Sensitivity and responsiveness of the EQ-5D-3L in patients with uncontrolled focal seizures: an analysis of Phase III trials of adjunctive brivaracetam.

PURPOSE: Preference-based measures are required to measure the impact of interventions for cost-effectiveness analysis. This study assessed the psychometric performance of the EQ-5D-3L in adults with uncontrolled focal (partial-onset) seizures. METHODS: Data from three Phase III studies of an antiepileptic drug (adjunctive brivaracetam; n = 1095) were used. Analysis included correlations between EQ-5D-3L and Quality of Life in Epilepsy Inventory (QOLIE-31P) and seizure frequency. Known group validity was based on ability of the EQ-5D-3L to discriminate between baseline QOLIE-31P total scores, seizure type and number of antiepileptic drugs using effect sizes (ES). Responsiveness assessed proportions reporting highest or lowest scores, overall change using standardized response means (SRM) and change by responder and clinician/patient evaluation groups using ES. RESULTS: Correlations were weak to moderate (ρ = 0.2-0.4) between EQ-5D-3L dimensions and QOLIE-31P subscales, apart from medication effects (ρ < 0.1); seizure frequency was not associated with either measure. Known group analysis had small ES. A quarter (24.9%) of patients had a baseline EQ-5D-3L utility score of 1 (full health) but lower average QOLIE-31P scores. SRMs were small (<0.1) in EQ-5D-3L compared with 0.1-0.4 for QOLIE-31P subscales. Results across the studies were mixed for responder status and clinician/patient evaluation of improvement for EQ-5D-3L. CONCLUSIONS: EQ-5D-3L had weak-to-moderate correlations with QOLIE-31P and varied with QOLIE-31P severity groups, but showed less responsiveness than QOLIE-31P. Given this lack of sensitivity, EQ-5D-3L may not be appropriate for measuring the impact of interventions in cost-effectiveness analysis in this population and disease-specific preference-based measures may be more appropriate

Use of generic and condition-specific measures of health-related quality of life in NICE decision-making: systematic review, statistical modelling and survey.

© Queen’s Printer and Controller of HMSO 2014Background: The National Institute for Health and Care Excellence recommends the use of generic preference-based measures (GPBMs) of health for its Health Technology Assessments (HTAs). However, these data may not be available or appropriate for all health conditions. Objectives: To determine whether GPBMs are appropriate for some key conditions and to explore alternative methods of utility estimation when data from GPBMs are unavailable or inappropriate. Design: The project was conducted in three stages: (1) A systematic review of the psychometric properties of three commonly used GPBMs [EQ-5D, SF-6D and Health Utilities Index Mark 3 (HUI3)] in four broadly defined conditions: visual impairment, hearing impairment, cancer and skin conditions. (2) Potential modelling approaches to ‘map’ EQ-5D values from condition-specific and clinical measures of health [European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and Functional Assessment of Cancer Therapy – General Scale (FACT-G)] are compared for predictive ability and goodness of fit using two separate data sets. (3) Three potential extensions to the EQ-5D are developed as ‘bolt-on’ items relating to hearing, tiredness and vision. They are valued using the time trade-off method. A second valuation study is conducted to fully value the EQ-5D with and without the vision bolt-on item in an additional sample of 300 people. Main outcome measures: Comparisons of EQ-5D, SF-6D and HUI3 in four conditions with various generic and condition-specific measures. Mapping functions were estimated between EORTC QLQ-C30 and FACT-G with EQ-5D. Three bolt-ons to the EQ-5D were developed: EQ + hearing/vision/tiredness. A full valuation study was conducted for the EQ + vision. Results: (1) EQ-5D was valid and responsive for skin conditions and most cancers; in vision, its performance varied according to aetiology; and performance was poor for hearing impairments. The HUI3 performed well for hearing and vision disorders. It also performed well in cancers although evidence was limited and there was no evidence in skin conditions. There were limited data for SF-6D in all four conditions and limited evidence on reliability of all instruments. (2) Mapping algorithms were estimated to predict EQ-5D values from alternative cancer-specific measures of health. Response mapping using all the domain scores was the best performing model for the EORTC QLQ-C30. In an exploratory analysis, a limited dependent variable mixture model performed better than an equivalent linear model. In the full analysis for the FACT-G, linear regression using ordinary least squares gave the best predictions followed by the tobit model. (3) The exploratory valuation study found that bolt-on items for vision, hearing and tiredness had a significant impact on values of the health states, but the direction and magnitude of differences depended on the severity of the health state. The vision bolt-on item had a statistically significant impact on EQ-5D health state values and a full valuation model was estimated. Conclusions: EQ-5D performs well in studies of cancer and skin conditions. Mapping techniques provide a solution to predict EQ-5D values where EQ-5D has not been administered. For conditions where EQ-5D was found to be inappropriate, including some vision disorders and for hearing, bolt-ons provide a promising solution. More primary research into the psychometric properties of the generic preference-based measures is required, particularly in cancer and for the assessment of reliability. Further research is needed for the development and valuation of bolt-ons to EQ-5D.UK Medical Research Council (MRC) as part of the MRC-NIHR methodology research programme (reference G0901486

Mapping the Health of Nation Outcomes Scale (HoNOS) onto the Recovering Quality of Life Utility Index (ReQoL-UI)

Aim: The aim of this project is to develop and assess a mapping function to predict ReQoL-UI (a patient-reported mental health-specific preference-based measure) scores from HoNOS scores (clinician-reported measure, Health of Nation Outcomes Score). Methods: Participants were recruited from 14 secondary mental health services in England, UK, and their clinician completed HoNoS. Mapping models were estimated using Ordinary Least Squares (OLS) on individual level and mean level data and different model specifications were explored. Model performance was assessed using mean absolute error (MAE), root mean square error (RMSE), percentage of observations with absolute errors greater than 0.1, and plots of the observed and predicted ReQoL-UI utilities and errors. Results: Matched ReQoL-UI and HoNOS scores were collected for 649 participants. The sample comprised 56% inpatients, with overall mean ReQoL-UI utility of 0.683 and range from 1 to -0.195. Correlations between ReQoL-UI (items and utility) and HoNOS scores were moderate (0.2<r<0.4) or small (<0.2). The best model was OLS estimated using mean level data, with lowest MAE (0.046) and RMSE (0.056). Discussion: There is little conceptual overlap between ReQoL-UI and HoNOS. They measure different concepts and, arguably, service users and clinicians, who complete the measures respectively, have different perspectives. Under these circumstances, caution is recommended when applying these estimates

Recruitment of older adults to three preventative lifestyle improvement studies

YesBackground: Recruiting isolated older adults to clinical trials is complex, time-consuming and difficult. Previous studies have suggested querying existing databases to identify appropriate potential participants. We aim to compare recruitment techniques (general practitioner (GP) mail-outs, community engagement and clinician referrals) used in three randomised controlled trial (RCT) studies assessing the feasibility or effectiveness of two preventative interventions in isolated older adults (the Lifestyle Matters and Putting Life In Years interventions). Methods: During the three studies (the Lifestyle Matters feasibility study, the Lifestyle Matters RCT, the Putting Life In Years RCT) data were collected about how participants were recruited. The number of letters sent by GP surgeries for each study was recorded. In the Lifestyle Matters RCT, we qualitatively interviewed participants and intervention facilitators at 6 months post randomisation to seek their thoughts on the recruitment process. Results: Referrals were planned to be the main source of recruitment in the Lifestyle Matters feasibility study, but due to a lack of engagement from district nurses, community engagement was the main source of recruitment. District nurse referrals and community engagement were also utilised in the Lifestyle Matters and Putting Life In Years RCTs; both mechanisms yielded few participants. GP mail-outs were the main source of recruitment in both the RCTs, but of those contacted, recruiting yield was low (< 3%). Facilitators of the Lifestyle Matters intervention questioned whether the most appropriate individuals had been recruited. Participants recommended that direct contact with health professionals would be the most beneficial way to recruit. Conclusions: Recruitment to the Lifestyle Matters RCT did not mirror recruitment to the feasibility study of the same intervention. Direct district nurse referrals were not effective at recruiting participants. The majority of participants were recruited via GP mail-outs, which may have led to isolated individuals not being recruited to the trials. Further research is required into alternative recruitment techniques, including respondent-driven sampling plus mechanisms which will promote health care professionals to recruit vulnerable populations to research.The Lifestyle Matters RCT was funded by the Medical Research Council (grant number G1001406); Sheffield Health and Social Research Consortium; National Institute for Health Research Public Health Research programme (project number 09/ 3004/01

Lifestyle Matters for maintenance of health and wellbeing in people aged 65 years and over: study protocol for a randomised controlled trial

Background Healthy, active ageing is strongly associated with good mental wellbeing which in turn helps to prevent mental illness. However, more investment has been made into research into interventions to prevent mental illness than into those designed to improve mental wellbeing. This applied research programme will provide high quality evidence for an intervention designed to improve and sustain mental wellbeing in older adults. Methods/Design This study was a multi-centre, pragmatic, two-arm, parallel group, individually randomised controlled trial to determine the population benefit of an occupational therapy based intervention for community living people aged 65 years or older. Participants (n = 268) will be identified in one city in the North of England and in North Wales through GP mail-outs, signposting by local authority, primary care staff and voluntary sector organisations and through community engagement. Participants will be randomised to one of two treatment arms: an intervention (Lifestyle Matters programme); or control (routine access to health and social care). All participants will be assessed at baseline, 6 and 24 months post-randomisation. The primary outcome, which is a person reported outcome, is the SF-36 Mental Health dimension at six months post randomisation. Secondary outcome measures have been selected to measure psychosocial, physical and mental health outcomes. They include other dimensions of the SF36, EQ-5D-3L, Brief Resilience Scale, General Perceived Self Efficacy Scale, PHQ-9, de Jong Gierveld Loneliness Scale, Health and Social Care Resource Use and the wellbeing question of the Integrated Household Survey 2011. A cost effectiveness analysis will investigate the incremental cost per Quality Adjusted Life Years (QALYs) of the Lifestyle Matters intervention compared with treatment as usual. Discussion The questions being posed through this research are important given the increasing numbers of older people, pressure on the public purse and the associated need to support good health in the extended lifespan. The proposed trial will determine the clinical and cost effectiveness of the intervention delivered in a UK context. The results will support commissioners and providers with decisions about implementation.</p

Comparison of Modes of Administration and Alternative Formats for Eliciting Societal Preferences for Burden of Illness.

BACKGROUND: Proposals for value-based assessment, made by the National Institute of Health and Care Excellence (NICE) in the UK, recommended that burden of illness (BOI) should be used to weight QALY gain. This paper explores some of the methodological issues in eliciting societal preferences for BOI. AIMS: This study explores the impact of mode of administration and framing in a survey for eliciting societal preferences for BOI. METHODS: A pairwise comparison survey with six arms was conducted online and via face-to-face interviews, involving two different wordings of questions and the inclusion/exclusion of pictures. Respondents were asked which of two patient groups they thought a publically funded health service should treat, where the groups varied by life expectancy without treatment, health-related quality of life (HRQOL) without treatment, survival gain from treatment, and HRQOL gain from treatment. Responses across different modes of administration, wording and use of pictures were compared using chi-squared tests and probit regression analysis controlling for respondent socio-demographic characteristics. RESULTS: The sample contained 371 respondents: 69 were interviewed and 302 completed the questionnaire online. There were some differences in socio-demographic characteristics across the online and interview samples. Online respondents were less likely to choose the group with higher BOI and more likely to treat those with a higher QALY gain, but there were no statistically significant differences by wording or the inclusion of pictures for the majority of questions. Regression analysis confirmed these results. Respondents chose to treat the group with larger treatment gain, but there was little support for treating the group with higher BOI. Respondents also preferred to treat the group with treatment gains in life expectancy rather than HRQOL. CONCLUSIONS: Mode of administration did impact on responses, whereas question wording and pictures did not impact on responses, even after controlling for the socio-demographic characteristics of respondents in the regression analysis

Enhancing HRQoL assessment for economic evaluation in dementia populations

INTRODUCTION This study aims to assess the feasibility, acceptability, and validity of EQ-5D instrument administration methods and proxy selection for evaluating health-related quality of life (HRQoL) in dementia populations. EQ-5D is a widely used measure of HRQoL and is recommended by the National Institute for Health and Care Excellence for cost-effectiveness analyses of health interventions. METHODS Individual-level data from three trials were analyzed separately to evaluate missing data rates, inter-rater agreement, responsiveness, and predictors of EQ-5D (EQ-5D-3L and EQ-5D-5L) dimensions and index values. The study used psychometric analyses, correlations, and multivariate linear regression models to evaluate EQ-5D dimension reports. Reports from both people with dementia (PwD) and proxies were compared to assess reliability across different settings and proxy types. RESULTS Proxy-reported EQ-5D achieved higher completion rates compared to reports from PwD, with proxies showing greater responsiveness to changes in symptom scores over time. Face-to-face instrument administration for informal proxies was favored over postal methods, and proxy selection was found to be crucial, with informal proxies recommended for community-dwelling PwD and staff proxies for institutionalized populations. Inter-rater agreement was strongest for the “mobility” dimension, with differences in reporting by dimension. Novel guidelines on integrating EQ-5D data reported by PwD and proxies are proposed. Combining self- and proxy-reported data to generate an integrated utility score potentially reflects a more holistic perspective and may enhance the accuracy of HRQoL assessment, compared to relying solely on one respondent's reports. DISCUSSION The importance of careful administration and proxy selection for HRQoL data collection and application in dementia trials and studies is highlighted. These findings have implications for informing economic evaluations of dementia interventions, emphasizing the potential need for tailoring approaches to HRQoL assessment based on the residential status of the PwD. Highlights The EQ-5D is a widely used measure in dementia trials, but challenges like missing data and discrepancies in inter-rater agreement highlight complexities in assessing health-related quality of life (HRQoL), especially in advanced stages. This study empirically examines the feasibility, acceptability, and validity of EQ-5D data from people with dementia and proxies, using individual-level data from three trials. Recommendations are provided to improve data collection practices, enhancing the reliability of HRQoL assessments in clinical trials for dementia interventions. Optimized proxy selection criteria and administration methods tailored to residential status can improve HRQoL assessments, supporting more accurate economic evaluations and better-informed care decisions