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 by permuted blocked randomization" (report) "SAS procedure PROC PLAN will be applied to generate the randomization schedule" (registry) "To maintain allocation concealment, we used sequentially numbered, opaque sealed envelopes (SNOSE) method" (report)
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “open-label clinical trial”
Comment: Unblinded study. No participant cross-over. Co-interventions of interest: antivirals and corticosteroids were reported and were balanced between groups. No information on administration of biologics. Hence, not sufficient information on whether deviations arose because of the trial context. Of note, 1 participant in the control arm was excluded due to early hospital discharge. 3 participants in the intervention arm and 2 in the control arm were excluded from the analysis because they were candidates to receive other unspecified treatments. This method may not be appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Missing outcome data |
Low |
Comment: 90 patients randomized; 82 patients analyzed.
Data available for 91% of population. >5% missing data. Reasons for missingness (early hospital discharge (1 vs 0), candidate to receive other interventions (2 vs 3), willingness to withdraw from the study (2 vs 0)) could be related to the true value of the outcome. However, the risk of bias associated with the majority of these missing data (candidates to receive other interventions) has already been taken into account in domain 2. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (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. Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). Clinical improvement (defined as one point decline in disease category in a five category ordinal scale) requires clinical judgement and could be affected by knowledge of intervention receipt. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). |
| Selection of the reported results |
Some concerns |
Comment: The trial registry was available.
Timepoint for outcome analysis in registry is either different from the paper (mortaltiy) or no timepoint was specified (clinical improvement). Results might have been selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Overall risk of bias |
Some concerns |