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. The evidence review used for the development of recommendations, conducted by ECRI, assessed the confidence in the quality of the evidence base using GRADE methodology and assigned a rating of High, Moderate, Low, or Very Low. The outcomes judged to be critical were used to determine the overall quality of evidence. Per GRADE, if the quality of evidence differs across the critical outcomes, the lowest quality of evidence for any of the relevant critical outcomes determines the overall quality of the evidence for a recommendation; the overall confidence cannot be higher than the lowest confidence in effect estimates for any outcome that is determined to be critical for clinical decision making.[12,150] The elements that go into the confidence in the quality of the evidence include: Is there high or moderate quality evidence that answers this question? What is the overall certainty of this evidence? Values and preferences is an overarching term that includes patients perspectives, beliefs, expectations, and goals for health and life. 