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: "Central telephone randomization was performed by the Clinical Research and Clinical Trials Unit (CRCTU) at the HUP using the program www.randomization.com with a 2:1 proportion and 5 blocks of 6 subjects. After checking that all entry criteria were met, the CRCTU communicated the
assigned treatment to the recruiting investigator, who reported the correct allocation in the electronic clinical record (ECR)."
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. Administration of co-interventions of interest: antivirals, corticosteroids and biologics are reported: Lopinavir/Ritonavir: 4 vs 1, methylprednisolone bolus: 14 vs 3 and Tocilizumab: 0 vs 3. This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. 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 (D28). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 30 participants randomized; 29 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). 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 Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). WHO SCORE 7 AND ABOVE For this outcome, 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 [discharged alive from the hospital by 28 days]) 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: Clinical improvement (D28). 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 outcome: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective protocol (dated April 6th, 2020), statistical analysis plan, registry were available.
Outcome 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). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |