Jonathan Tosh

Management of rheumatoid arthritis: summary of NICE guidance

Rheumatoid arthritis is a chronic, progressive autoimmune disease associated with inflammation principally in synovial joints and affecting over 400 000 people in the United Kingdom.1 In recent years it has become clear that pain and disability can be avoided if the disease is recognised early and treated promptly and appropriately. It is therefore crucial that all health professionals have knowledge of the recognition, management, and appropriate referral of patients with rheumatoid arthritis. This article summarises the recommendations in the guideline from the National Institute for Health and Clinical Excellence (NICE) on the management of rheumatoid arthritis, from early identification to managing chronic and severe disease.2 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the opinion of the Guideline Development Group (GDG) of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Referral, diagnosis, and investigations [ Based on high and moderate quality observational studies of early prognosis and identification or diagnosis ] [ Based on data from case series ]

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 instruments 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.

Pragmatic intervention for increasing self-directed exercise behaviour and improving important health outcomes in people with multiple sclerosis: A randomised controlled trial

Background: Exercise programmes that can demonstrate evidence of long-lasting clinical effectiveness are needed for people with multiple sclerosis (PwMS). Objective: The objective of this study was to assess the effects of a practically implemented exercise programme on self-directed exercise behaviour and important health outcomes in PwMS to nine months of follow-up. Methods: We conducted a parallel-arm, randomised controlled trial: 120 PwMS (Expanded Disability Status Scale (EDSS) 1.0–6.5) randomised to a three-month exercise intervention plus usual care, or usual care only. Two supervised plus one home-exercise session (weeks 1–6) were followed by one supervised and two home-exercise sessions (weeks 7–12). Cognitive-behavioural techniques promoted long-term exercise behaviour change. Outcomes were blindly assessed at baseline and at three and nine months after randomisation. The primary outcome was self-reported exercise behaviour (Godin Leisure Time Exercise Questionnaire (GLTEQ)). Secondary outcomes included fatigue and health-related quality of life (HRQoL). Results: The intervention increased self-reported exercise (9.6 points; 95% CI: 2.0 to 17.3 points; p = 0.01) and improved fatigue (p < 0.0001) and many HRQoL domains (p ≤ 0.03) at three months. The improvements in emotional well-being (p = 0.01), social function (p = 0.004) and overall quality of life (p = 0.001) were sustained for nine months. Conclusion: This pragmatic approach to implementing exercise increases self-reported exercise behaviour, improves fatigue and leads to a sustained enhancement of HRQoL domains in PwMS.

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.

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.

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

The Sheffield rheumatoid arthritis health economic model

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

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.

Pragmatic exercise intervention for people with multiple sclerosis (ExIMS Trial) : study protocol for a randomised controlled trial

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.

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

Exercise is an effective intervention for improving function, mobility and health-related quality of life in people with multiple sclerosis (PwMS). Questions remain however, regarding the effectiveness of pragmatic exercise interventions for evoking tangible and sustained increases in physical activity and long-term impact on important health outcomes in PwMS. Furthermore, dose-response relationships between exercise and health outcomes have not previously been reported in PwMS. These issues, and improved knowledge of cost effectiveness, are likely to influence key decisions of health policy makers regarding the implementation of exercise therapy as part of the patient care pathway for PwMS. Hence, the primary aim of this study is to investigate whether a 12-week tapered programme of supervised exercise, incorporating cognitive-behavioural techniques to facilitate sustained behaviour change, is effective for evoking improvements in physical activity and key health outcomes in PwMS over 9 months of follow-up. A total of 120 PwMS will be randomised (1:1) to either a 12-week pragmatic exercise therapy intervention or usual care control group. Participants will be included on the basis of a clinical diagnosis of MS, with an expanded disability status score (EDSS) between 1 and 6.5. Outcome measures, to be assessed before and after the intervention and 6 months later, will include physical activity, clinical and functional measures and health-related quality of life. In addition, the cost effectiveness of the intervention will be evaluated and dose-response relationships between physical activity and the primary/secondary outcomes in those with mild and more severe disease will be explored.