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

ObjectivesThe 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.MethodsA 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.ResultscTTO 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.ConclusionsEQ-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.     

Predicting Patient-Level 3-Level Version of EQ-5D Index Scores From a Large International Database Using Machine Learning and Regression Methods

ObjectivesThis study aimed to evaluate the performance of machine learning and regression methods in the prediction of 3-level version of EQ-5D (EQ-5D-3L) index scores from a large diverse data set.MethodsA total of 30 studies from 3 countries were combined. Predictions were performed via eXtreme Gradient Boosting classification (XGBC), eXtreme Gradient Boosting regression (XGBR) and ordinary least squares (OLS) regression using 10-fold cross-validation and 80%/20% partition for training and testing. We evaluated 6 prediction scenarios using 3 samples (general population, patients, total) and 2 predictor sets: demographic and disease-related variables with/without patient-reported outcomes. Model performance was evaluated by mean absolute error and percent of predictions within clinically irrelevant error range and within correct health severity group (EQ-5D-3L index <0.45, 0.45-0.926, >0.926).ResultsThe data set involved 26 318 individuals (clinical settings n = 6214, general population n = 20 104) and 26 predictor variables plus diagnoses. Using all predictors and the total sample, mean absolute error values were 0.153, 0.126, and 0.131, percent of predictions within clinically irrelevant error range were 47.6%, 39.5%, and 37.4%, and within the correct health severity group were 56.3%, 64.9%, and 63.3% by XGBC, XGBR, and OLS, respectively. The performance of models depended on the applied evaluation criteria, the target population, the included predictors, and the EQ-5D-3L index score range.ConclusionsRegression models (XGBR and OLS) outperformed XGBC, yet prediction errors were outside the clinically irrelevant error range for most respondents. Our results highlight the importance of systematic patient-reported outcome (EQ-5D) data collection. Dialogs between artificial intelligence and outcomes research experts are encouraged to enhance the value of accumulating data in health systems.     

Investigating 5-Level EQ-5D (EQ-5D-5L) Values Based on Preferences of Patients With Heart Disease

ObjectivesSeveral studies have shown that patients with heart disease value hypothetical health states differently from the general population. We aimed to investigate the health preferences of patients with heart disease and develop a value set for the 5-level EQ-5D (EQ-5D-5L) based on these patient preferences.MethodsPatients with confirmed heart disease were recruited from 2 hospitals in Singapore. A total of 86 EQ-5D-5L health states (10 per patient) were valued using a composite time trade-off method according to the international valuation protocol for EQ-5D-5L; 20-parameter linear models and 8-parameter cross-attribute level effects models with and without an N45 term (indicating whether any health state dimension at level 4 or 5 existed) were estimated. Each model included patient-specific random intercepts. Model performance was evaluated for out-of-sample and in-sample predictive accuracy in terms of root mean square error. The discriminative ability of the utility values was assessed using heart disease-related functional classes.ResultsA total of 576 patients were included in the analysis. The preferred model, with the lowest out-of-sample root mean square error, was a 20-parameter linear model including N45. Predicted utility values ranged from ?0.727 for the worst state to 1 for full health; the value for the second-best state was 0.981. Utility values demonstrated good discriminative ability in differentiating among patients of varied functional classes.ConclusionsAn EQ-5D-5L value set representing the preferences of patients with heart disease was developed. The value set could be used for patient-centric economic evaluation and health-related quality of life assessment for patients with heart disease.     

Health problems are more common,but less severe when measured using newer EQ-5D versions

ObjectivesThe EuroQol Group recently released youth (Y) and 5-level (5L) versions of its 3-level EQ-5D instrument (3L) that measures health-related quality of life. In this study, we (1) compare 3L, Y, and 5L responses among US adults and (2) assess construct validity.Study Design and SettingUsing a nationally representative sample of US adults (N = 2,619), we collected 3L, Y, and 5L responses in random order and estimated their associations and their relationship with a 0 to 100 numerical visual analog scale.ResultsThe prevalence of US adults in the best possible EQ-5D state (i.e., 11111) was lower for the Y (38%) and 5L (35%) than for the 3L (44%), capturing more health problems. However, the prevalence of extreme responses in pain/discomfort and anxiety/depression decreased substantially between the 3L and 5L (from 44% to 17% and from 29% to 13%, respectively).ConclusionCompared with the 3L, the Y and 5L versions describe population health as having more, yet milder, health problems. Although the 5L may have advantages in patient populations in which extreme problems are more prevalent, population studies or studies that follow patients from childhood may consider using the Y.     

Estimating Cost-Effectiveness Using Alternative Preference-Based Scores and Within-Trial Methods: Exploring the Dynamics of the Quality-Adjusted Life-Year Using the EQ-5D 5-Level Version and Recovering Quality of Life Utility Index

ObjectivesThis study aimed to explore quality-adjusted life-year (QALY) and subsequent cost-effectiveness estimates based on the more physical health–focused EQ-5D 5-level version (EQ-5D-5L) value set for England or cross-walked EQ-5D 3-level version UK value set scores or more mental health recovery-focused Recovering Quality of Life Utility Index (ReQoL-UI), when using alternative within-trial statistical methods. We describe possible reasons for the different QALY estimates based on the interaction between item scores, health state profiles, preference-based scores, and mathematical and statistical methods chosen.MethodsQALYs are calculated over 8 weeks from a case study 2:1 (intervention:control) randomized controlled trial in patients with anxiety or depression. Complete case and with missing cases imputed using multiple-imputation analyses are conducted, using unadjusted and regression baseline-adjusted QALYs. Cost-effectiveness is judged using incremental cost-effectiveness ratios and acceptability curves. We use previously established psychometric results to reflect on estimated QALYs.ResultsA total of 361 people (241:120) were randomized. EQ-5D-5L crosswalk produced higher incremental QALYs than the value set for England or ReQoL-UI, which produced similar unadjusted QALYs, but contrasting baseline-adjusted QALYs. Probability of cost-effectiveness <£30 000 per QALY ranged from 6% (complete case ReQoL-UI baseline-adjusted QALYs) to 64.3% (multiple-imputation EQ-5D-5L crosswalk unadjusted QALYs). The control arm improved more on average than the intervention arm on the ReQoL-UI, a result not mirrored on the EQ-5D-5L nor condition-specific (Patient-Health Questionnaire-9, depression; Generalized Anxiety Disorder-7, anxiety) measures.ConclusionsReQoL-UI produced contradictory cost-effectiveness results relative to the EQ-5D-5L. The EQ-5D-5L’s better responsiveness and “anxiety/depression” and “usual activities” items drove the incremental QALY results. The ReQoL-UI’s single physical health item and “personal recovery” construct may have influenced its lower 8-week incremental QALY estimates in this patient sample.     

Mapping World Health Organization Quality of Life–BREF Onto 5-Level EQ-5D in Thai Patients With Chronic Diseases

ObjectivesThis study aimed to map the World Health Organization Quality of Life–BREF (WHOQOL-BREF) onto the 5-level EQ-5D (EQ-5D-5L) using a real Thai valuation set of the EQ-5D-5L. The second objective was to explore the impacts of the differences between observed and predicted EQ-5D-5L index scores on the incremental cost-utility ratio (ICUR) using 5 hypothetical scenarios.MethodsThis is a secondary data analysis. A total of 800 outpatients with chronic diseases were recruited from 2 university hospitals in Bangkok, Thailand, between July 2014 and March 2015. The 800 patients were randomly divided into 2 samples: estimation and validation samples. The estimation sample was used to assess the relationships between the EQ-5D-5L index score and 4 WHOQOL-BREF dimension scores and to find the best-fit model and its equation. For the validation sample, the equation of the best-fit model from the estimation sample was used to calculate predicted EQ-5D-5L index scores.ResultsA multiple linear regression showed that only the physical domain of the WHOQOL-BREF was significantly associated with the EQ-5D-5L. Among 11 regression models, the curve estimation found that the inverse model was the best-fit model. The prediction equation of EQ-5D-5L was equal to 1.385 minus 7.572/physical domain of the WHOQOL-BREF. The impacts of the differences between the observed and predicted EQ-5D-5L index scores on ICUR were only 0.4% to 1.8% from the base case.ConclusionsA nonlinear relationship between the physical domain of the WHOQOL-BREF and EQ-5D-5L utility was shown. The impacts of the differences between the observed and predicted EQ-5D-5L index scores on ICUR were minimal.     

Quebec Health-Related Quality-of-Life Population Norms Using the EQ-5D-5L: Decomposition by Sociodemographic Data and Health Problems

ObjectivesPopulation norms for the EQ-5D-5L were published in Canada but only for Alberta province. The purpose of this study was to derive Quebec population norms from the EQ-5D-5L.MethodsThe data came from a larger study conducted between September 2016 and March 2018 using elicitation techniques for a quality-adjusted life-year project. The online survey was distributed randomly in the province of Quebec. To best describe the entire population, data were stratified by various sociodemographic characteristics such as age, gender, urban and rural populations, whether disadvantaged or not, immigrant or nonimmigrant, and health problems.ResultsA total of 2704 (53.8%) respondents completed the EQ-5D-5L. Mean (95% confidence interval) and median (interquartile range) utility scores were 0.824 (0.818-0.829) and 0.867 (0.802-0.911), respectively. The EQ-VAS scores were estimated at 75.9 (75.2-76.6) and 80 (69-90). Subjects with lower scores were those who had a low or high body mass index; were smokers; were single, divorced, or widowed; had no children; were unemployed or sick; had lower education or lower annual income; and had a family or personal history of serious illness. Immigrants had higher scores. There was no difference in gender and urban or rural population. The score logically decreased with worsening health status, from a mean score of 0.896 (0.884-0.908) to 0.443 (0.384-0.501; P < .0001. Similar results were observed for subjects’ satisfaction with their health or life. Subjects with lower scores were less willing to take risks. Subjects who declared they were affected by health problems presented significant lower utility scores, ranging from 0.554 (nervous problem) to 0.750 (cancer), compared with those without health problems (0.871; confidence interval: 0.867-0.876).ConclusionThis is the first study to present utility score norms for EQ-5D-5L for the Quebec population. These results will be useful for comparison with quality-adjusted life-year studies to better interpret their results. Moreover, utility norms were provided for 21 health problems, which was rarely done.     

Health related quality of life aspects not captured by EQ-5D-5L: Results from an international survey of patients

Background

In this paper we discuss and present evidence on whether a generic Health Related Quality of Life (HRQoL) measurement tool, the EQ-5D-5L, captures the dimensions of quality of life (QoL) which patients consider significant.

EQ-5D–Derived Health State Utility Values in Hematologic Malignancies: A Catalog of 796 Utilities Based on a Systematic Review

ObjectivesWe performed a systematic review of health state utility values (HSUVs) obtained using the EQ-5D questionnaire for patients with hematologic malignancies.MethodsThe following databases were searched up to September 2018: MEDLINE, EMBASE, The Cochrane Library, and the EQ-5D publications database on the EuroQol website. Additional references were extracted from reviewed articles. Only studies presenting EQ-Index results were incorporated. In view of the heterogeneity across the included publications, we limited ourselves to a narrative synthesis of original HSUVs found.ResultsFifty-nine studies (described in 63 articles) met the inclusion criteria. Data from 21 635 respondents provided 796 HSUV estimates for hematologic malignancy patients. EQ-Index scores ranged from –0.025 to 0.980. The most represented area was multiple myeloma (4 studies, 11 112 patients, and 249 HSUVs). In clinical areas such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and mantle cell lymphoma, we described over 50 health utilities in each. In contrast, we identified only 13 HSUVs (based on 4 studies and the data of 166 patients) for Hodgkin lymphoma. Areas without EQ-5D–based health utilities comprised: polycythemia vera, primary myelofibrosis, essential thrombocythemia, mastocytosis, myeloid sarcoma, chronic myelomonocytic, eosinophilic leukemia, and neutrophilic leukemia.ConclusionsThere is a wide range of HSUVs available for hematologic cancer patients with different indications. The review provides a catalog of utility values for use in cost-effectiveness models for hematologic malignancies.     

A Comparison of Generic and Condition-Specific Preference-Based Measures Using Data From Nivolumab Trials: EQ-5D-3L,Mapping to the EQ-5D-5L,and European Organisation for Research and Treatment of Cancer Quality of Life Utility Measure-Core 10 Dimensions

ObjectivesThere is growing interest in condition-specific preference measures, including the European Organisation for Research and Treatment of Cancer Quality of Life Utility Measure-Core 10 Dimensions (QLU-C10D). This research assessed the implications of using utility indices on the basis of the EQ-5D-3L, a mapping of EQ-5D-3L to the EQ-5D-5L, and the QLU-C10D, and compared their psychometric properties.MethodsData were taken from 8 phase 3 randomized controlled trials of nivolumab with or without ipilimumab for the treatment of solid tumors. Utilities for progression-related states were calculated using the UK and English value sets and incremental quality-adjusted life-years (QALYs) derived from established UK cost-effectiveness models. The psychometric properties of the utility indices were assessed using pooled trial data.ResultsCompared with the EQ-5D-3L index, the mapped EQ-5D-5L index yielded an average of 6% more and the QLU-C10D index an average of 2% fewer incremental QALYs for nivolumab versus comparators. All indices could differentiate between groups defined by performance status, cancer stage, or self-reported health status at baseline and detect meaningful changes in performance status, tumor response, health status, and quality of life over approximately 12 weeks of treatment.ConclusionsThe lower QALY yield of the QLU-C10D was balanced by evidence of greater validity and responsiveness. Benefits gained from using the QLU-C10D may be apparent when treatments affect targeted symptoms and functional aspects, including sleep, bowel function, appetite, nausea, and fatigue. The observed differences in QALYs may not be sufficiently large to affect health technology assessment decisions.     

Development of an EQ-5D Value Set for India Using an Extended Design (DEVINE) Study: The Indian 5-Level Version EQ-5D Value Set

ObjectivesThis study aimed to develop the Indian 5-level version EQ-5D (EQ-5D-5L) value set, which is a key input in health technology assessment for resource allocation in healthcare.MethodsA cross-sectional survey using the EuroQol Group’s Valuation Technology was undertaken in a representative sample of 3548 adult respondents, selected from 5 different states of India using a multistage stratified random sampling technique. The participants were interviewed using a computer-assisted personal interviewing technique. This study adopted a novel extended EuroQol Group’s Valuation Technology design that included 18 blocks of 10 composite time trade-off (c-TTO) tasks, comprising 150 unique health states, and 36 blocks of 7 discrete choice experiment (DCE) tasks, comprising 252 DCE pairs. Different models were explored for their predictive performance. Hybrid modeling approach using both c-TTO and DCE data was used to estimate the value set.ResultsA total of 2409 interviews were included in the analysis. The hybrid heteroscedastic model with censoring at ?1 combining c-TTO and DCE data yielded the most consistent results and was used for the generation of the value set. The predicted values for all 3125 health states ranged from ?0.923 to 1. The preference values were most affected by the pain/discomfort dimension.ConclusionsThis is the largest EQ-5D-5L valuation study conducted so far in the world. The Indian EQ-5D-5L value set will promote the effective conduct of health technology assessment studies in India, thereby generating credible evidence for efficient resource use in healthcare.     

Overview,Update, and Lessons Learned From the International EQ-5D-5L Valuation Work: Version 2 of the EQ-5D-5L Valuation Protocol

A standardized 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L) valuation protocol was first used in national studies in the period 2012 to 2013. A set of problems encountered in this initial wave of valuation studies led to the subsequent refinement of the valuation protocol. To clarify lessons learned and how the protocol was updated when moving from version 1.0 to the current version 2.1 and 2.0, this article will (1) present the challenges faced in EQ-5D-5L valuation since 2012 and how these were resolved and (2) describe in depth a set of new challenges that have become central in currently ongoing research on how EQ-5D-5L health states should be valued and modeled.     

Why Do Patients with Inflammatory Arthritis Often Score States “Worse than Death” on the EQ-5D? An Investigation of the EQ-5D Classification System

Objective:  Using inflammatory arthritis patients as an example, we investigate EuroQol-5D (EQ-5D) profiles resulting in states worse than death (WTD), and the heath status of patients occupying these states.
Methods:  Baseline data from two UK trials were used that reflected the range of arthritis states/severity found in routine practice. EQ-5D profiles resulting in negative valuations (i.e., states WTD) based on UK weights were identified. EQ-5D scores for these profiles from alternative valuation sets, including a reanalysis of the UK weights, were compared. The health status and characteristics of patients, and factors associated with patients in the low distribution of the EQ-5D and those with WTD EQ-5D scores were identified.
Results:  Seven hundred patients were included in the analysis. Sixty-two (9%) patients occupied states WTD. Patients occupied 9 of the possible 84health profiles with negative scores (53% occupied one profile); this profile was not rated WTD by any of the alternative EQ-5D scoring algorithms. All WTD profiles included severe pain/discomfort plus moderate problems in ≥3 other domains. Patients with WTD valuations reported higher levels of pain, and feeling downhearted and low on alternative health status measures.
Conclusions:  Pain was the predominant factor in the WTD EQ-5D profiles occupied by arthritis patients. Patients occupying states WTD have poorer health-related quality of life than patients in low "better than death" states. Valuations of profiles vary according to how sets of preference weights for health profiles were developed. Further research should explore whether WTD valuations are supported by qualitative evidence and reflect the patient's health and experience of disease.     

A Direct Comparison of the Measurement Properties of EQ-5D-5L,PROMIS-29+2 and PROMIS Global Health Instruments and EQ-5D-5L and PROPr Utilities in a General Population Sample

ObjectivesWe aimed to compare measurement properties of the 5-level version of EQ-5D (EQ-5D-5L) and 2 Patient-Reported Outcomes Measurement Information System (PROMIS) short forms, PROMIS-29+2 and PROMIS Global Health (PROMIS-GH-10), and of EQ-5D-5L and PROMIS-preference scoring system (PROPr) utilities.MethodsA cross-sectional survey was conducted in a general population sample in Hungary (N = 1631). We compared the following measurement properties at the level of items, domains, and utilities, the latter using corresponding US value sets: ceiling and floor, informativity (Shannon’s indices), agreement, convergent, and known-group validity. For the analyses, PROMIS items/domains were matched to EQ-5D-5L domains that cover similar concepts of health.ResultsThe majority of PROMIS items showed enhanced distributional characteristics, including lower ceilings and higher informativity than the EQ-5D-5L. Good convergent validity was established between EQ-5D-5L and PROMIS domains capturing similar aspects of health. Mean EQ-5D-5L utilities were substantially higher than those of PROPr (0.864 vs 0.535). EQ-5D-5L utilities correlated moderately or strongly with PROPr (r = 0.61), PROMIS-GH-10 physical (r = 0.68), and mental health summary scores (r = 0.53). EQ-5D-5L utilities decreased with age, whereas PROPr utilities slightly increased with age. EQ-5D-5L utilities discriminated significantly better in 12/28 (ratio of F-statistics) and 18/26 (area under the receiver-operating characteristics curve ratio) known groups defined by age, self-perceived health status, and self-reported physician-diagnosed health conditions, including hypertension, diabetes, coronary heart disease, chronic kidney disease, and stroke.ConclusionsThis study provides comparative evidence on the measurement properties of EQ-5D-5L, PROMIS-29+2, and PROMIS-GH-10 and informs decisions about the choice of instruments in population health surveys for assessment of patients’ health and for cost-utility analyses.     

Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L

Objectives

To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors.

Instrument-Defined Estimates of the Minimally Important Difference for EQ-5D-5L Index Scores

Background

The five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) is a preference-based measure of health-related quality of life (HRQOL), which yields an index score anchored at 0 (dead) and 1 (full health). We lack evidence on estimates for the minimally important difference (MID) of the EQ-5D-5L that will help in interpreting differences or changes in HRQOL measured by this scale score.

A Program of Methodological Research to Arrive at the New International EQ-5D-5L Valuation Protocol

ObjectivesTo describe the research that has been undertaken by the EuroQol Group to improve current methods for health state valuation, to summarize the results of an extensive international pilot program, and to outline the key elements of the five-level EuroQol five-dimensional (EQ-5D-5L) questionnaire valuation protocol, which is the culmination of that work.MethodsTo improve on methods of health state valuation for the EQ-5D-5L questionnaire, we investigated the performance of different variants of time trade-off and discrete choice tasks in a multinational setting. We also investigated the effect of three modes of administration on health state valuation: group interviews, online self-completion, and face-to-face interviews.ResultsThe research program provided the basis for the EQ-5D-5L questionnaire valuation protocol. Two different types of tasks are included to derive preferences: a newly developed composite time trade-off task and a forced-choice paired comparisons discrete choice task. Furthermore, standardized blocked designs for the selection of the states to be valued by participants were created and implemented together with all other elements of the valuation protocol in a digital aid, the EuroQol Valuation Technology, which was developed in conjunction with the protocol.ConclusionsThe EuroQol Group has developed a standard protocol, with accompanying digital aid and interviewer training materials, that can be used to create value sets for the EQ-5D-5L questionnaire. The use of a well-described, consistent protocol across all countries enhances the comparability of value sets between countries, and allows the exploration of the influence of cultural and other factors on health state values.     

Japanese Population Norms of EQ-5D-5L and Health Utilities Index Mark 3: Disutility Catalog by Disease and Symptom in Community Settings

ObjectivesThis study aimed to establish the Japanese population norms of the EQ-5D-5L and Health Utilities Index Mark 3 (HUI3) and estimate the disutility associated with diseases and symptoms.MethodsWe performed a door-to-door survey of the general population by random sampling. The planned sample size was 10 000 residents (age ≥16 years) of 334 districts in Japan. In addition to the EQ-5D-5L and HUI3 questionnaires, questions regarding demographic factors and self-reported main diseases and symptoms were asked. The EQ-5D-5L and HUI3 responses were converted to index values on the basis of Japanese value sets. Summary values by age and sex were calculated to obtain Japanese normative values. A multiple linear model was used to examine relationships between these values and diseases and symptoms.ResultsWe collected 10 183 responses from 334 districts. The mean EQ-5D-5L index values were 0.821 (male) and 0.774 (female) in the age group of 80 to 89 years, which were lower compared with 0.978 (male) and 0.967 (female) in the age group of 16 to 19 years. Similar trends were observed for the HUI3 values. Age, sex, household income, and education level had a significant influence on the values of both instruments. When measured with the EQ-5D-5L, Parkinson disease, dementia, and stroke were associated with the largest disutility (>0.2), and the disutility for depression was approximately 0.18. In contrast, the HUI3 disutility values for Parkinson disease and dementia were approximately 0.4.ConclusionsThis study established the Japanese population norms of the EQ-5D-5L and HUI3, which can be used in healthcare decision making and contribute to a more reliable analysis of economic evaluations.