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 |
Quotes: "Computer generated randomisation lists were prepared by the study statistician" "Clinical research nurses who were not
involved in endpoint evaluation did the randomisation using REDCap version 10.6.13 and prepared and administered the vaccine."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quotes: "Participants were masked to boost vaccine allocation at enrolment. Blinding was maintained by completing pages and by preparing vaccines out of sight of participants, and use of the same syringe type across vaccines, with the drawn volume concealed by applying a masking tape. " "Staff involved in study delivery, including in the assessment of adverse events, were aware of vaccine allocation."
Comment: Single blinded study (participants). Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. Modified intention-to-treat analysis was performed on the outcomes; participants with missing data or those that did not meet inclusion criteria were not analysed. As we are assessing the effect of assignment to intervention, the analysis method performed on these outcomes was considered appropriate. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 540 participants randomized; 540 participants analyzed for safety; 536 participants analyzed for reactogenicity; 481 to 502 participants analyzed for immunogenicity; 294 participants analyzed for cellular response.
Safety and reactogenicity data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. Immunogenicity data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: baseline seropositivity; missing/failed blood samples; logistical reasons/laboratory testing facilities not available at study centers. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome because proportions and reasons were balanced between groups. Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. |
| 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. Quote: "Staff involved in study delivery, including in the assessment of adverse events, were aware of vaccine allocation. Laboratory staff processing the immunology samples remained blinded to vaccine allocation." Comment: Participants self-reporting adverse events were blinded but adverse events were reviewed by unblinded investigators and adverse events were also collected by unblinded investigators at study visits. SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT, CELLULAR RESPONSE Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. LOCAL, SYSTEMIC, ADVERSE and 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: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registry (dated 12/03/2021) were 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: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |