| 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." |
| Deviations from intervention |
Some concerns |
Comment: Unblinded study. Co-intervention administration for corticosteroids(Dexamethasone), antivirals (Lopinavir/ritonavir and Remdesivir), biologics(Tocilizumub or Sarilizumub) and antibiotics(Azithromycin or other macrolides) are reported in Table S2 and in balanced per arm proportions. NI for co-intervention anticoagulants. Data were analyzed by using intent-to-treat analysis. |
| Missing outcome data |
Some concerns |
Comment: 4716 randomized, 4716 analyzed. Quote: "Follow-up information was complete for 4619 (98%) of the randomized patients." Risk assessed to be "low" for the outcomes: Mortality, Clinical Improvement, Score 7 and above. Since data related to major cardiac arrythmias was mandated to be collected from 12 May, the outcome Serious adverse effects is only available for a subset of the population. 698/1561 intervention arm and 1357/3155 control arm particpants had complete follow up forms with these data. Risk assessed to be "some concerns" for the outcome Serious adverse effects |
| Measurement of the outcome |
Some concerns |
Comment: The trial was not blinded to participants or study staff. The outcome mortality is observer-measured and does not involve clinical decision-making or involve assessor judgment. The outcomes Clinical Improvement (the definition is Discharge by D28) and Serious adverse effects, reflects a decision made by the intervention provider where 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 The outcome Score 7 and above, although is a judgement made by intervention provider we consider that the assessment cannot possibly be influenced b yknowledge of the intervention assignment Risk assessed to be "Low" for the outcomes: Mortality and Score 7 and above and "Some concerns" for the outcomes Clinical Improvement and Serious adverse effects. |
| Selection of the reported results |
Some concerns |
Comments: The protocol was available. The statistical analysis plan was available. Primary and secondary outcomes pre-especified. Serious adverse events considered "Subsidiary outcome" is not pre-specified. Risk assess to be "Low" for the outcomes Mortality. Clinical improvement. Score 7 and above. Risk assessed to be "Some concerns" for the outcome Serious adverse events. |
| Overall risk of bias |
Some concerns |