Budget Impact of Belantamab Mafodotin (Belamaf) Adoption in the Treatment of Patients with Relapsed or Refractory Multiple Myeloma in the United States.

PURPOSE: Estimate the budget impact of belantamab mafodotin (belamaf) for patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. METHODS: A budget impact analysis (BIA) was developed to estimate the cost difference between current (no belamaf) and projected (with belamaf) market scenarios over 3 years. Comparators were identified from a systematic literature review and included selinexor + dexamethasone or best supportive care. The number of treatment-eligible patients were estimated using an epidemiology model. Base-case analyses were conducted from a US commercial payer perspective (cost year: 2019). Model inputs included market share estimates, treatment duration, and costs of drug acquisition/administration, concomitant medications, adverse event (AE) management, treatment monitoring, and subsequent treatments based on published literature/cost databases. Budget impact, calculated as the difference in costs between current and projected scenarios over 3 years, was reported as cost per member per month (PMPM) and per member per year (PMPY). One-way sensitivity analysis assessed which key parameters most affected model outcomes. Alternative scenarios were tested (1- or 5-year time horizon; Medicare perspective; negligible cost of mental status change AE). RESULTS: In a hypothetical commercial payer health plan with 1 million members, 33 patients were identified as treatment-eligible over 3 years. Introducing belamaf for patients with RRMM resulted in an estimated budget-neutral PMPM cost of -$0.0003 and PMPY of -$0.004, based on n=9/33 patients receiving treatment. Sensitivity analyses showed that budget impact in the base case was most sensitive to changes in treatment duration and drug acquisition costs. Base-case results were consistent across all scenarios assessed. CONCLUSION: BIA indicates that adoption of belamaf in this patient population would be budget neutral for a US health plan.

Application of Constrained Optimization Methods in Health Services Research: Report 2 of the ISPOR Optimization Methods Emerging Good Practices Task Force.

BACKGROUND: Constrained optimization methods are already widely used in health care to solve problems that represent traditional applications of operations research methods, such as choosing the optimal location for new facilities or making the most efficient use of operating room capacity. OBJECTIVES: In this paper we illustrate the potential utility of these methods for finding optimal solutions to problems in health care delivery and policy. To do so, we selected three award-winning papers in health care delivery or policy development, reflecting a range of optimization algorithms. Two of the three papers are reviewed using the ISPOR Constrained Optimization Good Practice Checklist, adapted from the framework presented in the initial Optimization Task Force Report. The first case study illustrates application of linear programming to determine the optimal mix of screening and vaccination strategies for the prevention of cervical cancer. The second case illustrates application of the Markov Decision Process to find the optimal strategy for treating type 2 diabetes patients for hypercholesterolemia using statins. The third paper (described in Appendix 1) is used as an educational tool. The goal is to describe the characteristics of a radiation therapy optimization problem and then invite the reader to formulate the mathematical model for solving it. This example is particularly interesting because it lends itself to a range of possible models, including linear, nonlinear, and mixed-integer programming formulations. From the case studies presented, we hope the reader will develop an appreciation for the wide range of problem types that can be addressed with constrained optimization methods, as well as the variety of methods available. CONCLUSIONS: Constrained optimization methods are informative in providing insights to decision makers about optimal target solutions and the magnitude of the loss of benefit or increased costs associated with the ultimate clinical decision or policy choice. Failing to identify a mathematically superior or optimal solution represents a missed opportunity to improve economic efficiency in the delivery of care and clinical outcomes for patients. The ISPOR Optimization Methods Emerging Good Practices Task Force's first report provided an introduction to constrained optimization methods to solve important clinical and health policy problems. This report also outlined the relationship of constrained optimization methods relative to traditional health economic modeling, graphically illustrated a simple formulation, and identified some of the major variants of constrained optimization models, such as linear programming, dynamic programming, integer programming, and stochastic programming. The second report illustrates the application of constrained optimization methods in health care decision making using three case studies. The studies focus on determining optimal screening and vaccination strategies for cervical cancer, optimal statin start times for diabetes, and an educational case to invite the reader to formulate radiation therapy optimization problems. These illustrate a wide range of problem types that can be addressed with constrained optimization methods.

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.

The Cost-effectiveness of Sequences of Biological Disease-modifying Antirheumatic Drug Treatment in England for Patients with Rheumatoid Arthritis Who Can Tolerate Methotrexate.

OBJECTIVE: To ascertain whether strategies of treatment with a biological disease-modifying antirheumatic drug (bDMARD) are cost-effective in an English setting. Results are presented for those patients with moderate to severe rheumatoid arthritis (RA) and those with severe RA. METHODS: An economic model to assess the cost-effectiveness of 7 bDMARD was developed. A systematic literature review and network metaanalysis was undertaken to establish relative clinical effectiveness. The results were used to populate the model, together with estimates of Health Assessment Questionnaire (HAQ) score following European League Against Rheumatism response; annual costs, and utility, per HAQ band; trajectory of HAQ for patients taking bDMARD; and trajectory of HAQ for patients using nonbiologic therapy (NBT). Results were presented as those associated with the strategy with the median cost-effectiveness. Supplementary analyses were undertaken assessing the change in cost-effectiveness when only patients with the most severe prognoses taking NBT were provided with bDMARD treatment. The costs per quality-adjusted life-year (QALY) values were compared with reported thresholds from the UK National Institute for Health and Care Excellence of £20,000 to £30,000 (US$24,700 to US$37,000). RESULTS: In the primary analyses, the cost per QALY of a bDMARD strategy was £41,600 for patients with severe RA and £51,100 for those with moderate to severe RA. Under the supplementary analyses, the cost per QALY fell to £25,300 for those with severe RA and to £28,500 for those with moderate to severe RA. CONCLUSION: The cost-effectiveness of bDMARD in RA in England is questionable and only meets current accepted levels in subsets of patients with the worst prognoses.

Health state utility values for diabetic retinopathy: protocol for a systematic review and meta-analysis.

BACKGROUND: People with diabetic retinopathy tend to have lower levels of health-related quality of life than individuals with no retinopathy. Strategies for screening and treatment have been shown to be cost-effective. In order to reduce the bias in cost-effectiveness estimates, systematic reviews of health state utility values (HSUVs) are crucial for health technology assessment and the development of decision analytic models. A review and synthesis of HSUVs for the different stages of disease progression in diabetic retinopathy has not previously been conducted. METHODS/DESIGN: We will conduct a systematic review of the available literature that reports HSUVs for people with diabetic retinopathy, in correspondence with current stage of disease progression and/or visual acuity. We will search Medline, EMBASE, Web of Science, Cost-Effectiveness Analysis Registry, Centre for Reviews and Dissemination Database, and EconLit to identify relevant English-language articles. Data will subsequently be synthesized using linear mixed effects modeling meta-regression. Additionally, reported disease severity classifications will be mapped to a four-level grading scale for diabetic retinopathy. DISCUSSION: The systematic review and meta-analysis will provide important evidence for future model-based economic evaluations of technologies for diabetic retinopathy. The meta-regression will enable the estimation of utility values at different disease stages for patients with particular characteristics and will also highlight where the design of the study and HSUV instrument have influenced the reported utility values. We believe this protocol to be the first of its kind to be published. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014012891.

Consensus Decision Models for Biologics in Rheumatoid and Psoriatic Arthritis: Recommendations of a Multidisciplinary Working Party.

INTRODUCTION: Biologic therapies are efficacious but costly. A number of health economic models have been developed to determine the most cost-effective way of using them in the treatment pathway. These models have produced conflicting results, driven by differences in assumptions, model structure, and data, which undermine the credibility of funding decisions based on modeling studies. A Consensus Working Party met to discuss recommendations and approaches for future models of biologic therapies. METHODS: Our working party consisted of clinical specialists, modelers, and policy makers. Two 1-day meetings were held for members to arrive at consensus positions on model structure, assumptions, and appropriate data sources. These views were guided by clinical aspects of rheumatoid and psoriatic arthritis and the principles of evidence-based medicine. Where opinions differed, we sought to identify a research agenda that would generate the evidence needed to reach consensus. RESULTS: We gained consensus in four areas of model development: initial response to treatment; long-term disease progression; lifetime costs and benefits; and model structure. Consensus was also achieved on some key parameters such as choices of outcome measures, methods for extrapolation beyond trial data, and treatment switching. A research agenda to support further consensus was also identified. CONCLUSION: Consensus guidance that fully reflects current evidence and clinical understanding was gained successfully. In addition, research needs have been identified. Such guidance can be updated as evidence develops and policy questions change and need not be prescriptive as long as deviations from consensus are clearly explained and justified. FUNDING: Arthritis Research UK and the UK Medical Research Council Network of Hubs for Trials Methodology Research.

Health economic modelling of treatment sequences for rheumatoid arthritis: a systematic review.

The objective of the work reported in this paper was to critically assess how sequential disease-modifying anti-rheumatic drugs (DMARDs) have been modelled in the context of economic evaluation of the use of DMARDs for treatment of rheumatoid arthritis (RA). A secondary purpose was to identify the methodological challenges of modelling sequential therapies. Systematic searches of 10 databases were undertaken in February 2013. Studies were included if they were in the English language and a full comparative economic evaluation was reported. They were appraised by use of the Drummond checklist (Appendix to this paper). Data extracted included economic evaluation data, data relating to sequential treatment, and data on the modelling methods used. Fifty-seven studies were identified, with 25 (44 %) modelling a sequence of treatments. Forty-three (75 %) were cost-utility analyses. Eleven (19 %) were UK studies and 11 (19 %) were US. The remainder were mainly European (26 (46 %)). A distinction was made between studies of recent-onset RA (14 (25 %)) and those of established RA (42 (74 %)). One study (1 %) was unclear. Individual-level models were more likely to meet the Drummond criteria and evaluate sequences. No study identified an optimum sequence of multiple treatments given a set of treatment options. The level of reporting of the methods and evidence used to assess the effect of downstream treatments in the sequence was generally poor. When lifelong models and downstream treatment sequences were considered, evidence gaps were identified. The review discovered that methods have not been consistently applied, leading to varied estimates of cost-effectiveness. Treatment sequences have not been fully considered and modelled, potentially resulting in inaccurate estimates of cost-effectiveness.

Health Assessment Questionnaire disability progression in early rheumatoid arthritis: systematic review and analysis of two inception cohorts.

OBJECTIVE: The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. METHODS: Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. RESULTS: The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. CONCLUSION: Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit.

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

BACKGROUND: 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. SETTING: The valuation surveys were conducted using face-to-face interviews in the respondents' homes. PARTICIPANTS: Two representative samples of the UK general population from Yorkshire (n=600). INTERVENTIONS: None. 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. FUNDING: 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.

Innovation in health economic modelling of service improvements for longer-term depression: demonstration in a local health community.

BACKGROUND: The purpose of the analysis was to develop a health economic model to estimate the costs and health benefits of alternative National Health Service (NHS) service configurations for people with longer-term depression. METHOD: Modelling methods were used to develop a conceptual and health economic model of the current configuration of services in Sheffield, England for people with longer-term depression. Data and assumptions were synthesised to estimate cost per Quality Adjusted Life Years (QALYs). RESULTS: Three service changes were developed and resulted in increased QALYs at increased cost. Versus current care, the incremental cost-effectiveness ratio (ICER) for a self-referral service was £11,378 per QALY. The ICER was £2,227 per QALY for the dropout reduction service and £223 per QALY for an increase in non-therapy services. These results were robust when compared to current cost-effectiveness thresholds and accounting for uncertainty. CONCLUSIONS: Cost-effective service improvements for longer-term depression have been identified. Also identified were limitations of the current evidence for the long term impact of services.

Golimumab for the treatment of rheumatoid arthritis after the failure of previous disease-modifying antirheumatic drugs: a NICE single technology appraisal.

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of golimumab (Simponi(®); Merck Sharp & Dohme, USA) was invited to submit evidence for its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) after the failure of previous disease-modifying antirheumatic drugs (DMARDs). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at The University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article provides details of the manufacturer's initial submission, the ERG's clarification questions and the ERG report submitted to NICE. The decision made by NICE is provided alongside a brief comment on additional results produced from an additional analysis requested by NICE on behalf of the Committee. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based on upon the manufacturer's submission to NICE. The clinical evidence was derived from three randomized controlled trials of golimumab in the treatment of moderate to severe RA: GO-FORWARD and Kay et al. (DMARD-experienced population) and GO-AFTER (tumour necrosis factor [TNF]-α inhibitor-experienced population). The ERG considered that the trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. The trials for golimumab, as well as comparator treatments, were synthesized using mixed-treatment comparison methods for the DMARD-experienced population and an indirect comparison using the Bucher method for the TNF-α inhibitor-experienced population. The trials used were appropriate, although no definitive judgement regarding the comparative efficacy of golimumab with other biologics was possible. The manufacturer provided a DMARD-experienced population model and a TNF-α inhibitor-experienced population model. The models allowed sequences of treatments to be evaluated for each population, although a fully incremental analysis between the use of golimumab following DMARD failure and the use of golimumab following TNF-α inhibitor failure was not possible. Several limitations with the model were identified, and after a request from NICE and suspension of the appraisal, the manufacturer submitted sensitivity analyses with an additional American College of Rheumatology 70 % improvement criteria (ACR70) health state included, using SF-36 data directly from the GO-FORWARD study. The annual rate of the Health Assessment Questionnaire (HAQ) score increase for patients receiving palliative treatment was also changed from 0.09 to 0.06. The further analyses provided highlighted the particular sensitivity of the results to HAQ progression rates and the re-administration frequency for rituximab in the TNF-α inhibitor-experienced population. The Appraisal Committee concluded that golimumab should be recommended in combination with methotrexate as an option for patients with severe active RA who have failed on conventional DMARDs, or who have failed on a TNF-α inhibitor and are contraindicated to or withdrawn from rituximab.

The appropriateness of, and compliance with, telephone triage decisions: a systematic review and narrative synthesis.

AIM: This paper is a report of the synthesis of evidence on the appropriateness of, and compliance with, telephone triage decisions. BACKGROUND: Telephone triage plays an important role in managing demand for health care. Important questions are whether triage decisions are appropriate and patients comply with them. DATA SOURCES: CINAHL, Cochrane Clinical Trials Database, Medline, Embase, Web of Science, and Psyc Info were searched between 1980-June 2010. LITERATURE REVIEW: Rapid Evidence Synthesis. REVIEW METHODS: The principles of rapid evidence assessment were followed. RESULTS: We identified 54 relevant papers: 26 papers reported appropriateness of triage decision, 26 papers reported compliance with triage decision, and 2 papers reported both. Nurses triaged calls in most of the studies (n=49). Triage decisions rated as appropriate varied between 44-98% and compliance ranged from 56-98%. Variation could not be explained by type of service or method of assessing appropriateness. However, inconsistent definitions of appropriateness may explain some variation. Triage decisions to contact primary care may have lower compliance than decisions to contact emergency services or self care. CONCLUSION: Telephone triage services can offer appropriate decisions and decisions that callers comply with. However, the association between the appropriateness of a decision and subsequent compliance requires further investigation and further consideration needs to be given to the minority of calls which are inappropriately managed. We suggest that a definition of appropriateness incorporating both accuracy and adequacy of triage decision should be encouraged.

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

OBJECTIVE: 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 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 health-related assessment instrument's performance differed according to condition, with poor performance in age-related macular degeneration (AMD) and diabetic retinopathy. The more limited evidence on the HUI-3 instrument 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 instrument and showed it was able to differentiate between patients with AMD. CONCLUSIONS: 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 five-level version of EQ-5D may do better at the milder end of visual function.

The Sheffield rheumatoid arthritis health economic model.

The Sheffield RA health economic model has been used in several published cost-effectiveness analyses in both the UK and internationally to evaluate different treatments for patients with RA. This article presents the key methods and assumptions that underpin the model, including justifications for using an individual patient sampling methodology, and why the model has used the HAQ to track disease activity. The article also details how trial and observational data are used in the model to address specific questions. The model has been used to support health policy in both the UK and internationally, although the limited evidence still provides a challenge when using an economic model to determine the cost-effectiveness of RA treatments. The results of analyses using the Sheffield RA model are presented. The limitations of the model are discussed, and improvements are continually required to provide a model that is appropriate to address health economic questions in the future. The Sheffield RA model continues to be used and refined, and allows health economic questions to be answered using a transparent and flexible modelling methodology.

Cost-effectiveness of combination nonbiologic disease-modifying antirheumatic drug strategies in patients with early rheumatoid arthritis.

OBJECTIVE: To compare the costs and benefits of alternative combination strategies of disease-modifying antirheumatic drugs (DMARD) and DMARD monotherapy in patients with early, active rheumatoid arthritis (RA). METHODS: Data were drawn from randomized controlled trials that compared DMARD monotherapy or any DMARD combination strategy, with or without combined steroid therapy. Mixed treatment comparison methods were used to estimate the relative effectiveness of the different strategies. A mathematical model was developed to compare the longterm costs and benefits of the alternative strategies, combining data from a variety of sources. Costs were considered from a health sector viewpoint and benefits were expressed in terms of quality-adjusted life-years (QALY). RESULTS: If decision makers use a threshold of £20,000 (US$29,000) per QALY, then the strategies most likely to be cost-effective are either DMARD combination therapy with downward titration (probability of being optimal = 0.50) or intensive, triple DMARD combination therapy (probability of being optimal = 0.43). The intensive DMARD strategy generated an additional cost of £27,392 per additional QALY gained compared to the downward titration strategy. Other combination strategies were unlikely to be considered cost-effective compared to DMARD monotherapy. Results were robust to a range of scenario sensitivity analyses. CONCLUSION: Combination DMARD therapy is likely to be cost-effective compared to DMARD monotherapy where treatment entails rapid downward dose titration or intensive, triple DMARD therapy.

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.

Utility values in National Institute for Health and Clinical Excellence (NICE) Technology Appraisals.

OBJECTIVE: To review the selection and use of health-related utility values for economic models included in National Institute for Health and Clinical Excellence (NICE) Technology Appraisals. METHOD: A cross-sectional review of reports of economic models submitted to the Technology Appraisals program was undertaken to review the health-related utility data included. Data reviewed included identification and selection of data and the methods used for utility elicitation. The methods used were compared with those from the 2004 Methods Guide issued by NICE. RESULTS: Appraisals conducted after the implementation of the NICE 2004 Methods Guide were reviewed. After exclusion of documents that did not include a de novo cost-utility analysis, 71 submissions (53 manufacturer submissions, 18 assessment group reports) from 39 appraisals were identified, containing 284 unique utility values. Variation was found in the selection, elicitation, valuation, and use of the utility values. Thirty-nine submissions (55%) took utility values from published studies, of which only 31% were identified through a systematic review. Forty-seven (66%) submissions contained health state descriptions reported by patients, and 55 (77%) submissions applied a valuation set derived from the general population. The EQ-5D was used in 35 (49%) submissions, and mapping to a generic health-related quality of life measure was performed in 19 (27%) submissions. CONCLUSIONS: Only 56% of submissions to NICE and assessment reports included utility values that met the NICE 2004 reference case. This highlights variation in the methods used to select and incorporate utility values in economic models for NICE Technology Appraisals.