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

Evaluation of the Victorian Healthy Homes Program: protocol for a randomised controlled trial.

INTRODUCTION: The evaluation of the Victorian Healthy Homes Program (VHHP) will generate evidence about the efficacy and cost-effectiveness of home upgrades to improve thermal comfort, reduce energy use and produce health and economic benefits to vulnerable households in Victoria, Australia. METHODS AND ANALYSIS: The VHHP evaluation will use a staggered, parallel group clustered randomised controlled trial to test the home energy intervention in 1000 households. All households will receive the intervention either before (intervention group) or after (control group) winter (defined as 22 June to 21 September). The trial spans three winters with differing numbers of households in each cohort. The primary outcome is the mean difference in indoor average daily temperature between intervention and control households during the winter period. Secondary outcomes include household energy consumption and residential energy efficiency, self-reported respiratory symptoms, health-related quality of life, healthcare utilisation, absences from school/work and self-reported conditions within the home. Linear and logistic regression will be used to analyse the primary and secondary outcomes, controlling for clustering of households by area and the possible confounders of year and timing of intervention, to compare the treatment and control groups over the winter period. Economic evaluation will include a cost-effectiveness and cost-benefit analysis. ETHICS AND DISSEMINATION: Ethical approval was received from Victorian Department of Human Services Human Research Ethics Committee (reference number: 04/17), University of Technology Sydney Human Research Ethics Committee (reference number: ETH18-2273) and Australian Government Department of Veterans Affairs. Study results will be disseminated in a final report and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12618000160235

Psychometric Performance of HRQoL Measures: An Australian Paediatric Multi-Instrument Comparison Study Protocol (P-MIC).

BackgroundThere is a lack of psychometric evidence about pediatric health-related quality of life (HRQoL) instruments. Evidence on cost effectiveness, involving the measurement of HRQoL, is used in many countries to make decisions about pharmaceuticals, technologies, and health services for children. Additionally, valid instruments are required to facilitate accurate outcome measurement and clinical decision making. A pediatric multi instrument comparison (P-MIC) study is planned to compare the psychometric performance and measurement characteristics of pediatric HRQoL instruments.MethodsThe planned P-MIC study will collect data on approximately 6100 Australian children and adolescents aged 2-18 years via The Royal Children's Hospital Melbourne and online survey panels. Participants will complete an initial survey, involving the concurrent collection of a range of pediatric HRQoL instruments, followed by a shorter survey 2-8 weeks later, involving the collection of a subset of instruments from the initial survey. Children aged ≥7 years will be asked to self-report HRQoL. Psychometric performance will be assessed at the instrument, domain, and item level.ConclusionsThis paper describes the methodology of the planned P-MIC study, including benefits, limitations, and likely challenges. Evidence from this study will guide the choice of HRQoL measures used in clinical trials, economic evaluation, and other applications

Changes in undergraduate student alcohol consumption as they progress through university

BACKGROUND: Unhealthy alcohol use amongst university students is a major public health concern. Although previous studies suggest a raised level of consumption amongst the UK student population there is little consistent information available about the pattern of alcohol consumption as they progress through university. The aim of the current research was to describe drinking patterns of UK full-time undergraduate students as they progress through their degree course. METHOD: Data were collected over three years from 5895 undergraduate students who began their studies in either 2000 or 2001. Longitudinal data (i.e. Years 1–3) were available from 225 students. The remaining 5670 students all responded to at least one of the three surveys (Year 1 n = 2843; Year 2 n = 2219; Year 3 n = 1805). Results: Students reported consuming significantly more units of alcohol per week at Year 1 than at Years 2 or 3 of their degree. Male students reported a higher consumption of units of alcohol than their female peers. When alcohol intake was classified using the Royal College of Physicians guidelines [1] there was no difference between male and females students in terms of the percentage exceeding recommended limits. Compared to those who were low level consumers students who reported drinking above low levels at Year 1 had at least 10 times the odds of continuing to consume above low levels at year 3. Students who reported higher levels of drinking were more likely to report that alcohol had a negative impact on their studies, finances and physical health. Consistent with the reduction in units over time students reported lower levels of negative impact during Year 3 when compared to Year 1. CONCLUSION: The current findings suggest that student alcohol consumption declines over their undergraduate studies; however weekly levels of consumption at Year 3 remain high for a substantial number of students. The persistence of high levels of consumption in a large population of students suggests the need for effective preventative and treatment interventions for all year groups

Comparative Psychometric Performance of Common Generic Paediatric Health-Related Quality of Life Instrument Descriptive Systems: Results from the Australian Paediatric Multi-Instrument Comparison Study.

OBJECTIVE: The aim of this study was to compare the psychometric performance of common generic paediatric health-related quality-of-life instrument descriptive systems (PedsQL generic core 4.0, EQ-5D-Y-3L, EQ-5D-Y-5L, Child Health Utility 9D [CHU9D], Assessment of Quality of Life 6D [AQoL-6D], and Health Utilities Index Mark 3 [HUI3]) by child age, report type, and health status. METHODS: Data for children aged 5-18 years were from the Australian Paediatric Multi-Instrument Comparison study. Ceiling effects, test-retest reliability, known-group validity, convergent and divergent validity, and responsiveness were assessed in the total sample and by child age (5-12 years vs 13-18 years), report type (self- vs proxy report), and health status. Instruments were scored using an exploratory level sum score (LSS) approach. RESULTS: Survey data were available for 5945 children, with follow-up data available for 2346 children. The EQ-5D-Y-3L demonstrated ceiling effects. The PedsQL, EQ-5D-Y-3L, EQ-5D-Y-5L, and CHU9D demonstrated acceptable test-retest reliability. All instruments demonstrated known-group, convergent, and divergent validity. The EQ-5D-Y-3L, EQ-5D-Y-5L, and CHU9D demonstrated responsiveness to improvements in health and the PedsQL, EQ-5D-Y-3L, EQ-5D-Y-5L, and CHU9D to worsening health. The AQoL-6D and HUI3 had inconclusive test-retest reliability and responsiveness evidence due to small sample size. Importantly, ceiling effects, test-retest reliability and responsiveness varied by subgroup. CONCLUSION: Results reflect instrument performance using LSSs, which may differ to utility scores. In the total sample, the EQ-5D-Y-5L and CHU9D descriptive systems demonstrated evidence of good performance (i.e., meeting prespecified criteria) across all psychometric attributes tested. Performance varied by child age and report type, indicating room for considerations by population and study

Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation

Importance Neuroinflammatory disorders are a range of severe neurological disorders causing brain and spinal inflammation and are now increasingly recognized in the pediatric population. They are often characterized by marked genotypic and phenotypic heterogeneity, complicating diagnostic work in clinical practice and molecular diagnosis. Objective To develop and evaluate a next-generation sequencing panel targeting genes causing neuroinflammation or mimicking neuroinflammation. Design, Setting, and Participants Cohort study in which a total of 257 genes associated with monogenic neuroinflammation and/or cerebral vasculopathy, including monogenic noninflammatory diseases mimicking these entities, were selected. A customized enrichment capture array, the neuroinflammation gene panel (NIP), was created. Targeted high-coverage sequencing was applied to DNA samples taken from eligible patients referred to Great Ormond Street Hospital in London, United Kingdom, between January 1, 2017, and January 30, 2019, because of onset of disease early in life, family history, and/or complex neuroinflammatory phenotypes. Main Outcomes and Measures The main outcome was the percentage of individuals with definitive molecular diagnoses, variant classification, and clinical phenotyping of patients with pathogenic variants identified using the NIP panel. The NIP panel was initially validated in 16 patients with known genetic diagnoses. Results The NIP was both sensitive (95%) and specific (100%) for detection of known mutations, including gene deletions, copy number variants, small insertions and deletions, and somatic mosaicism with allele fraction as low as 3%. Prospective testing of 60 patients (30 [50%] male; median [range] age, 9.8 [0.8-20] years) presenting with heterogeneous neuroinflammatory phenotypes revealed at least 1 class 5 (clearly pathogenic) variant in 9 of 60 patients (15%); 18 of 60 patients (30%) had at least 1 class 4 (likely pathogenic) variant. Overall, a definitive molecular diagnosis was established in 12 of 60 patients (20%). Conclusions and Relevance The NIP was associated with molecular diagnosis in this cohort and complemented routine laboratory and radiological workup of patients with neuroinflammation. Unexpected genotype-phenotype associations in patients with pathogenic variants deviating from the classic phenotype were identified. Obtaining an accurate molecular diagnosis in a timely fashion informed patient management, including successful targeted treatment in some instances and early institution of hematopoietic stem cell transplantation in other

The RETRIEVE checklist for studies reporting the elicitation of stated preferences for child health related quality of life

Recent systematic reviews show varying methods for eliciting, modelling, and reporting preference-based values for child health-related quality-of-life (HRQoL) outcomes, producing value-sets with different characteristics. Checklists can improve standards of reporting; however, existing checklists do not address methodological issues for valuing child HRQoL. We aimed to develop a checklist for studies generating values for child HRQoL, including for disease-specific states and value-sets for generic child HRQoL instruments. A conceptual model provided a structure for grouping items into five modules. Potential items were sourced from an adult HRQoL checklist review, with additional items specific to children developed using recent reviews. Checklist items were reduced by eliminating duplication and overlap, then refined for relevance and clarity via an iterative process. Long and short checklist versions were produced for different user needs. The resulting long RETRIEVE contains 83 items, with modules for reporting methods (A-D) and characteristics of values (E), for researchers planning and reporting child health valuation studies. The short RETRIEVE contains 14 items for decision-makers or researchers choosing value-sets. Applying the RETRIEVE checklists to relevant studies suggests feasibility. RETRIEVE has the potential to improve completeness in the reporting of preference-based values for child HRQOL outcomes and to improve assessment of preference-based value-sets

Australian utility weights for the EORTC QLU-C10D, a multi-attribute utility instrument derived from the cancer-specific quality of life questionnaire, EORTC QLQ-C30

Background: The EORTC QLU-C10D is a new multi-attribute utility instrument derived from the widely-used cancer-specific quality of life questionnaire, EORTC QLQ-C30. The QLU-C10D contains ten dimensions (Physical, Role, Social and Emotional Functioning; Pain, Fatigue, Sleep, Appetite, Nausea, Bowel Problems), each with 4 levels. To be used in cost-utility analysis, country-specific valuation sets are required. Objective: To provide Australian utility weights for the QLU-C10D. Methods: An Australian online panel was quota sampled to ensure population representativeness by sex and age (≥18y). Participants completed a discrete choice experiment (DCE) consisting of 16 choice-pairs. Each pair comprised two QLU-C10D health states plus life expectancy. Data were analysed using conditional logistic regression, parameterised to fit the quality-adjusted life-year framework. Utility weights were calculated as the ratio of each QOL dimension-level coefficient to the coefficient on life expectancy. Results: 1979 panel members opted-in, 1904 (96%) completed at least one choice-pair, and 1846 (93%) completed all 16 choice-pairs. Dimension weights were generally monotonic: poorer levels within each dimension were generally associated with greater utility decrements. The dimensions that impacted most on choice were, in order, Physical Functioning, Pain, Role Functioning and Emotional Functioning. Oncology-relevant dimensions with moderate impact were Nausea and Bowel Problems. Fatigue, Trouble Sleeping and Appetite had relatively small impact. The value of the worst health state was -0.096, somewhat worse than death. Conclusions: This study provides the first country-specific value set for the QLU-C10D, which can facilitate cost-utility analyses when applied to data collected with the EORTC QLQ-C30, prospectively and retrospectively

Comparing the measurement equivalence of EQ-5D-5L across different modes of administration

Background: Interest in collecting Patient Reported Outcomes using electronic methods such as mobile phones has increased in recent years. However there is debate about the level of measurement equivalence between the traditional paper and newer electronic modes. Information about the acceptability of the electronic versions to respondents is also required. The aim of this study is to compare the equivalence of delivering a widely used generic measure of health status (EQ-5D-5L) across two administration modes (paper and mobile phone). Methods: Respondents from a research cohort of people in South Yorkshire were identified, and randomly allocated to one of two administration modes (paper vs. mobile phone) based on stratifications for age and gender (and across a range of self-reported health conditions). A parallel group design was used where each respondent only completed EQ-5D-5L using one of the modes. In total, 70 respondents completed the measure in the mobile phone arm, and 66 completed the standard paper version. Follow up usability questions were also included to assess the acceptability of the mobile version of EQ-5D-5L. Measurement equivalence was compared at the dimension, utility score and visual analogue scale level using chi square analysis and ANOVA, and by comparing mean differences to an estimated minimally important difference value. Results: Response rates were higher in the mobile arm. The mean EQ-5D-5L utility and VAS scores, and the frequency of respondents endorsing individual EQ-5D-5L dimension response levels did not significantly differ across the administration modes. The majority of the mobile arm agreed that the mobile version of EQ-5D-5L was easy to complete, and that the phone was easy to use, and that they would complete mobile health measures again. Conclusions: Completing health status measures such as EQ-5D using mobile phones produces equivalent results to more traditional methods, but with added benefits (for example lessening the burden of data entry). Respondents are positive towards completing questionnaires using these methods. The results provide evidence that electronic measures are valid for use to collect data in a range of settings including clinical trials, routine care, and in health diary settings