Document text
Analysis Data Reviewer ’s
Guide
sBLA (12-15 Years of Age )
BioNTech SE and PFIZER INC.
Study C4591001
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ANALYSIS DATA REVIEWER’S GUIDE
REVISION HISTORY
Version Summary of Major Change(s) and Impact Version Date
1.0 First approved version of Analysis Data Reviewer Guide 14-Dec-2021
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1. Introduction ................................................................................................................................. 5
1.1 Purpose ..................................................................................................................... 5
1.2 Acronyms ................................................................................................................. 6
1.3 Study Data Standards and Dictionary Inventory ...................................................... 7
1.4 Source Data Used for Analysis Dataset Creation ..................................................... 7
2. Protocol Description .................................................................................................................... 7
2.1 Protocol Number and Title ....................................................................................... 7
2.2 Protocol Design in Relation to ADaM Concepts ...................................................... 9
3. Analysis Considerations Related to Multiple Analysis Datasets ............................................... 11
3.1 Study Populations and Core Variables ................................................................... 11
3.2 Treatment Variable ................................................................................................. 16
3.3 Subject Issues that Require Special Analysis Rules ............................................... 18
3.4 Use of Visit Windowing, Unscheduled Visits, and Record Selection .................... 20
3.5 Imputation/Derivation Methods ............................................................................. 20
4. Analysis Data Creation and Processing Issues .......................................................................... 20
4.1 Split Datasets .......................................................................................................... 20
4.2 Data Dependencies ................................................................................................. 20
4.3 Intermediate Datasets ............................................................................................. 20
5. Analysis Dataset Descriptions ................................................................................................... 20
5.1 Overview ................................................................................................................ 20
5.2 Analysis Datasets ................................................................................................... 21
5.2.1 ADSL – Subject -Level Analysis Dataset ............................................................... 22
5.2.2 ADCEVD – Diary and CRF Event Analysis Dataset ............................................ 23
5.2.3 ADAE – Adverse Events Analysis Dataset ............................................................ 23
5.2.4 ADCM – Concomitant Medications Analysis Dataset ........................................... 23
5.2.5 ADDS – Disposition Analysis Dataset .................................................................. 24
5.2.6 ADDV – Protocol Deviation Analysis Dataset ...................................................... 24
5.2.7 ADFACEVD – Diary and Non -event Analysis Dataset ......................................... 24
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 .............................................................. 29
5.2.11 ADVA – Immunogenicity Analysis Dataset .......................................................... 31
6. Data Conformance Summary .................................................................................................... 32
6.1 Conformance Inputs ............................................................................................... 32
6.2 Issues Summary (Pinnacle 21 Enterprise Validation Report) ................................ 33
7. Submission of Programs ............................................................................................................ 36
7.1 ADaM Programs .................................................................................................... 36
7.2 Analysis Output Programs ...................................................................................... 36
8. Appendix ................................................................................................................................... 39
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4 Appendix I: Annotated Mocks for Key Tables ..................................................................... 39
Appendix II: Analysis plan AE windowing logic ................................................................ 51
Appendix III: Handling of Incomplete Dates ....................................................................... 54
Adverse events ............................................................................................................ 54
Concomitant medications/medical histories ............................................................... 56
Appendix IV: ADFACEVD Analysis Parameters ................................................................ 56
Appendix V: External files used during ADaM dataset creation ......................................... 57
Appendix VI: Surveillance Times ........................................................................................ 60
Appendix VII: Efficacy Flow Charts .................................................................................... 61
Appendix VIII: Detailed subsetting for Analysis: ................................................................ 65
1. Key Analysis Population Subsetting: ..................................................................... 65
2. Adverse Event Analysis Reporting Period Subsetting: .......................................... 66
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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. T his
ADRG covers :
• Efficacy analyses for age group 12- 15 years in blinded placebo- controlled follow -up
• Immunogenicity analysis for age groups 12-15 years vs 16- 25 years from Dose 1 to 1 month
after Dose 2
• Safety analysis for age groups 12- 15 years vs 16- 25 years
o From Dose 1 to 1 month after Dose 2 for both age groups
o From Dose 1 to cutoff date for 12 -15 years age group
• Additional reference safety data analysis for 16- 55 years age group
o From Dose 1 to 1 month after Dose 2
o From Dose 1 to unblinding date.
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6 1.2 Acronyms
Acronym Translation
ADaM Analysis Dataset Model
ADRG Analysis Data Reviewer’s Guide
AE Adverse Event
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.)
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
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 DDG WHO Drug Dictionary Global
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 WHODD GLOBALB3Mar2021
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 cutof f of 13Mar2021 was applied on SDTM data. Furthermore, any
data related to the booster portion of the P hase 1 subjects were 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 sBLA 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 assessment of VE against asymptomatic infection vis N -binding antibody
seroconversion and a potential intensive surveillance period for nasal swabbing, for assessment via NAAT :
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8 o Corresponding SoA and procedures added
Amendment 10: 2020-12-01
• Added the possibility of administering BNT162b2 to participants who originally
received placebo, following any local or national recommendations.
• Added the possibility of administering BNT162b2 to participants who originally received placebo, following completion of the active safety surveillance period.
Amendment 9: 2020-10-29
• To better align with the natural history of SARS -CoV-2 infection, adde d 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
consi dered as a single illness.
Amendment 6: 2020-09-08
• Removed exclusion criterion 2 (i.e., known infection with HIV, HCV, or HBV) for Phase 3 and added criteria for HIV- positive participants.
• Decreased the lower age limit and removed the upper age limit for inclusion in Phase 2/3 in order to evaluate BNT162b2 30 μg in older adolescents and those over 85 years of age; updated the title and other references to adults to align with this change.
• Clarified that inclusion criterion 4 (i.e., 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.
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9 • Stated that the vaccine candidate selected for Phase 2/3 evaluation is BNT162b2 at a
dose of 30 μg.
• Renamed Stage 1 to Phase 1, removed Stage 2, and renamed Stage 3 to Phase 2/3.
• Clarified which stopping rules apply to which phase of the study.
• Moved the immunogenicity objectives in Phase 2/3 to become exploratory.
• Modified exclusion criterion 5, so that participants with a previous clinical or
microbiological diagnosis of COVID -19 are excluded from all phases of the study.
Amendment 4: 2020-06-30
• BNT162b3 c andidate 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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Phase 1 For each vaccine candidate (4:1 randomization active:placebo)
Age: 18 -55 y Age: 65 -85 y
Low-dose-level 2 -dose group (n=15)
IRC (safety) IRC (safety Low-dose-level 2 -dose group (n=15)
after Dose 1)
Mid-dose-level 2 -dose group (n=15)
IRC (safety) IRC (safety Mid-dose-level 2 -dose group (n=15)
after Dose 1)
High -dose-level 2 -dose group (n=15)
IRC (safety High -dose-level 2 -dose group (n=15)
after Dose 1)
IRC choice of group(s) for Phase 2/3
(safety & immunogenicity after Doses 1 and 2)
Phase 2/3 Single vaccine candidate (1:1 randomization active:placebo)
Safety and immunogenicity analysis of
Phase 2 data (first 360 participants)
by unblinded team (these participants
will also be included in Phase 3
analyses) Age: ≥12
(Stratified 12 -15, 16 -55, or >55)
BNT162b2 30 µg or placebo 2 doses
(n~21,999 per group, total n~43.998)
Abbreviation: IRC = internal review committee.
Note: Participants ≥16 years of age who originally received placebo will be offered the opportunity to
receive BNT162b2 at defined points as part of the study.
The study will evaluate the safety, tolerability, and immunogenicity of 3 different SARS -CoV-2
RNA vaccine candidates against COV ID-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 suffi cient to provide 90% power to conclude true VE >30% with high
probability. The total number of participants enrolled in Phase 2/3 may vary depending on the
incidence of COVID -19 at the time of the enrollment, the true underlying VE, and a potential
early stop for efficacy or futility.
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3. Analysis Considerations Related to Multiple Analysis Datasets
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 detail 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
AGEGR4 Pooled age group 4 (based on Age at Dose 1, For
12 to 25 years of age for safety and noninferiority
assessment )
Including following age categories :
12-15 Years; 16 -25 Years
AGEGR4N Pooled age group 4 (N):
1= 12-15 Years; 2= 16-25 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
TRTSDTM Datetime of first exposure to treatment
TRTEDTM Datetime of last exposure to treatment
TR01SDTM Datetime of first exposure to treatment for blinded
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12 Variable Type Variable Name Variable Description
placebo -controlled period
TR01EDTM Datetime of last exposure to treatment for blinded
placebo -controlled period
TR02SDTM Datetime of first exposure to treatment for open
label vaccination period
TR02EDTM Datetime of last exposure to treatment for open
label vaccination period
TRT01A Actual Treatment for blinded placebo -controlled
period
TRT01AN Actual Treatment for blinded placebo -controlled
period (N)
TRT01P Planned Treatment for blinded placebo -controlled
period
TRT01PN Planned Treatment for blinded placebo -controlled
period (N)
TRT02A Actual Treatment for open label vaccination period
TRT02AN Actual Treatment for open label vaccination period
(N)
TRT02P Planned Treatment for open label vaccination
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
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13 Variable Type Variable Name Variable Description
included in DS6000;
"Phase 3" for other subjects from Phase 3
DS360 indicates 360 Phase 2 subjects. DS6000 indicates first 6000 subjects from Phase 3
with 3000 subjects receiving actual treatment, and 3000 subjects receiving placebo.
See more details in Appe ndix 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 unblind ing date
This is the start date of open -label follow
up/vaccination period for subjects who were
unblinded
BDCSRDT Censor date for blinded placebo -controlled follow
up period. This date is the earliest date of the day
before treatment unblinding date UNBLNDDT (if
applicable), the day before first dose date of
BNT162b2 at open label vaccination period (if
applicable), end of study date (if applicable),
complete of study date (if applicable) and the date of cutoff (13Mar2021).
This date is used for AE incidence rate summary table (Exposure adj usted) 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 follow 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 who had at least 6
months follow -up after Dos e 2, excluding the
subjects with multiple sites.
MULENRFL Subjects enrolled in 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
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14 Variable Type Variable Name Variable Description
from all of summary analysis.
REACTOFL Population flag for subjects in 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 .
PEDREAFL Population flag for 12 -15/16-25 years of age
reactogenicity subset
EV1MD2FL Population flag for subject s 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
enrolled at 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 population after excluding subjects enrolled
at multiple sites, HIV positive subjects and subjects
with all doses indeterminate
SAF2FL Safety population after excluding subjects enrolled
at multiple sites 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
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15 Variable Type Variable Name Variable Description
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
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 w indow 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
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16 Variable Type Variable Name Variable Description
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
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 TRT xxP
Are the values of ARM equivalent in meaning to values of TRT xxP?
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) -
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17 PHASE ARM TRT01P TRT02P
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 - -
SCREEN FAILURE - -
Note: Unit of dose ‘mcg’ was displayed as ‘μg’ in all of outputs.
ACTARM versus TRT xxA
If TRT xxA is used, then are the values of ACTARM equivalent in meaning to values of
TRT01A?
No, ACTARM represents the actual arm for the blinded placebo-controlled period.
TRT01A has the actual treatment for the blinded placebo -controlled period , TRT02 A
has the actual treatment of open label vaccination period for subjects who received
placebo only in the blinded placebo- controlled period and received BNT162b2 after
unblinding. See details in below table.
PHASE ACTARM TRT01A TRT02A
Phase 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.
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18 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.
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 who
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 analyses
of the overall study objectives, with the exception of the specific exploratory objective for this group. In the sBLA, Human immunodeficiency virus (HIV) -positive subjects are
included in the analysis populations the summary of analysis populations and shown as
part of the study demographics and study conduct tables but not included in the analyses of overall safety, immunogenicity and efficacy endpoints.
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19 • 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 from the regimen they were assigned will be in cluded 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 d ose 1 and 2 were summarized by follow ing the same rule
as reactogenicity for post dose 1 and post dose 2 summary.
The following table shows how subjects are assigned to treatment arms 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, demographic , and other study conduct tables by Safety Population (Follow
Overall Actual Arm )
• 6 Subject s were enrolled into the study more than once resulting in significant misconduct
and compromising the integrity of the study data . These subject s will not be included in any
analyses and will only be included in separate listings (disposition listing, AE listing , local
reaction listing and systemic events listing ) created specifically for this subject. The se
subject s 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 group . In the analyses these subjects will be:
For safety:
a. Excluded from all table/figures.
b. Included in all regular listings .
For efficacy:
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20 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.
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,
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21 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 P hase 1 subjects was also programmatically excluded from SDTM data.
Do the analysis datasets support all protocol- and statistical analysis plan- specified objectives?
No. Objectives on VE against asymptomatic infection and Phase 1 booster are not assessed .
The booster and variant strain assessment in P rotocol 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
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22
Dataset Label
Class
Efficacy
Safety
Baseline or
other subject
PK/PD
Primary
Structure
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
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)
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23 o Race (White, Black or African American and All Others)
Note: All Others = American Indian or Alaska N ative , Asian, Native Hawaiian 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
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 AD
AE – 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 coding,
WHODD GLOBALB3Mar2021 were used.
Partial start dates or partial end dates of nonstudy vaccines and concomitant medications were
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24 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:
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 w as 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 CUTUNBFL 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.
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25 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
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
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26
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
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 FA SCAT =
“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".
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27 PARAMN PARAMCD PARAM Derivation
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".
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".
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28 PARAMN PARAMCD PARAM Derivation
17 RIHNRA RHINORRHOEA Set to "RHINORRHOEA" when
upcase(FA.FAOBJ) contains "RUNNY
NOSE" or upcase(FA.FAOBJ) =
"RHINORRHOEA" and FA.FAOBJ ^=
"NEW OR INCREASED NASAL
DISCHARGE" and FA.FACAT =
"EFFICACY" and FA.FASCAT =
"RESPIRATORY ILLNESS".
18 NAUSEA NAUSEA Set to FA.FAOBJ when upcase(FA.FAOBJ) =
"NAUSEA" and FA.FACAT = "EFFICACY"
and FA.FASCAT = "RESPIRATORY
ILLNESS".
25 SARDFN SIGNIFICANT
ACUTE RENAL
DYSFUNCTION Set to CE.CESCAT when CE.CESCAT =
"SIGNIFICANT ACUTE RENAL
DYSFUNCTION".
30 SAHDFN SIGNIFICANT
ACUTE HEPATIC
DYSFUNCTION Set to CE.CESCAT when CE.CESCAT =
"SIGNIFICANT ACUTE HEPATIC
DYSFUNCTION".
35 SANDFN SIGNIFICANT
ACUTE
NEUROLOGIC
DYSFUNCTION Set to CE.CESCAT when CE.CESCAT =
"SIGNIFICANT ACUTE NEUROLOGIC
DYSFUNCTION".
40 SARSCOV2 SEVERE ACUTE
RESP SYNDROME
CORONAVIRUS 2 Set to MB.MBTEST when
upcase(MB.MBTESTCD) = "SARSCOV2"
and MB.MBMETHOD =
"IMMUNOCHROMATOGRAPHY".
41 RTCOV2NS CEPHEID RT -PCR
ASSAY FOR SARS -
COV -2 Set to MB.MBTEST when
upcase(MB.MBTESTCD) = "RTCOV2NS"
and MB.MBMETHOD = "REVERSE
TRANSCRIPTASE PCR".
50 RESP RESPIRATORY
RATE Set to VS.VSTEST when VS.VSTESTCD =
"RESP".
51 HR HEART RATE Set to VS.VSTEST when VS.VSTESTCD =
"HR".
52 OXYSAT OXYGEN
SATURATION Set to VS.VSTEST when VS.VSTESTCD =
"OXYSAT"
53 DIABP DIASTOLIC BLOOD
PRESSURE Set to VS.VSTEST when VS.VSTESTCD =
"DIABP".
54 SYSBP SYSTOLIC BLOOD
PRESSURE Set to VS.VSTEST when VS.VSTESTCD =
"SYSBP".
60 PO2FIO2 PP ARTERIAL
O2/FRACTION
INSPIRED O2 Set to LB.LBTEST when LB.LBTEST = "PP
Arterial O2/Fraction Inspired O2".
71 NIPPV NON -INVASIVE
POSITIVE
PRESSURE
VENTILATION Set to PR.PRTRT when upcase(PR.PRTRT) =
"NON -INVASIVE POSITIVE PRESSURE
VENTILATION".
74 MCHVENT MECHANICAL
VENTILATION Set to PR.PRTRT when upcase(PR.PRTRT) =
"MECHANICAL VENTILATION".
76 HFOXTHRP HIGH FLOW
OXYGEN Set to PR.PRTRT when upcase(PR.PRTRT) =
"HIGH FLOW OXYGEN THERAPY".
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29 PARAMN PARAMCD PARAM Derivation
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" ).
92 HCUHSP HOSPITALIZED
DUE TO COVID-19 ILLNESS? Set to "HOSP ITALIZED DUE TO COVID -19
ILLNESS" when SUPPHO .QNAM =
"HCUHSP " and SUPPHO.QVAL = "Y"
95 PRCDTH PRIMARY
CAUSE OF DEATH Set to "PRIMARY CAUSE OF DEATH "
when DD.DDTESTCD = "PRCDTH"
96 SECDTH SECONDARY
CAUSE OF
DEATH Set to DD.DDTEST when DD.DDTESTCD =
"SECDTH "
99 DEATH DEATH Set to DS.DSDECOD when DS.DSDECOD =
"DEATH".
5.2.10 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
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30 PARAMN PARAMCD PARAM
103 SEVCVS SEVERE COVID -19 SYMPTOMS - VITAL SIGNS
104 SEVCRF SEVERE COVID -19 SYMPTOMS - RESPIRATORY FAILURE
105 SEVCVSPR SEVERE COVID -19 SYMPTOMS - USE OF
VASOPRESSORS
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
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 DEFI NED COVID19 SYMPTOMS
151 ST1CD SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC DEFINED
COVID19 SYMPTOMS
152 ST17CD SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR CDC
DEFINED COVID19 SYMPTOMS
153 ST2CD SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR CDC DEFINED
COVID19 SYMPTOMS
154 ST27CD SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2 FOR CDC
DEFINED COVID19 SYMPTOMS
155 ST214CD SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR CDC
DEFINED COVID19 SYMPTOMS
161 ST1SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR PROTOCOL
DEFINED SEVERE COVID19 SYMPTOMS
162 ST17SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
163 ST2SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR PROTOCOL
DEFINED SEVERE COVID19 SYMPTOMS
164 ST27SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
165 ST214SE SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
PROTOCOL DEFINED SEVERE COVID19 SYMPTOMS
171 STC1SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS
172 STC17SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 1 FOR
CDC DEFINED SEVERE COVID19 SYMPTOMS
173 STC2SE SUBJECT'S SURVEILLANCE TIME AFTER DOSE 2 FOR CDC
DEFINED SEVERE COVID19 SYMPTOMS
174 STC27SE SUBJECT'S SURVEILLANCE TIME 7 DAYS AFTER DOSE 2 FOR
CDC DEFINED SEVERE COVID19 SYMPTOMS
175 STC214SE SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
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31 PARAMN PARAMCD PARAM
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
205 ST214PDA SUBJECT'S SURVEILLANCE TIME 14 DAYS AFTER DOSE 2 FOR
PROTOCOL DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
211 ST1CDA SUBJECT'S SURVEILLANCE TIME AFTER DOSE 1 FOR CDC
DEFINED COVID19 SYMPTOMS - ALL AVAILABLE
212 ST17CDA SUBJECT'S SURVEILLANCE TIME 7 DAYS AFT ER 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 D OSE 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 T IME 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
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Study C4591001 Analysis Data Reviewer’s Guide
32 programmatic ally fo r samples outside the visit window, not receiving correct vaccination as
randomized, no valid assay result; exclusion due to important deviations were provided in SUPPDV
dataset.
For Phase 1 for BNT162b2 30 mcg and e quivalent Placebo s ubjects (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 c onvalescent 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
Specify the version of the validation rules (i.e. CDISC, FDA) for the analysis datasets
CDISC ADaM -CT 2020-03-27
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Study C4591001 Analysis Data Reviewer’s Guide
33 Specify the software name and version for the define.xml
Pinnacle 21 Enterprise 4.1.4.
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%) CDRMUPF L 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 AS TDT >AEDNT 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).
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34 Check
ID Diagnostic
Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
AD0361 Value of ASTDT
is greate r 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 AS TDT >AEDNT and
ASTDY > AENDY.
AD1012 Secondary custom
variable is present
but its primary
variable is not present Warning ADDS 1
(7.14%) AD1012 check is limited to "standard"
ADaM variables explicitly defined in
ADaM IG documents. M1P2EXC is the
variable to capture the necessary
information. Any new custom variables
added to analysis data are out- of-scope
for AD1012 check.
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 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 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
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35 Check
ID Diagnostic
Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
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
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:
Mult iple
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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36 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.
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 m ock t able is also included as a reference (see the link to the individual mocks shown in the table belo w) to
give additional details for each output in Appendix I .
Table Program Name Output
Name
Title
Input Population Subset used
1 adsl-s005-demo -
ped-saf-sas.txt adsl_s005_demo_ped
_saf html Demographic Characteristics – Subjects 12
Through 15 and 16 Through 25 Years of Age –
Safety Population ADSL ADSL.PHASEN>1 and
ADSL.SAFFL eq "Y" and
ADSL.MULENRFL ne "Y" and
ADSL. AGEGR4N ne .
2 adds-s002-ped- adds s002 ped rand Disposition of All Randomized Subjects ADSL ADDS ADSL. RANDFL eq 'Y' and
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37 Table Program Name Output
Name
Title
Input Population Subset used
rand-sas.txt .html Through 1 Month After Dose 2 – Subjects 12
Through 15 and 16 Through 25 Years of Age ADSL.PHASEN > 1 and
ADSL .AGEGR4N ne . and
ADSL .MULENRFL ne "Y"
3 adsl-fu-d2-ped-
saf-sas.txt adsl_fu_d2_ped_saf.
html Follow -up Time After Dose 2 – Subjects 12
Through 15 and 16 Through 25 Years of Age –
Safety Population ADSL ADSL.PHASEN>1 and ADSL.SAFFL
eq "Y" and ADSL.MULENRFL ne "Y"
and ADSL. AGEGR4N ne .
4 adce-s010-lr-sev-
ped-saf-sas.txt adce s010 lr sev p
ed saf.html Local Reactions, by Maximum Severity,
Within 7 Days After Each Dose – Subjects 12
Through 15 and 16 Through 25 Years of Age
(Reactogenicity Subset) – Safety Population ADSL
ADFACEVD ADSL.SAFFL eq 'Y' and
ADFACEVD.CUTUNBFL ne "Y" and
ADSL.PEDREAFL="Y" and
ADSL.AGEGR4N ne . and
ADSL.HIVFL ne "Y" and ADSL.MULENRFL ne "Y" and
ADFACEVD.TRTAN in (8 9) and
ADFACEVD.KNOWVFL="Y" and ADFACEVD .FAOBJ in ("PAIN AT
INJECTION SITE" "SWELLING"
"REDNESS")
5 adce-s020-se-sev-
ped-saf-sas.txt adce s020 se sev p
ed saf.html Systemic Events, by Maximum Severity,
Within 7 Days After Each Dose – Subjects 12
Through 15 and 16 Thr ough 25 Years of Age
(Reactogenicity Subset) – Safety Population ADSL
ADFACEVD ADSL.SAFFL eq 'Y' and
ADFACEVD .CUTUNBFL ne "Y" and
ADSL.PEDREAFL="Y" and ADSL.HIVFL ne "Y" and
ADFACEVD .KNOWVFL="Y" and
ADFACEVD .TRTAN in (8 9) and
ADSL.AGEGR4N ne . and ADSL.MULENRFL ne "Y" and
ADFACEVD .
FAOBJ not in ("PAIN AT
INJECTION SITE" "SWELLING"
"REDNESS") and
index(upcase( ADFACEVD .FAOBJ),"H
OSPI")=0
6 adae-s091-pd2-
ped-saf-sas.txt adae s091 pd2 ped
saf html Number (%) of Subjects Reporting at Least
1 Adverse Event From Dose 1 Through 1
Month After Dose 2 – Subjects 12 Through ADSL
ADAE ADSL.SAFFL eq "Y" and
ADSL.AGEGR4N ne . and
ADSL.MULENRFL ne "Y" and
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38 Table Program Name Output
Name
Title
Input Population Subset used
15 and 16 Through 25 Years of Age
(Reactogenicity Subset) – Safety
Population ADSL.HIVFL ne 'Y' and
ADSL.PEDREAFL eq 'Y'
7 adae-s091-d1-cut-
ped-saf-sas.txt adae_ s091_d1_cut_
ped_saf.html Number (%) of Subjects Reporting at Least 1
Adverse Event From Dose 1 Through Cutoff Date (13MAR2021), Subjects 12 Through 15
Years of Age – Safety Population ADSL
ADAE ADSL.SAFFL eq "Y" and
ADSL.MULENRFL ne "Y" and ADSL.
AGEGR4N eq 1 and ADSL.HIVFL ne
"Y"
8 adva-s001-gmr-
ped-ev-eval-
sas.txt
adva s001 gmr ped
ev eval html
Summary of Geometric Mean Ratio –
NT50 – Comparison of Subjects 12
Through 15 Years of Age to Subjects 16 Through 25 Years of Age (Immunogenicity
Subset) – Subjects Without Evidence of
Infection up to 1 Month After Dose 2 –
Dose 2 Evaluable Immunogenicity
Population ADSL
ADVA ADVA. EVIMMFL eq ' Y' and
ADVA.PARAMN in (1) and 1<ADVA.AVISITN <=6 and
ADSL.PEDIMMFL eq "Y" and
ADSL.EV1MD2 FL eq "Y" and
ADVA.ANL01FL eq "Y"
9 adc19ef -ve-cov-
7pd2- peds-wo-
eval-sas.txt
adc19ef ve cov 7p
d2 peds wo eval ht
ml
Vaccine Efficacy – First COVID -19
Occurrence From 7 Days After Dose 2
– Blinded Placebo -Controlled Follow -up
Period – Subjects 12 Through 15 Years of
Age and Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population ADSL
ADC19 EF
ADSYMPT ADSL.EVALEFFL='Y' and
ADSL.MULENRFL ne "Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N' and ADC19EF.PDP27FL='Y' and 12 <=
ADSL. AGETR01 <= 15
10 adc19ef -ve-cov-
7pd2- peds-eval-
sas.txt adc19ef _ve_cov_7p
d2_peds_evalhtml Vaccine Efficacy– First COVID -19
Occurrence From 7 Days After Dose 2 –
Blinded Placebo-Contro lled Fo llow- up
Period – Subjects 12 Through 15 Years of
Age and With or Without Evidence of
Infection Prior to 7 Days After Dose 2 –
Evaluable Efficacy (7 Days) Population ADSL
ADC19EF
ADSYMPT ADSL.EVALEFFL='Y'and
ADSL.MULENRFLne"Y" and ADSL.PHASEN ne 1 and
ADSL.HIVFL = 'N' and 12 <=
ADSL.AGETR01 <= 15
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Study C4591001 Analysis Data Reviewer’s Guide
39 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 Through 1 Month After Dose 2 – Subjects 12 Through 15 and 16 Through 25 Years of Age
Vaccine Group (as Randomized)
BNT162b2 (30 μg) Placebo
12-15 Years 16-25 Years 12-15 Years 16-25 Years
(Na=xx) (Na=xx) (Na=xx) (Na=xx)
nb (%) nb (%) nb (%) nb (%)
Randomized
Not vaccinated
Vaccinated
Dose 1 x
Dose 2 x
Completed 1 -month after Dose 2 visit (vaccination period) xx (xxx.x) xx (xxx x) xx (xxx x) xx (xxx x)
Discontinued from vaccination period but continue in the study up to 1 -
month post –Dose 2 visit xx (xxx.x)
Discontinued after Dose 1 and before Dose 2 xx (xxx.x)
Discontinued after Dose 2 and before 1 -month post –Dose 2 visit xx (xxx.x)
Reason for discontinuation from vaccination period
Adverse event x
Withdrawal by subject x
Physician decision x
Death xx (xxx.x) xx (xxx.x) xx (xxx.x) xx (xxx.x)
Study terminated by sponsor
Pregnancy
Other
Withdrawn from the study before 1 -month after Dose 2 visit xx (xxx.x) xx (xxx.x) xx (xxx.x) xx (xxx.x) RANDFL in ('Y') RANDFL eq 'Y' and (VAX101DT
eq . and VAX102DT eq .)
RANDFL eq 'Y' and VAX101DT ne .
RANDFL eq 'Y' and VAX102DT ne .
RANDFL eq 'Y' and DSPHASEN=26 and dsdecodn=2 RANDFL eq 'Y' and DSPHASEN=26 and EOTDCDT ne . and (EOSDCDT eq . or
EOSDCDT>M1P2CUT>.) and dsdecodn not in (. 2) and (VAX101DT ne . or
VAX102DT ne .)
RANDFL eq 'Y' and DSPHASEN=26 and EOTDCDT ne . and (EOSDCDT eq .
or EOSDCDT>M1P2CUT>.) and dsdecodn not in (. 2) and vax101dt ne . and (vax102dt eq . or astdt < vax102dt)
RANDFL eq 'Y' and DSPHASEN=26 and EOTDCDT ne .
and (EOSDCDT eq . or EOSDCDT>M1P2CUT>.) and dsdecodn not in (. 2) and vax101dt ne . and vax102dt ne . and
(vax102dt <= astdt and (M1PD2DT eq . or astdt<M1PD2DT))
1. Subset below section with criteria: RANDFL eq 'Y' and DSPHASEN=26 and
EOTDCDT ne . and (EOSDCDT eq . or EOSDCDT>M1P2CUT>.) and
dsdecodn not in (. 2) and (VAX101DT ne . or VAX102DT ne .)
2. Report by each ADDS. DSDECOD.
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in (. 2)
and (VAX101DT ne . or VAX102DT ne .) and COMPLTDT=. ; where
COMPLT DT = ASTDT when DSDECODN=2 and DSPHASEN=26 AGEGR4N TRT01P
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Study C4591001 Analysis Data Reviewer’s Guide
40 Withdrawn after Dose 1 and before Dose 2 xx (xxx x) xx (xxx x) xx (xxx x) xx (xxx x)
Withdrawn after Dose 2 and before 1 -month post –Dose 2 visit x )
Reason for withdrawal from the study
Adverse event x
Withdrawal by subject x
Physician decision xx (xxx.x) xx (xxx.x) xx (xxx.x) xx (xxx.x)
Death
Pregnancy
Other
Note: Human immunodeficiency virus (HIV) -positive subjects are included in this summary but not included in the analyses of the overall study objectives.
Note: Subjects randomized but did not sign informed consent or had a significant quality event due to lack of PI oversight ar e not included in any analysis population.
Note: Because of a dosing error, subject[s] C4591001 xxxx xxxxx [and C4591001 xxxx xxxxxx] received an additional dose of 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. This value is the denominator for the percentage calculations.
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
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in
(. 2) and vax101dt ne . and (vax102dt eq . or astdt < vax102dt)
RANDFL eq 'Y' and DSPHASEN=31 and EOSDCDT ne . and dsdecodn not in
(. 2) and vax101dt ne . and vax102dt ne . and (vax102dt <=astdt and (M1PD2DT
eq . or astdt<M1PD2DT))
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 COMPLTDT=.
2. Report by each ADDS. DSDECOD.
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Study C4591001 Analysis Data Reviewer’s Guide
41
Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Subjects 12 Through 15 and 16 Through 25 Years
of Age (Reactogenicity Subset) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
12-15 Years 16-25 Years 12-15 Years 16-25 Years
Dose Local Reaction Na nb (%) (95% CIc) Na nb (%) (95% CIc) Na nb (%) (95% CIc) Na nb (%) (95% CIc)
1 Rednessd
Any NN nn
(xx x) (xx x xx x) NN
(xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Mild
N nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Moderate
N nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Severe
N nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Grade 4
N nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Swellingd
Any NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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) 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) 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) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Pain at the injection sitee ADSL.AGEGR4N
ADFACEVD.ATPTREF
ADFACEVD.FAOBJ ADFACE VD.TRTA
ADSL.SAFFL eq 'Y' and
ADFACEVD.CUTUNBFL ne "Y" and
ADSL.PEDREAFL="Y" and
ADSL.AGEGR4N ne . and ADSL.HIVFL
ne "Y" and ADSL.MULENRFL ne "Y"
and ADFACEVD.TRTAN in (8 9) and
ADFACEVD.KNOWVFL="Y" and
FAOBJ in ("PAIN AT INJECTION SITE"
"SWELLING" "REDNESS") ADFACEVD. FATESTCD="MAXSEV"
and ADFACEVD. AVALC ne "" and
ADFACEVD.EVENTFL="Y"
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Study C4591001 Analysis Data Reviewer’s Guide
42 Any NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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) 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) 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) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Any local reactionf NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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>
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: emergen cy room 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 sit e.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: abcdefgh Table Ge neration: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
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43
Systemic Events, by Maximum Severity, Within 7 Days After Each Dose – Subjects 12 Through 15 and 16 Through
25 Years of Age (Reactogenicity Subset) – Safety Population
Vaccine Group (as Administered)
BNT162b2 (30 µg) Placebo
12-15 Years 16-25 Years 12-15 Years 16-25 Years
Dose Systemic Event Na nb
(%) (95% CIc) Na nb
(%) (95% CIc) Na nb
(%) (95% CIc) Na nb
(%) (95% CIc)
1 Fever
≥38.0℃ nn
(xx x xx x)
nn
x.x)
, xx.x) NN nn
(xx.x) (xx.x, xx.x)
≥38.0℃ to 38.4℃
nn
x.x)
, xx.x) NN nn
(xx.x) (xx.x, xx.x)
>38.4℃ to 38.9℃
nn
x.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
>38.9℃ to 40.0℃
nn
x.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
>40.0℃
nn
x.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Fatigued
Any NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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) 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) 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) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Headached ADFACEVD.ATPTREF
ADFACEVD.FAOBJ ADSL.AGEGR4N
ADFACEVD.TRTA
ADSL.SAFFL eq 'Y' and
ADCE.CUTUNBFL ne "Y" and
ADSL.PEDREAFL="Y" and not
(ADCE.ADT>=ADCE.UNBLNDDT>.) and
ADSL.HIVFL ne "Y" and
ADCE.KNOWVFL="Y" and
ADCE.TRTAN in (8 9) and
ADSL.AGEGR4N ne . and
ADSL.MULENRFL ne "Y" and FAOBJ
not in ("PAIN AT INJECTION SIT E"
"SWELLING" "REDNESS") and
index(upcase(FAOBJ),"HOSPI")=0 ADFACEVD.FATESTCD in
("MAXSEV" "MAXTEMP"
"MEDTFVPN") and
ADFACEVD. AVALC ne "" and
ADFACEVD.EVENTFL="Y"
090177e198e31cd5\Final\Final On: 15-Dec-2021 18:40 (GMT)
FDA-CBER-2022-5812-0491903
Study C4591001 Analysis Data Reviewer’s Guide
44 Any NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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) 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) 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) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
Chillsd
Any NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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) 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) 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) 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) 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) 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) 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) 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) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
090177e198e31cd5\Final\Final On: 15-Dec-2021 18:40 (GMT)
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Study C4591001 Analysis Data Reviewer’s Guide
45 Diarrheaf
Any NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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) 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) 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) 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) 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) 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) 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) 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) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
New or worsened joint paind
Any NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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) 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) 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) NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x)
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Study C4591001 Analysis Data Reviewer’s Guide
46
Any systemic eventg NN nn
(xx.x) (xx.x, xx.x) NN nn
(xx.x) (xx.x, xx.x) 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) 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>
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 .
Note: Subject C4591001 1077 10771278 (13 years of age) experienced systemic events, including a temperature of 40.4°C, on the day of Dose 2. Since
these events were recorded as adverse events and not in the e -diary, they do not appear in this table.
a. N = number of subjects 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
hospitalization for severe fatigue, severe headache, severe muscle pain, or severe joint pain.
e. Mil d: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or
hospitalization for severe vomiting.
f. Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hou rs; 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 wo rsened 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: abcdefgh Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, S napshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
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47
Number (%) of Subjects Reporting at Least 1 Adverse Event From Dose 1 Through 1 Month After Dose 2 – Subjects 12
Through 15 and 16 Through 25 Years of Age (Reactogenicity Subset) – Safety Population
Vaccine Grou
BNT162b2 (30 μg) Placebo
12-15 Years 16-25 Years 12-15 Years 16-25 Years
(Na=xx) (Na=xx) (Na=xx) (Na=xx)
Adverse Event nb (%) nb (%) nb (%) nb (%)
Any event xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Life-threatening xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Any serious adverse event xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x)
Life-threatening xx (xx.x) xx (xx.x)
Any adverse event leading to withdrawal ( ) ( ) xx (xx.x) xx (xx.x)
Relatedc xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Severe xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Life-threatening xx (xx.x) xx (xx.x) xx (xx.x)
Death xx (xx.x) xx (xx.x) xx (xx.x) xx (xx.x)
Note: Adverse events that occurred on the day of or after subjects were unblinded are excluded from this summary.
Note: This table includes all subjects 12 through 15 years of age (all of whom are in the reactogenicity subset) and the subs et of subjects 16 through 25 years
of age who completed an e -diary.
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 specif ied event category. For “any event,” n = the 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: abcd efgh Table Generation: DDMMMYYYY (HH:MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN
ADAE.AECAT = 'ADVERSE EVENT' and ADSL. SAFFL="Y" and ADSL.AGEGR4N ne . and ADAE.VPHASEN
in (1,2) and ADAE.V01DT >= ADAE.ASTDT and (ADAE.UNBLNDDT = . or ADAE.UNBLNDDT >
ADAE.ASTDT) and ADSL.MULENRFL ne "Y" and ADSL.HIVFL ne 'Y' and ADSL.PEDREAFL='Y'
upcase(ADAE.AREL)=”RELATED”
ADAE.ATOXGRN=3
ADAE.ATOXGR=”GRADE 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.AGEGR4N ne . and
ADSL.MULENRFL ne "Y" and ADSL.HIVFL ne 'Y' and
ADSL.PEDREAFL='Y'
ADSL.AGEGR4N
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Study C4591001 Analysis Data Reviewer’s Guide
48
Summary of Geometric Mean Ratios – NT50 – Comparison of Subjects 12 Through 15 Years of Age to Subjects 16
Through 25 Years of Age (Immunogenicity Subset) – Subjects Without Evidence of Infection up to 1 Month After Dose
2 – Dose 2 Evaluable Immunogenicity Population
Vaccine Group (as Randomized)
BNT162b2 (30 μg)
12-15 Years 16-25 Years 12-15 Years/16 -25 Years
Assay Dose/Sampling
Time Pointa nb GMTc
(95% CIc) nb GMTc
(95% CIc) GMRd
(95% CId) Met
Noninferiority
Objectivee
(Y/N)
SARS -CoV -2
neutralization assay -
NT50 (titer) 2/1 Month xx xx.x
(xx.x, xx.x) xx xx.x
(xx.x, xx.x) xx.x
(xx.x, xx.x) Y
Abbreviations: GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of quantitation; NE = not estimable; NT50 = 50%
neutralizing titer; SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.
Note: Subjects who had no serological or virological evidence ( 1 th f i f th l d ) f SARS C V 2 i f i (i N
binding antibody [serum] negative at Visit 1 and SARS -CoV -
swab) at any unscheduled visit up to 1 month after Dose 2 we
blood sample collection.
valid and determinate assay
were calculated by exponent
t distribution). Assay results below the LLOQ were set to 0.5
d. GMRs and 2 -sided 95% CIs were calculated by exponen
[16-25 years]) and the corresponding CI (based on the Studen
e. Noninferiority is declared if the lower bound of the 2 -sid
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYY
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY
ADVA.PARAMN/PAR
AMCD/PARAM ADSL.TRT01P
ADVA AVISITN/AVISIT ADSL.AGEGR4N
if lcl>0.67 then Met
Noninferiority Objective=”Y”
Number of non -missing
ADVA.AVAL
Method used:
PROC TTEST DATA=_data12 plots = none;
by _DATASRT
%do _j=1 %to &_maxbyn;
_byvar&_j
%end;
; class _trt;
VAR log_aval; RUN;
data ttest; set stat;
where (ProbF > 0.05 and method = "Pooled") or (ProbF <=0.05 and method = "Satterthwaite");
geomean = exp(mean);
lcl=exp(lowerclmean);
ci = "("||strip(put(exp(lowerclmean),8.2))||", "||strip(put(exp(upperclmean), 8.2))||")";
format geomean 8.2;
keep _datasrt _byvar: geomean lcl ci;
run; Geometric mean and corresponding 95%
CI of ADVA.AVAL
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49
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period
– Subjects 12 Through 15 Years of Age and Without Evidence of Infection Prior to 7 Days After Dose 2
– Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized
BNT162b2 (30 µg) Placebo
(Na=nn) (Na=nn)
n1b Surveillance
Timec (n2d) n1b Surveillance
Timec (n2d) VE (%) (95% CIe)
Dose 2 xxx (nnn) x
≥7 days after Dose 2 to <2 Months after Dose 2 x
≥2 Months after Dose 2 to <4 Months after Dose xxx (nnn) xx.x (xx.x, xx.x)
≥4 Months after Dose 2 xxx (nnn) xx.x (xx.x, xx.x)
Abbreviations: N-binding = ification test;
SARS -CoV -2 = evere acut
No ical evidence (prior to 7 days after receipt of the last dose) of past SARS -CoV -2 infection (ie, N-
bin SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2, and had negative NAAT (nasal
swa ) y p y er Dose 2) were i ncluded in the analysis.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for the endpoint. Time period
for COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period for the overall row and from start to the end of the range
stated for each time interval.
d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: abcdefgh Table Generation: DDMMMYYYY (HH: MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd XNNN ADSL.EVALEFFL="Y" and ADC19EF.PDP27FL="Y" and
ADSL.AGEGR4N=1 ADSL.EVALEFFL="Y" and
ADC19EF.PARAMCD="C19ONST" and
index(upcase(ADC19EF.AVALC), "POS")>0 and ADC19EF.PDRMUPFL= "N" and ADC19EF.ILD27FL="Y"
and ADC19EF.FILOCRFL="Y" and ADC19EF.PDP27FL="Y". and ((not missing (DVSTDT) and adt <= DVSTDT) or
missing(DVSTDT))
ADC19EF.PDRMUPFL = "N" AND
ADC19EF.PDP27FL = "Y" AND ADC19EF.PARAMCD IN ("ST27PD") AND
ADC19EF.AVAL > 0
(Sum of ADC19EF.AVAL)/365.25/1000 where
ADC19EF.PARAMCD IN ("ST27PD")
(For subgroup the surveillance time will be custom and derived at reporting level for each period)
ADSL.TRT01P
not missing (ADC19EF.VAX102DT) and ADC19EF.VAX102DT + 7 <=
ADC19EF.ADT < ADC19EF.VAX102DT + 56
not missing (ADC19EF.VAX102DT) and ADC19EF.VAX102DT + 56 <=
ADC19EF.ADT < ADC19EF.VAX102DT + 112
not missing ( ADC19EF.VAX102DT) and
ADC19EF.VAX102DT + 112 <= ADC19EF.ADT
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50
Programming note: for this table: remove footnote “ Note: Subjects had no serological. ”
Vaccine Efficacy – First COVID -19 Occurrence From 7 Days After Dose 2 – Blinded Placebo -Controlled Follow -up Period
– Subjects 12 Through 15 Years of Age and With or Without Evidence of Inf ection Prior to 7 Days After Dose 2
– Evaluable Efficacy (7 Days) Population
Vaccine Group (as Randomized
BNT162b2 (30 µg) Plac
(Na=nn) (Na=
n1b Surveillance
Timec (n2d) n1b Surveillance
Timec (n2d) VE (%) (95% CIe)
Dose 2 xxx (nnn) xx
≥7 days after Dose 2 to <2 Months after Dose 2 xx
≥2 Months after Dose 2 to <4 Months after Dose xx ( ) ( , )
≥4 Months after Dose 2 xxx (nnn) xx.x (xx.x, xx.x)
Abbreviations: N-binding = ification test;
SARS -CoV -2 = severe acut
No ical evidence (prior to 7 days after receipt of the last dose) of past SARS -CoV -2 infection (ie, N-
bin SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2, and had negative NAAT (nasal
swa ) y p y er Dose 2) were i ncluded in the analysis.
a. N = number of subjects in the specified group.
b. n1 = Number of subjects meeting the endpoint definition.
c. Total surveillance time in 1000 person -years for the given endpoint across all subjects within each group at risk for the endpoint. Time period
for COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period for the overall row and from start to the end of the range
stated for each time interval.
d. n2 = Number of subjects at risk for the endpoint.
e. Confidence interval (CI) for VE is derived based on the Clopper and Pearson method adjusted for surveillance time.
PFIZER CONFIDENTIAL SDTM Creation: DDMMMYYYY (HH:MM) Source Data: abcdefgh Table Generation: DDMMMYYYY (HH: MM)
(Cutoff date: ddMmmYYYY, Snapshot Date: ddMmmYYYY) Output File: (CDISC)/C4591001/abcd_XNNN ADSL.EVALEFFL="Y" and ADC19EF.PDP27FL="Y" and
ADSL.AGEGR4N=1 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 ((not missing (DVSTDT) and adt <= DVSTDT) or mi ssing(DVSTDT))
ADC19EF.PDRMUPFL = "N" AND
ADC19EF.PDP27FL = "Y" AND ADC19EF.PAR AMCD IN ("ST27PD") AND
ADC19EF.AVAL > 0
(Sum of ADC19EF.AVAL)/365.25/1000 where
ADC19EF.PARAMCD IN ("ST27PD")
(For subgroup the surveillance time will be custom and derived at reporting level for each period)
ADSL.TRT01P
not missing (ADC19EF.VAX102DT) and ADC19EF.VAX102DT + 7 <=
ADC19EF.ADT < ADC19EF.VAX102DT + 56
not missing (ADC19EF.VAX102DT) and ADC19EF.VAX102DT + 56 <=
ADC19EF.ADT < ADC19EF.VAX102DT + 112
not missing ( ADC19EF.VAX102DT) and
ADC19EF.VAX102DT + 112 <= ADC19EF.ADT
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51
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.V01DT) and before or
on the day of 6 months follow up visit after Dose 2 (ADSL.V0 2DT)
See details in below section for ADSL.V02DT Blinded placebo -
controlled period
Follow Up 2 Event start after the day of 6 months follow up visit after Dose 2 (ADSL.V02DT) and before
unblinding Blinded placebo -
controlled period
After unblinding and before
Vaccination 3 Event start on or after unblinding 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 visit 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 month s Open label follow -up
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Study C4591001 Analysis Data Reviewer’s Guide
52 VPHASE Comments
follow up visit after Dose 4 (ADSL.V04DT)
See details in below section for ADSL.V04DT period
Follow Up 4 Event start after the day of 6 month s follow up visit after Dose 4 (ADSL.V04DT) Open label follow -up
period
For Phas e 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.V02 DT was reset to the day before unblinding. ADSL.V02DT=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 S V after unblinding.
If date of visit 103 from SV dataset is not available, then use date of Dose 4 + 35 days
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Study C4591001 Analysis Data Reviewer’s Guide
53 Else i f 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
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.V02DT=min
(V02DT, ADSL.UNBLNDDT -1).
For AE’s from Dose 1 to 6 months after Dose 2 (Whole study period without considering unblinding):
• Dose 1 start date <= ae start date <= 6 months follow up date (ADSL.V02OBDT)
V02OBDT is the blood sample collected date from visit 4.
If visit 4 blood sample collection date is not available from CO dataset, then use the date of visit 4 from SV dataset.
Else if date of visit 4 from SV dataset is not available, then use date of Dose 2 + 189 days
Else if date of Dose 2 is not available, then use date of Dose 1 + 189 + 23 days
Note: if a subject took Dose 3 in open label vaccination period before V02OBDT , then ADSL.V02OBDT was reset to the day before Dose 3 .
ADSL.V02OBDT =min (V02 OBDT, ADSL.VAX201DT -1).
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Study C4591001 Analysis Data Reviewer’s Guide
54 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
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
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Study C4591001 Analysis Data Reviewer’s Guide
55 Rules Programming Logic
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
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 ).
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56 Concomitant medications/medical histories
Incomplete CM/MH start and stop dates were imputed as follows:
Imputation applied to partial CM/MH start dates and stop dates (missing day, missing both month and day). For partial start dates, if missing
start day, the first day of the month was used; if missing start month and day, the first month of the year was used. For partial stop dates, if
missing stop day, the last day of the month was used; if missing stop month and day, the 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
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57 PARCAT1 PARCAT2 PARAM PARAMCD
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
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., P hase 1, Phase 2,
Phase 3) as well as categories of medical history data used as comorbidities. A copy of the data included in these files was combined
into a supplementaldatadefinitions.pdf file and is linked to the define.xml package for reference.
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58 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)
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)
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59 ID File Name Comments
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)
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)
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60 ID File Name Comments
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)
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-P hase 1 subjects from
DMW .xlsx Used for ADSL creation to flag the subject s from Phase 1
Phase2 first-C4591001 -360-participants -
enrolled -V1.0-13Aug2020-
update.xlsx Used for ADSL creation to flag the subject s from Phase 2
DS360 subset
Phase3
DS6000 newlist -C4591001 -6k-
participants -enrolled -V3.0-
17sep2020.csv Used for ADSL creation to flag the subject s 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 subject s from EUA 12-25
subset
BMI scale BMI-12-15-Scale .xlsx Used for ADSL creation to flag the obese subjects for 12 -15
years age group
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:
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61 Endpoint's Associated
Participant -Level Population Start -of-Surveillance Time
Evaluable Efficacy (7 days) Dose 2 + 7 days (Day 8 relative to Dose 2)
Dose 2 All-available Efficacy Dose 2 + 7 days (Day 8 relative to Dose 2)
Dose 1 All-available Efficacy Dose 1 (Day 1 relative to Dose 1)
End-of-surveillance time:
The end of surveillance time is then determined considering the following events:
1. When the first COVID-19 case occurs.
2. When the participant’s end of the study occurs due to, e.g. withdrawal or death or trial completion etc.
3. When the participant has first important protocol violation.
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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62
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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63 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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64
Evaluable efficacy population (7 days)
Presence of at least 1 of the following symptoms: fever, new or increased
cough, new or increased shortness of breath, chills, new or increased muscle
pain, new loss of taste or smell, sore throat, diarrhea, or vomiting.
NAAT positive for COVID -19 at central laboratory or acceptable
local test within the date window that symptoms were present
Onset date, ie, the date that first symptom occurs,
is at least 7 days after receipt of the second dose
COVID- 19 cases for second primary VE objective
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65 Appendix VIII: Detailed subsetting for Analysis:
1. Key A nalysis Population Subsetting :
Safety and Immunogenicity Analysis
Table Category Analysis Population Total Number of Subjects ( N)
Subset Condition for Total N 12-15 Years 16-25 Years Total
Conduct of
Study Randomized 1120 12489 8646 ADSL.PHASEN>1 and ADSL.RANDFL="Y" and
ADSL.MULENRFL^="Y" and ADSL.AGEGR4 N ^=.
Safety 2260 3770 6030 ADSL.PHASEN>1 and ADSL. SAFFL="Y" and
ADSL .MULENRFL^="Y" and ADSL. AGEGR4 N ^=.
Adverse Events
(Reactogenicity
Subset)
Safety population for AEs
reporting from Dose 1 2260 1097 3357 ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.HIVFL^="Y" and PEDREAFL= "Y"
Safety population for AEs
reporting from Dose 2 2241 1058 3299 ADSL.SAFFL="Y" and ADSL.MULENRFL ^="Y" and
ADSL.HIVFL^="Y" and PEDREAFL= "Y" and
ADSL.VAX102DT>. and
ADSL.VAX101=ADSL.VAX102 and
(ADSL.VAX102DT<ADSL.UNBLNDDT or
ADSL.UNBLNDDT=.)
Reactogenicitya Safety
(Reactogenicity
subset) Dose 1 2260 1098 3358 ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.VAX101 ne "" and PEDREAFL= "Y"
Dose 2 2241 1060 3301 ADSL.SAFFL="Y" and ADSL.MULENRFL^="Y" and
ADSL.VAX102 ^="" and PEDREAFL= "Y"
Immunogenicity Dose 2 All -Available 246 225 471 ADSL.PEDIMMFL= "Y" and ADSL.AA I02FL= "Y"
Dose 2 Evaluable 245 218 463 ADSL.PEDIMMFL= "Y" and ADSL.EVAL02FL= "Y"
a. For reactogenicity, the N listed here is the number of subjects in reactogenicity subset relative for the specified dose (Including HIV positive
and not transmitted e-diary subjects). And the numbers match with the number of subjects in e- diary transmission table (number of subjec ts
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
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66 response before unblinding for the specified reaction/events after the specified dose which is less than the N in this table. For the detailed
algorithm, please refer to Appendix I .
2. Adverse Ev ent 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
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67 Reporting Period Subset condition to determin e the AEs within corresponding
reporting period. (Note: Additional subset for analysis
population is needed)
Open label follow -up period
for subjects who originally
received BNT162b2 From unblinding date to the date of cut off 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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