A Systematic Review of Serum Biomarkers Anti-Cyclic Citrullinated Peptide and Rheumatoid Factor as Tests for Rheumatoid Arthritis

Table 1

Oxford Centre for Evidence-based Medicine definitions of levels of evidence. The following table summarizes the criteria that must be satisfied for the five different levels of evidence for both diagnostic and prognostic studies as well as the grading of recommendations assessment, development, and evaluation (GRADE) that studies with a given level of evidence will support.

Level of evidence	Grade of recommendation studies can support	Criteria for diagnostic studies	Criteria for prognostic studies
1	A	(a) systematic review/meta analysis of level 1 studies or clinical decision rule applied to level (b) multicenter studies; (b) cohort study with good reference standards that validate the diagnostic test or clinical decision rule in single center study; (c) specificity or sensitivity results that are so high that they can rule in or rule out a diagnosis	(a) systematic review/meta analysis of inception cohort studies or clinical decision rule that is validated in more than one population; (b) single inception cohort studies with ≥80% follow up of participants or clinical decision rule that is validated in one population only; (c) case series where results apply to either all or none of the subjects
2	B	(a) systematic review/meta analysis of ≥level 2 diagnostic studies; (b) exploratory cohort study with good reference standard or clinical decision rule applied to a split sample	(a) systematic review/meta analysis of retrospective cohort studies or untreated control groups in randomized clinical trials (RCTs); (b) retrospective cohort study or untreated control group from an RCT that is followed over time; (c) outcomes research
3	B	(a) systematic review/meta analysis of ≥level 3 diagnostic studies; (b) nonconsecutive study or study with inconsistent use of reference standards	N/A
4	C	Case-control study or study with poor reference standards	Case series or poor quality cohort studies
5	D	Expert opinion	Expert opinion

(http://www.cebm.net/index.aspx?o=1025).
Source: GRADE (grading of recommendations assessment, development, and evaluation) Working Group 2007 1 (modified by the EBM Guidelines Editorial Team).