Trial NCT04495933
Publication Chappell K, Lancet, 2021
Primary outcome on the report: The primary safety endpoints included the frequency, duration, and intensity of solicited local and systemic adverse events (AEs) for 7 days after each dose, the frequency, duration, intensity, and relatedness of unsolicited AEs through Day 57, and the frequency of serious AEs and AEs leading to study discontinuation throughout the study. The primary immunogenicity endpoints included the geometric mean of the serum antibody response to SARS-CoV-2 Sclamp compared with placebo by antigen-specific enzyme-linked immunosorbent assay (ELISA) at Day 29 and Day 57, and the geometric mean of the serum neutralising antibody titres to SARS-CoV-2 virus compared with placebo at Day 29 and Day 57.

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: “Participants were administered vaccine or placebo according to a randomisation scheme.”
Comment: Allocation sequence probably random. No information on allocation concealment.
Risk assessed to be some concerns for the outcomes: Solicted adverse events. Unsolicted adverse events. Withdrawals due to adverse events. Serious adverse events.
Deviations from intervention
Low 		Quote:"Participants and study personnel were masked to treatment, except the dose administration personnel who were not otherwise involved in the study. After day 57, specific study personnel were unmasked to allow data analysis; participants will remain masked until the end of the study."
Comment: Blinded study (participants, personnel, investigators).
All randomized participants who received at least one dose were analysed for safety outcomes.
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 outcomes: Adverse events. Withdrawals due to adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: Data from interim analysis
120 patients randomized; 120 patients analyzed.
Data available for >95% of population.
Risk assessed to be low for outcomes: Adverse events. Withdrawals due to adverse events. Serious adverse events.
Measurement of the outcome
Low 		Comment: Blinded study (participants, care providers, investigators)
Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Risk assessed to be low for the outcomes: adverse events. Withdrawals due to adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The restrospective trial registry was available. Protocol or SAP not available.
No information on whether the result was selected from multiple outcome measurements or analyses of the data.
No information on whether the trial was analyzed as pre-specified.
Risk assessed to be some concerns for outcomes: Adverse events. Withdrawals due to adverse events. Serious adverse events.
Overall risk of bias
Some concerns