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 in a 1:1 ratio was done by computer-generated program using randomization.com (http://www.jerrydallal.com/random/randomize.htm) by Clinical Research Coordinator (CRC), blinded to the rest of the study team" Comment: Allocation sequence random. Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: “The investigators and patients were blinded to the assignment.” Comment: Blinded study (participants and personnel/carers) ADVERSE and SERIOUS 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 low for the outcomes: Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 7 vs 14 participants were excluded from the analysis post-randomization because their first two RT-PCR tests were negative. 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: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
Comment: 116 participants randomized; 89 participants analyzed for efficacy; 116 participants analyzed for safety. ADVERSE and SERIOUS ADVERSE EVENTS Data available for all Participants randomized. Risk assessed to be low for the outcomes: Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: participants excluded from analysis because RT-PCR tests were negative soon after randomization. Any related bias taken into account in domain 2. The remaining 6 missing cases account for 5.2% of the population. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Incidence of viral negative conversion (D7). Adverse events. Serious adverse events |
| Selection of the reported results |
Some concerns |
Comment: The registry was available but retrospective (dated June 12, 2020) No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). Adverse events. Serious adverse events |
| Overall risk of bias |
Some concerns |