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 and consenting patients were assigned in a ratio of 2:1 to either usual standard of care or usual standard of care plus hydroxychloroquine or one of the other available treatment arms (see Supplementary Appendix) using web-based simple (unstratified) randomization with allocation concealment." Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "Participants and local study staff were not masked to the allocated treatment."
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: Administration of co-interventions of interest, antivirals, biologics and corticosteroids, reported and balanced between groups. In the intervention arm, 1430/1553 (7.9%) received hydroxychloroquine. In the control arm, 12/3140 received hydroxychloroquine (0.38%). Overall, the deviation was too small to affect the outcome. 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 low for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Missing outcome data |
Low |
Comment: 4716 patients randomized; 4716 patients analyzed. Follow-up information (compliance data) was available for 1553/1561 in HCQ arm and 3140/3155 in SC arm. Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28) |
| 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 is an observer-reported outcomes not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). Clinical improvement (defined as discharge from hospital) requires clinical judgement and could be affected by knowledge of intervention receipt. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available.
Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28) |
| Overall risk of bias |
Some concerns |