Trial NCT04368728
Publication Thomas S, N Engl J Med, 2021
Primary outcome on the report: Safety end points included solicited, prespecified local reactions, systemic events, and antipyretic or pain medication use during the first 7 days after receipt of each vaccine or placebo dose, which were recorded in an electronic diary; unsolicited adverse events after receipt of the first dose through 1 month after the second dose; and serious adverse events after receipt of the first dose through 1 and 6 months after the second dose was received. Safety data are presented for the blinded follow-up and open-label periods.
BNT162b2 efficacy against laboratory-confirmed Covid-19 with an onset of 7 days or more after the second dose was assessed and summarized descriptively in participants without serologic or virologic evidence of SARS-CoV-2 infection within 7 days after the second dose and in participants with or without evidence of previous infection. Efficacy against severe Covid-19 was also assessed. Lineages of SARS-CoV-2 detected in midturbinate specimens are reported here for Covid-19 cases that occurred 7 days or more after the second dose in South African participants without evidence of previous infection.

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 randomized 1:1 by an interactive web-based system."
Allocation sequence random. Allocation sequence concealed
Risk assessed to be low.
Deviations from intervention
Some concerns 		Quote: “observer blinded”
Comment: Blinded study (participants and personnel/carers)
Per-protocol analysis was performed on the efficacy outcomes
Reasons for exclusion: Positive at baseline (689 Vs 716) not received 2 vaccinations as randomized (326 Vs 430) Reasons foe exclusion in the 12-15 yo group not reported
As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately.
There was no substantial impact of failure to analyze participants according to their randomized assignment
Risk assessed to be some concerns for the outcome: Confirmed symptomatic COVID-19 (variant)
Missing outcome data
Low 		Comment: 46429 participants randomized (44165 participants aged ≥16 years randomized; 2264 participants aged 12-15 years randomized, previously reported, Frenck 2021) / 42094 participants aged ≥12 years analyzed for Confirmed symptomatic COVID-19
Data available for nearly all participants.
Variant classification: 9 cases identified /8 cases sequenced and classified
88.88% of cases analyzed for variants
Data not available for all or nearly allcases
No evidence that the result is not biased.
Quote: "Midturbinate specimens from 8 of 9 cases contained sufficient viral RNA for wholegenome sequencing"
Missingness could not depend on the true value of the outcome
Risk assessed to be low for the outcome: Confirmed symptomatic COVID-19 (variant)
Measurement of the outcome
Low 		Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.>br/>Blinded study (outcome assessor).
It is not clear if cases were unblinded at the moment of the identification of the variant however, we consider these results can't be affected by the knowledge of the intervention allocation.
Risk assessed to be low for the outcome: Confirmed symptomatic COVID-19 (variant)
Selection of the reported results
Some concerns 		Comment: The propective registry, protocol and statistical plan are available (April 30, 2020)
The outcome Confirmed symptomatic against Beta variant was not prespecified in the registry.
Post-hoc anlysis
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: Confirmed symptomatic COVID-19 (variant)
Overall risk of bias
Some concerns