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 randomization”
Comment: Allocation sequence random Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: “Single-blind. Investigators disclosed information regarding the allocated drugs to the enrolled patient only to the minimal necessary stakeholders of the trial site in order to minimize bias. The information on the allocated drugs was not disclosed to the patients or to the Central Committee, and the blinding was maintained throughout the trial.”
Comment: Single-blinded study (participants) Deviations from intended intervention arising because of the study context: Seven patients in the placebo group were switched to treatment with favipiravir. No information on administration of co-interventions of interest: biologics and corticosteroids. Antivirals were disallowed. There was at least no information on whether deviations arose because of the trial context. 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 outcomes 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). Adverse events. Serious adverse events. Time to viral negative conversion. |
| Missing outcome data |
Some concerns |
Comment: 156 participants randomized; 156 participants analyzed.
However, data was not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 16 placebo patients and 26 treatment patients were excluded from the analysis post-randomization because of lack of efficacy, negative for SARS-CoV-2 at pre-dose, withdrew consent, withdrew due to adverse events. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome as the reasons for the missing data and the proportions of missing data are similar between groups Risk assessed to be some concerns for the outcomes: Mortality (D28). Time to viral negative conversion. Adverse events. 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. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events. MORTALITY, TIME TO VIRAL NEGATIVE CONVERSION Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Time to viral negative conversion. ADVERSE and 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: Adverse events. Serious adverse events |
| Selection of the reported results |
Low |
Comment: The registry was available (dated 27/03/2020).
Negative conversion and safety outcomes pre-specified. 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 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). Time to viral negative conversion. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |