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 |
High |
Quote: "Randomization was done through random sequence generation by using statistical software"
"There is no allocation concealment (study registry)". Comment: Allocation sequence random. Allocation not concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Not blinded" (registry)
Comment: Unblinded study (participants and personnel/carers). No participant cross-over. No information on the administration of co-interventions of interest: Biologics and antivirals. Corticosteroids were reported and balanced between groups. Hence, no information on whether deviations arose because of the trial context. MORTALITY, SAE 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 some concerns for the outcomes: Mortality (D28). Serious adverse events. TIME TO DEATH Participants were analyzed according to their randomized groups for the outcome. Of note, 2 vs 7 participants were excluded from the analysis post-randomization. 2 vs 0 were due to reasons other than missing data (refused to end up with the drug). This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcome: Time to death. |
| Missing outcome data |
High |
Comment: 60 participants randomized; 51 participants analyzed.
Data not available for all or nearly all of the population. No evidence that the result is not biased. Reasons: 2 participants declined the treatment in intervention arm (accounted for in domain 2); 2 withdrew consent and 5 were lost to follow up (control arm). Missingness could depend on the true value of the outcome. Likely that missingness depended on the true value of the outcome (imbalance between arms) Risk assessed to be high for the outcomes: Mortality (D28). Time to death. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY, TIME TO DEATH Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). Time to death SERIOUS ADVERSE EVENTS The authors reported on serious adverse events that may have contained both clinically- and laboratory-detected outcomes. All these outcomes can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcome: Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available. The registry was available but was not prospective (dated April 17th, 2020).
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 outcomes: Mortality (D28). Time to death. Serious adverse events. |
| Overall risk of bias |
High |