Risk of bias assessment of included studies
Overall, twelve studies (25, 28, 30, 32, 33, 37, 40, 41, 42, 43, 50, 56) were regarded as having a low risk of bias, the remaining studies were found to have variable degrees of risk of bias. Thirteen studies had high risk of bias (34, 35, 36, 38, 44, 46, 47, 48, 49, 51, 53, 54, 55) with issues in randomisation and / or allocation concealment. Six studies (23, 24, 29, 39, 45, 52) had unclear bias as methodology was not described very well. One study was adjudged to have high risk of bias for selective outcome reporting due to early stoppage of the trial 27. The risk of bias of the included studies is depicted in E-Figure 2.
Primary Outcomes