Assessment of risk of bias
Risk of bias was assessed using the Cochrane Collaboration´s tool for assessing risk of bias in randomized trials20. This tool is composed by 5 domains: bias arising from the randomization process; bias due to deviations from intended interventions; bias due to missing outcome data; bias in measurement of the outcome; and bias in selection of the reported result. For each domain, the tool comprises:
a series of ‘signalling questions’; a judgement about risk of bias for the domain, which is facilitated by an algorithm that maps responses to the signalling questions to a proposed judgement; free text boxes to justify responses to the signalling questions and risk-of-bias judgements; and an option to predict (and explain) the likely direction of bias. Risk of bias was assessed by two independent reviewers. Possible disagreements between reviewers were resolved by discussion or arbitration by a third reviewer when consensus could not be reached.