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: “Following informed consent and screening, the patients were block randomised (in blocks of 4) by computer-generated random numbering to the favipiravir (1600 mg twice daily orally day one only, subsequently 600 mg BID PO days 2 to 10), hydroxychloroquine therapy (400 mg twice daily orally day one only, subsequently 200 mg twice daily orally from day 2 to day10) or standard treatment arms. The physicians on site would call the research coordinator to randomise the patients using the computer-generated random numbering, once deemed eligible and have given informed consent.”
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Unblinded. Patients and clinicians were not blinded to the treatment given.”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: corticosteroids. Biologics were reported and other antivirals were not allowed. Hence, no information on whether deviations arose because of the trial context. MORTALITY. CLINICAL IMPROVEMENT Our analysis for the binary outcome 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). Clinical improvement (D28). VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 14 vs 11 participants were not analyzed, presumably because of not testing. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
Comment: 106 participants randomized (in the 2 relevant arms); 106 participants analyzed for mortality, 100 participants analyzed for clinical improvement, 80 participants analyzed for viral conversion.
MORTALITY Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). CLINICAL IMPROVEMENT Data not available for all or nearly all participants randomized. No evidence that the result is not biased. 1 vs 5 participants were excluded from the analysis post-randomization. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons not reported; similar proportions between arms. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| 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, 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). CLINICAL IMPROVEMENT Clinical improvement (defined as 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). |
| Selection of the reported results |
Low |
Comment: The prospective registry was available. [dated May 14, 2020]
Outcomes pre-specified. 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). Incidence of viral negative conversion (D7). Clinical improvement (D28). |
| Overall risk of bias |
Some concerns |