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To ensure that the statements made in this document are evidence-based, the current literature was reviewed
and critically appraised. A comprehensive literature review of the studies published between January 1980 and
September 2015 was carried out.
The guidelines were retained if they were supported by sufficient high-level scientific evidence and/or when
a large consensus among experts was obtained. By default, a a clinical approach guideline is defined as being
the criterion-standard clinical approach. If an approach is judged to be acceptable but is not unanimously
recognized as a criterion-standard clinical approach, indication is given that it is still subject to discussion and/or
evaluation.
These guidelines have five different “strengh of guideline” ratings (SIGN grading system1):
A At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target
population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to the target
population, and demonstrating overall consistency of results
B A body of evidence including studies rated as 2++, directly applicable to the target population, and
demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+, directly applicable to the target population and
demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
✓ Recommended best practice based on the clinical experience of the guideline development group
1++ high quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias; 1+ well
conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias; 2++ high quality systematic reviews of case control or cohort
studies/high quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship
is causal; 2+ well conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the
relationship is causal; 3 non-analytic studies, e.g. case reports, case series; 4 expert opinions.
1 http://www.sign.ac.uk/guidelines/fulltext/50/annexoldb.html
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