| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Randomization is performed using a web-based system (Ennov Clinical software using a minimization algorithm. This study is double-blind with the use of a placebo that is impossible to distinguish from hydroxychloroquine tablets by appearance, odor, or taste. The presentation of treatments does not allow a distinction between HCQ and the placebo. Each item of treatment has a unique processing number. Only this number can identify the substance. The link between each processing number and the content is only known by the coordinating pharmacy. The coordinating pharmacy supervises the production, packaging, and distribution of treatment batches (HCQ/placebo). These tasks are carried out by an external service provider. The doctors and nurses taking care of the patients, as well as the patients themselves, do not know which treatment they have been assigned.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "The doctors and nurses taking care of the patients, as well as the patients themselves, do not know which treatment they have been assigned."
Comment: Double-blinded study (patients and physicians). Data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 250 patients randomized; 247 patients analyzed. Only 3 blinded participants withdrew from the study, less than 5% of the total sample size.
Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Incidence of clinical improvement. Incidence of WHO score 7 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor).
Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Incidence of clinical improvement. WHO score 7 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were available. Data analyzed and presented as pre-specified.
Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Incidence of clinical improvement. WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Low |