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: “Participants were randomly assigned in a 1:1 ratio to receive one dose of mRNA-1273 or BNT162b2 vaccine stratified on the vaccine received at the first dose. The randomization was stratified by center and by the vaccine received at the first dose (BNT162b2 or mRNA-1273 vaccine). We used a web-based randomization system (CleanWeb e-CRF, Telemedecine Technologies, S.A.S), with a centralized block randomization list with blocks of size four (not communicated to the investigating team). The randomization list was generated by an independent statistician from the trial clinical research unit (URC-EST). Participants were randomized by the investigator.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "Open-label"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. Pre-planned per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: Positive or doubtful anti-nucleocapsid IgG serology at day 0 and/or day 28, wrongly included, or missing primary endpoint. 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 balance between arms. Data for the safety outcome were analyzed using intention-to-treat analysis. As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 414 participants randomized; 390 participants analyzed for immunogenicity; 414 participants analyzed for safety.
Data available for all participants randomized for safety. Data not available for all or nearly all participants randomized for immunogenicity. No evidence that the result is not biased. Reasons: positive or doubtful anti-nucleocapsid IgG serology at day 0 and/or day 28, wrongly included, or missing primary endpoint. Missingness could not depend on the true value of the outcome. Most participants were excluded from the per protocol analysis due to positive or doubtful anti-nucelocapsid IgG serology at day 0 which is already accounted for in domain 2. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. 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. Unblinded study (outcome assessor) SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT Observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. SERIOUS ADVERSE EVENTS The authors reported on 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: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The study registry was available (25 May 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 outcomes: Specific antibody GMT. Neutralizing antibody GMT. Serious adverse events. |
| Overall risk of bias |
Some concerns |