Generic Preference-based Measures Research Articles

Cancer-Specific Health Utilities: Evaluation of Core Measurement Properties of the EORTC QLU-C10D in Lung Cancer Patients-Data from Four Multicentre LUX-Lung Trials, Applying Six Country Tariffs.

Cost-utility analysis generally requires valid preference-based measures (PBMs) to assess the utility of patient health. While generic PBMs are widely used, disease-specific PBMs may capture additional aspects of health relevant for certain patient populations. This study investigates the construct and concurrent criterion validity of the cancer-specific European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Utility-Core 10 dimensions (QLU-C10D) in non-small-cell lung cancer patients. We retrospectively analysed data from four multicentre LUX-Lung trials, all of which had administered the EORTC Quality of Life Questionnaire (QLQ-C30) and the EQ-5D-3L. We applied six country-specific value sets (Australia, Canada, Italy, the Netherlands, Poland, and the United Kingdom) to both instruments. Criterion validity was assessed via correlations between the instruments' utility scores. Correlations of divergent and convergent domains and Bland-Altman plots investigated construct validity. Floor and ceiling effects were assessed. The comparison of the EORTC QLU-C10D and EQ-5D-3L produced homogenous results for five of the six country tariffs. High correlations of utilities (r > 0.7) were found for all country tariffs except for the Netherlands. Moderate to high correlations of converging domain pairs (r from 0.472 to 0.718) were found with few exceptions, such as the Social Functioning-Usual Activities domain pair (max. r = 0.376). For all but the Dutch tariff, the EORTC QLU-C10D produced consistently lower utility values compared to the EQ-5D-3L (x̄ difference from -0.082 to 0.033). Floor and ceiling effects were consistently lower for the EORTC QLU-C10D (max. 4.67% for utilities). The six country tariffs showed good psychometric properties for the EORTC QLU-C10D in lung cancer patients. Criterion and construct validity was established. The QLU-C10D showed superior measurement precision towards the upper and lower end of the scale compared to the EQ-5D-3L, which is important when cost-utility analysis seeks to measure health change across the severity spectrum.

The EORTC QLU-C10D is a valid cancer-specific preference-based measure for cost-utility and health technology assessment in the Netherlands.

Cost-utility analysis typically relies on preference-based measures (PBMs). While generic PBMs are widely used, disease-specific PBMs can capture aspects relevant for certain patient populations. Here the EORTC QLU-C10D, a cancer-specific PBM based on the QLQ-C30, is validated using Dutch trial data with the EQ-5D-3L as a generic comparator measure. We retrospectively analysed data from four Dutch randomised controlled trials (RCTs) comprising the EORTC QLQ-C30 and the EQ-5D-3L. Respective Dutch value sets were applied. Correlations between the instruments were calculated for domains and index scores. Bland-Altman plots and intra-class correlations (ICC) displayed agreement between the measures. Independent and paired t-tests, effect sizes and relative validity indices were used to determine the instruments' performance in detecting clinically known-group differences and health changes over time. We analysed data from 602 cancer patients from four different trials. In overall, the EORTC QLU-C10D showed good relative validity with the EQ-5D-3L as a comparator (correlations of index scores r = 0.53-0.75, ICCs 0.686-0.808, conceptually similar domains showed higher correlations than dissimilar domains). Most importantly, it detected 63% of expected clinical group differences and 50% of changes over time in patients undergoing treatment. Both instruments showed poor performance in survivors. Detection rate and measurement efficiency were clearly higher for the QLU-C10D than for the EQ-5D-3L. The Dutch EORTC QLU-C10D showed good comparative validity in patients undergoing treatment. Our results underline the benefit that can be achieved by using a cancer-specific PBM for generating health utilities for cancer patients from a measurement perspective.

Psychometric Properties of the EQ-5D-Y-5L for Children With Intellectual Disability

ObjectivesThe EQ-5D-Y-5L is a generic preference-based measure of health-related quality of life for children. This study aimed to describe the distributional properties, test-retest reliability, and convergent validity of the EQ-5D-Y-5L in children with intellectual disability (ID). MethodsCaregivers of children with ID (aged 4 to 18 years) completed an online survey, including a proxy-report EQ-5D-Y-5L, the Quality-of-life Inventory-Disability, and disability-appropriate measures corresponding to the EQ-5D dimensions: mobility, self-care (SC), usual activities (UA), pain/discomfort (PD), and worry/sadness/unhappiness. Twenty-one participants repeated the EQ-5D-Y-5L a few weeks later. Test-retest reliability was computed using weighted kappa and intraclass correlation coefficients, and convergent validity using Spearman’s and Pearson’s correlation coefficients. ResultsCaregivers of 234 children completed the survey, with <1% missing values. Only 1.7% reported “no problems” on all dimensions (11111). The dimensions with the lowest percentage of “no problems” were SC and UA (both 8%). Test-retest reliability coefficients were fair to substantial for 4 dimensions (weighted kappa .30 to .79) but low for PD and overall health, as measured by the visual analog scale (EQ-VAS). Convergent validity was strong (Spearman’s correlation .65 to .87) for mobility, SC, and PD; moderate to strong for worry/sadness/unhappiness (.47 to .60) and the EQ-VAS (Pearson’s correlation .49); and weak to moderate for UA (.21 to .52). ConclusionsConvergent validity was generally good; test-retest reliability varied. Children with ID had lower scores on SC and UA than other populations, and their EQ-VAS could fluctuate greatly, indicating poorer and less stable health-related quality of life.

Psychometric performance of the CFQ-R-8D compared to the EQ-5D-3L and SF-6D in people with cystic fibrosis.

This study aimed to compare the psychometric performance of the Cystic Fibrosis Questionnaire-Revised-8 Dimensions (CFQ-R-8D), a new, condition-specific, preference-based measure, with that of generic preference-based measures EQ-5D-3L and Short Form 6 dimensions (SF-6D). Data from three trials of participants with CF aged ≥ 14 years who completed the CFQ-R and EQ-5D-3L or SF-6D were used. Analyses were undertaken to evaluate convergent validity based on correlations with CFQ-R domain scores. Known-group validity was assessed based on percent predicted forced expiratory volume in one second and pulmonary exacerbations. Responsiveness was based on correlation of change and sensitivity to change based on change in symptom severity. Effect sizes and standardized response means were estimated. CFQ-R-8D utilities and dimensions were strongly correlated with most of the overlapping CFQ-R domain scores (ρ > 0.5); EQ-5D-3L and SF-6D utilities and dimensions had moderate (ρ > 0.3) to strong correlations in dimensions capturing similar concepts. All measures showed evidence of known-group validity (P < 0.05). Change correlations were strong for CFQ-R-8D utilities and dimensions and CFQ-R, but they were moderate for SF-6D and mostly weak ((ρ > 0.1) for EQ-5D-3L. The SF-6D had the largest mean change over time and effect sizes, followed by CFQ-R-8D and then EQ-5D-3L. Neither CFQ-R-8D or SF-6D utility scores had ceiling effects (< 9% responses in full health) compared with those of EQ-5D-3L (61-62%). In participants classified as being in full health by EQ-5D-3L, CFQ-R-8D captured CF-specific health problems, particularly cough, abdominal pain, and breathing difficulty. The CFQ-R-8D reflected known-group differences and changes over time with stronger evidence of good psychometric performance than EQ-5D-3L and similar evidence as SF-6D. Additionally, the CFQ-R-8D captured more condition-specific symptoms than EQ-5D-3L or SF-6D, which are important determinants of health-related quality of life for people with CF.

Assessing the Content Validity of Preference-Based Measures in Cancer

ObjectivesThis study assessed the content validity of generic and condition-specific preference-based measures (PBMs) with patients treated for cancer, evaluated against 10 Consensus-Based Standards for the Selection of Health Measurement Instruments criteria for good content validity, to best inform measurement strategies regarding the use of PBMs in oncology development programs and real-world applications. MethodsIndividual, semistructured interviews were conducted with patients who received drug treatment for cancer in the United Kingdom (n = 47) and the United States (n = 49). During the interview, patients completed 3 generic PBMs (EQ-5D-5L, EuroQol Health and Wellbeing measure–Short Form, Château Santé Base) and 2 condition-specific PBMs (Quality of Life Utility-Core 10 Dimension, Functional Assessment of Cancer Therapy Eight Dimension [FACT-8D]). Interviews were conducted via teleconference, audio recorded, and transcribed verbatim. Transcripts were coded using thematic and content analysis methods. ResultsCondition-specific measures were evaluated as having better relevancy than generic PBMs. Overall, the FACT-8D was evaluated as holding the best content validity in terms of relevancy, and the EuroQol Health and Wellbeing measure–Short Form received the most favorable evaluation of relevancy for generic PBMs. All measures demonstrated comparable comprehensiveness, with all suggested by patients to be missing concepts. The EQ-5D-5L was evaluated best in terms of comprehensibility. This was followed by the Quality of Life Utility-Core 10 Dimension and FACT-8D; both received similar evaluations. ConclusionsAll measures were generally seen by patients as adequate in capturing appropriate aspects of health-related quality of life for measuring cancer outcomes, although together condition-specific measures were evaluated as having better relevancy than generic PBMs. Further health-related quality of life instrument development is encouraged, particularly with regard to the longer-term detrimental impacts of cancer and treatment side effects. Other developments could include new cancer-specific tools inclusive of conventional health items, treatment impacts, and psychological items.

Different Frameworks, Similar Results? Head-to-Head Comparison of the Generic Preference-Based Health-Outcome Measures CS-Base and EQ-5D-5L.

We compared two generic, preference-based health-outcome measures: the novel patient-centered Château-Santé Base (CS-Base), entailing a multi-attribute preference response framework, and the widely used EQ-5D-5L, regarding effects of different measurement frameworks and different descriptive systems. We conducted a cross-sectional study using a random sample of patients (3019 reached, 1988 included) in the USA with various health conditions. The CS-Base (12 attributes, each with four levels), EQ-5D-5L and the 5D-4L (an ad hoc, multi-attribute preference response-based measure that includes five attributes similar to the EQ-5D-5L, but with four levels) were used as health-outcome measures. We compared the proportions of problems reported on health attributes, statistical robustness and face validity of coefficients, attribute importance, differentiation between health states based on health-state values obtained with these measures, and user experience. All the CS-Base and 5D-4L coefficients had logical orders and significant differences from the reference level (p < 0.001). Substantial differences were observed in the CS-Base and 5D-4L coefficients between all levels on all attributes, while subtle differences were seen in those of the EQ-5D-5L. Attribute importance of usual (daily) activities were lowest or second lowest in all the three health-outcome measures. Attributes with the highest importance in the CS-Base, 5D-4L, and EQ-5D-5L were respectively mobility, anxiety/depression, and pain/discomfort. Four attributes are similar between the CS-Base and EQ-5D-5L, eight are exclusive to CS-Base. Of the eight, vision and hearing had the highest importance. Health-state values showed a smoother distribution with minimal discontinuity in the CS-Base and EQ-5D-5L than in the 5D-4L. In user experience evaluation, both CS-Base and the 5D-4L showed mean scores above 50 (indicating positive evaluation) in terms of the description of health and ease of understanding. This study demonstrated that CS-Base and 5D-4L, which are grounded in the multi-attribute preference response framework, produced statistically robust coefficients, with better face validity than those for the EQ-5D-5L. CS-Base and the EQ-5D-5L outperformed the 5D-4L in differentiating between health states. Notwithstanding differences in content, measurement frameworks, and estimated coefficients, the computed health-state values were similar between CS-Base and EQ-5D-5L.

Psychometric properties and comparison of four health utility approaches among myopia patients in China

BackgroundThe increased prevalence of myopia creates and earlier age of onset has created public health concerns for the long-term eye health, vision impairment and carries with it a significant economic burden. The quality of the economic evaluation is dependent on the sensitivity and validity of the approaches. Nowadays, there are many approaches to measure patients’ health state utility (HSU). However, little is known regarding the performance of direct approach and indirect approach in people with myopia. This study is aimed to compare the psychometric properties of four HSU approaches among patients with myopia in mainland China, including two direct approaches (TTO and SG), the generic preference-based measures (PBM) (AQoL-7D) and the disease-specific PBM (VFQ-UI).MethodsA convenience sampling framework was used to recruit patients with myopia who attended a large ophthalmic hospital in Jinan, China. Spearman’s rank correlations coefficient was used to assess concurrent validity. Known-group validity was analyzed by: (1) whether the patients wear corrective devices; (2) severity of myopia as low or moderate to high of the better eye; (3) duration of myopia as ≤ 10 years or > 10 years. Effect size (ES), relative efficiency (RE) statistic and the largest area under the receiver operating characteristic curve (AUC) were used to assess sensitivity. The intra-class correlation coefficient (ICC) and Bland–Altman plots were used to assess agreement.ResultsA valid sample size of 477 myopia patients was analyzed (median duration: 10 years). The mean HSU scores between TTO and SG were similar (0.95) and higher than AQoL-7D (0.89) and VFQ-UI (0.83). Overall, the VFQ-UI had the best performance based on the psychometric analysis. The agreement indicated that there was no pair of approaches that could be used interchangeably.ConclusionsThe VFQ-UI showed better psychometric properties than other three approaches for providing health state utility in Chinese myopia patients. Given the widespread use and its generic nature of the AQoL-7D, it could be used alongside with VFQ-UI to provide complementary health state utility from a generic and disease-specific perspective for economic evaluation. More evidence on the responsiveness of four health utility approaches in myopia patients is required.

EQ-5D and SF-6D health utility scores in patients with spinal and bulbar muscular atrophy.

This study assessed patient-reported health-related quality of life (HRQoL) using two generic preference-based measures in Chinese patients with spinal and bulbar muscular atrophy (SBMA) and identified demographic and clinical determinants of health utility scores in this population. This study used cross-sectional data of 212 Chinese patients with SBMA who completed both the EQ-5D and SF-6D. Association between response to EQ-5D and SF-6D dimensions was examined using Spearman's correlation coefficient, and the association between the two utility scores was assessed using Pearson's correlation coefficient. The variations in utility scores across patients in different subgroups were compared using one-way ANOVA. Bland-Altman (B-A) plot was used to assess the agreement of utility scores between EQ-5D and SF-6D. A multivariate Tobit regression model was employed to estimate the association between utility scores and the presence of symptoms and chronic conditions. The mean utility scores for the EQ-5D and SF-6D were 0.54 and 0.56, respectively. The hypothesized correlation between the EQ-5D and SF-6D dimensions ranged from 0.31 to 0.58, and the correlation between their utility scores was 0.64. An acceptable agreement between EQ-5D and SF-6D utility scores was identified by B-A plot. Patients with chronic diseases, misdiagnosis, high financial burden, and several clinical symptoms were highly likely to report a low health utility score. This study is the first to investigate the HRQoL of patients with SBMA worldwide. The estimated health utility scores for EQ-5D and SF-6D can be utilized as baseline data for future cost-utility analyses of SBMA-related interventions.

PMON260 Cost-Effectiveness of Testosterone Treatment for Men with Hypogonadism

Abstract Background Testosterone replacement therapy is the standard treatment for male hypogonadism (MH). Prescribing rates of testosterone in the UK have risen between 2001 and 2010 without an observable increase in the prevalence of hypogonadism, which may reflect increasing media awareness among men about hypogonadism. Currently, there is uncertainty about the safety and efficacy of testosterone treatment for MH, especially regarding its impact on cardiovascular risk, which has led to mandatory safety labelling in some countries. Aim We conducted an economic evaluation of testosterone therapy in men with hypogonadism, using individual patient data (IPD) of safety and efficacy outcomes in over 3000 participants as part of an international collaboration of investigators of 17 existing placebo-controlled RCTs assessing the safety and efficacy of testosterone treatment for MH (TestES Consortium). Methods A cost-utility analysis of the use of testosterone treatment for MH was conducted using a cohort Markov model developed following best practice. The model care pathway was informed by existing clinical guidelines, the results of the TestES Consortium individual patient data (IPD) meta-analysis, and discussions with clinical and methodological experts. Five Markov states were included: no complications, post-Cardiac pathology, post-Peripheral Vascular System Pathology, post-Cerebrovascular System Pathology, and Death. All-cause mortality, cardiovascular and cerebrovascular complications, and utility weights were obtained from the TestES IPD analyses. The UK NHS and personal and social services perspective was adopted for costs. Ten-year and lifetime time horizons were considered with costs and effects discounted annually at 3.5% rate. The model was run probabilistically using 10,000 Monte Carlo simulations. Three starting ages were defined (40, 60, and 75 years). Mean total cost, mean QALYs and incremental cost-effectiveness ratios were calculated. Results Cost-effectiveness of testosterone treatment appears to be dependent on the relative risk (RR) of all-cause mortality - favouring TRT - and the methods used to derive health state utility scores (i.e., SF-6D or a mapping between Beck Depression Inventory -BDI- score and EQ-5D score) for testosterone treatment versus standard care. When the RR of mortality and the BDI utilities were used, ICERs remained below the £20,000 ($27,400) UK conventional threshold, irrespective of the cohort starting age. However, ICERs increased above the £20,000 threshold when the difference in all-cause mortality was dropped, and the SF-6D utility scores were used. Conclusions We report the most in-depth economic analysis of male hypogonadism treatment to date. There remains limited data for generating preference-based health-related quality of life (HRQoL) weights for economic evaluation. Further clarity on the long-term cardiovascular safety of testosterone treatment in men with hypogonadism, and more in-depth mapping of clinical outcomes to generic preference-based measures of HRQoL will be crucial to inform robust estimates of the cost-effectiveness of testosterone treatment for MH. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Developing a New Region-Specific Preference-Based Measure in East and Southeast Asia

ObjectivesAlmost all preference-based measures (PBMs) have been developed in Western countries, with none having been formulated in Asian countries. In this study, we construct a new generic PBM based on concept elicitation using interview surveys in East and Southeast Asian countries and qualitative analysis. MethodsThis cross-sectional study included 225 adults recruited from 9 East and Southeast Asian countries or regions (Indonesia, Japan, Korea, mainland China, Malaysia, the Philippines, Singapore, Taiwan, and Thailand). Trained interviewers conducted semistructured interviews with 25 participants from the general population of each country/region. Qualitative data were analyzed using a content analysis approach. The selection of items was determined based on interview surveys and team member discussions. The description of items was considered based on a detailed qualitative analysis of the interview survey. ResultsA new region-specific PBM—the Asia PBM 7 dimensions instrument—was designed. It reflects East and Southeast Asian values and comprises 7 items: pain, mental health, energy, mobility, work/school, interpersonal interactions, and burden to others. ConclusionsThe new region-specific instrument is one of the first PBMs developed in the context of non-Western countries. The Asia PBM 7 dimensions contains 7 items that address the core concepts of health-related quality of life that are deemed important based on East and Southeast Asian health concepts.

Generic Health-Related Quality of Life Utility Measure for Preschool Children (Health Utilities Preschool): Design, Development, and Properties

ObjectivesHealth Utilities Preschool (HuPS) was developed to fill the need for a generic preference-based measure (GPM) applicable in early childhood. A GPM has all the properties for higher-order summary measures, such as quality-adjusted life-years, required to inform important policy decisions regarding health and healthcare services. MethodsDevelopment was in accordance with published standards for a GPM, statistical procedures, and modeling. HuPS incorporates key components of 2 existing measurement systems: Health Status Classification System for Preschool Children and Health Utilities Index Mark 3 (HUI3). The study included a series of 4 measurement surveys: definitional, adaptational, quantificational, and evaluational health-related quality of life (HRQL). HuPS measurements were evaluated for reliability, validity, interpretability, and acceptability. ResultsDefinitional measurements identified 8 Health Status Classification System for Preschool Children attributes in common with HUI3 (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain and discomfort), making the HUI3 scoring equation commensurate with HuPS health states. Adaptational measurements informed the content of attribute-level descriptions (n = 35). Quantificational measurements determined level scoring coefficients. HRQL scoring inter-rater reliability (intraclass correlation coefficient = 0.79) was excellent. Continuity of HRQL scoring with HUI3 was reliable (intraclass correlation coefficient = 0.80, P < .001) and valid (mean absolute difference = 0.016, P = .396). ConclusionsHuPS is an acceptable, reliable, and valid GPM. HRQL scoring is continuous with HUI3. Continuity expands the applicability of GPM (HUI3) scoring to include subjects as young as 2 years of age. Widespread applications of HuPS would inform important health policy and management decisions as HUI3 does for older subjects.

Are We Agreed? Self- Versus Proxy-Reporting of Paediatric Health-Related Quality of Life (HRQoL) Using Generic Preference-Based Measures: A Systematic Review and Meta-Analysis.

ObjectiveThe aim of this study was to examine the level of agreement between self- and proxy-reporting of health-related quality of life (HRQoL) in children (under 18 years of age) using generic preference-based measures.MethodsA systematic review of primary studies that reported agreement statistics for self and proxy assessments of overall and/or dimension-level paediatric HRQoL using generic preference-based measures was conducted. Where available, data on intraclass correlation coefficients (ICCs) were extracted to summarise overall agreement levels, and Cohen’s kappa was used to describe agreement across domains. A meta-analysis was also performed to synthesise studies and estimate the level of agreement between self- and proxy-reported paediatric overall and domain-level HRQoL.ResultsOf the 30 studies included, 25 reported inter-rater agreement for overall utilities, while 17 reported domain-specific agreement. Seven generic preference-based measures were identified as having been applied: Health Utilities Index (HUI) Mark 2 and 3, EQ-5D measures, Child Health Utility 9 Dimensions (CHU9D), and the Quality of Well-Being (QWB) scale. A total of 45 dyad samples were included, with a total pooled sample of 3084 children and 3300 proxies. Most of the identified studies reported a poor inter-rater agreement for the overall HRQoL using ICCs. In contrast to more observable HRQoL domains relating to physical health and functioning, the inter-rater agreement was low for psychosocial-related domains, e.g., ‘emotion’ and ‘cognition’ attributes of both HUI2 and HUI3, and ‘feeling worried, sad, or unhappy’ and ‘having pain or discomfort’ domains of the EQ-5D. Parents demonstrated a higher level of agreement with children relative to health professionals. Child self- and proxy-reports of HRQoL showed lower agreement in cancer-related studies than in non-cancer-related studies. The overall ICC from the meta-analysis was estimated to be 0.49 (95% confidence interval 0.34–0.61) with poor inter-rater agreement.ConclusionThis study provides evidence from a systematic review of studies reporting dyad assessments to demonstrate the discrepancies in inter-rater agreement between child and proxy reporting of overall and domain-level paediatric HRQoL using generic preference-based measures. Further research to drive the inclusion of children in self-reporting their own HRQoL wherever possible and limiting the reliance on proxy reporting of children’s HRQoL is warranted.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-022-01177-z.

China Health Related Outcomes Measures (CHROME): Development of a New Generic Preference-Based Measure for the Chinese Population.

Background and ObjectivesExisting generic preference-based measures were all developed in Western countries. Evidence shows that the Chinese population may have different perceptions about health and health-related quality of life. This study aimed at developing a descriptive system of a new generic preference-based measure under the initiative of China Health Related Outcomes Measures (CHROME).MethodsQualitative data were collected through semi-structured interviews conducted in-person or online. Respondents were recruited from both the general public and populations with chronic diseases. Open-ended questions about the respondent’s perception of general health and important aspects of health-related quality of life were asked. Probing questions based on a systematic review of existing generic preference-based measures were also used. The framework analysis was used to synthesize the qualitative data. Candidate items for the descriptive system were selected following the ISPOR and COSMIN guidelines. Expert panel review and cognitive debriefings were conducted for further revisions.ResultsQualitative interviews were conducted among 68 respondents, with 48.5% male and a mean age of 47.8 years (range 18–81 years). In total, 1558 codes were identified and then aggregated to 31 sub-themes and corresponding six themes to inform the development of the initial version of the descriptive system. Feedback from the expert panel survey and meeting (n = 15) and the cognitive debriefing interviews (n = 30) was incorporated into the revised version of the measure. Finally, the generic version of CHROME (CHROME-G) included 12 items across six domains, namely, pain, fatigue, appetite, mobility, vision, hearing, sleeping, daily activities, depression, worry, memory, and social interactions. The descriptive system used a mix of four-level and five-level response options and a 7-day recall period.ConclusionsThe CHROME-G is the first generic preference-based measure to be developed based on the inputs from the Chinese populations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-022-01151-9.

Using the EQ-5D to measure caregiver health-related quality of life in rare pediatric disease: a study in aromatic L-amino acid decarboxylase deficiency

Aims: To evaluate how well the EQ-5D-5L, a generic preference-based measure of health-related quality of life, captures caregiver burden in a rare pediatric neurotransmitter disease. Materials &amp; methods: Caregivers (n = 14) of individuals with aromatic L-amino acid decarboxylase (AADC) deficiency completed qualitative interviews on their experience as a caregiver, the EQ-5D-5L and a background questionnaire. Qualitative and quantitative data were compared to determine whether there was concordance or discordance in the findings. Results: No caregivers reported problems with mobility and self-care in either the qualitative interviews or on the EQ-5D-5L, and there was general concordance for pain/discomfort and anxiety/depression. However, discordance was found for usual activities, with 79% reporting no problems with this dimension on the EQ-5D-5L, compared with 100% describing substantial limitations during the interviews. Conclusion: The EQ-5D-5L may not be appropriate to evaluate caregiver burden in AADC deficiency, where caregivers' perceptions of “usual activities” differ substantially from the general population.

Assessment of the Relative Performance of the EQ-5D-3L, ICIQ-UI SF and POP-SS Using Data from the OPAL Trial.

Conducting economic evaluations alongside randomised controlled trials (RCTs) is an efficient way to collect cost-effectiveness data. Generic preference-based measures, such as EQ-5D, are often used alongside clinical data measures in RCTs. However, in the case of female urinary incontinence (UI), evidence of the relative performance of EQ-5D with condition-specific measures such as the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF), measuring severity of UI, and Pelvic Organ Prolapse Symptom Score (POP-SS), measuring severity of prolapse symptoms, is limited. This study employed secondary analysis of outcome measures data collected during the Optimal Pelvic floor muscle training for Adherence Long-term (OPAL) RCT, which compared biofeedback-mediated pelvic floor muscle training to basic pelvic floor muscle training for women with UI. The relative performance of EQ-5D-3L and ICIQ-UI SF, and EQ-5D-3L and POP-SS was assessed for concurrent validity and known-groups validity. Data for 577 women (mean age 48) were available for EQ-5D-3L/ICIQ-UI SF, and 555 women (mean age 47) for EQ-5D-3L/POP-SS. Overall, EQ-5D-3L exhibited very weak association with the ICIQ-UI SF total score, or any subscale. EQ-5D-3L and POP-SS were found to be weakly correlated. EQ-5D-3L was able to distinguish between groups with known differences in severity of UI and also between types of UI. These findings provide useful information to guide researchers in selecting appropriate outcome measures for use in future clinical trials.

Mapping naso-ocular symptom scores to EQ-5D-5L utility values in Japanese cedar pollinosis

BackgroundThe total naso-ocular symptom score (TSS) is widely used as an endpoint to evaluate the severity of seasonal allergic rhinitis. However, it is not a generic preference-based measure. We sought to develop an algorithm for mapping between the TSS and health utility in Japanese cedar pollinosis (JCP). We also performed a cost-utility analysis of sublingual immunotherapy (SLIT) for JCP by using this algorithm. MethodsPatients with JCP filled out the TSS questionnaire and EQ-5D-5L simultaneously during the pollen season in 2019 and in 2020. We estimated a direct utility mapping model by regressing responses to individual TSS questions directly onto utility. The incremental cost-effectiveness ratio (ICER) of active SLIT to a placebo was determined by examining the drug expense and the estimated quality-adjusted life year (QALY) using a dataset from a double-blind placebo-controlled clinical trial. ResultsA total of 238 records were included for analysis. The estimated utility decreased with increasing severity of rhinitis. Patients with comorbid asthma showed lower utility. A negative and significant correlation was seen between the TSS and utility in both 2019 and 2020. The estimated equations were: Y(utility) = −0.0161∗X(TSS) + 1.005 in non-asthmatic JCP patients. The ICER of active SLIT to the placebo was estimated to be 4,049,720 and 6,011,218 JPY/QALY in the first and second year, respectively. ConclusionsIt is possible to reasonably predict utility from the total naso-ocular symptom score by using regression models. In the estimated algorithm, pre-seasonal SLIT for JCP is cost-effective.

P-131: Use of the European Organisation for research and treatment of cancer quality of life Multiple Myeloma questionnaire (EORTC QLQ-MY20): a review of the literature 25 years after development

<h3>Background</h3> The EORTC QLQ-MY20 is a widely used myeloma-specific patient-reported outcome measure originally developed in 1999. It consists of 20 items covering Disease Symptoms (DS), Side Effects (SE), Future Perspectives (FP) and Body Image (BI). Novel treatments and multiple lines of therapy mean the treatment for myeloma patients and life expectancy has changed dramatically and there is a need to ensure the measurement of health-related quality of life remains current for these patients. The original validation study was almost exclusively in newly diagnosed patients reflecting the nature of clinical trials at the time. This review was conducted as part of an EORTC funded grant to update the QLQ-MY20, with the aim of summarising the published literature from the QLQ-MY20 to date including any further validation results for the QLQ-MY20. <h3>Methods</h3> Literature search was conducted using the Ovid SP platform (Medline, EMBASE and PsycINFO) from 1996 (first release of the questionnaire). Abstracts were included if they were reporting: a clinical study using the QLQ-MY20 or validation studies. Information about the study design was extracted alongside whether the population were newly diagnosed or relapsed, and the supplementary instruments used alongside the QLQ-MY20. For randomised control trials, information on the type of analysis and results were also extracted. For validation studies data on the instrument structure and data distribution, reliability, validity and ability to detect change/interpretation of change scores was extracted. <h3>Results</h3> 656 abstracts were screened to 74 included papers (65 clinical studies, of which 21 were interventional clinical trials, and 9 validation studies). Supplementary instruments used alongside QLQ-C30 and MY20 included BPI-SF (Brief pain inventory short form), EQ-5D-5L (generic preference-based measure), FACT-GOG-Ntx (neurotoxicity) and the EORTC QLQ-CIPN20 (chemotherapy induced peripheral neuropathy). In contrast with the original validation study, 34 out of 43 clinical studies included either exclusively relapsed patients (n=24) or a mix of newly diagnosed and relapsed (n=9). DS and SE were the most commonly reported results from the QLQ-MY20. Further validation studies supported the factor structure, reliability and validity, with the only potential issue being observed ceiling effects for the BI subscale. <h3>Conclusions</h3> The shift in HRQOL measurement to patients experiencing multiple lines of treatment and novel treatments, highlights the need for updating the conceptual model for the QLQ-MY20. Interviews are currently underway internationally with 90 patients and 20 healthcare professionals to identify the issues relevant to myeloma patients today. The current questionnaire has been shown to be psychometrically valid and can be supplemented in the interim using item banks or existing questionnaires to cover new side effects specific to novel treatments.

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 and Critical Evaluation of a Condition-Specific Preference-Based Measure Sensitive to Binaural Hearing in Adults: The York Binaural Hearing-Related Quality-of-Life System.

The widely-used generic preference-based measures of health-related quality of life-the EuroQol Descriptive System (EQ-5D) and the Health Utilities Index (HUI3)-are limited in their response to technologies that improve hearing. The EQ-5D lacks construct validity for hearing, while the HUI3 is restricted by a ceiling effect and by using speech reception as the only evidence of the ability to hear. Consequently, neither measure consistently registers benefits from binaural hearing, such as those from bilateral versus unilateral cochlear implantation. The objectives were to test whether informants value binaural hearing, to develop a condition-specific preference-based measure sensitive to binaural hearing, to assess the psychometric properties of the new instrument, and to determine whether it meets requirements for informing judgments of cost-effectiveness: does it measure greater gains than do the generic preference-based measures, while avoiding exaggerating losses, and displaying sensitivity to side effects? Three levels of function, ranging from no difficulty to great difficulty, were defined on each of three dimensions where listening is easier or more successful when hearing is binaural rather than monaural: perception of speech in spatially separated noise, localization of sounds, and effort and fatigue. Informants (N = 203) valued the 27 combinations of levels and dimensions in a time trade-off task with a 10-year time frame to provide a value of binaural-related quality of life ("binaural utility") for each combination. A questionnaire was compiled to allow respondents to report their level of function on each dimension so that a value of binaural utility could be assigned to them. The questionnaire and the age-standardized valuations constitute The York Binaural Hearing-Related Quality-of-Life System (YBHRQL). Adult users of unilateral implants (N = 8), bilateral implants (N = 11), or bimodal aiding (N = 9) undertook performance tests of spatial listening and completed the HUI3, EQ-5D, and Speech, Spatial, and Qualities of Hearing (SSQ) questionnaires. They completed the YBHRQL questionnaire 24 and 38 mo later. Despite long intervals between measurements, the YBHRQL demonstrated desirable psychometric properties: good construct validity evidenced by significant correlations with performance measures and the SSQ index; a greater ability than the EQ-5D or HUI3 to distinguish unilateral, bimodal, and bilateral listening; and good reproducibility. The YBHRQL did not exaggerate losses of utility but was insensitive to a potential side effect of implantation (pain/discomfort). It measured a gain in utility from bilateral compared with unilateral implantation (median = 0.11, interquartile range, 0.03 to 0.16) that was greater than the gain measured by the EQ-5D (0.00, 0.00 to 0.00) but not the HUI3 (0.00, 0.00 to 0.17). The YBHRQL summarizes the contribution of binaural hearing to quality of life by combining the functional status of a listener with the preferences of independent informants. It would be an efficient clinical outcome measure. In addition, if used alongside the EQ-5D or HUI3, it would provide evidence which could beneficially modulate confidence in the cost-effectiveness of interventions. Further research on its sensitivity to side effects, and on the size of the gains in utility which it measures, is needed to determine whether it could stand alone to inform resource-allocation decisions.

Measuring health-related quality of life and well-being: a head-to-head psychometric comparison of the EQ-5D-5L, ReQoL-UI and ICECAP-A.

ObjectiveThis study aimed to assess the psychometric properties of three generic preference-based measures and compare their performance in a sample of Hong Kong general population.MethodsData used for this analysis were obtained from a cross-sectional telephone-based survey in July 2020. Participants were asked to complete several measures, including The EuroQol five-dimensional five levels (EQ-5D-5L), Recovering Quality of Life-Utility Index (ReQoL-UI) and ICEpop CAPability measure for adults (ICECAP-A). Acceptability, reliability, convergent and discriminant validity of three measures were assessed as well as the agreement between these instruments.ResultsBased on data from 500 participants to the survey, a lower mean score of the ICECAP-A (mean = 0.85) was observed compared to the other two measures (meanReQoL-UI = 0.92; meanEQ-5D-5L = 0.92). All three measures showed an acceptable internal consistency reliability (Cronbach’s alpha = 0.74, 0.82 and 0.77, respectively) as well as good test–retest reliability (intra-class correlation coefficient = 0.74, 0.82 and 0.77, respectively). Correlation analyses confirmed satisfactory convergent validity and the ability of the measures to differentiate between participants with different health or from socioeconomic status groups. The Bland–Altman plot revealed poor agreement between the three measures.ConclusionsThis study confirmed that EQ-5D-5L, ReQoL-UI and ICECAP-A were psychometrically robust to measure HRQoL in the general HK population. The EQ-5D-5L was more suitable for assessing physical HRQoL, whereas the ICECAP-A and ReQoL-UI were more appropriate for measuring interventions aimed at improving people’s well-being and mental health.