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|
|Quote: "Participants were randomly assigned to one of 2 open-label vaccination schedules, with either 14 (0-14) or 28 (0-28) days interval between doses, in a 1:1 ratio."[Abarca] “The randomization process was done using a sealed enveloped system integrated into the electronic Case Report Forms (eCRF) in the OpenClinica platform.”[Bueno]
Comment: Allocation sequence random.
Allocation sequence concealed.
Imbalances in baseline characteristics appear to be compatible with chance
|Deviations from intervention||
Comment: Unblinded 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.
ITT analysis was used for safety outcomes reported after the first dose.
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: Local adverse events. Systemic adverse events.
Per-protocol analysis was performed on the efficacy outcomes.
Reasons for exclusion: 35/1090 and 16/1212 were out of window, 3 vs 2 received another SARS-CoV-2 vaccine, 1 vs 0 took a prohibited medication, 1 vs 2 developed a new chronic condition.
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 the small numbers.
Risk assessed to be some concerns for the outcomes: Confirmed COVID. Confirmed symptomatic COVID. Confirmed severe COVID.
|Missing outcome data||
|Comment: 2302 participants randomized; 2302 participants analyzed for safety; 2232 analyzed for efficacy
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Confirmed COVID. Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events.
|Measurement of the outcome||
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Unblinded study (outcome assessor)
Observer-reported outcome not involving judgement.
Risk assessed to be low for the outcomes: Confirmed COVID.
CONFIRMED SYMPTOMATIC COVID, CONFIRMED SEVERE COVID
This outcome requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic.
Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID.
LOCAL, SYSTEMIC ADVERSE EVENTS
The authors reported on adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic.
Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events.
|Selection of the reported results||
|Comment: The prospective registry was available
Outcome pre-specified for efficacy and safety.
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 outcome: Confirmed COVID. Confirmed symptomatic COVID. Confirmed severe COVID. Local adverse events. Systemic adverse events.
|Overall risk of bias||