Trial NCT04568031
Publication Asano M, Int J Infect Dis, 2021
Primary outcome on the report: 1) Immunogenicity, measured by anti-SARS-CoV-2 spike seroresponse (≥4-fold rise in titers from Day 1 baseline value) at Day 57; 2) Safety, measured by occurrence of solicited local and systemic reactogenicity signs/symptoms in the 6 days after each dose; occurrence of unsolicited AEs, serious AEs (SAEs), and AEs of special interest (AESIs) for 28 days after each dose; and change from baseline in safety laboratory measures

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 in each cohort were randomized (3:1) to receive either AZD1222 or placebo (saline) using a centralized Interactive Response Technology system"
Comment: Allocation sequence probably random.
Allocation sequence concealed.
Deviations from intervention
Low 		Quote: "AZD1222 and placebo were prepared by an unblinded pharmacist, in accordance with local and institutional regulations at each site. Participants, clinical investigators, and sponsor staff were blinded to the study vaccination received until completion of safety data lock up to Day 57."
Comment: Blinded study (participants and personnel/carers).
Intention-to-treat analysis.
As we are assessing the effect of assignment to intervention, the analysis method 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: 256 participants randomized; 256 participants analyzed.
Data available for 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 registry was available (first submitted 21 August 2020).
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: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned.
Results were probably not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcome: Mortality.
Overall risk of bias
Low