| 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 |
Comment: Unblinded study.
In the intervention arm, 1430/1553 received hydroxychloroquine. In the control arm, 12/3140 received hydroxychloroquine. Deviations too small to affect outcome (7.9% vs 0.38%). Co-intervention administration for corticosteroids, antivirals, biologics are reported and balanced between groups. Data were analyzed by using intent-to-treat analysis. |
| 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 >95% of population. Risk assessed to be low for the outcomes: Mortality. Incidence of clinical Improvement. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study (outcome assessor).
Mortality is an observer-measured and does not involve clinical decision-making or involve assessor judgment. Risk assessed to be low for outcome: Mortality. For incidence of clinical improvement (defined as discharge by D28) the assessment could possibly be influenced by knowledge of the intervention assignment however we did not consider this likely in the context of a pandemic. Risk assessed to be some concerns for outcome: Incidence of clinical improvement. |
| Selection of the reported results |
Low |
Comments: The protocol was available. The statistical analysis plan was available.
Result was not selected from multiple outcome measurements or analyses. Trial analyzed as prespecified. Risk assessed to be low for the outcomes: Mortality. Incidence of clinical improvement. |
| Overall risk of bias |
Some concerns |