1. Developing evidence based questions

The technical team drafted a series of clinical questions that covered the guideline scope. The GDG and Project Executive refine and approve these questions, which are shown in Appendix A.

2. Searching for the evidence

The information scientist developed a search strategy for each question. Key words for the search were identified by the GDG. In addition, the health economist searched for additional papers providing economic evidence or to inform detailed health economic work (for example, modelling). Papers that were published or accepted for publication in peer-reviewed journals were considered as evidence by the GDG. Conference paper abstracts and non-English language papers were excluded from the searches.

Each clinical question dictated the appropriate study design that was prioritised in the search strategy but the strategy was not limited solely to these study types. The research fellow or health economist identified titles and abstracts from the search results that appeared to be relevant to the question. Exclusion lists were generated for each question together with the rationale for the exclusion. The exclusion lists were presented to the GDG. Full papers were obtained where relevant. See Appendix A for literature search details.

3. Appraising the evidence

The research fellow or health economist, as appropriate, critically appraised the full papers. In general, no formal contact was made with authors however there were ad hoc occasions when this was required in order to clarify specific details. Critical appraisal checklists were compiled for each full paper. One research fellow undertook the critical appraisal and data extraction. The evidence was considered carefully by the GDG for accuracy and completeness.

All procedures are fully compliant with the:

• NICE methodology as detailed in the ‘Guideline Development Methods – Information for National Collaborating Centres and Guideline Developers’ Manual(National Institute for health and clinical excellence 2006a)
• NCC-CC Quality assurance document & systematic review chart available at: http://www.rcplondon.ac.uk/college/ceeu/ncccc_index.htm

4. Health economic evidence

Areas for health economic modelling were agreed by the GDG after the formation of the clinical questions. The health economist reviewed the clinical questions to consider the potential application of health economic modelling, and these priorities were agreed with the GDG. In this guideline, a broad cost-consequence comparison was performed. Details are given in Appendix C. An in-depth economic model was created to compare non-steroidal anti-inflammatory drugs (NSAIDs), including the selective COX-2 inhibitors, and this is described in section 8.3 with details in Appendix D.

The health economist performed supplemental literature searches to obtain additional data for modelling. Assumptions and designs of the models were explained to and agreed by the GDG members during meetings, and they commented on subsequent revisions.

5. Distilling and synthesising the evidence and developing recommendations

The evidence from each full paper was distilled into an evidence table and synthesised into evidence statements before being presented to the GDG. This evidence was then reviewed by the GDG and used as a basis upon which to formulate recommendations. The criteria for grading evidence are shown in Table 2.2.

Evidence tables are available on-line at (to be completed upon publication)

6. Grading the evidence statements

7. Agreeing the recommendations

The GDG employed formal consensus techniques to:

• ensure that the recommendations reflected the evidence-base
• approve recommendations based on lesser evidence or extrapolations from other situations
• reach consensus recommendations where the evidence was inadequate
• debate areas of disagreement and finalise recommendations.

The GDG also reached agreement on the following:

• five to ten recommendations as key priorities for implementation
• five key research recommendations
• algorithms.

In prioritising key recommendations for implementation, the GDG took into account the following criteria:

• high clinical impact
• high impact on reducing variation
• more efficient use of NHS resources
• allowing the patient to reach critical points in the care pathway more quickly.

Audit criteria will be produced for NICE by CASPE Research following publication in order to provide suggestions of areas for audit in line with the key recommendations for implementation.

8. Structuring and writing the guideline

The guideline is divided into sections for ease of reading. For each section the layout is similar and contains:

• Clinical introduction
  • Sets a succinct background and describes the current clinical context
• Methodological introduction
  • Describes any issues or limitations that were apparent when reading the evidence base
• Evidence statements
  • Provides a synthesis of the evidence-base and usually describes what the evidence showed in relation to the outcomes of interest
• Health economics
  • Presents, where appropriate, an overview of the cost effectiveness evidence-base, or any economic modelling
• From evidence to recommendations
  • This section sets out the Guideline Development Group (GDG) decision-making rationale providing a clear and explicit audit trail from the evidence to the evolution of the recommendations.
• Recommendations
  • Provides stand alone, action orientated recommendations.
• Evidence tables
  • The evidence tables are not published as part of the full guideline but are available on-line at (to be completed upon publication). These describe comprehensive details of the primary evidence that was considered during the writing of each section.

9. Writing the guideline

The first draft version of the guideline was drawn up by the technical team in accord with the decisions of the GDG, incorporating contributions from individual GDG members in their expert areas and edited for consistency of style and terminology. The guideline was then submitted for a formal public and stakeholder consultation prior to publication. The registered stakeholders for this guideline are detailed on the NICE website www.nice.org.uk. Editorial responsibility for the full guideline rests with the GDG.

The following versions of the guideline are available:

• Full version: Details the recommendations., the supporting evidence base and the expert considerations of the GDG. Published by the NCC-CC. Available at (to be completed upon publication)
• NICE version: Documents the recommendations without any supporting evidence.
  Available at (to be completed upon publication)
• “Quick reference guide”: An abridged version.
  Available online upon publication
• “Understanding NICE guidance”: A lay version of the guideline recommendations
  Available online upon publication

10. 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 16 April 2007 to be considered. Future guideline updates will consider evidence published after this cut-off date.

Two years after publication of the guideline, NICE will ask a National Collaborating Centre to determine whether the evidence base has progressed significantly to alter the guideline recommendations and warrant an early update. If not, the guideline will be considered for update approximately four years after publication.