eTable 1. The SIGN classification of levels of evidence.

Level of evidence	Description
1++	High quality meta-analyses. systematic reviews of RCTs. or RCTs with a very low risk of bias
1+	Well-conducted meta-analyses. systematic reviews. or RCTs with a low risk of bias
1−	Meta-analyses. systematic reviews. or RCTs with a high risk of bias
2++	High quality systematic reviews of case–control or cohort or studies High quality case–control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+	Well-conducted case–control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2−	Case–control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3	Non-analytic studies. e.g. case reports. case series
4	Expert opinion

RCT. randomized controlled trial; SIGN. Scottish Intercollegiate Guidelines Network