Algorithm for assigning evidence grades to therapy recommendations (step 1); (a) Randomized controlled trial (RCT) with blinded assessment of outcomes, intention-to-treat analysis, adequate follow-up (ie, at least 90%, or losses to follow-up are too few to materially affect the results) and sufficient sample size to detect a clinically important difference with power >80%; (b) Subgroup analysis was a priori, performed within an adequate RCT and one of only a few tested, and there was sufficient sample size within the examined subgroup to detect a clinically important difference with power >80%; (c) Sytematic review (SR), or meta-analysis, in which the comparison arms are derived from head-to-head comparisons within the same RCT; (d) SR in which the comparison arms are derived from different placebo-controlled RCTs and then extrapolations are made across RCTs (continued in and )