Quality

Appraisal
Study Type of Study Tool Comparison Table
1 Martoni C.J RCT RoB 2
2 Catinean A RCT RoB 2
3 Bahruddin M.F RCT RoB 2
4 Begtrup Luise RCT RoB 2
5 Capello C RCT RoB 2
6 Cremon C RCT RoB 2
7 de Chambrun RCT RoB 2
8 Eskesen D RCT RoB 2
9 Faghihi A H RCT RoB 2
10 Gupta A K RCT RoB 2
11 Hod K RCT RoB 2
12 Ishaque S RCT RoB 2
13 Jafari E RCT RoB 2
14 Ko, Seok-Jae RCT RoB 2
15 Leventogiannis K Non-randomised Control Trial to be excluded, quality appraisal not yet done
16 Lewis E.D RCT RoB 2
Sponsor considered from here on
17 Li, Ming Phase II RCT RoB 2
18 Liu, Yang RCT RoB 2
19 Lorenzo Z V RCT RoB 2
20 Martoni C.J 2020 RCT RoB 2
21 Mezzasalma V RCT RoB 2
22 Oh J H (2019) RCT RoB 2
23 Oh J H (2022) RCT RoB 2
24 Sadrin S RCT RoB 2
25 Sisson G RCT RoB 2
26 Skrzydlo-Radomanska
RCT
B (2020) RoB 2
27 Skrzydlo-Radomanska
RCT
B (2022) RoB 2
28 Sun Y Y RCT RoB 2
29 Urgesi R RCT RoB 2
30 Yoon H RCT RoB 2
Ait Abdellah, S. Non-RCT ROBINS I

de Cruchet Review Article AMSTAR

Cochrane Bias Assessment Tool (RoB 2) (Table 1)

1. Martoni C.J (2023) 2. Catinean. A 3. Bahruddin M.F 4. Begtrup Luise 5. Capello C 6. Cremon C 7. de Chambrun 8. Eskesen D 9. Faghihi A H 10. Gupta A K 11. Hod K 12. Ishaque S 13. Jafari E 14. Ko, Seok-Jae 15. Lewis E.D
Overall Overall
Domain Singnalling Questions Response Bias Response Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias
1.1 Was the allocation sequence random? Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y

Randomisation 1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions? Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y
process 1.3 Did baseline differences between intervention groups suggest a problem with the randomization process? N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW
2.1 Were participants aware of their assigned intervention during the trial? N Y N N N N N N N N N N N N N
2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial? N Y N N N N N N N N N N N N N
2.3 If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the trial context? NA N NA NA NA NA NA NA NA NA NA NA NA NA NA
2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome? NA NA NA NA NA NA NA NA NA NA NA N NA NA NA
2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups? NA NA NA NA NA NA NA NA NA NA NA NI NA NA NA

Deviation from 2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention? Y Y Y Y PY Y Y Y PY Y Y N Y Y Y
intended 2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the SOME
interventions group to which they were randomized? NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW CONCERNS NA LOW NA LOW NA LOW
3.1 Were data for this outcome available for all, or nearly all, participants randomized? Y Y Y N Y Y Y PY PY Y Y Y Y Y PY
3.2 If N/PN/NI to 3.1: Is there evidence that the result was not biased by missing outcome data? NA NA NA PN NA NA NA NA NA NA NA NA NA NA NA

Missing outcome 3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value? NA NA NA PY NA NA NA NA NA NA NA NA NA NA NA
data 3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value? NA LOW NA LOW NA LOW PY HIGH NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW
4.1 Was the method of measuring the outcome inappropriate? N N N PN N PN N N N N PN N N N N
4.2 Could measurement or ascertainment of the outcome have differed between intervention groups? N N N N N PN N N N N N N N N N
4.3 If N/PN/NI to 4.1 and 4.2: Were outcome assessors aware of the intervention received by study participants? N Y N N N N N N N N N N N N N

Measurement of the 4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received? NA N NA NA NA NA NA NA NA NA NA NA NA NA NA
outcome 4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received? NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW
5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized
before unblinded outcome data were available for analysis? Y Y Y PN Y Y Y PY Y Y Y PN Y Y Y
Is the numerical result being assessed likely to have been selected, on the basis of the results, from...

Selection of the 5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain? N N N PN SOME N N N N N N N N SOME N N N
reported result 5.3 ... multiple eligible analyses of the data? N LOW N LOW N LOW PN CONCERNS N LOW N LOW N LOW N LOW N LOW N LOW N LOW N CONCERNS N LOW N LOW N LOW
BIAS LOW LOW LOW SOME CONCERNS LOW LOW LOW LOW LOW LOW LOW SOME CONCERNS LOW LOW LOW

Cochrane Bias Assessment Tool (RoB 2) (Table 2) 16. Li Ming 17. Liu Yang 18. Lorenzo Z V 19. Martoni CJ (2020) 20. Mezzalasma V 21. Oh J H (2019) 22. Oh J H (2022) 23. Sadrin S 24. Sisson G 25. Skrzydlo-Radomanska B (2020)26. Skrzydlo-Radomanska B (2022)27. Sun Y Y 28. Urgesi R 29. Yoon H
Overall Overall
Domain Singnalling Questions Response Bias Response Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias Response Overall Bias
1.1 Was the allocation sequence random? Y Y Y Y Y Y Y Y Y Y Y Y Y Y

Randomisation 1.2 Was the allocation sequence concealed until participants were enrolled and assigned to interventions? Y Y Y Y Y Y Y Y Y Y Y Y Y Y
process 1.3 Did baseline differences between intervention groups suggest a problem with the randomization process? N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW
2.1 Were participants aware of their assigned intervention during the trial? Y N N N N N N N N N N N N N
2.2 Were carers and people delivering the interventions aware of participants' assigned intervention during the trial? Y N N N N N N N N N N N N N
2.3 If Y/PY/NI to 2.1 or 2.2: Were there deviations from the intended intervention that arose because of the trial context? N NA NA NA NA NA NA NA NA NA NA NA NA NA
2.4 If Y/PY to 2.3: Were these deviations likely to have affected the outcome? NA NA NA NA NA NA NA NA NA NA NA NA NA NA
2.5. If Y/PY/NI to 2.4: Were these deviations from intended intervention balanced between groups? NA NA NA NA NA NA NA NA NA NA NA NA NA NA

Deviation from 2.6 Was an appropriate analysis used to estimate the effect of assignment to intervention? PY Y Y Y Y Y Y Y Y Y Y Y Y Y
intended 2.7 If N/PN/NI to 2.6: Was there potential for a substantial impact (on the result) of the failure to analyse participants in the
interventions group to which they were randomized? NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW
3.1 Were data for this outcome available for all, or nearly all, participants randomized? Y PY PY Y Y Y Y Y PY Y Y PY Y Y
3.2 If N/PN/NI to 3.1: Is there evidence that the result was not biased by missing outcome data? NA NA NA NA NA NA NA NA NA NA NA NA NA NA

Missing outcome 3.3 If N/PN to 3.2: Could missingness in the outcome depend on its true value? NA NA NA NA NA NA NA NA NA NA NA NA NA NA
data 3.4 If Y/PY/NI to 3.3: Is it likely that missingness in the outcome depended on its true value? NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW
4.1 Was the method of measuring the outcome inappropriate? N N N N N N N N N N N N N N
4.2 Could measurement or ascertainment of the outcome have differed between intervention groups? N N N N N N N N N N N N N N
4.3 If N/PN/NI to 4.1 and 4.2: Were outcome assessors aware of the intervention received by study participants? Y N N N N N N N N N N N N N

Measurement of the 4.4 If Y/PY/NI to 4.3: Could assessment of the outcome have been influenced by knowledge of intervention received? N NA NA NA NA NA NA NA NA NA NA NA NA NA
outcome 4.5 If Y/PY/NI to 4.4: Is it likely that assessment of the outcome was influenced by knowledge of intervention received? NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW NA LOW
5.1 Were the data that produced this result analysed in accordance with a pre-specified analysis plan that was finalized
before unblinded outcome data were available for analysis? Y Y Y Y Y Y Y Y Y Y Y Y Y Y
Is the numerical result being assessed likely to have been selected, on the basis of the results, from...

Selection of the 5.2 ... multiple eligible outcome measurements (e.g. scales, definitions, time points) within the outcome domain? N N N N N N N N N N N N N N
reported result 5.3 ... multiple eligible analyses of the data? N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW N LOW
BIAS LOW LOW LOW LOW (funding) LOW LOW LOW LOW LOW LOW LOW LOW LOW LOW

AMSTAR
Item Type Xie P
1 Non critical Did the research questions and inclusion criteria for the review include the components of PICO? Y
Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the
2 Critical report justify any significant deviations from the protocol? Y
Did the review authors explain their selection of the study designs for inclusion in the
3 Non critical review? Y
4 Critical Did the review authors use a comprehensive literature search strategy? Y
5 Non critical Did the review authors perform study selection in duplicate? Y
6 Non critical Did the review authors perform data extraction in duplicate? Y
7 Critical Did the review authors provide a list of excluded studies and justify the exclusions? Y
8 Non critical Did the review authors describe the included studies in adequate detail? Y
9 Critical Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review? Y
10 Non critical Did the review authors report on the sources of funding for the studies included in the review? Y
11 Critical If meta-analysis was performed, did the review authors use appropriate methods for statistical combination of results? Y
If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-
12 Non critical analysis or other evidence synthesis? Y
13 Critical Did the review authors account for RoB in individual studies when interpreting/ discussing the results of the review? Y
14 Non critical Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review? Y
If they performed quantitative synthesis, did the review authors carry out an adequate investigation of publication bias (small study bias) and
15 Critical discuss its likely impact on the results of the review? Y
16 Non critical Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review? Y
High
Confidence