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 |
Low |
Quote: "Randomization was accomplished by using a random table that was generated in SAS software at 1:1. Each enrolled subject (meeting all the inclusion criteria and not meeting any of the exclusion criteria) was given a number, randomly assigned to the FNC group and control group according to a predetermined random table (Figure S1, Supporting Information), and received treatment according to the corresponding treatment regimen."
Contact with authors: Treatment allocation was concealed with the use of sequentially coded, sealed, opaque envelopes. Comment: Allocation sequence random. Allocation sequence concealed. |
Deviations from intervention |
Some concerns |
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context: No participant cross-over. Co-intervention administration of antivirals, biologics and corticosteroids were reported. 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). Incidence of viral negative conversion (D7). Time to viral negative conversion. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Missing outcome data |
Low |
Comment: 20 participants randomized; 20 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious 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, (TIME TO) 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). Time to viral negative conversion. WHO SCORE 7 AND ABOVE For 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: WHO score 7 and above (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge from hospital) 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 and SERIOUS 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. Serious adverse events. |
Selection of the reported results |
Some concerns |
Comment: There is no protocol or statistical plan available in English. (Available in Chinese). The prospective registry was available in English (dated February 15th, 2020).
MORTALITY, (TIME TO) VIRAL NEGATIVE CONVERSION Outcomes pre-specified but with no timepoints. 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 outcome: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. CLINICAL IMPROVEEMNT, WHO SCORE 7 AND ABOVE, AE, SAE Outcomes not pre-specified No information on whether these results were 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: Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |