Table 3: Quality of Evidence of Included Studies According to Study Design.

Study Design	Level of Evidence	Number of Eligible Studies
Systematic review(s) of large RCTs*	1a	0
Large RCT	1b
Large RCT unpublished but reported to an international scientific meeting	1(g)†	0
Small RCT	2	0
Small RCT unpublished but reported to an international scientific meeting	2(g)	0
Non-RCT with contemporaneous controls	3a	1
Non-RCT with historical controls	3b	0
Non-RCT presented at international conference	3(g)	0
Surveillance (database or register)	4a	n/a
Case series (multisite)	4b	n/a
Case series (single site)	4c	n/a
Retrospective review, modeling	4d	n/a
Case series presented at international conference	4(g)	n/a

^*RCT refers to randomized controlled trial. A large RCT is defined as one that has adequate power to detect differences in the primary outcome.

^†gindicates gray literature.