Table 1 Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence from Guyatt et al. [3]

 Strong recommendation, high-quality evidence

Benefits clearly outweigh risk and burdens, or vice versa

RCTs without important limitations or overwhelming evidence from observational studies

Strong recommendation, applies to most patients in most circumstances without reservation

 Strong recommendation, moderate-quality evidence

Benefits clearly outweigh risk and burdens, or vice versa

RCTs with important limitations (inconsistent results, methodological flaws, indirect analyses, or imprecise conclusions) or exceptionally strong evidence from observational studies

Strong recommendation, applies to most patients in most circumstances without reservation

 Strong recommendation, low-quality or very low-quality evidence

Benefits clearly outweigh risk and burdens, or vice versa

Observational studies or case series

Strong recommendation but subject to change when higher quality evidence becomes available

 Weak recommendation, high-quality evidence

Benefits closely balanced with risks and burden

RCTs without important limitations or overwhelming evidence from observational studies

Weak recommendation, best action may differ depending on the patient, treatment circumstances, or social values

 Weak recommendation, moderate-quality evidence

Benefits closely balanced with risks and burden

RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies

Weak recommendation, best action may differ depending on the patient, treatment circumstances, or social values

 Weak recommendation, low-quality or very low-quality evidence

Uncertainty in the estimates of benefits, risks, and burden; benefits, risk, and burden may be closely balanced

Observational studies or case series

Very weak recommendation; alternative treatments may be equally reasonable and merit consideration