| 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). Cross-over: One patient was prescribed interferon alpha instead of rSIFN-co due to the attending physician’s misinterpretation of the randomization result. Administration of co-interventions of interest reported: antivirals, corticosteroids, biologics. No information on anticoagulants. Appropriate analysis method used; participants analyzed according to their intervention assignment |
| Missing outcome data |
Low |
Comment: 96 patients randomized; 94 patients analyzed.
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. Data available for >95% of population. Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Incidence of clinical improvement. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. 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. Incidence of WHO score 7 and above. Clinical improvement (defined as improvement of two points on a seven-category ordinal scale) and incidence of WHO score 6 and above require clinical judgement and 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. Incidence of WHO score 6 and above. 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. Result was not selected from multiple outcome measurements nor multiple analyses of the data. Trial was analyzed as pre-specified, with respect to these outcomes. Risk assessed to be low for outcomes: Incidence of viral negative conversion. Incidence of clinical improvement. In the registry, the remaining outcomes did not contain timepoints and clinical status on the seven category scale was not specified. For mortality, adverse events and serious adverse events, the results were unlikely to have been 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). No information on whether the data for WHO score 6 and above and WHO score 7 and above were selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified, with respect to these outcomes. Risk assessed to be some concerns for the outcomes: Mortality. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |