Trial NCT04368728
Publication Walsh E, N Engl J Med, 2020
Primary outcome on the report: The primary end points in phase 1 of this trial were solicited local reactions (i.e., specific local reactions as prompted by and recorded in an electronic diary), systemic events, and use of antipyretic or pain medication within 7 days after the receipt of vaccine or placebo, as prompted by and recorded in an electronic diary; unsolicited adverse events and serious adverse events (i.e., those reported by the participants, without electronic diary prompts), assessed from the receipt of the first dose through 1 month and 6 months, respectively, after the receipt of the second dose; clinical laboratory abnormalities, assessed 1 day and 7 days after the receipt of vaccine or placebo; and grading shifts in laboratory assessments between baseline and 1 day and 7 days after the first dose and between 2 days and 7 days after the second dose.

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: "Using an interactive Web-based response technology system, we randomly assigned trial participants"
Comment: Allocation sequence random. Allocation sequence concealed.
Risk assessed as low.
Deviations from intervention
Low 		Quote: “study staff receiving, storing, dispensing, preparing, and administering the study interventions will be unblinded. All other study and site personnel, including the investigator, investigator staff, and participants, will be blinded to study intervention assignments”
Comment: Some study staff were not blinded; patients and investigators were blinded.
No participant cross-over.
Unlikely to have been deviations from intended intervention.
Data were analyzed using intention-to-treat 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: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 195 randomized/195 analyzed for safety and mortality
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. 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. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective protocol and statistical analysis plan were available (15 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: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Overall risk of bias
Low