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: “A randomization list was developed according to a unique computer-generated number sequence. Randomization was unbalanced in a 1:2:4:2 ratio, and processed in permuted blocks of sizes two, four and six, that were stored in sequentially numbered sealed opaque envelopes that were opened after informed consent at randomization.”
Comment: Allocation sequence random. Allocation sequence concealed. |
Deviations from intervention |
Some concerns |
Quote: “Open-label. Investigators and patients were blinded to the viral load results during the study dosing period.”
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: antivirals and biologics. Corticosteroids were reported. Hence, no information on whether deviations arose because of the trial context. ADVERSE EVENTS 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 outcome: Adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 1 participant assigned to the IVM 100 mcg/kg arm was excluded from the analysis post-randomization because they did not receive the drug. One participant assigned to standard care was excluded due to a protocol violation. This method was considered inappropriate to estimate the effect of assignment to intervention. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
Missing outcome data |
Low |
Comment: 32 participants randomized; 31 participants analyzed for safety; 30 participants analyzed for viral negative conversion.
ADVERSE EVENTS Data available for all or nearly all participants randomized for safety. 1 participant dropped out prior to receiving medication which was taken into account in domain 2. Risk assessed to be low for the outcome: Adverse events. VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reason for exclusion: 1 participant dropped out prior to receiving medication and another participant had protocol violation which were taken into account in domain 2. Missingness could not depend on the true value of the outcome. Risk assessed to be low 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). Viral negative conversion is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Incidence of viral negative conversion (D7). The authors reported on adverse events that contain both clinically- and laboratory-detected outcomes and 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 outcome: Adverse events. |
Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available. The trial registry was available.
Several changes were made to procedures and outcomes in the prospective trial registry after commencement of the study. No review-specific outcomes were pre-specified in the prospective (June 11th, 2020) version of the registry. 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 outcomes: Incidence of viral negative conversion (D7). Adverse events. |
Overall risk of bias |
Some concerns |