Document text
Analysis Data Reviewer Guide
BLA Analysis for Participants ≥16 Years of Age
BioNTech SE and PFIZER INC.
Study C4591001
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Study C4591001 Analysis Data Reviewer’s Guide
2 ANALYSIS DATA REVIEWER GUIDE
REVISION HISTORY
Version Summary of Major Change(s) and Impact Version Date
1.0 First approved version of Analysis Data Reviewer Guide 3-May-2021
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3 Analysis Data Reviewer Guide
Contents
1.Introduction ................................ ................................ ................................ ................................ . 6
1.1 Purpose ................................ ................................ ................................ ..................... 6
1.2 Acronyms ................................ ................................ ................................ ................. 7
1.3 Study Data Standards and Dictionary Inventory ................................ ...................... 8
1.4 Source Data Used for Analysis Dataset Creation ................................ ..................... 8
2.Protocol Description ................................ ................................ ................................ .................... 8
2.1 Protocol Number and Title ................................ ................................ ....................... 8
2.2 Protocol Design in Relation to ADaM Concepts ................................ .................... 10
3.Analysis Considerations Related to Multiple Analysis Datasets ................................ ............... 11
3.1 Study Populations and Core Variables ................................ ................................ ... 12
3.2 Treatment Variable ................................ ................................ ................................ . 17
3.3 Subject Issues that Require Special Analysis Rules ................................ ............... 19
3.4 Use of Visit Windowing, Unscheduled Visits, and Record Selection .................... 20
3.5 Imputation/Derivation Methods ................................ ................................ ............. 21
4.Analysis Data Creation and Processing Issues ................................ ................................ .......... 21
4.1 Split Datasets ................................ ................................ ................................ .......... 21
4.2 Data Dependencies ................................ ................................ ................................ . 21
4.3 Intermediate Datasets ................................ ................................ ............................. 21
5.Analysis Dataset Descriptions ................................ ................................ ................................ ... 21
5.1 Overview ................................ ................................ ................................ ................ 21
5.2 Analysis Datasets ................................ ................................ ................................ ... 22
5.2.1 ADSL – Subject-Level Analysis Dataset ................................ ............................... 23
5.2.2 ADCEVD – Diary and CRF Event Analysis Dataset ................................ ............ 23
5.2.3 ADAE – Adverse Events Analysis Dataset................................ ............................ 24
5.2.4 ADCM – Concomitant Medications Analysis Dataset ................................ ........... 24
5.2.5 ADDS – Disposition Analysis Dataset ................................ ................................ .. 24
5.2.6 ADDV – Protocol Deviation Analysis Dataset ................................ ...................... 25
5.2.7 ADFACEVD – Diary and Non-event Analysis Dataset ................................ ......... 25
5.2.8 ADMH – Medical History Analysis Dataset ................................ ......................... 26
5.2.9 ADSYMPT – Covid-19 Signs and Symptoms ................................ ....................... 26
5.2.10 ADC19EF – Covid-19 Efficacy Analysis ................................ .............................. 30
5.2.11 ADVA – Immunogenicity Analysis Dataset ................................ .......................... 32
6.Data Conformance Summary ................................ ................................ ................................ .... 33
6.1 Conformance Inputs ................................ ................................ ............................... 33
6.2 Issues Summary (Pinnacle 21 Enterprise Validation Report) ................................ 34
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4 7. Submission of Programs ................................ ................................ ................................ ............ 37
7.1 ADaM Programs ................................ ................................ ................................ .... 37
7.2 Analysis Output Programs ................................ ................................ ...................... 37
8. Appendix ................................ ................................ ................................ ................................ ... 42
Appendix I: Annotated Mocks for Key Tables ................................ ................................ ..... 42
Mock Table 2 ................................ ................................ ................................ .............. 42
Mock Table 3 ................................ ................................ ................................ .............. 45
Mock Table 4 ................................ ................................ ................................ .............. 46
Mock Table 5 ................................ ................................ ................................ .............. 48
Mock Table 6 ................................ ................................ ................................ .............. 51
Mock Table 7 ................................ ................................ ................................ .............. 52
Mock Table 8 ................................ ................................ ................................ .............. 53
Mock Table 9 ................................ ................................ ................................ .............. 54
Mock Table 10 ................................ ................................ ................................ ............ 55
Mock Table 11 ................................ ................................ ................................ ............ 57
Mock Table 12 ................................ ................................ ................................ ............ 57
Mock Table 13 ................................ ................................ ................................ ............ 58
Mock Table 14 ................................ ................................ ................................ ............ 60
Mock Table 15 ................................ ................................ ................................ ............ 61
Mock Table 16 ................................ ................................ ................................ ............ 61
Mock Table 17 ................................ ................................ ................................ ............ 62
Mock Table 18 ................................ ................................ ................................ ............ 63
Mock Table 19 ................................ ................................ ................................ ............ 65
Appendix II: Analysis plan AE windowing logic ................................ ................................ 66
Appendix III: Handling of Incomplete Dates ................................ ................................ ....... 70
Adverse events ................................ ................................ ................................ ............ 70
Concomitant medications/medical histories ................................ ............................... 71
Appendix IV: ADFACEVD Analysis Parameters ................................ ................................ 72
Appendix V: External files used during ADaM dataset creation ................................ ......... 73
Appendix VI: Surveillance Times ................................ ................................ ........................ 76
Appendix VII: Efficacy Flow Charts................................ ................................ .................... 77
Appendix VIII: Detailed subsetting for Analysis: ................................ ................................ 81
1. Key Analysis Population Subsetting: ................................ ................................ ..... 81
1.1 BLA Phase 2/3 Safety Analysis ................................ ................................ ............. 81
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5 1.2 BLA Phase 2/3 Efficacy Analysis ................................ ................................ .......... 82
1.3 BLA Phase 1 Safety and Immunogenicity Analysis for BNT162b2 30 mcg and
Equivalent Placebo Subjects ................................ ................................ ............................ 83
2. Adverse Event Analysis Reporting Period Subsetting: ................................ .......... 84
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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 does not include asymptomatic surveillance, asymptomatic infection analysis,
manufacturing process 1 process 2 lot analysis, Phase 1 booster analysis and Phase 2/3
booster and new variant strain analysis. This ADRG covers :
• Updated Efficacy analyses in blinded placebo -controlled follow -up evaluated duration of
protection (data cutoff date: 13 March 2021).
• Immunogenicity analyses of adults (18 to 85 years of age) includ ing data up to 1 month
after Dose 2 in Phase 2, and up to 6 months after Dose 2 in Phase 1.
• Safety data presented for
▪ Blinded placebo -controlled period: Dose 1 to 1 month after Dose 2 and to unblinding
date:
o Phase 1 participants randomized to BNT162b2 30µg
o Phase 2/3 participants including HIV+ subset
▪ Open-label observational period: from time of unblinding to data cutoff date:
o Phase 2/3 participants originally randomized to BNT162b2 30µg
o Phase 2/3 participants originally randomized to placebo who then
received BNT162b2 30µg
Cumulative follow -up from Dose 1 to 6 months after Dose 2: Phase 2/3 participants originally
randomized to BNT162b2 (inclusive of blinded data and open -label data), comprised of at least
3000 in each age group (16 to 55 years of age, >55 years of age)
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7 1.2 Acronyms
Acronym Translation
ADaM Analysis Dataset Model
ADRG Analysis Data Reviewer’s Guide
AE Adverse Event
BLA Biologics License Application
COVID-19 Coronavirus Disease 2019
eCRF Electronic Case Report Form
eDT Electronic Data Transfer (e.g. central lab data, ECG vendor data, PK
data, etc.)
EUA Emergency Use Authorization
HIV Human Immunodeficiency Virus
ICD Informed Consent Document
IG Implementation Guide
IWR Interactive Web -based Response
LAR Legally Acceptable Representative
LLOQ Lower Limit of Quantification
MedDRA Medical Dictionary for Regulatory Activities
modRNA nucleoside -modified messenger ribonucleic acid
NA Not Applicable
NAAT nucleic acid amplification test
PI principal investigator
SAP Statistical Analysis Plan
SDTM Study Data Tabulation Model
SoA Schedule of Activities
TAUG Therapeutic Area User Guide
WHO World Health Organization
VE Vaccine Efficacy
WHO DDE WHO Drug Dictionary Enhanced
WOCBP Women of childbearing potential
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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
ADaM •ADaM v2.1
•ADaM-IG v1.1
ADaM Controlled Terminology CDISC ADaM Controlled Terminology, 2020-03-27
Data Definitions Define-XML v2.0
Medications Dictionary WHO DDE v202003
Medical Events Dictionary MedDRA v23.1
Pinnacle 21 Pinnacle 21 Enterprise 4.1.4
1.4 Source Data Used for Analysis Dataset Creation
For analysis, a data cutoff of 13Mar2021 was applied on SDTM data. Furthermore , any
data related to the booster portion of the Phase 1 subjects was also programmatically
excluded from SDTM data.
The ADaM datasets for this study were derived from the SDTM datasets.
External files used during ADaM dataset creation are listed in Appendix V.
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 BLA and have not been included in this ADRG.
Protocol Versions:
Amendment 12: 2020 -01-08
• 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: 2020-01-04
• Added a potential intensive surveillance period for nasal swabbing, for assessment via
NAAT:
o Corresponding SoA and procedures added
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9 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
secondary efficacy objectives, estimands, and endpoints to include COVID-19 cases
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: 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.
• Decreased the lower age limit and remove d 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.
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10 • 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.
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 3 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 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]).
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 tr ue 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.
3. Analysis Considerations Related to Multiple Analysis Datasets
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12 3.1 Study Populations and Core Variables
A description of the key analysis subject populations used in this study along with the
subsetting criteria required to identify those subjects in each population from the ADaM
datasets and the expected N associated with each analysis is described in detai l in Appendix
VIII Section 1 .
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
AGEGR1 Pooled age group 1 (based on Age at Dose 1)
Including following age categories:
12-15 Years; 16 -55 Years; >55 Years for Phase 2/3
subjects.
18-55 Years; 65 -85 Years for Phase 1 subjects.
AGEGR1N Pooled age group 1 (N):
1= 12-15 Years; 2= 16-55 Years; 3= 18-55 Years;
4= 65-85 Years; 5= >55 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; ASIAN; MULTIPLE; NATIVE
HAWAIIAN OR OTHER PACIFIC
ISLANDER; OTHER; NOT REPORTED
Baseline Status COVBLST Baseline SARS -CoV-2 status: Positive or Negative
HIVFL HIV positive subjects Flag
Treatment Variables ARM Description of Planned Arm
ARMCD Planned Arm Code
ACTARM Description of Actual Arm
ACTARMCD Actual Arm Code
DOSALVL Actual Dosing Level for Phase 1 subjects only
DOSALVLN Actual Dosing Level (N) for Phase 1 subjects only
DOSPLVL Planned Dosing Level for Phase 1 subjects only
DOSPLVLN Planned Dosing Level (N) for Phase 1 subjects only
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
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13 Variable Type Variable Name Variable Description
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 Tr eatment for open label vaccination period
TRT02AN Actual Treatment for open label vaccination period
(N)
TRT02P Planned Treatment for open label vaccination
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
Study Phase PHASE Study Phase
"Phase 1" for subjects from Phase 1;
"Phase 2_ds360/ds6000" for subjects from Phase 2;
"Phase 3_ds6000" for subjects from Phase 3 and
included in DS6000;
"Phase 3" for other subjects from Phase 3
DS360 indicates the 360 Phase 2 subjects.
DS6000 indicates first 6000 subjects from Phase 3
with 3000 subjects receiving actual treatment, and
3000 subjects receiving placebo.
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14 Variable Type Variable Name Variable Description
See more details in Appendix V
PHASEN Study phase (N).
1 = Phase 1; 2 = Phase 2_ds360/ds6000 ; 3 = Phase
3_ds6000 ; 4 = Phase 3
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), en d of study date (if applicable),
complete of study date (if applicable) and the date
of cutoff (13Mar2021).
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 (13Mar2021).
This date is used for AE incidence rate summary
table for open label foll ow up period.
Population Flags** DS3KFL Flag of phase2/3 subjects with at least 6 months
of follow-up time after Dose 2 (28*6=168) days
after Dose 2 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 12006 subjects in
total from safety population by excluding the
subjects with multiple sites.
MULENRFL Subjects with multiple site s are excluded from
all analysis.
Note: Subjects flagged as YES -POP4 in
variable SUPPDV. QNAM = ”CAPE” are the
subjects with multiple sites and were excluded
from all of summary analysis.
REACTOFL Population flag for subjects from
reactogenicity subse t
PEDIMMFL
Population flag for 12 -15/16-25 years of age
subjects in immunogenicity subset (280 subjects
from active group and 50 subjects from placebo
group for each age group) These 660 subjects were
randomly selected for immunobridging assessment.
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15 Variable Type Variable Name Variable Description
PEDREAFL
Population flag for 12 -15/16-25 years of age
reactogenicity subset
EV1MD2FL
Population flag for subjects without evidence of
infection up to 1 Month After Dose 2
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.
RAND1FL Randomized population by excluding the subjects
with multiple site s
SAFFL Safety population flag defined as:
All randomized participants who receive at least
1 dose of the study intervention.
Analyses of reactogenicity endpoints will be based
on a subset of the safety population that includes
participants with any e-diary data reported after
vaccination
Note: Subjects flagged as both YES -POP1 and
YES-POP5 in variable SUPPDV. QNAM =
”CAPE” were excluded from safety population for
unreliable data due to lack of principal investigator
oversight.
SAF1FL Safety populati on by excluding multiply enrolled
subjects, HIV positive subjects and subjects with all
doses indeterminate
SAF2FL Safety population by excluding multiply enrolled
subjects and subjects with all doses indeterminate
AAI01FL Dose 1 all -available Immunogenicity Population
Flag defined as:
For Phase 1 only: all randomized participants who
receive at least 1 dose of the study intervention
with at least 1 valid and determinate
immunogenicity result after Dose 1 but before
Dose 2.
AAI02FL Dose 2 all -available Immunogenicity Population
Flag defined as:
All randomized participants who receive at least 1
dose of the study intervention with at least 1 valid
and determinate immunogenicity result after Dose
2.
Note: Subjects flagged as YES-POP5 in variable
SUPPDV. QNAM = ”CAPE” were excluded from
all-available immunogenicity population for
unreliable data due to lack of principal investigator
oversight.
EVAL01FL Dose 1 evaluable Immunogenicity Population Flag
defined as:
For Phase 1 only, all eligible randomized
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16 Variable Type Variable Name Variable Description
participants who receive the vaccine to which they
are randomly assigned at the first dose, have at
least 1 valid and determinate immunogenicity
result from the blood collection within an
appropriate window after Dose 1 (same as visit
window, ie, within 19-23 days after Dose 1), and
have no other important protocol deviations as
determined by the clinician.
EVAL02FL Dose 2 evaluable Immunogenicity Population Flag
defined as:
All eligible randomized participants who receive 2
doses of the vaccine to which they are randomly
assigned, with Dose 2 received within the
predefined window (within 19-42 days after Dose
1), have at least 1 valid and determinate
immunogenicity result after Dose 2 from the blood
collection within an appropriate window after
Dose 2 (within 6-8 days after Dose 2 for Phase 1
and within 28-42 days after Dose 2 for Phase 2/3),
and have no other i mportant protocol deviations as
determined by the clinician.
Note: Subjects flagged as YES-POP3 in variable
SUPPDV. QNAM = ”CAPE” were excluded from
evaluable immunogenicity population due to
important protocol deviation identified by clinical .
AAI1EFFL Dose 1 all-available efficacy population
flag defined as:
All randomized participants who receive at
least 1 vaccination.
Used for efficacy analysis.
Note: Subjects flagged as YES-POP5 in variable
SUPPDV. QNAM = ”CAPE” were excluded from
all-available efficacy population for unreliable data
due to lack of principal investigator oversight.
AAI2EFFL Dose 2 all-available efficacy population
flag defined as:
All randomized participants who complete
2 vaccination doses.
Used for efficacy analysis.
Note: Subjects flagged as YES-POP5 in variable
SUPPDV. QNAM = ”CAPE” were excluded from
all-available efficacy population for unreliable data
due to lack of principal investigator oversight.
EVALEFFL Evaluable efficacy population flag (7 days) defined
as:
All eligible randomized participants who receive
all vaccination(s) as randomized, with Dose 2
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17 Variable Type Variable Name Variable Description
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.
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 VIII 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, TRT01P is null when ARM equals to “NOT ASSIGNED” or “SCREEN FAILURE” .
ARM represents the planned arm for the blinded placebo-controlled period based on
randomization file . TRT01P ha s 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 1 BNT162b1 Phase 1 (10
mcg) BNT162b1 Phase 1 (10
mcg) -
BNT162b1 Phase 1 (20
mcg) BNT162b1 Phase 1 ( 20
mcg) -
BNT162b1 Phase 1 (30
mcg) BNT162b1 Phase 1 ( 30
mcg) -
BNT162b1 Phase 1 (100/10
mcg) BNT162b1 Phase 1 (100/10
mcg) -
BNT162b2 Phase 1 (10
mcg) BNT162b 2 Phase 1 (10
mcg) -
BNT162b2 Phase 1 (20
mcg) BNT162b 2 Phase 1 (20
mcg) -
BNT162b2 Phase 1 (30
mcg) BNT162b 2 Phase 1 (30
mcg) -
Placebo Placebo -
Placebo Placebo BNT162b2 Phase 1
(30 mcg)
NOT ASSIGNED - -
SCREEN FAILURE - -
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 ASSIGNED - -
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18 PHASE ARM TRT01P TRT02P
SCREEN FAILURE - -
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 ha s the actual treatment for the blinded placebo -controlled period , TRT02A
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 1 BNT162b1 Phase 1 (10 mcg) BNT162b1 Phase 1 (10 mcg) -
BNT162b1 Phase 1 (20 mcg) BNT162b1 Phase 1 (20 mcg) -
BNT162b1 Phase 1 (30 mcg) BNT162b1 Phase 1 (30 mcg) -
BNT162b1 Phase 1 (100/10
mcg) BNT162b1 Phase 1 (100/10
mcg) -
BNT162b2 Phase 1 (10 mcg) BNT162b 2 Phase 1 (10 mcg) -
BNT162b2 Phase 1 (20 mcg) BNT162b 2 Phase 1 (20 mcg) -
BNT162b2 Phase 1 (30 mcg) BNT162b 2 Phase 1 (30 mcg) -
Placebo Placebo -
Placebo Placebo BNT162b2 Phase 1
(30 mcg)
NOT ASSIGNED - -
SCREEN FAILURE - -
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 - -
NOT ASSIGNED - -
SCREEN FAILURE - -
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, immunogenicity analysis and
disposition table. Actual treatment variable was used across safety analysis.
See details in below table.
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19 Reporting Period Analysis
Population Treatment
Variables
Used in
Analysis Applicable analysis
Blinded p lacebo-
controlled period
or
Open label follow -up
period Safety TRT01A Conduct of study , Adverse
Event, Medical History,
Concomitant
Medications /Vaccinations,
Reactogenicity
Randomized TRT01P Vaccine as Administered ,
Disposition , Immunogenicity,
efficacy
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 used in analysis
3.3 Subject Issues that Require Special Analysis Rules
• Subjects whose data is considered potentially unreliable due to lack of PI oversight
identified as significant quality event were excluded from analysis populations.
• According to the Protocol, HIV -positive subjects in Phase 3 will not be included in ana lyses
of the overall study objectives, with the exception of the specific exploratory objective for
this group. In the BLA, Human immunodeficiency virus (HIV) -positive subjects are
included in the analysis populations the summary of analysis populations a nd shown as part
of the study demographics and study conduct tables but not included in the analyses of
overall safety, immunogenicity and efficacy endpoints.
• Handling of Misallocation of Vaccine:
o For AE summaries , demographics and all other tables by safety population , count the
subjects in active treatment group as long as one of the doses is active vaccination
BNT162b2 .
o For reactogenicity analyses by dose, subjects who received a different investigational
product regimen fro m the regimen they were assigned will be included in the safety
population for the summaries of individual vaccinations up until the point their regimen
differs from the assigned regimen, at which point they would no longer be included .
o Immediate AE and AEs post dose 1 and 2 were summarized by following the same rule
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20 as reactogenicity for post dose 1 and post dose 2 summary.
The following table shows how subjects are assigned to treatment arm s for safety related analyses
under all possible vaccination scenarios:
Vaccine Dose
Actual Arm
(Overall) Analysis
Scenario Actual
Dose 1 Actual
Dose 2 Reactoge-
nicity Post
Dose 1 Reactoge-
nicity Post
Dose 2 Reactoge-
nicity
post any
Dose AE Post
Dose 1 AE Post
Dose 2 Other*
1 Active Active Active Active Active Active Active Active Active
2 Placebo Placebo Placebo Placebo Placebo Placebo Placebo Placebo Placebo
3 Active Active Active Exclude Active Active Exclude Active
4 Placebo Placebo Placebo Exclude Placebo Placebo Exclude Placebo
5 Active Placebo Active Active Exclude Active Active Exclude Active
6 Placebo Active Active Placebo Exclude Active Placebo Exclude Active
* Other includes all other AE summary, demog raphic, and other study conduct tables by Safety Population (Follow
Overall Actual Arm )
• 6 Subjects were enrolled into the study more than once . These subjects will not be included
in any analyses and will only be included in separate listings (disposition listi ng, AE listing ,
local reaction listing and systemic events listing ) created specifically for this subject. The se
subjects will be excluded from other outputs using the exclusion flag (MULENRFL) in
ADSL.
Duplicated
Subject # SUBJID at 1st Site SUBJID at 2nd site
1 10561101 11331382
2 11101123 11331405
3 11491117 12691090
4 12691070 11351357
5 11341006 10891112
6 11231105 10711213
• Subjects C4591001 1163 11631006, C4591001 1163 11631005, C4591001 1163 11631008,
are vaccinated as per CRF, but due to lack of matching actual vaccination data, these are not
assigned to any dosing grou p. In the analyses these subjects will be:
For safety:
a. Excluded from all table/figures.
b. Included in all regular listings.
For efficacy:
a. Excluded from the evaluable population by the definition in the
SAP, because it is not possible to confirm if they received the vaccination as
randomized.
b. Included in all tables/figures/listings based on all-available population.
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.
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21 Were unscheduled visits used in any analyses?
Yes. please refer to Section 5.2.7 and 5.2.9 for more details.
Based on protocol guidance, multiple unscheduled Covid illness visits that are less than
four 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?
Yes, DTYPE was used in ADFACEVD and ADVA. For details on DTYPE, please refer
to Section 5.2.7 and 5.2.11.
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?
Yes. Subjects with ‘NOTASSGN’ ‘SCRNFAIL ’ are included in ADSL, ADAE, ADCM,
ADDS, ADDV, ADMH and ADVA
Are data taken from an ongoing study?
Yes. All data up through 13Mar2021 cutoff are included in the SDTM datasets and used
for ADaM datasets and analyses. Furthermore, any data related to the booster portion of
the Phase 1 subjects was also programmatically excluded from SDTM data.
Do the analysis datasets support all protocol - and statistical analysis plan-specified objectives?
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22
No. Objectives on VE against asymptomatic infection and Phase 1 booster are not assessed.
The booster and variant strain assessment in Protocol amendment 14 and SAP V5 are also
not included.
Additional Content of Interest
No additional content of Interest.
5.2 Analysis Datasets
Dataset Label
Class
Efficacy
Safety
Baseline or
other subject
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
adverse event per event
start date
ADCEVD
Diary and CRF
Event Analysis
Dataset OCCURRENCE
DATA
STRUCTURE X One record or multiple
records per subject per
clinical event
ADFACEVD
Diary and Non-
event Analysis
Dataset BASIC DATA
STRUCTURE X X One record or multiple
records per subject per
analysis parameter per
analysis timepoint
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
Deviation
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
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23
Dataset Label
Class
Efficacy
Safety
Baseline or
other subject
PK/PD
Primary
Structure
ADC19EF
Covid-19
Efficacy
Analysis BASIC DATA
STRUCTURE X X One record or multiple
records per subject per
analysis parameter per
analysis timepoint
ADSYMPT
Covid-19 Signs
and Symptoms BASIC DATA
STRUCTURE X X One record or multiple
records per subject per
analysis parameter per
analysis timepoint
ADVA
Immunogenicity
Analysis Dataset BASIC DATA
STRUCTURE X One record or multiple
records per subject per
analysis parameter per
analysis visit
5.2.1 ADSL – Subject-Level Analysis Dataset
ADSL included all subjects in the DM domain and contained relevant subject level information,
treatment variables and analysis set flags. This dataset supported the creation of all other analysis
datasets. ADSL also comprised the variables to support baseline characteristics and disposition
analyses, and the classification variables used for subgroup analyses and used as covariates for
statistical analyses.
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 Age group (details described in Section 3.1 Core Variables for Age group)
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 Hawa iian or other
Pacific Islander, multiracial, and not reported race categories.
o Ethnicity (Hispanic/Latino, Non -Hispanic/Non -Latino and Not Reported)
o Baseline SARS -CoV-2 Status (Positive and Negative )
o Flag for Comorbidities (Y/N)
o Obese Flag for Adolescent (Y/N)
5.2.2 ADCEVD – Diary and CRF Event Analysis Dataset
This dataset contains information on duration of local reactions (LR: redness, swelling, and pain
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24 at the injection site) and systemic events (SE: fever, chills, diarrhea, fatigue, headache, joint pain,
muscle pain and vomiting) and is used to generate the summaries of duration of these reactions
or events.
Duration of each reaction or event is defined as the number of days from the start of the first
reported event to the resolution of the last reported event (ADURN = AENDT – ASTDT+1),
which is the sum of the duration of the reactogenicity event in the assessment period and beyond
the assessment period if a reactogenicity event continued beyond the assessment interval. Those
clinical assessments at unscheduled visits within 7 days after each dose were involved in the
derivation of duration and summary analysis.
No imputation was carried out for partial or missing symptom resolved dates from investigator
data collected on the CRF. Those events with the resolution date partial or missing (AENDT eq
missing), were included in the “Unknown” category for any reporting. However, if a reaction is
ongoing at the time of a subsequent vaccination, the end date/day for the ongoing reaction would
be the date/day that the next vaccine is administered, which will be used for the duration
computation. Participants with no reported reaction have no duration.
5.2.3 ADAE – Adverse Events Analysis Dataset
This is the main safety analysis dataset comprised of adverse events recorded on the CRF. For
dictionary coding, MedDRA version 23.1 was used. 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 VIII .
5.2.4 ADCM – Concomitant Medications Analysis Dataset
The dataset contains information of nonstudy vaccines (CMCAT = “VACCINATIONS”) ,
concomitant medications (CMCAT = “GENERAL CONCOMITANT MEDICATIONS”) and
prohibited concomitant medications (CMCAT in (’ CONCOMITANT IMMUNOSUPPRESSIVE
THERAPY’,’ CORTICOSTEROIDS’,’ IMMUNOGLOBULINS’)) . For dictionary codin g, WHO
DDE v20 2003 were used.
Partial start dates or partial end dates of nonstudy vaccines and concomitant medications were
imputed using rules described in Appendix III.
5.2.5 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:
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25 DSCAT DSPHASE
DISPOSITION EVENT SCREENING
DISPOSITION EVENT REPEAT S CREENING 1
DISPOSITION EVENT VACCINATION
DISPOSITION EVENT OPEN LABEL TREATMENT
DISPOSITION EVENT FOLLOW -UP
5.2.6 ADDV – Protocol Deviation 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 exclusion flag was capture in SUPPDV.QNAM=’CAPE’ .
5.2.7 ADFACEVD – Diary and Non-event Analysis Dataset
This is a primary analysis dataset for vaccine studies, including information of occurrence,
severity level and maximum severity of reactogenicity assessments reported in the e-diary.
Reactogenicity assessments cover 3 parts: local reactions, systemic events and use of
antipyretic/pain medication which were assessed within 7 days after each dose.
ADFACEVD is a dataset using BDS structure, which contains one or multiple records per
subject per analysis parameter (PARAM) per analysis timepoint (ATPT). Variables PARAM and
PARAMCD were used to distinguish different measurements or findings. The detailed list of
parameters included in this dataset are described in Appendix IV.
Unscheduled visits of clinical assessments within 7 days after each vaccination for reactogenicity
from FACE and VS dataset were considered for summary analysis.
Reactogenicity assessments reported in the e-diary on or after the date of treatment unblinding
(ADSL.UNBLNDDT) were excluded from onset and maximum severity summary analysis.
However, events with onset before unblinding that continue after the date of unblinding were used
in duration calculation. The events reported on the same day of unblinding were flagged as ‘Y’ in
variable CUTUNB FL in ADFACEVD .
Maximum severity records were created in this dataset with DTYPE equal to "MAXIMUM". For
all subjects, each local reaction or systemic event was targeted to have 7 assessments from Day 1
to Day 7. The maximum severity value reported during the interval was stored in an additional
record with DTYPE equaled “MAXIMUM” (see the table as below) which is then used to
summarize the maximum severity of these events.
PARAM DTYPE
Redness maximum severity MAXIMUM
Redness maximum diameter MAXIMUM
Swelling maximum severity MAXIMUM
Swelling maximum diameter MAXIMUM
Pain at injection site maximum severity MAXIMUM
Chills maximum severity MAXIMUM
Diarrhea maximum severity MAXIMUM
Fatigue maximum severity MAXIMUM
Fever maximum temperature MAXIMUM
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26 PARAM DTYPE
Headache maximum severity MAXIMUM
Joint pain maximum severity MAXIMUM
Muscle pain maximum severity MAXIMUM
Vomiting maximum severity MAXIMUM
ADFACEVD includes the following key flags to support reactogenicity analyses:
• KNOWVFL – Y for that reaction or event if a subject had at least one record reported from
day 1 to day 7 after each dose for a given reaction or event. This was derived per subject per
dose per parameter (/event).
• EVENTFL – Y for that reaction or event if a subject had at least one record where the event
occurred (where diameter>2.0 cm for redness and swelling or 38 ℃<=temperature<=42 ℃ for
fever or presence=yes for other symptoms) from day 1 to day 7 after each dose for a given
reaction or event. This was derived per subject per dose per parameter (/event).
• KNOWVDFL – Y for a valid record (where the event was reported regardless if it occurred
or not) at that day from day 1 to day 7 after each dose for a given reaction or event. This was
derived per subject per dose per parameter (/event) per day.
• EVENTDFL – Y for a record where the event occurred (where diameter>2.0 cm for redness
and swelling or 38 ℃<=temperature<=42 ℃ for fever or with any valid severity/intensity or
presence=yes for other symptoms) at that day from day 1 to day 7 after each dose. This was
derived per subject per dose per parameter (/event) per day.
• Category variables FTEMCATN / FTEMCAT were used for fever summary analyses:
FTEMCATN FTEMCAT
. Missing
0 <38.0°C
1 ≥38.0°C to 38.4°C
2 >38.4°C to 38.9°C
3 >38.9°C to 40.0°C
4 >40.0°C
• AVALCA1N / AVALCAT1 was derived based on diameter value and for parameters
“Redness maximum severity” and “Swelling maximum severity” the maximum severity
was derived per below table.
AVALCA1N AVALCAT1 SEVERITY
0 >0-2.0 NONE
1 >2.0-5.0 MILD
2 >5.0-10.0 MODERATE
3 >10.0 SEVERE
5.2.8 ADMH – Medical History Analysis Dataset
This dataset contains all medical histories (MHCAT = “GENERAL MEDICAL HISTORY”)
collected on the CRF. MedDRA version 23.1 was used for dictionary coding of medical
histories. Partial start dates or partial end dates medical histories were imputed using rules
described in Appendix III .
5.2.9 ADSYMPT – Covid-19 Signs and Symptoms
The purpose of this dataset is to gather all signs/symptoms/conditions/laboratory results
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27 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, DD, DS, HO, FA, IS, LB, MB, MH, PR, 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, MBMETHOD 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 threat, Vomiting, Loss of
taste/smell”.
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".
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".
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28 PARAMN PARAMCD PARAM Derivation
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.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".
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".
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29 PARAMN PARAMCD PARAM Derivation
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".
80 VSOPRES VASOPRESSORS
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" ).
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30 PARAMN PARAMCD PARAM Derivation
92 HCUHSP HOSPITALIZED
DUE TO COVID -
19 ILLNESS? Set to "HOSPITALIZED 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".
5.2.10 ADC19EF – Covid-19 Efficacy Analysis
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 during blinded
placebo-controlled follow -up period, 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 VI and Appendix VII 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 OF SARS-COV-2
90 C19NIG N-BINDING ANTIBODY
91 HCUICU SUBJECT IN ICU DUE TO POTENTIAL COVID-19
ILLNESS
92 HCUHSP HOSPITALIZED DUE TO COVID -19 ILLNESS?
95 PRCDTH PRIMARY CAUSE OF DEATH
96 SECDTH SECONDARY CAUSE OF DEATH
100 DTHODC19 DEATH OCCURRED DUE TO COVID -19 ILLNESS?
101 PRPDSAD PRESENCE OF PROTOCOL DEFINED SYMPTOMS AFTER DOSE
102 PRCDCSAD PRESENCE OF CDC DEFINED SYMPTOMS AFTER DOSE
103 SEVCVS SEVERE COVID-19 SYMPTOMS - VITAL SIGNS
104 SEVCRF SEVERE COVID-19 SYMPTOMS - RESPIRATORY FAILURE
105 SEVCVSPR SEVERE COVID-19 SYMPTOMS - USE OF
106 SEVCRHN SEVERE COVID-19 SYMPTOMS - SIGNIFICANT ACUTE RENAL,
HEPATIC, OR NEUROLOGIC DYSFUNCTION
107 PRSVCSAD PRESENCE OF PROTOCOL DEFINED SEVERE COVID-19 SYMPTOMS
AFTER DOSE
108 PRSCDCAD PRESENCE OF CDC DEFINED SEVERE COVID -19 SYMPTOMS AFTER
DOSE
110 NAATRAD COVID-19 NAAT RESULT AFTER DOSE
120 C19ONST PROTOCOL DEFINED COVID-19 ILLNESS ONSET
125 CDCONST CDC DEFINED COVID -19 ILLNESS ONSET
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31 PARAMN PARAMCD PARAM
130 SEVCONST 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 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 DEF INED
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 AVAILABLE
202 ST17PDA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
203 ST2PDA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR PROTOCOL
DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
204 ST27PDA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
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32 PARAMN PARAMCD PARAM
205 ST214PDA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
211 ST1CDA SUBJECT'S SURVEILLANCE TI ME 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 AVAILABLE
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 AVAILABLE
215 ST214CDA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
CDC DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
221 ST1SEA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR PROTOCOL
DEFINED SEVERE COVID19 SYMPTOMS - ALL AVAILABLE
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 AVAILABLE
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 AVAILABLE
232 STC17SA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR
CDC DEFINED SEVERE COVID19 SYMPTOMS - ALL AVAILABLE
233 STC2SA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS - ALL AVAILABLE
234 STC27SA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2 FOR
CDC DEFINED SEVERE COVID19 SYMPTOMS - ALL AVAILABLE
235 STC214SA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
CDC DEFINED SEVERE COVID19 SYMPTOMS - ALL AVAILABLE
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
5.2.11 ADVA – Immunogenicity Analysis Dataset
This dataset contains immunogenicity assessments for subjects f or Phase 1, Phase 2 and pediatri c
analysis (12 -15 years age group and randomly selected subjects from 16 -25 years age group) . Due
to additional follow-up as well as ongoing data cleaning, there may be minor differences due to
difference in database snapshots and cutoff dates applied to SDTM and ADaM in this case.
Subjects excluded from the evaluable immunogenicity populations were identified
programmatically fo r samples outside the visit window, not receiving correct vaccination as
randomize d, no valid assay result; exclusion due to important deviations were provided in SUPPDV
dataset.
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33 For Phase 1 for BNT162b2 30 mcg and equivalent Placebo subjects (30 subjects in total), visits
‘V1_DAY1_VAX1_S ’,’ V4_WEEK3_VAX2_S ’ and ‘V7_MONTH1_S ’ were retested by lab. And
for these retested visits (flagged as ‘ REPEAT TEST ’ in ISTSTDTL) , only the retested values were
used for analysis.
Assay results collected within a dose-specified sample collection window, either Dose 1 or Dose
2, that were not distinguished by the dose-specified immunogenicity population flags (EVIMMFL
for evaluable immunogenicity population , AAIMMFL for all-available immunogenicity
population) , were excluded from analysis of the corresponding immunogenicity population.
Flags (ABLFL/APSBLFL/ABLPBLFL) used for identifying baseline and post baseline records
are also available for each parameter. The ratio from post -baseline to baseline (R2BASE) was
calculated as AVAL/BASE for fold rise summaries.
Assay results collected at COVID convalescent visit within 28 -42 days after Dose 2, were used
for the 1-month post Dose 2 analysis for subjects without a Visit 3 serology assay collected.
Assay results below the corresponding LLOQ were set to 0.5 × LLOQ and missing assay
results were not imputed. DTYPE was set to “LLOQIMP” for parameters that needed
imputation for LLOQ. All analysis parameters are presented in below table.
Note: When determinate subjects achieved 4-fold rise post baseline, assay results at baseline
below the corresponding LLOQ were set to LLOQ.
PARCAT1 PARAMCD PARAMN PARAM ISLLOQ
SEROLOGY C2NGNT50 1 SARS-CoV-2 serum neutralizing titer 50 (titer) -
Virus Neutralization Assay 20
SEROLOGY C2NGNT90 2 SARS-CoV-2 serum neutralizing titer 90 (titer) -
Virus Neutralization Assay 20
SEROLOGY C19S1IGG 3 COVID-19 S1 IgG (U/mL) - Luminex Immunoassay 1.2665
SEROLOGY C19RBDIG 4 COVID-19 RBD IgG (U/mL) - Luminex Immunoassay 1.1505
SEROLOGY C19NIG 5 N-binding antibody - N-binding Antibody Assay NA
SEROLOGY NT50_S1 11 SARS-CoV-2 serum neutralizing titer 50 to
COVID-19 S1 IgG NA
SEROLOGY NT90_S1 12 SARS-CoV-2 serum neutralizing titer 90 to
COVID-19 S1 IgG NA
6. Data Conformance Summary
6.1 Conformance Inputs
Specify the software name and version for the analysis datasets
Pinnacle 21 Enterprise 4.1.4., Validation Engine version 1907.2
Pinnacle Validation Engine FDA 2010.1 was also used to evaluate the data. And there's no
significant change identified .
Specify the version of the validation rules (i.e. CDISC, FDA) for the analysis datasets
CDISC ADaM-CT 2020-03-27
Specify the software name and version for the define.xml
Pinnacle 21 Enterprise 4.1.4.
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34 Specify the version of the validation rules (i.e. CDISC, FDA) for the define.xml
CDISC ADaM CT 2020-03-27
6.2 Issues Summary (Pinnacle 21 Enterprise Validation Report )
Check
ID Diagnostic
Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
AD0018 Variable label
mismatch between
dataset and ADaM
standard Error ADVA 3
(4.00%) On Page 21 of ADaM IG 1.1 descriptive
text is allowed at the end of the labels of
variables whose names contain indexes
“y” or “zz”; Therefore, all labels for
variables that contain indexes will throw
false positive error messages.
AD0034 PDRMUPFL
value is not Y or
null Error ADC19EF 2089175
(97.22%) 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.
AD0034 CDRMUPFL
value is not Y or
null Error ADC19EF 2085470
(97.04%) 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.
AD0099 ASTDY is greater
than AENDY Error ADC19EF 7579
(0.39%) ASTDT is greater than AENDT in some
cases, as surveillance time could start at
various time points for some subjects.
For example, a subject's surveillance
time could be prior to the start of event
due to positive COVID case or other
criteria as noted in the define.xml
leading to ASTDT >AED NT and
ASTDY > AENDY.
AD0124 Inconsistent value
for PARCAT1
within a unique
PARAMCD Error ADSYMPT 17 (<
0.1%) Observations for
PARAMCD="HCUICU" are included
when we have ICU observations from
either SDTM HO or from HCUICU
observations in SUPPHO. The
PARCAT1 differs based on the different
categories (HOCAT) picked from the
SDTM. Therefore, the different
PARCAT1 values for
PARAMCD="HCUICU" are
acceptable.
AD0253 Record key from
SDTM AE is not
traceable to
ADaM ADAE
(not enough
ADAE recs) Error AE 2192
(5.55%) AECAT=”REACTOGENICITY”
records (from ediary) was not kept in
ADAE (Based on CDISC Vaccine
TAUG flat model).
AD0361 Value of ASTDT
is greater than
value of AENDT Error ADC19EF 7579
(0.39%) ASTDT is greater than AENDT in some
cases, as surveillance time could start at
various time points for some subjects.
For example, a subject's surveillance
time could be prior to the start of event
due to positive COVID case or other
criteria as noted in the define.xml
leading to ASTDT >AEDNT and
ASTDY > AENDY.
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35 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 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 nec essary
information. Any new custom variables
added to analysis data are out -of-scope
for AD1012 check.
AD1012 Secondary custom
variable is present
but its primary
variable is not
present Warning ADFACEVD 1
(7.14%) AD1012 check is limited to "standard"
ADaM variables explicitly defined in
ADaM IG documents. EVENTOCC
stands for Occurrences of Event. Any
new custom variables added to analysis
data are out -of-scope for AD1012
check.
AD1012 Secondary custom
variable is present
but its primary
variable is not
present Warning ADSL 5
(22.73%) AD1012 check is limited to "standard"
ADaM variables explicitly defined in
ADaM IG documents.
FUP1CA1N/SCREEN/FUP2CA1N/FP
X1CA1N/FUP2CA2N are the variable
to capture the necessary infor mation.
Any new custom variables added to
analysis data are out -of-scope for
AD1012 check.
AD1012 Secondary custom
variable is present
but its primary
variable is not
present Warning ADVA 2
(16.67%) AD1012 check is limited to "standard"
ADaM variables explicitly defined in
ADaM IG documents.
BSSEROC/BSSERON stands for
baseline sero status. 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 52998
(2.47%) New terms were added to extensible
codelist RACE for the study protocol
needs:
Multiple
CT2002 RACE value not
found in 'Race'
extensible codelist Warning ADCEVD 6921
(2.55%) 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 230
(1.15%) 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 2915
(2.37%) 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 828
(2.23%) New terms were added to extensible
codelist RACE for the study protocol
needs:
Multiple
CT2002 RACE value not
found in 'Race'
extensible codelist Warning ADFACEVD 58677
(2.60%) New terms were added to extensible
codelist RACE for the study protocol
needs:
Multiple
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36 Check
ID Diagnostic
Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
CT2002 RACE value not
found in 'Race'
extensible codelist Warning ADMH 2854
(1.45%) 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 1166
(2.42%) 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 9090
(2.77%) New terms were added to extensible
codelist RACE for the study protocol
needs:
Multiple
CT2002 DTYPE value not
found in
'Derivation Type'
extensible codelist Warning ADVA 12084
(10.57%) New terms were added to extensible
codelist DTYPE for the study protocol
needs:
LLOQIMP and Derived
CT2002 RACE value not
found in 'Race'
extensible codelist Warning ADVA 2716
(2.37%) New terms were added to extensible
codelist RACE for the study protocol
needs:
Multiple
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37
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. 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 suppmb mh pr 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
adcevd-sas.txt adcevd.xpt ce face vs ex suppce suppface suppvs adsl NA
adfacevd-sas.txt adfacevd.xpt face vs ex suppface suppvs adsl NA
admh-sas.txt admh.xpt mh suppmh adsl NA
adva-sas.txt adva.xpt is suppis adsl NA
adc19ef-sas.txt adc19ef.xpt adsympt adsl NA
adsympt-sas.txt adsympt.xpt ce cm dd ds face ho suppho is mb mh lb pr vs adsl NA
7.2 Analysis Output Programs
Below is the list of outputs for which SAS programs have been provided to replicate the results in the tables. For the more complex
outputs, a detailed annotated mock table is also included as a reference (see the link to the individual mocks shown in the table below) to
give additional details for each output in Appendix I .
Table Program
Name Output Name Title Input Population Subset used
1 adsl-s005-demo-
all-p3-saf-sas.txt adsl_s005_demo_al
l_p3_safhtml Demographic Characteristics – Phase 2/3
Subjects ≥16 Years of Age – Safety Population ADSL ADSL.SAFFL eq "Y" and ADSL.PHASEN > 1
and ADSL.AGEGR1N > 1 and
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38 Table Program
Name Output Name Title Input Population Subset used
ADSL.MULENRFL ne "Y" and ADSL.TRT01A
ne ""
2 adds-s002-all-p3-
rand-sas.txt adds s002 all p3 r
and.html Disposition of All Randomized Subjects –
Phase 2/3 Subjects ≥16 Years of Age ADSL
ADDS ADSL.RANDFL eq 'Y' and ADSL.PHASEN ne 1
and ADSL. AGEGR1N >1 and
ADSL.MULENRFL ne "Y"
3 adsl-fu-d2-p3-saf-
sas.txt adsl fu d2 p3 saf.
html
Follow-up Time After Dose 2 – Phase 2/3
Subjects ≥16 Years of Age – Safety Population ADSL ADSL.SAFFL eq "Y" and ADSL.PHASEN > 1
and ADSL.AGEGR1N > 1 and
ADSL.MULENRFL ne "Y" and ADSL.TRT01A
ne ""
4 adce-s010-lr-p3-
saf-sas.txt adce s010 lr p3 s
af.html Local Reactions, by Maximum Severity,
Within 7 Days After Each Dose, by Age Group
(Reactogenicity Subset) – Phase 2/3 Subjects
≥16 Years of Age – Safety Population ADSL
ADFACEVD ADSL.SAFFL="Y" and ADSL.HIVFL="N" and
ADSL.PHASEN > 1 and ADSL.AGEGR1N > 1
and ADSL.MULENRFL ne 'Y' and
ADFACEVD.TRTA ne "" and
ADFACEVD.FAOBJ in ("PAIN AT INJECTION
SITE" "SWELLING" "REDNESS") and
ADFACEVD .KNOWVFL="Y" and
ADFACEVD .CUTUNBFL ne "Y"
5 adce-s020-se-p3-
saf-sas.txt adce s020 se p3 s
af.html Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose, by Age Group
(Reactogenicity Subset) – Phase 2/3 Subjects
≥16 Years of Age – Safety Population ADSL
ADFACEVD ADSL.SAFFL="Y" and ADSL.HIVFL='N' an d
ADSL.PHASEN > 1 and ADSL.AGEGR1N > 1
and ADSL.MULENRFL ne 'Y' and
ADFACEVD.TRTA ne "" and
ADFACEVD.FAOBJ not in ("PAIN AT
INJECTION SITE" "SWELLING" "REDNESS")
and
index(upcase(ADFACEVD.FAOBJ),"HOSPI")=0
and ADFACEVD .KNOWVFL="Y" and
ADFACEVD .CUTUNBFL ne "Y"
6 adae-s091-all-pd2-
p3-saf1-sas.txt adae s091 all pd2
p3 saf1html Number (%) of Subjects Reporting at Least 1
Adverse Event From Dose 1 to 1 Month After
Dose 2 – Blinded Placebo -Controlled Follow -
up Period – Phase 2/3 Subjects ≥16 Years of
Age – Safety Population ADSL
ADAE ADSL.SAFFL="Y" and ADSL.PHASEN > 1 and
ADSL.AGEGR1N > 1 and ADSL.MULENRFL ne
"Y" and ADSL.HIVFL ne 'Y' and NOT
(ADSL.VAX101=’’ and ADSL.VAX102=’’)
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Study C4591001 Analysis Data Reviewer’s Guide
39 Table Program
Name Output Name Title Input Population Subset used
7 adae-s092-all-unb-
p3-saf-sas.txt adae-s092-all-unb-
p3-saf.html Incidence Rates of at Least 1 Adverse Event
From Dose 1 to Unblinding Date – Phase 2/3
Subjects ≥16 Years of Age – Safety Population ADSL
ADAE ADSL.SAFFL=’Y’ and ADSL.PHASEN in (2,3,4)
and ADSL.AGETR01 >=16 and
ADSL.MULENRFL ne ‘Y’ and ADSL.HIVFL ne
'Y' and (ADSL.VAX101DT ne . and
ADSL.BDCSRDT ne .) and ADSL.TRT01A ne ""
8 adae-vax-tier2-p3-
saf-sas.txt adae vax tier2 p3
saf.html Tier 2 Adverse Events Reporte d From Dose 1
to 1 Month After Dose 2, by System Organ
Class and Preferred Term – Blinded Placebo -
Controlled Follow -up Period – Phase 2/3
Subjects ≥16 Years of Age – Safety Population ADSL
ADAE ADSL.SAFFL = "Y" and ADSL.PHASEN > 1 and
ADSL.AGEGR1N > 1 and ADSL.MULENRFL ne
"Y" and ADSL.HIVFL ne "Y" and ADSL.TRT01A
ne ""
9 adae-s091-all-pd2-
p3-saf2-sas.txt adae s091 all pd2
p3 saf2.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 ≥16 Years of Age (Subjects Who
Originally Received BNT162b2) – Safety
Population ADSL
ADAE ADSL.SAFFL="Y" and ADSL. PHASEN > 1 and
ADSL.AGEGR1N > 1 and ADSL.MULENRFL ne
"Y" and ADSL.HIVFL ne 'Y' and
ADSL.TRT01AN = 8 and ADSL.DS3KFL='Y'
10 adae-s092-cr-cut-
p3x-saf-sas.txt
adae-s092-cr-cut-
p3x-saf.html
Incidence Rates of at Least 1 Adverse Event
From Dose 3 to Data Cutoff Date
(13MAR2021) – Open-Label Follow -up
Period – Subjects Who Originally Received
Placebo and Then Received BNT162b2 After
Unblinding –
Phase 2/3 Subjects ≥16 Years of Age – Safety
Population ADSL
ADAE ADSL.SAFFL=’Y’ and ADSL.PHASEN > 1 and
ADSL.AGETR01 ge 16 and ADSL.MULENRFL
ne 'Y' and ADSL.HIVFL ne 'Y' and
ADSL.ARM=’Placebo’ and ADSL.VAX201DT>.
and ADSL.X1CSRDT>.
11 adc19ef-ve-cov-
7pd2-wo-eval-
sas.txt adc19ef ve cov 7p
d2 wo eval.html Vaccine Efficacy – First COVID -19
Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period
– Subjects Without Evidence of Infection Prior
to 7 Days After Dose 2 – Evaluable Efficacy (7
Days) Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL='Y' and ADSL.MULENRFL
ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N' and ADC19EF.PDP27FL='Y'
12 adc19ef-ve-cov-adc19ef ve cov 7p Vaccine Efficacy – First COVID -19 ADSL ADSL.EVALEFFL='Y' and ADSL.MULENRFL
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40 Table Program
Name Output Name Title Input Population Subset used
7pd2-eval-sas.txt d2 eval.html Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period
– Subjects With or Without Evidence of
Infection Prior to 7 Days After Dose 2 –
Evaluable Efficacy (7 Days) Po pulation ADC19EF
ADSYMPT ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N'
13 adc19ef-ve-cov-
7pd2-wo-sg-eval-
sas.txt adc19ef ve cov 7p
d2 wo sg evalht
ml Vaccine Efficacy – First COVID -19
Occurrence From 7 Days After Dose 2, by
Subgroup – Blinded Placebo -Controlled
Follow-up Period – Subjects Without Evidence
of Infection Prior to 7 Days After Dose 2 –
Evaluable Efficacy (7 Days) Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL='Y' and ADSL.MULENRFL
ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N' and ADC19EF.PDP27FL='Y'
14 adc19ef-ve-cov-
7pd2-sg-eval-
sas.txt adc19ef ve cov 7p
d2 sg evalhtml Vaccine Efficacy – First COVID -19
Occurrence From 7 Days After Dose 2, by
Subgroup – Blinded Placebo -Controlled
Follow-up Period – Subjects With or Without
Evidence of Infection Prior to 7 Days After
Dose 2 – Evaluable Efficacy (7 Days)
Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL='Y' and ADSL.MULENRFL
ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N'
15 adc19ef-ve-sev-
cov-7pd2-wo-
eval-sas.txt adc19ef ve sev co
v 7pd2 wo evalht
ml Vaccine Efficacy – First Severe COVID-19
Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period
– Subjects Without Evidence of Infection Prior
to 7 Days After Dose 2 – Evaluable Efficacy (7
Days) Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL='Y' and ADSL.MULENR FL
ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N' and ADC19EF.PDP27FL='Y'
16 adc19ef-ve-sev-
cov-7pd2-eval-
sas.txt adc19ef ve sev co
v 7pd2 evalhtml Vaccine Efficacy – First Severe COVID -19
Occurrence From 7 Days After Dose 2 –
Blinded Placebo -Controlled Follow -up Period
– Subjects With or Without Evidence of
Infection Prior to 7 Days After Dose 2 –
Evaluable Efficacy (7 Days) Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL='Y' and ADSL.MULENRFL
ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N'
17 adc19ef-ve-sev-
cov-pd1-aai-adc19ef ve sev co
v pd1 aaihtml Vaccine Efficacy – First Severe COVID -19
Occurrence After Dose 1 – Blinded Placebo -ADSL
ADC19EF ADSL.AAI1EFFL='Y' and ADSL.MULENRFL ne
"Y" and ADSL.PHASEN ne 1 and ADSL.HIVFL
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Study C4591001 Analysis Data Reviewer’s Guide
41 Table Program
Name Output Name Title Input Population Subset used
sas.txt Controlled Follow-up Period – Dose 1 All -
Available Efficacy Population ADSYMPT = 'N'
18 adsl-demo-7d-
eval-eff-sas.txt adsl demo 7d eval
effhtml Demographic Characteristics – Blinded
Placebo-Controlled Follow -up Period –
Subjects Without Evidence of Infection Prior
to 7 Days After Dose 2 – Evaluable Efficacy (7
Days) Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL=”Y” and ADSL.MULENRFL
ne "Y" and ADSL.PHASEN ne 1 and
ADC19EF.PDP27FL='Y'
19 adsl-demo-7d-
wwo-eval-eff-
sas.txt adsl demo 7d ww
o eval effhtml Demographic Characteristics – Blinded
Placebo-Controlled Follow -up Period –
Subjects With or Without Evidence of
Infection Prior to 7 Days After Dose 2 –
Evaluable Efficacy (7 Days) Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL=”Y” and ADSL.MULENRFL
ne "Y" and ADSL.PHASEN ne 1 and
ADC19EF.PDP27FL in ('Y' ‘N’)
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Study C4591001 Analysis Data Reviewer’s Guide
42 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 .
Disposition of All Randomized Subjects – Phase 2/3 Subjects ≥16 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo Total
(Na=xx) (Na=xx) (Na=xx)
nb (%) nb (%) nb (%)
Randomized xx (xxx.x) xx (xxx.x)
Not vaccinated ( ) xx (xxx.x) xx (xxx.x)
Original blinded placebo -controlled follow -up period
Vaccinated xx (xxx.x)
Dose 1 xx (xxx.x)
Dose 2 xx (xxx.x) xx (xxx.x) xx (xxx.x)
Discontinued from original blinded placebo -controlled follow -up vaccination
periodc )
Reason for discontinuation
Adverse event )
Withdrawal by subject )
Physician decision )
Death xx (xxx.x)
Pregnancy xx (xxx.x)
Other xx (xxxx)
Unblinded before 1 -month post –Dose 2 visit xx (xxx.x) xx (xxx.x) xx (xxx.x)
Completed 1 -month post –Dose 2 visit xx (xxx.x) xx (xxx.x) xx (xxx.x)
xx (xxx.x) xx (xxx.x) xx (xxx.x) ADSL.TRT01P
ADSL.RANDFL eq 'Y' and ADSL.PHASEN ne 1 and
ADSL.AGEGR3N ne . and ADSL.MULENRFL ne "Y"
ADSL.RANDFL eq 'Y'
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.VAX101DT ne . or ADSL.VAX102DT ne .)
ADSL.RANDFL eq 'Y' and ADSL.VAX101DT ne . ADSL.RANDFL eq 'Y' and ADSL.VAX102DT ne . and
(ADSL.VAX102DT< ADSL.UNBLNDDT or ADSL.UNBLNDDT=.)
ADSL.RANDFL eq 'Y' and ADDS.DSPHASEN=26 and ADSL.EOTDCDT ne .
and ADDS.dsdecodn not in (. 2) and (ADSL.VAX101DT ne . or ADSL.VAX102DT
ne .) and (ADSL.unblnddt=. or ADSL.eotdcdt< ADSL.unblnddt)
1. Subset below section with criteria: ADSL.RANDFL eq 'Y' and ADDS.DSPHASEN=26 and
ADSL.EOT DCDT 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 ADSL.UNBLNDDT ne . and
(ADSL.UNBLNDDT<= ADDS.M1PD2DT or ADDS.M1PD2DT=.)
ADSL.RANDFL eq 'Y' and ((ADDS.DSPHASEN=26 and ADDS.dsdecodn=2)) and (ADSL.unblnddt=.
or ADDS.astdt< ADSL.unblnddt)
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Study C4591001 Analysis Data Reviewer’s Guide
43
Withdrawn from the study
Withdrawn after Dose 1 and before Dose 2 xx (xxx.x)
Withdrawn after Dose 2 and before 1 -month post –Dose 2 visit xx (xxxx)
Withdrawn after 1 -month post –Dose 2 visit
Reason for withdrawal from the study
Adverse event
Withdrawal by subject
Physician decision xx.x)
Death xx.x)
Pregnancy xx.x)
Other xx.x)
Open-label follow -up period
Originally randomized to BNT162b2
Received Dose 2/unplanned dose xx (xxx.x)
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
Pregnancy
Other
Originally randomized to placebo
Withdrawn from the study after unblinding and before Dose 3 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=. or ADSL.eosdcdt<
ADSL.unblnddt) and ADSL.EOSDCDT ne ADSL .EOTXDCDT
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=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.eosd cdt< 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
ADSL.RANDFL eq 'Y' and (ADSL.UNBLNDDT ne . or ADSL.vax201dt ne .) and index(ADSL.arm,'BNT')
ADSL.RANDFL eq 'Y' and ((ADSL.VAX102DT>= ADSL.UNBLNDDT) or (index(ADSL.VAX10u,'BNT') and
ADSL.VAX10UDT>=UNBLNDDT )) and ADSL.UNBLNDDT ne . and index( ADSL.arm,'BNT')
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') RANDFL eq 'Y' and vax101dt ne . and vax102dt ne .
and M6PD2DT ne . and (UNBLNDDT ne . or vax201dt
ne .) and index(arm,'BNT')
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and (VAX101DT
ne . or VAX102DT ne .) and (unblnddt ne . and eosdcdt>=unblnddt) and index(arm,'BNT')
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and (VAX101DT ne . or VAX102DT
ne .) and (M6PD2DT=. or M6PD2DT> astdt) and (unblnddt ne . and eosdcdt>=unblnddt) and index(arm,'BNT')
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and vax101dt ne . and vax102dt
ne . and M6PD2DT ne . and M6PD2DT le astdt and (unblnddt ne . and eosdcdt>=unblnddt) and index(arm,'BNT')
1. Subset below section with criteria : RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (.
2) and (VAX101DT ne . or VAX102DT ne .) and (unblnddt ne . and eosdcdt>=unblnddt) and index(arm,'BNT')
2. Report by each ADDS. DSDECOD. RANDFL eq 'Y' and
(UNBLNDDT ne . or
vax201dt ne .) and
index(armcd,'PLACEBO')
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and
(VAX201DT=. and VAX202DT=.) and (unblnddt ne . and eosdcdt>=unblnddt) and
index(armcd,'PLACEBO')
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Study C4591001 Analysis Data Reviewer’s Guide
44 Received Dose 3 (first dose of BNT162b2 [30 µg]) xx (xxx.x)
Received Dose 4 (second dose of BNT162b2 [30 µg])
Discontinued from open -label vaccination periodd
Reason for discontinuation from open -label vaccination period
Adverse event
Withdrawal by subject xx (xxx.x)
Physician decis ion
Death
Pregnancy
Other xx (xxx.x)
Completed 1 -month post –Dose 4 visit xx (xxxx)
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 xx (xxx.x)
Reason for withdrawal from the study
Adverse event
Withdrawal by subject
Physician decision
Death
Pregnancy
Other
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported separately.
Note: Subjects randomized but did not sign informed consent or had a significant quality event due to lack of PI oversight are not included in any analysis population
Note: Because of a dosing error, Subject[s] C4591001 xxxx xxxxx [and C4591001 xxxx xxxxxx] received an a dditional dose of BNT162b2 (30 µg) at an unscheduled
visit after receiving 1 dose of BNT162b2 (30 µg) and 1 dose of placebo.
a. N = number of randomized 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. Original blinded placebo -controlled vaccination period is defined as the time period from Dose 1 to 1 month post –Dose 2.
d. Open -label vaccination period is defined as the time period from Dose 3 (first dose of BNT162b2 [30 μg]) to 1 month post –Dose 4 (second dose of BNT162b2 [30
μg]).
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generatio n: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN RANDFL eq 'Y' and index(VAX201,'BNT') and index(armcd,'PLACEBO')
RANDFL eq 'Y' and index(VAX202,'BNT') and index(armcd,'PLACEBO')
RANDFL eq 'Y' and DSPHASEN=7 and EOTXDCDT ne . and dsdecodn
not in (. 2) and vax201dt ne . and index(armcd,'PLACEBO')
1. Subset below section with criteria: RANDFL eq 'Y' and DSPHASEN=7 and EOTXDCDT
ne . and dsdecodn not in (. 2) and vax201dt ne . and index(armcd,'PLACEBO')
2. Report by each ADDS. DSDECOD.
RANDFL eq 'Y' and ((DSPHASEN=7 and dsdecodn=2)) and index(armcd,'PLACEBO')
1. Subset below section with criteria RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and
(VAX201DT ne . or VAX202DT ne .) and ((unblnddt ne . and eosdcdt>=unblnddt) or eosdcdt=eotxdcdt) and index(armcd,'PLACEBO')
2. Report by each ADDS. DSDECOD.
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and (VAX201DT ne . or VAX202DT ne
.) and ((unblnddt ne . and eosdcdt>=unblnddt) or eosdcdt=eotxdcdt) and index(armcd,'PLACEBO')
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and vax201dt ne . and
((vax201dt<=astdt and vax202dt eq .) or vax201dt<=astdt < vax202dt) and ((unblnddt ne . and
eosdcdt>=unblnddt) or eosdcdt=eotxdcdt) and index(armcd,'PLACEBO')
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and vax201dt ne . and vax202dt ne . and (vax202dt <= astdt
and (M1PX2DT eq . or astdt<M1PX2DT)) and ((unblnddt ne . and eosdcdt>=unblnddt) or eosdcdt=eotxdcdt) and index(armcd,'PLACEBO ')
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2) and vax201dt ne . and vax202dt ne . and M1PX2DT
ne . and M1PX2DT le astdt and ((unblnddt ne . and eosdcdt>=unblnddt) or eosdcdt=eotxdcdt) and index(armcd,'PLACEBO')
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Study C4591001 Analysis Data Reviewer’s Guide
45
Follow-up Time After Dose 2 – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg)
(Na=xx)
nb (%) Placebo
(Na=xx)
nb (%) Total
(Na=xx)
nb (%)
Subjects (%) with length of follow -up of:
Original blinded placebo -controlled vaccination period
<2 Months xx (xx.x) xx (xx.x)
≥2 Months to <4 months xx (xx.x) xx (xx.x)
≥4 Months to <6 months xx (xx.x) xx (xx.x) xx (xx.x)
≥6 Months xx (xx.x) xx (xx.x) xx (xx.x)
Total exposure from Dose 2 to cutoff date
<2 Months
≥2 Months to <4 months
≥4 Months to <6 months xx (xx.x)
≥6 Months xx (xx.x)
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but analyzed and reported separately.
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)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADSL.SAFFL eq "Y" and ADSL.PHASEN ne 1 and ADSL.AGEGR1N not in (. 1) and ADSL.MULENRFL ne "Y"
ADSL.FUP2CA2N in (1,2)
ADSL.FUP2CA2N in (3,4)
ADSL.FUP2CA2N in (5,6)
ADSL.FUP2CA2N >6 ADSL.TRT01A
ADSL.FUP2CA1N in (1,2)
ADSL.FUP2CA1N in (3,4)
ADSL.FUP2CA1N in (5,6)
ADSL.FUP2CA1N >6
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Study C4591001 Analysis Data Reviewer’s Guide
46
Local Reactions, by Maximum Severity, Within 7 Days After Each Dose, by Age Group (Reactogenicity Subset) – Phase 2/3 Subjects ≥
16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
Age
Group Dose Local Reaction Na nb (%) (95% CIc) Na nb (%) (95% CIc)
16-55
Years 1 Rednessd
Any x, xx.x) xx.x) (xx.x, xx.x)
Mild x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Swellingd
Any x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate ( ) ( x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Pain at the
injection sitee
Any NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
ADSL.AGEGR1
ADFACEVD.FAOBJ
ADSL.SAFFL="Y" and ADSL.HIVFL="N"
and ADFACEVD. FAOBJ in ("PAIN AT
INJECTION SITE" "SWELLING"
"REDNESS") and ADSL.KNOWVFL="Y"
and ADFACEVD. TRTA ne "" and
ADSL.PHASEN ne 1 and ADSL.AGEGR1N^=1
and ADSL.MULENRFL^='Y' and
ADSL.CUTUNBFL ne "Y"
For Dose ne “Any Dose”:
if ADFACEVD. ATPTREF = "VACCINATION
2" and ADSL.VAX101 ne ADSL.VAX102 then
delete;
ADFACEVD.FATESTCD
=’MAXSEV’ and AVALC
ne ‘’ and EVENTF=’Y’
ADFACEVD.ATPTREF ADFACEVD. TRTA
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023111
Study C4591001 Analysis Data Reviewer’s Guide
47 Any local reactionf NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
2 <Repeat for Dose
2>
Any
dose <Repeat for any
dose>
<Repeat
for each
age
group>
Note: Reactions were collected in the electronic diary (e -diary) from Day 1 through Day 7 after each dose.
Note: Grade 4 reactions were classified by the investigator or medically qualified person .
a. N = number of subjects reporting at least 1 yes or no response for the specified reaction after the specified dose .
b. n = Number of subjects with the specified characteristic.
c. Exact 2-sided CI based on the Clopper and Pearson method.
d. Mild: >2.0 to 5.0 cm; moderate: >5.0 to 10.0 cm; s evere: >10.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness
category only).
e. Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity; Grade 4: emergency r oom visit or hospitalization
for severe pain at the injection site.
f. Any local reaction: any redness >2.0 cm, any swelling >2.0 cm, or any pain at the injection site.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Genera tion: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023112
Study C4591001 Analysis Data Reviewer’s Guide
48
Systemic Events, by Maximum Severity, Within 7 Days After Each Dose, by Age Group (Reactogenicity Subset) – Phase 2/3 Subjects ≥16 Years
of Age – Safety Population
Vaccine Group (as Administered)
Age Group Dose Systemic Event BNT162b2 (30 µg) Placebo
Na nb (%) (95% CIc) Na nb (%) (95% CIc)
16-55
Years 1 Fever
≥38.0℃ x.x, x ) (xx.x, xx.x)
≥38.0℃ to 38.4℃ x.x, x ) (xx.x, xx.x)
>38.4℃ to 38.9℃ x.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
>38.9℃ to 40.0℃ x.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
>40.0℃ x.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Fatigued
Any x.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild x.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Headached
Any NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Chillsd ADSL.AGEGR1 ADFACEVD.ATPTREF
ADFACEVD.FAOBJ
ADSL.SAFFL="Y" and ADFACEVD .TRTA ne ""
and ADFACEVD .FAOBJ not in ("PAIN AT
INJECTION SITE" "SWELLING" "REDNESS")
and
index(upcase( ADFACEVD .FAOBJ),"HOSPI")=0
and ADSL.KNOWVFL="Y" and ADSL.PHASEN
ne 1 and ADSL.AGEGR1N^=1 and
ADSL.MULENRFL^='Y' and ADSL.HIVFL='N'
and ADSL.CUTUNBFL ne "Y"
For Dose ne “Any Dose”:
if ADFACEVD .ATPTREF= "VACCINATION 2"
and ADSL.VAX101 ne ADSL.VAX102 then delete;
FATESTCD in ("MAXSEV"
"MAXTEMP" "MEDTFVPN") and
EVENTFL="Y" and AVALC ne “” ADFACEVD .TRTA
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023113
Study C4591001 Analysis Data Reviewer’s Guide
49 Any NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Vomitinge
Any NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Diarrheaf
Any NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
New or worsened muscle
paind
Any NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
New or worsened joint
paind
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023114
Study C4591001 Analysis Data Reviewer’s Guide
50 Any NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Mild NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Moderate NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Severe NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Grade 4 NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Any systemic eventg NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
Use of antipyretic or pain
medicationh NN nn (xx.x) (xx.x, xx.x) NN nn (xx.x) (xx.x, xx.x)
2 <Repeat for Dose 2>
Any
dose <Repeat for any dose>
<Repeat for
each age
group>
Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 through Day 7 after each dose. Grade 4 events were
classified by the investigator or medically qualified person .
a. N = number of subjec ts reporting at least 1 yes or no response for the specified event after the specified dose.
b. n = Number of subjects with the specified characteristic.
c. Exact 2-sided CI based on the Clopper and Pearson method.
d. Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or h ospitalization for
severe fatigue, severe headache, severe muscle pain, or severe joint pain.
e. Mild: 1 to 2 times in 24 hours ; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or hospitalization fo r severe
vomiting.
f. Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours; Grade 4: emergency room visit or
hospitalization for severe diarrhea.
g. Any systemic event: any fever ≥38.0℃, any fatigue, any vomiting, any chills, any diarrhea, any headache, any new or worsened muscle pain, or any new or
worsened joint pain.
h. Severity was not collected for use of antipyretic or pain medication.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023115
Study C4591001 Analysis Data Reviewer’s Guide
51
Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 to 1 Month After Dose 2 – Blinded Placebo -
Controlled Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
(Na=xx) (Na=xx)
Adverse Event nb (%) nb (%)
Any event xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x)
Life-threatening xx (xx.x) xx (xx.x)
Any serious adverse event xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x)
Severe ( ) xx (xx.x)
Life-threatening xx (xx.x)
Any adverse event leading to withdrawal xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x)
Life-threatening (xx.x) xx (xx.x)
Death xx (xx.x) xx (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 of subjects reporting at least
1 occurrence of any event.
c. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generat ion: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
AECAT='ADVERSE EVENT' and ADSL.SAFFL=’Y’ and ADAE.VPHASEN in (1,2,3) and
ADSL.PHASEN ne 1 and ADSL.AGEGR1N ne 1 and ADSL.HIVFL ne 'Y' and
ADSL.MULENRFL ne "Y" and ADSL.V01DT >= ADAE.ASTDT
upcase(ADAE.AREL)=”RELATED”
ADAE.ATOXGRN=3
ADAE.ATOXGR N=4
ADAE.AESER=”Y”
index (upcase(ADAE.AEACN),'DRUG
WITHDRAWN') > 0 or ADAE.AESUBJDC='Y')
ADAE.AESDTH=’Y’ or ADAE.AEOUT=’FATAL’ ADSL.TRT01A ADSL.SAFFL="Y" and ADSL.PHASEN ne 1 and ADSL.AGEGR1N ne 1
and ADSL.MULENRFL ne "Y" and ADSL.HIVFL ne 'Y' and NOT
(ADSL.VAX101=’’ and ADSL.VAX102=’’)
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023116
Study C4591001 Analysis Data Reviewer’s Guide
52
Incidence Rates of at Least 1 Adverse Event From Dose 1 to Unblinding Date – Phase 2/3 Subjects ≥16 Years of Age – Safety
Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
(Na=xxx, TEb =xxx) (Na=xxx, TEb =xxx)
Adverse Event n IR (/100 PY)d (95% CIc) nc IR (/100 PY)d (95% CIc)
Any event xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Relatedf xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Severe x.x (xx.x, xx.x) xx
Life-threatening x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Any serious adverse event x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Relatedf xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Severe xx.x) xx x.x (xx.x, xx.x)
Life-threatening xx.x) xx x.x (xx.x, xx.x)
Any adverse event leading to withdrawal xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Relatedf xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Severe xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Life-threatening x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Death xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
a. N = number of subjects in the specified group.
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 blinded follow -up. This value is the d enominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For “any event,” n = the numb er 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 rel ated to investigational product.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
upcase(ADAE.AREL)=”RELATED”
ADAE.ATOXGRN=3
ADAE.ATOXGR N=4
ADAE.AESER=”Y”
upcase(ADAE.AEACN)='DRUG
WITHDRAWN' or ADAE.AESUBJDC='Y'
upcase(ADAE.AEOUT)=’FATAL’
SUM(ADSL. FUP1UNB)/(365.25*100)
ADSL.TRT01A ADAE.AECAT = 'ADVERSE EVENT' and ADSL. SAFFL=’Y’ and ADSL.AGETR01 >=16 and
ADSL.PHASEN in (2,3,4) and ADAE.VPHASEN>0 and ADSL.MULENRFL ne ‘Y’ and
ADSL.HIVFL ne 'Y' and (.<ADSL.VAX101DT<=ADAE.ASTDT<=ADSL.BDCSRDT) ADSL.SAFFL=’Y’ and ADSL.AGETR01 >=16 and ADSL.PHASEN
in (2,3,4) and ADSL.MULENRFL ne ‘Y’ and ADSL.HIVFL ne 'Y'
and (ADSL.VAX101DT ne . and ADSL.BDCSRDT ne .)
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023117
Study C4591001 Analysis Data Reviewer’s Guide
53
Tier 2 Adverse Events Reported From Dose 1 to 1 Month After Dose 2, by System Organ Class and Preferred Term –
Blinded Placebo -Controlled Follow -up Period – Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 μg) Placebo
(Na=xx) (Na=xx) Difference
System Organ Class
Preferred Term nb (%) (95% CIc) nb (%) (95% CIc) %d (95% CIe)
<System organ class>
<Preferred term> (xx.x, xx.x) xx.x (xx.x, xx.x)
<Preferred term> (xx.x, xx.x) xx.x (xx.x, xx.x)
<System organ class>
<Preferred term> xx (xx.x) (xx.x, xx.x) xx
<Preferred term> xx (xx.x) (xx.x, xx.x) xx
Note: MedDRA (v23.1) coding dictionary applied.
Note: Tier 2 events are "common" adverse events with an incidence rate ≥1.0% in any vacc
at this stage for this program.
Note: The 95% confidence interval quantifies the precision of the risk difference estimate. C
only be used to identify potentially important adverse events.
a. N = number of su bjects 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 adverse event.
c. Exact 2 -sided CI based on the Clopper and Pearson method.
d. Difference in proportions, expressed as a percentage (BNT162b2 [30 μg] – placebo).
e. 2-Sided CI, based on the Miettinen and Nurminen method for the difference in proportions, expressed as a percentage.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMY YYY (HH:MM) Source Data: xxxx Table Generation: DDMMYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADAE.AEBODSYS
ADAE.AEDECOD ADSL.TRT01A
ADAE.AECAT = 'ADVERSE EVENT' and ADAE.VPHASEN in (1,2)
and ADAE.V01DT >= ADAE.ASTDT and (ADAE.UNBLNDDT = . or
ADAE.UNBLNDDT > ADAE.ASTDT) and ADSl.AGEGR1N ne 1 and
ADSL.MULENRFL ne "Y" and ADSL.HIVFL ne "Y"
Method Used:
proc binomial data=XXXX out=XXXX1 max_time=120 alpha=0.95 ;
by _event;
RISKDIFF / AS ONE STD;
popl _trt_id;
outcome _exist;
run;
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023118
Study C4591001 Analysis Data Reviewer’s Guide
54
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 ≥16 Years of Age (Subjects Who Originally
Received BNT162b2) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
(Na=xx) (Na=xx)
Adverse Event nb (%) nb (%)
Any event xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x)
Life-threatening xx (xx.x) xx (xx.x)
Any serious adverse event xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x)
Life-threatening xx (xx.x)
Any adverse event leading to withdrawal xx (xx.x)
Relatedc xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x)
Life-threatening x (xx.x) xx (xx.x)
Death xx (xx.x) xx (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 = the number of subjects report ing at
least 1 occurrence of any event.
c. Assessed by the investigator as related to investigational product.
PFIZER CONFIDENT IAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: xxxx Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
upcase(ADAE.AREL)=”RELATED”
ADAE.ATOXGRN=3
ADAE.ATOXGR N=4
ADAE.AESER=”Y”
index (upcase(ADAE.AEACN),'DRUG
WITHDRAWN') > 0 or ADAE.AESUBJDC='Y') ADAE.SAFFL="Y" and ADSL.HIVFL ne 'Y' and ADSL.PHASEN
ne 1 and ADSL.AGEGR1N ne 1 and MULENRFL ne "Y" and
TRT01AN = 8 and DS3KFL='Y'
ADAE.AESDTH=’Y’ or ADAE.AEOUT=’FATAL’ ADSL.TRT01A
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023119
Study C4591001 Analysis Data Reviewer’s Guide
55
Incidence Rates of at Least 1 Adverse Event From Dose 3 to Data Cutoff Date (DDMMMYYYY) – Open-Label
Vaccination Period – Subjects Who Originally Received Placebo and Then Received BNT162b2 After Unblinding –
Phase 2/3 Subjects ≥16 Years of Age – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
(Na=xxx, TEb =xxx) (Na=xxx, TEb =xxx)
Adverse Event nc IR (/100 PY)d (95% CIc) nc IR (/100 PY)d (95% CIc)
Any event xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Relatedf xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Severe x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Life-threatening x.x (xx.x, xx.x) xx
Any serious adverse event x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Relatedf xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Severe x) xx x.x (xx.x, xx.x)
Life-threatening x) xx x.x (xx.x, xx.x)
Any adverse event leading to withdrawal xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Relatedf xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Severe xx x x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Life-threatening (xx.x, xx.x) xx x.x (xx.x, xx.x)
Death xx x.x (xx.x, xx.x) xx x.x (xx.x, xx.x)
Note: Dose 3 = First dose of BNT162b2 (30 ug).
a. N = number of subjects in the specified group.
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 blinded follow -up. This value is the d enominator for the incidence rate calculation.
c. n = Number of subjects reporting at least 1 occurrence of the specified event category. For “any event,” n = the numb er 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) upcase(ADAE.AREL)=”RELATED”
ADAE.ATOXGRN=3
ADAE.ATOXGR N=4
ADAE.AESER=”Y”
index (upcase(ADAE.AEACN),'DRUG
WITHDRAWN') > 0 or ADAE.AESUBJDC='Y')
upcase(ADAE.AEOUT)=’FATAL’
SUM(ADSL. FPX1CUT)/(365.25*100)
ADSL.TRT02A ADAE.AECAT='ADVERSE EVENT' and ADSL.S AFFL=’Y’ and ADAE.VPHASEN >=5
and ADAE.VPHASEN ne 99 and ADSL.PHASEN ne 1 and ADSL.AGETR01 ge 16 and
ADSL.MULENRFL ne "Y" and ADSL.HIVFL ne 'Y' and ADSL.ARM=’Placebo’ and
.<ADSL.VAX201DT <= ADAE.ASTDT<=ADSL.X1CSRDT ADSL.SAFFL=’Y’ and ADSL.HIVFL ne 'Y' and ADSL.PHASEN ne 1 and
ADSL.AGETR01 ge 16 and ADSL.MULENRFL ne ‘Y’ and
ADSL.ARM=’Placebo’ and ADSL.VAX201DT>. and ADSL.X1CSRDT>.
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
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Study C4591001 Analysis Data Reviewer’s Guide
56 (Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
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Study C4591001 Analysis Data Reviewer’s Guide
57
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period – Subjects 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=nn) (Na=nn)
Efficacy Endpoint
n1b Surveillance
Timec (n2d) n1b Surveillance
Timec (n2d) VE (%) (95% CIe) Pr (VE >30% | data)f
First COVID -19 occurrence from 7 days after
nnn xxx (nnn) nnn xxx (nnn) xx.x (xx.x,
xx.x) x.xxxx
AT = nucleic acid amplification test; SARS CoV-2 = severe acute respiratory syndrome
7 days aft er receipt of t
asal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days a fter 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 da ys 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. Posterior probability (Pr) was calculated using a beta -binomial model with prior beta (0.700102, 1) adjusted for surveillance time. Refer to the statistical analysis
plan, Appendix 2, for more details.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Da ta: abcdefgh Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 – Blinded Placebo-Controlled Follow -up Period – Subjects
With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population
• Follow the same annotations as above mock, except do not use PDP27FL=”Y” subset condition as this table is for subject s With or Without
Evidence of Infection Prior to 7 Days After Dose 2
ADSL.EVALEFFL=”Y” and ADSL.MULENRFL ne
"Y" and ADSL.PHASEN ne 1 and ADSL.HIVFL = 'N' ADSL.EVALEFFL=”Y” and ADSL.MULENRFL ne
"Y" and ADSL.PHASEN ne 1 and ADSL.HIVFL =
'N' and ADC19EF. PDP27FL = "Y"
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(ADSL.DVSTDT) and
ADC19EF.ADT <= ADSL.DVSTDT) or missing(ADSL.DVSTDT)). ADC19EF.PDRMUPFL = "N" AND ADC19EF.PDP27FL = "Y" AND
ADC19EF.PARAMCD IN ("ST27PD") AND ADC19EF.AVAL > 0
Sum of ADC19EF.AVAL where
ADC19EF.PARAMCD IN ("ST27PD") ADSL.RANDFL=”Y”
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Study C4591001 Analysis Data Reviewer’s Guide
58
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2, by Subgroup – Blinded Placebo-Controlled Follow -up Period
– Subjects 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 Survei
Timec (n2) VE (%)
(95% CIe)
First COVID -19 occurrence from 7 days after Dose 2
Overall xx xxx (xx) xx
Age group (years)
12 to 15 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
16 to 55 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
>55 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
≥65 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
16 to 17 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
16 to 25 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
16 to 64 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
18 to 64 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
55 to 64 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
65 to 74 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
≥75 x xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
75 to 85 xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
>85 xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Sex
Male xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Female xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Race ADSL. EVALEFFL =”Y” and
ADSL.MULENRFL ne "Y" and
ADSL.PHASEN ne 1 and ADSL.HIVFL
= 'N' and ADC19EF. PDP27FL = "Y" 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(ADSL.DVSTDT) and ADC19EF.ADT <= ADSL.DVSTDT) or
missing(ADSL.DVSTDT)).
Sum of ADC19EF.AVAL where
ADC19EF.PARAMCD IN ("ST27PD")
ADC19EF.PDRMUPFL = "N" AND
ADC19EF.PDP27FL = "Y" AND
ADC19EF.PARAMCD IN ("ST27PD") AND
ADC19EF.AVAL > 0
ADSL.AGETR01
12<=AGETR01<=15 for 12 to 15
16<=AGETR01<=55 for 16 to 55
AGETR01>55 for >55
AGETR01>=65 for >65
16<=AGETR01<=17 for 16 to 17
16<=AGETR01<=25 for 16 to 25
16<=AGETR01<=64 for 16 to 64
18<=AGETR01<=64 for 18 to 64
55<=AGETR01<=64 for 55 to 64
65<=AGETR01<=74 for 65 to 74
AGETR01>=75 for >75
75<=AGETR01<=85 for 75 to 85
AGETR01>85 for >85
ADSL.ARACE
ADSL.SEX
ADSL.RANDFL=”Y” ADSL.EVALEFFL=”Y” and
ADSL.MULENRFL ne "Y" and
ADSL.PHASEN ne 1 and ADSL.HIVFL = 'N'
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
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Study C4591001 Analysis Data Reviewer’s Guide
59 White xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Black or African American 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)
All othersf xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Racial designation
Japanese 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
Argentina xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Brazil xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Germany xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
South Africa xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
xx xxx (xx) xx.x (xx.x, xx.x)
xx xxx (xx) xx.x (xx.x, xx.x)
Prior SARS -CoV-2 status
Positive at baselineg xx xxx (xx) xx xxx (xx) xx.x (xx.x, xx.x)
Positive N-binding only
Positive NAAT only
Positive NAAT and N -binding
Negative at baseline but positive prior to 7 days after
Dose 2h
Negative prior to 7 days after Dose 2i x, xx.x)
Unknown x, xx.x)
Abbreviations: N le ndrome
coronavirus 2; VE = vaccine efficacy. ADSL.RACIALDN=5
ADSL.COUNTRY
ADC19EF.VRBLNGFL='N' or ADC19EF.CRD1NGFL='N' or ADC19EF.C19ILHFL="Y" or
IE.IESTRESC='Y'
ADC19EF.VRBLNGFL='N' or ADC19EF.CRD1NGFL='N' or ADC19EF.C19ILHFL="Y" or
IE.IESTRESC='Y' and (ADSL.NIGV1FL = "N" and ADSL.NAATNFL ne "N") ADSL.ETHNIC
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.CRD2NGFL="N" or
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"
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
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Study C4591001 Analysis Data Reviewer’s Guide
60 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 surveill ance 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. All others = American Indian or Alaska native, Asian, Native Hawaiian or other Pacific Islander, multiracial, and not reported race categories.
g. Positive N -binding antibody result at Visit 1, positive NAAT result at Visit 1, or medical history of COVID -19.
h. Negative N -binding antibo dy result and negative NAAT result at Visit 1, positive NAAT result at Visit 2 or at unscheduled visit, if any, prior to 7 da ys
after Dose 2 .
i. Negative N -binding antibody result at Visit 1, negative NAAT result at Visit 1 and Visit 2, and negative N AAT result at unscheduled visit, if any, prior to
7 days after Dose 2 .
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
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2, by Subgroup – Blinded Placebo -Controlled Follow -up
Period – Subjects With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Ef ficacy (7 Days) Population
• Follow the same annotations as above mock, except do not use PDP27FL=”Y” subset condition as this table is for subject With o r Without
Evidence of Infection Prior to 7 Days After Dose 2
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
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Study C4591001 Analysis Data Reviewer’s Guide
61
Vaccine Efficacy – First Severe COVID 19 Occurrence From 7 Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period –
Subjects Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Popul ation
Vaccine Group (as Randomized)
BNT162b2 (30 µg) Placebo
(Na=nnn) (Na=nnn)
Efficacy Endpoint
n1b Surveillance
Timec (n2d) n1b Surveillance
Timec (n2d) VE (%) (95% CIe) Pr (VE >30% | data)f
First severe COVID -19 occurrence from 7 days
after Dose 2 nnn xxx (nnn) nnn xxx (nnn) xx.x (xx.x, xx.x) xx.xx%
AT = nucleic acid amplification test; SAR COV2 = severe cute respir tory syndrome coron virus
7 days after receipt of the last dose
b] at Visits 1 and 2), and had nega
j p g p
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endp Time period for COVID -19 case
accrual is from 7 days after Dose 2 to the end of the surveillance per
d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interva l (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
f. Posterior probability (Pr) was calculated using a beta -binomial model with prior beta (0.700102,1) adjusted for surveillance time. Refer to the statistical analysis plan,
Appendix 2, for more details.
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_XN NN
Vaccine Efficacy – First Severe COVID -19 Occurrence From 7 Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period –
Subjects With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Popula tion
• Follow the same annotations as above mock, except do not use PDP27FL=”Y” subset condition as this table is for subject With o r Without
Evidence of Infection Prior to 7 Days After Dose 2
ADSL.EVALEFFL=”Y” and ADSL.MULENRFL
ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N' and ADC19EF. PDP27FL =
Y ADSL.EVALEFFL=”Y” and
ADSL.MULENRFL ne "Y" and
ADSL.PHASEN ne 1 and ADSL.HIVFL = 'N' ADSL.TRT01P
ADSL.EVALEFFL="Y" and ADC19EF.PARAMCD="SEVCONST"
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(ADSL.DVSTDT) and ADC19EF.ADT <= ADSL.DVSTDT) or
missing(ADSL.DVSTDT)).
Sum of ADC19EF.AVAL where ADC19EF.PARAMCD IN
("ST27SE") ADC19EF.PDRMUPFL = "N" AND ADC19EF.PDP 27FL =
"Y" AND ADC19EF.PARAMCD IN ("ST27SE") AND
ADC19EF.AVAL > 0
ADSL.RANDFL=”Y”
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62
Vaccine Efficacy – First Severe COVID-19 Occurrence After Dose 1 – Blinded Placebo -Controlled Follow -up Period – Dose 1 All -
Available Efficacy Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
(Na=xx)
Placebo
(Na=xx)
Efficacy Endpoint
Subgroup n1b Surveillance
Timec (n2d) n1b Surveillance
Timec (n2d) VE (%) (95% CIe)
First Severe COVID -19 occurrence after Dose 1 x xx (xx) x
After Dose 1 to before Dose 2 x xx (xx) x
Dose 2 to 7 days after Dose 2 x
≥7 days after Dose 2 x xx (xx) x xx(xx) xx (xx, xx)
Abbreviations: VE = vaccine efficacy.
d group.
ndpoint definition.
-years for the given en riod for COVID -19 case
accrual is from Dose 1 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
PFIZER CONFIDENTIAL SDTM Creation: 17NOV2020 (0 ) ( )
(Cutoff Date: 14NOV2020, Snapshot Date: 16NOV2020) Output File: ./nda2_unblinded/C4591001_Efficacy_FA_164/adc19ef_ve_cov_7pd2_wo_sg_e val
ADSL.RANDFL=”Y
ADSL.AAI1EFFL="Y" and ADC19EF.PARAMCD="SEVCONST"
and find(ADC19EF.AVALC, 'POS' , 'i') and
ADC19EF.PDRMUPFL="N" and ADC19EF.ADT >=
ADC19EF.VAX101DT and upcase(ADC19EF.FILOCRFL) = "Y". ADSL.TRT01P
Sum of ADC19EF.AVAL where
ADC19EF.PARAMCD IN ("ST1SEA") ADC19EF.PDRMUPFL = "N" AND
ADC19EF.PARAMCD IN ("ST1SEA") AND
ADC19EF.AVAL > 0
(not missing(ADC19EF.VAX101DT) and not
missing(ADC19EF.VAX102DT) and ADC19EF.VAX101DT <=
ADC19EF.ADT < ADC19EF.VAX102DT) or ((not
missing(ADC19EF.VAX101DT) and missing(ADC19EF.VAX102DT) and
ADC19EF.VAX101DT <= ADC19EF.ADT).
not missing(ADC19EF.VAX102DT) and ADC19EF.VAX102DT <=
ADC19EF.ADT < ADC19EF.VAX102DT + 7. not missing(ADC19EF.VA X102DT) and
ADC19EF.ADT >=
ADC19EF.VAX102DT + 7. ADSL.AAI1EFFL=”Y” and ADSL.MULENRFL ne
"Y" and ADSL.PHASEN ne 1 and ADSL.HIVFL = 'N'
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023127
Study C4591001 Analysis Data Reviewer’s Guide
63
Demographic Characteristics – Blinded Placebo -Controlled Follow -up Period – Subjects Without Evidence of
Infection Prior to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Population
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 x) xx (xxx.x)
Black or African American ( ) ( ) xx (xxx.x)
American Indian or Alaska Native ( ) ( ) xx (xxx.x)
Asian (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)
All othersc 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 (xxxx) xx (xxx.x) xx (xxx.x)
Non-Hispanic/non -Latino ( ) xx (xxx.x) xx (xxx.x)
Not reported xx (xxx.x) xx (xxx.x) xx (xxx.x)
Country
Argentina xx (xxx.x) xx (xxx.x) xx (xxx.x) ADSL.EVALEFFL=”Y” and
ADC19EF. PDP27FL='Y' and
ADSL.MULENRFL ne "Y"
and ADSL.PHASEN ne 1
ADSL.TRT01P
ADSL.SEX=”M”
ADSL.ARACE=”WHITE”
ADSL. RACIALDN=5
ADSL.ETHNIC=”HISPANIC OR LATINO”
ADSL.COUNTRY=”ARG” ADSL.ETHNIC=”NOT HISPANIC OR LATINO”
ADSL.ETHNIC=”NOT REPORTED” ADSL.ARACE=”BLACK OR AFRICAN AMERICAN”
ADSL.ARACE=”AMERICAN INDIAN OR ALASKA NATIVE”
ADSL.ARACE=”ASIAN”
ADSL.ARACE=”NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER”
ADSL.ARACE=”MULTIRACIAL”
ADSL.ARACE=”NOT REPORTED”
ADSL.ARACE not in (”WHITE” ”BLACK OR AFRICAN AMERICAN”)
ADSL.SEX=”F”
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
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Study C4591001 Analysis Data Reviewer’s Guide
64 Brazil xx (xxx.x) xx (xxx.x) xx (xxx.x)
Germany xx (xxx.x) xx (xxx.x)
South Africa xx (xxx.x) xx (xxx.x) xx (xxx.x)
Turkey xx (xxx.x) xx (xxx.x)
USA xx (xxx.x) xx (xxx.x) xx (xxx.x)
Age group (years)
12 to 15 xx (xxx.x) xx (xxx.x) xx (xxx.x)
16 to 55 xx (xxxx) xx (xxx.x) xx (xxx.x)
≥55 xx (xxx.x) xx (xxx.x)
≥65 xx (xxx.x) xx (xxx.x)
16 to 17 ( ) xx (xxx.x) xx (xxx.x)
16 to 25 xx (xxx.x) xx (xxx.x)
16 to 64 xx (xxx.x) xx (xxx.x) xx (xxx.x)
18 to 64 xx (xxx.x) xx (xxx.x)
55 to 64 xx (xxx.x) xx (xxx.x) xx (xxx.x)
65 to 64 xx.x) xx (xxx.x) xx (xxx.x)
≥75 ( xx.x) xx (xxx.x) xx (xxx.x)
75 to 85 xx (xxx.x) xx (xxx.x) xx (xxx.x)
>85 xx (xxx.x) xx (xxx.x) xx (xxx.x)
Comorbiditiesd
Yes (xxx.x) xx (xxx.x) xx (xxx.x)
No (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) ADSL.12<= AGETR01<=15
ADSL.COMBODFL=”Y” or (BMICATN = 4
and AGETR01 >=16) or OBESEFL="Y"
then COMORBIDITIES = Yes else
COMORBIDITIES = No
ADSL.COVBLST=”POS”
ADSL.AGETR01
ADSL.COVBLST=”NEG”
ADSL.COVBLST not in (“NEG” “POS”)
ADSL.COUNTRY=”BRA ”
ADSL.COUNTRY=”DEU”
ADSL.COUNTRY=”ZAF”
ADSL.COUNTRY=”TUR”
ADSL.COUNTRY=”USA”
ADSL. 16<=AGETR01<=55
ADSL. AGETR01>=55
ADSL.AGETR01>=65
ADSL.16<= AGETR01<=17
ADSL.16<= AGETR01<=25
ADSL.55<= AGETR01>=64
ADSL. AGETR01>85
ADSL.16<= AGETR01<=64
ADSL.18<= AGETR01<=64
ADSL.65<= AGETR01<=64
AGETR01>=75
ADSL.75<= AGETR01<=85
090177e196f38d37\Final\Final On: 04-May-2021 20:03 (GMT)
FDA-CBER-2021-5683-0023129
Study C4591001 Analysis Data Reviewer’s Guide
65 Median xx.x xx.x xx.x
Min, max (xx, xx) (xx, xx) (xx, xx)
Note: HIV -positive subjects are included in this summary but not included in the analyses of the overall study objectives.
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.
c. All others = American Indian or Alaska nativ e, Asian, Native Hawaiian or other Pacific Islander, multiracial, and not reported race categories.
d. 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 ≥30 kg/m2 (≥16 Years of age) or BMI ≥95th percentile (12 -15 Years of age).
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 D ate: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
Demographic Characteristics – Blinded Placebo -Controlled Follow -up Period – Subjects With or Without Evidence of Infection Prior
to 7 Days After Dose 2 – Evaluable Efficacy (7 Days) Po pulation
• Follow the same annotations as above mock, change subset condition , as below
ADSL.EVALEFFL=”Y” and ADC19EF. PDP27FLin (“Y” “N”) and ADSL.MULENRFL ne "Y" and ADSL.PHASEN ne 1
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66 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’
window. Dose x could be Dose 1, Dose 2, Dose 3 or Dose 4 .
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.V0 1DT) 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) a nd before
unblinding Blinded placebo -
controlled period
After unblinding and before
Vaccination 3 Event start on or after unblinding and Dose 3 is missing Open label follow -up
period
Event start on or after unblinding and before 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 vi sit after Dose 4
(ADSL.V03DT)
See details in below section for ADSL.V03DT Open label follow -up
period
Follow Up 3 Event start after 1 month follow up visit after Dose 4 and before or on the day of 6 months
follow up visit after Dose 4 (ADSL.V04DT)
See details in below section for ADSL.V04DT Open label follow-up
period
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67 VPHASE Comments
Follow Up 4 Event start after the day of 6 months follow up visit after Dose 4 (ADSL.V04DT) Open label follow-up
period
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68 For Phase 1 for BNT162b2 30 mcg and Equivalent Placebo Subjects :
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 7.
If visit 7 blood sample collection date is not available from CO dataset, then use the date of visit 7 from SV dataset.
Else if date of visit 7 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 7 (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 8.
If visit 8 blood sample collection date is not available from CO dataset, then use the date of visit 8 from SV dataset.
Else if date of visit 8 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 8 (V02DT), then ADSL.V0 2DT 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 8.
If visit 8 blood sample collection date is not available from CO dataset, then use the date of visit 8 from SV dataset.
Else if date of visit 8 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
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 available, 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
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69 For Phase 2/3:
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.V0 2DT 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.V02 OBDT)
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
Note: if a subject took Dose 3 in open label vaccination period before V02OBDT , then ADSL.V02 OBDT was reset to the day before Dose 3.
ADSL.V02OBDT =min (V02 OBDT, ADSL. VAX201DT -1).
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 available, 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.
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70 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:
- 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
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71 Rules Programming Logic
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
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72 missing stop day, the last day of the month was used; if missing stop month and day, the last month of the year was used.
Appendix IV: ADFACEVD Analysis Parameters
PARCAT1 PARCAT2 PARAM PARAMCD
REACTOGENICITY ADMINISTRATION SITE Hospitalized for injection site pain occurrence indicator OCHIS
REACTOGENICITY ADMINISTRATION SITE Pain at injection site maximum severity MSPIS
REACTOGENICITY ADMINISTRATION SITE Pain at injection site occurrence indicator OCPIS
REACTOGENICITY ADMINISTRATION SITE Pain at injection site severity/intensity SEVPIS
REACTOGENICITY ADMINISTRATION SITE Redness diameter cm DIARE
REACTOGENICITY ADMINISTRATION SITE Redness grade 4 criteria met G4CRR
REACTOGENICITY ADMINISTRATION SITE Redness maximum diameter MDIRE
REACTOGENICITY ADMINISTRATION SITE Redness maximum diameter cm MADRE
REACTOGENICITY ADMINISTRATION SITE Redness maximum severity MSERE
REACTOGENICITY ADMINISTRATION SITE Redness minimum diameter cm MIDRE
REACTOGENICITY ADMINISTRATION SITE Redness occurrence indicator OCISR
REACTOGENICITY ADMINISTRATION SITE Redness severity/intensity SEVREDN
REACTOGENICITY ADMINISTRATION SITE Swelling diameter cm DIASW
REACTOGENICITY ADMINISTRATION SITE Swelling grade 4 criteria met G4CRS
REACTOGENICITY ADMINISTRATION SITE Swelling maximum diameter MDISW
REACTOGENICITY ADMINISTRATION SITE Swelling maximum diameter cm MADSW
REACTOGENICITY ADMINISTRATION SITE Swelling maximum severity MSESW
REACTOGENICITY ADMINISTRATION SITE Swelling minimum diameter cm MIDSW
REACTOGENICITY ADMINISTRATION SITE Swelling occurrence indicator OCINS
REACTOGENICITY ADMINISTRATION SITE Swelling severity/intensity SEVSWEL
REACTOGENICITY MEDICATIONS GIVEN Medications duration MEDDUR
REACTOGENICITY MEDICATIONS GIVEN Medications medication to treat fever or pain MEDTFVPN
REACTOGENICITY MEDICATIONS GIVEN Medications stop date meds given to trt/pnt symptoms STPDMEDP
REACTOGENICITY SYSTEMIC Chills maximum severity MAXCHIL
REACTOGENICITY SYSTEMIC Chills occurrence indicator OCCHILLS
REACTOGENICITY SYSTEMIC Chills severity/intensity SEVCHIL
REACTOGENICITY SYSTEMIC Diarrhea maximum severity MAXDIAR
REACTOGENICITY SYSTEMIC Diarrhea occurrence indicator OCDIAR
REACTOGENICITY SYSTEMIC Diarrhea severity/intensity SEVDIAR
REACTOGENICITY SYSTEMIC Fatigue maximum severity MAXSFAT
REACTOGENICITY SYSTEMIC Fatigue occurrence indicator OCFATIG
REACTOGENICITY SYSTEMIC Fatigue severity/intensity SEVFATI
REACTOGENICITY SYSTEMIC Fever maximum temperature MAXTEMP
REACTOGENICITY SYSTEMIC Fever occurrence indicator OCFEVER
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73 PARCAT1 PARCAT2 PARAM PARAMCD
REACTOGENICITY SYSTEMIC Headache maximum severity MAXSHEA
REACTOGENICITY SYSTEMIC Headache occurrence indicator OCHEAD
REACTOGENICITY SYSTEMIC Headache severity/intensity SEVHEAD
REACTOGENICITY SYSTEMIC Hospitalized for chills occurrence indicator OCHOCHIL
REACTOGENICITY SYSTEMIC Hospitalized for diarrhea occurrence indicator OCHODI
REACTOGENICITY SYSTEMIC Hospitalized for headache occurrence indicator OCHOHE
REACTOGENICITY SYSTEMIC Hospitalized for joint pain occurrence indicator OCHOJP
REACTOGENICITY SYSTEMIC Hospitalized for muscle pain occurrence indicator OCHOMP
REACTOGENICITY SYSTEMIC Hospitalized for tiredness (fatigue) occurrence indicator OCHOFA
REACTOGENICITY SYSTEMIC Hospitalized for vomiting occurrence indicator OCHOVO
REACTOGENICITY SYSTEMIC Joint pain maximum severity MAXSJP
REACTOGENICITY SYSTEMIC Joint pain occurrence indicator OCJOPAIN
REACTOGENICITY SYSTEMIC Joint pain severity/intensity SEVJOIN
REACTOGENICITY SYSTEMIC Muscle pain maximum severity MAXSMP
REACTOGENICITY SYSTEMIC Muscle pain occurrence indicator OCMPNIS
REACTOGENICITY SYSTEMIC Muscle pain severity/intensity SEVMUSP
REACTOGENICITY SYSTEMIC Vomiting maximum severity MAXSVOM
REACTOGENICITY SYSTEMIC Vomiting occurrence indicator OCVOMI
REACTOGENICITY SYSTEMIC Vomiting severity/intensity SEVVOMI
Appendix V: 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. Along with the xlsx file s, pdf versions of the
same files have been included.
ID File Name Comments
Rheumatic report-cci-rheumatic.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.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)
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74 ID File Name Comments
Pulmonary report-cci-pulmonary.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.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.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.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.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.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.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.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)
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75 ID File Name Comments
Leukemia report-cci-leukemia.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.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.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.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.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.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.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.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.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)
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76 ID File Name Comments
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.
Phase1 c4591001-phase-1-subjects-from
dmw.xlsx Used for ADSL creation to flag the subjects from Phase 1
Phase2 first-c4591001-360-
participants-enrolled-
v1-13aug20-update.xlsx Used for ADSL creation to flag the subjects from Phase 2
DS360 subset
Phase3
DS6000 newlist-c4591001-6k-
participants -enrolled-v3-
17sep2020.csv Used for ADSL creation to flag the subjects from Phase 3
DS6000 subset
HIV PT 201114-hiv-preferred-terms.xlsx Used for ADSL creation to flag the HIV Positive
EUA 12-25
Age group c4591001-subject-list-for-12-25-
immuno-analysis-27jan2021.xlsx Used for ADSL creation to flag the subjects 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
Appendix VI: 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:
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77
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.
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
Appendix VII: 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:
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78
The central laboratory NAAT result will be used for the case definition, unless no result is available from the central laboratory, 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
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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79 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:
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80
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 sympt om occurs,
is at least 7 days after receipt of the second dose
COVID-19 cases for second primary VE objective
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81 Appendix VIII: Detailed subsetting for Analysis:
1.Key Analysis Population Subsetting :
1.1 BLA Phase 2/3 Safety Analysis
Table Category Analysis Population Total Number of Subjects (N) Subset Condition for
Total N 16-55 Years >55 Years Total
Conduct of
Study Randomized 26236 17929 44165 ADSL.PHASEN>1 and ADSL.AGEGR1N>1 and
ADSL.RANDFL ="Y" and ADSL.MULENRFL ^= "Y"
Safety 26164 17883 44047 ADSL.PHASEN>1 and ADSL.AGEGR1N>1 and
ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.TRT01A^=""
Adverse Events Safety population for AEs
reporting from Dose 1 to the
specified reporting window 26021 17826 43847 ADSL.PHASEN>1 and ADSL.AGEGR1N>1 and
ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y" and ADSL.TRT01A^=""
Safety population for AEs
reporting from Dose 1 to 6
month after Dose 2 for
subjects originally received
BNT162b2. Including all of
AEs within 6 -month after
Dose 2 regardless of
unblinding or not. 6666 5340 12006 ADSL.PHASEN>1 and ADSL.AGEGR1N>1 and
ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y" and ADSL.TRT01A^="" and
DS3KFL="Y"
Safety population for AEs
reporting from Dose 2 to the
specified reporting window 25484 17636 43120 ADSL.PHASEN>1 and ADSL.AGEGR1N>1 and
ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y" and ADSL.VAX102DT>. and
ADSL.VAX101=ADSL.VAX102 and
(ADSL.VAX102DT<ADSL.UNBLNDDT or
ADSL.UNBLNDDT=.)
Safety population for AEs
reporting from Dose 3 to the
specified reporting window 11346 8179 19525 ADSL.PHASEN>1 and ADSL. AGEGR1N >1 and
ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y" and ADSL.VAX201DT>. and
ADSL.TRT02A ^=""
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82 Table Category Analysis Population Total Number of Subjects (N) Subset Condition for
Total N 16-55 Years >55 Years Total
Safety population for AEs
reporting from Dose 4 to the
specified reporting window 8534 7377 15911 ADSL.PHASEN>1 and ADSL. AGEGR1N >1 and
ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y" and ADSL.VAX202DT>. and
ADSL.VAX201=ADSL.VAX202
Safety population for AEs
reporting from unblinding
date to the date of cutoff for
subjects originally received
BNT162b2 11786 8523 20309 ADSL.PHASEN>1 and ADSL.AGEGR1N>1 and
ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y" and ADSL.UNBLNDDT ^= . and
ADSL.TRT01A="BNT162b2 Phase 2/3 (30 mcg)"
Reactogenicitya Safety
(Reactogenicity
subset) Dose 1 5979 4086 10065 ADSL.PHASEN>1 and ADSL. AGEGR1N >1 and
ADSL. SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.VAX101 ^="" and ADSL.REACTOFL= "Y"
Dose 2 5847 4051 9898 ADSL.PHASEN>1 and ADSL. AGEGR1N >1 and
ADSL. SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.VAX102 ^="" and ADSL.REACTOFL= "Y" and
ADSL.VAX102DT ^= .
a. For reactogenicity, the N listed here is the number of subjects in reactogenicity subset relative for the specified dose (Inc luding HIV positive
and not transmitted e -diary subjects). And the numbers match with the number of subjects in e -diary transmission table (number of subjects
vaccinated at Dose 1/Dose2) . The N in the maximum severity tables are the number of HIV negative subjects reporting at least 1 yes or no
response before unblinding for the specified reaction/events after the specified dose which is less than the N specified in this table. For the
detailed algorithm, please refer to Appendix I .
1.2 BLA Phase 2/3 Efficacy Analysis
Table
Category Analysis Population Total Number of Subjects ( N) (BNT162b2) Subset Condition for
Total N Sub-Category 12-15 Years 16-55 Years >55 Years Total
Efficacy Dose 1 All -Available
Efficacy 1132 13059 8949 23140 Refer to Appendix I for more
details. ADSL.PHASEN>1 and
ADSL.MULENRFL ^= ‘Y’ and
ADSL.AAI1EFFL = ‘Y’
Evaluable Efficacy Subjects without
evidence of 1006 11752 8311 21069 Refer to Appendix I for more
details. ADSL.EVALEFFL="Y"
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83 Table
Category Analysis Population Total Number of Subjects ( N) (BNT162b2) Subset Condition for
Total N Sub-Category 12-15 Years 16-55 Years >55 Years Total
infection prior to 7
days after Dose 2 and ADC19EF.PDP27FL='Y' and
ADSL.PHASEN ne 1 and
ADSL.MULENRFL ne "Y".
Evaluable Efficacy Subjects with or
without evidence of
infection prior to 7
days after Dose 2 1120 12489 8646 22255 Refer to Appendix I for more
details ADSL.EVALEFFL="Y"
and ADC19EF.PDP27FL in ('Y',
‘N’) and ADSL. PHASEN ne 1
and ADSL.MULENRFL ne "Y".
1.3 BLA Phase 1 Safety and Immunogenicity Analysis for BNT162b2 30 mcg and Equivalent Placebo Subjects
Table Category Analysis Population Total Number of Subjects ( N)
Subset Condition for Total N 18-55 Years 65-85 Years Total
Disposition
Randomized 15 15 30 ADSL.PHASEN =1 and ADSL.COHORTN in (1.18, 1.38)
and ADSL.RANDFL= "Y" and ADSL.MULENRFL ^="Y"
Adverse Events Safety population for
AEs reporting from
Dose 1 15 15 30 ADSL.PHASEN =1 and ADSL.COHORTN in (1.18, 1.38)
and ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y"
Immunogenicity Dose 1 all -available 15 15 30 ADSL.PHASEN =1 and ADSL.COHORTN in (1.18, 1. 38)
and ADSL.AAI01FL= "Y"
Dose 2 all-available 15 15 30 ADSL.PHASEN =1 and ADSL.COHORTN in (1.18, 1.38)
and ADSL.AAI0 2FL="Y"
Dose 1 evaluable 14 14 28 ADSL.PHASEN=1 and ADSL.COHORTN in (1.18, 1.38)
and ADSL.EVAL01FL= "Y"
Dose 2 evaluable 13 14 27 ADSL.PHASEN=1 and ADSL.COHORTN in (1.18, 1.38)
and ADSL.EVAL0 2FL="Y"
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84 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 Immediate adverse event after Dose 1 ADAE.AECAT=’ADVERSE EVENT’ and ADAE.AEIMMFL='Y'
and ADAE.VPHASEN=1
Immediate adverse event after Dose 2 ADAE.AECAT=’ADVERSE EVENT’ and ADAE.AEIMMFL='Y'
and ADAE.VPHASEN=2
From Dose 1 to 7 days after Dose 1 ADAE.AECAT=’ADVERSE EVENT’ and ADAE.VPHASEN=1
and ADSL.VAX101DT<=ADAE.ASTDT <=ADSL.VAX101DT+7
From Dose 2 to 7 days after Dose 2 ADAE.AECAT=’ADVERSE EVENT’ and ADAE.VPHASEN=2
and ADSL.VAX102DT<=ADAE.ASTDT <=ADSL.VAX102DT+7
From Dose 1 to 1 month after Dose 2 ADAE.AECAT=’ADVERSE EVENT’ and ADAE.VPHASEN in
(1,2)
From Dose 1 to unblinding (the day before
unblinding) ADAE.AECAT=’ADVERSE EVENT’ and ADAE.VPHASEN in
(1,2,3,99)
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 ADAE.AECAT=’ADVERSE EVENT’ and ADAE.VPHASEN>=1
and . <ADAE.ASTDT<=ADSL.V02OBDT
Open label follow-up 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) 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 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 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 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 ADAE.AECAT=’ADVERSE EVENT’ and ADAE.VPHASEN>= 4
and ADAE.VPHASEN ne 99 and .<ADAE.ASTDT<=ADSL .
X1CSRDT
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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