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.