Trial NCT04922788
Publication Nguyen TP, medRxiv, 2022
Primary outcome on the report: 1) number and percentage of participants with solicited local and systemic adverse events which occurred within 7 days of vaccination and laboratory results (serum biochemistry and hematology) at days 0, 7, 28 and 42 according to FDA toxicity scoring; 2) anti-S IgG responses to Nanocovax evaluated by a chemiluminescence immunoassay (CLIA); 3) vaccine efficacy (VE) against severe illness and death; VE against symptomatic Covid-19 cases with clinical symptoms with onset at least 14 days after the second dose.

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 were randomly assigned to either the vaccinate or placebo groups by the Electronic Clinical Data Management (ECDM) system.
Comment: Allocation sequence random
Allocation sequence concealed
Imbalances in baseline characteristics appear to be compatible with chance
Deviations from intervention
Some concerns 		Quote: “Double blinding. Trial staff responsible for the vaccine/placebo administration, as well as participants were unaware of vaccine/placebo assignment.” Comment: Blinded study (participants and personnel/carers) Per-protocol analysis was performed on the efficacy outcomes. Reasons for exclusion: 4.1% vs 3.9% did not receive 2nd injection, 0.2% vs 0.2% contracted Covid-19 after 1st injection, <0.1% vs <0.1% contracted Covid-19 less than 14 days post 2nd injection. 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 similar numbers between arms.
Risk assessed to be some concerns for the outcome: Confirm symptomatic COVID variant Delta
Missing outcome data
Low 		Comment: 13007 participants randomized; 12690 participants analyzed Data available for all or nearly all participants randomized for safety and efficacy. Risk assessed to be low for the outcomes: Confirmed symptomatic 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.
Selection of the reported results
Low 		Comment: The prospective registry was available If data analyzed and presented as pre-specified Outcome 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 outcome: Confirmed symptomatic COVID.
Overall risk of bias
Some concerns