Francis Ruiz

GRADE guidelines: 10. Considering resource use and rating the quality of economic evidence

OBJECTIVES In this article, we describe how to include considerations about resource utilization when making recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. STUDY DESIGN AND SETTINGS We focus on challenges with rating the confidence in effect estimates (quality of evidence) and incorporating resource use into evidence profiles and Summary of Findings (SoF) tables. RESULTS GRADE recommends that important differences in resource use between alternative management strategies should be included along with other important outcomes in the evidence profile and SoF table. Key steps in considering resources in making recommendations with GRADE are the identification of items of resource use that may differ between alternative management strategies and that are potentially important to decision makers, finding evidence for the differences in resource use, making judgments regarding confidence in effect estimates using the same criteria used for health outcomes, and valuing the resource use in terms of costs for the specific setting for which recommendations are being made. CONCLUSIONS With our framework, decision makers will have access to concise summaries of recommendations, including ratings of the quality of economic evidence, and better understand the implications for clinical decision making.

Newer agents for blood glucose control in type 2 diabetes: summary of NICE guidance

Management of type 2 diabetes is complex and aims to prevent and reduce the impact of complications by encouraging a healthy lifestyle, controlling blood pressure and blood lipids, and lowering blood glucose concentrations. In recent years new drugs have become available for blood glucose control, including the long acting insulin analogues (insulin detemir and insulin glargine); glucagon-like peptide-1 (GLP-1) mimetics (exenatide); and dipeptidylpeptidase-4 (DPP-4) inhibitors (sitagliptin and vildagliptin). In addition, safety concerns have surfaced recently about the use of the thiazolidinediones (pioglitazone and rosiglitazone). This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the use of newer agents for control of blood glucose in type 2 diabetes1 and updates the relevant section of the NICE clinical guideline on the management of type 2 diabetes.2 NICE recommendations are based on systematic reviews of best available evidence. When minimal evidence is available, recommendations are based on the Guideline Development Group’s experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### DPP-4 inhibitors and thiazolidinediones DPP-4 inhibitors stabilise concentrations of endogenous glucagon-like peptide and increase insulin secretion. [ Based on evidence ranging from low to moderate quality from randomised controlled trials; a meta-analysis; current NICE guidance 2 ; and a health economic analysis ]

Introducing GRADE across the NICE clinical guideline program

OBJECTIVES Grading of Recommendations Assessment, Development and Evaluation (GRADE) is a system for rating the confidence in estimates of effect and grading guideline recommendations. It promotes evaluation of the quality of the evidence for each outcome and an assessment of balance between desirable and undesirable outcomes leading to a judgment about the strength of the recommendation. In 2007, the National Institute for Health and Clinical Excellence began introducing GRADE across its clinical guideline program to enable separation of judgments about the evidence quality from judgments about the strength of the recommendation. STUDY DESIGN AND SETTING We describe the process of implementing GRADE across guidelines. RESULTS Use of GRADE has been positively received by both technical staff and guideline development group members. CONCLUSION A shift in thinking about confidence in the evidence was required leading to a more structured and transparent approach to decision making. Practical problems were also encountered; these have largely been resolved, but some areas require further work, including the application of imprecision and presenting results from analyses considering more than two alternative interventions. The use of GRADE for nonrandomized and diagnostic accuracy studies needs to be refined.

Applying rapid 'de-facto' HTA in resource-limited settings: experience from Romania.

BACKGROUND In attempting to constrain healthcare expenditure growth, health technology assessment (HTA) can enable policy-makers to look beyond budget impact and facilitate more rational decision-making. However lack of technical capacity and poor governance can limit use in some countries. Undertaking de facto HTA by adapting decisions taken in countries with established processes is a method that may be applied while building domestic HTA capacity. We explored the potential for applying this approach in Romania. METHODS As part of a review of the basic health benefits available to insured Romanians we examined the listing process and content of the Romanian drug reimbursement formulary. We assessed value for money indirectly by drawing on appraisals by UKs NICE, and for products considered cost effective in the UK, adjusting prices by the ratio of Romanian per capita GDP to UK per capita GDP. FINDINGS We found more than 30 of the top 50 medicines on the Romanian formulary unlikely to be cost-effective, suggesting that existing external reference pricing mechanisms may not be delivering good value for money. CONCLUSIONS While not taking into account local costs or treatment patterns, absent local considerations of value for money, this method offers a guide for both drug selection and pricing. Until robust local HTA processes are established this approach could support further analysis of existing prices and pricing mechanisms. Applied more generally, it is arguably preferable to external reference pricing, product delisting or arbitrary price cuts, and may support the future development of more rigorous, evidence-based decision-making.

How long has NICE taken to produce Technology Appraisal guidance? A retrospective study to estimate predictors of time to guidance

Objectives To assess how long the UKs National Institute for Health and Clinical Excellences (NICE) Technology Appraisal Programme has taken to produce guidance and to determine independent predictors of time to guidance. Design Retrospective time to event (survival) analysis. Setting Technology Appraisal guidance produced by NICE. Datasource All appraisals referred to NICE by February 2010 were included, except those referred prior to 2001 and a number that were suspended. Outcome measure Duration from the start of an appraisal (when the scope document was released) until publication of guidance. Results Single Technology Appraisals (STAs) were published significantly faster than Multiple Technology Appraisals (MTAs) with median durations of 48.0 (IQR; 44.3–75.4) and 74.0 (IQR; 60.9–114.0) weeks, respectively (p <0.0001). Median time to publication exceeded published process timelines, even after adjusting for appeals. Results from the modelling suggest that STAs published guidance significantly faster than MTAs after adjusting for other covariates (by 36.2 weeks (95% CI −46.05 to −26.42 weeks)) and that appeals against provisional guidance significantly increased the time to publication (by 42.83 weeks (95% CI 35.50 to 50.17 weeks)). There was no evidence that STAs of cancer-related technologies took longer to complete compared with STAs of other technologies after adjusting for potentially confounding variables and only weak evidence suggesting that the time to produce guidance is increasing each year (by 1.40 weeks (95% CI −0.35 to 2.94 weeks)). Conclusions The results from this study suggest that the STA process has resulted in significantly faster guidance compared with the MTA process irrespective of the topic, but that these gains are lost if appeals are made against provisional guidance. While NICE processes continue to evolve over time, a trade-off might be that decisions take longer but at present there is no evidence of a significant increase in duration.

Mind the costs, too : towards better cost-effectiveness analyses of PBF programmes

### Summary box In the last two decades, performance-based financing (PBF) has gained worldwide prominence. As of September 2016, the Health Results Innovation Trust Fund (HRITF) at the World Bank supported 29 low-income and middle-income countries in the introduction, implementation and evaluation of 35 PBF programmes, with expenditure near

S1– An evaluation of pathway modeling to assess cost-effectiveness in guidelines

2.5 billion. Although PBF is perceived as a tool to achieve the Sustainable Development Goals, several global health experts have pointed to its mixed evidence base.1 In recent years, PBF has become one of the most divisive topics in the global health community, as illustrated by the lively discussions following the publication of Paul et al ’s piece.2 Policy-makers need to assess whether PBF is an appropriate policy choice for their countries, given the substantial budget constraints they face and that are likely to worsen with transition from aid. In practice, whether the investments required to implement PBF are ‘worthwhile’ is a question that can be answered by a cost-effectiveness analysis (CEA). However, a recent review found no studies making clear connections between the costs and effects of PBF.3 Our search yielded three CEAs …

Prophylaxis against infective endocarditis for dental procedures – summary of the NICE guideline

PRIMARY TRACK: Evidence generation and synthesis SECONDARY TRACK: Cost-effectiveness research BACKGROUND (INTRODUCTION): With health-care systems under increasing financial pressures, cost-effectiveness analysis is an area of increasing interest. The economic modeling of pathways of care and service configuration is not common, but potentially could offer significant and valuable information on the organization of health care. In association with National Collaborating Centres, the National Institute for Health and Clinical Excellence (NICE) produces guidelines on the appropriate treatment and care of people, which have included pathway modeling. We will explore the methods, opportunities, and challenges pathway modeling offers in clinical guidelines. LEARNING OBJECTIVES (TRAINING GOALS): 1. Learn of methods to carry out cost-effectiveness analysis of clinical pathways. 2. Understand the challenges and opportunities of using more extensive cost-effectiveness analysis in guideline development. 3. Identify potential areas of future development for health economics in clinical guidelines. METHODS: A retrospective analysis of published NICE clinical guidelines, with the aim of identifying and extracting methodology applied to analyzing the cost-effectiveness of pathways of care and service configuration. We will examine how these analyses relate to the final recommendations. RESULTS: We will present a review of the methodologies utilized when modeling clinical pathways in NICE guidelines. We will examine how the methods chosen relate to the clinical questions under discussion. We will examine how decision makers interpreted these analyses and how they affected the formation of recommendations. We will present an outline of the challenges facing guideline developers when incorporating pathway modeling into their cost-effectiveness analysis. DISCUSSION (CONCLUSION): We will assess the appropriateness of the methodologies used and whether they had a significant impact on the decision-making process. We will examine the potential benefits and opportunities of modeling pathways of care. We will also discuss the potential challenges these methods pose to guideline developers in terms of skills and resourcing. Finally, we will consider what the future of pathway modeling is in clinical guidelines and how methods could develop. TARGET AUDIENCE(S): 1. Health economists 2. Guideline developer 3. Developer of guideline-based products 4. Health care policy analyst/policymaker