Trial NCT04368728
Publication Mulligan MJ, Nature, 2020
Primary outcome on the report: the proportion of participants reporting solicited local reactions, systemic events, and use of antipyretic and/or pain medication within 7 days after vaccination, AEs and SAEs (available through up to ~45 days after Dose 1), and the proportion of participants with clinical laboratory abnormalities 1 and 7 days after vaccination and grading shifts in laboratory assessments between baseline and 1 and 7 days after Dose 1 and between Dose 2 and 7 days after Dose 2.

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: "This is an randomized controlled trial. Study participants were randomly assigned to a vaccine group using an interactive web-based response technology system" Comment: Randomisation sequence was most likely generated satisfactorily and concealed from study investigators through the web-based system but this was not clearly stated
Deviations from intervention
Some concerns 		Quote: "This is an observer blinded study which is investigator blinded but Sponsor unblinded during Stage 1 (the stage from which data in the manuscript are presented). Investigators were unblinded to group level data but not subject level data for the purposes of interpretation and summary of the results included in this interim report." Quote: "Eligible participants were then randomized to vaccine or placebo in a blinded manner. These processes therefore did not led themselves to enrollment biases however participants who did not know about the study may have had less of an opportunity to participate." Comment: Blinded study (patients and investigators). ITT analysis was used to assess safety outcomes, it was not reported what analysis was used to assess immunogenicity outcomes (we do not know if there were missing data, excluded data, or participant cross-over). Risk of bias assessed as Low for safety outcomes and some concerns for immunogenicity outcomes.
Missing outcome data
High 		Comment: 45 randomized, 45 analyzed for adverse events and mortality; number analyzed for immunogenicity outcomes (GMTs) were not reported, data were not reported for some groups for certain timepoints, 95% CIs were not reported. Risk assessed to be Low for adverse events and mortality, and High for GMTs.
Measurement of the outcome
Low 		Comment: Investigator blinded to subject data. Risk assessed to be Low for the outcomes: Mortality, GMTs, Adverse events, and Serious adverse events.
Selection of the reported results
Some concerns 		Comment: Neither the protocol nor the statistical analysis plan was available. Risk assessed to be some concerns for the outcomes: Mortality, GMTs, Adverse events, Serious adverse events.
Overall risk of bias
High