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This project was funded by the UK Medical Research Council (MRC) as part of the MRC-NIHR methodology research programme (reference G0901486) and will be published in full in Health Technology Assessment; Vol. 18, No. 9. See the NIHR Journals Library website for further project information.

Quality-adjusted life-years (QALYs) are widely used as an outcome for the economic evaluation of health interventions. However, preference-based measures used to obtain health-related utility values to produce QALY estimates are not always included in key clinical studies. Furthermore, organizations responsible for reviewing or producing health technology assessments (HTAs) may have preferred instruments for obtaining utility estimates for QALY calculations. Where data using a preference-based measure or the preferred instrument have not been collected, it may be possible to "map" or "crosswalk" from other measures of health outcomes. The aims of this study were 1) to provide an overview of how mapping is currently used as reported in the published literature and in an HTA policy-making context, specifically at the National Institute for Health and Clinical Excellence in the United Kingdom, and 2) to comment on best current practice on the use of mapping for HTA more generally. The review of the National Institute for Health and Clinical Excellence guidance found that mapping has been used since first established but that reporting of the models used to map has been poor. Recommendations for mapping in HTA include an explicit consideration of the generalizability of the mapping function to the target sample, reporting of standard econometric and statistical tests including the degree of error in the mapping model across subsets of the range of utility values, and validation of the model(s). Mapping can provide a route for linking outcomes data collected in a trial or observational study to the specific preferred instrument for obtaining utility values. In most cases, however, it is still advantageous to directly collect data by using the preferred utility-based instrument and mapping should usually be viewed as a "second-best" solution.

BackgroundThe EQ-5D, a generic health status questionnaire that is widely used in health economic evaluation, was recently expanded to the EQ-5D-5L to address criticisms of unresponsiveness and ceiling effect.AimsTo describe the validity, responsiveness and minimum important difference of the EQ-5D-5L in COPD.MethodsStudy 1: The validity of the EQ-5D-5L utility index and visual analogue scale (EQ-VAS) was compared with four established disease-specific health status questionnaires and other measures of disease severity in 616 stable outpatients with COPD. Study 2: The EQ-5D-5L utility index and EQ-VAS were measured in 324 patients with COPD before and after 8 weeks of pulmonary rehabilitation. Distribution and anchor-based approaches were used to estimate the minimum important difference.ResultsThere were moderate-to-strong correlations between utility index and EQ-VAS with disease-specific questionnaires (Pearson's r=0.47–0.72). A ceiling effect was seen in 7% and 2.6% of utility index and EQ-VAS. Utility index decreased (worsening health status) with indices of worsening disease severity. With rehabilitation, mean (95% CI) changes in utility index and EQ-VAS were 0.065 (0.047 to 0.083) and 8.6 (6.5 to 10.7), respectively, with standardised response means of 0.39 and 0.44. The mean (range) anchor estimates of the minimum important difference for utility index and EQ-VAS were 0.051 (0.037 to 0.063) and 6.9 (6.5 to 8.0), respectively.ConclusionsThe EQ-5D-5L is a valid and responsive measure of health status in COPD and may provide useful additional cost-effectiveness data in clinical trials.

BackgroundLiver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established.ObjectiveTo assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease.Data sourcesWe searched various databases from 1998 to April 2012, recent conference proceedings and reference lists.MethodsWe included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted.ResultsGiven a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822.LimitationsA substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments.ConclusionsTreating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD.Study registrationThis study is registered as PROSPERO CRD42011001561.FundingThe National Institute for Health Research Health Technology Assessment programme.