A Qualitative Investigation to Develop an Adapted Version of the EQ-5D-Y-3L for Use in Children Aged 2-4 Years.

OBJECTIVES: Few preference-weighted health-related quality-of-life measures exist for children under 5 years of age. Young children are substantial consumers of healthcare services. This project aims to assess EQ-5D-Y-3L's appropriateness in children aged 2 to 4 years and to coproduce with parents a suitable adaptation. METHODS: Purposive sampling at the Murdoch Children's Research Institute and Royal Children's Hospital was used to recruit parents or carers of children aged 2 to 4 years in Australia. Online focus groups were conducted consisting of 13 parents of healthy children, and 6 parents of children with moderate to severe health conditions. Parents provided feedback on each dimension of the proxy EQ-5D-Y-3L. Recordings were transcribed and thematic analysis was conducted. Qualitative findings guided the design of adaptations to the instrument. The adaptations were piloted to obtain feedback and refined to improve language translatability and comparability with other EuroQol instruments. RESULTS: The adapted EQ-5D-Y-3L was considered generally acceptable by the parents. Parents provided a wide range of examples of how each domain related to their children, with varied examples provided across ages 2 to 4 years and health status. Additional or alternative wording was suggested by parents to improve the applicability of the instrument to this age group. One example of this was the change of the domain wording "walking about" to "movement"-ID5:"In this age group, movement is more important than walking." CONCLUSIONS: The adapted EQ-5D-Y-3L has improved relevance for 2-4-year olds and appears easy to complete. Further testing of the adapted instrument is required to evaluate acceptability, reliability, and validity.

A European, prospective, observational study of enzalutamide in patients with metastatic castration-resistant prostate cancer: PREMISE.

In randomized clinical trials, the androgen-receptor inhibitor enzalutamide has demonstrated efficacy and safety in metastatic castration-resistant prostate cancer (mCRPC). This study captured efficacy, safety and patient-reported outcomes (PROs) of enzalutamide in mCRPC patients in a real-world European setting. PREMISE (NCT0249574) was a European, long-term, prospective, observational study in mCRPC patients prescribed enzalutamide as part of standard clinical practice. Patients were categorized based on prior docetaxel and/or abiraterone use. The primary endpoint was time to treatment failure (TTF), defined as time from enzalutamide initiation to permanent treatment discontinuation for any reason. Secondary endpoints included prostate-specific antigen (PSA) response, time to PSA progression, time to disease progression and safety. PROs included EuroQol 5-Dimension, 5-Level questionnaire, Functional Assessment of Cancer Therapy-Prostate and Brief Pain Inventory-Short Form. Overall, 1732 men were enrolled. Median TTF with enzalutamide was 12.9 months in the chemotherapy- and abiraterone-naïve cohort (Cohort 1) and 8.4 months in the postchemotherapy and abiraterone-naïve cohort (Cohort 2). Clinical outcomes based on secondary endpoints also varied between cohorts. Cohorts 1 and 2 showed small improvements in health-related quality of life and pain status. The proportions of patients reporting treatment-emergent adverse events (TEAEs) were 51.0% and 62.2% in Cohorts 1 and 2, respectively; enzalutamide-related TEAEs were similar in both cohorts. The most frequent TEAE across cohorts was fatigue. These data from unselected mCRPC patients in European, real-world, clinical-practice settings confirmed the benefits of enzalutamide previously shown in clinical trial outcomes, with safety results consistent with enzalutamide's known safety profile.

Criteria for developing, assessing and selecting candidate EQ-5D bolt-ons.

PURPOSE: 'Bolt-on' dimensions are additional items added to multi-attribute utility instruments (MAUIs) such as EQ-5D that measure constructs not included in the core descriptive system. The use of bolt-ons has been proposed to improve the content validity and responsiveness of the descriptive system in certain settings and health conditions. EQ-5D bolt-ons serve a particular purpose and thus satisfy a certain set of criteria. The aim of this paper is to propose a set of criteria to guide the development, assessment and selection of candidate bolt-on descriptors. METHODS: Criteria were developed using an iterative approach. First, existing criteria were identified from the literature including those used to guide the development of MAUIs, the COSMIN checklist and reviews of existing bolt-ons. Second, processes used to develop bolt-ons based on qualitative and quantitative approaches were considered. The information from these two stages was formalised into draft development and selection criteria. These were reviewed by the project team and iteratively refined. RESULTS: Overall, 23 criteria for the development, assessment and selection of candidate bolt-ons were formulated. Development criteria focused on issues relating to i) structure, ii) language, and iii) consistency with the existing EQ-5D dimension structure. Assessment and selection criteria focused on face and content validity and classical psychometric indicators. CONCLUSION: The criteria generated can be used to guide the development of bolt-ons across different health areas. They can also be used to assess existing bolt-ons, and inform their inclusion in studies and patient groups where the EQ-5D may lack content validity.

Development of a United Kingdom-centric cost-effectiveness model for denture cleaning strategies.

STATEMENT OF PROBLEM: Denture stomatitis is a prevalent condition in denture wearers. Economic evaluations of health care can help stakeholders, including patients, make better decisions about treatments for a given condition. Economic models to assess the costs and benefits of different options for managing denture stomatitis are lacking. PURPOSE: The purpose of this study was to explore the feasibility of developing a cost-effectiveness model to assess denture cleaning strategies aimed at preventing denture stomatitis from a denture-wearer perspective in the United Kingdom. MATERIAL AND METHODS: A model was developed to identify and estimate the costs and effects associated with 3 denture cleaning strategies. These were low care (LC)-cleaning by brushing and soaking overnight in water; medium care (MC)-brushing with toothpaste and soaking overnight in water; and optimum care (OC)-brushing and soaking overnight in water and antimicrobial denture cleanser. Costs, outcome measures (denture stomatitis-free days), and probabilities (incidence of stomatitis, unscheduled dentist visits, prescription charges, self-medication) associated with each strategy were defined. A sensitivity analysis was used to identify key drivers and test the robustness of the model. RESULTS: The model showed that the total costs for 2015 ranged from £1.07 (LC) to £18.42 (OC). Costs associated with LC were derived from unscheduled dentist visits and use of medication and/or prescription charges. Incremental costs per denture stomatitis-free day were £0.64 (MC) and £1.81 (OC) compared with LC. A sensitivity analysis showed that varying either or both key parameters (baseline incidence of denture stomatitis and relative effectiveness of MC and OC strategies) had a substantial effect. Incremental cost-effectiveness ratios ranged from £4.11 to £7.39 (worst-case scenario) and from £0.21 to £0.61 (best-case scenario). CONCLUSIONS: A model was developed to assess the relative cost-effectiveness of different denture cleaning strategies to help improve denture hygiene. An important finding of the study was the lack of evidence on the relative effectiveness of different cleaning strategies, meaning that several assumptions had to be incorporated into the model. The model output would therefore likely be considerably improved and more robust if these evidence gaps were filled.

A note on the relationship between age and health-related quality of life assessment.

PURPOSE: To extend existing analyses of whether and how the age of respondents is related to their time trade-off (TTO) valuations of hypothetical EQ-5D-3L health states, and to contribute to the existing debate about the rationale and implications for using age-specific utilities in health technology assessment (HTA). METHODS: We use data from the MVH UK valuation study. For each profile, the mean TTO value-adjusted by sex, education, self-reported health and personal experience of serious illness-is pairwise compared across the different age groups. A Bonferroni correction is applied to the multiple testing of significant differences between means. Smile plots illustrate the results. A debate regarding whether there is a case for using age-specific utilities in HTAs complements the analysis. RESULTS: Results show that the oldest respondents value health profiles lower than younger age groups, particularly for profiles describing problems in the mobility dimension. CONCLUSION: The findings raise the possibility of using age-specific value sets in HTAs, since a technology may not be cost-effective on average but cost-effective for a sub-group whose preferences are more closely aligned to the benefits offered by the technology.

Using EQ-5D-3L and OAB-5D to assess changes in the health-related quality of life of men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

OBJECTIVES: To assess changes in the health status of men with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) using the EQ-5D-3L and OAB-5D instruments and to evaluate the sensitivity of the instruments. METHODS: Data were available from a large randomised phase III trial of men with moderate-to-severe storage and voiding LUTS/BPH (NEPTUNE). Men received a fixed-dose combination of solifenacin 6 mg plus oral controlled absorption system (OCAS™) formulation of tamsulosin (TOCAS, 0.4 mg), TOCAS monotherapy or placebo and completed the EQ-5D-3L and OAB-5D at baseline and weeks 4, 8 and 12. Analysis of covariance was used to estimate changes in EQ-5D-3L Index, EQ-VAS and OAB-5D. Changes in dimension level were summarised using the Paretian Classification of Health Change (PCHC). RESULTS: Improved health-related quality of life from baseline was seen in all treatment arms on EQ-5D-3L and OAB-5D at week 12, although only OAB-5D showed statistically significant differences between active treatment and placebo, both on the index score and using the PCHC approach. Effect sizes in the active treatment groups were large (>0.8) on OAB-5D but small (≈0.2) on EQ-5D-3L. EQ-5D-3L showed a very high ceiling effect (45% of men reported full health at baseline) and a substantial proportion of these men reported improvements at week 12 in several dimensions of OAB-5D. CONCLUSIONS: A large ceiling effect on EQ-5D-3L substantially limited its sensitivity in this population. OAB-5D proved more sensitive to changes in health status and could be considered a complement to ED-5D-3L as a source of utilities for health economic modelling.

An exploration of differences between Japan and two European countries in the self-reporting and valuation of pain and discomfort on the EQ-5D.

PURPOSE: To investigate the systematic differences in the self-reporting and valuation of overall health and, in particular, pain/discomfort between three countries (England/UK, Japan, and Spain) on the EQ-5D. METHODS: Existing datasets were used to explore differences in responses on the EQ-5D descriptive system between Japan (3L and 5L), the UK (3L), England (5L), and Spain (5L), particularly on the dimension of pain/discomfort. The role of different EQ dimensions in determining self-reported overall health scores for the EuroQol visual analog scale (EQ-VAS) was investigated using ordinary least squares regression. Time trade-off (TTO) results from Japanese and UK respondents for the EQ-5D-3L as well as Japanese and English respondents for the EQ-5D-5L were compared using t tests. RESULTS: For the EQ-5D-3L, a higher percentage of respondents in Japan than in the UK reported 'no pain/discomfort' (81.6 vs 67.0%, respectively); for the EQ-5D-5L, the proportions were 79.2% in Spain, 73.2% in Japan, and 63-64% in England, after adjusting for age differences in samples. The 'pain/discomfort' dimension had the largest impact on respondents' self-reported EQ-VAS only for EQ-5D-3L in Japan. Using the EQ-5D-3L, Japanese respondents were considerably less willing to trade off time to avoid pain/discomfort than the UK respondents; for example, moving from health state, 11121 (some problems with pain/discomfort) to 11131 (extreme pain/discomfort) represented a decrement of 0.65 on the observed TTO value in the UK compared with 0.15 in Japan. Using the EQ-5D-5L, Japanese respondents were also less willing to trade off time to avoid pain/discomfort than respondents in England; however, the difference in values was much smaller than that observed using EQ-5D-3L data. CONCLUSIONS: This study provides evidence of between-country differences in the self-reporting and valuation of health, including pain/discomfort, when using EQ-5D in general population samples. The results suggest a need for caution when comparing or aggregating EQ-5D self-reported data in multi-country studies.

Assessing the health of the general population in England: how do the three- and five-level versions of EQ-5D compare?

BACKGROUND: The EQ-5D is a brief, generic measure of health status that can be easily incorporated into population health surveys. There are two versions of the EQ-5D for use in adult populations, one with 3 response levels in each of the instrument's 5 dimensions (EQ-5D-3L) and one with 5 levels in each dimension (EQ-5D-5L). We compared the two versions as measures of self-reported health status in representative samples of the English general population. METHODS: EQ-5D-5L data were available from 996 respondents selected at random from residential postcodes who took part in the EQ-5D-5L value set for England study. EQ-5D-3L data were available from 7294 participants included in the 2012 Health Survey for England. Responses on the 3L and 5L versions of EQ-5D were compared by examining score distributions on the two versions, both in terms of the profile (dimensions) and the EQ-VAS. To determine the extent of variations in score according to respondent characteristics, we analysed health status reporting on the descriptive profile, EQ-5D Index, and EQ-VAS of both versions of EQ-5D by age, sex, and educational background. We used X (2) to test for differences between respondent categories when analyzing EQ-5D profile data and the t test when analyzing EQ-5D Index and VAS scores. RESULTS: The 5L version of EQ-5D led to a considerably reduced ceiling effect and a larger proportion of respondents reporting severe health problems compared to the 3L. The 5L version also led to the use of a wider spread of health states; just 3 health states on the 3L covered 75 % of the sample, compared to 12 states on the 5L. Both versions showed poorer health status in older respondents, females, and those in a lower educational category and the EQ-5D-5L descriptive system, though not the Index or VAS, discriminated better between age groups than the 3L. There were no appreciable differences between the two versions in their ability to discriminate between groups defined by gender or educational level. CONCLUSIONS: The new, expanded 5L version of EQ-5D may be a more useful instrument for the measurement of health status in population health surveys than the original 3L version.

A New Approach to Assessing Children's Interpretation of Severity Qualifiers in a Multi-Attribute Utility Instrument-The EQ-5D-Y-5L: Development and Testing.

INTRODUCTION: The beta EQ-5D-Y-5L is a new patient-reported outcome measure (PROM) for children aged 8-15 years that is currently under development by the EuroQol Group. The EQ-5D-Y-5L is similar to the EQ-5D-Y but has five levels of severity per dimension rather than three. The increased number of levels increases the granularity of the responses but possibly has also increased the difficulty of distinguishing between levels. The EuroQoL's Version Management Committee (VMC) required a robust method to determine how well children distinguish between the five EQ-5D-Y-5L ordinal severity qualifiers (i.e. 'no problems' through to 'extreme problems'), which are a critical aspect of both health measurement and the valuation of health states. OBJECTIVE: This paper describes the development, testing, selection, and piloting of such a method. METHODS: Following a literature review and consultation with the wider VMC and a Language Support Services agency, a range of exercises were developed to assess the ordering and comprehension of the five severity qualifiers. Three exercises were pre-tested with children in Spain and New Zealand. One exercise, preferred and understood by children, was then piloted. RESULTS: Five children in Spain and 11 in New Zealand tested the three exercises. In both countries, all children found the three exercises easy to understand and complete. Of the 12 children who expressed a preference, nine said they preferred the card ranking. Card ranking also allowed the interviewer to observe difficult choices being made as the children physically rearranged the card order until they settled on their final order. Following rigorous assessment of translatability and cultural portability by an independent Language Support Service, card ranking was piloted in South Africa (n = 9) and in Indonesia (n = 10), where it highlighted severity qualifier order inversions that would otherwise not have been detected. CONCLUSION: The card ranking exercise was found to be a preferred and acceptable means of testing the ordering of translations of severity qualifiers among children. Additional formal testing of the exercise in other countries and languages is now underway. The approach developed and tested by the VMC for cognitive debriefing of beta EQ-5D-Y-5L language/country versions may also be useful in determining the adequacy of translated qualifiers in debriefing of adult EQ-5D-5L versions and other PROMs.

Discriminative capacity of the EQ-5D, SF-6D, and SF-12 as measures of health status in population health survey.

PURPOSE: To compare the EQ-5D, SF-6D, and SF-12 in terms of their capacity to discriminate between groups defined by relevant socio-demographic and health characteristics in a general population survey. METHODS: Data were obtained from the 2006 Catalan Health Interview Survey, a representative sample (n = 4,319) of the general population of Catalonia (Spain). Effect sizes (ES) and Receiver Operating Characteristic (ROC) curves were calculated to evaluate the instruments' capacity to distinguish between groups based on socio-demographic variables, recent health problems, perceived health, psychological distress, and selected chronic conditions. RESULTS: All instruments showed a similar discriminative capacity between groups based on socio-demographic variables, recent medical visit (ES = 0.47-0.55), activity limitations (ES = 0.92-0.98), perceived health (ES = 0.97-1.33), and psychological well-being (ES = 1.17-1.57). Effect sizes between respondents with and without any of fourteen selected chronic conditions were large (0.76-1.04) for 4, moderate (0.55-0.74) for 8, and small (0.17-0.39) for two on the EQ-5D index. A similar pattern was observed for the SF-12 but ES were predominantly moderate (7 conditions) or small (6 conditions) on the SF-6D. CONCLUSIONS: The EQ-5D and SF-12 were largely comparable in estimating the health burden of chronic conditions, recent health problems, and social inequalities. The SF-6D was less sensitive than the EQ-5D index and SF-12, particularly for physical chronic conditions.

Principles and methodology for translation and cross-cultural adaptation of the Nordic Occupational Skin Questionnaire (NOSQ-2002) to Spanish and Catalan.

BACKGROUND: Occupational skin diseases are among the most frequent work-related diseases in industrialized countries. The Nordic Occupational Skin Questionnaire (NOSQ-2002), developed in English, is a useful tool for screening of occupational skin diseases. OBJECTIVES: To culturally adapt the NOSQ-2002 to Spanish and Catalan and to assess the clarity, comprehension, cultural relevance and appropriateness of the translated versions. METHODS: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) principles of good practice for the translation and cultural adaptation of patient-reported outcomes were followed. RESULTS: After translation into the target language, a first consensus version of the questionnaire was evaluated in multiple cognitive debriefing interviews. The expert panel introduced some modifications in 39 (68%) and 27 (47%) items in the Spanish and Catalan version, respectively (e.g. addition of examples and definitions, reformulation of instructions and use of direct question format). This version was back translated and submitted to the original authors, who suggested a further seven and two modifications in the Spanish and Catalan versions, respectively. A second set of cognitive interviews were performed. A consensus version of both questionnaires was obtained after final modifications based on comments by the patients. CONCLUSIONS: The final versions of the Spanish and Catalan NOSQ-2002 questionnaires are now available at www.NRCWE.dk/NOSQ.

Assessing Preference-Based Outcome Measures for Overactive Bladder: An Evaluation of Patient-Reported Outcome Data from the BESIDE Clinical Trial.

OBJECTIVES: The aim of this study was to compare outcomes using two preference-based measures of health status (EQ-5D-5L and OAB-5D) in patients with overactive bladder (OAB) treated with solifenacin plus mirabegron or solifenacin monotherapy in the BESIDE trial. METHODS: Patients with OAB who remained incontinent after 4 weeks' treatment with solifenacin 5 mg were randomized 1:1:1 to combination treatment (solifenacin 5 mg plus mirabegron [25 mg for the first 4 weeks/50 mg for the last 8 weeks]), solifenacin 5 mg, or solifenacin 10 mg. EQ-5D-5L and OAB-q were administered at baseline, weeks 4, 8, 12, and end of treatment (EoT). OAB-5D scores were derived from OAB-q results. Responder analysis was carried out using several definitions of minimally important difference. RESULTS: A total of 2054 patients received one or more doses of study treatment (combination, n = 694; solifenacin 5 mg, n = 684; solifenacin 10 mg, n = 676). EQ-5D-5L Index mean score changes (from baseline to EoT) were greater with combination (0.059) than with solifenacin 5 mg (0.040) and 10 mg (0.044) monotherapy, but the differences were not statistically significant. A significantly greater improvement was observed for combination on OAB-5D (0.107 vs 0.085 for 5 mg, and 0.087 for 10 mg; p ≤ 0.01). The dimensions most improved overall were anxiety/depression, pain/discomfort, and usual activities on EQ-5D-5L, and urge, urine loss, and coping on OAB-5D. The proportion of responders was significantly greater with combination compared with monotherapy using OAB-5D only. CONCLUSIONS: Improvements were observed in all study arms on both the EQ-5D-5L and OAB-5D, although only the OAB-5D showed a statistically significant benefit for combination versus solifenacin monotherapy. Combining generic and condition-specific preference-based health status measures allowed for assessment of dimensions that were particularly relevant to this patient population, while permitting comparison with outcomes from other studies, treatments, and populations via EQ-5D.

Valid screening questions useful to diagnose hand and forearm eczema are available in the Spanish language, a new tool for global research.

UNLABELLED: Hand eczema is an impacting cutaneous disease. Globally valid tools that help to diagnose hand and forearm eczema are required. OBJECTIVE: To validate the questions to detect hand and/or forearm eczema included in the "Nordic Occupational Skin Questionnaire" (NOSQ-2002) in the Spanish language. MATERIALS AND METHODS: A prospective pilot study was conducted with 80 employees of a cleaning company and a retrospective one involving 2,546 individuals. The responses were analysed for sensitivity, specificity and positive and negative predictive values. The final diagnosis according to the patients' hospital records, the specialty care records and the physical examination was taken as gold standard. The Dermatology Life Quality Index (DLQI) was also evaluated. RESULTS: Sensitivity and specificity, in a worst case scenario (WC) combining both questions, were 96.5% and 66.7%, respectively, and in a per protocol (PP) analysis, were 96.5% and 75.2%. CONCLUSION: The questions validated detected eczema effectively, making this tool suitable for use e.g. in multicentre epidemiological studies or clinical trials.

Being bullied: associated factors in children and adolescents 8 to 18 years old in 11 European countries.

OBJECTIVES: To analyze the prevalence of bullying victims among children and adolescents aged 8 to 18 years in 11 European countries and to investigate the associated sociodemographic, physical, and psychosocial factors. METHODS: Being a bullying victim was measured by using the social acceptance (bullying) scale from the Kidscreen-52, a health-related quality-of-life questionnaire administered to 16 210 children and adolescents aged 8 to 18 and their parents in postal or school-based surveys in 11 European countries. Standardized mean differences (effect size) were computed to measure the percentage of children/adolescents scoring 1 SD below the mean on the Kidscreen bullying scale. Logistic regression models were used to determine which sociodemographic, physical, and psychosocial factors were associated with being bullied. RESULTS: The percentage of children being bullied was 20.6% for the entire sample, ranging from 10.5% in Hungary to 29.6% in the United Kingdom. In almost all countries the factors most strongly associated with being bullied were younger age, having probable mental health problems, having a low score on the Kidscreen-52 moods and emotions dimensions, and poor social support. Using the grand mean for all countries as the reference category, there was an above-average likelihood of children or adolescents reporting that they had been victims of bullying in 5 countries (Austria, Netherlands, Spain, Switzerland, and the United Kingdom), and a below-average likelihood in 3 countries (France, Greece, Hungary). CONCLUSIONS: This study indicated considerable variation between countries in the prevalence of those perceiving themselves to be victims of bullying but also revealed a clear profile of those likely to be bullied. The study also suggests that the Kidscreen bullying scale could be useful in identifying potential bullying victims.