*2.9. Classification of the Level of Evidence*

We used the GRADE, developed by the Cochrane GRADE working group, to determine the level of evidence and the grade of recommendation [9]. In the GRADE, the level of evidence is preferentially determined according to the study design. RCTs are categorized as having a high level of evidence while observational studies are categorized as having a low level of evidence. If there is a risk of bias, inconsistency, indirectness, imprecision, or publication bias through the evaluation of evidence in a systematic literature review, the level of evidence is lowered by the first or second grade. If the effect size is large, the confounding variable reduces the effect size or if there is a dose–response relationship, the level of evidence can be increased.

The GRADE categorizes the level of evidence into four categories: high, moderate, low, and very low [10]. In the past, the definition of the level of evidence meant the possibility of change according to future research; however, since further research is not always possible, it has been revised to be the level of confidence now. In our CPGs, the classification of the classical text-based (CTB) level of evidence was also applied. The levels of evidence and definitions are provided in Table 1.

**Table 1.** GRADE level of evidence.

