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: “Patients were stratified according to baseline severity into three groups and randomized by a computer generated block-randomization technique (1:1) to either one of two treatment groups. The randomization was conducted centrally by a statistician not involved in patient care and the random allocation sequence was concealed by opaque sealed envelopes.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Open-label”
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 co-interventions of interest: biologics and corticosteroids. Antivirals were the intervention in the experimental arm. Hence, no information on whether deviations arose because of the trial context. Our analysis for the 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 (D28). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 89 participants randomized; 89 participants analyzed (85 complete follow up).
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: 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 outcomes: WHO score 7 and above (D28). (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined as normalization of fever (≤37.2°C), respiratory rate (≤24 breaths/min) and oxygen saturation (≥ 94% on room air), sustained for at least 24 hours with improvement of at least 2 points at the WHO-8-point-ordinal-scale (described above in procedure section)) requires clinical judgement and could be affected by knowledge of intervention receipt, but it is not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Time to clinical improvement. SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which 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 outcomes: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (15th June 2020).
Outcomes pre-specified. Results were 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 (D28). Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |