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: "Eligible participants were randomly assigned (1:1) to
ZyCoV-D vaccine or placebo using a randomisation
schedule generated using SAS software (version 9.4 or
higher) with the help of an interactive web response
systems (IWRS). The IWRS was used for randomisation
(blocks of four) of participants as well as to enrol individuals
aged 60 years and older with or without comorbid
conditions, and those aged 12–17 years. It was also used to
identify 600 participants for immunogenicity (blocks of six).
Investigators at sites received random allocation
information through the IWRS. The randomisation
sequence was generated by an independent statistician
using SAS and fed into the IWRS. Participants were
enrolled by investigators with the help of the IWRS"
Comment: Allocation sequence random Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: "Double blinded. The masking of individual allocation was
maintained for all investigators and participants."
Comment: Blinded study (participants and personnel/carers) 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; the immunogenicity population was a selected subset. Reasons for exclusion: participants who did not complete 28 days after the third dose (not reported by arm). 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 large sample size. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Specific antibody GMT. Neutralizing antibody GMT. |
| Missing outcome data |
Low |
Comment: 27703 participants randomized; 27701 participants analyzed for safety; 24670 participants analyzed for efficacy; 265/97 participants analyzed for immunogenicity
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Data not available for all or nearly all participants randomized for efficacy or the immunogenicity subgroup. No evidence that the result is not biased. Reasons: Missingness could not depend on the true value of the outcome. Protocol violations were addressed in ROB2. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Specific antibody GMT. Neutralizing antibody GMT. |
| 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. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (Date January 12th, 2021)
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. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. |
| Overall risk of bias |
Some concerns |