| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Using a centralized electronic system, we randomly assigned enrolled patients to hydroxychloroquine or placebo in a 1:1 ratio stratified by enrolling hospital using randomization block sizes of 2 and 4. Allocation was concealed.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Patients, treating clinicians, trial personnel, and outcome assessors were blinded to group assignment.”
Comment: Blinded study (patients and physicians). Data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 479 patients randomized; 479 patients analyzed by imputation (last observation carried forward or value assigned for up to 9.6% of participants).
Quote: "Primary outcome assessment of the COVID Outcomes Scale 14 days after randomization was completed for 433 (90.4%) of 479 randomized patients; 46 patients who were discharged from the hospital before primary outcome assessment, including 25 in the hydroxychloroquine group and 21 in the placebo group, were not successfully contacted for primary outcome evaluation and had values imputed based on a follow-up call on day 7 or were assigned a score of 6 if no call was completed on day 7. Follow-up information on survival through day 28 was completed for 477 (99.6%) of 479 randomized patients; 1 patient in the hydroxychloroquine group and 1 patient in the placebo group were lost to follow-up for vital status." For clinical improvement (discharge) there is no missing data since those 'missing' were discharge. Missingness does not depend on the true value of the outcomes WHO score 6 and above, WHO score 7 and above and Serious adverse events (defined as death or prolongation of hospitalization). Risk assessed to be low for the outcomes: Mortality. Time to death. Incidence of clinical improvement. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor).
Risk assessed to be low for the outcomes: Mortality. Time to death. Incidence of clinical improvement. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The trial registry, protocol and statistical analysis plan were available. Trial analyzed as pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcomes: Mortality. Time to death. Incidence of clinical improvement. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events. |
| Overall risk of bias |
Low |