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:"randomized using a web-based interactive response system in a 2:1 ratio"..."Only unblinded site personnel managed study vaccine logistics/preparation and had no other role in trial conduct."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. Risk assessed to be low. |
| Deviations from intervention |
Some concerns |
Quote:“Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)” “Only unblinded site personnel managed study vaccine logistics/preparation and had no other role in trial conduct.” “The trial is ongoing, and investigators and Novavax clinical team remain blinded to participant-level treatment assignments.”
Comment: Blinded study (participants and personnel/carers) SAFETY Data for the safety outcomes were analyzed using modified intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. EFFICACY Per-protocol analysis was performed on the efficacy outcomes. Reasons for exclusion: Were Anti-NP or PCR positive at baseline (vaccine 6.2%, placebo 6.8%), did not receive two Nv-CXoV2373 doses or were dosed out of window (vaccine 3.2%, placebo 4.6%), had major protocol deviation, were unblinded, or had a censoring event (vaccine 3.3%, placebo 6.9%). As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to relatively equal attrition in both arms. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Mortality. |
| Missing outcome data |
Low |
Comment: 29949 participants randomized; 29582 participants analyzed for safety; 25452 participants analyzed for efficacy.
Data available for all or nearly all participants randomized for safety. Data not available for all or nearly all participants randomized for efficacy, but this potential source of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. Mortality. |
| 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: Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. Mortality. |
| Selection of the reported results |
Low |
Comment: The trial protocol, statistical plan and registry were availalbe (dated 2 Nov 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: Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. Mortality. |
| Overall risk of bias |
Some concerns |