Statistical TABLE ] (Continued) Grade of Recommendation Bene t vs Risk and Burdens Methodologic Strength of Supporting Evidence Implications Weak (conditional) recommendation, very- low quality evidence Uncertainty in the estimates of bene ts, risks, and burden; bene ts, risk and burden may be closely balanced We have very little con dence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect Other alternatives may be equally reasonable. Higher quality research is likely to have an important impact on our con dence in the estimate of effect and may well change the estimate Ungraded consensus-based suggestions Ungraded Consensus- Based Statement Uncertainty due to lack of evidence but expert opinion that bene ts outweigh risk and burdens or vice versa Insuf cient evidence for a graded recommendation Future research may well have an important impact on our con dence in the estimate of effect and may change the estimate heterogeneity of the pooled results was assessed using the Higgins I2 and the c2 tests. A Higgins I2 value of $ 50% or c2 P < .05 was considered to represent signi cant heterogeneity. Assessing the Overall Quality of the Evidence The overall certainty (quality) of the evidence was assessed for each critical or important outcome of interest using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) Evidence pro les were created using the Guideline Development Tool, which categorized the overall quality of the body of evidence into 1 of 4 levels: high, moderate, low, or very low. Drafting Recommendations The panel drafted and graded recommendations based on the results of the meta-analyses and evidence pro les. Recommendations were graded according to CHEST s grading system, which uses the GRADE approach (Table 2).11,12 The recommendations were either strong or weak according to this approach. 