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: "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 random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "open-label"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Co-intervention administration of corticosteroids, biologics and antivirals are reported and balanced between groups. Hence, deviations did not arise because of the trial context. 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). Time to viral negative conversion. WHO score 7 and above (D28). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 33 participants randomized, 33 participants analyzed.
Data available for all or nearly all participants randomized. 2 in the HCQ group and 1 in the SOC group withdrew consents "before the first dose was administered", which is unrelated to the outcome. Risk assessed to be low for outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). 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). SERIOUS ADVERSE EVENTS The authors reported on this outcome 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: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: Statistical analysis plan not available. The protocol and registry were available but the registry was retrospective, hence the prospective (March 29th, 2020) version of the protocol was consulted.
Outcome pre-specified. 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 (D28). Serious adverse events. Outcome data acquired from contact with authors. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |