The methodological manual for the development of the NHS’s CPG includes a detailed description of the methodology employed to develop these guidelines and is freely available on the GuiaSalud website (http://www.guiasalud.es )¹⁷.

The following steps have been followed:

1. Creation of the guideline development group, comprised of primary (family and community medicine) and specialised (neurology, cardiology, internal medicine, geriatrics, haematology and pharmacology). These professionals were contacted through the different scientific societies related with CPG. In order to develop material for patients, a discussion group and interviews with patients has been created.
2. Formulation of clinical questions following the PICO format: patient, intervention, comparison and outcomes.
3. Bibliographic search that has prioritised the identification of systematic reviews (SRs) and other critical synthesis documents of scientific literature such as health technologies assessment reports. In order to do this, the first phase has included carrying out a search for other CPGs to determine what systematic reviews were considered to support their recommendations (the main CPGs used as secondary sources are included in annex 7). Subsequently, additional systematic reviews have been identified after the search date of selected CPGs. In this first phase the following electronic databases have been consulted:
• TRIP Database
• NHS National Library of Guidelines
• AHRQ National Guideline Clearinghouse
• Cochrane Database of Systematic Reviews (The Cochrane Library)
• Database of Abstracts of Reviews of Effects (DARE)
• Health Technology Assessment Database
• NHS Economic Evaluation Database (NHS EED)
• MEDLINE (accessed through PubMed)
• EMBASE (accessed through Ovid)
4. Additionally, several technology assessment agencies such as the National Institute for Clinical Excellence (NICE), agencies that develop CPG such as SIGN and international societies such as the American Heart Association have been consulted.
5. In the second phase, a broader search has been performed for individual studies to update relevant systematic reviews in order to answer the questions of the CPG. The search has mainly attempted to identify randomised clinical trials (RCTs) and observational studies maintaining the original search strategy for relevant systematic reviews. When this strategy has not been available, a specific strategy for each of the questions has been designed and in each case filters validated for the identification of RCTs and observational studies have been added. In this phase the following databases have been consulted: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (accessed through Ovid).
6. No linguistic limits have been incorporated to the searches performed, but the studies considered have been mainly in Spanish, English and French. Searches until September 2007 have been performed, even though relevant studies have been identified in the most influential biomedical journals throughout the CPG development process.
7. The search strategies corresponding to each section of the guideline are available at the Iberoamerican Cochrane Centre (tsc@cochrane.es).
8. Quality assessment of the evidence and grading of recommendations has been performed using the system pertaining to the Scottish Intercollegiate Guidelines Network (SIGN) (see annex 1). Controversial recommendations or those lacking evidence have been resolved by means of simple consensus of the development group.
9. The text has been reviewed by a multidisciplinary team of external reviewers that included patients. The final version of the guideline’s text has been reviewed and approved by the group of authors.
10. The CPG is to be updated every three years; however, its electronic version may be updated more frequently if necessary.
11. The group of authors has participated in all stages of the process except in the search, quality assessment and synthesis of the literature, which were carried out by the authors from the Iberoamerican Cochrane Centre.