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 random allocation process was concealed from both participants and the field investigation team, by way of pre-assignment based on a computer-generated sequence of random numbers administered by clicking a randomization button in the online data collection tool REDCap. Participants received two-dose CoronaVac or BNT162b2 were randomised separately to receive a third dose of either vaccine in a 1:1 ratio. We used a block randomization structure with block sizes of 2, 4 and 6. The sequence of random numbers was generated prior to the start of the study by a statistician using the computer software package R. For logistical reasons individuals were randomized at the time vaccination appointments were made, and there were dropouts after randomization and before vaccination. However, both the participants and field investigation
team were not aware of the intervention until after vaccination, as the vaccination was done by separate unblinded nurses at the community vaccination centres."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: "open-label" trial.
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. Per-protocol analysis was performed on the outcomes. Reasons for exclusion: 319 participants (out of 770 randomized) were ineligible at final confirmation assessment before booster so they did not receive the intervention; plus 84 did not follow the protocol (e.g., received a booster elsewhere). For nAb GMT, this was only measured in a random subset of n=20 per group. 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 proportions between groups. Risk assessed to be some concerns for the outcomes: Confirmed COVID. Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. |
| Missing outcome data |
Some concerns |
Comment: 770 participants randomized; 378 participants analyzed for COVID; 80 analyzed for nAb.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: Most exclusions were accounted for in domain 2; and those missing for nAb GMT. Also, for COVID outcomes, 84% of participants agreed to participate in active surveillance, had reported information on prior COVID-19 infection, and participated in systematic monitoring through self-administered COVID-19 RAT at least once during the active surveillance period, including 85/101 (84%) in CC-C, 104/118 (88%) in CC-B, 96/118 (81%) in BB-C and 93/114 (82%) in BB-B. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Confirmed COVID. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor). NEUTRALIZING ANTIBODY GMT Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. CONFIRMED COVID This outcome was self reported before active surveillance. Risk assessed to be some concerns for the outcomes: Confirmed COVID. |
| Selection of the reported results |
Some concerns |
Comment: The prospective registry was available (dated September 27, 2021).
Neutralizing antibody GMT 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: Neutralizing antibody GMT. Confirmed COVID, Neutralizing antibody GMT Omicron Outcome not pre-specified. 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 outcomes: Confirmed COVID. Neutralizing antibody GMT Omicron |
| Overall risk of bias |
Some concerns |