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: “The subjects included were randomly distributed (1:1) to 2 groups: I) placebo and II) 50 µg RBD (Abdala vaccine). Randomisation was carried out in the supply group of the Clinical Research Direction of CIGB, in blocks of 4 individuals, for each clinical site, by means of a computerised random number generator. The sites received the product in such blocks, in masked vials in order to prevent their identification. The organoleptic characteristics and presentations of vaccine and placebo were identical. Therefore, the decision to accept or reject a participant was made, and informed consent was obtained from the participant, in ignorance of the assignment in the sequence.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “Double-blind. The trial participants, investigators, and monitors, were unaware of the trial-group assignments during the whole trial. Statistical analyses were done without knowledge of the groups´ identity.”
Comment: Blinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. ADVERSE EVENTS Safety analysis was conducted on those who received at least one dose of the intervention. 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: Adverse events. CONFIRMED SYMPTOMATIC COVID-19. CONFIRMED SEVERE COVID-19 Per-protocol analysis was performed on the efficacy outcomes. Reasons for exclusion: dropout, SARS-CoV-2 infection, non-adherence to the protocol by subjects (optional decision provided in the research protocol), decompensation of chronic diseases, pregnancy, death ; 78 vs 63 did not adhere to the protocol, 26 vs 32 had decompensated chronic diseases, 14 vs 23 became pregnant, 4 vs 15 Other (no information). 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 balance between groups. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. |
| Missing outcome data |
Low |
Comment: 48290 participants randomized; 48290 participants analyzed for safety; 39363 participants analyzed for efficacy.
ADVERSE EVENTS Data available for all or nearly all participants randomized for safety. Risk assessed to be low for the outcome: Adverse events. CONFIRMED SYMPTOMATIC COVID-19. CONFIRMED SEVERE COVID-19 Data not available for all or nearly all participants randomized for efficacy. No evidence that the result is not biased. Reasons: 310 vs 385 lost due to voluntary dropout. Other reasons taken into account in domain 2. Missingness could not depend on the true value of the outcome. The majority of the other missing participants were addressed in ROB 2. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. |
| 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. Adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective registry was available (Date 18/03/2021).
CONFIRMED SYMPTOMATIC COVID-19. CONFIRMED SEVERE COVID-19 Effectiveness 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. ADVERSE EVENTS Outcome not pre-specified for safety No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Adverse events. |
| Overall risk of bias |
Some concerns |