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 |
Some concerns |
Quote: "SAS software was used to generate the random number and the treatment group corresponding to the random number. After the subjects passed screening, the researchers assigned the random number according to the order of enrollment, removed the random envelope according to the random number, and treated the subjects according to the random envelope group and treatment plan. The blind method is not suitable for this trial."
Comment: Allocation sequence random. Unclear reporting of allocation concealment. |
| 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 indication of participant crossover. Administration of all co-interventions of interest were reported: antivirals, biologics, corticosteroids. There were some imbalances among arms. 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. Data for the outcome were analyzed using 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). Incidence of viral negative conversion incidence (D7). 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 nearly all participants randomized. 1 withdrew from the study and "excluded from final analysis because of discontinuation of favipiravir after Day 1 treatment." Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion incidence (D7). Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Quote: "The blind method is not suitable for this trial."
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY, VIRAL NEGATIVE CONVERSION Mortality and viral negative conversion are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). 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). CLINICAL IMPROVEMENT Clinical improvement 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 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 |
Some concerns |
Comment: There was no protocol, or pre-specified analysis plan in the appendix. Only the latest version of the registry was accessible and it was retrospective (dated February 12th, 2020).
No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Mortality (D28). Incidence of viral negative conversion incidence (D7). Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |