Table 1 Rating the levels of evidence (LoE) for EFSUMB CPGs based on the Oxford Center of Evidence-Based Medicine (OCEBM) system, version 2 (2011; modified from ³⁶ ).

Clinical question	LoE 1*	LoE 2*	LoE 3*	LoE 4*	LoE 5*
How common is the problem?	Local and current random sample surveys (or censuses)	Systematic review of surveys that allow matching to local circumstances**	Local non-random sample**	Case series**	Not applicable
Is this diagnostic test accurate? (Diagnosis)	Systematic review of cross-sectional studies with consistently applied reference standard and blinding	Individual cross-sectional study with consistently applied reference standard and blinding	Non-consecutive studies, or studies without consistently applied reference standards**	Case control studies or poor or non-independent reference standard**	Mechanism-based reasoning
What will happen if we do not add a therapy? (Prognosis)	Systematic review of inception cohort studies	Inception cohort studies	Cohort study or control arm of randomized trial**	Case series or case control studies or poor quality prognostic cohort study**	Not applicable
Does this intervention help? (Treatment Benefits)	Systematic review of randomized trials or n -of-1 trials	Randomized trial or observational study with dramatic effect	Non-randomized controlled cohort/follow-up study**	Case series, case control studies, or historically controlled studies**	Mechanism-based reasoning
What are the common harms? (Treatment Harms)	Systematic review of randomized trials, systematic review of nested case control studies, n -of-1 trial with the patient you are raising the question about, or observational study with dramatic effect	Individual randomized trial or (exceptionally) observational study with dramatic effect	Non-randomized controlled cohort/follow-up study (post-marketing surveillance) provided there are sufficient numbers to rule out a common harm (for long-term harms the duration of follow-up must be sufficient)**	Case series, case control studies, or historically controlled studies**	Mechanism-based reasoning
What are the rare harms? (Treatment Harms)	Systematic review of randomized trials or n -of-1 trial	Randomized trial or (exceptionally) observational study with dramatic effect
Is this (early detection) test worthwhile? (Screening)	Systematic review of randomized trials	Randomized trial	Non-randomized controlled cohort/follow-up study**	Case series, case control studies, or historically controlled studies**	Mechanism-based reasoning

* LoE may be graded down on the basis of study quality, imprecision, indirectness (study PICO does not match questions PICO), because of inconsistency between studies, or because the absolute effect size is very small; LoE may be graded up if there is a large or very large effect size. PICO : P atient, P opulation, or P roblem; I ntervention, Prognostic factor, or Exposure; C omparison of intervention (if appropriate); O utcome you would like to measure or achieve)

** A systematic review is generally better than an individual study.