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:"Subjects will be enrolled into treatment groups in each phase of the study based on a computer-
generated randomization schedule prepared by or under the supervision of Medicago before the
study. The randomization number and treatment will be recorded along with a unique subject
number for each subject in the investigational product accountability log.†(Protocol)
Comment: Allocation sequence random. Unclear allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "Double blinded. The masking of individual allocation was maintained for all investigators and participants." Comment: Blinded study (participants and personnel/carers) Per-protocol analysis was performed on the efficacy outcomes. Reasons for exclusion: participants who did not complete 28 days after the third dose (not reported by arm). As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to the large sample size. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. |
| Missing outcome data |
Low |
Comment: 27703 participants randomized; 24670 participants analyzed Data not available for all or nearly all participants randomized for efficacy. No evidence that the result is not biased. Reasons:Missingness could not depend on the true value of the outcome. Protocol violations were addressed in ROB2. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. |
| 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: Confirmed symptomatic COVID. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (Date January 12th, 2021) 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 outcome: Confirmed symptomatic COVID. |
| Overall risk of bias |
Some concerns |