also analyzed the difference between related health states within studies by funding source with a linear regression. After identifying 26,222 HSUVs from 4198 CEAs, we matched 2573 HSUVs to the 31 predefined health states. We observed large variations within each health state: 12 of 31 health states included a range of HSUVs greater than 0.5. The point estimate model showed 1 statistically significant difference of 31 comparisons between studies with any industry funding and those without. The utility difference model found 3 significant differences out of 39 comparisons between CEAs with any industry funding and those without. Inclusion of unpublished CEAs may have affected our conclusions about the effect of industry funding on selection of HSUVs. We also relied on free-text descriptions of health states available in the CEA Registry and did not include adjustment for multiple comparisons. Limited evidence exists that industry-funded studies select different HSUVs compared to non-industry-funded studies for the health states we considered.

PRO131 A Societal Utility Study to Elicit Values for Stages of Metachromatic Leukodystrophy (MLD) in the United Kingdom

Metachromatic leukodystrophy (MLD) is an ultra-rare, neurodegenerative disease which leads to motor and cognitive decline, and premature death. Hitherto, its impact on health-related quality of life (HRQL) of infants and juveniles has not been quantified. The aim of this study was to elicit societal utility values for infantile and juvenile MLD to support the economic evaluation of therapies. Health states were segregated by age of disease onset: infant (<30 months) and juvenile (30 months to 16 years). Infant health states were defined by the Gross Motor Function Classification (GMFC-MLD); whilst juvenile health states were defined by GMFC-MLD and by Development Quotient (DQ) scores for three cognitive functioning levels from normal/mild, moderate, and severe. Health state descriptions were informed by literature review and interviews with clinical experts (N=6) - who also validated the draft states in cognitive debriefing interviews. The finalised health states were valued by UK general public (n=101) who completed a visual analogue scale (VAS) and time trade-off (TTO) assessment with the lead time method. Amongst infantile states, the mean TTO values ranged from 0.71 (GMFC-MLD1) to -0.47 (GMFC-MLD6). Each decline in GMFC-MLD was associated with worsening TTO and VAS scores. The juvenile states had considerably lower utility values than infantile states and also declined with worsening cognitive status. In the normal cognitive group, the mean utility values ranged from 0.90 (GMFC-MLD1) to -0.07 (GMFC-MLD4). In the moderate group, the mean scores ranged from 0.85 (GMFC-MLD0) to -0.62 (GMFC-MLD6). In the severe group, mean scores ranged from 0.37 (GMFC-MLD0) to -0.70 (GMFC-MLD5). This study has generated de novo utility estimates for infantile and juvenile MLD health states, and is one of the first studies to measure the cognitive dimension of an ultra-rare disease. The utility values confirm that the preferences of the general public recognise the severity of MLD.

PRO133 Validating Vignettes for a Rare Disease Using Clinician Interviews to Evaluate the Impact on Health-Related Quality of Life in Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency in France

In the absence of utilities from clinical trials, health related quality of life (HRQoL) can be estimated using health utilities derived through vignette studies and discrete choice experiments (DCE). This enables treatment evaluation in cost-utility analysis for HTA assessments. Vignettes should have face and content validity; obtaining input into the design from caregivers/parents of aromatic l-amino acid decarboxylase (AADC) deficiency patients, and clinicians treating these patients is, thus, critical. The study objective was to validate the vignettes and DCE attributes already developed and validated for the UK– this time specifically for France. These will be used in a subsequent study to estimate patient HRQoL in France. Initial vignettes were developed based on a literature review, interactions with clinicians, as well as parents via interviews, advisory boards and anonymised surveys. To capture improvements on therapy, input into key DCE attributes were also obtained. The health states were bedridden, head control, sitting unsupported, standing with assistance, and walking with assistance aligned to major motor developmental milestones and outcomes in the clinical trials. The vignettes and DCE attributes were translated including full reconciliation. In a second step, the French translation as well as the content of the vignettes were validated using 4 French clinicians’ input. The translation process resulted in minor amends to the vignette wordings for each health state. The French clinicians supported the health state descriptions with 6 suggested changes including the addition of ‘tiredness’ as a symptom to two health states and minor revisions to the language translation. While this project supported the face and content validity of the vignettes and attributes previously developed for the UK, it also showed that it is important to validate with local experts the language when planning to derive utilities for a cost-effectiveness model of an AADC deficiency treatment in a specific country.