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: “The randomization was performed using the permuted block method. Block sizes of 2 and 4 were selected. According to the list of random numbers created by Excel software, the statistician designed sequentially numbered opaque envelopes and then delivered to the clinical investigators.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “The statistician was unaware of the treatment group assignment. In addition, patients and clinical providers were blind regarding the randomization process. In terms of the treatment group assignment, patients but not physicians were blind.”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of all co-interventions of interest: biologics. However, antivirals reported and balanced between groups. Corticosteroids were the intervention. Hence, no information on whether deviations arose because of the trial context. MORTALITY Our analysis for the binary outcome is an 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 (D60 or more). TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT. Participants were analyzed according to their randomized groups for the outcome. Of note, 1 vs 7 vs 2 participants were excluded from the analysis post-randomization because [0 vs 4 vs 1 were ruled out of covid-19 diagnosis and 1 vs 3 vs 1 were transferred to another hospital]. 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 outcomes: Time to death. Time to clinical improvement. |
| Missing outcome data |
Some concerns |
Comment: 144 participants randomized; 133 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 0 vs 4 vs 1 found not to have COVID; 0 vs 1 vs 0 declined to continue study; 1 vs 3 vs 1 transferred to a different trial. Missingness could depend on 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 (D60 or more). Time to death. Time to clinical improvement. |
| 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 outcomes: Mortality (D60 or more). Time to death TIME TO CLINICAL IMPROVEMENT Clinical improvement (defined as an improvement of two or more points on an 8-point ordinal scale) 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 outcomes: Time to clinical improvement. |
| Selection of the reported results |
Low |
Comment: The registry was available (dated 8th Oct 2020).
Clinical improvement outcome included in the registry with different wording. Mortality outcome was not pre-specified in the 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 (D60 or more). Time to death. Time to clinical improvement. |
| Overall risk of bias |
Some concerns |