Trial NCT04436276
Publication Sadoff J, N Engl J Med, 2021
Primary outcome on the report: The primary end points were the safety and re-actogenicity of each dose schedule. Follow-up visits to evaluate reactogenicity, safety, and im-munogenicity were scheduled on days 7, 28, and 71 after vaccination in each cohort.

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 (IWRS) and stratified by site using randomly permuted blocks. Participants and investigators remain blinded at individual participant level throughout the study. Vaccine and placebo were provided in masked identical syringes."
Comment: Allocation sequence random. Allocation sequence concealed.
Risk assessed to be low for this outcome.
Deviations from intervention
Low 		Quote: "Participants and investigators remain blinded at individual participant level throughout the study. Vaccine and placebo were provided in masked identical syringes."
Comment: Blinded study (patients and investigators)
All participants randomized were included in the 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: Local adverse events. Systemic adverse events. Adverse events.
Missing outcome data
Low 		Comment: 805 patients randomized; 805 patients analyzed
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
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: Local adverse events. Systemic adverse events. Adverse events.
Selection of the reported results
Low 		Comment: The prospective protocol and statistical plan were available (20 April 2020).
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: Local adverse events. Systemic adverse events. Adverse events.
Overall risk of bias
Low