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: unclear reporting of allocation concealment. |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study.
No indication of participant crossover. Administration of all co-interventions of interest were reported: antivirals, biologics, corticosteroids. There were some imbalances among arms. Appropriate analysis method was used. |
| Missing outcome data |
Low |
Comment: 30 randomized; 29 analyzed. 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. Negative viral conversion incidence. Clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Quote: "The blind method is not suitable for this trial." Comment: the trial was not blinded. Mortality and viral negative conversion are observer-reported outcomes not involving judgement. We consider that the outcome WHO clinical progression scale score 7 and above cannot be influenced by knowledge of the intervention assignment. Risk assessed to be low for the outcomes: Mortality. Viral Negative Conversion incidence. WHO score 7 and above. Clinical improvement and WHO score 6 and above involve clinical decision-making, and the assessment could theoretically be influenced by knowledge of the intervention assignment, though we do not consider this likely in the context of the pandemic. The outcomes in question do not seem to differ significantly between-groups. Some adverse events were patient-reported or involved assessor judgment. Risk assessed to be some concerns for the outcomes: WHO score 6 or above. Clinical improvement. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: There was no protocol, or pre-specified analysis plan in the appendix. The registry was available.
Mortality was appropriately registered as reported in the paper. The outcomes related to WHO score 6 and above and adverse events were listed in the registry but not reported as outcomes in the paper. WHO score 7 and above and Incidence of clinical improvement were neither reported as outcomes in the registry nor the paper. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as prespecified. Risk assessed to low for outcomes: Mortality. Clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events. The outcome related to Negative viral conversion is mentioned without timepoints in the study registry but reported with timepoints in the paper. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for outcome: Incidence of viral negative conversion. |
| Overall risk of bias |
Some concerns |