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: “Eligible subjects were randomly assigned in a 1:1 ratio to receive either PEG IFN-α2b along with SOC or SOC alone. Randomization was generated using SAS® software (Version 9.4).” (Report) “Method of Concealment: Not applicable.” (Registry) Comment: Allocation sequence random. Unclear allocation concealment. |
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: biologics, antivirals and corticosteroids. Hence, no information on whether deviations arose because of the trial context. MORTALITY, CLINICAL IMPROVEMENT, ADVERSE EVENTS Our analysis for the binary outcomes is an 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). Clinical improvement (D28). Adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the negative conversion outcome. Of note, 28 patients were not included in the negative conversion analysis due to missing data which is accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). |
Missing outcome data |
Some concerns |
Comment: 250 participants randomized; 250 participants analyzed for mortality and safety; 242 participants analyzed for clinical improvement and negative conversion.
Data available for all or nearly all participants randomized for mortality, clinical improvement and safety. Data not available for all or nearly all participants randomized for negative conversion (113/119 intervention arm; 109/123 control arm) No evidence that the result is not biased. Reasons: Day 7 negative conversion outcome was not reported for a total of 25 participants (4 in the treatment arm and 21 in the control arm) Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome: Day 15 negative conversion outcome was reported for almost all participants. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). Adverse events. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
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). Incidence of viral negative conversion (D7). CLINICAL IMPROVEMENT Clinical improvement (defined as a 2-point improvement on an ordinal scale) 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 (D28). ADVERSE EVENTS The authors reported on 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 prospective registry was available
Outcomes 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). Incidence of viral negative conversion (D7). Clinical improvement (D28). Adverse events. |
Overall risk of bias |
Some concerns |