Certainty of Evidence
Certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. The certainty of evidence was categorized into 4 levels ranging from very low to high. Within the GRADE framework, evidence from randomized controlled trials (RCTs) starts as high-certainty evidence and observational studies start out as low-certainty evidence, but can be rated down for the following reasons: risk of bias, inconsistency, indirectness, imprecision, and publication bias. Additionally, evidence from well-conducted observational studies start as low-certainty evidence, but can be rated up for large effects or dose–response.14