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 will be randomised to investigational vaccine or placebo (0.9% NaCl) in a 1:1 allocation, using
block randomisation. Block sizes of 10 will be used for all groups (5 IP and 5 placebo).
All participants and clinical study staff, except unblinded pharmacist and vaccine dispenser will be blinded
to the trial arm that participants have been allocated to, whether investigational vaccine or placebo. The
trial staff administering the vaccine will not be blinded. Vaccines will be prepared out of sight of the
participant and syringes will be covered with an opaque object/material until ready for administration to
ensure blinding." Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote:"Injections were administered into the
deltoid muscle of the nondominant arm, and
participants were observed for 30 minutes after
the injection for acute reactions. Injections were
prepared and administered by site staff who
were aware of participants’ trial-group assignments
but were not involved in any other trial
procedures. Trial participants and all other trial
staff remain unaware of trial-group assignments."
Comment: Blinded study (participants, personnel, investigators). Per-protocol analysis was performed on the efficacy outcomes (as planned in the trial protocol) Reasons for exclusions were balanced between treatment groups (148 [14.6%] vs 129 [12.7%]), with the majority of those excluded due to positive or unknown baseline SARS-CoV-2 status (38 vs 29). Another reasons for exclusion were: "Did not receive second placebo shot" (25 Vs 30), "Had Covid-19 illness within 14 days after receiving second shot" (31 Vs 24), "Received an underdose of second shot" (27 Vs 23), "received and underdose of place or vaccine" (21 Vs 21). As we are assessing the effect of assignment to intervention (intent-to-treat effect), this domain was evaluated as some concerns for the efficacy outcomes: Confirmed symptomatic against Beta variant. |
| Missing outcome data |
Low |
Comment: data from interim analysis.
2026 participants randomized; 1467 participants analyzed for efficacy. Data not available for all or nearly all participants randomized. Most patients were excluded because the planned analysis was a per-protocol analysis and the bias had been taken into account in domain 2. EFFICACY AGAINST VARIANTS Variant sequence: 42 cases identified /41 cases sequenced and classified 97.61% of cases analyzed for variants. Data available for all or nearly all cases. Risk assessed to be low for the outcome: Confirmed symptomatic against Beta variant |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Comment: Method of measuring the outcome probably appropriate. Blinded study (outcome assessor). It is not clear if cases were unblinded at the moment of the identification of the variant however, we consider these results can't be affected by the knowledge of the intervention allocation. Risk assessed to be low for the outcome: Confirmed symptomatic against Beta variant |
| Selection of the reported results |
Some concerns |
Comment: the prospective register (June 23, 2020) and restrospective protocol(February 9, 2021) were available
EFFICACY AGAINST VARIANTS The outcome Confirmed symptomatic against Beta variant was not prespecified in the registry. The outcome Confirmed symptomatic against Beta variant was prespecified in the retrospective protocol. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for the outcome: Confirmed symptomatic against Beta variant. |
| Overall risk of bias |
Some concerns |