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: "Randomization was performed in blocks of variable size (2, 4 and 6) in a centralized web-based automated system and stratified by site and whether the patient was on IMV. The allocated group was disclosed to the investigator only after all information regarding patient enrollment had been recorded in the web system"
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “open-label”
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. Co-interventions of interest: use of antivirals and corticosteroids were balanced between groups during the intervention. Biologics (tocilizumab and convalescent plasma) were not available for any participant in the study. Hence, deviations did probably not arise because of the trial context. 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). |
| Missing outcome data |
Some concerns |
Comment: 142 participants randomized; 105 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 15 [21%] vs 18 [25%] negative RT-PCR, 3 [4%] vs 0 withdrawal of informed consent, 0 vs 1 [1%] screening failure (>48hrs from admission), 0 vs 1 [1%] loss to follow-up. Missingness due to screening failure and negative RT-PCR test could not depend on the true value of the outcome, but missingness due to withdrawal of informed consent and loss to follow-up could depend of the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). |
| 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). WHO SCORE 7 AND ABOVE For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcome: WHO score 7 and above (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as hospital discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available, and the registry was retrospective.
MORTALITY Mortality outcome was not pre-specified in a protocol or registry that we could access, 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 outcome: Mortality (D28). CLINICAL IMPROVEMENT AND WHO SCORE 7 OR ABOVE 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: Clinical improvement (D28). WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |