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 randomized in a 1:1 ratio using a computer-generated random number table” Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
"Quote: ""single blind""
Comment: Blinded study (patients were blinded and physicians were not blinded). Deviations from intended intervention arising because of the study context: One patient was prescribed interferon alpha instead of rSIFN-co due to the attending physician's misinterpretation of the randomization result. Deviation too small to affect the outcome Administration of co-interventions of interest reported: antivirals, corticosteroids, biologics. Antivirals were imbalanced but by <10% between arms (50% vs 58%) 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. Appropriate analysis method used; participants analyzed according to their intervention assignment" Risk assessed to be some concerns for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. Clinical improvement (D28).Time to clinical improvement. WHO score 7 and above (D28).Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 96 patients randomized; 94 patients analyzed.
Data available for all or nearly all participants randomized. data missing for two patients - One patient in the rSIFN-co arm did not receive the study drug because of death within 24 hours of randomization, and was excluded from all analyses. One patient in the rSIFN group received the wrong study drug and was included in the control group for safety analysis. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28)Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study (outcome assessor).
Mortality and viral negative conversion are observer-reported outcomes not involving judgement. For the incidence of 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: Mortality. Incidence of viral negative conversion (D7). Time to viral negative conversion. Incidence of WHO score 7 and above (D28). Clinical improvement (defined as improvement of two points on a seven-category ordinal scale) could be affected by knowledge of intervention receipt. Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes. All these outcomes 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: Incidence of clinical improvement (D28).Time to clinical improvement. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: Neither the protocol nor the statistical analysis plan was available.
The prospective registry pre-specified viral negative conversion and clinical improvement outcomes with details such as timepoints, which were reported as such in the paper. Outcomes related to WHO score 7 and above were neither registered nor reported as outcomes in the paper. Results were probably not selected from multiple outcome measurements nor multiple analyses of the data of these outcomes Trial was probably analyzed as pre-specified with respect to these outcomes. Risk assessed to be low for outcomes: Incidence of viral negative conversion. Time to viral negative conversion. Incidence of clinical improvement (D28).Time to clinical improvement. WHO score 7 and above(D28). In the registry, the remaining outcomes did not contain timepoints. For mortality, adverse events and serious adverse events, there is no information on whether the results were selected from multiple outcome measurements (e.g. time points) or analyses of the data. Trial was not analyzed in accordance with a pre-specified, finalized analysis plan (since the time points had not been finalized). Risk assessed to be some concerns for the outcomes: Mortality(D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |