TABLE 1. Classification of Methodological Quality of Individual Studies

	Intervention	Diagnostic Accuracy Assessment	Harm or Side Effects, Etiology, Prognosis∗
A1	Systematic review of at least two mutually independent studies of A2-level
A2	Randomized double-blind comparative clinical study of good quality and sufficient size	Study comparing with a reference test (a ‘gold standard’) with previously defined cut-off values and independent assessment of the results of study test and gold standard regarding a sufficiently large series of consecutive patients who all were administered the index and reference test	Prospective cohort study of sufficient size and follow-up, adequately controlled for confounding and with satisfactory exclusion of selective follow-up
B	Comparative study, but not possessing all qualities mentioned under A2 (this category also includes patient-checkup study, cohort study)	Study comparing with a reference test, but not possessing all qualities mentioned under A2	Prospective cohort study, but not possessing all qualities mentioned under A2, or retrospective cohort study or patient-checkup study
C	Non-comparative study
D	Expert opinion

^∗This classification only applies to situations in which controlled trials are not feasible for ethical or other reasons. If they should be feasible, the classification for interventions applies.