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: (protocol): “The IWRS (Interactive Web Response System) will be used by authorized study site personnel to randomize eligible participants. It is an intranet-based application that is hosted behind the VA firewall on a VA server at the CSPCRPCC. It is only accessible on the VA network to authenticated VA personnel. Access to study data is restricted to personnel that have registered in the IWRS and have been authorized by the study team. All communication to or from the IWRS is encrypted using Hypertext Transfer Protocol Secure (HTTPS) and is secured using a VA furnished Secure Sockets Layer (SSL) certificate."
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Low |
Quote: “triple blinding”
Comment: Blinded study (participants and personnel/carers) Our analysis for the outcome is an 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: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 75 participants randomized; 64 participants analyzed for clinical improvement; 70 participants analyzed for all other outcomes.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 1 vs 1 were lost to follow up and 3 vs 0 withdrew at the time of randomization. 4 vs 2 were not included in the analysis because they died (Clinical improvement outcome only). 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: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Serious adverse events. |
| 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: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The retrospective protocol and statistical analysis plan version 1.9 were available (dated September 10, 2021). The registry was utilized for assessemnt and consulted up to version dated November 18, 2020).
Outcome pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Time to WHO score 7 and above. Serious adverse events. |
| Overall risk of bias |
Some concerns |