Measuring health related quality of life (HRQoL) in Lysosomal Storage Disorders (LSDs): a rapid scoping review of available tools and domains.

BACKGROUND: Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders, consisting of over 70 diseases that are characterised by lysosomal dysfunction. Due to their varied and progressive symptoms, LSDs have a continual impact on patients' health-related quality of life (HRQoL). Several recently published studies have provided insight into the HRQoL of individuals with LSDs. However, it is challenging to meaningfully synthesise this evidence, since studies often focus upon a particular type of LSD and / or utilise different self-report questionnaires or patient-reported outcome measures (PROMs) to assess HRQoL. AIMS: The aim of this study was to review the published literature in LSDs, to identify the PROMs which have been used to assess HRQoL and generate a conceptual map of HRQoL domains measured in individuals diagnosed with LSDs. METHODS: Three electronic databases were searched in March 2022. Primary studies of any design which utilised multi-item PROMs to assess at least one aspect of HRQoL in individuals with LSDs since 2017 were identified. Data were extracted to assess both the characteristics of each study and of the PROMs utilised within each study. The extraction of HRQoL domains and synthesis were informed by an a priori framework, inductively modified to reflect data emerging from the identified literature. Selection and extraction was undertaken independently by two reviewers; discrepancies were ratified by a third reviewer. RESULTS: Sixty nine studies were identified which were published 2017-2022, with a combined total of 52 PROMs (71 variants) used to assess HRQoL in individuals with LSDs. The final extracted HRQoL framework included 7 domains (Activities; Physical sensations; Autonomy; Cognition; Feelings and emotions; Self-identity; Relationships), characterised by 37 sub-domains. CONCLUSIONS: This review highlights the breadth and variety of HRQoL domains assessed in individuals with LSDs, across three broad domains of physical, psychological and social functioning. The resultant framework and mapped PROMs will aid researchers and clinicians in the selection of PROMs to assess aspects of HRQoL in people living with LSDs, based on their conceptual coverage.

Measuring Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: A Systematic Review and Conceptual Framework.

BACKGROUND AND OBJECTIVES: The assessment of health-related quality of life (HRQoL) in patients with amyotrophic lateral sclerosis (ALS) is heterogeneous and inconsistent. The objectives of this study were (1) to develop a comprehensive conceptual framework of HRQoL in ALS and (2) map the content of existing patient-reported outcome measures (PROMs) used in ALS to this novel framework. METHODS: Our model of HRQoL in ALS (Health-related Quality of life in Amyotrophic Lateral Sclerosis, QuALS) was developed from a systematic literature review and consultative input from key stakeholders (patients, carers, and health care professionals). Five electronic databases were searched in April 2022. Primary studies of any design that assessed HRQoL in ALS by using a multi-item PROM and/or qualitative methods were identified. Using an a priori framework, HRQoL themes were extracted and iteratively modified from the content of each PROM and qualitative study quotations identified in the literature. The conceptual framework was ratified by stakeholders with lived experience and clinical experts. The QuALS framework was used to map the content of identified PROMs and qualitative studies based on thematic coverage. RESULTS: QuALS covers 3 high-level domains of HRQoL (physical, psychological, and social functioning) and consists of 7 themes (Activities; Physical Health; Autonomy; Cognition; Feelings and Emotions; Self-identity; Relationships), characterized by 42 subthemes. Of 8,220 studies identified, 274 were included in the review that informed QuALS. In these studies, 111 PROMs were used to assess at least 1 aspect of HRQoL, and 11 studies used qualitative methods. Of the 3 high-level domains, physical functioning was the most commonly assessed, particularly within ALS-specific PROMs where almost one-quarter of PROMs exclusively assessed physical functioning. None of the PROMs or qualitative studies identified assessed all aspects of HRQoL in the QuALS framework. DISCUSSION: This study presents a new comprehensive conceptual framework of HRQoL in ALS (QuALS), informed by a robust systematic review of existing literature and stakeholder input, incorporating lived experience. QuALS provides a valuable resource for researchers and clinicians interested in taking a holistic approach to assessing and understanding the full impact of ALS on HRQoL and how this may be affected by treatments.

Psychometric Performance of the EQ Health and Wellbeing Short in a United Kingdom Population Sample.

OBJECTIVES: This study assessed the psychometric performance and construct validity of the EQ Health and Wellbeing Short (EQ-HWB-S), using a validated measure, the EQ-5D-5L, as a comparator. METHODS: The experimental version of the EQ-HWB-S was compared with the EQ-5D-5L to assess the psychometric performance of the measures. Data were drawn from the valuation stages of the Extending the Quality-Adjusted Life-Year project (UK general population, n = 429) and the EQ-5D-5L UK valuation pilot study (UK general population, n = 248). Construct validity was assessed based on convergent validity, using Spearman correlations and Pearson correlations. Known-group validity was assessed by estimating effect sizes to assess the ability of the EQ-HWB-S and EQ-5D-5L to discriminate between known groups based on "healthy" status, presence of a long-term condition, health and life satisfaction, age, and employment status. The degree of agreement in utility values across instruments was also evaluated using Bland-Altman plots. RESULTS: Strong associations (rs ≥ 0.5, P < .001) were found between conceptually overlapping dimensions and the utility scores of the EQ-HWB-S and EQ-5D-5L. The instruments performed comparably in discriminating between known groups including healthy versus unhealthy groups (based on the visual analog scale ≥ 80), long-term condition (vs no long-term condition), and above versus below average health and life satisfaction and employed (vs unemployed and long-term sick). CONCLUSIONS: The EQ-HWB-S performs favorably with utility values successfully discriminating between groups in which differences are expected. Convergence between the EQ-HWB-S and EQ-5D-5L is evident, especially between conceptually overlapping dimensions.

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.

A Systematic Review of the Methodologies and Modelling Approaches Used to Generate International EQ-5D-5L Value Sets.

BACKGROUND: The international protocol for valuing EQ-5D-5L focuses upon prescribed preference elicitation methods and design. However, there are no recommendations around sampling, recruitment, data analysis or modelling to generate the EQ-5D-5L value set. This review examines methods used to generate international EQ-5D-5L values sets, across sampling, recruitment, data analysis, modelling, assessing model performance and selection of the recommended value set. METHODS: All published EQ-5D-5L value sets were identified by a systematic search and confirmed by the EuroQol Group. Data were extracted to assess sampling, recruitment, preference elicitation techniques and design, data analysis, modelling, assessing model performance, and vale set selection. These are summarised in tables. RESULTS: The review included 29 studies with 27 value sets generated using time-trade-off (TTO) data (n = 10) only or using a hybrid model that combines TTO and discrete choice experiment data (n = 17). TTO data were most commonly estimated using a heteroscedastic Tobit model with censoring at - 1, and the hybrid model using a specially created program. Model performance was generally assessed using goodness of fit, logical consistency and significance of coefficients, suitability of the model for the data characteristics and parsimony, though not all selected models account for the specific characteristics of the data. DISCUSSION: Different assessments of model performance and reasoning are provided for the selection of the recommended value set for a country. This raises the question of valid criteria for selecting a recommended value set and whether this should rely upon researchers' recommendations when value sets are often used to inform public policy.

A Comparison of the SF-6Dv2 and SF-6D UK Utility Values in a Mixed Patient and Healthy Population.

BACKGROUND: This paper describes the first evaluation of the construct validity and performance of the newly developed preference-based measure of health, the SF-6D version 2 (SF-6Dv2). METHOD: Utilising data from the Multi-Instrument Comparison (MIC) project (n = 7932), we explored the descriptive differences in utility values between the SF-6Dv2 and the SF-6D and evaluated the known group validity of both measures by testing the statistical significance of differences in utility values and calculating the effect sizes across known groups. The convergent validity of the SF-6Dv2 was explored by examining whether the SF-6Dv2 is related to alternative validated measures, including the EQ-5D-5L and AQoL-8D. RESULTS: Differences between the utility values of the SF-6Dv2 and SF-6D were evident; utilities were generally lower for the SF-6Dv2, with larger standard deviations resulting in larger absolute differences between groups. The SF-6Dv2 performed well in terms of known-group validity and successfully distinguished disease severity and between the disease and healthy groups, outperforming the SF-6D in some but not all groups. Convergent validity analyses indicated strong associations between the SF-6Dv2 and the SF-6D, EQ-5D-5L and AQoL-8D utilities. CONCLUSIONS: The psychometric performance of the SF-6Dv2 is favourable with respect to known group validity and convergent validity, but does not seem to have improved, compared with the SF-6D. However, the new method of valuation has had a substantial impact on the size of absolute differences in utility values, which could impact quality-adjusted life-year results. The economic evaluation of health interventions may therefore be influenced by the choice of the SF-6Dv2 over the SF-6D.

The internet and children's psychological wellbeing.

Late childhood and adolescence is a critical time for social and emotional development. Over the past two decades, this life stage has been hugely affected by the almost universal adoption of the internet as a source of information, communication, and entertainment. We use a large representative sample of over 6300 children in England over the period 2012-2017, to estimate the effect of neighbourhood broadband speed, as a proxy for internet use, on a number of wellbeing outcomes, which reflect how these children feel about different aspects of their life. We find that internet use is negatively associated with wellbeing across a number of domains. The strongest effect is for how children feel about their appearance, and the effects are worse for girls than boys. We test a number of potential causal mechanisms, and find support both for the 'crowding out' hypothesis, whereby internet use reduces the time spent on other beneficial activities, and for the adverse effect of social media use. Our evidence adds weight to the already strident calls for interventions that can reduce the adverse effects of internet use on children's emotional health.