1. Confounding factors.

	Did the study restrict participant selection so that all groups had the same value for the confounder?	Did the study demonstrate balance between groups for the confounder?	Did the study match on the confounder?	Did the study adjust for the confounder in statistical analyses to quantify the effect size?
Confounder 1 (Age)	yes/no	yes/no	yes/no	yes/no
Confounder 2 (Sex)	yes/no	yes/no	yes/no	yes/no
Confounder 3 (Pain diagnosis)	yes/no	yes/no	yes/no	yes/no
Confounder 4 (Methadone dose and route of administration)	yes/no	yes/no	yes/no	yes/no
Confounder 5 (Duration of methadone treatment)	yes/no	yes/no	yes/no	yes/no

Confounding factors in each non‐randomized study were assessed according to this table