| Study |
Bias |
| Randomisation process |
Deviations from intended interventions |
Missing outcome data |
Measurement of the outcome |
Selection of the reported results |
Overall |
| Authors' judgement |
Support for judgement |
Authors' judgement |
Support for judgement |
Authors' judgement |
Support for judgement |
Authors' judgement |
Support for judgement |
Authors' judgement |
Support for judgement |
Authors' judgement |
Support for judgement |
| Maskin 2021 |
Low risk of bias |
No issues with randomisation. |
Some concerns |
Minor issues with deviations (2/51 patients from the control received not intended intervention) and appropriate analysis. |
Low risk of bias |
No relevant amount of missing data. |
Low risk of bias |
No relevant issues with measurement. |
Low risk of bias |
No relevant issues with reporting. |
Some concerns |
Some minor concerns regarding deviations in about 5% of patients and their exclusion from analysis. |
| Munch 2021b |
Low risk of bias |
No issues with randomisation process. |
Low risk of bias |
No issues with deviations from intended interventions |
Low risk of bias |
Few, balanced, and blinded exclcusions for similar reasons in both arms. |
Low risk of bias |
No issues with measurement |
Low risk of bias |
No issues with potential selection. |
Low risk of bias |
Low risk of bias in all domains. |
| Taboada 2021 |
Some concerns |
There are no further information regarding the concealment of the allocation sequence |
Low risk of bias |
Both participants and those delivering the intervention were aware of intervention received, but there was no information on deviations from intended intervention. The analysis was appropriate. |
Low risk of bias |
Data for this outcome was available for all 200 participants randomised. |
Low risk of bias |
The measurement of the outcome was appropriate and it is unlikely that it differed between intervention groups. The outcome assessors were aware of the intervention received, but it is unlikely that knowledge of intervention received could have affected outcome measurement |
Low risk of bias |
Protocol available. Outcome pre‐specified. |
Some concerns |
For this outcome, there is low risk of bias due to deviations from intended interventions, due to missing outcome data and in measurement of the outcome. However, there are some concerns for bias in the randomisation process. |
| Toroghi 2021 |
Low risk of bias |
Participants were block randomised, and the allocation sequence was concealed. There are no baseline differences that would suggest a problem with randomisation. |
High risk of bias |
The study design was blind on patient level, but there were no arrangements that ensured blinding. Therefore, we do not know whether the higher dropout rate in the intermediate/high‐dose groups occurred due to the assigned intervention. No information on treatment adherence was reported. |
Low risk of bias |
Data was available for nearly all participants. |
Low risk of bias |
The measurement of the outcome was appropriate, and it is unlikely that it differed between intervention groups. The outcome assessors were unaware of the intervention received. |
Some concerns |
There was a trial register entry, which provided details of the pre‐specified outcomes, but "mortality" was not pre‐specified at trial registration and in the protocol |
High risk of bias |
The study design was blind on patient level, but there were no arrangements that ensured blinding. Therefore, we do not know whether the higher dropout rate in the intermediate/high‐dose groups occurred due to the assigned intervention. No information on treatment adherence was reported. |
