| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "Eligible subjects were randomly assigned by an interactive web response system in a 2:1 ratio to receive either HCQ plus standard of care (SOC) or SOC alone" Quote from contact with authors: "After informed consents signed, a random number were generated by computer" Comment: Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study.
No cross-over. Co-intervention administration of corticosteroids and antivirals are reported. No information on biologics. Analysis was performed on the total number of randomized patients per group. |
| Missing outcome data |
Low |
Comment: More than 5% of missing data per arm (two in the HCQ group and one in the SOC group). Reason: "withdrawn consents before the first dose was administered".
Missingness due to documented reasons unrelated to the outcome. Risk assessed to be low for outcomes: Mortality. Incidence of viral negative conversion. Time to viral negative conversion. WHO score 6 and above. WHO score 7 and above. 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 reflect decisions made by the intervention provider. However, we consider that the assessment of mortality, WHO Score 7 and above and viral negative conversion cannot possibly be influenced by knowledge of the intervention assignment. Risk assessed to be low for outcome: Mortality. Incidence of viral negative conversion. Time to viral negative conversion. WHO score 7 and above. For WHO score 6 and above, although the assessment could possibly be influenced by knowledge of the intervention assignment, we did not consider this likely to have happened in the context of a pandemic. Serious adverse events may contain both clinically- and laboratory-detected outcomes, therefore it can be influenced by knowledge of the intervention assignment, but is not likely to. Risk assessed to be some concerns for outcomes: WHO score 6 and above. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: Statistical analysis plan not available. The protocol and registry were available.
Outcomes related to WHO score 6 and above and WHO score 7 and above were neither specified in the registry nor reported as outcomes in the paper. All other outcomes were registered and reported accordingly. Results were not selected from multiple outcome measurements nor analyses of the data. Trial analyzed as prespecified. Risk assessed to be low for outcomes: Mortality. Incidence of viral negative conversion. Time to viral negative conversion. Incidence of recovery. WHO score 6 and above. WHO score 7 and above. Serious adverse events. |
| Overall risk of bias |
Some concerns |