Trial NCT04405908
Publication Richmond P, Lancet, 2021
Primary outcome on the report: The primary objective of this study was to assess the safety and reactogenicity of SCB-2019 when administered alone or as one of two adjuvanted formulations with AS03 or CpG and Alum. The primary immunogenicity endpoint was based on the anti-SCB-2019 IgG antibody titre at each blood sampling timepoint, measured by ELISA.

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: "Participants were randomly assigned to either non-adjuvanted, AS03-adjuvanted, or CpG/Alum-adjuvanted groups using randomisation lists prepared by the study funder and formatted in accordance with Medidata standards (Medidata Solutions, New York, NY, USA), with randomisation codes uploaded through the Medidata randomisation and trial management system (RTMS). Only unblinded personnel had access to this list through Medidata RTMS. Participants were assigned a study number at enrolment and were vaccinated according to the randomisation list."
Comment: Allocation sequence random. Allocation sequence concealed
Deviations from intervention
Low 		Quote: "All participants and personnel involved in safety data collection and immunogenicity assessments were blinded to the study treatment. Vaccine preparation and administration were performed by different unblinded study personnel, using opacified syringes to maintain the participant blind as the vaccine and placebo are visually different." (report) "Masking: Triple (Participant, Investigator, Outcomes Assessor)" (trial registry)
Comment: Blinded study (patients and investigators).
No participant cross-over.
As we are assessing the effect of assignment to intervention, the intention-to-treat analysis method performed on these outcomes, was considered appropriate.
Risk assessed to be low for all outcomes.
Missing outcome data
Low 		Comment: 151 patients randomized; 150 patients analyzed.
Data available for all or nearly all participants.
Risk assessed to be low for all outcomes.
Measurement of the outcome
Low 		Comment: Probably appropriate method of measuring the outcome.
Measurement or ascertainment of outcome probably not differ between groups.

Comment: Blinded study (outcome assessor).
Risk assessed to be low for all outcomes.
Selection of the reported results
Low 		Comment: The trial registry and protocol were available.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for all outcomes.
Overall risk of bias
Low