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: "Patients were randomly assigned via computer-generated random numbering (1:1) to either start favipiravir on day 1 (early treatment group) or on day 6 of study participation (late treatment group)."
Quote: "This was an open label study, thus the allocation sequence was not concealed to the local study
personnel who enrolled participants."
Comment: Allocation sequence random. Allocation concealment unclear. |
| Deviations from intervention |
Low |
Quote: "An open-label design was adopted as placebo was not readily available at the time of study initiation"
Comment: Unblinded study. No participant cross-over. Co-interventions of interest reported and balanced between groups. Data were analyzed using intention-to-treat analysis |
| Missing outcome data |
Low |
Comment: 89 patients randomized; 88 patients analyzed for outcomes mortality, clinical improvement, Time to clinical improvement, WHO score 7 and above and WHO score 6 and above. 82 participants analyzed in the safety population for the outcomes adverse events and serious adverse events.8 patients in the early favipiravir arm and 11 in the late favipiravir arm were excluded due to negative PCR on day 1. However, this exclusion was due to the failure in meeting the inclusion criteria and is not considered to affect the results.
Risk assessed to be low for outcomes: Mortality. Clinical improvement. Time to clinical improvement. Score WHO 6 and above. Incidence of WHO score 7 and above. Viral negative coversion. Time to viral negative conversion. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study
Mortality and viral negative conversion are observer-reported outcomes not involving judgement. WHO score 7 and above cannot be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: Mortality. Viral negative conversion. Time to viral negative conversion. Incidence of WHO score 7 and above. Clinical improvement (defined as hospital discharge), WHO score 6 and above, adverse events and serious adverse events requires clinical judgement and could be affected by knowledge of intervention receipt, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcome: Time to clinical improvement. Clinical improvement. WHO score 6 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were available. The analysis plan was dated May 15 and recruitment ended May 18th. This was probably not before unblinded data were available to principal investigators,hence not pre-specified. The study registry only presents viral negative convertion.
Result was not selected from multiple outcome measurements nor multiple analyses of the data. Trial was probably not analyzed in accordance with a pre-specified plan. Risk assessed to be some concerns for the outcomes: Mortality. Clinical improvement. Time to clinical improvement. Score WHO 6 and above. Incidence of WHO score 7 and above.Time to viral negative conversion. Adverse events. Serious adverse events. Risk assessed to be low for the outcome: Viral negative conversion. |
| Overall risk of bias |
Some concerns |