Searching for and identifying the relevant evidence
The Information Scientist developed a search strategy for each question. Key words for the search were identified by the GDG.
Systematic literature searches were undertaken to identify evidence within published literature in order to answer the clinical questions. Clinical databases were searched using relevant medical subject headings, free-text terms and study type filters. Non-English studies were not reviewed and were therefore excluded from searches.
Each database was searched up to 18th June 2009. One initial search was performed for the whole guideline topic which looked for systematic reviews, guidelines and economic papers in the non-STEMI acute coronary syndrome populations.
The clinical questions were formulated using the PICO (Population, Intervention, Comparison, and Outcome) format and this was used as a basis for constructing a search strategy. Quality assurance of search strategies were approached by checking relevant key papers were retrieved, and amending search strategies if appropriate. The questions, the study types applied, the databases searched and the years covered can be found in Appendix F.
When looking for health economic evidence a whole guideline search looking for economic evidence relating to an ACS population was undertaken on the NHS economic evaluation database (EED) and health technology assessment (HTA) databases with no date restrictions. Additionally, it was run, with a specific economic filter, on Medline and Embase from 2007 to present, to ensure recent publications that may have not yet been indexed by these databases were identified. This was supplemented by an additional search that looked for economic papers specifically relating to revascularisation (PCI or CABG) on the NHS EED and HTA database as it became apparent that some papers in this area were not being identified through the first search. Additionally, ad hoc searches were carried out for individual questions as required.
Titles and abstracts of retrieved papers were reviewed by the Research Fellow or Health Economist and full papers were ordered for studies potentially relevant to each clinical question. The full papers were reviewed against pre-specified inclusion and exclusion criteria.
Where the guideline updated Technology Appraisals on clopidogrel or glycoprotein IIb/IIIa inhibitors, the inclusion criteria for clinical evidence was RCTs published beginning of 2003 (update of clopidogrel TA) or 2002 (update of glycoprotein IIb/IIIa inhibitors TA) with a sample size ≥250 and at least 60% of the people enrolled given the diagnosis of unstable angina or non-ST-segment-elevation ACS. Where possible, results were reported in the subgroup of patients with unstable angina/ non-ST-segment-elevation myocardial infarction. In addition, the trial should report on the six key clinical outcomes agreed for this guideline (30 day survival, reinfarction, LV function, revascularisation, quality of life, and serious complications). Review papers were checked for additional relevant studies which were then ordered. Additional papers identified by the GDG were ordered and reviewed.
For the remainder of the guideline, inclusion criteria were as above, except there was no restriction on sample size. For areas in which there were no RCTs, other evidence (observational studies, diagnostic studies) were included.
From a health economic perspective studies were prioritised for inclusion if they were from a UK perspective, based intervention effectiveness on data from one or more RCT and these met the clinical data population cut offs (e.g. >60% UA/NSTEMI population). A judgement was made on a question by question basis regarding whether to include studies from a non-UK perspectivea, that used observational evidence or that used data that did not meet the clinical data population cut-offs, depending on the availability and quality of the other evidence.
Full economic evaluations (cost-effectiveness, cost-utility and cost-benefit analyses), cost-consequence analyses and comparative costing studies that addressed the clinical question and included UA/NSTEMI adult patients were included.
Studies that only reported cost per hospital (not per patient), or only report average cost effectiveness without disaggregated costs and effects were excluded. Abstracts, posters, reviews, letters/editorials, foreign language publications and unpublished studies were excluded. Studies judged to have an applicability rating of ‘not applicable’ were excluded. A judgement was made on a question by question basis regarding whether to include studies with a quality rating of ‘very serious limitations’, although these would usually be excluded.
Any publication date cut-offs applied to the clinical evidence were also applied to the economic evidence.
Exclusion lists were generated for each question together with the rationale for the exclusion. The exclusion lists were presented to the GDG.
Assessing the cost effectiveness of interventions
It is important to investigate whether healthcare interventions are cost effective as well as clinically effective. That is they offer good value for money. This helps us to get the most health gain from available NHS resources. In any healthcare system resources are finite and choices must be made about how best to spend limited budgets. We want to prioritise interventions that provide a high health gain relative to their cost.
Cost-effective analysis compares the costs and health outcomes of two or more alternative healthcare interventions. The criteria applied to an intervention to be considered cost effective were either:
The intervention dominated other relevant strategies – that is, it is both less costly in terms of resource use and more clinically effective when compared to other relevant strategies
The intervention cost less than £20,000 per quality-adjusted life-year (QALY) gained compare with the next best strategy
Where health outcomes were not expressed in QALYs or economic evidence was not available the GDG made a judgement based on the available evidence.
The GDG agreed a priority area for original health economic modelling for the guideline. The analysis undertaken looked at alternative combined antiplatelet and antithrombin strategies. See Appendix C for the full report. A summary of relevant results is also included in each relevant chapter of the guideline.
The following general principles were adhered to:
The GDG was consulted during the construction and interpretation of the model.
The model was based on clinical evidence identified from the systematic review of clinical evidence.
Model inputs and assumptions were reported fully and transparently.
Sensitivity analysis was used to explore uncertainties in model inputs and methods.
Costs were estimated from an NHS perspective.
Updating the guideline
Literature searches were repeated for all of the evidence based questions at the end of the GDG development process allowing any relevant papers published up until 6 April 2009 to be considered. Future guideline updates will consider evidence published after this cut-off date.
Following publication and in accordance with the technical manual, NICE will ask a National Collaborating Centre to determine whether the evidence base has progressed significantly to alter the guideline recommendations and warrant an update.
Disclaimer
Healthcare providers need to use clinical judgement, knowledge and expertise when deciding whether it is appropriate to apply guidelines. The recommendations cited here are a guide and may not be appropriate for use in all situations. The decision to adopt any of the recommendations cited here must be made by the practitioner in light of individual patient circumstances, the wishes of the patient, clinical expertise and resources.
The Nation Collaborating Centre for Chronic Conditions (now a part of the National Clinical Guideline Centre for Acute and Chronic Conditions) disclaim any responsibility for damages arising out of the use or non-use of these guidelines and the literature used in support of these guidelines.
Funding
The National Collaborating Centre for Chronic Conditions (now a part of the National Clinical Guideline Centre) were commissioned by the National Institute for Health and Clinical Excellence to undertake the work on this guideline.
