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: “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: “Observer-blinded” [report]; "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)" [registry]
Comment: Blinded study (participants and personnel/carers) Data for the safety and efficacy outcomes were analyzed amongst those who received at least one dose of the intervention. This method was considered appropriate to estimate the effect of assignment to intervention. As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate. Reactogenicity subset included participants who had received both doses following the protocol-prescribed dosing regimen and who had completed at least 2 months of safety follow-up, post dose 2. 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 similar reasons and proportions between arms. Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 24,141 participants randomized; 24,076 participants analyzed for safety and efficacy; 7,819 participants analyzed for reactogenicity.
Data available for nearly all participants randomized for safety and efficacy. Data not available for all or nearly all participants randomized for reactogenicity. No evidence that the result is not biased. This potential source of risk of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events. Adverse events. 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: Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available.
Outcomes 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: Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |