The GDG was involved in the design of the model, selection of inputs and interpretation of the results. When published data was not available GDG expert opinion was used to populate the model. Model inputs and assumptions were reported fully and transparently. The results were subject to sensitivity analysis and limitations were discussed. The model was peer-reviewed by another health economist at the NCGC. Full methods for the cost analyses are described in Appendices L, M and N in the full version of the original guideline document. In the Absence of Economic Evidence When no relevant published studies were found, and a new analysis was not prioritized, the GDG made a qualitative judgement about cost effectiveness by considering expected differences in resource use between options and relevant UK NHS unit costs alongside the results of the clinical review of effectiveness evidence. Methods Used to Formulate the Recommendations Expert Consensus Informal Consensus Description of Methods Used to Formulate the Recommendations Note from the National Guideline Clearinghouse (NGC): This guideline was developed by the National Clinical Guideline Centre (NCGC) on behalf of the National Institute for Health and Care Excellence (NICE). See the “Availability of Companion Documents” field for the full version of this guidance. A multidisciplinary Guideline Development Group (GDG) comprising professional group members and consumer representatives of the main stakeholders developed this guideline. The group met every 5 to 6 weeks during the development of the guideline. Staff from the NCGC provided methodological support and guidance for the development process. The team working on the guideline included a project manager, systematic reviewers, health economists and information scientists. They undertook systematic searches of the literature, appraised the evidence, conducted meta-analysis and cost effectiveness analysis where appropriate and drafted the guideline in collaboration with the GDG. Developing Recommendations Over the course of the guideline development process, the GDG was presented with: Evidence tables of the clinical and economic evidence reviewed from the literature. All evidence tables are in Appendix E (clinical evidence) and Appendix F (economic evidence) in the full version of the original guideline document. Summary of clinical and economic evidence and quality (as presented in chapters 5-10 in the full version of the original guideline document) Forest plots and summary ROC curves (see Appendix G in the full version of the original guideline document) A description of the methods and results of the cost-sensitivity analysis undertaken for the guideline (see Appendices L, M, N in the full version of the original guideline document) Recommendations were drafted based on GDG interpretation of the available evidence, taking into account the balance of benefits and harms and evidence of cost effectiveness. When clinical and economic evidence was of poor quality, conflicting or absent, the GDG drafted recommendations based on expert opinion. The considerations for making consensus-based recommendations included the balance between potential harms and benefits, economic or implications compared to the benefits, current practices, recommendations made in other relevant guidelines, patient preferences and equality issues. Consensus on recommendations was achieved through discussions in the GDG meetings. The GDG also considered areas where the uncertainty was sufficient to justify delaying making a recommendation to await further research, considering the potential harm of failing to make a clear recommendation. The main considerations specific to each recommendation are outlined in the Evidence to Recommendation Section preceding the recommendation section. Rating Scheme for the Strength of the Recommendations Strength of Recommendations Some recommendations can be made with more certainty than others. The Guideline Development Group (GDG) makes a recommendation based on the trade-off between the benefits and harms of an intervention, considering the quality of the underpinning evidence. For some interventions, the GDG is confident that, given the information it has looked at, most patients would choose the intervention. The wording used in the recommendations in this guideline denotes the certainty with which the recommendation is made (the strength of the recommendation). Interventions That Must (or Must Not) Be Used the GDG usually uses ‘must’ or ‘must not’ only if there is a legal duty to apply the recommendation. Occasionally ‘must’ (or ‘must not’) is used if the consequences of not following the recommendation could be extremely serious or potentially life threatening. Interventions That Should (or Should Not) Be Used – a ‘Strong’ Recommendation The GDG uses ‘offer’ (and similar words such as ‘refer’ or ‘advise’) when confident that, for the vast majority of patients, an intervention will do more good than harm, and be cost-effective. Similar forms of words (for example, ‘Do not offer…’) are used when the GDG is confident that an intervention will not be of benefit for most patients. Interventions That Could Be Used the GDG uses ‘consider’ when confident that an intervention will do more good than harm for most patients, and be cost-effective, but other options may be similarly cost-effective. The choice of intervention, and whether or not to have the intervention at all, is more likely to depend on the patient’s values and preferences than for a strong recommendation, and so the healthcare professional should spend more time considering and discussing the options with the patient. Cost Analysis Cost-effectiveness Criteria In general, an intervention was considered to be cost effective if either of the following criteria applied (given that the estimate was considered plausible): The intervention dominated other relevant strategies (that is, it was both less costly in terms of resource use and more clinically effective compared with all the other relevant alternative strategies), or The intervention cost less than £20,000 per quality adjusted life year (QALY) gained compared with the next best strategy. If the GDG recommended an intervention that was estimated to cost more than £20,000 per QALY gained, or did not recommend one that was estimated to cost less than £20,000 per QALY gained, the reasons for this decision are discussed explicitly in the ‘from evidence to recommendations’ section of the relevant chapter with reference to issues regarding the plausibility of the estimate or to the factors set out in the National Institute for Health and Care excellence (NICE) report ‘Social value judgements: principles for the development of NICE guidance’. If a study reported the cost per life year gained but not QALYs, the cost per QALY gained was estimated by multiplying by an appropriate utility estimate to aid interpretation. The estimated cost per QALY gained is reported in the economic evidence profile with a footnote detailing the life-years gained and the utility value used. When QALYs or life years gained are not used in the analysis, results are difficult to interpret unless one strategy dominates the others with respect to every relevant health outcome and cost.
