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: "The participants were randomly assigned in a 1:1 ratio. In order to generate an allocation sequence, simple random allocation was applied using an Excel file; 80 eligible patients were enrolled in the study (40 individuals in each group). For allocation sequence concealment, the study arm for each patient was contained in a sealed envelope labelled with a number from 1 to 80"
Comment: Allocation sequence probably random. Unclear allocation sequence concealment (no information on opacity of envelopes) |
| Deviations from intervention |
Some concerns |
Quote: "Open-label" (report); "In this study, single blind- patients will be kept blind to the type of treatment" (registry)
Comment: Unclear blinding (participants and personnel/carers) Deviations from intended intervention arising because of the study context: Three patients in the control arm received study drug (sofosbuvir/velpatasvir) at the physician's discretion. No information on administration of co-interventions of interest: biologics. 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. MORTALITY, (TIME TO) CLINICAL IMPROVEMENT Data for the outcomes 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). Clinical improvement (D28). Time to clinical improvement. ADVERSE EVENTS Participants were not analyzed according to their randomized groups for the outcome adverse events. Of note, 3 participants randomized to the control group received the study drug and were analyzed in the intervention group and one patient who died within 24 hours after admission and did not receive the study drug and was excluded from safety analyses. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcomes: Adverse events. |
| Missing outcome data |
Low |
Comment: 80 participants randomized; 80 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). Time to clinical improvement. 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 outcomes not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). br/> (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined two point reduction in oxygen supplementation scale or discharge) 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). Time to clinical improvement. ADVERSE EVENTS The authors reported on adverse events that 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. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available. The prospective registry was available (dated 30 March 2020).
MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Mortality (D28). (TIME TO) CLINICAL IMPROVEMENT, ADVERSE EVENTS Outcomes not pre-specified. 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: Clinical improvement (D28). Time to clinical improvement. Adverse events. |
| Overall risk of bias |
Some concerns |