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 |
Some concerns |
Quote: " Patients were randomly assigned to treatment groups at a ratio of 2:2:1 (Figure 1)"
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study (participants and personnel/carers).
Deviations from intended intervention arising because of the study context: No participant cross-over. No information on any co-interventions of interest were reported: antivirals, biologics, corticosteroids. Hence, no information on whether deviations arose 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 some concerns for the outcomes: Mortality (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
High |
Comment: 67 participants randomized; 43 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missing data: "Seven patients in the chloroquine arm, 6 patients in the hydroxychloroquine arm, and 2 patients in the control arm were excluded from analysis because COVID-19 manifested as mild symptoms only. There were an additional 4 patients in the hydroxychloroquine arm who were misdiagnosed with COVID-19 and therefore excluded. 5 patients with no symptoms were also excluded (2 in the chloroquine arm and 3 in the hydroxychloroquine arm). Missingness could depend depend on the true value of the outcome. Likely that missingness depended on the true value of the outcome (different proportions and reasons for missingness among arms). Risk assessed to be high for outcomes: Mortality (D28). Adverse events. 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for outcome: Mortality (D28). ADVERSE and SERIOUS ADVERSE EVENTS the authors reported on adverse events and serious adverse events 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 outcomes: Adverse Events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: Neither the protocol nor the statistical analysis plan were available. The registry was available.
MORTALITY Mortality outcome was not pre-specified, 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 outcome: Mortality (D28). SERIOUS ADVERSE EVENTS Outcome presented as 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 outcome: Serious adverse events. ADVERSE EVENTS Outcome not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for outcome: Adverse events. |
| Overall risk of bias |
High |