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: “Subjects were randomized to either HCQ or placebo in blocks of 8, using established randomization software (SealedEnvelope.com, Clerkenwell Workshops).”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “double-blind, placebo-controlled”.
"5 subjects (2 in the HCQ arm and 3 in the placebo arm) developed progressive symptoms (an increase in symptoms score of 2 points on any day on study) while on study and were unblinded after completing 7 days of their originally assigned study treatment." Comment: Partially blinded study (some participants unblinded and personnel/carers blinded). Deviations from intended intervention arising because of the study context: 3 participants in the placebo group received intervention. In the outpatient setting, we consider no important cointerventions of interest. This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. 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: Hospitalization or Death. Mortality (D28). Mortality (D60 or more). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Data from interim analysis
Comment: 34 participants randomized; 34 participants analyzed for safety outcomes (according to results section of registry) Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Hospitalization or Death. Mortality (D28). Mortality (D60 or more). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Hospitalization or Death. Mortality (D28). Mortality (D60 or more). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and registry were available.
The protocol provided was an updated version dated June 17, 2020 (retrospective) but it was transparent in terms of the changes made to the protocol and adverse events was not among the changes. Furthermore, mortality pre-specified, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Hospitalization was pre-specified in the registry. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial probably analyzed as pre-specified. Risk assessed to be low for the outcomes: Hospitalization or Death. Mortality (D28). Mortality (D60 or more). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |