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 (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. Co-interventions of interest reported and balanced between groups. Hence, deviations did not arise because of the trial context. MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE 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 low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 8 vs 11 participants were excluded from the analysis post-randomization due to negative PCR on day 1. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be low for the outcomes: Incidence of viral negative conversion (D7). Time to viral negative conversion. TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 0 vs 1 participants were excluded from the analysis post-randomization due to missing data which is accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be low for the outcome: Time to clinical improvement. |
| Missing outcome data |
High |
Comment: 89 participants randomized; 88 participants analyzed for all outcomes except safety (82 participants analyzed) and viral negative conversion (69 participants analyzed).
MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE Data available for all or nearly all participants randomized. Risk assessed to be low for outcomes: Mortality (D28). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 8 patients in the early favipiravir arm and 11 in the late favipiravir arm were excluded due to negative PCR on day 1 (accounted for in domain 2) Missingness could not depend on the true value of the outcome. Risk assessed to be low for outcomes: Incidence of viral negative conversion (D7). Time to viral negative conversion. ADVERSE and SERIOUS ADVERSE EVENTS Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 6 in control group did not take favipiravir, 1 in control group withdrew Missingness could depend on the true value of the outcome. Likely that missingness depended on the true value of the outcome (imbalance in proportion of missingness between arms). Risk assessed to be high for the outcomes: 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. Unblinded study (outcome assessor) MORTALITY, (TIME TO) 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). Time to viral negative conversion. 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). (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined as hospital discharge) 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). Time to clinical improvement. 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 |
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 prospective version of the study registry was not available.
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 (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |