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: "Randomization was performed using a computer-generated schedule in blocks of 4. Randomization was generated by someone not related to other aspects of study implementation. Allocation was concealed by ensuring the individual preparing syringes was not involved in other aspects of study implementation"
Comment: Allocation sequence random. Allocation sequence concealed. Risk assessed to be low. |
| Deviations from intervention |
Low |
Quote: "The contents of both mRNA-1273 and placebo vaccine for injection were concealed with opaque tape to ensure blinding. The patients, and study team members who obtained consent, administered vaccine, and assessed adverse events were blinded to vaccine assignment. The laboratory team was also blinded to vaccine assignment"
Comment: Blinded study (participants and personnel/carers). Data for the outcome 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: Confirmed symptomatic COVID. Specific antibody titers. Cellular response. Local adverse events. Systemic adverse events. |
| Missing outcome data |
Some concerns |
Comment: 120 participants randomized; 120 participants analyzed for efficacy; 119 participants analyzed for safety; 117 participants analyzed for specific antibodies; 65 participants analyzed for cellular response.
SAFETY.EFFICACY.SPECIFIC ANTIBODY GMT Safety, efficacy, and specific antibody GMT data were available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Specific antibody GMT. Local adverse events. Systemic adverse events. CELLULAR RESPONSE Cellular response data not available for all or nearly all participants randomized; 46% missing data. No evidence that the result is not biased. Reasons for missing data were not reported. We do not know whether missingness could depend on the true value of the outcome, but missing data were balanced between groups so it was unlikely. Risk assessed to be some concerns for the outcome: Cellular response. |
| 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. Specific antibody GMT. Cellular reponse. Local adverse events. Systemic adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registry were available (dated 13 May 2021).
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. Specific antibody GMT. Cellular response. Local adverse events. Systemic adverse events. |
| Overall risk of bias |
Some concerns |