Trial NCT04436276
Publication Stephenson K, JAMA, 2021
Primary outcome on the report: 1. Solicited adverse events (AEs), collected through a diary, were recorded for each vaccination from the time of vaccination until 7 days after vaccination. 2. All other unsolicited AEs and special reporting situations, whether serious or nonserious, were reported for each vaccination from the time of vaccination until 28 days after vaccination. Unsolicited AEs with the onset date outside the timeframe defined above (>28 days after previous study vaccination), which were ongoing on the day of the subsequent vaccination, were recorded as such. 3. All serious AEs and AEs leading to participant discontinuation (regardless of the causal relationship) were reported for all participants from the moment of first vaccination until completion of the participant’s last study-related procedure, which may include contact for safety follow-up.

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 done by an Interactive Web Response System using randomly permuted blocks of 5... To preserve blinding, they placed an overlay on the syringes".
Comment: Allocation sequence random.
Allocation sequence probably concealed.
Risk assessed to be low.
Deviations from intervention
Low 		Quote: "double-blind, placebo-controlled clinical trial".
Comment: Blinded study (participants and personnel/carers).
ITT analysis (10 randomized).
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.
Missing outcome data
Low 		Comment: 10 participants randomized; 10 participants analyzed.
Data available for all participants randomized.
Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT.
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: Specific antibody GMT. Neutralizing antibody GMT.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan and registry were available (dated June 18, 2020).
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.
Overall risk of bias
Low