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: "randomization was done with a computer-based software “randomize R package” of version 1.4.2" (pre-print), "The randomization will be done using a secured central computer-based randomization using a secure website using a central, computer-based randomisation program in a ratio of 1:1 in the non-severe category
and 1:1:1 in the severe category" (protocol)
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: "Open-label"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: antivirals, corticosteroids or biologics were reported. Hence, no information on whether deviations arose 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 some concerns for the outcomes: Mortality (D28). |
| Missing outcome data |
Some concerns |
Comment: 71 participants randomized; 63 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: In the HCQ+RBV arm 2 were voluntarily withdrawn, 1 quit due to an adverse reaction; 2 participants are missing from the LPV/r+RBV arm and 3 from the SC arm for unknown reasons. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcome: Mortality (D28). |
| Measurement of the outcome |
Low |
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 outcome: Mortality (D28). |
| Selection of the reported results |
Low |
Comment: The protocol(retrospective, dated October 20th, 2020) and registry were available (prospective, dated June 3rd, 2020).
Outcome pre-specified. 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 outcome: Mortality (D28). |
| Overall risk of bias |
Some concerns |