Validity and responsiveness of EQ-5D-Y in children with haematological malignancies and their caregivers.

The psychometric properties of the EQ-5D-Y have not been widely tested in severely ill children. The aim of this study was to assess and compare the validity and responsiveness of the EQ-5D-Y-3L and EQ-5D-Y-5L in paediatric inpatients with haematological malignancies and caregivers. Respondents completed the interviewer-administered self-complete or proxy version of the EQ-5D-Y-3L and EQ-5D-Y-5L and an overall health assessment twice on different days. Known-groups validity was assessed by comparing patients who differed in overall health and Eastern Cooperative Oncology Group (ECOG) performance. Responsiveness to worsened health was assessed using standardised effect size (SES) for patients with worsened ECOG grade, self-reported rating, or chemotherapy initiation. Ninety-six dyads completed the baseline questionnaires. A smaller proportion of patients reported "no problems" on the EQ-5D-Y-5L compared to EQ-5D-Y-3L for most of the five dimensions. Patients in poor health reported more problems in all dimensions and had higher EQ-5D-Y-5L level sum score, lower EQ VAS and EQ-5D-Y-3L index scores (Cohen's d ES: 0.32-1.38 for patients; 0.50-2.05 for caregivers). There was a mild to good responsiveness to worsened health condition based on ECOG (SES: 0.14-0.61 for patients; 0.40-0.96 for caregivers), suggesting the proxy version was slightly responsive than the self-complete version of both instruments. The results demonstrated validity and responsiveness for both the self-complete and proxy versions of the EQ-5D-Y-3L and EQ-5D-Y-5L. The proxy and 5-level versions of the instrument were more sensitive than the self-complete and 3-level versions in this patient group.

Psychometric Performance Comparison of the Adapted versus Original Versions of the EQ-5D-Y-3L and -Y-5L in Proxy Respondents for 2- to 4-Year-Olds.

INTRODUCTION: Few preference-weighted instruments are available to measure health-related quality of life in young children (2-4 years of age). The EQ-5D-Y-3L and EQ-5D-Y-5L were recently modified for this purpose. OBJECTIVE: The aim of this study was to test the psychometric properties of these adapted versions for use with parent proxies of children aged 2-4 years and to compare their performance with the original versions. It was hypothesised that the adapted instrument wording would result in improved psychometric performance. METHODS: Survey data of children aged 2-4 years were obtained from the Australian Paediatric Multi-Instrument Comparison study. Distributional and psychometric properties tested included feasibility, convergence, distribution of level scores, ceiling effects, known-group validity (Cohen's D effect sizes for prespecified groups defined by the presence/absence of special healthcare needs [SHCNs]), test-retest reliability (intraclass correlation coefficients [ICCs]), and responsiveness (standardised response mean [SRM] effect sizes for changes in health). Level sum scores were used to provide summary outcomes. Supplementary analysis using utility scores (from the Swedish EQ-5D-Y-3L value set) were conducted for the adapted and original EQ-5D-Y-3L, and no value sets were available for the EQ-5D-Y-5L. RESULTS: A total of 842 parents of children aged 2-4 years completed the survey. All instruments were easy to complete. There was strong convergence between the adapted and original EQ-5D-Y-3L and EQ-5D-Y-5L. The adapted EQ-5D-Y-3L and adapted EQ-5D-Y-5L showed more responses in the severe levels of the five EQ-5D-Y dimensions, particularly in the usual activity and mobility dimensions (EQ-5D-Y-5L: mobility level 1: adapted n = 478 [83%], original n = 253 [94%]; mobility level 4/5: adapted n = 17 [2.9%], original n = 4 [1.5%)]). The difference in the distribution of responses was more evident in children with SHCNs. Assessment of known-group validity showed a greater effect size for the adapted EQ-5D-Y-3L and adapted EQ-5D-Y-5L compared with the original instruments (EQ-5D-Y-5L: adapted Cohen's D = 1.01, original Cohen's D = 0.83) between children with and without SHCNs. The adapted EQ-5D-Y-3L and adapted EQ-5D-Y-5L showed improved reliability at 4-week follow-up, with improved ICCs (EQ-5D-Y-5L: adapted ICC = 0.83, original ICC = 0.44). The responsiveness of all instruments moved in the hypothesised direction for better or worse health at follow-up. Probability of superiority analysis showed little/no differences between the adapted and original EQ-5D-Y-3L and EQ-5D-Y-5L. Supplementary psychometric analysis of the adapted and original EQ-5D-Y-3L using utilities showed comparable findings with analyses using level sum scores. CONCLUSIONS: The findings suggest improved psychometric performance of the adapted version of the EQ-5D-Y-3L and EQ-5D-Y-5L in children aged 2-4 years compared with the original versions.

Psychometric Properties of Generic Preference-Weighted Measures for Children and Adolescents: A Systematic Review.

INTRODUCTION: Preference-weighted measures (PWMs)-also referred to as preference-based measures in the literature-of health status/health-related quality of life plays an essential role in estimating quality-adjusted life-years (QALY) for use in economic evaluations of healthcare products and interventions. However, as PWMs are first and foremost intended to accurately reflect respondent health status, they should ideally demonstrate good psychometric properties for the population in question. This study aimed to systematically review published evidence on the measurement properties of commonly used PWMs for children and adolescents. METHODS: Three electronic databases (PubMed, Medline, and PsycINFO) were searched for articles assessing the psychometric properties (content validity, construct validity-including convergent validity and known-group validity, test-retest reliability, and responsiveness) of the PWMs of interest (AQoL-6D, CHU9D, HUI2, HUI3, and EQ-5D-Y). The COsensus-based Standards for the selection of health Measurement INstruments methodology (COSMIN) guidelines were used to assess (a) the methodological quality of the studies included and (b) the psychometric performance of the instruments covered. Data were analysed overall as well as by population (country and disease group) and perspective (self-report or proxy-report). The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021277296). RESULTS: In total, 53 articles were included in this systematic review. Health Utilities Index (HUI) was tested only in patient populations, CHU9D was most frequently tested in general population samples, while EQ-5D-Y was tested in both populations. Overall, there was high-quality evidence supporting sufficient construct validity for all instruments except AQoL-6D. Evidence supporting test-retest and responsiveness was scarce. There was high-quality evidence supporting sufficient responsiveness of HUI2 and HUI3, and inconsistent test-retest reliability of CHU9D and EQ-5D-Y. Evidence for content validity was minimal and therefore not extracted and synthesized for any PWMs. CONCLUSION: This review provides updated evidence on the measurement properties of existing generic PWMs for children and adolescents. High-quality evidence for all relevant psychometric properties and across a range of populations was not available for any of the instruments included, indicating that further work is needed in this direction. This study has identified some of the most noticeable evidence gaps for each of the individual measures. Users can use this information to guide their decision on the choice of PWM to administer.

A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome.

BACKGROUNDPrimary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and plasma B cell subsets; and increases stringency on B cell selection during reconstitution. Anti-CD20 therapeutics (e.g., rituximab) bind and deplete CD20-expressing B cells in circulation but are less effective in depleting tissue-resident CD20+ B cells. Combined, these 2 mechanisms may achieve synergistic effects.METHODSThis 68-week, phase II, double-blind study (GSK study 201842) randomized 86 adult patients with active pSS to 1 of 4 arms: placebo, s.c. belimumab, i.v. rituximab, or sequential belimumab + rituximab.RESULTSOverall, 60 patients completed treatment and follow-up until week 68. The incidence of adverse events (AEs) and drug-related AEs was similar across groups. Infections/infestations were the most common AEs, and no serious infections of special interest occurred. Near-complete depletion of minor salivary gland CD20+ B cells and a greater and more sustained depletion of peripheral CD19+ B cells were observed with belimumab + rituximab versus monotherapies. With belimumab + rituximab, reconstitution of peripheral B cells occurred, but it was delayed compared with rituximab. At week 68, mean (± standard error) total EULAR Sjögren's syndrome disease activity index scores decreased from 11.0 (1.17) at baseline to 5.0 (1.27) for belimumab + rituximab and 10.4 (1.36) to 8.6 (1.57) for placebo.CONCLUSIONThe safety profile of belimumab + rituximab in pSS was consistent with the monotherapies. Belimumab + rituximab induced enhanced salivary gland B cell depletion relative to the monotherapies, potentially leading to improved clinical outcomes.TRIAL REGISTRATIONClinicalTrials.gov NCT02631538.FUNDINGFunding was provided by GSK.

Efficacy and Tolerability of 6-Month Treatment with Tamsulosin Plus the Hexanic Extract of Serenoa repens versus Tamsulosin Plus 5-Alpha-Reductase Inhibitors for Moderate-to-Severe LUTS-BPH Patients: Results of a Paired Matched Clinical Study.

The objective of this subset analysis was to evaluate and compare the efficacy and tolerability of two combination treatments for men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Data were from a real-world, open-label, prospective, and multicenter study performed in outpatient urology clinics. Men with moderate-to-severe LUTS/BPH received 6-month treatment with tamsulosin (TAM) in combination with either the hexanic extract of S. repens (HESr) or a 5-alpha-reductase inhibitor (5ARI). Changes in urinary symptoms and quality of life were measured using the IPSS and BII questionnaires, respectively. Treatment tolerability was assessed by recording adverse effects (AEs). Patients in the two study groups were matched using iterative and propensity score matching approaches. After iterative matching, data were available from 136 patients (n = 68 treated with TAM + 5ARI, n = 68 with TAM + HESr). After 6 months of treatment, mean (SD) IPSS total score improved by 7.7 (6.3) and 6.7 (5.0) points in the TAM + 5ARI and TAM + HESr groups, respectively (p = 0.272); mean BII total scores improved by 3.1 (2.9) and 2.9 (2.4) points (p = 0.751), respectively. AEs were reported by 26.5% and 10.3% of patients in the same groups, mostly affecting sexual function (p < 0.027). When used in a real-world setting to treat patients with moderate-severe LUTS/BPH, 6-month treatment with TAM + HESr was as effective as TAM + 5ARI, but with better tolerability.

Perceptions of the General Public About Health-related Quality of Life and the EQ-5D Questionnaire: A Qualitative Study in Korea.

OBJECTIVES: The aim of this qualitative study was to investigate how members of the general public in Korea interpret the concept of health, and which dimensions of health are most important to them. We also explored their perceptions of the EuroQoL 5-Dimension (EQ-5D), including the EuroQoL visual analogue scale (EQ-VAS). METHODS: We conducted face-to-face, in-depth interviews with 20 individuals from the general population, using a semi-structured interview guide. Content analysis was performed with verbatim transcripts and field notes to identify codes and categorize them according to their similarities and associations. RESULTS: In total, 734 different codes were derived and classified into 4 categories. Participants cited the importance of both the mental and physical aspects of health, although they emphasized that the physical aspects appeared to play a larger role in their conceptualization of health. Participants noted that the EQ-5D has the advantage of being composed of 5 dimensions that are simple and contain both physical and mental areas necessary to describe health. However, some of them mentioned the need to add more dimensions of mental health and social health. Participants showed great satisfaction with the visually well-presented EQ-VAS. However, participants opined that the EQ-VAS scores might not be comparable across respondents because of different ways of responding to the scale. CONCLUSIONS: While physical health is a fundamental aspect of health, mental and social aspects are also important to Koreans. The content of the EQ-5D broadly matched the attributes of health considered important by Koreans.

Efficacy and Safety of the Hexanic Extract of Serenoa repens vs. Watchful Waiting in Men with Moderate to Severe LUTS-BPH: Results of a Paired Matched Clinical Study.

We investigated changes in symptoms and quality of life (QoL) in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) receiving the hexanic extract of Serenoa repens (HESr) and compared results with a matched group on watchful waiting (WW). Data was from a real-world, open-label, prospective, multicenter study. This sub-group analysis included patients with moderate-to-severe symptoms receiving either the HESr 320 mg/daily for six months (HESr) or who remained untreated for LUTS/BPH (WW). Changes in urinary symptoms and QoL were measured by IPSS and BII questionnaires. Two statistical approaches (iterative matching and propensity score pairing) were used to maximize between-group comparability at baseline. Tolerability was assessed in the HESr group. After iterative matching, data for analysis was available for 783 patients (102 WW, 681 HESr). IPSS scores improved by a mean (SD) of 3.8 (4.4) points in the HESr group and by 2.2 (4.5) points in the WW group (p = 0.002). Changes in BII score were 1.8 (2.4) points and 1.0 (2.2) points, respectively (p < 0.001). Three patients (0.9%) treated with the HESr reported mild adverse effects. Moderate-severe LUTS/BPH patients treated for six months with the HESr showed greater improvements in symptoms and QoL than matched patients on WW, with a very low rate of adverse effects.

Clinical management and impact of scarlet fever in the modern era: findings from a cross-sectional study of cases in London, 2018-2019.

OBJECTIVES: In response to increasing incidence of scarlet fever and wider outbreaks of group A streptococcal infections in London, we aimed to characterise the epidemiology, symptoms, management and consequences of scarlet fever, and to identify factors associated with delayed diagnosis. DESIGN AND SETTING: Cross-sectional community-based study of children with scarlet fever notified to London's three Health Protection Teams, 2018-2019. PARTICIPANTS: From 2575 directly invited notified cases plus invitations via parental networks at 410 schools/nurseries with notified outbreaks of confirmed/probable scarlet fever, we received 477 responses (19% of those directly invited), of which 412 met the case definition. Median age was 4 years (range <1 to 16), 48% were female, and 70% were of white ethnicity. OUTCOME MEASURES: Preplanned measures included quantitative description of case demographics, symptoms, care-seeking, and clinical, social, and economic impact on cases and households. After survey completion, secondary analyses of factors associated with delayed diagnosis (by logistic regression) and consequences of delayed diagnosis (by Cox's regression), and qualitative analysis of free text comments were added. RESULTS: Rash was reported for 89% of cases, but followed onset of other symptoms for 71%, with a median 1-day delay. Pattern of onset varied with age: sore throat was more common at onset among children 5 years and older (OR3.1, 95% CI 1.9 to 5.0). At first consultation, for 28%, scarlet fever was not considered: in these cases, symptoms were frequently attributed to viral infection (60%, 64/106). Delay in diagnosis beyond first consultation occurred more frequently among children aged 5+ who presented with sore throat (OR 2.8 vs 5+without sore throat; 95% CI 1.3 to 5.8). Cases with delayed diagnosis took, on average, 1 day longer to return to baseline activities. CONCLUSIONS: Scarlet fever may be initially overlooked, especially among older children presenting with sore throat. Raising awareness among carers and practitioners may aid identification and timely treatment.

Patient-caregiver agreement and test-retest reliability of the EQ-5D-Y-3L and EQ-5D-Y-5L in paediatric patients with haematological malignancies.

BACKGROUND: In 2019, the EuroQol Group developed a 'beta' 5-level version of EQ-5D-Y (Y-5L) by increasing the number of descriptive levels to five for each health dimension, as compared to the standard 3-level EQ-5D-Y (Y-3L). OBJECTIVE: To assess patient-caregiver agreement and test-retest reliability of the Y-5L and Y-3L in paediatric patients with haematological malignancies. METHODS: Paediatric inpatients aged 8-17 years were interviewed with the Y-5L and Y-3L questionnaires twice, while their caregivers were interviewed at the same time using the proxy versions of the questionnaires. Patient-caregiver agreement and test-retest reliability were assessed using Gwet's agreement coefficient (Gwet's AC1) for EQ-5D dimensions and the intraclass correlation coefficient (ICC) for the EQ VAS. RESULTS: Ninety-six patient-caregiver dyads participated in the study. Patient-caregiver agreement on the EQ-5D-Y descriptive system was moderate to good for both the Y-3L and Y-5L, but poor on the EQ VAS. Test-retest reliability of the descriptive system was good to very good for the Y-3L and moderate to good for the Y-5L in children, and fair to good for both versions of EQ-5D-Y in proxies. The EQ VAS showed good test-retest reliability in both children and caregivers. In a subgroup analysis of results in younger patients aged 8-10 years, patient-caregiver agreement and test-retest reliability were also observed to range from moderate to very good. CONCLUSION: Both the Y-3L and Y-5L descriptive systems showed acceptable patient-caregiver agreement and test-retest reliability when used to assess the HRQoL of children and adolescents with haematological malignancies, including in younger patients.

Structure and Functional Characterization of a Humanized Anti-CCL20 Antibody following Exposure to Serum Reveals the Formation of Immune Complex That Leads to Toxicity.

mAbs have revolutionized the treatment of autoimmune disorders. Even though mAbs have shown impressive efficacy in blocking T cell or B cell activation and/or recruitment to sites of inflammation, this group of biologicals are not devoid of adverse effects. The most serious adverse effects include infusion reactions, including the activation of the complement pathway. In this study, we present a detailed structure-function study of an anti-CCL20 humanized IgG1 mAb that neutralizes CCL20 chemokine and prevents the recruitment of Th17 cells to sites of inflammation. We demonstrate that the anti-CCL20 Ab changes significantly following administration to humans and monkeys and exposure to human serum. Analysis of the drug product revealed that the anti-CCL20 Ab has unexpectedly high C1q binding. This high binding was linked to immune complex formation in vivo but not during in vitro serum incubation. The immune complex contained multiple complement components. Anti-CCL20 Ab-mediated, complement-dependent cytotoxicity occurred when the Ab bound to CCL20 tethered to the cell membrane of target cells. Taken together, these results provide a likely cause for the animal toxicity observed. In addition, anti-CCL20 revealed progressive acidification because of N100 (located in CDR) deamidation over time, which did not directly impact Ag binding. Our study demonstrates that the safety profiling of mAbs should include the evaluation of effector functions in addition to typical stressed conditions.

How Do Respondents Interpret and View the EQ-VAS? A Qualitative Study of Three Asian Populations.

BACKGROUND: This study aimed to understand how respondents from three Asian countries interpret and perceive the EuroQol Visual Analogue Scale (EQ-VAS). METHOD: Data were from a project that aimed to examine the cultural appropriateness of EQ-5D in Asia. Members of the general public from China, Japan, and Singapore were interviewed one-to-one in their preferred languages. Open-ended questions (e.g. What does "best imaginable health" mean to you?) were used to elicit participants' interpretation of the labels of EQ-VAS. How the scale could be improved was also probed. Thematic and content analyses were performed separately for each country before pooling for comparison. RESULTS: Sixty Chinese, 24 Japanese, and 60 Singaporeans were interviewed. Interpretations of the label "Best Imaginable Health" varied among the participants. Interestingly, some participants indicated that "Best Imaginable Health" is unachievable. Interpretations for "Worst Imaginable Health" also varied, with participants referring primarily to one of three themes, namely, "death," "disease," and "disability." There were different opinions as to what changes in health would correspond to a 5- to 10-point change on the EQ-VAS. While participants opined that EQ-VAS is easy to understand, some criticized it for being too granular and that scale labels are open to interpretation. Findings from the three countries were similar. CONCLUSION: It appears that interpretations of the EQ-VAS vary across Asian respondents. Future studies should investigate whether the variations are associated with any respondent characteristics and whether the EQ-VAS could be modified to achieve better respondent acceptance.

Which multi-attribute utility instruments are recommended for use in cost-utility analysis? A review of national health technology assessment (HTA) guidelines.

BACKGROUND: Several multi-attribute utility instruments (MAUIs) are available from which utilities can be derived for use in cost-utility analysis (CUA). This study provides a review of recommendations from national health technology assessment (HTA) agencies regarding the choice of MAUIs. METHODS: A list was compiled of HTA agencies that provide or refer to published official pharmacoeconomic (PE) guidelines for pricing, reimbursement or market access. The guidelines were reviewed for recommendations on the indirect calculation of utilities and categorized as: a preference for a specific MAUI; providing no MAUI preference, but providing examples of suitable MAUIs and/or recommending the use of national value sets; and recommending CUA, but not providing examples of MAUIs. RESULTS: Thirty-four PE guidelines were included for review. MAUIs named for use in CUA: EQ-5D (n = 29 guidelines), the SF-6D (n = 11), HUI (n = 10), QWB (n = 3), AQoL (n = 2), CHU9D (n = 1). EQ-5D was a preferred MAUI in 15 guidelines. Alongside the EQ-5D, the HUI was a preferred MAUI in one guideline, with DALY disability weights mentioned in another. Fourteen guidelines expressed no preference for a specific MAUI, but provided examples: EQ-5D (n = 14), SF-6D (n = 11), HUI (n = 9), QWB (n = 3), AQoL (n = 2), CHU9D (n = 1). Of those that did not specify a particular MAUI, 12 preferred calculating utilities using national preference weights. CONCLUSIONS: The EQ-5D, HUI, and SF-6D were the three MAUIs most frequently mentioned in guidelines. The most commonly cited MAUI (in 85% of PE guidelines) was EQ-5D, either as a preferred MAUI or as an example of a suitable MAUI for use in CUA in HTA.

Assessing the Content Validity of the EQ-5D Questionnaire Among Asians in Singapore: A Qualitative Study.

INTRODUCTION: Although the EQ-5D questionnaire is widely used to measure health status internationally, there is little evidence of its content validity in Asian populations. This qualitative study aimed to explore the content validity of the EQ-5D in Singapore. MATERIALS AND METHODS: Sixty Singaporeans (Chinese: 20; Malay: 20; Indian: 20) completed semi-structured interviews in which they were asked about health concepts which were important to them and the relevance and comprehensiveness of the EQ-5D descriptive system (DS). Thematic analysis employing open, focused and axial coding was used to identify the themes and subthemes from the interviews. RESULTS: A total of 70 health concepts were identified which fall into the broad categories of 'physical health', 'mental well-being', 'social relationships', 'medical conditions and treatment', and 'health promotion knowledge and behaviours'. The 5 dimensions in the EQ-5D DS were among the health concepts nominated by participants. Some participants suggested that content validity could be improved by adding social relationships, medical conditions and treatment, and health promotion knowledge and behaviours to the EQ-5D DS. CONCLUSIONS: This study confirmed that EQ-5D dimensions are important and relevant aspects of health to Asians in Singapore, although some dimensions that could be important to Singaporeans are absent.

Immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against CCL20 is associated with complement-containing drug aggregates.

Despite the potential for the chemokine class as therapeutic targets in immune mediated disease, success has been limited. Many chemokines can bind to multiple receptors and many receptors have multiple ligands, with few exceptions. One of those exceptions is CCL20, which exclusively pairs to CCR6 and is associated with several immunologic conditions, thus providing a promising therapeutic target. Following successful evaluation in a single dose, first time in human clinical study, GSK3050002-a humanized IgG1 monoclonal antibody against human CCL20-was evaluated in a 26-week cynomolgus monkey toxicology study. A high incidence of unexpected vascular and organ inflammation was observed microscopically, leading to the decision to halt clinical development. Here we report a dose-responsive increase in the incidence and severity of inflammation in multiple organs from monkeys receiving 30 and 300 mg/kg/week by either subcutaneous or intravenous injection. Histomorphological changes resembled an immune complex-mediated pathology, which is often due to formation of anti-drug antibodies in monkeys receiving a human protein therapeutic and thus not predictive of clinical outcome. However, the presentation was atypical in that there was a clear dose response with a very high incidence of inflammation with a low incidence of ADA that did not correlate well individually. Additionally, the immunohistologic presentation was atypical in that the severity and distribution of tissue inflammation was greater than the numbers of associated immune complexes (i.e., granular deposits). An extensive ex vivo analysis of large molecular weight protein complexes in monkey serum from this study and in human serum samples demonstrated a time-dependent aggregation of GSK3050002, that was not predicted by in vitro assays. The aggregates also contained complement components. These findings support the hypothesis that immune complexes of drug aggregates, not necessarily including anti-drug antibodies, can fix complement, accumulate over time, and trigger immune complex disease. A situation which may have increased clinical relevance than typical anti-drug antibody-associated immune complex disease in monkeys administered human antibody proteins.

Testing the validity and responsiveness of a new cancer-specific health utility measure (FACT-8D) in relapsed/refractory mantle cell lymphoma, and comparison to EQ-5D-5L.

BACKGROUND: The FACT-8D is a new cancer-specific, preference-based measure (PBM) of health, derived from the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire. The FACT-8D's measurement properties have not been tested to date. We assessed it's validity and responsiveness in relapsed/refractory mantle cell lymphoma (RR MCL) and compared the results to the EQ-5D-5L. METHODS: Blinded analysis of pooled data from a phase 3 clinical trial. FACT-8D baseline and follow-up data (weeks 4, 7, 16, 31) were scored using Australian preference weights, the first available value-set. Convergent validity was assessed by estimating baseline correlations with the FACT-Lym total score, Trial Outcome Index (TOI), FACT-Lym lymphoma-specific sub-scale (LymS), EQ-5D Visual Analog Scale (VAS), and haemoglobin (HgB). Relevant clinical variables were used to categorise patients to test known groups' validity and responsiveness was investigated using data from baseline (n = 250) and week 31 (n = 130). Results were compared with EQ-5D-5L, scored using the UK 3L crosswalk and the 5L England value-sets. RESULTS: The FACT-8D showed good convergent validity and responsiveness; baseline Pearson correlation coefficients between FACT-8D Index scores and other PRO measures were moderate to very strong (range: 0.49 for the EQ-VAS to 0.79 for FACT TOI) and the size of the change in FACT-8D Index scores at week 31 differed significantly (p < 0.005) between patients categorised as improved, worsened or stable using the FACT-Lym total score, LymS, and HgB. However, when assessing known groups' validity, FACT-8D failed to discriminate between patients categorised by health status on four of the seven variables analysed. Overall, FACT-8D and EQ-5D-5L performed similarly, although EQ-5D-5L showed better known groups' validity. CONCLUSIONS: This is the first investigation into the psychometric properties of the FACT-8D. In this RR MCL trial dataset, it showed good convergent validity and responsiveness, but poorer known groups' validity, and EQ-5D performed as well or better on the tests conducted. The FACT-8D may offer an alternative method to generate utilities for the cost-effectiveness analysis of cancer treatments but needs further testing in other types of cancer patients. Evaluation of utility gains may have been limited by high baseline performance status in this RR MCL trial sample.

Avances y retos en la medida de la calidad de vida relacionada con la salud en la población infantil y adolescente / Advances and challenges in the measurement of health related quality of life in the child and adolescent population

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EQ-5D-Y-5L: developing a revised EQ-5D-Y with increased response categories.

PURPOSE: EQ-5D-Y is a generic measure of health status for children and adolescents aged 8-15 years. Originally, it has three levels of severity in each dimension (3L). This study aimed to develop a descriptive system of EQ-5D-Y with an increased number of severity levels and to test comprehensibility and feasibility. METHODS: The study was conducted in Germany, Spain, Sweden and the UK. In Phase 1, a review of existing instruments and focus group interviews were carried out to create a pool of possible labels for a modified severity classification. Participants aged 8-15 rated the severity of the identified labels in individual sorting and response scaling interviews. In Phase 2, preliminary 4L and 5L versions were constructed for further testing in cognitive interviews with healthy participants aged 8-15 years and children receiving treatment for a health condition. RESULTS: In Phase 1, a total of 233 labels was generated, ranging from 37 (UK) to 79 labels (Germany). Out of these, 7 to 16 possible labels for each dimension in the different languages were rated in 255 sorting and response scaling interviews. Labels covered an appropriate range of severity on the health continuum in all countries. In Phase 2, the 5L version was generally preferred (by 68-88% of the participants per country) over the 4L version. CONCLUSIONS: This multinational study has provided a version of the EQ-5D-Y with 5 severity levels in each dimension. This extended version (EQ-5D-Y-5L) requires testing its psychometric properties and its performance compared to that of the original EQ-5D-Y-3L.

Valuation of EuroQol Five-Dimensional Questionnaire, Youth Version (EQ-5D-Y) and EuroQol Five-Dimensional Questionnaire, Three-Level Version (EQ-5D-3L) Health States: The Impact of Wording and Perspective.

BACKGROUND: Valuations of health states were affected by the wording of the two instruments (EQ-5D-3L and EQ-5D-Y) and by the perspective taken (child or adult). OBJECTIVES: There is a growing demand for value sets for the EQ-5D-Y (EQ-5D instrument for younger populations). Given the similarities between EQ-5D-Y and EQ-5D-3L, we investigated whether valuations of health states were affected by the differences in wording between the two instruments and by the perspective taken in the valuation exercise (child or adult). STUDY DESIGN: Respondents were randomly assigned to EQ-5D-3L or EQ-5D-Y (instrument) and further into two groups that either valued health states for an adult or for a 10-year-old child (perspective). The valuation tasks were composite time trade-off (C-TTO) and discrete choice experiments (DCE), including comparisons with death (DCE + death). Members of the adult general population in four countries (Germany, Netherlands, Spain, England) participated in computer-assisted personal interviews. METHODS: Two-way multivariate analysis of variance (MANOVA) and post hoc tests were used to compare C-TTO responses and chi-square tests were conducted to compare DCE + death valuations. RESULTS: A significant interaction effect between instrument and perspective for C-TTO responses was found. Significant differences by perspective (adult and child) occurred only for the EQ-5D-3L. Significant differences in values between instruments (EQ-5D-3L and EQ-5D-Y) occurred only for the adult perspective. Both significant results were confirmed by the DCE + death results. When comparing EQ-5D-3L for adult perspective and EQ-5D-Y for child perspective, values were also significantly different. CONCLUSIONS: The results identified an interaction effect between wording of the instrument and perspective on elicited values, suggesting that current EQ-5D-3L value sets should not be employed to assign values to EQ-5D-Y health states.