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: “web-based simple (unstratified) randomisation with
allocation concealed
until after randomisation.”
Comment: Allocation sequence random. Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: "open-label"
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: Administration of co-interventions of interest, antivirals and biologics were reported and balanced between arms. 5 of 3410 patients with completed follow-up allocated to usual care received lopinavir-ritonavir. 1394 of 1603 patients with completed follow-up at time of analysis allocated to lopinavir-ritonavir received lopinavir-ritonavir. Overall, the deviation was too small to affect the outcome. Hence, deviations did not arise because of the trial context. 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: 5040 participants randomized; 5040 participants analyzed.
Data available for all or nearly all participants randomized. Follow-up information was complete for 5018 (>99%) of 5040 patients. 4 vs 7 participants withdrew consent. 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge from hospital alive) requires clinical judgement and could be affected by knowledge of intervention receipt, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and 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 |