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: "Eighty-six (86) volunteers were divided into two groups by block randomization in a 1:1 ratio (randomization by the “sealed envelope” method)" "The investigator physician, by opening an envelope with the lowest number in the set, knew which randomization number should be assigned and which study preparation should be administered to the volunteer. When the next volunteer was included in the study, the next envelope was opened"
Comment: Allocation sequence probably random. Unclear allocation concealment. |
| Deviations from intervention |
Low |
Quote: "Single-blind" "For the sake of objectification, the volunteers did not know what study preparation was administered to them. The study preparations were delivered to the trial facility in a ready-to-use (coded) form. To ensure masking, before injection, the study preparations were prepared in a treatment room behind a screen."
Comment: Single blind study (participants were blinded, personnel and investigators were not blinded). Deviations from intended intervention arising because of the study context: No participant cross-over. No indication that co-interventions were administered or imbalanced. Hence, deviations did probably not arise because of the trial context. 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 low for the outcomes: Local adverse events. Systemic adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 86 participants randomized; 86 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Withdrawals due to 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. Unclear blinding (outcome assessor). 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: Local adverse events. Systemic adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The registry was available. It was first posted online 10 days after phase 2 commencement, likely before data analyses had started.
Local-, systemic-, and serious adverse events outcomes were listed in the registry. Results for these outcomes were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified for these outcomes. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Serious adverse events. Withdrawals due to adverse events was not listed in the registry as an outcome. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for the outcome: Withdrawals due to adverse events. |
| Overall risk of bias |
Some concerns |