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|
|Quote: "This was a randomized, open-label, parallel group study. Patients eligible for the
study were assigned, in a 1:1:1 ratio, to Novaferon, Novaferon plus Lopinavir/Ritonavir,
or Lopinavir/Ritonavir group. A SAS generated simple randomization schedule was
prepared by a statistician not involved in the trial. Based on the sequence that patients
enrolled into the study, the patients were assigned to a treatment group which was
implemented by a research assistant."
Quote from the protocol: "The randomization method is the stratified block randomization according to the center stratification."
Comment: the randomization method changed from protocol to implementation, because the study was initially designed as a multi-center RCT, but implemented as a single-center RCT. The authors provide a clear explanation for this in the paper. The method of allocation concealment used, if any, is unreported. The baseline data provided are limited, but do not suggest a problem with the randomization process.
|Deviations from intervention||
|Comment: Unblinded study.
No participant cross-over.
There was no administration of any co-interventions of interest: antivirals, biologics, corticosteroids (retrieved from contact with authors)
Efficacy outcome data were analyzed by using intention-to-treat analysis.
|Missing outcome data||
|Comment: 89 randomized/89 analyzed. LOCF used for missing data for the outcome Viral negative conversion incidence at day 6 (1 in combination arm, 2 in Novaferon arm, 2 in Lopinavir/Ritonavir arm)
Risk assessed to be low for the outcomes: Mortality. Viral negative conversion incidence. Time to Viral negative conversion. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events.
|Measurement of the outcome||
|Comment: Mortality, Incidence of viral negative conversion and Time to viral negative conversion are observer-reported outcomes not involving judgement. WHO Score 6 and above and Score 7 and above are outcomes that reflect decisions made by the intervention provider. We consider that the assessment of Mortality, Incidence of viral negative conversion/Time to viral negative conversion and WHO Score 7 and above cannot possibly be influenced by knowledge of the intervention assignment.
Risk assessed to be low for outcomes: Mortality. Incidence of viral negative conversion/Time to viral negative conversion. WHO Score 7 and above.
For WHO Score 6 and above, although the assessment could possibly be influence by knowledge of the intervention assignment, we did not consider this likely to have happened in the context of a pandemic. Adverse events and serious adverse events may contain both clinically- and laboratory-detected outcomes, therefore it can be influenced by knowledge of the intervention assignment, but is not likely to.
Risk assessed to be some concerns for outcomes: WHO Score 6 and above. Adverse events. Serious adverse events.
|Selection of the reported results||
|Comment: the protocol and statistical analysis plan were available.
Trial analyzed as prespecified.
Results were not selected from multiple outcome measurements or analyses of the data.
Risk assessed to be low for the outcomes: Mortality. Negative viral conversion incidence. Time to negative viral conversion. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events.
|Overall risk of bias||