Developing a health state classification system from NEWQOL for epilepsy using classical psychometric techniques and Rasch analysis: a technical report

Aims: Resource allocation amongst competing health care interventions is informed by evidence of both clinical- and cost-effectiveness. Cost-utility analysis is increasingly used to assess cost effectiveness through the use of Quality Adjusted Life Years (QALYs). This requires health state values. Generic measures of health related quality of life (HRQL) are usually used to produce these values, but there are concerns about their relevance and sensitivity in epilepsy. This study develops a health state classification system for epilepsy from the NEWQOL battery, a validated questionnaire measuring QoL in epilepsy. The classification system will be amenable to valuation for calculating QALYs. Methods: Factor and other psychometric analyses were undertaken to investigate the factor structure of the battery, and assess the validity and responsiveness of the items. These analyses were used alongside Rasch analysis to select the dimensions included in the classification system, and the items used to represent each domain. Analysis was carried out on a trial dataset of patients with epilepsy (n=1611). Rasch and factor analysis were performed on one half of the sample and validated on the remaining half. Dimensions and items were selected that performed well across all analyses. Results: The battery was found to demonstrate reliability and validity but responsiveness across time periods for many of the items was low. A six dimension classification system was developed: worry about seizures, depression, memory, cognition, stigmatism and control, each with four response levels. Conclusions: It is feasible to develop a health state classification system from a battery of instruments using a combination of classical psychometric, factor and Rasch analysis. This is the first condition-specific health state classification developed for epilepsy and the next stage will produce preference weights to enable the measure to be used in cost-utility analysis.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; epilepsy

Developing a new version of the SF-6D health state classification system from the SF-36v2: SF-6Dv2

Objective: The objective of this study was to develop the classification system for version of the SF-6D (SF-6Dv2) from the SF-36v2. SF-6Dv2 is an improved version of SF-6D, one of the most widely used generic measures of health for the calculation of quality-adjusted life years. Study Design and Setting: A 3-step process was undertaken to generate a new classification system: (1) factor analysis to establish dimensionality; (2) Rasch analysis to understand item performance; and (3) tests of differential item function. To evaluate robustness, Rasch analyses were performed in multiple subsets of 2 large cross-sectional datasets from recently discharged hospital patients and online patient samples. Results: On the basis of factor analysis, other psychometric evidence, cross-cultural considerations, and amenability to valuation, the 6-dimension classification used in SF-6D was maintained. SF-6Dv2 resulted in the following modifications to SF-6D: a simpler classification of physical function with clearer separation between levels; a more detailed 5-level description of role limitations; using negative wording to describe vitality; and using pain severity rather than pain interference. Conclusions: The SF-6Dv2 classification system describes more distinct levels of health than SF-6D, changes the descriptions used for a number of dimensions and provides clearer wording for health state valuation. The second stage of the study has developed a utility value set using discrete choice methods so that the measure can be used in health technology assessment. Further work should investigate the psychometric characteristics of the new instrument

Use of generic and condition-specific measures of health-related quality of life in NICE decision-making: systematic review, statistical modelling and survey.

© Queen’s Printer and Controller of HMSO 2014Background: The National Institute for Health and Care Excellence recommends the use of generic preference-based measures (GPBMs) of health for its Health Technology Assessments (HTAs). However, these data may not be available or appropriate for all health conditions. Objectives: To determine whether GPBMs are appropriate for some key conditions and to explore alternative methods of utility estimation when data from GPBMs are unavailable or inappropriate. Design: The project was conducted in three stages: (1) A systematic review of the psychometric properties of three commonly used GPBMs [EQ-5D, SF-6D and Health Utilities Index Mark 3 (HUI3)] in four broadly defined conditions: visual impairment, hearing impairment, cancer and skin conditions. (2) Potential modelling approaches to ‘map’ EQ-5D values from condition-specific and clinical measures of health [European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and Functional Assessment of Cancer Therapy – General Scale (FACT-G)] are compared for predictive ability and goodness of fit using two separate data sets. (3) Three potential extensions to the EQ-5D are developed as ‘bolt-on’ items relating to hearing, tiredness and vision. They are valued using the time trade-off method. A second valuation study is conducted to fully value the EQ-5D with and without the vision bolt-on item in an additional sample of 300 people. Main outcome measures: Comparisons of EQ-5D, SF-6D and HUI3 in four conditions with various generic and condition-specific measures. Mapping functions were estimated between EORTC QLQ-C30 and FACT-G with EQ-5D. Three bolt-ons to the EQ-5D were developed: EQ + hearing/vision/tiredness. A full valuation study was conducted for the EQ + vision. Results: (1) EQ-5D was valid and responsive for skin conditions and most cancers; in vision, its performance varied according to aetiology; and performance was poor for hearing impairments. The HUI3 performed well for hearing and vision disorders. It also performed well in cancers although evidence was limited and there was no evidence in skin conditions. There were limited data for SF-6D in all four conditions and limited evidence on reliability of all instruments. (2) Mapping algorithms were estimated to predict EQ-5D values from alternative cancer-specific measures of health. Response mapping using all the domain scores was the best performing model for the EORTC QLQ-C30. In an exploratory analysis, a limited dependent variable mixture model performed better than an equivalent linear model. In the full analysis for the FACT-G, linear regression using ordinary least squares gave the best predictions followed by the tobit model. (3) The exploratory valuation study found that bolt-on items for vision, hearing and tiredness had a significant impact on values of the health states, but the direction and magnitude of differences depended on the severity of the health state. The vision bolt-on item had a statistically significant impact on EQ-5D health state values and a full valuation model was estimated. Conclusions: EQ-5D performs well in studies of cancer and skin conditions. Mapping techniques provide a solution to predict EQ-5D values where EQ-5D has not been administered. For conditions where EQ-5D was found to be inappropriate, including some vision disorders and for hearing, bolt-ons provide a promising solution. More primary research into the psychometric properties of the generic preference-based measures is required, particularly in cancer and for the assessment of reliability. Further research is needed for the development and valuation of bolt-ons to EQ-5D.UK Medical Research Council (MRC) as part of the MRC-NIHR methodology research programme (reference G0901486

Developing a health state classification system from NEWQOL for epilepsy using classical psychometric techniques and Rasch analysis: A technical report

Aims: Resource allocation amongst competing health care interventions is informed by evidence of both clinical- and cost-effectiveness. Cost-utility analysis is increasingly used to assess cost effectiveness through the use of Quality Adjusted Life Years (QALYs). This requires health state values. Generic measures of health related quality of life (HRQL) are usually used to produce these values, but there are concerns about their relevance and sensitivity in epilepsy. This study develops a health state classification system for epilepsy from the NEWQOL battery, a validated questionnaire measuring QoL in epilepsy. The classification system will be amenable to valuation for calculating QALYs. Methods: Factor and other psychometric analyses were undertaken to investigate the factor structure of the battery, and assess the validity and responsiveness of the items. These analyses were used alongside Rasch analysis to select the dimensions included in the classification system, and the items used to represent each domain. Analysis was carried out on a trial dataset of patients with epilepsy (n=1611). Rasch and factor analysis were performed on one half of the sample and validated on the remaining half. Dimensions and items were selected that performed well across all analyses. Results: The battery was found to demonstrate reliability and validity but responsiveness across time periods for many of the items was low. A six dimension classification system was developed: worry about seizures, depression, memory, cognition, stigmatism and control, each with four response levels. Conclusions: It is feasible to develop a health state classification system from a battery of instruments using a combination of classical psychometric, factor and Rasch analysis. This is the first condition-specific health state classification developed for epilepsy and the next stage will produce preference weights to enable the measure to be used in cost-utility analysis

Developing preference-based measures for diabetes: DHP-3D and DHP-5D

© 2017 Diabetes UK Aims: The aim of this study was to develop two diabetes-specific preference-based measures [the Diabetes Health Profile–3 Dimension (DHP-3D) and the Diabetes Health Profile–5 Dimension (DHP-5D)] for use in the calculation of Quality Adjusted Life Years, a key outcome in economic evaluation. These measures were based on the non-preference-based instrument the Diabetes Health Profile. Methods: For DHP-3D, psychometric and Rasch analyses were used to develop a health state classification system based on the Diabetes Health Profile–18 (DHP-18). The DHP-5D added two dimensions to the DHP-3D to extend the range of impacts measured. Each classification system was valued by 150 general public respondents in the United Kingdom using Time Trade Off (TTO). Multivariate regression was used to estimate utility value sets. The matched dimensions across each measure were compared using z-score tests. Results: The DHP-3D included three dimensions defined as mood, eating and social limitations, and the DHP-5D added dimensions defined as hypoglycaemic attacks and vitality. For both, the random effects generalized least squares regression model produced consistent value sets, with the DHP-3D and DHP-5D ranging from 0.983 (best state) to 0.717 (worst state), and 0.979 to 0.618 respectively. The addition of the two extra dimensions leads to significant differences for the more severe levels of each matched dimension. Conclusions: We have developed two diabetes-specific preference-based measures that, subject to psychometric assessment, can be used to provide condition-specific utility values to complement generic utilities from more widely validated measures such as the EuroQol-5 Dimension

Using a discrete choice experiment involving cost to value a classification system measuring the quality of life impact of self-management for diabetes

Objective: This paper describes the use of a novel approach in health valuation of a discrete choice experiment (DCE) including a cost attribute to value a recently developed classification system for measuring the quality of life impact (both health and treatment experience) of self-management for diabetes. Methods: A large online survey was conducted using DCE with cost on UK respondents from the general population (n=1,497) and individuals with diabetes (n=405). The data was modelled using a conditional logit model with robust standard errors. The marginal rate of substitution (MRS) was used to generate willingness to pay estimates for every state defined by the classification system. Robustness of results was assessed by including interaction effects for household income. Results: There were some logical inconsistencies and insignificant coefficients for the milder levels of some attributes. There were some differences in the rank ordering of different attributes for the general population and diabetes patients. The willingness to pay to avoid the most severe state was £1,118.53 per month for the general population and £2,356.02 per month for the diabetes patient population. The results were largely robust. Conclusion: Health and self-management can be valued in a single classification system using DCE with cost. The MRS for key attributes can be used to inform cost-benefit analysis of self-management interventions in diabetes using results from clinical studies where this new classification system has been applied. The method shows promise, but found large willingness to pay estimates exceeding the cost levels used in the survey

A Comparison of Methods for Converting DCE Values onto the Full Health-Dead QALY Scale.

Preference elicitation techniques such as time trade-off (TTO) and standard gamble (SG) receive criticism for their complexity and difficulties of use. Ordinal techniques such as discrete choice experiment (DCE) are arguably easier to understand but generate values that are not anchored onto the full health-dead 1-0 quality-adjusted life-year (QALY) scale required for use in economic evaluation

Patchy Interspecific Sequence Similarities Efficiently Identify Positive cis-Regulatory Elements in the Sea Urchin

We demonstrate that interspecific sequence conservation can provide a systematic guide to the identification of functional cis-regulatory elements within a large expanse of genomic DNA. The test was carried out on the otx gene of Strongylocentrotus purpuratus. This gene plays a major role in the gene regulatory network that underlies endomesoderm specification in the embryo. The cis-regulatory organization of the otx gene is expected to be complex, because the gene has three different start sites (X. Li, C.-K. Chuang, C.-A. Mao, L. M. Angerer, and W. H. Klein, 1997, Dev. Biol. 187, 253–266), and it is expressed in many different spatial domains of the embryo. BAC recombinants containing the otx gene were isolated from Strongylocentrotus purpuratus and Lytechinus variegatus libraries, and the ordered sequence of these BACs was obtained and annotated. Sixty kilobases of DNA flanking the gene, and included in the BAC sequence from both species, were scanned computationally for short conserved sequence elements. For this purpose, we used a newly constructed software package assembled in our laboratory, “FamilyRelations.” This tool allows detection of sequence similarities above a chosen criterion within sliding windows set at 20–50 bp. Seventeen partially conserved regions, most a few hundred base pairs long, were amplified from the S. purpuratus BAC DNA by PCR, inserted in an expression vector driving a CAT reporter, and tested for cis-regulatory activity by injection into fertilized S. purpuratus eggs. The regulatory activity of these constructs was assessed by whole-mount in situ hybridization (WMISH) using a probe against CAT mRNA. Of the 17 constructs, 11 constructs displayed spatially restricted regulatory activity, and 6 were inactive in this test. The domains within which the cis-regulatory constructs were expressed are approximately consistent with results from a WMISH study on otx expression in the embryo, in which we used probes specific for the mRNAs generated from each of the three transcription start sites. Four separate cis-regulatory elements that specifically produce endomesodermal expression were identified, as well as ubiquitously active elements, and ectoderm-specific elements. We confirm predictions from other work with respect to target sites for specific transcription factors within the elements that express in the endoderm

A local-global principle for linear dependence of noncommutative polynomials

A set of polynomials in noncommuting variables is called locally linearly dependent if their evaluations at tuples of matrices are always linearly dependent. By a theorem of Camino, Helton, Skelton and Ye, a finite locally linearly dependent set of polynomials is linearly dependent. In this short note an alternative proof based on the theory of polynomial identities is given. The method of the proof yields generalizations to directional local linear dependence and evaluations in general algebras over fields of arbitrary characteristic. A main feature of the proof is that it makes it possible to deduce bounds on the size of the matrices where the (directional) local linear dependence needs to be tested in order to establish linear dependence.Comment: 8 page

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v