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 |
Some concerns |
Quote: "Patients were randomised to one of two treatment groups (SNG001 or placebo) in a 1:1 ratio according to a prespecified randomisation schedule in addition to standard of care"
"Simple randomisation was done manually by use of sealed envelopes, with trained clinical research staff assigning the patient the next available randomisation number on the randomisation list." Comment: Allocation sequence probably random. Unclear allocation concealment. (No information on sequentially numbered, opaque envelopes) |
| Deviations from intervention |
Low |
Quote: "Study investigators, all research and analysis teams, and patients were masked to treatment allocation."
Comment: Blinded study (participants and personnel/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. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 101 participants randomized; 98 participants analyzed.
Up to 29% missing data in the intervention group (15/51) and 22% in the control group (11/50) were imputed using the last-observation-carried-forward method. Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar proportion of missingness between arms). Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol (version dated June 8th, 2020) and statistical analysis plan and registry (dated May 11th, 2020) were available but were all retrospective.
MORTALITY Mortality outcome was not pre-specified in the [protocol/SAP/registry], however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. 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). CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |