Table 1.

Grading of methodological quality of individual studies

Level of evidence	Interventional studies	Diagnostic accuracy studies	Harm, side effects, etiology, prognosis
A1	Systematic review / meta-analysis of at least 2 independently conducted studies of A2 level
A2	Randomized, double-blind trial with good study quality and a adequate number of study participants	Indextest compared to reference test (reference standard); cut-offs were defined a priori; independent interpretation of test results; an adequate number of consecutive patients were enrolled; all patients received both tests.	Prospective cohort study of sufficient magnitude and follow-up, adequately controlled for ‘confounding’ and no selective follow-up.
B	Clinical trial, but without all the features mentioned for level A2 (including case-control study, cohort study).	Index test compared to reference test, but without all the features mentioned for level A2.	Prospective cohort study, but without all the features mentioned for level A2 or retrospective cohort study or case-control study.
C	Non-comparative studies
D	Expert opinion