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PF-07302048 (BNT162 RNA-Based COVID-19 Vaccines)
Protocol C4591001

receiving a positive result and counseled on whether to take any precautionary measures
pending confirmatory testing.

Participants who have a positive SARS-CoV-2 NAAT result prior to Visit 2 should be
handled as follows:

• Positive SARS-CoV-2 test with no symptoms, either at Visit 1 or any time between Visit
1 and Visit 2: A positive test in an asymptomatic participant does not meet exclusion
criterion 5; therefore, Vaccination 2 should proceed as normal.

• Confirmed COVID-19 (ie, symptoms and positive SARS-CoV-2 test): This meets
exclusion criterion 5; therefore, Vaccination 2 should not be given but the participant
should remain in the study.

9. STATISTICAL CONSIDERATIONS
Methodology for summary and statistical analyses of the data collected in this study is
described here and further detailed in a statistical analysis plan (SAP), which will be
maintained by the sponsor. The SAP may modify what is outlined in the protocol where
appropriate; however, any major modifications of the primary endpoint definitions or their
analyses will also be reflected in a protocol amendment.

9.1. Estimands and Statistical Hypotheses
9.1.1. Estimands

The estimand corresponding to each primary, secondary, and tertiary/exploratory objective is
described in the table in Section 3.

In the primary safety objective evaluations, missing reactogenicity e-diary data will not be
imputed. Missing AE dates will be imputed according to Pfizer safety rules. No other
missing information will be imputed in the safety analysis.

The estimands to evaluate the immunogenicity objectives are based on evaluable populations
for immunogenicity (Section 9.3). These estimands estimate the vaccine effect in the
hypothetical setting where participants follow the study schedules and protocol requirements
as directed. Missing antibody results will not be imputed. Immunogenicity results that are
below the LLOQ will be set to 0.5 × LLOQ in the analysis; this may be adjusted once
additional data on the assay characteristics become available.

The estimands to evaluate the efficacy objectives are based on evaluable populations for
efficacy (Section 9.3). These estimands estimate the vaccine effect in the hypothetical
setting where participants follow the study schedules and protocol requirements as directed.
In addition, VE will also be analyzed by all-available efficacy population. Missing laboratory
results will not be imputed for the primary analysis, but missing data imputation for the
efficacy endpoint may be performed as a sensitivity analysis.

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