Development and Valuation of a Preference-Weighted Measure in Age-Related Macular Degeneration From the Vision Impairment in Low Luminance Questionnaire: A MACUSTAR Report.

OBJECTIVES: This study generates VILL-UI (Vision Impairment in Low Luminance - Utility Index), a preference-weighted measure (PWM) derived from the VILL-33 measure for use in patients with age-related macular degeneration (AMD) and valued to generate United Kingdom and German preference weights. METHODS: A PWM consists of a classification system to describe health and utility values for every state described by the classification. The classification was derived using existing data collected as part of the MACUSTAR study, a low-interventional study on AMD, conducted at 20 clinical sites across Europe. Items were selected using psychometric and Rasch analyses, published criteria around PWM suitability, alongside instrument developer views and concept elicitation work that informed VILL-33 development. An online discrete choice experiment (DCE) with duration of the health state was conducted with the United Kingdom and German public. Responses were modeled to generate utility values for all possible health states. RESULTS: The classification system has 5 items across the 3 domains of VILL-33: reading and accessing information, mobility and safety, and emotional well-being. The DCE samples (United Kingdom: n = 1004, Germany: n = 1008) are broadly representative and demonstrate good understanding of the tasks. The final DCE analyses produce logically consistent and significant coefficients. CONCLUSIONS: This study enables responses to VILL-33 to be directly used to inform economic evaluation in AMD. The elicitation of preferences from both United Kingdom and Germany enables greater application of VILL-UI for economic evaluation throughout Europe. VILL-UI fills a gap in AMD in which generic preference-weighted measures typically lack sensitivity.

Exploring health preference heterogeneity in the UK: Using the online elicitation of personal utility functions approach to construct EQ-5D-5L value functions on societal, group and individual level.

A new method has recently been developed for valuing health states, called 'Online elicitation of Personal Utility Functions' (OPUF). In contrast to established methods, such as time trade-off or discrete choice experiments, OPUF does not require hundreds of respondents, but allows estimating utility functions for small groups and even at the individual level. In this study, we used OPUF to elicit EQ-5D-5L health state preferences from a (not representative) sample of the UK general population, and then compared utility functions on the societal-, group-, and individual level. A demo version of the survey is available at: https://eq5d5l.me. Data from 874 respondents were included in the analysis. For each respondent, we constructed a personal EQ-5D-5L value set. These personal value sets predicted respondents' choices in three hold-out discrete choice tasks with an accuracy of 78%. Overall, preferences varied greatly between individuals. However, PERMANOVA analysis showed that demographic characteristics explained only a small proportion of the variability between subgroups. While OPUF is still under development, it has important strengths: it can be used to construct value sets for patient reported outcome instruments such as EQ-5D-5L, while also allowing examination of underlying preferences in an unprecedented level of detail. In the future, OPUF could be used to complement existing methods, allowing valuation studies in smaller samples, and providing more detailed insights into the heterogeneity of preferences across subgroups.

Using the Online Elicitation of Personal Utility Functions Approach to Derive a Patient-Based 5-Level Version of EQ-5D Value Set: A Study in 122 Patients With Rheumatic Diseases From Germany.

OBJECTIVES: Traditional preference elicitation methods, such as discrete choice experiments or time trade-off, usually require large sample sizes. This can limit their applicability in patient populations, where recruiting enough participants can be challenging. The objective of this study was to test a new method, called the Online elicitation of Personal Utility Functions (OPUF) approach, to derive an EQ-5D-5L value set from a relatively small sample of patients with rheumatic diseases. METHODS: OPUF is a new type of online survey that implements compositional preference elicitation techniques. Central to the method are 3 valuation steps: (1) dimension weighting, (2) level rating, and (3) anchoring. An English demo version of the OPUF survey can be accessed at https://valorem.health/eq5d5l. From the responses, a personal EQ-5D-5L utility function can be constructed for each participant, and a group-level value set can be derived by aggregating model coefficients across participants. RESULTS: A total of 122 patients with rheumatic disease from Germany completed the OPUF survey. The survey was generally well received; most participants completed the survey in less than 20 minutes and were able to derive a full EQ-5D-5L value set. The precision of mean coefficients was high, despite the small sample size. CONCLUSIONS: Our findings demonstrate that OPUF can be used to derive an EQ-5D-5L value set from a relatively small sample of patients. Although the method is still under development, we think that it has the potential to be a valuable preference elicitation tool and to complement traditional methods in several areas.

Symptom burden in patients with idiopathic multicentric Castleman disease and its impact on daily life: an international patient and caregiver survey.

Background: Idiopathic Multicentric Castleman Disease (iMCD) is a rare inflammatory lymphoproliferative disorder with heterogenous clinical presentations. The symptomatology in iMCD patients remains poorly understood. The aim of this study was to identify the type, frequency and severity of iMCD-related symptoms and the impact of these on the daily lives of iMCD patients and informal-caregivers. Methods: We conducted two bespoke 45-question online surveys for iMCD patients and informal-caregivers of patients recruited from the US, UK, Australia and Canada between April 14 and November 8, 2021. Descriptive data was collected, and a Likert scale was used to quantify the impact of symptoms on various aspects of daily life. Ordinal logistic regression analysis was used to determine associations between age, gender, employment status and symptom burden with aspects of daily life. Findings: Eligible respondents included 51 iMCD patients and 11 informal-caregivers. Patients reported up to 27 unique symptoms, the mean number of symptoms experienced by a patient was 6.7 (range 0-22 symptoms). Most symptoms had a moderate to severe impact on patients' daily lives, with 'pain/discomfort', 'ability to travel', and 'sexual functioning' being the most impacted. iMCD patient characteristics such as being 40 years or older, female, and either disabled or unemployed was significantly associated with adverse impact on several aspects of daily life. Among caregivers, the aspects of daily life that were disproportionately affected was their own social life and freedom, emotional wellbeing, travel/relocation, and work. Interpretation: iMCD patients have widely varied and unappreciated symptomatology. High symptom burden adversely impacts several aspects of patient daily lives as well as their caregivers. Funding: Funding was provided by EUSA Pharma.

Discrete Choice Experiments in Health State Valuation: A Systematic Review of Progress and New Trends.

BACKGROUND: Discrete choice experiments (DCEs) are increasingly used in health state valuation studies. OBJECTIVE: This systematic review updates the progress and new findings of DCE studies in the health state valuation, covering the period since the review of June 2018 to November 2022. The review reports the methods that are currently being used in DCE studies to value health and study design characteristics, and, for the first time, reviews DCE health state valuation studies published in the Chinese language. METHODS: English language databases PubMed and Cochrane, and Chinese language databases Wanfang and CNKI were searched using the self-developed search terms. Health state valuation or methodology study papers were included if the study used DCE data to generate a value set for a preference-based measure. Key information extracted included DCE study design strategies applied, methods for anchoring the latent coefficient on to a 0-1 QALY scale and data analysis methods. RESULTS: Sixty-five studies were included; one Chinese language publication and 64 English language publications. The number of health state valuation studies using DCE has rapidly increased in recent years and these have been conducted in more countries than prior to 2018. Wide usage of DCE with duration attributes, D-efficient design and models accounting for heterogeneity has continued in recent years. Although more methodological consensus has been found than in studies conducted prior to 2018, this consensus may be driven by valuation studies for common measures with an international protocol (the 'model' valuation research). Valuing long measures with well-being attributes attracted attention and more realistic design strategies (e.g., inconstant time preference, efficient design and implausible states design) were identified. However, more qualitative and quantitative methodology study is still necessary to evaluate the effect of those new methods. CONCLUSIONS: The use of DCEs in health state valuation continues to grow dramatically and the methodology progress makes the method more reliable and pragmatic. However, study design is driven by international protocols and method selection is not always justified. There is no gold standard for DCE design, presentation format or anchoring method. More qualitative and quantitative methodology study is recommended to evaluate the effect of new methods before researchers make methodology decisions.

Unmet Parenthood Goals, Health-Related Quality of Life and Apparent Irrationality: Understanding the Value of Treatments for Infertility.

An increasing number of prospective parents are experiencing infertility along with associated negative impacts on mental health and life satisfaction that can extend across a network of individuals and family members. Assistive reproductive technologies (ART) can help prospective parents achieve their parenthood goals but, like any health technology, they must demonstrate acceptable 'value for money' to qualify for public funding. We argue that current approaches to understanding the value of ART, including quality-adjusted life-year (QALY) gains based on changes in health-related quality of life (HRQOL) and, more often, cost per live birth, are too narrow to capture the full impact of unmet parenthood goals and ART. We see a fundamental disconnect between measures of HRQOL and broader measures of wellbeing associated with met and unmet parenthood goals. We also suggest that simple concepts such as 'patient' and 'carer' are of limited applicability in the context of ART, where 'spillovers' extend across a wide network of individuals, and the person receiving treatment is often not the infertile individual. Consideration of individual and societal wellbeing beyond HRQOL is necessary to understand the full range of negative impacts associated with unmet parenthood goals and the corresponding positive impacts of successful ART. We suggest moving towards a wellbeing perspective on value to achieve a fuller understanding of value and promote cross-sector allocative efficiency.

Anticancer evaluation of new organometallic ruthenium(ii) flavone complexes.

Targeting multiple malignancy features such as angiogenesis, proliferation and metastasis with one molecule is an effective strategy in developing potent anticancer agents. Ruthenium metal complexation to bioactive scaffolds is reported to enhance their biological activities. Herein, we evaluate the impact of Ru chelation on the pharmacological activities of two bioactive flavones (1 and 2) as anticancer candidates. The novel Ru complexes (1Ru and 2Ru) caused a loss of their parent molecules' antiangiogenic activities in an endothelial cell tube formation assay. 1Ru enhanced the antiproliferative and antimigratory activities of its 4-oxoflavone 1 on MCF-7 breast cancer cells (IC50 = 66.15 ± 5 µM and 50% migration inhibition, p < 0.01 at 1 µM). 2Ru diminished 4-thioflavone's (2) cytotoxic activity on MCF-7 and MDA-MB-231 yet significantly enhanced 2's migration inhibition (p < 0.05) particularly on the MDA-MB-231 cell line. The test derivatives also showed non-intercalative interaction with VEGF and c-myc i-motif DNA sequences.

Chemical Synthesis of Oligonucelotide Sequences: Phosphoramidite Chemistry.

Oligonucleotides are used in a variety of molecular biology techniques, from next-generation sequencing to genetic testing. Maintaining the sequence fidelity of synthetic oligonucleotides is critical to their use. This chapter describes the steps of solid phase oligonucleotide synthesis and purification, which enables the synthesis of oligonucleotides with specific sequences and high purity.

Valuing the EQ Health and Wellbeing Short Using Time Trade-Off and a Discrete Choice Experiment: A Feasibility Study.

OBJECTIVES: The EQ Health and Wellbeing Short (EQ-HWB-S) is a new generic measure that covers health and wellbeing developed for use in economic evaluation in health and social care. The aim was to test the feasibility of using composite time trade-off (cTTO) and a discrete choice experiment (DCE) based on an international protocol to derive utilities for the EQ-HWB-S and to generate a pilot value set. METHODS: A representative UK general population was recruited. Online videoconference interviews were undertaken where cTTO and DCE tasks were administered using EuroQol Portable Valuation Technology. Quality control (QC) was used to assess interviewers' performance. Data were modeled using Tobit, probit, and hybrid models. Feasibility was assessed based on the distribution of data, participants, and reports of understanding from the interviewer, QC and modeling results. RESULTS: cTTO and DCE data were available for 520 participants. Demographic characteristics were broadly representative of the UK general population. Interviewers met QC requirements. cTTO values ranged between -1 to 1 with increasing disutility associated with more severe states. Participants understood the tasks and the EQ-HWB-S states; and the interviewers reported high levels of understanding and engagement. The hybrid Tobit heteroscedastic model was selected for the pilot value set with values ranging from -0.384 to 1. Pain, mobility, daily activities, and sad/depressed had the largest disutilities, followed by loneliness, anxiety, exhaustion, control, and cognition in the selected model. CONCLUSIONS: EQ-HWB-S can be valued using cTTO and DCE. Further methodological work is recommended to develop a valuation protocol specific to the EQ-HWB-S.

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.

Development of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised.

OBJECTIVES: Cystic fibrosis (CF) limits survival and negatively affects health-related quality of life (HRQOL). Cost-effectiveness analysis (CEA) may be used to make reimbursement decisions for new CF treatments; nevertheless, generic utility measures used in CEA, such as EQ-5D, are insensitive to meaningful changes in lung function and HRQOL in CF. Here we develop a new, CF disease-specific, preference-based utility measure based on the adolescent/adult version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely used, CF-specific, patient-reported measure of HRQOL. METHODS: Blinded CFQ-R data from 4 clinical trials (NCT02347657, NCT02392234, NCT01807923, and NCT01807949) were used to identify discriminating items for a classification system using psychometric (eg, factor and Rasch) analyses. Thirty-two health states were selected for a time trade-off (TTO) exercise with a representative sample of the UK general population. TTO utilities were used to estimate a preference-based scoring algorithm by regression analysis (tobit models with robust standard errors clustered on participants with censoring at -1). RESULTS: A classification system with 8 dimensions (CFQ-R-8 dimensions; physical functioning, vitality, emotion, role functioning, breathing difficulty, cough, abdominal pain, and body image) was generated. TTO was completed by 400 participants (mean age, 47.3 years; 49.8% female). Among the regression models evaluated, the tobit heteroscedastic-ordered model was preferred, with a predicted utility range from 0.236 to 1, no logical inconsistencies, and a mean absolute error of 0.032. CONCLUSION: The CFQ-R-8 dimensions is the first disease-specific, preference-based scoring algorithm for CF, enabling estimation of disease-specific utilities for CEA based on the well-validated and widely used CFQ-R.

Hypothetical versus experienced health state valuation: a qualitative study of adult general public views and preferences.

OBJECTIVES: Responses from hypothetical and experienced valuation tasks of health-related quality of life differ, yet there is limited understanding of why these differences exist, what members of the public think about them, and acceptable resolutions. This study explores public understanding of, opinions on, and potential solutions to differences between hypothetical versus experienced responses, in the context of allocating health resources. METHODS: Six focus groups with 30 members of the UK adult public were conducted, transcribed verbatim, and analysed using framework analysis. Participants self-completed the EQ-5D-5L, before reporting the expected consequences of being in two hypothetical EQ-5D-5L health states for ten years. Second, participants were presented with prior results on the same task from a public (hypothetical) and patient (experienced) sample. Third, a semi-structured discussion explored participants': (1) understanding, (2) opinions, and (3) potential resolutions. RESULTS: Twenty themes emerged, clustered by the three discussion points. Most participants found imagining the health states difficult without experience, with those aligned to mental health harder to understand. Participants were surprised that health resource allocation was based on hypothetical responses. They viewed experienced responses as more accurate, but noted potential biases. Participants were in favour of better informing, but not influencing the public. Other solutions included incorporating other perspectives (e.g., carers) or combining/weighting responses. CONCLUSION: Members of the UK public appear intuitively not to support using potentially uninformed public values to hypothetical health states in the context of health resource allocation. Acceptable solutions involve recruiting people with greater experience, including other/combinations of views, or better informing respondents.

Producing a preference-based quality of LIFE measure to quantify the impact of HYPOGLYCAEMIA on people living with diabetes: A mixed-methods research protocol.

BACKGROUND: Assessment of patient-reported outcome measures (PROMs), including quality of life (QoL), is essential in diabetes research and care. However, a recent review concluded that current hypoglycaemia-specific PROMs have limited evidence of validity, reliability and responsiveness for assessing the impact of hypoglycaemia on QoL in people living with diabetes. None of the PROMs identified could be used directly to inform the cost-effectiveness of treatments and interventions. There is a need for a new hypoglycaemia-specific QoL PROM, which can be used directly to inform economic evaluations. AIMS: This project has three aims: (a) To develop draft PROM content for measuring the impact of hypoglycaemia on QoL in adults with diabetes. (b) To refine the draft content using cognitive debriefing interviews and psychometrics. This will result in a condition-specific PROM that can be used to quantify the impact of hypoglycaemia upon QoL. (c) To generate a preference-based measure (PBM) that will enable utility values to be calculated for economic evaluation. METHODS: A mixed-methods, three-stage design is used: (a) Qualitative interviews will inform the draft PROM content. (b) Cognitive debriefing interview data will be used to refine the draft PROM content. The PROM will be administered in a large-scale survey to enable psychometric validation. Final item selection for the PROM will be informed by psychometric performance, translatability assessment and input from stakeholder groups. (c) A classification system will be generated, comprising a reduced number of items from the PROM. A valuation survey will be conducted to derive a value set for the PBM.

Deciding Between SF-6Dv2 Health States: A Think-Aloud Study of Decision-Making Strategies Used in Discrete Choice Experiments.

OBJECTIVE: This study aimed to gain insight into decision-making strategies individuals used when evaluating pairs of SF-6Dv2 health states in discrete choice experiments (DCEs). METHODS: This qualitative, cross-sectional, noninterventional study asked participants to use a think-aloud approach to compare SF-6Dv2 health states in DCEs. Thematic analysis focused on comprehension and cognitive strategies used to compare health states and make decisions. RESULTS: Participants (N = 40) used 3 main strategies when completing DCEs: (1) trading, (2) reinterpretation, and (3) relying on previous experience. Trading was the most common strategy, used by everyone at least once, and involved prioritizing key attributes, such as preferring a health state with significant depression but no bodily pain. Reinterpretation was used by 17 participants and involved reconstructing health states by changing underlying assumptions (eg, rationalizing selecting a health state with significant pain because they could take pain medications). Finally, some (n = 13) relied on previous experience when making decisions on some choice tasks. Participants with experience dealing with pain, for instance, prioritized health states with the least impact in this dimension. CONCLUSIONS: Qualitatively evaluating the decision-making strategies used in DCEs allows researchers to evaluate whether the tasks and attributes are interpreted accurately. The findings from this study add to the understanding of the generation of SF-6Dv2 health utility weights and the validity of these weights (e.g., reinterpreting health states could undermine the validity of DCEs and utility weights), and the overall usefulness of the SF-6Dv2. The methodology described in this study can and should be carried forth in valuing other health utility measures, not just the SF-6Dv2.

The Online Elicitation of Personal Utility Functions (OPUF) tool: a new method for valuing health states.

Introduction Standard valuation methods, such as TTO and DCE are inefficient. They require data from hundreds if not thousands of participants to generate value sets. Here, we present the Online elicitation of Personal Utility Functions (OPUF) tool; a new type of online survey for valuing EQ-5D-5L health states using more efficient, compositional elicitation methods, which even allow estimating value sets on the individual level. The aims of this study are to report on the development of the tool, and to test the feasibility of using it to obtain individual-level value sets for the EQ-5D-5L. Methods We applied an iterative design approach to adapt the PUF method, previously developed by Devlin et al., for use as a standalone online tool. Five rounds of qualitative interviews, and one quantitative pre-pilot were conducted to get feedback on the different tasks. After each round, the tool was refined and re-evaluated. The final version was piloted in a sample of 50 participants from the UK. A demo of the EQ-5D-5L OPUF survey is available at: https://eq5d5l.me Results On average, it took participants about seven minutes to complete the OPUF Tool. Based on the responses, we were able to construct a personal EQ-5D-5L value set for each of the 50 participants. These value sets predicted a participants' choices in a discrete choice experiment with an accuracy of 80%. Overall, the results revealed that health state preferences vary considerably on the individual-level. Nevertheless, we were able to estimate a group-level value set for all 50 participants with reasonable precision. Discussion We successfully piloted the OPUF Tool and showed that it can be used to derive a group-level as well as personal value sets for the EQ-5D-5L. Although the development of the online tool is still in an early stage, there are multiple potential avenues for further research.

Estimation of a Canadian preference-based scoring algorithm for the Veterans RAND 12-Item Health Survey: a population survey using a discrete-choice experiment.

BACKGROUND: The Veterans RAND 12-Item Health Survey (VR-12) is a generic patient-reported outcome measure derived from the widely used 36- and 12-item Short Form Health Surveys. We aimed to estimate a Canadian preference-based scoring algorithm for the VR-12, enabling the derivation of health utility values for generating quality-adjusted life years (QALYs). METHODS: We conducted a discrete-choice experiment in a sample of the Canadian population in January and February 2019. Participants - recruited from a consumer research panel - completed an online survey, in English or French, that included 11 discrete-choice questions, each comprising 2 health profiles. We defined the health profiles using 8 VR-12 items and a duration attribute. Using conditional logit regressions, where each level of the respective VR-12 items was interacted with duration, we applied the coefficients to estimate health utility values interpretable on a scale of 0 (dead) to 1 (full health). Negative values reflect states considered worse than dead. RESULTS: A total of 3380 individuals completed the survey. Of these, 1688 (49.9%) were females, and 3101 (91.7%) completed the English version of the survey. Across all models, "feel downhearted and blue all of the time" and "pain interferes with your normal work extremely" were associated with the largest decrements in health utility. Excluding the 685 respondents (20.3%) who provided inconsistent responses had a negligible effect on the results. The recommended model, weighted to match population demographics, had health utility values ranging from -0.589 to 1.000. INTERPRETATION: Health utility values that reflect the preferences of the Canadian population can now be derived from responses to the VR-12. These values can be used to generate QALYs in future analyses.

Development of the SF-6Dv2 health utility survey: comprehensibility and patient preference.

BACKGROUND: The SF-6Dv2 classification system assesses health states in six domains-physical functioning, role function, bodily pain, vitality, social functioning, and mental health. Scores have previously been derived from the SF-36v2® Health Survey. We aimed to develop a six-item stand-alone SF-6Dv2 Health Utility Survey (SF-6Dv2 HUS) and evaluate its comprehensibility. METHODS: Two forms of a stand-alone SF-6Dv2 HUS were developed for evaluation. Form A had 6 questions with 5-6 response choices, while Form B used 6 headings and 5-6 statements describing the health levels within each domain. The two forms were evaluated by 40 participants, recruited from the general population. Participants were randomized to debrief one form of the stand-alone SF-6Dv2 HUS during a 75-min interview, using think-aloud techniques followed by an interviewer-led detailed review. Participants then reviewed the other form of SF-6Dv2 and determined which they preferred. Any issues or confusion with items was recorded, as was as overall preference. Data were analyzed using Microsoft Excel and NVivo Software (v12). RESULTS: Participants were able to easily complete both forms. Participant feedback supported the comprehensibility of the SF-6Dv2 HUS. When comparing forms, 25/40 participants preferred Form A, finding it clearer and easier to answer when presented in question/response format. The numbered questions and underlining of key words in Form A fostered quick and easy comprehension and completion of the survey. However, despite an overall preference for Form A, almost half of participants (n = 19) preferred the physical functioning item in Form B, with more descriptive response choices. CONCLUSION: The results support using Form A, with modifications to the physical functioning item, as the stand-alone SF-6Dv2 HUS. The stand-alone SF-6Dv2 HUS is brief, easy to administer, and comprehensible to the general population.

Qualitative Review on Domains of Quality of Life Important for Patients, Social Care Users, and Informal Carers to Inform the Development of the EQ-HWB.

OBJECTIVES: To identify the themes to inform the content of a new generic measure, the EQ-HWB (EQ Health and Wellbeing), that can be used in economic evaluation across health, social care, and public health, based on the views of users and beneficiaries of these services including informal carers. METHODS: A qualitative review was undertaken. Systematic and citation searches were undertaken focusing on qualitative evidence of the impact on quality of life from reviews for selected health conditions, informal carers, social care users, and primary qualitative work used in the development of selected measures. A subset of studies was included in the review. Framework analysis and synthesis were undertaken based on a conceptual model. RESULTS: A total of 42 reviews and 24 primary studies were selected for inclusion in the review. Extraction and synthesis resulted in 7 high-level themes (with subthemes): (1) feelings and emotions (sadness, anxiety, hope, frustration, safety, guilt/shame); (2) cognition (concentration, memory, confusion, thinking clearly); (3) self-identity (dignity/respect, self-esteem); (4) "coping, autonomy, and control" relationships; (5) social connections (loneliness, social engagement, stigma, support, friendship, belonging, burden); (6) physical sensations (pain, discomfort, sleep, fatigue); and (7) activity (self-care, meaningful activities, mobility, communication, hearing, vision). Apart from physical sensations, most of the other themes and subthemes were relevant across both health and social care, including for informal carers. CONCLUSIONS: The findings from this broad review identified themes that go beyond health and that are relevant to patients, informal carers, and social care users. The themes and subthemes informed the domains for the EQ-HWB.

Developing a New Generic Health and Wellbeing Measure: Psychometric Survey Results for the EQ-HWB.

OBJECTIVES: The development of measures such as the EQ-HWB (EQ Health and Wellbeing) requires selection of items. This study explored the psychometric performance of candidate items, testing their validity in patients, social carer users, and carers. METHODS: Article and online surveys that included candidate items (N = 64) were conducted in Argentina, Australia, China, Germany, United Kingdom, and the United States. Psychometric assessment on missing data, response distributions, and known group differences was undertaken. Dimensionality was explored using exploratory and confirmatory factor analysis. Poorly fitting items were identified using information functions, and the function of each response category was assessed using category characteristic curves from item response theory (IRT) models. Differential item functioning was tested across key subgroups. RESULTS: There were 4879 respondents (Argentina = 508, Australia = 514, China = 497, Germany = 502, United Kingdom = 1955, United States = 903). Where missing data were allowed, it was low (UK article survey 2.3%; US survey 0.6%). Most items had responses distributed across all levels. Most items could discriminate between groups with known health conditions with moderate to large effect sizes. Items were less able to discriminate across carers. Factor analysis found positive and negative measurement factors alongside the constructs of interest. For most of the countries apart from China, the confirmatory factor analysis model had good fit with some minor modifications. IRT indicated that most items had well-functioning response categories but there was some evidence of differential item functioning in many items. CONCLUSIONS: Items performed well in classical psychometric testing and IRT. This large 6-country collaboration provided evidence to inform item selection for the EQ-HWB measure.