Trial NCT04712110
Publication Masuda T, Vaccine, 2022
Primary outcome on the report: 1) solicited AEs for 7 days after each injection; 2) unsolicited AEs for 49 days after the first injection (i.e., 21 days following first injection [day of injection + 20 subsequent days] and 28 days following second injection [day of second injection + 27 subsequent days]); 3) MAAEs, SAEs, AEs leading to injection discontinuation and 4) AEs leading to withdrawal from the trial up to and including day 50; and 5) the proportion of participants with SARS-CoV-2 infection through day 50. 6) Serum IgG Ab levels against SARS-CoV-2 rS protein on day 36.

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
Some concerns 		Quote: “Randomization tables were used by unblinded designees or sponsor personnel to assign the randomization to NVX-CoV2373 or placebo. To prepare and administer the vaccines, designated site personnel were unblinded to the assigned groups, and had no further involvement in data collection or post-injection evaluation.”
Comment: Allocation sequence random.
No information on allocation concealment.
Deviations from intervention
Low 		Quote: “The investigators (data collectors), participants, and data evaluators were blinded to trial-group assignment.”
Comment: Blinded study (participants and personnel).
Safety analysis included all participants.
As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate.
Per-protocol analysis was performed on the immunogenicity outcomes.
Reasons for exclusion: 0 vs 1 participants did not receive the second dose (placebo arm).
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 the small number.
Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 200 participants randomized; 200 participants analyzed for safety; 199 participants analyzed for efficacy and immunogenicity.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Adverse events. Serious 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective registry was available (Date January 15, 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:Mortality. Specific antibody GMT. Neutralizing antibody GMT. Adverse events. Serious adverse events.
Overall risk of bias
Some concerns