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 |
Some concerns |
Quote: “Patients were randomly assigned” (report)
"Random number table method" (registry) Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: "open-label trial"
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. Administration of co-interventions of interest: biologics and corticosteroids were reported. Biologics administration between arms (3/26 vs 6/24). This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect 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). Mortality (D60 or more). Incidence of viral negative conversion (D7). Clinical improvement (D60 or more). Adverse events. |
| Missing outcome data |
Low |
Comment: 50 participants randomized; 48 participants analyzed.
Two participants dropped out from the combination treatment group after adverse reactions. Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Incidence of viral negative conversion (D7). Clinical improvement (D60 or more). 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, 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). Mortality (D60 or more). Incidence of viral negative conversion (D7). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge whose criteria include "significant improvements of respiratory symptoms and CT imaging") requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D60 or more). 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. |
| Selection of the reported results |
Some concerns |
Comment: Neither the protocol nor the statistical analysis plan was available. The prospective registry (dated February 22nd, 2020) was available and utilized.
MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. 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 outcomes: Mortality (D28). Mortality (D60 or more). VIRAL NEGATIVE CONVERSION, CLINICAL IMPROVEMENT, ADVERSE EVENTS Outcome not pre-specified No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). Clinical improvement (D28). Adverse events. |
| Overall risk of bias |
Some concerns |