The GRADE system uses the following four domains to assess the strength of each Balance of desirable and undesirable outcomes Confidence in the quality of the evidence Values and preferences Other implications, as appropriate, Resource use Equity Acceptability Feasibility Subgroup considerations The following sections further describe each domain. Balance of desirable and undesirable outcomes refers to the size of anticipated benefits (e.g., increased longevity, reduction in morbid event, resolution of symptoms, improved quality of life, decreased resource use) and harms (e.g., decreased longevity, immediate serious complications, adverse event, impaired quality of life, increased resource use, inconvenience/hassle) relative to each other. This domain is based on the understanding that the majority of clinicians will offer patients therapeutic or preventive measures as long as the advantages of the intervention exceed the risks and AEs. The certainty or uncertainty of the clinician about the risk-benefit balance will greatly influence the strength of the recommendation. Some of the discussion questions that fall under this domain include: Given the best estimate of typical values and preferences, are you confident that the benefits outweigh the harms and burden or vice versa? Are the desirable anticipated effects large? Are the undesirable anticipated effects small? Are the desirable effects large relative to undesirable effects? Confidence in the quality of the evidence reflects the quality of the evidence base and the certainty in that evidence. This second domain reflects the methodological quality of the studies for each outcome variable. In general, the strength of recommendation follows the level of evidence, but not always, as other domains may increase or decrease the strength. 