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: "In this study, the statistical software SAS9.4 was used to generate a random grouping table to divide the subjects the experimental group and the control group in a 1: 1 distribution ratio. The specific random process was as follows: after confirming that the subjects provide informed consent, and meet all the inclusion criteria and does not meet any of the exclusion criteria, the pre-generated randomization table was used to obtain the subject's random number and drug allocation information." Comment: Allocation sequence random. No information on allocation concealment. |
| 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. Antivirals, corticosteroids and biologics were reported but unbalanced between two arms, patients in the umifenovir received more antivirals and corticosteroids. 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. Our analysis for the binary outcome 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). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 240 participants randomized, 236 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (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: The protocol was available (dated February 22nd, 2020).
MORTALITY No timepoint for mortality in the registry No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Mortality (D28). ADVERSE and SERIOUS ADVERSE EVENTS Outcome pre-specified. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial probably analyzed as pre-specified. Risk assessed to be low for the outcomes: Adverse events. Severe adverse events. |
| Overall risk of bias |
Some concerns |