Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.
| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Patients were assigned to treatment group using a stratified, blocked randomized design. Randomization tables were generated via the SAS 9.4.”
Quote from contact with authors: "Allocation sequence was concealed in our study. Our study employed a central randomization strategy through a secure computer system following patient enrolment. Only the qualified staff involved in randomization and preparation of the infusions was unblinded to the assignment. The product label did not differentiate between UC-MSC or vehicle solution (control). The final product container was opaque. The clinical team managing the subjects and the assessors were both blinded to treatment allocation." Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “The study was double-blinded: neither the patient nor the assessing physician were aware of the treatment assignment, the staff responsible for product administration were blinded to group assignment.”
Comment: Blinded study (patients and physicians/carers). Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Of note, 1 vs 0 participants were excluded from the analysis post-randomization due to failed intubation.This method was considered inappropriate to estimate the effect of assignment to intervention for all time-to-event outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement.Adverse events. Serious adverse events |
| Missing outcome data |
Low |
Comment: 24 patients randomized; 24 patients analyzed.(23 partients analysed for time to event data).
Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. Adverse events. Serious adverse events |
| Measurement of the outcome |
Low |
Comment: Appropriate method of measuring the outcome.
Measurement or ascertainment of outcome do not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. Adverse events. Serious adverse events |
| Selection of the reported results |
Some concerns |
Comment: The study's prospective registry was available.
Mortality was not pre-specified in the registry but we do not consider the reporting of this outcome to be selective as mortality should be reported even if not explicitly planned. Clinical improvement data was acquired from contact with authors. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. Safety outcomes were also not pre-specified at the timepoint reported in the paper (31 days after first infusion). In the registry AE had a timepoint at 5 days and SAE at 90 days. No information on whether the results were selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for outcomes: Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |