Document text
Analysis Data Reviewer’s Guide
sBLA Analysis for Participants 12-15 Years of
Age
BioNTech SE and PFIZER INC.
Study C4591001
ADRG Template Version 2019-07- 23
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ANA LYSIS DATA REVI EWER GUIDE
REVISION HISTORY
Version Summary of Major Change(s) and Impact Version Date
1.0 First approved version of Analysis Data Reviewer Guide 06-Dec-2021
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1. Introduction ................................................................................................................................. 5
1.1 Purpose ..................................................................................................................... 5
1.2 Acronyms ................................................................................................................. 5
1.3 Study Data Standards and Dictionary Inventory ...................................................... 5
1.4 Source Data Used for Analysis Dataset Creation ..................................................... 6
2. Protocol Description .................................................................................................................... 6
2.1 Protocol Number and Title ....................................................................................... 6
2.2 Protocol Design in Relation to ADaM Concepts ..................................................... 8
2.2.1 Phase 1 ................................................................................................................... 10
2.2.2 Phase 2/3 ................................................................................................................ 11
3. Analysis Considerations Related to Multiple Analysis Datasets ............................................... 12
3.1 Core Variables ........................................................................................................ 12
3.2 Treatment Variable ................................................................................................. 15
3.3 Subject Issues that Require Special Analysis Rules ............................................... 17
3.4 Use of Visit Windowing, Unscheduled Visits, and Record Selection .................... 17
3.5 Imputation/Derivation Methods ............................................................................. 17
4. Analysis Data Creation and Processing Issues .......................................................................... 18
4.1 Split Datasets .......................................................................................................... 18
4.2 Data Dependencies ................................................................................................. 18
4.3 Intermediate Datasets ............................................................................................. 18
5. Analysis Dataset Descriptions ................................................................................................... 18
5.1 Overview ................................................................................................................ 18
5.2 Analysis Datasets ................................................................................................... 19
5.2.1 ADSL – Subject -Level Analysis Dataset ............................................................... 20
5.2.2 ADAE – Adverse Events Analysis Dataset ............................................................ 20
5.2.3 ADCM – Concomitant Medications Analysis Dataset ........................................... 21
5.2.4 ADDS – Disposition Analysis Dataset .................................................................. 21
5.2.5 ADDV – Protocol Deviations Analysis Dataset ..................................................... 21
5.2.6 ADMH – Medical History Analysis Dataset ......................................................... 22
5.2.7 ADSYMPT – Covid- 19 Signs and Symptoms Analysis Dataset ........................... 22
5.2.8 ADC19EF – Covid-19 Efficacy Analysis Dataset ................................................. 25
5.2.9 ADXB – Sequencing Analysis Dataset .................................................................. 27
6. Data Conformance Summary .................................................................................................... 28
6.1 Conformance Inputs ............................................................................................... 28
6.2 Issues Summary ..................................................................................................... 29
7. Submission of Programs ............................................................................................................ 31
7.1 ADaM Programs .................................................................................................... 31
7.2 Analysis Output Programs ...................................................................................... 31
8. Appendix ................................................................................................................................... 35
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Page 4 of 72 Appendix I: Annotated Mocks for Key Tables ......................................................................... 35
Mock Table 1 ........................................................................................................................ 35
Mock Table 2 ........................................................................................................................ 38
Mock Table 3 ........................................................................................................................ 41
Mock Table 4 ........................................................................................................................ 42
Mock Table 5 ........................................................................................................................ 43
Mock Table 6 ........................................................................................................................ 45
Mock Table 7 ........................................................................................................................ 47
Mock Table 8 ........................................................................................................................ 49
Mock Table 9 ........................................................................................................................ 50
Mock Table 10 ...................................................................................................................... 52
Mock Table 11 ...................................................................................................................... 53
Mock Table 12 ...................................................................................................................... 54
Mock Table 13 ...................................................................................................................... 57
Mock Table 14 ...................................................................................................................... 58
Mock Table 15 ...................................................................................................................... 60
Appendix II: Analysis plan AE windowing logic ..................................................................... 61
Appendix III: Handling of Incomplete Dates............................................................................ 63
Adverse events ...................................................................................................................... 63
Concomitant medications/medical histories ......................................................................... 64
Appendix IV: External files used during ADaM dataset creation ............................................ 65
Appendix V: Surveillance Times .............................................................................................. 68
Appendix VI: Efficacy Flow Charts ......................................................................................... 69
Appendix VII: Detailed subsetting for Analysis: ...................................................................... 71
1. Key Analysis Population Subsetting: ................................................................................ 71
2. Adverse Event Analysis Reporting Period Subsetting: ..................................................... 72
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1. Introduction
1.1 Purpose
This document provides context for the analysis datasets and terminology that benefit from
additional explanation beyond the Data Definition document (define.xml) for an individual
study. In addition, this document provides a summary of ADaM conformance findings. This
ADRG covers
• Updated e fficacy analyses in blinded placebo -controlled follow -up evaluated duration of
protection (data cutoff date: 02Sep 2021).
• Updated sequencing analysis for SARS -CoV-2 Variants of Concern or Variants of Interest.
• Safety data presented for
Blinded placebo -controlled period: Dose 1 to unblinding date .
Open -label observational period: from time of unblinding to data cutoff date:
o Phase 3 12-15 years of age participants originally randomized to BNT162b2 30µg
o Phase 3 12-15 years of age participants orig inally randomized to placebo who
then received BNT162b2 30µg
Cumulative follow -up from Dose 1 to 6 months after Dose 2 for participants originally
randomized to BNT162b2 30µg (inclusive of data from blinded and open- label periods)
New or updated Adverse events reported after EUA snapshot over both blinded and
open- label time periods.
1.2 Acronyms
Acronym Translation
COVID -19 Coronavirus Disease 2019
IWR Interactive Web -based Response
LAR Legally Acceptable Representative
modRNA nucleoside -modified messenger ribonucleic acid
NA Not Applicable
NAAT nucleic acid amplification test
SoA Schedule of Activities
VE Vaccine Efficacy
WHO DD G WHO Drug Dictionary Global
WOCBP Women of childbearing potential
1.3 Study Data Standards and Dictionary Inventory
Standard or Dictionary Versions Used
SDTM •SDTM v1.4
•SDTM -IG v3.2
SDTM Controlled Terminology CDISC SDTM Controlled Terminology, 2020 -03-27
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•ADaM -IG v1.1
ADaM Controlled Terminology CDISC ADaM Controlled Terminology, 2020 -03-27
Data Definitions Define -XML v2.0
Medications Dictionary WHODD GLOBALB3Mar 2021
Medical Events Dictionary MedDRA v24.0
1.4 Source Data Used for Analysis Dataset Creation
This study is currently ongoing, and analysis data up to cut-off date: 02Sep2021 are included.
Data cut -off is applied during SDTM creation.
The ADaM datasets for this study were derived from the SDTM datasets. SDTM datasets were prepared according to SDTM -IG version 3.2.
External files used during ADaM dataset creation are listed in Appendix IV.
2. Protocol Description
2.1 Protocol Number and Title
Protocol Number: C4591001
Protocol Short Title: A Phase 1/2/3 Study to Evaluate the Safety, Tolerability,
Immunogenicity, and Efficacy of RNA Vaccine Candidates Against COVID-19 in
Healthy Individuals.
Note: Protocol Amendment’s 13, 14 and beyond mentioned elsewhere in the submission documentation are out of scope for this analysis and have not been included in this ADRG.
Protocol Versions:
Amendment 12: 2021-01-14
• Because of a formatting error in protocol amendment 11, exclusion criterion 4 was
inadvertently added to exclusion criterion 3 and the subsequent criteria renumbered.
This amendment corrects that error.
Amendment 11: 2021 -01-04
• Added a potential intensive surveillance period for nasal swabbing, for assessment
via NAAT:
o Corresponding SoA and procedures added
Amendment 10: 2020-12-01
• Added the possibility of administering BNT162b2 to participants who
originally received placebo, following any local or national recommendations.
• Added the possibility of administering BNT162b2 to participants who
originally received placebo, following completion of the active safety
surveillance period.
Amendment 9: 2020-10-29
• To better align with the natural history of SARS -CoV -2 infection, added Phase 2/3
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that occur from 14 days after the second dose; also modified the existing secondary
efficacy objectives, estimands, and endpoints to include COVID-19 cases that occur
from 14 days, as well as 7 days, after the second dose;
o Made corresponding changes to the study design, study assessments and
procedures, and statistical analysis sections.
• Clarified that interim analyses will be conducted after accrual of at least 62, 92, and
120 cases.
• Included any participants 16 through 17 years of age enrolled under this amendment
in the reactogenicity subset.
• Clarified that serology data after a postbaseline positive SARS -CoV-2 test result will
not be included in the analysis based on the evaluable immunogenicity populations.
Amendment 8: 2020-10-15
• Clarified that for participants who are not in the reactogenicity subset, local
reactions and systemic events following vaccination should be detected and reported
as AEs.
• Clarified that premenarchal females are not WOCBP.
Amendment 7: 2020-10-06
• Reduced the lower age range to include adolescents 12 to 15 years of age and
added corresponding objectives.
• Added that 2 periods of potential COVID-19 symptoms within 4 days will
be considered as a single illness.
Amendment 6 (Germany-specific): 2020-09-23
• According to regulatory request, inclusion criterion 1 now specifies that participants
less than 18 years of age will not be enrolled in the EU.
Amendment 6: 2020-09-08
• Removed exclusion criterion 2 (ie, known infection with HIV, HCV, or HBV) for
Phase 3 and added criteria for HIV-positive participants.
• D ecreased the lower age limit and removed the upper age limit for inclusion in Phase
2/3 in order to evaluate BNT162b2 30 μg in older adolescents and those over 85 years
of age; updated the title and other references to adults to align with this change.
• Clarified that inclusion criterion 4 (ie, participants at higher risk for acquiring COVID-
19) is applicable for Phase 2/3 only, and provided some examples
Amendment 5: 2020-07-24
• Clarified that a single vaccine candidate, administered as 2 doses 21 days apart, will
be studied in Phase 2/3.
• Stated that the vaccine candidate selected for Phase 2/3 evaluation is BNT162b2 at a
dose of 30 μg.
• Renamed Stage 1 to Phase 1, removed Stage 2, and renamed Stage 3 to Phase 2/3.
• Clarified which stopping rules apply to which phase of the study.
• Moved the immunogenicity objectives in Phase 2/3 to become exploratory.
• Modified exclusion criterion 5, so that participants with a previous clinical or
microbiological diagnosis of COVID- 19 are excluded from all phases of the
study.
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Amendment 4: 2020-06-30
• BNT162b3 candidate has been added to the protocol.
• Further nonclinical data are available to support the study of the BNT162b3
candidate in humans, and the candidate has been added to the protocol.
• The 6-month safety follow -up telephone contact has been changed to an in-person
visit for Stage 3 participants, to allow collection of an immunogenicity blood sample.
Amendment 3: 2020-06-10
• 20-μg dose level is formally included for BNT162b1 and BNT162b2.
• In order to increase flexibility enrolling participants, an extended screening window
(increased from 14 to 28 days) for sentinel participants in Stage 1 has been added.
This is considered acceptable since eligible participants are expected to be either
healthy or have stable medical conditions.
Amendment 2: 2020-05-27
• Added a 50- μg dose level for vaccine candidates based on the modRNA platform
(ie, BNT162b1, BNT162b2, and BNT162b3).
Amendment 1: 2020-05-13
• Decreased the dose levels for BNT162a1 and BNT162c2
• Modified exclusion criteria and prohibited inhaled/nebulized corticosteroids
for sentinel participants in Stage 1.
Original Protocol 2020- 04-15
2.2 Protocol Design in Relation to ADaM Concepts
The study consists of 2 parts. Phase 1: to identify preferred vaccine candidate(s) and dose
level(s); Phase 2/3: an expanded cohort and efficacy part. These parts, and the progression
between them, are detailed in the schema.
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The study will evaluate the safety, tolerability, and immunogenicity of 2 different SARS -CoV -2
RNA vaccine candidates against COVID -19 and the efficacy of 1 candidate:
o As a 2 -dose (separated by 21 days) schedule;
o At various different dose levels in Phase 1;
o In 3 age groups: (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3:
≥12 years of age [stratified as 12- 15, 16-55, or >55 years of age]).
Dependent upon safety and/or immunogenicity data generated during the course of this study, or
the BioNTech study conducted in Germany (BNT162- 01), it is possible that groups in Phase 1
may be started at the next highest dose, groups may not be started, gr oups may be terminated
early, and/or groups may be added with dose levels below the lowest stated dose or intermediate between the lowest and highest stated doses.
The study is observer -blinded, as the physical appearance of the investigational vaccine
candidates and the placebo may differ. The participant, investigator, study coordinator, and other site staff will be blinded. At the study site, only the dispenser(s)/administrator(s) are unblinded.
To facilitate rapid review of data in real time, sponsor staff will be unblinded to vaccine
allocation for the participants in Phase 1.
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Page 10 of 72 2.2.1 Phase 1
Each group (vaccine candidate/dose level/age group) will comprise 15 participants; 12
participants will be randomized to receive active vaccine and 3 to receive placebo.
For each vaccine candidate/dose level/age group, the following apply:
• Additional safety assessments (see protocol, Section 8.2)
• Controlled enrollment (required only for the first candidate and/or dose level studied):
• No more than 5 participants (4 active, 1 placebo) can be vaccinated on the first day
• The first 5 participants must be observed by blinded site staff for at least 4 hours after
vaccination for any acute reactions
• Vaccination of the remaining participants will commence no sooner than 24 hours
after the fifth participant received his or her vaccination
• Application of stopping rules
• IRC review of safety data to determine escalation to the next dose level in the 18- to 55- year
age cohort:
• Escalation between dose levels will be based on IRC review of at least 7 -day post –
Dose 1 safety data in this study and/or the BioNTech study conducted in Germany
(BNT162 -01)
• Note that, since both candidates are based upon the same RNA platform, dose
escalation for the second candidate studi ed may be based upon the safety profile of the first
candidate studied being deemed acceptable at the same, or a higher, dose level by the IRC
Groups of participants 65 to 85 years of age will not be started until safety data for the RNA
platform have been deemed acceptable at the same, or a higher, dose level in the 18- to 55- year
age cohort by the IRC.
In this phase, 13 groups will be studied, corresponding to a total of 195 participants.
The IRC will select 1 vaccine candidate that, in Phase 1, has an established dose level per age
group based on induction of a post– Dose 2 immune response, including neutralizing antibodies,
which is expected to be associated with protection against COVID- 19, for progression into
Phase 2/3.
Participants who originally received placebo and become eligible for receipt of BNT162b2 or
another COVID- 19 vaccine according to local or national recommendations (detailed
separately, and available in the electronic study reference portal) will have the opportunity to
receive BNT162b2 as part of the study. The investigator will ensure the participant meets at
least 1 of the recommendation criteria. Any Phase 1 placebo recipient who has not already been
offered the opportunity to receive BNT162b2 will be given this opportunity at the approximate
time participants in Phase 2/3 reach Visit 4. Any participant who originally received placebo
but then goes on to receive BNT162b2 will move to a new visit schedule (Protocol Section
1.3.3).
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Page 11 of 72 2.2.2 Phase 2/3
On the basis of safety and/or immunogenicity data generated during the course of this study,
and/or the BioNTech study conducted in Germany (BNT162 -01), 1 vaccine candidate was
selected to proceed into Phase 2/3. Participants in this phase will be ≥12 years of age, stratified
as follows: 12 to 15 years, 16 to 55 years, or >55 years. The 12- to 15- year stratum will
comprise up to approximately 2000 participants enrolled at selected investigational sites. It is
intended that a minimum of 40% of participants will be in the >55-year stratum.
Commencement of each age stratum will be based upon satisfactory post–Dose 2 safety and
immunogenicity data from the 18- to 55- year and 65- to 85- year age groups in Phase 1,
respectively. The vaccine candidate selected for Phase 2/3 evaluation is BNT162b2 at a dose of
30 μg.
Phase 2/3 is event-driven. Under the assumption of a true VE rate of ≥60%, after the second
dose of investigational product, a target of 164 primary -endpoint cases of confirmed COVID-
19 due to SARS -CoV -2 occurring at least 7 days following the second dose of the primary
series of the candidate vaccine will be sufficient to provide 90% power to conclude true
VE >30% with high probability. The total number of participants enrolled in Phase 2/3 may
vary depending on the incidence of COVID -19 at the time of the enrollment, the true
underlying VE, and a potential early stop for efficacy or futility.
Assuming a COVID -19 attack rate of 1.3% per year in the placebo group, accrual of 164 first
primary -endpoint cases within 6 months, an estimated 20% non -evaluable rate, and 1:1
randomization, the BNT162b2 vaccine candidate selected for Phase 2/3 is expected to comprise
approximately 21,999 vaccine recipients. This is the number of participants initially targeted for
Phase 2/3 and may be adjusted based on advice from DMC analyses of case accumulation and
the percentage of participants who are seropositive at baseline. Dependent upon the evolution of
the pandemic, it is possible that the COVID- 19 attack rate may be much higher, in which case
accrual would be expected to be more rapid, enabling the study’s primary endpoint to be
evaluated much sooner.
The first 360 participants enrolled (180 to active vaccine and 180 to placebo, stratified equally
between 18 to 55 years and >55 to 85 years) will comprise the “Phase 2” portion. Safety data
through 7 days after Dose 2 and immunogenicity data through 1 month after Dose 2 from these
360 participants will be analyzed by the unblinded statistical team, reviewed by the DMC, and
submitted to appropriate regulatory authorities for review. Enrollment may continue during this
period and these participants would be included in the efficacy evaluation in the “Phase 3”
portion of the study.
In Phase 3, up to approximately 2000 participants, enrolled at selected sites, are anticipated to
be 12 to 15 years of age. Noninferiority of immune response to prophylactic BNT162b2 in
participants 12 to 15 years of age to response in participants 16 to 25 years of age will be
assessed based on the GMR of SARS -CoV -2 neutralizing titers using a 1.5- fold margin. A
sample size of 225 evaluable participants (or 280 vaccine recipients) per age group will provide
a power of 90.8% to declare the noninferiority in terms of GMR (lower limit of 95% CI for
GMR >0.67). A random sample of 280 participants from each of the 2 age groups (12 to 15
years and 16 to 25 years) will be selected as an immunogenicity subset for the noninferiority
assessment.
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Page 12 of 72 The initial BNT162b2 was manufactured using “Process 1”; however, “Process 2” was
developed to support an increased scale of manufacture. In the study, each lot of “Process 2”-
manufactured BNT162b2 will be administered to approximately 250 participants 16 to 55 years
of age. The safety and immunogenicity of prophylactic BNT162b2 in individuals 16 to 55 years
of age vaccinated with “Process 1” and each lot of “Process 2” study intervention will be
described. A random sample of 250 participants from those vaccinated with study intervention
produced by manufacturing “Process 1” will be selected for this descriptive analysis.
Participants are expected to participate for up to a maximum of approximately 26 months. The
duration of study follow -up may be shorter among participants enrolled in Phase 1 dosing arms
that are not evaluated in Phase 2/3.
Participants ≥ 16 years of age who originally received placebo and become eligible for receipt
of BNT162b2 or another COVID -19 vaccine according to local or national recommendations
(detailed separately, and available in the electronic study reference portal) will have the
opportunity to receive BNT162b2 as part of the study. The investigator will ensure the
participant meets at least 1 of the recommendation criteria.
Any Phase 2/3 placebo recipient ≥16 years of age who has not already been offered the
opportunity to receive BNT162b2 will be given this opportunity from 6 months after
Vaccination 2 (at the time of the originally planned Visit 4).
Any participant who originally received placebo but then goes on to receive BNT162b2 will
move to a new visit schedule (Protocol Section 1.3.3).
An intensive period of surveillance to evaluate the efficacy of BNT162b2 against asymptomatic
SARS -CoV -2 infection may be conducted at selected sites among Phase 2/3 participants
following approval of protocol amendment 11. After an initial in -person visit where a blood
sample will be collected and a nasal (midturbinate) swab obtained, nasal (midturbinate) swabs
will be obtained from consented participants every 2 weeks until Visit 4, or a sufficient number
of cases of SARS -CoV- 2 infection have accrued to evaluate this objective, whichever is sooner,
per the SoA. The swabs will be tested at a central laboratory using NAAT to detect SARS- CoV -
2. Participants who originally received placebo and become eligible for receipt of BNT162b2 according to local or national recommendations and then receive BNT162b2 as part of the study will not participate in surveillance for asymptomatic SARS -CoV -2 infection; if they become
eligible during the surveillance period, the swabbing every 2 weeks will cease.
3. Analysis Considerations Related to Multiple Analysis Datasets
3.1 Core Variables
Core variables are those that are represented across all/most analysis datasets.
Variable Type Variable Name Variable Description
Study/Site/Subject
ID variables STUDYID Study identifier used for this protocol
USUBJID Unique subject identifier
SUBJID Subject identifier for the study
SITEID Study site identifier
Demographics AGE Age at ICD
AGETR01 Age at Dose 1
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Page 13 of 72 Variable Type Variable Name Variable Description
AGEGR 4 Pooled age group 4 (based on Age at Dose 1)
Including following age categories:
12-15 Years;
Note: There is o ne subject who is 15 years of age
at ICD and 16 years of age at dose 1 in SDTM
datasets, this subject was excluded from all ADAM
datasets.
AGEGR 4N Pooled age group 4 (N):
1= 12-15 Years;
SEX Sex: F=Female; M=Male
ETHNIC Ethnicity, Including HISPANIC OR LATINO;
NOT HISPANIC OR LATINO; NOT REPORTED
RACE Race, including WHITE; BLACK OR AFRICAN
AMERICAN; AMERICAN INDIAN OR
ALASKA NATIVE ; ASIAN; MULTIPLE;
NATIVE HAWAIIAN OR OTHER PACIFIC
ISLANDER; NOT REPORTED
Baseline Status COVBLST Baseline SARS -CoV -2 status: Positive , Negative or
Missing
HIVFL HIV positive subjects Flag
Note: No HIV positive subjects from the 12-15
years of age.
Treatment Variables ARM Description of Planned Arm
ARMCD Planned Arm Code
ACTARM Description of Actual Arm
ACTARMCD Actual Arm Code
TRTSDTM Datetime of first exposure to treatment
TRTEDTM Datetime of last exposure to treatment
TR01SDTM Datetime of first exposure to treatment for blinded
placebo -controlled period
TR01EDTM Datetime of last exposure to treatment for blinded
placebo -controlled period
TR02SDTM Datetime of first exposure to treatment for open -
label vaccination period
TR02EDTM Datetime of last exposure to treatment for open -
label vaccination period
TRT01A Actual Treatment for blinded placebo -controlled
period
TRT01AN Actual Treatment for blinded placebo -controlled
period (N)
TRT01P Planned Treatment for blinded placebo -controlled
period
TRT01PN Planned Treatment for blinded placebo -controlled
period (N)
TRT02A Actual Treatment for open -label vaccination period
TRT02AN Actual Treatment for open -label vaccination period
(N)
TRT02P Planned Treatment for open -label vaccination
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Page 14 of 72 Variable Type Variable Name Variable Description
period
TRT02PN Planned Treatment for open -label vaccination
period (N)
VAX101 Actual vaccination taken at dose 1 for blinded
placebo -controlled period
VAX102 Actual vaccination taken at dose 2 for blinded
placebo -controlled period
VAX10U Actual vaccination taken at unplanned dose for
blinded placebo -controlled period
VAX201 Actual vaccination taken at dose 1 for open -label
vaccination period
VAX202 Actual vaccination taken at dose 2 for open -label
vaccination period
VAX20U Actual vaccination taken at unplanned dose for
open -label vaccination period
VAX101DT Date of dose 1 for blinded placebo -controlled
period
VAX102DT Date of dose 2 for blinded placebo -controlled
period
VAX10UDT Date of unplanned dose for blinded placebo -
controlled period
VAX201DT Date of dose 1 for open -label vaccination period
VAX202DT Date of dose 2 for open -label vaccination period
VAX20UDT Date of unplanned dose for open -label vaccination
period
Date/Time
variables UNBLNDDT Treatment unblinding date
This is the start date of open -label follow-
up/vaccination period for subjects who were
unblinded
BDCSRDT Censor date for blinded placebo -controlled follow -
up period. This date is the earliest date of the day
before treatment unblinding date UNBLNDDT (if
applicable), the day before first dose date of
BNT162b2 at open -label vaccination period (if
applicable), end of study date (if applicable), complete of study date (if applicable) and the date
of cutoff ( 02Sep2021).
This date is used for AE incidence rate summary
table (Exposure adjusted) for blinded placebo-
controlled follow -up period.
X1CSRDT Censor date for open -label follow -up period. This
date is the earliest date of end of study date (if applicable), complete of study date (if applicable)
and the date of cutoff (02 Sep2021 ).
This date is used for AE incidence rate summary
table for open -label follow -up period.
Population Flags** DS3KFL Flag of subjects with at least 6 months of follow -
up time after dose 2 (28*6=168) days after dose 2
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Page 15 of 72 Variable Type Variable Name Variable Description
by the date of cutoff) for subjects originally
received BNT162b2.
This flag is used to subset the subjects for AE
summary tables with reporting period from dose 1 to 6-month after dose 2 regardless of unblinding or not. There are 1113 subjects in total from safety population for subjects from 12 to 15 years
of age at dose 1 .
ENRLFL Enrolled population flag defined as:
All participants who have a signed ICD.
RANDFL Randomized population flag defined as:
All participants who are assigned a randomization
number in the IWR system.
SAFFL Safety population flag defined as:
All randomized participants who receive at least
1 dose of the study intervention.
AAI1EFFL Dose 1 all-available efficacy population flag
defined as:
All randomized participants who receive at
least 1 vaccination.
AAI2EFFL Dose 2 all-available efficacy population flag
defined as:
All randomized participants who complete
2 vaccination doses.
EVALEFFL Evaluable efficacy population flag (7 days) defined
as:
All eligible randomized participants who receive
all vaccination(s) as randomized, with Dose 2
received within the predefined window (within 19 -
42 days after Dose 1) and have no other important
protocol deviations as determined by the clinician
on or before 7 days after Dose 2.
Note: Subjects unblinded or took an unplanned dose within 7 days post dose 2
were excluded from
this evaluable efficacy populations.
Used for efficacy analysis.
Note: Subjects flagged as YES -POP2 in variable
SUPPDV.QNAM = ”CAPE” were excluded from
evaluable efficacy population due to important
protocol deviation identified by clinical.
**See Appendix VII for additional variables used when subsetting data for each analysis.
3.2 Treatment Variable
ARM versus TRTxxP
Are the values of ARM equivalent in meaning to values of TRTxxP?
No, ARM represents the planned arm for the blinded placebo -controlled period based on
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Page 16 of 72 randomization file . TRT01P has the planned treatment for the blinded placebo-controlled
period. TRT02P has the planned treatments of open -label vaccination period for subjects
who received placebo only in the blinded placebo-controlled period and become eligible for
receipt of BNT162b2 after unblinding. See details in below table.
PHASE ARM TRT01P TRT02P
Phase 2/3
BNT162b2 Phase 2/3
(30 mcg) BNT162b2 Phase 2/3
(30 mcg) -
Placebo Placebo -
Placebo Placebo BNT162b2 Phase 2/3
(30 mcg)
Note: Unit of dose ‘mcg’ was displayed as ‘μg’ in all of outputs.
ACTARM versus TRTxxA
If TRTxxA is used, then are the values of ACTARM equivalent in meaning to values of
TRT01A?
No, ACTARM represents the actual arm for the blinded placebo- controlled period.
TRT01A has the actual treatment for the blinded placebo-controlled period, TRT02 A
has the actual treatment of open- label vaccination period for subjects who received
placebo only in the blinded placebo-controlled period and received BNT162b2 after
unblinding. See details in below table.
PHASE ACTARM TRT01A TRT02A
Phase
2/3
BNT162b2 Phase 2/3
(30 mcg) BNT162b2 Phase 2/3
(30 mcg) -
Placebo Placebo -
Placebo Placebo BNT162b2 Phase
2/3 (30 mcg)
Not Treated - -
Note: Unit of dose ‘mcg’ was displayed as ‘μg’ in all of outputs.
Use of ADaM Treatment Variables in Analysis
Are both planned and actual treatment variables used in analyses?
Yes. Both actual treatment and planned treatment were used in the analysis. Planned
treatment variable was used across efficacy analysis and disposition table . Actual
treatment variable was used across safety analysis.
See details in below table.
Reporting Period Analysis
Population Treatment
Variables
Used in
Analysis Applicable analysis
Blinded p lacebo -controlled
period
or Safety TRT01A Conduct of study , Adverse
Event, Medical History,
Concomitant
Medications /Vaccinations
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Page 17 of 72 Reporting Period Analysis
Population Treatment
Variables
Used in
Analysis Applicable analysis
Open -label follow -up period Randomized TRT01P Vaccine as Administered ,
Disposition , Efficacy ,
Sequencing
Open -label follow -up period
(For subjects received placebo
only in the blinded placebo-controlled period and then received BNT162b2 after
unblinding) Safety TRT02A Adverse Event
Note: Unit of dose ‘mcg’ was displayed as ‘μg’ in all of outputs.
Use of ADaM Treatment Grouping Variables in Analysis
Are both planned and actual treatment grouping variables used in analysis?
No. Neither planned nor actual treatment grouping variables are not used in analysis
3.3 Subject Issues that Require Special Analysis Rules
NA
3.4 Use of Visit Windowing, Unscheduled Visits, and Record Selection
Was windowing used in one or more analysis datasets?
Yes. windowing was considered during the derivation of ADAE.VPHASE. Please refer
to Appendix II for more details.
Were unscheduled visits used in any analyses?
Yes. please refer to Section 5.2.7 for more details.
Based on protocol guidance, multiple unscheduled Covid illness visits that are less than
4 days apart are collapsed in ADSYMPT into their respective earlier visit/s and are
considered as single unscheduled illness visit during the analysis.
3.5 Imputation/Derivation Methods
If date imputation was performed, were there rules that were used in multiple analysis datasets?
Yes, date imputations for partial or missing dates were performed for adverse events ,
medical history and concomitant medication described in Appendix III.
Was DTYPE used in one or more analysis datasets?
No.
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4. Analysis Data Creation and Processing Issues
4.1 Split Datasets
There are no split datasets.
4.2 Data Dependencies
All datasets pull core variable values from ADSL . ADC19EF also uses the ADSYMPT dataset
as an input to create efficacy parameter variables.
4.3 Intermediate Datasets
No intermediate analysis datasets were created in this trial.
5. Analysis Dataset Descriptions
5.1 Overview
Are data for screen failures, including data for run- in screening (for example, SDTM values of
ARMCD=’SCRNFAIL’, or ‘NOTASSGN’) included in ADaM datasets?
No. Subjects with ‘NOTASSGN’ ‘SCRNFAIL ’ are not included.
Are data taken from an ongoing study?
Yes. All data up through 02Sep2021 cutoff are included in the SDTM datasets and
used for ADaM datasets and analyses.
Do the analysis datasets support all protocol- and statistical analysis plan -specified objectives?
No.
Additional Content of Interest
No additional content of Interest.
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5.2 Analysis Datasets
Dataset Label
Class
Efficacy
Safety
Baseline or
other subject
characteristics
PK/PD
Primary Structure
ADSL
Subject -Level
Analysis Dataset SUBJECT
LEVEL
ANALYSIS
DATASET X One record per subject
ADAE
Adverse Events
Analysis Dataset OCCURRENCE
DATA STRUCTURE X X One record or multiple
records per subject per
each adverse event per
event start date
ADCM
Concomitant
Medications Analysis
Dataset OCCURRENCE
DATA STRUCTURE X One record or multiple
records per subject per recorded medication occurrence or constant -
dosing interval
ADDS
Disposition
Analysis Dataset OCCURRENCE
DATA STRUCTURE X One record or multiple
records per subject per disposition status or protocol milestone
ADDV
Protocol Deviations
Analysis Dataset OCCURRENCE
DATA STRUCTURE X One record or multiple
records per subject per protocol deviation per
event start date
ADMH
Medical History
Analysis Dataset OCCURRENCE
DATA
STRUCTURE X One record or multiple
records per subject per
medical history event
ADC19EF
Covid -19 Efficacy
Analysis Dataset BASIC DATA
STRUCTURE X X One record or multiple
records per subject per
analysis parameter per
analysis timepoint
ADSYMPT
Covid -19 Signs and
Symptoms Analysis
Dataset BASIC DATA
STRUCTURE X X One record or multiple
records per subject per
analysis parameter per
analysis timepoint
ADXB
Sequencing
Analysis Datase t BASIC DATA
STRUCTURE X One record per subject
per analysis parameter
per analysis timepoint
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5.2.1 ADSL – Subject -Level Analysis Dataset
ADSL includes the following information for each subject:
• Subject identifier
• Demographic information
• Planned treatment and actual treatment (details described in Section 3.1 Core Variables )
• Population flags (details described in Section 3.1 Core Variables )
• Key dates and datetime related to conduct of study (details described in Section 3.1 Core
Variables )
• Variables to support subgroup analyses
o Sex (Female and Male)
o Race (White, Black or African American and All Others)
Note: All Others = American Indian or Alaska Native, Asian, Native Hawaiian or other
Pacific Islander, multiracial, and not reported race categories.
o Ethnicity (Hispanic/Latino and Non -Hispanic/Non- Latino)
o Baseline SARS -CoV-2 Status ( Positive and Negative )
o Comorbidities (Yes and No)
o Obese (Yes and No)
5.2.2 ADAE – Adverse Events Analysis Dataset
This is the main safety analysis dataset comprised of adverse events recorded on the CRF. Partial
start dates or partial end dates of adverse events were imputed using rules described in
Appendix III.
AE data is reported excluding the reactogenicity events [AECAT not in
(”REACTOGENICITY”)]. AE summaries were analyzed based on the specific reporting
periods. The vaccine phase (VPHASE) was derived based on the start date of the AE and the
phase date (ADSL.V01DT, ADSL.V02DT , ADSL.V02OBDT, ADSL.V03DT, ADSL.V04DT ),
please refer to Appendix II for more details , and was applied to select AEs for summaries based
on different reporting period. See details in Appendix VII .
DATCHGFL is used to identify the new AEs that occurred since the data cutoff used for the
EUA Amendment submission for individuals 12 through 15 years of age.
Note: One AE record was dropped since the data cutoff used for the EUA Amendment
submission for individuals 12 through 15 years of age. See the AE as below.
USUBJID AESPID AETERM AEDECOD AESTDTC AEENRTPT
C4591001 1131
11311301 2 broken collar
bone Clavicle
fracture 2021 -02-19 ONGOING
DATACHGC is used to ident ify what type of AE data change occurred since the data cutoff
used for the EUA Amendment submission for individuals 12 through 15 years of age.
See t ype of updates as below.
Type of Updates (DATACHGC )
AE onset date changed from EUA to sBLA
AE outcome changed from EUA to sBLA
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AERELTXT changed from EUA to sBLA
Note: AERELTXT = Event Due to Other Specify
Minor AE term changed from EUA to sBLA
AEDECOD changed from EUA to sBLA
Note: AEDECOD= Dictionary -Derived Term
Note: One AE recor d could have multiple types of change combined in DATACHGC and EUA
refers to the EUA Amendments submission in Apr2021 for 12-15 Years of age (EUA snapshot
25Mar2021 with the cutoff date 13Mar2021). DATCHGFL and DATACHGC are derived to address FDA’s response for question 1.a ‘please include an interim summary of new or updated safety events that occurred/have been updated
since the data cutoff used for the EUA Amendment submission for individuals 12 through 15 years of age, using the same time periods, and insert a flag into the datasets to indicate which safety events are new/updated’ of
“IND 19736.434_Comments_ReqCommentsAdvice_sBLA_12-15yoa”. In addition, a set of AE tables have ‘New Adverse Events After the EUA Snapshot‘ as part of title and a listing has ‘Adverse Events Updated After the EUA Snapshot’ as part of title are generated to respond FDA’s response.
5.2.3 ADCM – Concomitant Medications Analysis Dataset
The dataset contains information of nonstudy vaccines (CMCAT = “VACCINATIONS”) and
prohibited concomitant medications (CMCAT=’ CORTICOSTEROIDS ’).
Partial start dates or partial end dates of nonstudy vaccines and concomitant medications were imputed using rules described in Appendix III.
5.2.4 ADDS – Disposition Analysis Dataset
This dataset contains information for various disposition events (DSCAT = “DISPOSITION
EVENT”) for each subject throughout the study. The phases in the disposition event are
presented in the table below as DSPHASE. The subject's completion status or reason for
discontinuation is identified in DSDECOD (Standardized Disposition Term).
Disposition phases included in this study are as follows:
DSCAT DSPHASE
DISPOSITION EVENT SCREENING
DISPOSITION EVENT REPEAT S CREENING 1
DISPOSITION EVENT VACCINATION
DISPOSITION EVENT OPEN LABEL TREATMENT
DISPOSITION EVENT FOLLOW -UP
5.2.5 ADDV – Protocol Deviations Analysis Dataset
This dataset contains information about protocol deviation events and causes for protocol
deviations. Important protocol deviations were flagged as “ Important ” in variable DV CAT and
the corresponding population exclusion flag was capture in SUPPDV.QNAM=’CAPE’ .
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This dataset contains all medical histories (MHCAT = “GENERAL MEDICAL HISTORY”)
collected on the CRF. Partial start dates or partial end dates medical histories were imputed
using rules described in Appendix III .
5.2.7 ADSYMPT – Covid-19 Signs and Symptoms Analysis Dataset
The purpose of this dataset is to gather all signs/symptoms/conditions/laboratory results
associated with SARS -CoV -2 from unscheduled Covid illness visits which will then be used to
create the efficacy endpoint dataset ADC19EF. The main SDTM domains that were used to
create the ADSYMPT dataset were CE, CM, DS, HO, SUPPHO, FA (FACE) , IS, LB, MB, MH,
VS and the analysis dataset ADSL. Some of the important variables that make up this dataset
are PARAMCD, PARAM, PARAMN, PARCAT1, PARCAT2, AVAL, AVALC, ADT,
ASTDT, AENDT, VSSTRESU, MB METHOD and ISMETHOD. Algorithms used to create
each of these variables are included in the define.xml.
Protocol defined symptoms include “Chills, Diarrhea, Fever, New loss of taste or smell, New or
increased cough, New or increased muscle pain, New or increased sore throa t, Vomiting .”.
These data were identified and captured in the ADSYMPT dataset as follows:
• From FA all records with FACAT = “EFFICACY” and FASCAT =
“RESPIRATORY ILLNESS” provides the COVID-19 signs and symptoms.
• Subjects with local lab swab samples are identified using MB.MBTESTCD= "SARSCOV2"
and MB.MBMETHOD = "IMMUNOCHROMATOGRAPHY".
• Subjects with central swab samples are identified using MB.MBTESTCD = "RTCOV2NS"
and MB.MBMETHOD = "REVERSE TRANSCRIPTASE PCR".
• For the severe COVID-19 data from vital signs, subjects with admission to ICU, deaths, lab
oxygenation data, ECG/oxygen therapy/intubation, etc., please refer to SAP Appendix 3 for
more details
All COVID -19 signs, symptoms and conditions were defined as shown in the table below.
PARAMN PARAMCD PARAM Derivation
1 CHILLS CHILLS Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"CHILLS" and FA.FACAT = "EFFICACY"
and FA.FASCAT = "RESPIRATORY
ILLNESS".
2 DIARRHEA DIARRHEA Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"DIARRHEA" and FA.FACAT =
"EFFICACY" and FA.FASCAT =
"RESPIRATORY ILLNESS".
3 FEVER FEVER Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"FEVER" and FA.FACAT = "EFFICACY"
and FA.FASCAT = "RESPIRATORY
ILLNESS".
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Page 23 of 72 PARAMN PARAMCD PARAM Derivation
4 NLTSTSML NEW LOSS OF
TASTE OR SMELL Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"NEW LOSS OF TASTE OR SMELL" and
FA.FACAT = "EFFICACY" and FA.FASCAT
= "RESPIRATORY ILLNESS".
5 NCOUG NEW OR
INCREASED
COUGH Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"NEW OR INCREASED COUGH" and
FA.FACAT = "EFFICACY" and FA.FASCAT
= "RESPIRATORY ILLNESS".
6 NMUSPN NEW OR
INCREASED
MUSCLE PAIN Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"NEW OR INCREASED MUSCLE PAIN"
and FA.FACAT = "EFFICACY" and
FA.FASCAT = "RESPIRATORY ILLNESS".
7 NSTBRTH NEW OR
INCREASED
SHORTNESS OF
BREATH Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"NEW OR INCREASED SHORTNESS OF
BREATH" and FA.FACAT = "EFFICACY"
and FA.FASCAT = "RESPIRATORY
ILLNESS".
8 NSRTHROT NEW OR
INCREASED SORE
THROAT Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"NEW OR INCREASED SORE THROAT"
and FA.FACAT = "EFFICACY" and
FA.FASCAT = "RESPIRATORY ILLNESS".
9 VOMIT VOMITING Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"VOMITING" and FA.FACAT =
"EFFICACY" and FA.FASCAT =
"RESPIRATORY ILLNESS".
11 NNSLCONG NEW OR
INCREASED NASAL
CONGESTION Set to "NEW OR INCREASED NASAL
CONGESTION" when upcase(FA.FAOBJ) =
"NEW OR INCREASED NASAL
CONGESTION" or "NASAL
CONGESTION" and FA.FACAT =
"EFFICACY" and FA.FASCAT =
"RESPIRATORY ILLNESS".
14 WHEEZ NEW OR
INCREASED
WHEEZING Set to "NEW OR INCREASED WHEEZING"
when upcase(FA.FAOBJ) = "NEW OR
INCREASED WHEEZING" or
upcase(FA.FAOBJ) = "WHEEZING" and
FA.FACAT = "EFFICACY" and FA.FASCAT
= "RESPIRATORY ILLNESS".
15 FATIGUE FATIGUE Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"FATIGUE" and FA.FACAT = "EFFICACY"
and FA.FASCAT = "RESPIRATORY
ILLNESS".
16 HEADACHE HEADACHE Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"HEADACHE" and FA.FACAT =
"EFFICACY" and FA.FASCAT =
"RESPIRATORY ILLNESS".
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17 RIHNRA RHINORRHOEA Set to "RHINORRHOEA" when
upcase(FA.FAOBJ) contains "RUNNY
NOSE" or upcase(FA.FAOBJ) =
"RHINORRHOEA" and FA.FAOBJ ^=
"NEW OR INCREASED NASAL
DISCHARGE" and FA.FACAT =
"EFFICACY" and FA.FASCAT =
"RESPIRATORY ILLNESS".
18 NAUSEA NAUSEA Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"NAUSEA" and FA.FACAT = "EFFICACY"
and FA.FASCAT = "RESPIRATORY
ILLNESS".
25 SARDFN SIGNIFICANT
ACUTE RENAL
DYSFUNCTION Set to CE.CESCAT when CE.CESCAT =
"SIGNIFICANT ACUTE RENAL
DYSFUNCTION".
30 SAHDFN SIGNIFICANT
ACUTE HEPATIC
DYSFUNCTION Set to CE.CESCAT when CE.CESCAT =
"SIGNIFICANT ACUTE HEPATIC
DYSFUNCTION".
35 SANDFN SIGNIFICANT
ACUTE
NEUROLOGIC
DYSFUNCTION Set to CE.CESCAT when CE.CESCAT =
"SIGNIFICANT ACUTE NEUROLOGIC
DYSFUNCTION".
40 SARSCOV2 SEVERE ACUTE
RESP SYNDROME
CORONAVIRUS 2 Set to MB.MBTEST when
upcase(MB.MBTESTCD) = "SARSCOV2"
and MB.MBMETHOD =
"IMMUNOCHROMATOGRAPHY".
41 RTCOV2NS CEPHEID RT -PCR
ASSAY FOR SARS -
COV -2 Set to MB.MBTEST when
upcase(MB.MBTESTCD) = "RTCOV2NS"
and MB.MBMETHOD = "REVERSE
TRANSCRIPTASE PCR".
50 RESP RESPIRATORY
RATE Set to VS.VSTEST when VS.VSTESTCD =
"RESP".
51 HR HEART RATE Set to VS.VSTEST when VS.VSTESTCD =
"HR".
52 OXYSAT OXYGEN
SATURATION Set to VS.VSTEST when VS.VSTESTCD =
"OXYSAT"
53 DIABP DIASTOLIC BLOOD
PRESSURE Set to VS.VSTEST when VS.VSTESTCD =
"DIABP".
54 SYSBP SYSTOLIC BLOOD
PRESSURE Set to VS.VSTEST when VS.VSTESTCD =
"SYSBP".
60 PO2FIO2 PP ARTERIAL
O2/FRACTION
INSPIRED O2 Set to LB.LBTEST when LB.LBTEST = "PP
Arterial O2/Fraction Inspired O2".
71 NIPPV NON -INVASIVE
POSITIVE
PRESSURE
VENTILATION Set to PR.PRTRT when upcase(PR.PRTRT) =
"NON -INVASIVE POSITIVE PRESSURE
VENTILATION".
74 MCHVENT MECHANICAL
VENTILATION Set to PR.PRTRT when upcase(PR.PRTRT) =
"MECHANICAL VENTILATION".
76 HFOXTHRP HIGH FLOW
OXYGEN Set to PR.PRTRT when upcase(PR.PRTRT) =
"HIGH FLOW OXYGEN THERAPY".
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Page 25 of 72 PARAMN PARAMCD PARAM Derivation
80 VSOPRES VASOPRESSO
RS AGENTS Set to CM.CMSCAT when CM.CMCAT =
"GENERAL CONCOMITANT
MEDICATIONS" and CM.CMSCAT = "VASOPRESSORS AGENTS". Keep only
one record per subject per CM.CMSTDTC
where CM.CMTRT is not missing.
90 C19NIG N-BINDING
ANTIBODY Set to IS.ISTEST when IS.ISTESTCD =
"C19NIG"
91 HCUICU SUBJECT IN
ICU DUE TO POTENTIAL COVID -19
ILLNESS Set to "SUBJECT IN ICU DUE TO
POTENTIAL COVID -19 ILLNESS" when
HOTERM = "ICU' or (SUPPHO.QNAM = "HCUICU" and SUPPHO.QVAL = "Y") .
92 HCUHSP HOSPITALIZE
D DUE TO COVID -19
Set to "HOSP ITALIZED DUE TO COVID -19
ILLNESS" when SUPPHO .QNAM =
"HCUHSP " and SUPPHO.QVAL = "Y"
95 PRCDTH PRIMARY
CAUSE OF DEATH Set to "PRIMARY CAUSE OF DEATH "
when DD. DDTESTCD = "PRCDTH"
96 SECDTH SECONDARY
CAUSE OF
DEATH Set to DD.DDTEST when DD.DDTESTCD =
"SECDTH "
99 DEATH DEATH Set to DS.DSDECOD when DS.DSDECOD =
"DEATH".
5.2.8 ADC19EF – Covid-19 Efficacy Analysis Dataset
The purpose of this dataset is to gather all signs/symptoms/conditions associated with SARS -
COV-2 and derive case onset, severe illness onset, and surveillance time for various end point
analyses. This dataset contains all derivations to account for surveillance times, and variables to
support the first primary end point and secondary endpoints as defined in the Statistical Analysis
Plan. Details around the derivation of surveillance times and the flow charts for identification of
first and secondary primary end points are available in Appendix V and Appendix VI
respectively. Detailed algorithms for each parameter are included in the define.xml.
Variables used to identify the primary end points as well the other endpoints of special interest
are listed in the table below:
PARAMN PARAMCD PARAM
40 SARSCOV2 SEVERE ACUTE RESP SYNDROME CORONAVIRUS 2
41 RTCOV2NS CEPHEID RT -PCR ASSAY FOR SARS -COV -2
90 C19NIG N-BINDING ANTIBODY
92 HCUHSP HOSPITALIZED DUE TO COVID -19 ILLNESS?
101 PRPDSAD PRESENCE OF PROTOCOL DEFINED SYMPTOMS AFTER
102 PRCDCSAD PRESENCE OF CDC DEFINED SYMPTOMS AFTER DOSE
103 SEVCVS SEVERE COVID -19 SYMPTOMS - VITAL SIGNS
107 PRSVCSAD PRESENCE OF PROTOCOL DEFINED SEVERE COVID -19
SYMPTOMS AFTER DOSE
108 PRSCDCAD PRESENCE OF CDC DEFINED SEVERE COVID -19 SYMPTOMS
AFTER DOSE
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110 NAATRAD COVID -19 NAAT RESULT AFTER DOSE
120 C19ONST PROTOCOL DEFINED COVID -19 ILLNESS ONSET
125 CDCONST CDC DEFINED COVID -19 ILLNESS ONSET
130 SEVCONST PROTOCOL DEFINED SEVERE COVID -19 ILLNESS ONSET
135 CDCSONST CDC DEFINED SEVERE COVID -19 ILLNESS ONSET
141 ST1PD SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS
142 ST17PD SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS
143 ST2PD SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS
144 ST27PD SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS
145 ST214PD SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS
151 ST1CD SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC
DEFINED COVID19 SYMPTOMS
152 ST17CD SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR
CDC DEFINED COVID19 SYMPTOMS
153 ST2CD SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR CDC
DEFINED COVID19 SYMPTOMS
154 ST27CD SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2 FOR
CDC DEFINED COVID19 SYMPTOMS
155 ST214CD SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
CDC DEFINED COVID19 SYMPTOMS
161 ST1SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
162 ST17SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
163 ST2SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
164 ST27SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2
FOR PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
165 ST214SE SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2
FOR PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
171 STC1SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS
172 STC17SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1
FOR CDC DEFINED SEVERE COVID19 SYMPTOMS
173 STC2SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS
174 STC27SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2
FOR CDC DEFINED SEVERE COVID19 SYMPTOMS
175 STC214SE SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2
FOR CDC DEFINED SEVERE COVID19 SYMPTOMS
201 ST1PDA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS - ALL
202 ST17PDA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1
FOR PROTOCOL DEFINED COVID19 SYMPTOMS - ALL
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Page 27 of 72 PARAMN PARAMCD PARAM
203 ST2PDA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS - ALL
204 ST27PDA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2
FOR PROTOCOL DEFINED COVID19 SYMPTOMS - ALL
205 ST214PDA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2
FOR PROTOCOL DEFINED COVID19 SYMPTOMS - ALL
211 ST1CDA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC
DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
212 ST17CDA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1
FOR CDC DEFINED COVID19 SYMPTOMS - ALL
213 ST2CDA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR CDC
DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
214 ST27CDA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2
FOR CDC DEFINED COVID19 SYMPTOMS - ALL
215 ST214CDA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2
FOR CDC DEFINED COVID19 SYMPTOMS - ALL
221 ST1SEA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS - ALL
222 ST17SEA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1
FOR PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS -
ALL AVAILABLE
223 ST2SEA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS - ALL
224 ST27SEA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2
FOR PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS -
ALL AVAILABLE
225 ST214SEA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2
FOR PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS -
ALL AVAILABLE
231 STC1SA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS - ALL
232 STC17SA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1
FOR CDC DEFINED SEVERE COVID19 SYMPTOMS - ALL
233 STC2SA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS - ALL
234 STC27SA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2
FOR CDC DEFINED SEVERE COVID19 SYMPTOMS - ALL
235 STC214SA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2
FOR CDC DEFINED SEVERE COVID19 SYMPTOMS - ALL
301 ST1PDX SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS - CROSSOVER
331 STC1SX SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS - CROSSOVER
5.2.9 ADXB – Sequencing Analysis Dataset
The purpose of this dataset is to get SARS-CoV-2 lineage (WHO classification) phylogenetic
analysis information for the COVID-19 cases . Key variable used for this analysis is FC19D27 that
indicates subjects who had their first COVID -19 occurrence 7 days post dose 2.
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Page 28 of 72 6. Data Conformance Summary
6.1 Conformance Inputs
Was a validator used to evaluate conformance? Yes
If yes, specify the version(s) of the validation rules: Pinnacle 21 Enterprise version 4.2.1
Validation En gine version 2010.1
Were sponsor -defined validation rules used to evaluate conformance? No
If yes, describe any significant sponsor -defined validation rules: NA
Were the ADaM datasets evaluated in relation to define.xml? Yes
Was define.xml evaluated? Yes
Provide any additional compliance evaluation information: NA
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Page 29 of 72
6.2 Issues Summary
Check ID Diagnostic
Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
AD0034 CDRMUPFL
value is not Y
or null Error ADC19EF 119345
(98.14%) CDRMUPFL is not defined as
parameter level flags. It is subject level flags based on series of events therefore having values of
Y/N are acceptable.
AD0034 PDRMUPFL
value is not Y or null Error ADC19EF 119455
(98.23%) PDRMUPFL is not defined as
parameter level flags. It is subject level flags based on series of events therefore having values of
Y/N are acceptable.
AD0099 ASTDY is
greater than AENDY Error ADC19EF 234
(0.25%) ASTDT is greater than AENDT in
some cases when deriving surveillance times since surveillance times are defined to start at various time points in the
study for a given subject, it
possible that subject’s surveillance time may have come to an end prior to starting due a positive Covid case or other def initions
described in specifications and in
these instances ASTDT would be
greater than AENDT. As a result, ASTDY is also greater than
AENDY.
AD0253 Record key
from SDTM
AE is not
traceable to ADaM ADAE (not enough
ADAE recs) Error AE 481
(30.87%) AECAT=”REACTOGENICITY”
records (from ediary) was not kept
in ADAE (Based on flat model).
AD0361 Value of
ASTDT is
greater than value of AENDT Error ADC19EF 234
(0.25%) ASTDT is greater than AENDT in
some cases when deriving surveillance times since survei llance times are defined to
start at various time points in the study for a given subject, it
possible that subject’s surveillance
time may have come to an end prior to starting due a positive Covid case or other definitions described in specifications and in
these instances ASTDT would be
greater than AENDT.
AD1012 Secondary
custom variable is present but its
primary
variable is not present Warning ADDS 1
(7.14%) AD1012 check is limited to
"standard" ADaM variables explicitly defined in ADaM IG documents. M1P2EXC is the
variable to capture the necessary
information. Any new custom variables added to analysis data are
out-of-scope for AD1012 check.
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Page 30 of 72 Check ID Diagnostic
Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
AD1012 Secondary
custom
variable is present but its primary variable is not present Warning ADSL 5
(21.74%) AD1012 check is limited to
"standard" ADaM variables explicitly defined in ADaM IG documents. FUP1CA1N/SCREEN/FUP2CA1N/FPX1CA1N/FUP2CA2N are the variable to capture the necessary
information. Any new custom
variables added to analysis data are
out-of-scope for AD1012 check.
CT2002 RACE value
not found in 'Race'
extensible
codelist Warning ADC19EF 2919
(2.40%) New terms were added to
extensible codelist RACE for the
study protocol needs:
Multiple
CT2002 RACE value
not found in 'Race'
extensible
codelist Warning ADCM 3
(0.73%) New terms were added to
extensible codelist RACE for the
study protocol needs:
Multiple
CT2002 RACE value
not found in 'Race' extensible
codelist Warning ADDS 161
(2.44%) New terms were added to
extensible codelist RACE for the study protocol needs:
Multiple
CT2002 RACE value
not found in 'Race' extensible
codelist Warning ADDV 87
(2.61%) New terms were added to
extensible codelist RACE for the study protocol needs:
Multiple
CT2002 RACE value
not found in 'Race' extensible
codelist Warning ADMH 120
(2.74%) New terms were added to
extensible codelist RACE for the study protocol needs:
Multiple
CT2002 RACE value
not found in 'Race' extensible
codelist Warning ADSL 53
(2.34%) New terms were added to
extensible codelist RACE for the study protocol needs:
Multiple
CT2002 RACE value
not found in 'Race' extensible
codelist Warning ADSYMPT 793
(2.28%) New terms were added to
extensible codelist RACE for the study protocol needs:
Multiple
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Page 31 of 72
7. Submission of Programs
All programs for analysis datasets as well as primary safety and efficacy results are submitted as shown below. All programs
were created on a SAS platform using 9.4. ADSL.sas (adsl -sas.txt) must be run first before any other ADaM datasets; all other
programs are dependent on ADSL output. ADXB is dependent on ADC19EF. ADC19EF program is dependent on ADSYMPT.
Annotated Mock Tables for each output are also included for reference in Appendix I .
7.1 ADaM Programs
Program
Name
Output Input
Macro Used
adsl-sas.txt adsl.xpt dm suppdm ex suppex ds suppds is co lb cm ie dv
suppdv vs sv mb mh face ce ho suppho NA
adds-sas.txt adds.xpt ds suppds sv adsl NA
adae-sas.txt adae.xpt ae suppae ex adsl NA
addv -sas.txt addv.xpt dv suppdv adsl NA
adcm -sas.txt adcm.xpt cm suppcm adsl NA
admh -sas.txt admh.xpt mh suppmh adsl NA
adc19ef -sas.txt adc19ef.xpt adsympt adsl NA
adsympt -sas.txt adsympt.xpt ce cm ds fa ce ho suppho is mb mh lb vs adsl NA
adxb -sas.txt adxb.xpt mb adsl adc19ef NA
7.2 Analysis Output Programs
Table Program
Name Output Name Title Input Population Subset used
1 adsl-s005-all1-
ped6 -saf-sas.txt adsl s005 all1 ped
6 saf.html Demographic Characteristics – Phase 2/3
Subjects 12 Through 15 Years of Age – Safety
Population ADSL ADSL.SAFFL ="Y" and
ADSL.AGEGR4N=1
2 adds-s002 -all1-
ped6 -sas.txt adds s002 all1 ped
6 html Disposition of All Randomized Subjects –
Phase 2/3 Subjects 12 Through 15 Years of
Age ADSL,
ADDS ADSL.RANDFL ="Y" and
ADS L.AGEGR4N =1
3 adsl-fu-d21-ped6 -adsl fu d21 ped6 h Follow -up Time After Dose 2 – Phase 2/3 ADSL ADSL.SAFFL ="Y" and
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Page 32 of 72 Table Program
Name Output Name Title Input Population Subset used
sas.txt tml Subjects 12 Through 15 Years of Age – Safety
Population ADSL.AGEGR4N=1
4 adae-s092- all-
unb1- ped6 -sas.txt adae s092 all unb
1 ped6.html Incidence Rates of at Least 1 Adverse Event
From Dose 1 to Unblinding Date – Blinded
Placebo -Controlled Follow -up Period – Phase
2/3 Subjects 12 Through 15 Years of Age –
Safety Population ADSL
ADAE ADSL.SAFFL="Y" and ADSL.AGEGR4N
=1
5 adae-s091- 6m1-
ped6 -sas.txt adae s091 6m1 pe
d6 html Number (%) of Subjects Reporting at Least 1 Adverse Event From
Dose 1 to 6 Months After
Dose 2 – Subjects With at Least 6 Months of
Follow -up Time After Dose 2 – Phase 2/3
Subjects 12 Through 15 Years of Age (Subjects Who Originally Received
BNT162b2) – Safety Population ADSL
ADAE ADSL.SAFFL="Y" and
ADSL. TRT01AN=8 and
ADSL.DS3KFL= "Y" and
ADSL.AGEGR4N=1
6 adae-s092-cut1-
ped6 -sas.txt adae s092 cut1 pe
d6 html Incidence Rates of at Least 1 Adverse Event
From Dose 3 to Data Cutoff Date
(02SEP2021) – Open -Label Follow -up Period
– Subjects Who Originally Received Placebo
and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12 Through
15 Years of Age – Safety Population ADSL
ADAE ADSL.SAFFL="Y" and
ADSL. TRT01AN= 9 and
ADSL. TRT02AN=8 and
ADSL. VAX201DT > . and
ADSL. X1CSRDT > . and
ADSL.AGEGR4N=1
7 adae-s091- all-
unb2 -ped6 -sas.txt adae s091 all unb
2 ped6.html Number (%) of Subjects Reporting at Least 1
New Adverse Event After the EUA Snapshot, From Dose 1 to Unblinding Date – Blinded
Placebo -Controlled Follow -up Period – Phase
2/3 Subjects 12 Through 15 Years of Age –
Safety Population ADSL
ADAE ADSL.SAFFL="Y" and (ADSL.EOSDCDT
gt input(“13MAR2021”, date9.) or
ADSL.EOSDCDT =. ) and
ADSL.AGEGR4N=1
8 adae- s130- sae-
unb2 -ped6 -sas.txt adae s130 sae unb
2ped6.html Number (%) of Subjects Reporting at Least 1
New Serious Adverse Event After the EUA
Snapshot, From Dose 1 to Unblinding Date , by
System Organ Class and Preferred Term – ADSL
ADAE ADSL.SAF FL="Y" and (ADSL.EOSDCDT
gt input(“13MAR2021”, date9.) or ADSL.EOSDCDT =. ) and
ADSL.AGEGR4N =1
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Page 33 of 72 Table Program
Name Output Name Title Input Population Subset used
Blinded Placebo -Controlled Follow -up Period
– Phase 2/3 Subjects 12 Through 15 Years of
Age – Safety Population
9 adae- s091- 6m2-
ped6 -sas.txt adae s091 6m2 pe
d6html Number (%) of Subjects Reporting at Least 1
New Adverse Event After the EUA Snapshot,
From Dose 1 to 6 Months After Dose 2 – Subjects With at Least 6 Months of Follow -up
Time After Dose 2 – Phase 2/3 Subjects 12
Through 15 Years of Age (Subjects Who Originally Received BNT162b2) – Safety
Population ADSL
ADAE ADSL.SAFFL="Y" and
ADSL.TRT01AN =8 and
ADSL.DS3KFL= "Y" and
ADSL.AGEGR4N =1
10 adc19ef -ve-cov-
7pd2- peds-wo-
eval-sas.txt adc19ef ve cov 7p
d2 peds wo eval .h
tml Vaccine Efficacy – First COVID- 19
Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period
– Subjects 12 Through 15 Years of Age and
Without Evidence of Infection Prior to 7 Days
After Dose 2 – Evaluable Efficacy (7 Days)
Population ADSL
ADC19 EF
ADSYMPT ADSL.EVALEFFL ="Y" and
ADC19EF.PDP27FL ="Y" and
ADSL.AGEGR4N=1
11 adc19ef -ve-cov-
7pd2- peds-eval-
sas.txt adc19ef ve cov 7p
d2 peds eval .html Vaccine Efficacy – First COVID -19
Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period
– Subjects 12 Through 15 Years of Age and
With or Without Evidence of Infection Prior to
7 Days After Dose 2 – Evaluable Efficacy (7
Days) Population ADSL
ADC19 EF
ADSYMPT ADSL.EVALEFFL= "Y" and
ADSL.AGEGR4N =1
12 adc19ef -ve-cov-
7pd2-p- wo-sg-
eval-sas.txt adc19ef ve cov 7p
d2 p wo sg eval h
tml Vaccine Efficacy – First COVID- 19
Occurrence From 7 Days After Dose 2, by Subgroup – Blinded Placebo -Controlled
Follow -up Period – Subjects 12 Through 15
Years of Age and Without Evidence of
Infection Prior to 7 Days After Dose 2 – ADSL
ADC19 EF
ADSYMPT ADSL.EVALEFFL ="Y" and
ADC19EF.PDP27FL ="Y" and
ADSL.AGEGR4N=1
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Page 34 of 72 Table Program
Name Output Name Title Input Population Subset used
Evaluable Efficacy (7 Da ys) Population
13 adc19ef -ve-cov-
7pd2-p- sg-eval-
sas.txt adc19ef ve cov 7p
d2 p sg eval html Vaccine Efficacy – First COVID -19
Occurrence From 7 Days After Dose 2, by
Subgroup – Blinded Placebo -Controlled
Follow -up Period – Subjects 12 Through 15
Years of Age and With or Without Evidence of
Infection Prior to 7 Days After Dose 2 –
Evaluable Efficacy (7 Days) Population ADSL
ADC19 EF
ADSYMPT ADSL.EVALEFFL= "Y" and
ADSL.AGEGR4N =1
14 adsl-demo -7d-
peds-eval-eff-
sas.txt adsl demo 7d ped
s eval eff.html Demographic Characteristics – Blinded
Placebo -Controlled Follow -up Period –
Subjects 12 Through 15 Years of Age and
Without Evidence of Infection Prior to 7 Days
After Dose 2 – Evaluable Efficacy (7 Days)
Population ADSL
ADC19 EF
ADSYMPT ADSL.EVALEFFL ="Y" and
ADC19EF.PDP27FL ="Y" and
ADSL.AGEGR4N=1
15 adsl-demo -7d-
wwo -peds-eval-
eff-sas.txt adsl demo 7d ww
o peds eval eff.ht
ml Demographic Characteristics – Blinded
Placebo -Controlled Follow -up Period –
Subjects 12 Through 15 Years of Age and With or Without Evidence of I
nfection Prior to
7 Days After Dose 2 – Evaluable Efficacy (7
Days) Population ADSL
ADC19 EF
ADSYMPT ADSL.EVALEFFL= "Y" and
ADSL.AGEGR4N =1
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Page 35 of 72 8. Appendix
Appendix I: Annotated Mocks for Key Tables
General n ote: Each row subsetting is based on N criteria plus additional criteria annotated on the mocks .
Mock Table 1
Demographic Characteristics – Phase 2/3 Subjects 12 Through 15 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg) Placebo Total
(Na=xx) (Na=xx) (Na=xx)
nb (%) nb (%) nb (%)
Sex
Male xx (xxx.x) xx (xxx.x) xx (xxx.x)
Female xx (xxx.x) xx (xxx.x) xx (xxx.x)
Race
White xx.x) xx (xxx.x) xx (xxx.x)
Black or African American ( xx.x) (xxx.x) xx (xxx.x)
All Others xx (xxx x) xx (xxx.x) xx (xxx.x)
American Indian or Alaska Native xx (xxx.x) xx (xxx.x)
Asian xxx.x) xx (xxx.x) xx (xxx.x)
Native Hawaiian or other Pacific Islander xx (xxx.x) xx (xxx.x) xx (xxx.x)
Multiracial xx (xxx.x) xx (xxx.x)
Not reported xx (xxx.x) xx (xxx.x) xx (xxx.x)
Racial designation
Japanese xx (xxx.x) xx (xxx.x) xx (xxx.x)
Ethnicity
Hispanic/Latino xx (xxx.x) xx (xxx.x) xx (xxx.x) ADSL.TRT0 1A
ADSL. SAFFL eq 'Y' and ADSL. AGEGR4N =1
ADSL.SEX=”M”
ADSL.SEX=”F”
ADSL.ARACEN= 2
ADSL.ARACEN= 3
ADSL.ARACEN= 4
ADSL.ARACEN= 5
ADSL.ARACEN= 6
ADSL.RACIALDN=5 ADSL.ARACEN=1
ADSL. ETHNICN =1 ADSL.ARACEN in (3,4,5,6,7)
ADSL.ARACEN= 7
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Page 36 of 72 Non-Hispanic/non -Latino xx (xxx.x) xx (xxx.x) xx (xxx.x)
Not reported xx (xxx.x) xx (xxx.x) xx (xxx.x)
Country
USA xx (xxx.x) xx (xxx.x) xx (xxx.x)
Baseline SARS -CoV -2 status
Positivec xx (xxx.x) xx (xxx.x) xx (xxx.x)
Negatived xx (xxx.x) xx (xxx.x) xx (xxx.x)
Missing xx (xxx.x) xx (xxx.x) xx (xxx.x)
Comorbiditiese
Yes xx (xxx.x) xx (xxx.x) xx (xxx.x)
No xx (xxx.x) xx (xxx.x) xx (xxx.x)
Obesef
Yes xx (xxx.x) xx (xxx.x) xx (xxx.x)
No xx (xxx.x) xx (xxx.x) xx (xxx.x)
Age at vaccination (years)
Mean (SD) xx.x (xx.xx) xx.x (xx.xx) xx.x (xx.xx)
Median xx.x xx.x xx.x
Min, max (xx.x, xx.x) (xx.x, xx.x) (xx.x, xx.x)
Abbreviation: SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage calcula tions.
b. n = Number of subjects with the specified characteristic.
c. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
d. Negative N -binding antibody result at Visit 1, negative NAAT result at Visit 1, and no medical history of COVID -19.
e. Number of subjects who have 1 or more comorbidities that increase the risk of severe COVID -19 disease: defined as subjects who had at least one of the Charlson
comorbidity index category or BMI ≥95th percentile.
f. Obese is defined as BMI ≥95th percentile from the growth chart. Refer to the CDC growth charts at https://www.cdc.gov/growthcharts/html_charts/bmiagerev.ht m.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM) ADSL. COUNTRY =”USA” ADSL. ETHNICN =2
ADSL. ETHNICN =3
ADSL. COVBLST= ”POS”
ADSL.AGETR0 1 ADSL. COVBLST= ”NEG”
ADSL. COVBLST= ” ”
ADSL. COMBODFL= ”Y”
ADSL. COMBODFL= ”N”
ADSL. OBESEFL= ”Y”
ADSL. OBESEFL= ”N”
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Page 37 of 72 (Data Cutoff date: d dMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
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Page 38 of 72 Mock Table 2
Disposition of All Randomized Subjects – Phase 2/3 Subjects 12 Through 15 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo Total
(Na=xx) (Na=xx) (Na=xx)
b %) nb (%) nb (%)
Randomized x.x) xx (xxx.x) xx (xxx.x)
Not vaccinated xx (xxx x) xx (xxx x) xx (xxx.x)
Original blinded placebo -controlled follow -up period
Vaccinated xx (xxx x) xx (xxx.x) xx (xxx.x)
Dose 1 xx (xxx.x) xx (xxx.x)
Dose 2
Discontinued from original blinded placebo -controlled vaccination periodc
Reason for discontinuation
Adverse event xx (xxx.
Withdrawal by subject
Physician decision
Death
Pregnancy
Other xx (xxx.x) xx (xxx x)
Unblinded before 1 -month post –Dose 2 visit xx (
Completed 1 -month post –Dose 2 visit xx (
Withdrawn from the study
Withdrawn after Dose 1 and before Dose 2
Withdrawn after Dose 2 and before 1 -month post–Dose 2 visit
Withdrawn after 1 -month post–Dose 2 visit
Reason for withdrawal from the study
Adverse event
ADSL.TRT0 1P ADSL. RANDFL eq 'Y' and
ADSL. AGEGR4N eq 1 ADSL. RANDFL="Y" and
ADSL. AGEGR4N =1
ADSL. RANDFL eq 'Y' and ( ADSL. VAX101DT eq . and ADSL. VAX102DT eq .
and ADSL. VAX10UDT=. and ADSL. VAX201DT eq . and ADSL. VAX202DT eq .)
ADSL. RANDFL eq 'Y' and ADSL.AGEGR4N=1 and (ADSL. VAX101DT ne . or ADSL. VAX102DT ne .)
ADSL. RANDFL eq 'Y' and ADSL.AGEGR4N=1 and ADSL. VAX101DT ne .
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=26 and ADDS. EOTDCDT ne . and
ADDS. dsdecodn not in (. 2) and ( ADSL. VAX101DT ne . or ADSL. VAX102DT ne .)
and ( ADSL. unblnddt=. or ADSL. eotdcdt <ADSL. unblnddt) ADSL. RANDFL eq 'Y' and ADSL. VAX102DT ne . and ( ADSL. VAX102DT< ADSL. UNBLNDDT or ADSL. UNBLNDDT=.)
ADSL. RANDFL eq 'Y' and ADSL.AGEGR4N=1
and ADSL. UNBLNDDT ne . and
(ADSL. UNBLNDDT<= ADDS. M1PD2DT or
ADDS. M1PD2DT=.) 1. Subset below section with criteria:
ADSL.RANDFL eq 'Y' and ADDS.DSPHASEN=26
and ADDS.EOTDCDT ne . and ADDS.dsdecodn not
in (. 2) and (ADSL.VAX101DT ne . or
ADSL.VAX102DT ne .) and (ADSL.unblnddt=. or
ADSL.eotdcdt<ADSL.unblnddt)
2. Report by each ADDS. DSDECOD.
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and
ADDS. dsdecodn not in (. 2) and ( ADSL. VAX101DT ne . or ADSL. VAX102DT ne .) and
(ADSL. unblnddt=. or ADSL. eosdcdt< ADSL. unblnddt) and ADSL. EOSDCDT ne
ADSL. EOTXDCDT
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
ADSL. vax101dt ne . and (( ADSL. vax101dt<= ADDS. astdt and ADSL. vax102dt eq .) or ADSL. vax101dt<= ADDS. astdt
< ADSL. vax102dt) and ( ADSL. unblnddt=. or ADSL. eosdcdt< ADSL. unblnddt) and ADSL. EOSDCDT ne
ADSL. EOTXDCDT ADSL. RANDFL eq 'Y' and
((ADDS. DSPHASEN=26 and
ADDS. dsdecodn=2) and
(ADSL. unblnddt=. or
ADDS. astdt< ADSL. unblnddt)
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
ADSL. vax101dt ne . and ADSL. vax102dt ne . and ( ADSL. vax102dt <= ADDS. astdt and ( ADDS. M1PD2DT eq . or
ADDS. astdt< ADDS. M1PD2DT)) and (ADSL. unblnddt=. or ADSL. eosdcdt< ADSL. unblnddt) and ADSL. EOSDCDT ne
ADSL. EOTXDCDT
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
ADSL. vax101dt ne . and ADSL. vax102dt ne . and ADDS. M1PD2DT ne . and ADDS. M1PD2DT le ADDS. astdt and
(ADSL. unblnddt=. or ADSL. eosdcdt< ADSL. unblnddt) and ADSL. EOSDCDT ne ADSL. EOTXDCDT 1. Subset below section with criteria: ADSL.RANDFL eq 'Y' and
ADDS.DSPHASEN=31 an d ADSL.EOSDCDT ne . and ADDS.dsdecodn not in
(. 2) and (ADSL.VAX101DT ne . or ADSL.VAX102DT ne .) and (ADSL.unblnddt=. or ADSL.eosdcdt<ADSL.unblnddt) and ADSL.EOSDCDT
ne ADSL.EOTXDCDT
2. Report by each ADDS. DSDECOD.
090177e198d550b8\Final\Final On: 10-Dec-2021 03:00 (GMT)
FDA-CBER-2022-5812-0492199
Study C4591001 Analysis Data Reviewer’s Guide
Page 39 of 72 Death xx (xxx.x) xx (xxx.x)
Pregnancy xx (xxx.x) xx (xxx.x) xx (xxx.x)
Other (xxx.x) xx (xxx.x)
Open -label follow -up period
Originally randomized to BNT162b2
Received Dose 2/unplanned dose
Completed 1 -month post –Dose 2 visit
Completed 6 -month post –Dose 2 visit
Withdrawn from the study
Withdrawn before 6 -month post–Dose 2 visit
Withdrawn after 6 -month post–Dose 2 visit
Reason for withdrawal from the study
Adverse event
Withdrawal by subject
Physician decision
Death xx (xxx x)
Pregnancy
Other
Originally randomized to placebo
Withdrawn from the study after unblinding and b
Received Dose 3 (first dose of BNT162b2 [30 µg
Received Dose 4 (second dose of BNT162b2 [30 µg])
Discontinued from open -label vaccination periodd
Reason for disc cination period
Adverse eve
Other
ADSL. RANDFL eq 'Y' and ( ADSL. UNBLNDDT ne . or ADSL. vax201dt ne .) and index( ADSL. arm,'BNT')
ADSL. RANDFL eq 'Y' and and (ADSL. UNBLNDDT ne . or ADSL.VAX201DT NE .) and index( ADSL. arm,'BNT') and
(ADSL. VAX102DT>= ADSL. UNBLNDDT) or (index( ADSL. VAX10u,'BNT') and ADSL. VAX10UDT>= ADSL. UNBLNDDT )
ADSL. RANDFL eq 'Y' and (( ADDS. DSPHASEN=26 and ADDS. dsdecodn=2)) and ( ADSL. unblnddt ne . and
ADDS. astdt>= ADSL. unblnddt) and index( ADSL. arm,'BNT')
ADSL. RANDFL eq 'Y' and ADSL. vax101dt ne . and ADSL. vax102dt ne . and ADDS. M6PD2DT ne . and
(ADSL. UNBLNDDT ne . or ADSL. vax201dt ne .) and index( ADSL. arm,'BNT')
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and ( ADSL. VAX101DT
ne . or ADSL. VAX102DT ne .) and ( ADSL. unblnddt ne . and ADSL. eosdcdt>= ADSL. unblnddt) and index( ADSL. arm,'BNT')
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
(ADSL. VAX101DT ne . or ADSL. VAX102DT ne .) and ( ADDS. M6PD2DT=. or ADDS. M6PD2DT> ADDS. astdt) and
(ADSL. unblnddt ne . and ADSL. eosdcdt>= ADSL. unblnddt) and index( ADSL. arm,'BNT')
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
ADSL. vax101dt ne . and ADSL. vax102dt ne . and ADDS. M6PD2DT ne . and ADDS. M6PD2DT le ADDS. astdt and
(ADDS. unblnddt ne . and ADSL. eosdcdt>= ADSL. unblnddt) and index( ADSL. arm,'BNT')
1. Subset below section with criteria: ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne .
and ADDS. dsdecodn not in (. 2) and ( ADSL. VAX101DT ne . or ADSL. VAX102DT ne .) and ( ADSL. unblnddt ne .
and ADSL. eosdcdt>=ADSL. unblnddt) and index( ADSL. arm,'BNT')
2 Report by each ADDS. DSDECOD.
ADSL. RANDFL eq 'Y' ADSL.AGEGR4N=1 and ( ADSL. UNBLNDDT ne . or ADSL. vax201dt ne .) and
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2)
and ( ADSL. VAX201DT=. and ADSL. VAX202DT=.) and ( ADSL. unblnddt ne . and
ADSL. eosdcdt>=ADSL. unblnddt) and index( ADSL. armcd,'PLACEBO') ADSL. RANDFL eq 'Y' and
index( ADSL. VAX201,'BNT')
and
index( ADSL. armcd,'PLACEBO') ADSL. RANDFL eq 'Y' and
index( ADSL. VAX202,'BNT')
and index( ADSL. armcd,'PLACEBO')
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=7 and
ADSL. EOTXDCDT ne . and ADDS. dsdecodn not in (. 2)
and ADSL. vax201dt ne . and
index( ADSL. armcd,'PLACEBO') 1. Subset below section with criteria: ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=7 and
ADSL. EOTXDCDT ne . and ADDS. dsdecodn not in (. 2) and ADSL. vax201dt ne . and
index( ADSL. armcd,'PLACEBO')
2. Report by each ADDS. DSDECOD.
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Study C4591001 Analysis Data Reviewer’s Guide
Page 40 of 72 Completed 1 -month post –Dose 4 visit
Withdrawn from the study
Withdrawn after Dose 3 and before Dose 4
Withdrawn after Dose 4 and before 1 -month post–Dose 4 visit
Withdrawn after 1 -month post–Dose 4 visit
Reason for withdrawal from the study
Adverse event .x)
Withdrawal by subject .x)
Physician decision xx (xxx.x) xx (xxx.x)
Death
Pregnancy
Other
Note: Subjects who were randomized but did not sign an informed co
included in any analysis population.
Note: Because of a dosing error, Subject[s] C4591001 xxxx xxxxx [and C4591001 xxxx xxxxxx] received an additional dose of BNT 162b2 (30 µg) at an unscheduled visit
e tions.
d
m ond dose of BNT162b2 [30 μg])
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:M )
(Data Cutoff date: ddMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=7 and ADDS. dsdecodn=2 and
index( ADSL. armcd,'PLACEBO')
1. Subset below section with criteria: ADSL. RANDFL eq 'Y' and
ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not
in (. 2) and ( ADSL. VAX201DT ne . or ADSL. VAX202DT ne .) and
((ADSL. unblnddt ne . and ADSL. eosdcdt>= ADSL. unblnddt) or
ADSL. eosdcdt= ADSL. eotxdcdt) and index( ADSL. armcd,'PLACEBO')
2. Report by each ADDS. DSDECOD. ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
ADSL. vax201dt ne . and (( ADSL. vax201dt<= ADDS. astdt and ADSL. vax202dt eq .) or
ADSL. vax201dt<= ADDS. astdt < ADSL. vax202dt) and (( ADSL. unblnddt ne . and
ADSL. eosdcdt>=ADSL. unblnddt) or ADSL. eosdcdt= ADSL. eotxdcdt) and index( ADSL. armcd,'PLACEBO')
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
ADSL. vax201dt ne . and ADSL. vax202dt ne . and ( ADSL. vax202dt <= ADDS. astdt and ( ADDS. M1PX2DT eq . or
ADDS. astdt< ADDS. M1PX2DT)) and (( ADSL. unblnddt ne . and ADSL. eosdcdt>= ADSL. unblnddt) or
ADSL. eosdcdt= ADSL. eotxdcdt) and index( ADSL. armcd,'PLACEBO')
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne . and ADDS. dsdecodn not in (. 2) and
ADSL. vax201dt ne . and ADSL. vax202dt ne . and ADDS. M1PX2DT ne . and ADDS. M1PX2DT le ADDS. astdt
and (( ADSL. unblnddt ne . and ADSL. eosdcdt>= ADSL. unblnddt) or ADSL. eosdcdt= ADSL. eotxdcdt) and
index( ADSL. armcd,'PLACEBO')
ADSL. RANDFL eq 'Y' and ADDS. DSPHASEN=31 and ADSL. EOSDCDT ne .
and ADDS. dsdecodn not in (. 2) and ( ADSL. VAX201DT ne . or
ADSL. VAX202DT ne .) and (( ADSL. unblnddt ne . and
ADSL. eosdcdt>=ADSL. unblnddt) or ADSL. eosdcdt= ADSL.eotxd cdt) and
index( ADSL. armcd,'PLACEBO')
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Study C4591001 Analysis Data Reviewer’s Guide
Page 41 of 72 Mock Table 3
Follow -up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age – Safety P
Vaccine Group (as Administered)
BNT162b2 (30 μg) Placebo Total
(Na=xx) (Na=xx) (Na=xx)
nb (%) nb (%) nb (%)
Original blinded placebo -controlled follow -up period
<2 Months xx (xx.x) xx (xx.x) xx (xx.x)
≥2-<4 Months x (xx.x) xx (xx.x) xx (xx.x)
≥4-<6 Months xx (xx.x) xx (xx.x) xx (xx.x)
≥6 Months xx (xx.x) xx (xx.x) xx (xx.x)
Mean (SD) xx.x (xx.xx) xx.x (xx.xx) xx.x (xx.xx)
Median xx.x xx.x xx.x
Min, max (xx.x, xx.x) (xx.x, xx.x) (xx.x, xx.x)
Total follow -up period from Dose 2 to cutoff date
<2 Months xx (xx x)
≥2-<4 Months
≥4-<6 Months xx (xx.x)
≥6-<8 Months xx (xx x)
≥8-<10 Months
≥10 Months xx (xx.x)
Mean (SD) xx.x (xx.xx)
Median xx.x
Min, max (xx.x, xx.x)
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage calculat ions.
b. n = Number of subjects with the specified characteristic.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: abcdefgh Table Generation: DDMMMYYYY (HH:MM)
(Data Cutoff date: ddMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADSL.SAF FL eq 'Y' and ADSL. AGEGR4N eq 1
ADSL.TRT0 1A
ADSL.AGEGR4N=1 and .<ADSL.FUP2CA2N<=2
2<ADSL.FUP2CA2N <=4
4<ADSL.FUP2CA2N <=6
6<ADSL. FUP2CA2N
2<ADSL.FUP2CA1N<=4
.<ADSL.FUP2CA1N<=2
4<ADSL.FUP2CA1N<=6
6<ADSL.FUP2CA1N<=8
8<ADSL.FUP2CA1N<=10
10<ADSL.FUP2CA1N
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Study C4591001 Analysis Data Reviewer’s Guide
Page 42 of 72 Mock Table 4
Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date – Blinded Placebo -Controlled Follow -up Period
– Phase 2/3 Subjects 12 Through 15 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
(Na=xxx, TEb =xxx.x) (Na=xxx, TEb =xxx.x)
Adverse Event nc (%) IRd (95% CIc) nc (%) IRd (95% CIc)
Any event x x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Relatedf xx (xx.x) x.x (xx.x, xx.x) xx (xx.x) x x (xx x xx x)
Severe xx (xx.x) x.x (xx.x, xx.x) xx (xx.x)
Life-threatening x.x) ( ( ) ( x.x)
Any serious adverse event xx (xx.x) x.x)
Relatedf x.x) ( , ) ( ) ( , x.x)
Severe xx (xx.x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Life-threatening xx (xx x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Any nonserious adverse event x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Relatedf xx (xx.x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Severe (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Life-threatening (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Any adverse event leading to withdrawal xx (xx.x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Relatedf xx (xx.x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Severe xx (xx.x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Life-threatening x (xx.x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
Death xx (xx.x) x.x (xx.x, xx.x) xx (xx.x) x.x (xx.x, xx.x)
a. N = number of subjects in the specified group . This value is the denominator for the percentage calculations .
b. TE = total exposure time in 100 person -years across all subjects in the specified group. Exposure time for a subject is the time from Dose 1 to the end of
the blinded follow -up period. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specifie d event category. For “any event,” n = number of subjects reporting at least 1
occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person- years (PY) across all subjects in the specified
group.
e. 2 -sided CI based on Poisson distribution.
f. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
(Data Cutoff date: ddMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADSL.SAFFL="Y" and
ADSL.AGEGR4N=1
ADSL.TRT01A
SUM(ADSL.FUP1UNB)/(356.25*100)
ADAE.AECAT="ADVERSE EVENT" and ADAE.VPHASEN >0 and ADSL.SAFFL="Y" and
ADSL.AGEGR4N eq 1 and ( .<ADSL.VAX101DT<=ADAE.ASTDT <= ADSL.BDCSRDT )
ADAE.ATOXGRN=3
upcase(ADAE.AREL)=”RELATED”
ADAE.ATOXGRN=4
ADAE.AESER=”Y”
ADAE.AESER in (‘N’,’ ’)
Z
ADAE.AESUBJDC = 'Y' or ADAE AEACN
= 'DRUG WITHDRAWN'
ADAE.AEOUT=’FATAL
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Study C4591001 Analysis Data Reviewer’s Guide
Page 43 of 72 Mock Table 5
Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to 6 Months After Dose 2 – Subjects With at Least
6 Months of Follow- up Time After Dose 2 – Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who Originally
Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg)
(Na=xx)
Adverse Event nb (%)
Any event xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx x) (xx x xx x)
Severe
Life-threatening
Any serious adverse event xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx.x) (xx.x, xx.x)
Severe xx (xx.x) (xx.x, xx.x)
Life-threatening xx (xx.x) (xx.x, xx.x)
Any nonserious adverse event xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx.x) (xx.x, xx.x)
Severe (xx.x) (xx.x, xx.x)
Life-threatening (xx.x) (xx.x, xx.x)
Any adverse event leading to withdrawal xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx.x) (xx.x, xx.x)
Severe xx (xx.x) (xx.x, xx.x)
Life-threatening xx (xx.x) (xx.x, xx.x)
Death xx (xx.x) (xx.x, xx.x)
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For “any event,” n = number o f subjects reporting at least 1
occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson met hod.
d. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
ADSL.TRT01A
ADSL.SAFFL="Y" and ADSL.TRT01AN=8 and
ADSL.DS3KFL="Y" and ADSL.AGEGR4N=1
upcase(ADAE.AREL)=”RELATED”
ADAE.AECAT="ADVERSE EVENT" and ADSL.SAFFL="Y" and (ADAE.ASTDT
NE . and ADSL.V02OBDT >= ADAE.ASTDT) and ADAE.VPHASEN >0 and
ADSL.TRT01AN=8 and ADSL.DS3KFL="Y"
ADAE.ATOXGRN=3
ADAE.ATOXGRN=4
ADAE.AESER=”Y”
ADAE.AESER IN (‘N’,’ ’)
Z
ADAE.AESUBJDC = 'Y' or ADAE.AEACN
= 'DRUG WITHDRAWN'
ADAE.AEOUT=’FATAL
090177e198d550b8\Final\Final On: 10-Dec-2021 03:00 (GMT)
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Study C4591001 Analysis Data Reviewer’s Guide
Page 44 of 72 (Data Cutoff date: ddMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
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Study C4591001 Analysis Data Reviewer’s Guide
Page 45 of 72 Mock Table 6
Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff Date (DDMMMYYYY) – Open -Label Follow -up
Period – Subjects Who Originally Received Placebo and Then Received BNT162b2 After Unblinding – Phase 2/3 Subjects 12
Through 15 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg)
(Na=xxx, TEb =xxx.x)
Adverse Event nc (%) IRd (95% CIc)
Any event xx (xx.x) x.x (xx.x, xx.x)
Relatedf xx (xx.x) x.x
Severe xx (xx.x) x.x (xx.x, xx.x)
Life-threatening xx (xx.x) x.x
Any serious adverse event xx (xx.x) x.x
Relatedf xx (xx.x) x.x
Severe xx (xx.x) x x (xx x xx x)
Life-threatening xx (xx.x)
Any nonserious adverse event xx (xx.x)
Relatedf ( x) x.x (xx.x, xx.x)
Severe x) x.x (xx.x, xx.x)
Life-threatening xx (xx.x) x.x (xx.x, xx.x)
Any adverse event leading to withdrawal xx (xx.x) x.x (xx.x, xx.x)
Relatedf xx (xx.x) x.x (xx.x, xx.x)
Severe xx (xx.x) x.x (xx.x, xx.x)
Life-threatening xx (xx.x) x.x (xx.x, xx.x)
Death xx (xx.x) x.x (xx.x, xx.x)
Note: Dose 3 = First dose of BNT162b2 (30 μg).
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations .
b. TE = total exposure time in 100 person -years across all subjects in the specified group. Exposure time for a subject is the time from Dose 3 to data cutoff
date. This value is the denominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For “any event,” n = number o f subjects reporting at least 1
occurrence of any event.
d. Incidence rate (IR) is calculated as number of subjects reporting the event/total exposure time in 100 person- years (PY) across all subjects in the specified
group.
e. 2 -sided CI based on Poisson distribution.
f. Assessed by the investigator as related to investigational product.
ADSL.TRT0 2A
ADSL.SAFFL="Y" and ADSL.TRT01AN=9 and
ADSL.TRT02AN=8 and ADSL.VAX201DT > . and
ADSL.X1CSRDT > . and ADSL.AGEGR4N=1
SUM(ADSL.FPX1CUT)/(356.25*100)
upcase(ADAE.AREL)=”RELATED”
ADAE.AECAT="ADVERSE EVENT" and ADAE.VPHASEN ge 5 and ADAE.VPHASEN ne 99
and ADSL.SAFFL="Y" and ADSL.AGEGR4N eq 1 and (.<ADSL.VAX201DT<=ADAE.ASTDT
<= ADSL.X1CSRDT ) and ADSL.TRT01AN=9 and ADSL.TRT02AN=8
ADAE.ATOXGRN=3
ADAE.ATOXGRN=4
ADAE.AESER=”Y”
ADAE.AESER in (‘N’,’ ’)
ADAE.AESUBJDC = 'Y' or ADAE.AEACN
= 'DRUG WITHDRAWN'
ADAE.AEOUT=’FATAL
090177e198d550b8\Final\Final On: 10-Dec-2021 03:00 (GMT)
FDA-CBER-2022-5812-0492206
Study C4591001 Analysis Data Reviewer’s Guide
Page 46 of 72 PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
(Data Cutoff date: ddMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC) /C4591001/abcd_XNNN
090177e198d550b8\Final\Final On: 10-Dec-2021 03:00 (GMT)
FDA-CBER-2022-5812-0492207
Study C4591001 Analysis Data Reviewer’s Guide
Page 47 of 72 Mock Table 7
Number (%) of Subjects Reporting at Least 1 New Adverse Event After the EUA Snapshot, From Dose 1 to Unblinding
Date – Blinded Placebo -Controlled Follow- up Period – Phase 2/3 Subjects 12 Through 15 Years of Age – Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
(Na=xx) (Na=xx)
Adverse Event nb (%) (95% CIc) nb (%) (95% CIc)
Any event (xx.x) (xx.x, xx.x) xx
Relatedd xx (xx.x) (xx.x, xx.x) xx
Severe xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Life-threatening xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Any serious adverse event xx
Relatedd xx
Severe xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Life-threatening xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Any nonserious adverse event xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Severe (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Life-threatening (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Any adverse event leading to withdrawal xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Severe xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Life-threatening xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Death xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Abbreviation: EUA = emergency use authorization.
a. N = number of subjects in the specified group, subjects who end of study before EUA snapshot are not included. This value is the denominator for the
percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For “any event,” n = number o f subjects reporting at least 1
occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
ADSL.TRT01A
ADSL.SAFFL="Y" and (ADSL.EOSDCDT gt
input(“13MAR2021”, date9.) or
ADSL.EOSDCDT =. ) and ADSL.AGEGR4N=1
upcase(ADAE.AREL)=”RELATED”
ADAE.AECAT="ADVERSE EVENT" and ADAE.DATCHGFL= “Y” and ADAE.VPHASEN >0 and
ADSL.SAFFL="Y" and ADSL.AGEGR4N eq 1 and (.<ADSL.VAX101DT<=ADAE.ASTDT <=
ADSL.BDCSRDT )
ADAE.ATOXGRN=3
ADAE.ATOXGRN=4
ADAE.AESER=”Y”
ADAE.AESER IN (‘N’,’ ’)
ADAE.AESUBJDC = 'Y' or ADAE.AEACN
= 'DRUG WITHDRAWN'
ADAE.AEOUT=’FATAL
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Study C4591001 Analysis Data Reviewer’s Guide
Page 48 of 72 d. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
(Data Cutoff date: ddMmmY YYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
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Page 49 of 72 Mock Table 8
Number (%) of Subjects Reporting at Least 1 New Serious Adverse Event After the EUA Snapshot, From Dose 1 to
Unblinding Date, by System Organ Class and Preferred Term – Blinded Placebo -Controlled Follow -up Period – Phase
2/3 Subjects 12 Through 15 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg) Placebo
(Na=xx) (Na=xx)
System Organ Class
Preferred Term nb (%)
(95% CIc) nb (%
<Any event> xx (xx.x) (xx.x, xx.x) xx (xx
<System organ class> xx (xx.x) (xx x, xx.x) xx (xx.x) (xx.x, xx.x)
<Preferred term> xx (xx.x , xx.x)
<Preferred term> xx (xx.x , xx.x)
<System organ class> xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
<Preferred term> xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
<Preferred term> xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Abbreviation: EUA = emergency use authorization.
Note: MedDRA (v24.0) coding dictionary applied.
Note: Adverse events that occurred on the day of or after subjects were unblinded are excluded from this summary.
a. N = number of subjects in the specified group, subjects who end of study before EUA snapshot are not included. This v alue is the deno minator for
the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event. For “any event,” n = number of subjects reporting at least 1
occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
PFIZER CONFIDENTIAL SDTM Creation: DDMMYYY (HH:MM) Source Data: ADSL Table Generation: DDMMYYY (HH:MM)
(Data Cutoff date: ddMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADAE.AEBODSYS
ADSL.TRT01A
ADSL.SAFFL="Y" and (ADSL.EOSDCDT gt
input(“13MAR2021”, date9.) or
ADSL.EOSDCDT =. ) and ADSL.AGEGR4N=1
ADAE.AEDECOD
ADAE.AECAT="ADVERSE EVENT" and ADAE.DATCHGFL=”Y” and ADAE.VPHASEN >0
and ADSL.SAFFL="Y" and and ADAE.AESER=”Y” and ADSL.AGEGR4N eq 1 and
(.<ADSL.VAX101DT<=ADAE.ASTDT <= ADSL.BDCSRDT )
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Study C4591001 Analysis Data Reviewer’s Guide
Page 50 of 72 Mock Table 9
Number (%) of Subjects Reporting at Least 1 New Adverse Event After the EUA Snapshot,
From Dose 1 to 6 Months After Dose 2 – Subjects With at Least 6 Months of Follow -up Time After Dose 2 –
Phase 2/3 Subjects 12 Through 15 Years of Age (Subjects Who Originally Re ceived BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
(Na=xx) (Na=xx)
Adverse Event nb (%) (95% CIc) nb (%) (95% CIc)
Any event xx (xx.x) (xx.x, xx.x) x
Relatedd xx (xx.x) (xx.x, xx.x) x ( , )
Severe xx (xx.x) (xx x xx x) xx (xx x) (xx x xx x)
Life-threatening xx (xx.x)
Any serious adverse event xx (xx.x)
Relatedd xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Severe xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Life-threatening xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Any nonserious adverse event .x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Severe (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Life-threatening (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Any adverse event leading to withdrawal xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Relatedd xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Severe xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Life-threatening xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Death xx (xx.x) (xx.x, xx.x) xx (xx.x) (xx.x, xx.x)
Abbreviation: EUA = emergency use authorization.
a. N = number of subjects in the specified group. This value is the denominator for the percentage calculations.
b. n = Number of subjects reporting at least 1 occurrence of the specified event category. For “any event,” n = number of subjects reporting at least 1
occurrence of any event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
d. Assessed by t he investigator as related to investigational product.
ADSL.TRT01A
ADSL.SAFFL="Y" and ADSL.TRT01AN=8 and
ADSL.DS3KFL="Y" and ADSL.AGEGR4N =1
upcase(ADAE.AREL)=”RELATED”
ADAE.AECAT="ADVERSE EVENT" and ADAE.DATCHGFL=”Y” and
ADAE.VPHASEN >0 and ADSL.SAFFL="Y" and (ADAE.ASTDT NE . and
ADSL.V02OBDT >= ADAE.ASTDT) and ADSL.TRT01AN=8 and ADSL.DS3KFL="Y"
ADAE.ATOXGRN=3
ADAE.ATOXGRN=4
ADAE.AESER=”Y”
ADAE.AESER IN (‘N’,’ ’)
Z
ADAE.AESUBJDC = 'Y' or ADAE.AEACN
= 'DRUG WITHDRAWN'
ADAE.AEOUT=’FATAL
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Study C4591001 Analysis Data Reviewer’s Guide
Page 51 of 72 PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
(Data Cutoff date: ddMmmYYYY, Data Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abc d_XNNN
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Page 52 of 72 Mock Table 10
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period
ears of Age and Without Evidence of Infection Prior to 7 Days After Dose 2
– Evaluable Efficacy (7 Days) Population
Vaccine Group (as Random
BNT162b2 (30 µg)
(Na=nn) (N=nn)
n1b Surveillance Timec
(n2d) n1b Surveillance
Timec (n2d) VE (%) (95% CIe)
First COVID -19 occurrence from 7 days after Dose 2
≥7 days after Dose 2 to <2 Months after Dose 2
≥2 Months after Dose 2 to <4 Months xxx ( nnn) xx.x (xx.x, xx.x)
≥4 Months after Dose 2 nnn xxx (nnn) nnn xxx (nnn) xx.x (xx.x, xx.x)
opro
S me
Note: Subjects who had no serological or virological evidence (prior to 7 days after receipt of the last dose) of past SARS -CoV-2 infection (ie, N -binding
antibody [serum] negative at Visit 1 and SARS- CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2 , and had negative NAAT (nasal swab) at any
unscheduled visit prior to 7 days after Dose 2) were included in the analysis.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for the endpoint. Time period for
COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period for the overall row and from start to the end of the range stated for
each time interval. d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: abcdefgh Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY , Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADSL.EVALEFFL="Y" and
ADC19EF.PARAMCD="C19ONST" and
index(upcase(ADC19EF.AVALC), "POS")>0 and ADC19EF.PDRMUPFL="N" and
ADC19EF.ILD27FL="Y" and
ADC19EF.FILOCRFL="Y" and ADC19EF.PDP27FL="Y". and ((not missing (DVSTDT)
and ADT <= DVSTDT) or missing(DVSTDT))
ADSL.EVALEFFL="Y" and
ADC19EF.PDP27FL="Y" and ADSL.AGE GR4N=1
ADSL.TRT01P
(Sum of ADC19EF.AVAL)/365.25/1000 where
ADC19EF.PARAMCD IN ("ST27PD")
(For subgroup the surveillance time will be custom and derived at reporting level for each period)
ADC19EF.PDRMUPFL = "N" AND
ADC19EF.PDP27FL = "Y" AND
ADC19EF.PARAMCD IN ("ST27PD")
AND ADC19EF.AVAL > 0
not missing (ADC19EF.VAX102DT) and ADC19EF.VAX102DT + 7 <=
ADC19EF.ADT < ADC19EF.VAX102DT + 56
not missing (ADC19EF.VAX102DT) and ADC19EF.VAX102DT + 56 <=
ADC19EF.ADT < ADC19EF.VAX102DT + 112
not missing (ADC19EF.VAX102DT) and
ADC19EF.VAX102DT + 112 <= ADC19EF.ADT
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Study C4591001 Analysis Data Reviewer’s Guide
Page 53 of 72 Mock Table 11
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period – Subjects
12 Through 15 Years of Age and With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days)
Population
Programming note : for tables 11 : remove footnote “ Note: Subjects had no serological.. ”
Follow same annotations as table 10 except remove ADC19EF. PDP27FL = "Y" from subset condition as this table is for subject W ith or
Without Evidence of Infection Prior to 7 Days After Dose 2
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Study C4591001 Analysis Data Reviewer’s Guide
Page 54 of 72 Mock Table 12
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2, by Subgroup
– Blinded Placebo -Controlled Follow- up Period
– Subjects 12 Through 15 Years of Age and Without Evidence of Infection Prior to 7 Days After Dose 2
– Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized)
BNT162b2 (30 µg) Placebo
(Na=nnn) (Na=nnn)
Efficacy Endpoint
Subgroup n1b Surveillance Timec
(n2d) n1b Surveillance
Timec (n2d) VE (%)
(95% CIe)
First COVID -19 occurrence f 7 d ft D 2
Overall xxx (xx) xx.x (xx.x, xx.x)
Sex
Male xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Female ( ) ( x) xx.x (xx.x, xx.x)
Race
White xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Black or xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
All others xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
American Indian or Alaska native xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Asian xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Native Hawaiian or other Pacific Islander xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Multiracial xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Not reported xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Ethnicity
Hispanic/Latino xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Non -Hispanic/non -Latino xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Not reported xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Country
USA xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
ADSL.EVALEFFL="Y" an d
ADC19EF.PDP27FL="Y" and
ADSL.AGEGR4N=1
ADSL.TRT01P
ADSL.EVALEFFL="Y" and
ADC19EF.PARAMCD="C19ONST" and
index (upcase (ADC19EF.AVALC), "POS")>0 and ADC19EF.PDRMUPFL="N" and
ADC19EF.ILD27FL="Y" and
ADC19EF.FILOCRFL="Y" and ADC19EF.PDP27FL="Y". and ((not missing
(DVSTDT) and adt <= DVSTDT) or missing
(DVSTDT))
(Sum of ADC19EF.AVAL)/365.25/1000 where
ADC19EF.PARAMCD IN ("ST27PD")
ADC19EF.PDRMUPFL = "N" AND
ADC19EF.PDP27FL = "Y" AND ADC19EF.PARAMCD IN ("ST27PD")
AND ADC19EF.AVAL > 0
ADSL.SEX
ADSL.ARACE
ADSL.ETHNIC
ADSL.COUNTRY
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Page 55 of 72 Comorbiditiesf
Yes xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
No xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Obeseg
Yes xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
No xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Prior SARS -CoV-2 status
Positive at baselineh xx xxx (xx) xx xxx (xx) xx x (xx.x, xx.x)
Positive N -binding only x (xx.x, xx.x)
Positive NAAT only x (xx.x, xx.x)
Positive NAAT and N -binding (xx.x, xx.x)
Negative at baseline but positive
Dose 2i (xx.x, xx.x)
Negative prior to 7 days after Dos (xx.x, xx.x)
Unknown (xx.x, xx.x)
Abbreviatio
SARS -CoV-2 = severe acute respirato
Note: Subjects who had no serological or virological evidence (prior to 7 days after receipt of the last dose) of past SARS -CoV-2 infection (ie, N -binding
antibody [serum] negative at Visit 1 and SARS- CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2 and had negative NAAT (nasal swab) at any
unscheduled visit prior to 7 days after Dose 2) were included in the analysis.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for the endpoint. Time period for COVID -
19 case accrual is from 7 days after Dose 2 to the end of the surveillance period .
d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
f. Comorbidities are defined as having at least one of the Charlson comorbidity index category or obesity (BMI ≥95th percentile).
g. Obese is defined as BMI ≥95th percentile from the growth chart. Refer to the CDC growth charts at
https://www.cdc.gov/growthcharts/html_charts/bmiagerev.htm.
h. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
i. Negative N -binding antibody result and negative NAAT result at Visit 1, positive NAAT result at Visit 2 or at unscheduled visit, if any, prior to 7 days
after Dose 2.
j. Negative N -binding antibody result at Visit 1, negative NAAT result at Visit 1 and Visit 2, and negative NAAT result at unscheduled visit, if any, prior to 7
days after Dose 2.
If ADSL.COMBODFL=” Y” or ADSL.
OBESEFL="Y" then “Yes” else “No”
If ADSL. OBESEFL="Y" then
“Yes” else “No”
ADC19EF.VRBLNGFL='N' or ADC19EF.CRD1NGFL='N' or ADC19EF.C19ILHFL="Y" or IE.
ADC19EF.VRBLNGFL='N' or ADC19EF.CRD1NGFL='N' or ADC19EF.C19ILHFL="Y" or IE.
IESTRESC='Y' and (ADSL.NIGV1FL = "N" and ADSL.NAATNFL ne "N")
ADC19EF.VRBLNGFL='N' or ADC19EF.CRD1NGFL='N' or ADC19EF.C19ILHFL="Y" or IE. IESTRESC='Y' and
(ADSL.NIGV1FL ne "N" and ADSL.NAATNFL = "N")
ADC19EF.VRBLNGFL='N' or ADC19EF.CRD1NGFL='N' or ADC19EF.C19ILHFL="Y" or IE. IESTRESC='Y' and
(ADSL.NIGV1FL = "N" and ADSL.NAATNFL = "N")
ADC19EF.VRBLNGFL='Y' and ADC19EF.CRD1NGFL='Y' and (ADC19EF.PARAMCD in ("NAATRAD",
“RTCOV2NS”, “C19ONST”) and ADC19EF.AVALC="POS" and ADC19EF.VAX101DT ^=. and
ADC19EF.VAX102DT ^=. and ADC19EF.VAX101DT < ADC19EF.ADT < sum (ADC19EF.VAX102DT,7))
ADC19EF.PDP27FL="Y
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Study C4591001 Analysis Data Reviewer’s Guide
Page 56 of 72 PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: abcdefgh Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
Programming note:
1) Remove any rows with zero counts if present in both the treatment groups. If n1 is zero across both placebo and bnt then delete that row in the table. This applies to all the similar tables in the document.
2) Prior Infection status rows (Prior SARS -CoV-2 Status and subrows) will be only part of 7 days post dose 2, Eval efficacy population, Dose 2 All -
Available population With or Without evidence of infection tables. This section is to be presented only for table 13. Add ‘unknown’ row if
there are subjects with unclassified status due to missing test.
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Study C4591001 Analysis Data Reviewer’s Guide
Page 57 of 72 Mock Table 13
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2, by Subgroup – Blinded Placebo -Controlled Follow -up
Period – Subjects 12 Through 15 Years of Age and With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population
Programming Note: Remove the “Note: Subjects who had no …”.
Follow same annotations as table 12 except remove ADC19EF. PDP27FL = "Y" from subset condi tion as this table is for subject With or Without
Evidence of Infection Prior to 7 Days After Dose 2
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Study C4591001 Analysis Data Reviewer’s Guide
Page 58 of 72 Mock Table 14
Demographic Characteristics – Blinded Placebo -Controlled Follow -up Period – Subjects 12 Through 15 Years of Age
and Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluabl Effic cy (7 D y ) P ul ti
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo Total
(Na=xx) (Na=xx) (Na=xx)
nb (%) nb (%) nb (%)
Sex
Male xx (xxx.x) xx (xxx.x) xx (xxx.x)
Female xx (xxx.x) xx (xxx.x) xx (xxx.x)
Race
White xx (xxx.x) xx (xxx.x) xx (xxx.x)
Black or African American xx (xxx.x) xx (xxx.x) xx (xxx.x)
All others
American Indian or Alaska Native xx (xxx.x) xx (xxx.x) xx (xxx.x)
Asian xx (xxx.x) xx (xxx.x) xx (xxx.x)
Native Hawaiian or other Pacific Islander xx (xxx.x) xx (xxx.x) xx (xxx.x)
Multiracial xx (xxx.x) xx (xxx.x) xx (xxx.x)
Not reported xx (xxx.x) xx (xxx.x) xx (xxx.x)
Ethnicity
Hispanic/Latino xx (xxx.x) xx (xxx.x) xx (xxx.x)
Non -Hispanic/non -Latino xx (xxx.x) xx (xxx.x) xx (xxx.x)
Not reported xx (xxx.x) xx (xxx.x) xx (xxx.x)
Country
USA xx (xxx.x) xx (xxx.x) xx (xxx.x)
Comorbiditiesc
ADSL.EVALEFFL="Y" and
ADC19EF.PDP27FL="Y" and ADSL.AGEGR4N=1
ADSL.TRT01P
ADSL.SEX
ADSL.ARACE
ADSL.ETHNIC
ADSL.COUNTRY
If ADSL.COMBODFL=” Y” or ADSL.
OBESEFL="Y” then “Yes” else “No”
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Page 59 of 72 Yes xx (xxx.x) xx (xxx.x) xx (xxx.x)
No xx (xxx.x) xx (xxx.x) xx (xxx.x)
Obesed
Yes xx (xxx.x) xx (xxx.x) xx (xxx.x)
No xx (xxx.x) xx (xxx.x) xx (xxx.x)
Baseline SARS -CoV-2 status
Positivee xx (xxx.x) xx (xxx.x) xx (xxx.x)
Negativef xx (xxx.x) xx (xxx.x) xx (xxx.x)
Unknown xx (xxx.x) xx (xxx.x) xx (xxx.x)
Age at vaccination (years)
Mean (SD) xx.x (xx.xx) xx.x (xx.xx) xx.x (xx.xx)
Median xx.x xx.x xx.x
Min, max (xx, xx) (xx, xx) (xx, xx)
a. N = number of subjects in the specified group, or the total sample. This value is the denominator for the percentage calculations.
b. n = Number of subjects with the specified characteristic.
c. Number of subjects who have 1 or more comorbidities that increase the risk of severe COVID -19 disease: defined as subjects who had at least
one of the Charlso n comorbidity index category or BMI ≥95th percentile.
d. Obese is defined as BMI ≥95th percentile from the growth chart. Refer to the CDC growth charts at
https://www.cdc.gov/growthcharts/html_charts/bmiagerev.htm.
e. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
f. Negative N -binding antibody result at Visit 1, negative NAAT result at Visit 1, and no medical history of COVID -19.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: abcdefgh Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
Prog ramming note: for without evidence of infection don’t show “Baseline SARS -CoV-2 status section”. Also adjust the footnotes
accordingly.
If ADSL.OBESEFL="Y" then “Yes” else “No”
ADSL.COVBLST
ADSL.AGETR01
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Page 60 of 72 Mock Table 15
Demographic Characteristics – Blinded Placebo -Controlled Follow -up Period – Subjects 12 Through 15 Yea rs of Age and With or
Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population
Follow same annotations as table 14 except remove ADC19EF. PDP27FL = "Y" from subset condition as this table is for subject With or Without
Evidence of Infection Prior to 7 Days After Dose 2
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Study C4591001 Analysis Data Reviewer’s Guide
Page 61 of 72 Appendix II: Analysis plan AE windowing logic
AEs that occurred on the same day of a dose and without detailed AE start time are considered as occurring after dose but not
considered as immediate AEs. An immediate AE is defined as an AE that occurred within 30 minutes (including 30 minutes)
after dose.
AEs without start time and started on the same day of Dose x or AEs (with start time) started on or after the timepoint of dose x
are included in ‘AE’s from dose x to 7 days after dose x’, ‘ AE’s from dose x to 1 months after dose x’ and ‘AE’s from dose x
to 6 months after dose x’ etc. window. Dose x could be Dose 1, Dose 2, Dose 3 ( first dose of BNT162b2 [30 μg]) or Dose 4
(second dose of BNT162b2 [30 μg]) .
ADAE.VPHASE is derived based on AE window per the table below :
VPHASE Comments
Pre-Vaccination Event start before Dose 1 Blinded placebo -
controlled period
Vaccination 1 Event start on or after Dose 1 and before Dose 2 Blinded placebo -
controlled period
Vaccination 2 Event started on or after dose 2 and before or on the day of 1 month follow -up visit
after dose 2 (ADSL .V01DT)
See details in below section for ADSL.V01DT Blinded placebo -
controlled period
Follow Up 1 Event start after the day of 1 month follow -up visit after dose 2 (ADSL.V01DT)
and before or on the day of 6 months follow -up visit after dose 2 (ADSL.V0 2DT)
See details in below section for ADSL.V02DT Blinded placebo -
controlled period
Follow Up 2 Event start after the day of 6 months follow -up visit after dose 2 (ADSL.V02DT)
and before unblinding Blinded placebo -
controlled period
After unblinding and
before Vaccination 3 Event start on or after unblinding (for subje cts unblinded without dose 3) Open -label follow -up
period
Event start on or after unblinding and before dose 3 (for subjects unblinded and take
dose 3) Open -label follow -up
period
Vaccination 3 Event start on or after dose 3 and before dose 4 Open -label follow -up
period
Vaccination 4 Event start on or after dose 4 and before or on 1 month follow -up visit after dose 4
(ADSL.V03DT)
See details in below section for ADSL.V03DT Open -label follow -up
period
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Page 62 of 72 VPHASE Comments
Follow Up 3 Event start after 1 month follow -up visit after dose 4 and before or on the day of 6
month s follow-up visit after dose 4 (ADSL.V04DT)
See details in below section for ADSL.V04DT Open -label follow -up
period
Follow Up 4 Event s tart after the day of 6 month s follow -up visit after dose 4 (ADSL.V04DT) Open -label follow -up
period
For AE’s from dose 1 to 1 month after dose 2 (Blinded placebo- controlled period) :
• Dose 1 start date <= ae start date <= 1 month follow-up date or the day before unblinding which one is earlier
(ADSL.V01DT)
V01DT is the blood sample collected date from visit 3.
If visit 3 blood sample collection date is not available from CO dataset, then use the date of visit 3 from SV dataset.
Else if date of visit 3 is not available, then use date of dose 2 + 35 days
Else if date of dose 2 is not available, then use date of dose 1+ 35 + 23 days
Note: if a subject was unblinded before visit 3 (V01DT), then ADSL.V01DT was reset to the day before unblinding.
ADSL.V01DT=min (V01DT, ADSL.UNBLNDDT -1).
For AE’s from dose 1 to 6 months after dose 2 (Blinded placebo- controlled period) :
• Dose 1 start date <= ae start date <= 6 months follow-up date or the day before unblinding which one is earlier
(ADSL.V02DT) V02DT is the blood sample collected date from visit 4.
If visit 4 blood sample collection date is not available from CO dataset, then use the date of visit 4 from SV dataset.
Else if date of visit 4 from SV dataset is not available, then use date of dose 2 + 189 days
Else if date of dose 2 is not available, then use date of dose 1+ 189 + 23 days
Note: if a subject was unblinded before visit 4 (V02DT), then ADSL.V02 DT was reset to the day before unblinding.
ADSL.V0 2DT=min (V02DT, ADSL.UNBLNDDT -1).
For AE’s from dose 1 to 6 months after dose 2 (Whole study period without considering unblinding):
• Dose 1 start date <= ae start date <= 6 months follow-up date (ADSL.V02OBDT)
V02OBDT is
the blood sample collected date from visit 4.
If visit 4 blood sample collection date is not available from CO dataset, then use the date of visit 4 from SV dataset.
Else if date of visit 4 from SV dataset is not available, then use date of dose 2 + 189 days
Else if date of dose 2 is not available, then use date of dose 1 + 189 + 23 days
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Page 63 of 72
ADSL.V03DT is the date of visit 103 (1-month post dose 4 for follow -up vaccination period) from SV after unblinding.
If date of visit 103 from SV dataset is not avai lable, then use date of dose 4 + 35 days
Else if date of dose 4 is not available, then use date of dose 3 + 35 + 23 days
ADSL.V04DT is the date of visit 104 (6-months post dose 4 for follow -up period) from SV after unblinding.
If date of visit 104 from SV dataset is not available, then use date of dose 4 + 189 days
Else if date of dose 4 is not available, then use date of dose 3 + 189 + 23 days
Appendix III: Handling of Incomplete Dates
Adverse events
Incomplete AE start and stop dates were imputed as follows:
Imputation only applied to partial AE start dates (missing day, missing both month and day). The purpose of imputation was
only for allocating analysis interval on AE summary, the original partial date format was recorded or kept in the data and
listings. No imputation on Diary data from subjects or symptom resolved date from Investigator collected as partial date. No
imputation is carried out for completely missing AE start dates. No imputation is carried out for partial or completely missing
AE stop dates. All information on AE stop date was used for imputation logic check as part of the imputation rules for partial
AE start date.
Pfizer imputation rule applied:
Rules Programming Logic
General rules Imputation only applies to partial AE start dates (missing day, missing both month and day). The purpose of
imputation is only for allocating analysis interval on AE summary, the original partial date format should be
recorded or kept in the data and listings. No imputation on Diary data from subjects or symptom resolved
date from Investigator collected as partial date.
General Pfizer imputation rule applied: For Start date:
- For missing Day: impute Day = first day of the month (01), e.g.
November 1990 is treated as 01NOV1990
- For missing Month and Day: impute Month = first month of the year (JAN), impute Day = first
day of the month (01), e.g. 1990 is treated as 01JAN1990
For Stop date:
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Page 64 of 72 Rules Programming Logic
- For missing Day: impute Day = last day of the month (30 or 31), e.g. November 1990 is
treated as 30NOV1990
- For missing Month and Day: impute Month = first month of the year (DEC), impute Day = last
day of the month (31), e.g. 1990 is treated as 31DEC1990
completely missing
start dates No imputation
completely missing
stop dates No imputation
partial stop dates No imputation
the day portion of
ASTDTM was
initially missing • Apply general imputation first, after general Pfizer imputation rule is applied , compare the month of
the AE start date (ASTDTM) with the month of subsequent doses/vaccinations (EXSTDTC)
• If the start date MONTH and YEAR of (ASTDTM) and any of the subsequent dose dates MONTH and
YEAR of (EXSTDTC) are equal , and the stop date (AENDTM) is later than the dose date (EXSTDTC) ,
whether the stop date (AENDTM) comes from partial or complete dates, or AE stop date is missing then
reset ASTDTM to numeric value of first EXSTDTC of that month.
• Otherwise if the AE start date MONTH and YEAR of (ASTDTM) do not match any month of subsequent
doses/vaccination (EXSTDTC) MONTH and YEAR, or the stop date (AENDTM) comes from partial or
complete dates is earlier than corresponding EXSTDTC , don’t do the second imputation and retain the
first imputation
day and month
portion of ASTDTM
were initially missing • Apply general imputation first, compare the imputed AE start date (ASTDTM) with the dosing dates
(EXSTDTC) in the same calendar year and the AE stop date (AENDTM). If the stop date is earlier than the
earliest dosing date in the same calendar year, the AE start date will remain the first day of the calendar
year. Otherwise, the AE start date (ASTDTM) will be imputed to the earliest dosing date (EXSTDTC) in
that calendar year that is less than the AE stop date (AENDTM ).
Concomitant medications/medical histories
Incomplete CM/MH start and stop dates were imputed as follows:
Imputation applied to partial CM/MH start dates and stop dates (missing day, missing both month and day). For partial start
dates, if missing start day, the first day of the month was used; if missing start month and day, the first month of the year was
used. For partial stop dates, if missing stop day, the last day of the month was used; if missing stop month and day, the las t month
of the year was used.
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Page 65 of 72 Appendix IV: External files used during ADaM dataset creation
The following files were used in the creation of specific ADaM datasets to identify specific subsets of subjects (e.g., phase
1, phase 2, phase 3) as well as categories of medical history data used as comorbidities. A copy of the data included in
these files was combined into a supplementaldatadefinitions.pdf file and is linked to the define.xml package for reference.
ID File Name Comments
Rheumatic report -cci-rheumatic -
06aug2021.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Renal report -cci-renal -30oct2020 .xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Pulmonary report -cci-pulmonary -
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Periph vasc report -cci-periph -vasc-
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Peptic ulcer report -cci-peptic -ulcer -
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Mod sev liver report -cci-mod-sev-
liver-06aug2021.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Mild liver report -cci-mild-liver-
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
MI report -cci-mi-30oct2020 .xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Metastatic
tumour report -cci-metastatic -
tumour -30oct2020 .xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Lymphoma report -cci-lymphoma -
30oct2020 .xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
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Page 66 of 72 ID File Name Comments
Used for ADSL creation to flag the subject with comorbidities (subject level)
Leukemia report -cci-leukemia -
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Hemiplegia report -cci-hemiplegia -
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Diabetes
without
comp report -cci-diabetes -without -
comp -30oct2020 .xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Diabetes
with comp report -cci-diabetes -with-
comp -06aug2021.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Dementia report -cci-dementia -
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
CHF report -cci-chf-30oct2020 .xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Cerebrovascu
lar report -cci- cerebrovascular -
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Any
malignancy report -cci-any-
malignancy -
06aug2021 .xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
AIDS HIV report -cci-aids-hiv-
30oct2020.xlsx Used for ADMH creation to flag the medical history terms with comorbidities
(record level)
Used for ADSL creation to flag the subject with comorbidities (subject level)
Comorbidity
Categories comorbidity -
categories.xlsx Used for ADMH creation to derive the Charlson Comorbidity Index categories by
record level. One MH term may meet multiple Charlson Comorbidity Index
categories.
Phase2 first-c4591001 -360-participants -
enrolled -v1-13aug20 -
update.xlsx Used for ADSL creation to flag the subjects from Phase 2 DS360 subset
Phase3 newlist -c4591001 -6k- Used for ADSL creation to flag the subject s from Phase 3 DS6000 subset
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Page 67 of 72 ID File Name Comments
DS6000 participants -enrolled -v3-
17sep2020.csv
HIV PT 201114 -hiv-preferred -terms.xlsx Used for ADSL creation to flag the HIV Positive subjects
EUA 12-25
Age group c4591001 -subject -list-for-12-
25-immuno -analysis -
27jan2021.xlsx
Used for ADSL creation to flag the subject s from EUA 12-25 subset
BMI scale bmi-12-15-scale .xlsx Used for ADSL creation to flag the obese subjects for 12 -15 years age group
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Page 68 of 72 Appendix V: Surveillance Times
Start -of-surveillance time:
For all VE-related endpoints in this study, the start-of-surveillance times are summarized as follows:
Endpoint's Associated
Participant -Level Population Start -of-Surveillance Time
Evaluable Efficacy (7 days) Dose 2 + 7 days (Day 8 relative to Dose 2)
Dose 2 All-available Efficacy Dose 2 + 7 days (Day 8 relative to Dose 2)
Dose 1 All-available Efficacy Dose 1 (Day 1 relative to Dose 1)
End-of-surveillance time:
The end of surveillance time is then determined considering the following events:
1. When the first COVID-19 case occurs.
2. When the participant’s end of the study occurs due to, e.g. withdrawal or death or trial completion etc.
3. When the participant has first important protocol violation (only for analysis based on the evaluable efficacy population).
4. When the participant is unblinded at the time of being eligible for receipt of BNT162b2 or other reasons.
For all VE-related endpoints in this study, the end of a surveillance period for each participant is summarized below:
Endpoint's Associated Participant -Level
Population End-of-Surveillance Time
Evaluable Efficacy Earliest of event (1), (2), (3) and (4)
Dose 2 All-available Efficacy Earliest of event (1) and (2) and (4)
Dose 1 All-available Efficacy Earliest of event (1) and (2) and (4)
Using the above start and stop times for surveillance time, the overall surveillance time is derived as: End-of-
surveillance time – Start -of-surveillance time + 1
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Page 69 of 72 Appendix VI: Efficacy Flow Charts
1. The flowchart for deriving the COVID-19 cases included below for the first primary endpoints in evaluable efficacy
participants with no serological or virological evidence of past SARS -CoV-2 infection:
The central laboratory NAAT result will be used for the case definition, unless no result is available from the central laboratory,
Evaluable efficacy population (7 days)
N-binding antibody negative at baseline
No virological evidence by NAAT prior to 7
days after receipt of the second dose
Presence of at least 1 of the following symptoms: fever, new or increased
cough, new or increased shortness of breath, chills, new or increased
muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting.
NAAT positive for COVID -19 at central laboratory or acceptable
local test within the date window that symptoms were present
Onset date, ie, the date that first symptom
occurs, is at least 7 days after receipt of the
COVID-19 cases for first primary VE objective
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Page 70 of 72 in which case a local NAAT result may be used if it was obtained using 1 of the following assays:
a. Cepheid Xpert Xpress SARS -CoV-2
b. Roche cobas SARS -CoV-2 real -time RT-PCR test (EUA200009/A001)
c. Abbott Molecular/RealTime SARS -CoV -2 assay (EUA200023/A001)
2. The flowchart for deriving the COVID- 19 cases included below for the second primary endpoints in evaluable efficacy
participants:
Evaluable efficacy population (7 days)
Presence of at least 1 of the following symptoms: fever, new or increased
cough, new or increased shortness of breath, chills, new or increased muscle
pain, new loss of taste or smell, sore throat, diarrhea, or vomiting.
NAAT positive for COVID -19 at central laboratory or acceptable
local test within the date window that symptoms were present
Onset date, ie, the date that first symptom occurs,
is at least 7 days after receipt of the second dose
COVID-19 cases for second primary VE objective
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Page 71 of 72 Appendix VII: Detailed subsetting for Analysis:
1. Key A nalysis Population Subsetting :
1.1 Safety Analysis
1.2 Efficacy Analysis
Table
Category Analysis Population Number of Subjects ( N)
Subset Condition for
Total N Sub-Category BNT162b2
(30 μg) Placebo Total
Efficacy Dose 1 All -
Available Efficacy 1131 1129 2260 Refer to Appendix I for more
details. ADSL.AAI1EFFL= "Y"
and ADSL.AGEGR4N =1
Dose 2 All -
Available Efficacy Subjects without evidence
of infection prior to 7 days
after dose 2 1061 1037 2098 Refer to Appendix I for more
details. ADSL.AAI2EFFL= "Y"
and ADC19EF.PDP27FL= "Y"
and ADSL.AGEGR4N =1
Evaluable Efficacy
Evaluable Efficacy Subjects without evidence
of infection prior to 7 days
after dose 2 1057 1030 2087 Refer to Appendix I for more
details. ADSL.EVALEFFL="Y"
and ADC19EF.PDP27FL= "Y"
and ADSL.AGEGR4N =1
Subjects with or without
evidence of infection prior
to 7 days after dose 2 1119 1109 2228 Refer to Appendix I for more
details ADSL.EVALEFFL="Y"
and ADSL.AGEGR4N =1
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Page 72 of 72 2. Adverse Event Analysis Reporting Period Subsetting :
Reporting Period Subset condition to determin e the AEs within corresponding
reporting period. (Note: Additional subset for analysis
population is needed)
Blinded Placebo -
Controlled Follow -up
Period From dose 1 to unblinding (the day
before unblinding) All AEs ADAE.AECAT= "ADVERSE EVENT " and ADAE.VPHASEN in
(1,2,3,99)
New AEs
after the
EUA
Snapshot ADAE.AECAT ="ADVERSE EVENT " and ADAE.VPHASEN in
(1,2,3,99) and ADAE. DATCHGFL ="Y"
Blinded Placebo -
Controlled Follow -up
Period + Open -label
follow -up period for
subjects who originally received
BNT162b2 From dose 1 to 6 Month after dose 2
Note: This is for subjects originally received BNT162b2 and with at least 6 months of follow -up time after dose
2 (28*6 days after dose 2), Including all of the AEs within 6 -month after
dose 2 regardless of unblinding or not All AEs ADAE.AECAT= "ADVERSE EVENT " and ADAE.VPHASEN>=1 and .
<ADAE.ASTDT<=ADSL.V02OBDT
New AEs
after the EUA Snapshot ADAE.AECAT= "ADVERSE EVENT " and ADAE.VPHASEN>=1 and
. <ADAE.ASTDT<=ADSL.V02OBDT and ADAE .DATCHGFL ="Y"
Open -label
vaccination period for subjects who received placebo and then received BNT162b2 After unblinding Immediate adverse event after dose 3
(1st dose of BNT162b2 after unblinding)/dose 4 (2nd dose of
BNT162b2 after unblinding) All AEs ADAE.AECAT= "ADVERSE EVENT " and ADAE.AEIMMFL= "Y" and
ADAE.VPHASEN in (5, 6)
From dose 3 (1st dose of BNT162b2
after unblinding) to 7 days after dose 3 All AEs ADAE.AECAT= "ADVERSE EVENT " and ADAE.VPHASEN=5 and
ADSL.VAX201DT<=ADAE.ASTDT <=ADSL.VAX201DT+7
From dose 4 (2nd dose of BNT162b2
after unblinding) to 7 days after dose 4 All AEs ADAE.AECAT= "ADVERSE EVENT " and ADAE.VPHASEN=6 and
ADSL.VAX202DT<=ADAE.ASTDT <=ADSL.VAX202DT+7
From dose 3 (1st dose of BNT162b2
after unblinding) to the date of cutoff All AEs ADAE.AECAT= "ADVERSE EVENT " and ADAE.VPHASEN>=5 and
ADAE.VPHASEN ne 99 and .<ADAE.ASTDT<=ADSL.X1CSRDT
Open -label follow -up
period for subjects who originally
received BNT162b2 From unblinding date to the date of
cutoff All AEs ADAE.AECAT= "ADVERSE EVENT " and ADAE.VPHASEN>= 4 and
ADAE.VPHASEN ne 99 and .<ADAE.ASTDT<=ADSL . X1CSRDT
Note: Immediate AEs were those events occurring within the first 30 minutes after each dose, which were flagged as “Y” in
ADAE.AEIMMFL.
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