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: "Patients were randomly assigned to either the triple combination lopinavir–ritonavir, ribavirin, and interferon beta-1b group or the control group (lopinavir–ritonavir only), in the ratio of 2:1, by simple randomisation with no stratification. Randomised treatment was open-label. Patients were assigned to a serial number by the study coordinator. Each serial number was linked to a computer-generated randomisation list assigning the antiviral treatment regimens. The study medications were dispensed by the hospital pharmacy and then to the patients by the medical ward nurses."
Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Low |
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context: No participant cross-over. A higher proportion of participants in the treatment received glucocorticoids, compared to the control arm (69,7% vs 48,7%); however this difference is small in absolute values (i.e., number of participants that received glucocorticoids per arm: 6 vs 2). 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). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 127 participants randomized, 127 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| 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, (TIME TO) VIRAL NEGATIVE CONVERSION Mortality and viral negative conversion are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. WHO SCORE 7 AND ABOVE For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: WHO score 7 and above (D28). ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: the registry (version dated February 17th, 2020) was available and consulted.
MORTALITY, TIME TO VIRAL NEGATIVE CONVERSION, AE, SAE 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 outcomes: Mortality (D28). Time to viral negative conversion. Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERISON, WHO SCORE 7 AND ABOVE Outcome data acquired from contact with authors. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Incidence of viral negative conversion (D7). WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |