A review of generic preference-based measures of health-related quality of life in visual disorders

Purpose: This review examines generic preference based measures and their ability to reflect health related quality of life in patients with visual disorders. Methods: A systematic search was undertaken to identify clinical studies of patients with visual disorders where health state utility values (HSUVs) were measured and reported. Data were extracted to assess the validity and responsiveness of the measures. A narrative synthesis of the data was undertaken due to the heterogeneity between different studies. Results: There was considerable heterogeneity in the 31 studies identified in terms of patient characteristics, visual disorders and outcomes reported. Vision loss was associated with a reduction in scores across the preference-based measure, but the evidence on validity and responsiveness was mixed. The EQ-5D’s performance differed according to condition, with poor performance in age-related macular degeneration and diabetic retinopathy. The more limited evidence on the HUI-3 found it performed best in differentiating between severity groups of patients with glaucoma, AMD, cataracts and diabetic retinopathy. One study reported data on the SF-6D and showed it was able to differentiate between patients with AMD. Conclusion: The performance of the EQ-5D in visual disorders was mixed. The HUI-3 seemed to perform better in some conditions, but the evidence on this and SF-6D is limited. More head to head comparisons of these three measures are required. The new 5-level version of EQ-5D may do better at the milder end of visual function and there is research being undertaken into adding a vision relevant dimension

Bridging the gap between methods research and the needs of policy makers: A review of the research priorities of the National Institute for Health and Clinical Excellence

Objectives: The aim of this study was to establish a list of priority topics for methods research to support decision making at the National Institute for Health and Clinical Excellence (NICE). Methods: Potential priorities for methods research topics were identified through a focused literature review, interviews, an email survey, a workshop and a Web-based feedback exercise. Participants were members of the NICE secretariat and its advisory bodies, representatives from academia, industry, and other organizations working closely with NICE. The Web exercise was open to anyone to complete but publicized among the above groups. Results: A list of potential topics was collated. Priorities for further research differed according to the type of respondent and the extent to which they work directly with NICE. Priorities emerging from the group closest to NICE included: methodology for indirect and mixed treatment comparisons; synthesis of qualitative evidence; research relating to the use of quality-adjusted life-years (QALYs) in decision making; methods and empirical research for establishing the cost-effectiveness threshold; and determining how data on the uncertainty of effectiveness and cost-effectiveness data should be taken into account in the decision-making process. Priorities emerging from the broadest group of respondents (through the Web exercise) included: methods for extrapolating beyond evidence observed in trials, methods for capturing benefits not included in the QALY and methods to assess when technologies should be recommended in the context of further evidence gathering. Conclusions: Consideration needs to be given to the needs of those who use the outputs of research for decision making when determining priorities for future methods research.NIHR Medical Research Council

Proceed with caution: an economic perspective on the UK's value based pricing proposals

The shift from the Pharmaceutical Pricing Regulation Scheme to Value Based Pricing (VBP) is an important change in the way that medicines will be priced, and consequently, reimbursed in the United Kingdom. Whilst the opportunity to purchase new medicines based on value to society is one that should be welcomed, we should proceed with caution. We highlight ten issues that should be considered relating to innovation, the role and meaning of funding threshold and the adjustments to reflect burden of illness, therapeutic innovation and improvement and wider societal factors. Most importantly, the assessment of value should continue to be based on the characteristics of the displaced activities (e.g. the health produced). To a large extent, all that is changing under VBP are the characteristics being considered; weighted health rather than unweighted health. In addition, we should not totally abandon a cost-utility framework for appraisal just because its current formulation does not match the wider perspective now desired by government

Mouse models of aneuploidy to understand chromosome disorders

An organism or cell carrying a number of chromosomes that is not a multiple of the haploid count is in a state of aneuploidy. This condition results in significant changes in the level of expression of genes that are gained or lost from the aneuploid chromosome(s) and most cases in humans are not compatible with life. However, a few aneuploidies can lead to live births, typically associated with deleterious phenotypes. We do not understand why phenotypes arise from aneuploid syndromes in humans. Animal models have the potential to provide great insight, but less than a handful of mouse models of aneuploidy have been made, and no ideal system exists in which to study the effects of aneuploidy per se versus those of raised gene dosage. Here, we give an overview of human aneuploid syndromes, the effects on physiology of having an altered number of chromosomes and we present the currently available mouse models of aneuploidy, focusing on models of trisomy 21 (which causes Down syndrome) because this is the most common, and therefore, the most studied autosomal aneuploidy. Finally, we discuss the potential role of carrying an extra chromosome on aneuploid phenotypes, independent of changes in gene dosage, and methods by which this could be investigated further

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

RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro

Peer reviewedPublisher PD

A cost-effectiveness analysis of condom distribution programmes for the prevention of sexually transmitted infections in England

Background Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. Methods An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts. Models were developed for young people (13–24 years), black ethnic minorities, MSM and the general English population. Effectiveness evidence came from a recent systematic review. For young people, a CDP was modelled (relative risk for condom use=1.23), along with an exploratory analysis of the impact on unintended pregnancies. For other populations, threshold analyses were used to identify the combination of costs and effect size required to make a programme cost-effective. Results The base case predicted that CDP for all young people in England could avert 5123 STI cases per annum, with an incremental cost–effectiveness ratio of £17 411. In addition, it could avert 118 pregnancies and 82 abortions and save £333 000 in associated costs. Schemes for black ethnic minorities and MSM could also be cost-effective even with relatively high costs and small effect sizes. Conclusion CDPs for young people are likely to be cost-effective or cost-saving. CDPs for other high-risk populations may also be cost-effective if they can increase condom use, since high HIV prevalence in these groups imposes a considerable health and cost burden