12.2.1  The GRADE approach

The Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE Working Group) has developed a system for grading the quality of evidence (GRADE Working Group 2004, Schünemann 2006b, Guyatt 2008a, Guyatt 2008b).  Over 20 organizations including the World Health Organization (WHO), the American College of Physicians, the American College of Chest Physicians (ACCP), the American Endocrine Society, the American Thoracic Society (ATS), the Canadian Agency for Drugs and Technology in Health (CADTH), BMJ Clinical Evidence, the National Institute for Health and Clinical Excellence (NICE) in the UK, and  UpToDate® have adopted the GRADE system in its original format or with minor modifications (Schünemann 2006b, Guyatt 2006a, Guyatt 2006b). The BMJ encourages authors of clinical guidelines to use the GRADE system (www.bmj.com/advice/sections.shtml). The Cochrane Collaboration has adopted the principles of the GRADE system for evaluating the quality of evidence for outcomes reported in systematic reviews. This assessment is being phased in together with the introduction of the ‘Summary of findings’ table (see Chapter 11, Section 11.5).


For purposes of systematic reviews, the GRADE approach defines the quality of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the quantity of specific interest. Quality of a body of evidence involves consideration of within-study risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias, as described in Section 12.2.2. The GRADE system entails an assessment of the quality of a body of evidence for each individual outcome.


The GRADE approach specifies four levels of quality (Table 12.2.a). The highest quality rating is for randomized trial evidence. Review authors can, however, downgrade randomized trial evidence to moderate, low, or even very low quality evidence, depending on the presence of the five factors in Table 12.2.b. Usually, quality rating will fall by one level for each factor, up to a maximum of three levels for all factors.  If there are very severe problems for any one factor (e.g. when assessing limitations in design and implementation, all studies were unconcealed, unblinded, and lost over 50% of their patients to follow-up), randomized trial evidence may fall by two levels due to that factor alone.


Review authors will generally grade evidence from sound observational studies as low quality.  If, however, such studies yield large effects and there is no obvious bias explaining those effects, review authors may rate the evidence as moderate or – if the effect is large enough – even high quality (Table 12.2.c). The very low quality level includes, but is not limited to, studies with critical problems and unsystematic clinical observations (e.g. case series or case reports).