To what extent does the use of crosswalks instead of EQ-5D value sets impact reimbursement decisions?: a simulation study.

PURPOSE: Inconsistent results have been found on the impact of using crosswalks versus EQ-5D value sets on reimbursement decisions. We sought to further investigate this issue in a simulation study. METHODS: Trial-based economic evaluation data were simulated for different conditions (depression, low back pain, osteoarthritis, cancer), severity levels (mild, moderate, severe), and effect sizes (small, medium, large). For all 36 scenarios, utilities were calculated using 3L and 5L value sets and crosswalks (3L to 5L and 5L to 3L crosswalks) for the Netherlands, the United States, and Japan. Utilities, quality-adjusted life years (QALYs), incremental QALYs, incremental cost-effectiveness ratios (ICERs), and probabilities of cost-effectiveness (pCE) obtained from values sets and crosswalks were compared. RESULTS: Differences between value sets and crosswalks ranged from -0.33 to 0.13 for utilities, from -0.18 to 0.13 for QALYs, and from -0.01 to 0.08 for incremental QALYs, resulting in different ICERs. For small effect sizes, at a willingness-to-pay of €20,000/QALY, the largest pCE difference was found for moderate cancer between the Japanese 5L value set and 5L to 3L crosswalk (difference = 0.63). For medium effect sizes, the largest difference was found for mild cancer between the Japanese 3L value set and 3L to 5L crosswalk (difference = 0.06). For large effect sizes, the largest difference was found for mild osteoarthritis between the Japanese 3L value set and 3L to 5L crosswalk (difference = 0.08). CONCLUSION: The use of crosswalks instead of EQ-5D value sets can impact cost-utility outcomes to such an extent that this may influence reimbursement decisions.

Value Set for the EQ-5D-Y-3L in Hungary.

BACKGROUND: The Hungarian health technology assessment guidelines recommend the use of the EuroQol instrument family in quality-adjusted life-year calculations. However, no national value set exists for the EQ-5D-Y-3L or any other youth-specific instrument. OBJECTIVE: This study aims to develop a national value set of the EQ-5D-Y-3L for Hungary based on preferences of the general adult population. METHODS: This study followed the international valuation protocol for the EQ-5D-Y-3L. Two independent samples, representative of the Hungarian general adult population in terms of age and sex were recruited to complete online discrete choice experiment (DCE) tasks and composite time trade-off (cTTO) tasks by computer-assisted personal interviews. Adults valued hypothetical EQ-5D-Y-3L health states considering the health of a 10-year-old child. DCE data were modelled using a mixed logit model with random-correlated coefficients. Latent DCE utility estimates were mapped onto mean observed cTTO utilities using ordinary least squares regression. RESULTS: Overall, 996 and 200 respondents completed the DCE and cTTO surveys, respectively. For each domain, the value set resulted in larger utility decrements with more severe response levels. The relative importance of domains by level 3 coefficients was as follows: having pain or discomfort > feeling worried, sad or unhappy > mobility > doing usual activities > looking after myself. Overall, 12.3% of all health states had negative utilities in the value set, with the worst health state having the lowest predicted utility of - 0.485. CONCLUSION: This study developed a national value set of the EQ-5D-Y-3L for Hungary. The value set enables to evaluate the cost utility of health technologies for children and adolescents based on societal preferences in Hungary.

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

OBJECTIVES: This 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. METHODS: A 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. RESULTS: A 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. CONCLUSIONS: This 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.

Estimation of an EORTC QLU-C10 Value Set for Spain Using a Discrete Choice Experiment.

BACKGROUND: The EORTC QLU-C10D is a preference-based measure derived from the EORTC QLQ-C30. For use in economic evaluations, country-specific value sets are needed. This study aimed to generate an EORTC QLU-C10 value set for Spain. METHODS: A sample of the Spanish general population completed an online discrete choice experiment. An attribute-balanced incomplete block design was used to select 960 choice tasks, with a total of 1920 health states. Each participant was randomly assigned 16 choice sets without replacement. Data were modelled using generalized estimating equations and mixed logistic regressions. RESULTS: A total of 1625 panel members were invited to participate, 1010 of whom were included in the study. Dimension decrements were generally monotonic with larger disutilities at increased severity levels. Dimensions associated with larger decrements were physical functioning and pain, while the dimension with the smallest decrement was sleep disturbances. The PITS state (i.e. worst attainable health) for the Spanish population is - 0.043. CONCLUSIONS: This study generated the first Spanish value set for the QLU-C10D. This can facilitate cost-utility analyses when applied to data collected with the EORTC QLQ-C30.

Methods Used to Identify, Test, and Assess Impact on Preferences of Bolt-Ons: A Systematic Review.

OBJECTIVES: The question of whether additional dimensions should be added to the EQ-5D, so-called bolt-ons, has been researched since the 1990s. Several candidate bolt-ons have been tested. The aim of this systematic review was to provide an overview of EQ-5D bolt-on studies, including the origin of possible suitable bolt-ons, their format, and methods that were used to examine their value. METHODS: Studies were identified through database search and reference screening and assessed based on a set of inclusion criteria. All studies that investigated bolt-ons for the EQ-5D were eligible for inclusion. Two reviewers independently extracted information from all included studies on objectives, study design, EQ-5D version used, the investigated bolt-ons, methods used to achieve objectives, and outcomes. RESULTS: Of 308 initially identified studies, 28 studies met the inclusion criteria. Of these studies, 3 identified potentially suitable bolt-on dimensions, 13 investigated the psychometric performance of EQ-5D + bolt-on(s), and 6 investigated the impact of the bolt-on on health state preferences. In total, 26 bolt-ons were identified, of which cognition was the most frequently mentioned. A wide variety of bolt-on identification methods, psychometric performance tests, and health state valuation methods were used in the included studies. CONCLUSION: A range of bolt-on dimensions has been investigated using diverse methods. Guidelines are needed to standardize the wording of the bolt-on dimension and response options, evaluate minimal important gain of the bolt-on, and facilitate quality assessment of bolt-on studies. Subsequently, guidelines will facilitate decision making on whether or not to implement a bolt-on dimension to the EQ-5D.

The EQ-5D-5L Valuation Study in Egypt.

INTRODUCTION: No value sets exist for either the EQ-5D-3L or the EQ-5D-5L in Egypt, despite local pharmacoeconomic guidelines recommending the use of the EQ-5D to derive utility. Most published Egyptian economic evaluation studies have used utility values from other published studies and systematic reviews. OBJECTIVE: Our objective was to develop an Egyptian EQ-5D-5L value set using the international EuroQol standardized protocol (EQ-VT-2.1). METHODS: Adult Egyptian participants were recruited from public places using multi-stratified quota sampling based on age, sex, and geographical distribution. Two elicitation techniques were applied: the composite time trade-off (cTTO) and discrete-choice experiments (DCEs). Before actual data collection, interviewers' performance was assessed in a pilot phase. Data were modelled using generalized least square, Tobit, heteroskedastic, logit, and hybrid models, and the best fitting model was selected based on the value range between observed and predicted values, logical consistency of the parameters, significance level, and prediction accuracy. RESULTS: A total of 1378 interviews were conducted, of which 188 were excluded because they were incomplete or did not comply with protocol, 216 were pilot interviews, and 974 were included in the final analysis. The heteroskedastic model (model 4) based on the cTTO data was selected as the preferred model to generate the value set. Values ranged from - 0.93 for the worst health state (55555) to 1 for full health (11111), with 1136 (36.3%) of all predicted health states being worse than dead. Mobility had the largest impact on health state preference values. CONCLUSION: This is the first value set for the EQ-5D-5L based on social preferences obtained from a nationally representative sample in Egypt or any Arabic-speaking country. The value set can be used as a scoring system for economic evaluations and to improve the quality of health technology assessment in the Egyptian healthcare system.

Comparing the EQ-5D-5L crosswalks and value sets for England, the Netherlands and Spain: Exploring their impact on cost-utility results.

This study compares the five-level EuroQol five-dimension questionnaire (EQ-5D-5L) crosswalks and the 5L value sets for England, the Netherlands, and Spain and explores the implication of using one or the other for the results of cost-utility analyses. Data from two randomized controlled trials in depression and diabetes were used. Utility value distributions were compared, and mean differences in utility values between the EQ-5D-5L crosswalk and the 5L value set were described by country. Quality-adjusted life years (QALYs) were calculated using the area-under-the-curve method. Incremental cost-effectiveness ratios (ICERs) were calculated, and uncertainty around ICERs was estimated using bootstrapping and graphically shown in cost-effectiveness acceptability curves. For all countries investigated, utility value distributions differed between the EQ-5D-5L crosswalk and 5L value set. In both case studies, mean utility values were lower for the EQ-5D-5L crosswalk compared with the 5L value set in England and Spain, but higher in the Netherlands. However, these differences in utility values did not translate into relevant differences across utility estimation methods in incremental QALYs and the interventions' probability of cost-effectiveness. Thus, our results suggest that EQ-5D-5L crosswalks and 5L value sets can be used interchangeably in patients affected by mild or moderate conditions. Further research is needed to establish whether these findings are generalizable to economic evaluations among severely ill patients.

Selecting Bolt-On Dimensions for the EQ-5D: Examining Their Contribution to Health-Related Quality of Life.

BACKGROUND: Generic preference-based measures may miss dimensions important for the health-related quality of life (HRQOL) of patients. When this happens, a possible solution is to add bolt-ons. Finch et al. (Finch AP, Brazier JE, Mukuria C, Bjorner JB. An exploratory study on using principal component analysis and confirmatory factor analysis to identify bolt-on dimensions: the EQ-5D case study. Value Health 2017;10:1362-75) have recently shown that bolt-ons can be systematically identified using factor analysis. Nevertheless, because for each bolt-on option a complete re-evaluation may be required, methods to select between them are needed. OBJECTIVES: To investigate the possibility of selecting bolt-ons using their ability to predict differences in HRQOL. It tests six factors (energy/vitality, satisfaction, relationships, hearing, vision, and speech), and 37 items loading on them, using the EuroQol five-dimensional questionnaire as a case study. METHODS: Data were obtained from the Multi-Instrument Comparison study, an online survey on health and well-being measures carried out in six countries. Two tests were performed. In the first test, linear regressions were fitted to determine whether different bolt-ons helped explain variations in HRQOL as measured by the Health visual analogue scale. The upper anchor (100) of this scale represents excellent physical, mental, and social health, and the lower anchor (0) represents death. Bolt-on relevance was judged comparing the strength, direction, and statistical significance of unadjusted ß coefficients. In the second test, linear regressions were fitted to further investigate whether different factors and items helped explain the negative effect of six chronic conditions on HRQOL. A reduction in the coefficients for the chronic condition dummies meant that the factor or item detected the effect. RESULTS: Energy/vitality, relationships, and satisfaction reported substantially larger coefficients than did speech, vision, and hearing. Also, items loading on energy/vitality, relationships, and satisfaction generally presented larger coefficients than did those loading on speech, vision, and hearing. The second test did not detect consistent decrements in the coefficients for chronic conditions when testing factors, but it generally did detect consistent decrements when testing items. CONCLUSIONS: The first test appeared useful for bolt-on selection. Further research is needed before using the second test.

Doxycycline Added to Prednisolone in Outpatient-Treated Acute Exacerbations of COPD: A Cost-Effectiveness Analysis Alongside a Randomised Controlled Trial.

BACKGROUND: Most patients with mild to severe chronic obstructive pulmonary disease (COPD) experience exacerbations, which are also associated with increased healthcare costs. Despite limited evidence of antibiotics' benefits for exacerbations in outpatients, antibiotics are frequently prescribed. The aim of this study was to investigate whether doxycycline added to prednisolone is cost-effective compared to placebo plus prednisolone for the treatment of COPD acute exacerbations. METHODS: An economic evaluation from the societal perspective was performed alongside a 2-year randomised trial in 301 COPD patients in the Netherlands. The primary outcome was cost per quality-adjusted life year (QALY). The secondary outcome was cost per exacerbation prevented. Healthcare utilisation and loss of productivity were measured using retrospective questionnaires and clinical report forms. Missing data were imputed using multiple imputations by chained equations. Bootstrapping was employed to estimate statistical uncertainty surrounding cost-effectiveness outcomes. A sensitivity analysis from the healthcare perspective was performed. RESULTS: On average, costs in the doxycycline group were €898 higher than in the placebo group [95% confidence interval (CI) - 2617 to 4409] for the 2 years of follow-up. QALY values were higher in the doxycycline group (0.03; 95% CI - 0.00 to 0.06), but patients in this group suffered 0.01 more exacerbations than patients in the placebo group (95% CI - 0.14 to 0.11). Cost-effectiveness acceptability curves showed that the probability of doxycycline being cost-effective compared to placebo was 61% and 43% at a willingness-to-pay threshold of €34,000 per QALY and per exacerbation avoided, respectively. The sensitivity analysis showed similar results from the healthcare system perspective. CONCLUSIONS: In patients with mild to severe COPD treated for exacerbations in an outpatient setting, doxycycline added to prednisolone is not cost-effective compared to prednisolone plus placebo over a 2-year period.

An Exploratory Study on Using Principal-Component Analysis and Confirmatory Factor Analysis to Identify Bolt-On Dimensions: The EQ-5D Case Study.

OBJECTIVE: Generic preference-based measures such as the EuroQol five-dimensional questionnaire (EQ-5D) are used in economic evaluation, but may not be appropriate for all conditions. When this happens, a possible solution is adding bolt-ons to expand their descriptive systems. Using review-based methods, studies published to date claimed the relevance of bolt-ons in the presence of poor psychometric results. This approach does not identify the specific dimensions missing from the Generic preference-based measure core descriptive system, and is inappropriate for identifying dimensions that might improve the measure generically. This study explores the use of principal-component analysis (PCA) and confirmatory factor analysis (CFA) for bolt-on identification in the EQ-5D. METHODS: Data were drawn from the international Multi-Instrument Comparison study, which is an online survey on health and well-being measures in five countries. Analysis was based on a pool of 92 items from nine instruments. Initial content analysis provided a theoretical framework for PCA results interpretation and CFA model development. PCA was used to investigate the underlining dimensional structure and whether EQ-5D items were represented in the identified constructs. CFA was used to confirm the structure. CFA was cross-validated in random halves of the sample. RESULTS: PCA suggested a nine-component solution, which was confirmed by CFA. This included psychological symptoms, physical functioning, and pain, which were covered by the EQ-5D, and satisfaction, speech/cognition,relationships, hearing, vision, and energy/sleep which were not. These latter factors may represent relevant candidate bolt-ons. CONCLUSIONS: PCA and CFA appear useful methods for identifying potential bolt-ons dimensions for an instrument such as the EQ-5D.

Generic Preference-based Measures for Low Back Pain: Which of Them Should Be Used?

STUDY DESIGN: Systematic review. OBJECTIVE: This systematic review examines validity and responsiveness of three generic preference-based measures in patients with low back pain (LBP). SUMMARY OF BACKGROUND DATA: LBP is a very common incapacitating disease with a significant impact on health-related quality of life (HRQoL). Health state utility values can be derived from various preference-based HRQoL instruments, and among them the most widely ones are EuroQol 5 dimensions (EQ-5D), Short Form 6 Dimensions (SF-6D), and Health Utilities Index 3 (HUI III). The ability of these instruments to reflect HRQoL has been tested in various contexts, but never for LBP populations. METHODS: A systematic search on electronic literature databases was undertaken to identify studies of patients with LBP where health state utility values were reported. Records were screened using a set of predefined eligibility criteria. Data on validity (correlations and known group methods) and responsiveness (effect sizes, standardized response means, tests of statistical significance) of instruments were extracted using a customized extraction template, and assessed using predefined criteria. RESULTS: There were substantial variations in the 37 included papers identified in relation to study design and outcome measures used. EQ-5D demonstrated good convergent validity, as it was able to distinguish between known groups. EQ-5D was also able to capture changes of health states as results of different interventions. Evidence for SF-6D and HUI III was limited to allow an appropriate evaluation. CONCLUSION: EQ-5D performs well in LBP population and its scores seem to be suitable for economic evaluation of LBP interventions. However, the paucity of information on the other instruments makes it impossible to determine its relative validity and responsiveness compared with them.