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 patients were randomly assigned (1:1) to receive either HCQ/AZT or placebo. An independent pharmacist dispensed all trial medications (or placebo) according to a computer-generated randomization list.”
Comment: Allocation sequence random Allocation sequence concealed |
| Deviations from intervention |
Low |
Quote: “Double-blinded. Patients, treating clinicians, and study personnel were all blinded to study group assignment. ”
Comment: Blinded study (participants and personnel/carers) 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 low for the outcomes: Mortality (D28). Hospitalization or death. Incidence of viral negative conversion (D7). Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 84 participants randomized; 84 participants analyzed for negative conversion; 82 participants analyzed for mortality, hospitalization and safety.
Of note, there was missing follow-up for 2 vs 0 participants and negative RT-PCR for 4 vs 8 participants Data not available for all or nearly all participants randomized. Missingness (from lack of follow-up) could depend on the true value of the outcome. Negative RT-PCR could not depend on the true value of the outcome Likely that missingness (from lack of follow-up) depended on the true value of the outcome. However, they only represented 2% of the participants, as such we will deviate from the algorithm and judge this domain to be some concerns of risk of bias. Risk assessed to be some concerns for the outcomes: Mortality (D28). Hospitalization or death. Incidence of viral negative conversion (D7). Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Hospitalization or death. Incidence of viral negative conversion (D7). Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The registry was retrospective (dated 04/29/2020) however it was registered before unblinded data was available for analysis.
HOSPITALIZATION OR DEATH, VIRAL NEGATIVE CONVERSION, SAE Outcome pre-specified. 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: Hospitalization or death. Incidence of viral negative conversion (D7). Serious adverse events. MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. 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: Mortality (D28). |
| Overall risk of bias |
Some concerns |