Document text
Analysis Data Reviewer’s Guide
Pfizer Inc.
BioNTech SE
Study BNT162-01
This document contains confidential information belonging to Pfizer Inc. Except as may be otherwise
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authorized purposes. In the event of actual or suspected breach of this obligation, Pfizer Inc. should be
promptly notified.
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Contents
1. Introduction ....................................................................................................................... 4
1.1 Purpose ...................................................................................................................... 4
1.2 Acronyms ................................................................................................................... 4
1.3 Study Data Standards and Dictionary Inventory ................................................................ 4
1.4 Source Data Used for Analysis Dataset Creation ............................................................... 4
2. Protocol Description............................................................................................................ 5
2.1 Protocol Number and Title ............................................................................................ 5
2.2 Protocol Design in Relation to ADaM Concepts ............................................................... 5
3. Analysis Considerations Related to Multiple Analysis Datasets.................................................. 8
3.1 Core Variables ............................................................................................................. 8
3.2 Treatment Variables ....................................................................................................10
3.3 Subject Issues that Require Special Analysis Rules ..........................................................11
3.4 Use of Visit Windowing, Unscheduled Visits, and Record Selection ...................................11
3.5 Imputation/Derivation Methods .....................................................................................11
4. Analysis Data Creation and Processing Issues ........................................................................11
4.1 Split Datasets .............................................................................................................11
4.2 Data Dependencies ......................................................................................................12
4.3 Intermediate Datasets ...................................................................................................12
5. Analysis Dataset Descriptions ..............................................................................................13
5.1 Overview ................................................................................................................... 13
5.2 Analysis Datasets ........................................................................................................13
5.2.1 ADSL - S
ubject-Level Analysis Dataset ........................................................................14
5.2.2 ADAE - Adverse Events Analysis Dataset .....................................................................15
5.2.3 ADCEVD - Reactogenicity Analysis Dataset ..................................................................16
5.2.4 ADFACEVD - Reactogenicity Findings Analysis Dataset ................................................
17
5.2.5 ADLB - Laboratory Analysis Dataset ............................................................................18
5.2.6 ADVA - Immunogenicity Analysis Dataset ....................................................................18
5.2.7 ADVS - Vital Signs Analysis Dataset............................................................................19
6. Data Conformance Summary ...............................................................................................20
6.1 Conformance Inputs ....................................................................................................20
6.2 Issues Summary ..........................................................................................................20
7. Submission of Programs .....................................................................................................21
7.1 ADaM Programs .........................................................................................................21
7.2 Analysis Output Programs ............................................................................................21
7.3 Macro Programs .........................................................................................................21
8. Appendix ..........................................................................................................................22
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8.1 Appendix I: Lab Parameters ...............................................................................................22
8.2 Appendix II: Look Up Table ..............................................................................................25
8.3 Appendix III: Methods to derive key ADAE variables ...........................................................27
8.4 Appendix IV: ADFACEVD Analysis Parameters ..................................................................31
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1. Introduction
1.1 Purpose
This document provides context for the analysis datasets and terminology that benefit from additional ex-
planation beyond the Data Definition document ( define.xml ). In addition, this document provides a sum-
mary of ADaM conformance findings.
1.2 Acron yms
Acronym Translation
CRF Case Report Form
P/B Prime/Boost: a dosing regimen, comprising a priming immunization and a
boost immunization
modRNA Nucleoside modified messenger RNA
FIH first-in-human
SRC Safety Review Committee
COVID-19 Coronavirus Disease 2019
IMP Investigational Medicinal Product
SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2
TEAE Treatment Emergent Adverse Event
1.3 Study Data Standards and Dictionary Inventory
Standard or Dictionary Version s 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
TAUG (if applicable) Vaccines Therapeutic Area User Guide v1.1
Medical Events Dictionary MedDRA 23.0
Other standards (optional) WHODRUG GLOBAL B3 March 1, 2020
1.4 Source Data Use d for A nalysis Dataset Creation
The ADaM datasets were derived from SDTM version 3.2 and ADaM -IG version 1.1. The CSR datasets
(SDTM) are based on ongoing data cut as of 23OCT2020.
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2. Protocol Description
2.1 Protocol Number and Title
Protocol Number: BNT162-01
Protocol Title: A Multi-site, Phase I/II, 2 -Part, Dose -Escalation Trial Investigating the Safety
and Immunogenicity of Four Prophylactic SARS -CoV-2 RNA Vaccines Against
COVID-19 Using Different Dosing Regimens in Healthy Adults
Protocol Versions: CorVAC-BNT162-01_CTP_v1.0_2020-03-24_final.pdf
CorVAC-BNT162-01_CTP_v2.0_2020-04-09_final_mod2.pdf
CorVAC-BNT162-01_CTP_v3.0_2020-04-17_final.pdf
CorVAC-BNT162-01_CTP_v4.0_2020-05-13_final_v1.2.pdf
CorVAC-BNT162-01_CTP_v5.0_2020-05-26_final.pdf
CorVAC-BNT162-01_CTP_v6.0_2020-06-09.pdf
CorVAC-BNT162-01_CTP_v7.0_2020-06-26_final.pdf
BNT162-01_CTP_v8.0_2020-07-21.pdf
BNT162-01_CTP_v9.0_2020-10-05_final.pdf
There were 8 amendments to the protocol. A detailed description of each amendment, with rational e for
change, is provided in the protocol v 9.0 under section 10.10. Some changes were also implemented to
align data collection and reporting in this trial with the data collection and reporting in other trials with
BNT162 vacci nes candidates (to facilitate data merging). Some of the critical changes are listed here.
o Allow the assessment of additional intermediate and low dose cohorts for BNT162b modRNA
vaccine candidates to support identification of a suitable dose for Phase II/III evaluation.
o Allow the assessment of BNT162b1 modRNA vaccine candidate in elderly subjects, given its fa-
vorable safety, tolerability, and immunogenicity profile in younger adults to date and recently available non -human primate immunogenicity data for the BNT162b1 and other modRNA vac-
cine candidates.
o Plan the assessment of BNT162b2 modRNA vaccine candidate in elderly subjects.
o Allow revision of safety assessment & dose limiting toxicity criteria.
o Add additional for blood draws for explorative biomarker/immunogenicity research purposes.
o BNT162b1 and BNT162b2 are both non -modified uridine RNAs, while BNT162a1 and
BNT162c2 are both nucleoside -modified pseudomethyl -uridine containing. This modification is
known to impact the extent of innate immune activation at a given dose level, and thus potentially
the extent of reactogenicity. Therefore, tolerability dat obtained with one of the vaccine variants
of each of these pairs may be potentially informative for the respective other one and should be
taken in consideration by the SRC for recommendations of lower or interim doses.
o Leftover blood may be used for additional biomarker analysis (blood sampling for research) .
o Align diary data collection with other BNT162 studies .
2.2 Protocol Design in Relation to ADaM Concepts
Four different vaccines (BNT162a1, BNT162b1, BNT162b2, and BNT162c2) will be tested.
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This trial has two parts. Part A is for dose ranging with dose escalation and de -escalation plus the evalua-
tion of interim dose levels. It also includes dose ranging in older subjects. Part B is dedicated to recruit
expansion cohorts with dose levels whic h are selected from data generated in Part A.
The vaccines BNT162a1, BNT162b1, BNT162b2, and BNT162c2 will be administered using a P/B regi-men. The vaccine BNT162c2 will also be administered using a SD regimen.
The chosen trial design reflects discussion and advice from the Paul -Ehrlich Institute (PEI) obtained in
scientific advice meetings held in February, March, and June 2020.
Part A
Trial subjects with the first -in-human [FIH] immunization will be immunized using a sentinel dosing/sub-
ject staggerin g (EMA 2017 guidance “Strategies to Identify and Mitigate Risks for First -in-Human and
Early Clinical Trials with Investigational Medicinal Products ”). The FIH starting dose and the planned
escalation/de- escalation doses are given in Table 1 of protocol version 8. Dose escalation rules have been
defined in this protocol to guide dose escalation.
For all cohorts, if the investigator considers necessary, the planned observation periods before proceeding
to dose further subjects in the same group may be prolonged by 24 h.
Dose de-escalation in the case of possible vaccine -related toxicities will be guided by the Safety Review
Committee (SRC), as required.
In Cohort 1, the sentinel dosing/subject staggering process will be as follows:
• One sentinel subject will be dosed on one day.
• If the dosing in this subject was considered to be safe and well tolerated by the investigator after
24±2 h observation on site, 5 further subjects will be dosed (with intervals of at least 1 h between
subjects).
• If the dosing in these 5 subjects was considered to be safe and well tolerated by the investigator based on 48 h data (24±2 h observation on site and phone interview for assessment 48±2 h after
immunization; in addition to the available 48±2 h data from the sentinel subject):
o The remaining 6 subjects in the group will be dosed (with intervals of at least 30 min be-
tween subjects).
o If approved by the SRC, the next planned escalation dose will be initiated. The data as-
sessed by the SRC comprises 48 h data for 6 subjects including observation on site, short
summary of phone interview (including statement about diary reports), vital signs, inves-
tigator reported local and systemic reactions, TEAEs, solicited local & systemic reac-
tions, blood/clinical laboratory data, and brief physical examination outcome.
o If approved by the SRC, the planned de -escalation dose in Cohort 3 will be initiated.
For any subsequent dose -escalation cohorts (to doses higher than the maximum already tested for a vac-
cine candidate), the sentinel/subject staggering process will be as follows:
• Two sentinel subjects will be dosed on one day (with intervals of at least 30 min between sub-
jects).
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• If the dosing in these subjects was considered to be safe and well tolerated by the investigator af-
ter 24±2 h observation on site, 4 further subjects will be dosed (with intervals of at least 30 min
between subjects).
• If the dosing in these 4 subjects was considered to be safe and well tolerated by the investigator
based on 48 h data (24±2 h observation on site and phone interview for assessment 48±2 h after
immunization; in addition to the available 48 h data from the sentinel s ubjects):
o The remaining 6 subjects in the group will be dosed (with intervals of at least 30 min be-tween subjects).
o If approved by the SRC, the next planned escalation dose (see Table 1) will be initiated.
The data assessed by the SRC comprises 48 h data for 6 subjects including observation on site, short summary of phone interview (including statement about diary reports), vital
signs, investigator reported local and systemic reactions, TEAEs, solicited local & sys-
temic reactions, blood/clinical laboratory data, and brief physical examination outcome.
The maximum allowed dose for each vaccine candidate is defined in the protocol.
For the planned dose de -escalation cohorts, 12 subjects may be dosed on one day (with intervals of at
least 30 min between subjects). The doses in these cohorts in younger adults must be lower than doses
than doses that have shown acceptable tolerability in younger adults (based on the data from 12 subjects
up until 48 h after the first dose). The same dose will not be administered twice, i.e., in two cohorts.
For BNT162b1 and BNT162b2, administration of the planned 10 µg dose in older subjects (Cohort 8)
may start once at least a 30 -µg dose has shown acceptable tolerability in younger adults (based on the
data from 12 subjects up until 48 h after the boost dose). The dose in Cohort 8 must also be confirmed by
the SRC. In Cohort 8, 12 subjects will be dosed using a sentinel dosing/subject staggering (2-4- 6) process
with intervals of at least 1 h between the first 6 subjects and then at least 30 min intervals for the remain-
ing 6 subjects.
For BNT162b1 and BNT162b2, administration of the planned dose escalation cohorts in older adults (Co-
horts 9 and 10), 12 subjects will be dosed using a sentinel dosing/subject staggering (2-4-6) process with
intervals of at least 30 min between subjects. The doses planned in these cohorts will only be adminis-tered if the dose is confirmed by the SRC.
For the unplanned dose de -escalation cohorts, i.e., where the SRC requests the use of a reduced dose for
safety reasons, 12 subjects may be dosed on one day with intervals of at least 30 min between subjects (as for planned de -escalation cohorts).
Note: BNT162b1 and BNT162b2 are modified uridine RNAs, while BNT162a1 and
BNT162c2 are both nucleosi de-modified pseudomethyl -uridine containing RNAs. RNA modification is
known to impact the extent of innate immune activation at a given dose level, and thus potentially the ex-tent of reactogenicity. Therefore, tolerability data obtained with one of the vaccine variants of each of these pairs may be potentially informative for the respective other one and should be taken in considera-tion by the SRC for recommendations of lower or interim doses.
In the case that an individual experiences dose limiting toxicities or that the frequency or pattern of AEs
within a sub- cohort gives cause for concern, the investigator may request by phone an ad hoc review by
the SRC, at any time, before further doses of a given vaccine construct are administered.
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Part B
Part B will only be started if approved using a substantial protocol amendment.
Details of Part B will be defined using a protocol amendment after thorough evaluation of immunogenic-
ity and safety data from Part A for each vaccine candidate individually. Part B may be initiated for one or
more vaccines while Part A is still ongoing, depending on the available data.
Safety data to be evaluated includes the package used by the SRC to assess individual dose levels and in
addition any other safety observations that may be reported until the data cut off. Immunogenicity of all
doses will be thoroughly assessed.
The protocol amendment will include a summary of relevant safety and tolerability data collected in Part A. This protocol amendment will also include Part B specific inclusion/exclusion criteria, objectives/end-
points, a description of the planned statistical analyses, and descriptions of any added trial assessments and procedures.
Part B will use a randomized, placebo -controlled design in the likely target population (e.g., higher risk
populations such as immune compromised populations). Part B may employ a surrogate marker as a
measure of vaccine efficacy.
3. Analysis Considerations Related to Multiple Analysis Datasets
3.1 Core Variables
Core variables are those that are represented across all/most analysis datasets.
Variable Name Variable Description
STUDYID Study Identifier
USUBJID Unique Subject Identifier
SUBJID Subject Identifier for the Study
SUBJIDN Subject Identifier for the Study (N)
SITEID Study Site Identifier
AGE Age
AGEU Age Units
AGEGR1 Pooled Age Group 1
AGEGR1N Pooled Age Group 1 (N)
SEX Sex
SEXN Sex (N)
RACE Race
RACEN Race (N)
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Variable Name Variable Description
SCRFL Screened Population Flag
SCRFN Screened Population Flag (N)
SAFFL Safety Population Flag
SAFFN Safety Population Flag (N)
SAFBFL Safety Boost Population Flag
SAFBFN Safety Boost Population Flag (N)
IMMFL Immunogenicity Population Flag
IMMFN Immunogenicity Population Flag (N)
EXIMM1 Reason for Exclusion Immunogenicity Set
PPROTFL Per-Protocol Population Flag
PPROTFN Per-Protocol Population Flag (N)
EXPPROT1 Reason 1 for Exclusion Per -Protocol Set
CP7FL Prime + 7 Days Completers Set
CP7FN Prime + 7 Days Completers Set (N)
CPBP28FL Prime to Boost or Prime +28 D. Comp. Set
CPBP28FN Pri. to Bo. or Pri. +28 D. Comp. Set (N)
CB7FL Boost + 7 Days Completers Set
CB7FN Boost + 7 Days Completers Set (N)
CB28FL Boost + 28 Days Completers Set
CB28FN Boost + 28 Days Completers Set (N)
CPB28FL Prime or Boost + 28 Days Completers Set
CPB28FN Prime or Boost + 28 Days Comp. Set (N)
COMPLFL Completers Population Flag
COMPLFN Completers Population Flag (N)
COHORT Cohort
COHORTN Cohort (N)
COHCAT1 Cohort Category 1
COHCAT1N Cohort Category 1 (N)
COHCAT2 Cohort Category 2
COHCAT2N Cohort Category 2 (N)
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Variable Name Variable Description
GROUP Group
GROUPN Group (N)
ARM Description of Planned Arm
ACTARM Description of Actual Arm
TRTP Planned Treatment
TRTPN Planned Treatment (N)
TRTA Actual Treatment
TRTAN Actual Treatment (N)
TRTSDT Date of First Exposure to Treatment
TRTSTM Time of First Exposure to Treatment
TRTSDTM Datetime of First Exposure to Treatment
TRTEDT Date of Last Exposure to Treatment
TRTETM Time of Last Exposure to Treatment
TRTEDTM Datetime of Last Exposure to Treatment
ALLOCDT Date of Allocation
ALLOCTM Time of Allocation
ALLOCDTM Datetime of Allocation
PRIMDT Date of Prime Immunization
PRIMTM Time of Prime Immunization
PRIMDTM Datetime of Prime Immunization
BOIMDT Date of Boost Immunization
BOIMTM Time of Boost Immunization
BOIMDTM Datetime of Boost Immunization
3.2 Treatment Variables
ARM versus TRTxxP
Are the values of ARM equivalent in meaning to values of TRTxxP?
Yes, the values of ARM are equivalent in meaning to values of TRT01P. ARM and TRT01P
correspond to the planned treatment.
ACTARM versus TRTxxA
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If TRTxxA is used, then are the values of ACTARM equivalent in meaning to values of TRTxxA?
Yes, the values of ACTARM are equivalent in meaning to values of TRT01A. ACTARM and
TRT01A corresponds to the actual treatment. It has same value as TRT01P for the treated
subjects.
Use of ADaM Treatment Variables in Analysis
Are both planned and actual treatment variables used in analys is?
No, only actual treatment variables were used in analyses. Actual treatment variables were
used for safety analysis and Immunogenicity related report analysis.
Use of ADaM Treatment Grouping Variables in Analysis
Are both planned and actual treatment grouping va riables used in analysis?
No
3.3 Subject Issues that Require Special Analysis Rules
There are no subject issue s that require special analysis rules.
3.4 Use of Visit Windowing, Unscheduled Visits, and Record Selection
Was windowing used in one or more analysis dat asets?
No.
Were unscheduled visits used in any analyses?
No. Data collected at unscheduled visits will not be included and analyzed for safety and efficacy
analysis.
3.5 Imputation/Derivation Methods
If date imputation was performed, were there rules that were used in multiple analysis datasets?
No. Date imputations were not performed for this study.
Additional Content of Interest
DTYPE was used in analysis dataset ADVA and ADLB to indicate the type of derivations used in creat-
ing additional rows based on source data. Details about the derivation of DTYPE can be found in Section
5.2 in subsections specific to analysis datasets.
4. Analysis Data Creation and Processing Issues
4.1 Split Datasets
There are no split datasets.
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4.2 Data Dependencies
All datasets get core variable values from ADSL. There were no other processing dependencies.
4.3 Intermediate Datasets
No intermediate analysis datasets were created in this trial.
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5. Analysis Dataset Descriptions
5.1 Overview
Are data for screen failures, including data for run- in screening (for example, SDTM values of
ARMCD=’SCRNFAIL’, or ‘NOTASSGN’) included in ADaM datasets? No
No. There are no Subjects with ARMCD=’SCRNFAIL’, or ‘NOTASSGN’ included in ADSL or
any other datasets.
Are data taken from an ongoing study?
Yes.
Do the analysis datasets support all protocol - and statistical analysis plan -specified objectives?
The analysis datasets support a subset of protocol- and statistical analysis plan -specified data
presentations included in an interim abbreviated clinical study report featuring a data cutoff date
of October 23, 2020 .
Additional Content of Interest
The dataset cutoff date used for the generation of the SDTM domains from which the ADaM da-
tasets were created was 2020 -10-23.
5.2 Analysis Datasets
Dataset Label Class
Efficacy
Safety
Baseline or
other subject
characteristics
PK/PD
Primary
Objective
Structure
ADSL
Subject-Level
Analysis Dataset SUBJECT LEVEL
ANALYSIS DATASET X One record per subject
A-
DAE Ad-
verse Events Anal-
ysis Dataset OCCURRENCE DATA
STRUCTURE X One record per subject per
adverse event per event start date
ADCEVD
Reactogenicity
Analysis Dataset OCCURRENCE DATA STRUCTURE X X One record per subject per
clinical event per analysis
timepoint per vaccination period
(identified by traceability variable
CESEQ)
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Dataset Label Class
Efficacy
Safety
Baseline or
other subject
characteristics
PK/PD
Primary
Objective
Structure
ADFACEVD
Reactogenicity
Findings Analysis
Dataset BASIC DATA
STRUCTURE X One record per subject per
analysis parameter per analysis
timepoint
ADLB
Laboratory
Analysis Dataset BASIC DATA
STRUCTURE X One record per subject per
analysis parameter per analysis
timepoint
ADVA
Immunogenicity Analysis Dataset BASIC DATA
STRUCTURE X One record per subject per
analysis parameter per analysis
timepoint
ADVS
Vital Signs
Analysis Dataset BASIC DATA
STRUCTURE X One record per subject per
analysis parameter per analysis
timepoint
5.2.1 ADSL - Subject -Level Analysis Dataset
ADSL includes all subjects in the DM domain and contains relevant subject level information, treatment
variables and analysis set flags. This dataset supported the creation of all other analysis datasets. ADSL
also contains the variables to support baseline characteristics and disposition analyses .
ADSL include s the following information for each subject.
• Subject identifier
• Demographic information
• Planned treatment and actual treatment
• Population flags
- SCRFL (Screened Population Flag)
- SAFFL (Safety Population Flag)
- SAFBFL ( Safety Boost Population Flag)
- IMMFL ( Immunogenicity Population Flag)
- PPROTFL ( Per-Protocol Population Flag)
- CP7FL (Prime + 7 Days Completers Set )
- CPBP28FL (Pri. to Bo. or Pri. +28 D. Comp. Set)
- CB7FL (Boost + 7 Days Completers Set)
- CB28FL ( Boost + 28 Days Completers Set )
- CPB28FL ( Prime or Boost + 28 Days Completers Set )
- COMPLFL ( Completers Population Flag)
• Key dates and datetime related to conduct of the study
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- Date of First Exposure to Treatment (TRTSDT)
- Date of Last Exposure to Treatment (TRTEDT)
- Datetim e of First Exposure to Treatment (TRTSDTM)
- Datetime of Last Exposure to Treatment (TRTEDTM)
- Date of Informed Consent (RFICDT)
- Datetime of Informed Consent (RFICDTM)
- Date of Screening (SCRDT)
- Date of Last Visit (LVDT)
- End of Study Date (EOSDT)
- End of Follow -up Date (EOFUDT)
- Datetime of Prime Immunization (PRIMDT M)
- Datetime of Boost Immunization (BOIMDT M)
- Date of first Informed Consent (FIRICDT)
- Datetime of Informed Consent Reconsented 1 (ICR1DT M)
- Datetime of Informed Consent Reconsented 2 (ICR2DT M)
- Datetime of Informed Consent Reconsented 3 (ICR3DT M)
- Datetime of Informed Consent Reconsented 4 (ICR4DTM)
- Date of Prime Immunization (PRIMDT)
- Date of Boost Immunization (BOIMDT)
- Date of Informed Consent Reconsented 1 (ICR1DT)
- Date of Informed Consent Reconsented 2 (ICR2DT)
- Date of Informed Consent Reconsented 3 (ICR3DT)
- Date of Informed Consent Reconsented 4 (ICR4DT)
- Date of Death (DTHDT)
• Key variables related to treatment for reporting
- Cohort (COHORT)
- Group (GROUP)
- Description of Planned Arm (ARM)
- Description of Actual Arm (ACTARM)
- Planned Treatment for Period 01 (TRT01P)
- Actual Treatment for Period 01 (TRT01A)
5.2.2 ADAE - Adve rse Events Analysis Dataset
This is a main safety analysis dataset comprised of adverse events recorded on the CRF. For dictionary
coding, including specific terms for COVID -19, MedDRA version 23.0 was used. Source data can be
traced back to the SDTM.AE domain using AESEQ. This dataset produces all outputs related to adverse
events analysis. Safety summary for AE were performed based on treatment -emergent adverse events
(TEAE). TEAE is defined as any AE with an onset date on or after the first immunization or worsened
after the first immunization (if the AE was present before the first immunization). AEs with an onset date
more than 28 days after the last immunization will be considered as treatment emergent only if assessed as related to IMP by the investigator. AEs that cannot be determined to not be treatment emergent due to
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missing date or time will be defined as TEAE and flagged as “Y” in ADAE.TRTEMFL. The TEAEs were
evaluated for the following time intervals:
• Prime immunization up to day 7 (inclusive) af ter initial immunization (TMINT1FL)
• Prime immunization up to boost immunization or day 28 (inclusive) after initial immunization
( whatever comes first) (TMINT2FL)
• Boost immunization up to day 7 (inclusive) after boost immunization (TMINT3FL)
• Boost immunization up to day 28 (inclusive) after boost immunization (TMINT4FL)
• Prime immunization up to day 28 (inclusive) after boost immunization (TMINT5FL)
A look up table has been used to derive Preferred Term based on diary entry (PTDIAFL) which is de-
scribed in Appendix II .
Some of the key ADAE variables/Flags used for analysis are describe d below.
Variable Description
TRTEMFL Treatment Emergent Analysis Flag
PTDIAFL Preferred Term based on diary entry
AEEPRELI Epi/Pandemic Related Indicator
AEEMREL Treatment emergent related AE
AEEMSREL Treatment emergent severe related AE
AEEMSER Serious treatment emergent AE
AEEMSER R Serious treatment emergent related AE
AEACN Action taken with study treatment
AETOXGR Standard Toxicity Grade
ASEV Analysis Severity/Intensity
TMINT1FL Time Interval 1 Flag
TMINT2FL Time Interval 2 Flag
TMINT3FL Time Interval 3 Flag
TMINT4FL Time Interval 4 Flag
TMINT5FL Time Interval 5 Flag
Methods used to derive these key variables are described in Appendix I II.
5.2.3 ADCEVD – Reactogenicity Analysis Dataset
ADCEVD follows the ADaM Occurrence Data Structure to support the analysis of reactogenicity events.
This dataset contains information regarding the occurrence (variable CEOCCUR) and severity (variable
ASEV) of local and systemic reactions (identified by variable ACAT1) as reported by the subject in a
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daily diary during the 7 ±1-day assessment period following each vaccination. Specific reactions are iden-
tified by CETERM, and occurrence flag variables (see table below) provide information regarding occur-
rences at the categorical level. Individual daily records from the diary can be viewed in the ADFACEVD
dataset. Reactions which are first reported beyond the assessment period (with a value of ATPTN > 8 in
ADFACEVD) are not considered in the population of occurrence and severity variables in ADCEVD but
are considered in the population of the Analysis End Date (variable AENDT).
Key variables from ADCEVD utilized for analysis are the occurrence flags described here:
Occurrence
Flag Variable Label Selection Criteria
[Flags 1st record having CEOCCUR = ‘Y’ and meeting
the additional selection criteria specified for a given
USUBJI D whe n s orte d by ASTDT and CETERM .]
AOCCLRFL 1st Occurrence Local Reaction ACAT1 = 'local'
AOCCL3FL 1st Occur Gr>=3 Local Reaction ACAT1 = 'local' and SEVGR1 = 'grade >= 3'
AOCCLPFL 1st Occurrence Local Reaction -Prime ACAT1 = 'local' and ATPTREF = 'Prime'
AOCCXPFL 1st Occur Gr>=3 Local Reaction- Prime ACAT1 = 'local' and SEVGR1 = 'grade >= 3' and
ATPTREF = 'Prime'
AOCCLBFL 1st Occurrence Local Reaction -Boost ACAT1 = 'local' and ATPTREF = 'Boost’
AOCCXBFL 1st Occur Gr>=3 Local Reaction-Boost ACAT1 = 'local' and SEVGR1 = 'grade >= 3' and
ATPTREF = 'Boost'
AOCCSRFL 1st Occurrence Systemic Reaction ACAT1 = 'systemic'
AOCCS3FL 1st Occur Gr>=3 Systemic Reaction ACAT1 = 'systemic' and SEVGR1 = 'grade >= 3'
AOCCSPFL 1st Occurrence Systemic Reaction -
Prime ACAT1 = 'systemic' and ATPTREF = ‘Prime’
AOCCYPFL 1st Occur Gr>=3 Systemic Reaction -
Prime ACAT1 = 'systemic' and SEVGR1 = 'grade >= 3' and
ATPTREF = 'Prime'
AOCCSBFL 1st Occurrence Systemic Reaction -
Boost ACAT1 = 'systemic' and ATPTREF = 'Boost'.
AOCCYBFL 1st Occur Gr>=3 Systemic Reaction -
Boost ACAT1 = 'systemic' and SEVGR1 = 'grade >= 3' and
ATPTREF = 'Boost'
5.2.4 ADFACEVD – Reactogenicity Findings Analysis Dataset
ADFACEVD follows the ADaM Basic Data Structure ( BDS) to support the analysis of reactogenicity
event findings. This dataset contains information regarding the occurrence and severity of local and sys-
temic reactions (identified by variable PARCAT1), as well as the timing of first reactions in relation to
treatment start and the duration of reactions from earliest to latest report. Variables PARAM and PARAMCD are used to distinguish different findings. The detailed parameters are described in
Appendix
IV.
Key variables from ADFACEVD utilized for analysis include the following: AVAL C (analysis value for
occurrence and severity parameters), AVAL (analysis value for time to first reaction and time from first to last reaction parameters), PARCAT1 (identifies reactions as local or systemic), AVALCAT1 (identifies reactions as having grade >= 3), ATPTREF (identifies reactions as being related to the Prime or Boost vaccination) , and ANL01FL (identifies reactions included in frequency analyses, as those reported to
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have occurred prior to the associated vaccination date/time – presumably due to data issue – are not in-
cluded in frequency analyses).
5.2.5 ADLB – Laboratory Analysis Dataset
This dataset follows ADaM Basic Data Structure (BDS) supporting the analysis of laboratory data. The
data can be pulled by any specific PARAMCD to view a certain lab endpoint. The AVAL value represents
the result in the standard unit. New records have been imputed for qualifying parameters and DTYPE (Der-
ivation Type) is populated as “HALFLLOQ”. Lab parameters are described i n Appendix I.
Laboratory data includes the flags which help understand the incidence of laboratory abnormalities (clini-
cally significant or not) in the dataset. ANRIND, BNRIND, NABCS described below are abnormality flags. The reference ranges, ANRLO (Analysis Normal Range Lower Limit) and ANRHI (Analysis Normal
Range Upper Limit) are used to determine the laboratory abnormalities. In addition to above variables there
is an additional flag WPBLFL (Worst Post -Baseline Flag) which captures the first incidence of post-base-
line abnormali ty. The analysis flags ANL01FL, ANL02FL are also included in the data. This dataset is used
for the lab listings and lab abnormality/summary tables.
ANL01FL: Flag for all scheduled visits.
ANL02FL: Flag for all observed/original collected values. Will be NULL for imputed records.
ANRIND: Any Abnormality Criteria.
BNRIND: Abno rmality at Baseline.
DTYPE: If any parameter has result captured as “<X” then a new record is imputed with AVAL as 0.5*X
and DTYPE is populated as HALFLLOQ.
NABCS: Abnormality with Clinical Significance
WPBLFL: First occurrence of unique post- baseline abnormality. if there is no abnormality then first post -
baseline record is flagged for each parameter .
Key Variables : PARAM, AVISIT, AVISITN, AVAL, AVALC, BASE, CHG, PARCAT1, ANRIND,
BNRIND, NABCS, ADT, ADY.
5.2.6 ADVA – Immunogenicity Analysis Dataset
This is a main analysis dataset and contains immunogenicity assessments in IS dataset.
Assay result below the corresponding LLOQ were set to 0.5 × LLOQ and DTYPE was set to “HALF L-
LOQ”, and missing assay results was not imputed. All analysis parameters are presented in below table.
The ratio from post -baseline to baseline was calculated as AVAL/ BASE for fold rise summaries .
PARCAT1 PARAMCD PARAMN PARAM ISLLOQ
IMMUNOGENICITY C19RBDIG 1 COVID-19 RBD IgG (U/mL) 1.1505
IMMUNOGENICITY C19S1IGG 2 COVID-19 S1 IgG (U/mL) 1.2665
IMMUNOGENICITY C2NGNT50 3 SARS-CoV-2 Serum Neutralizing Titer 50 20
IMMUNOGENICITY C2NGNT90 4 SARS-CoV-2 Serum Neutralizing Titer 90 20
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PARCAT1 PARAMCD PARAMN PARAM ISLLOQ
IMMUNOGENICITY FRC19RBD 5 COVID-19 RBD IgG Fold Rise
IMMUNOGENICITY FRC19S1I 6 COVID-19 S1 IgG Fold Rise
IMMUNOGENICITY FRC2NT50 7 SARS-CoV-2 Serum Neutralizing Titer 50 Fold Rise
IMMUNOGENICITY FRC2NT90 8 SARS-CoV-2 Serum Neutralizing Titer 90 Fold Rise
Key Variables: P ARAM, AVISIT, AVISITN, AVAL, AVAL C, BASE, CHG, PCHG, CRIT1, CRIT1FL,
PARCAT1, ADT, ADY.
5.2.7 ADVS – Vital Signs Analysis Dataset
This dataset follows ADaM Basic Data Structure (BDS) supporting the analysis of vital signs measure-
ment. The data can be pulled by any specific PARAMCD to view at any timepoint. The AVAL value rep-
resents the result in the standard unit.
Vitals data includes the flags which help understand the incidence of abnormalities (clinically significant
or not) in the dataset. ANRIND, BNRIND, NABCS described below are abnormality flags. The reference
ranges, ANRLO (Analysis Normal Range Lower Limit) and ANRHI ( Analysis Normal Range Upper
Limit) are used to determine the abnormalities. The analysis flags ANL01FL, ANL02FL are also included in the data. This dataset is used for the vital signs’ listings and abnormality/summary tables.
ANL01FL: Flag for all schedul ed visits.
ANL02FL: Flag for all observed/original collected values. Will be NULL for imputed records.
ANRIND: Any Abnormality Criteria.
BNRIND: Abnormality at Baseline.
NABCS: Abnormality with Clinical Significance
Listed below are the parameters used in reporting.
PARAMCD PARAMN PARAM
BMI 1 Body Mass Index [kg/m2]
DIABP 2 Diastolic Blood Pressure [mmHg]
HEIGHT 3 Height [cm]
PULSE 4 Pulse Rate [beats/min]
RESP 5 Respiratory Rate [breaths/min]
SYSBP 6 Systolic Blood Pressure [mmHg]
TEMP 7 Temperature [C]
WEIGHT 9 Weight [kg]
TEMPR 8 Temperature (Reactogenicity) [C]
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Key Variables: PARAM, PARAMCD, PARCAT1, PARCAT2, VSCLSIG , AVISIT, AVISITN, AVAL,
BASE, CHG, PCHG, ANRIND, BNRIND, NABCS, ADTM, ATPT, ADT, ADY.
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
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 Sum m ary
Check
ID Diagnostic Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
SD1229 AVAL value is null when
PARAMCD == 'EOSLEBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-
276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'LYMLEBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-
276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'NEUTLEBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-
276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'BASOBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-
276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'NEUTBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'EOSBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'BASOLEBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-
276-02-0191 at Day 29 visit.
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Check
ID Diagnostic Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
SD1229 AVAL value is null when
PARAMCD == 'MONOBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-
276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'LYMBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-
276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD = =
'MONOLEBS' Error ADLB 1 (4.55%) Lab was unable to analyze
cells for subject BNT162-01-276-02-0191 at Day 29 visit.
SD1229 AVAL value is null when
PARAMCD == 'TEMP' Error ADVS 3 (< 0.1%) Temperature was not rec-
orded for subject BNT162-
01-276-02- 0242 at 1, 3, and
6-hour timepoints following
boost vaccination.
SD1229 AVALC value is null when
PARAMCD == 'TEMP' Error ADVS 3 (< 0.1%) Temperature was not rec-
orded for subject BNT162-01-276-02- 0242 at 1, 3, and
6-hour timepoints following
boost vaccination.
7. Submission of Progr ams
All programs for analysis datasets as well as primary safety and secondary immunogenicity
results are not submitted.
7.1 ADaM Programs
Programs are not submitted.
7.2 Analysis Output Programs
Outputs are not submitted.
7.3 M acro Programs
Macro programs are not submitted.
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8. Appendix
8.1 Appendix I: Lab Parameters
PARAM PARAMCD PARAMN
Alanine Aminotransferase [U/L] ALT 1
Albumin [g/L] ALB 2
Alkaline Phosphatase [U/L] ALP 3
Amphetamine AMPHET 4
Amylase [U/L] AMYLASE 5
Anisocytes ANISO 6
Aspartate Aminotransferase [U/L] AST 7
Bacteria [/HPF] BACT 8
Barbiturates BARB 9
Basophils (Blood Smear) [10^9/L] BASOBS 14
Basophils (Blood) [10^9/L] BASOB 11
Basophils/Leukocytes (Blood Smear) [%] BASOLEBS 17
Basophils/Leukocytes (Blood) [%] BASOLEB 16
Benzodiazepine BNZDZPN 18
Bilirubin (Serum) [umol/L] BILIS 19
Bilirubin (Urine) [umol/L] BILIU 20
C Reactive Protein [mg/L] CRP 21
Calcium [mmol/L] CA 22
Cannabinoids CANNAB 23
Casts [/HPF] CASTS 24
Choriogonadotropin Beta HCG 25
Cocaine COCAINE 26
Creatine Kinase [U/L] CK 27
Creatinine [umol/L] CREAT 28
Crystals [/HPF] CRYSTALS 29
Eosinophils (Blood) [10^9/L] EOSB 31
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Eosinophils (Blood Smear) [10^9/L] EOSBS 34
Eosinophils/Leukocytes (Blood) [%] EOSLEB 36
Eosinophils/Leukocytes (Blood Smear) [%] EOSLEBS 37
Epithelial Cells [ /HPF] EPIC 38
Ery. Mean Corpuscular HGB Concentration [mmol/L] MCHC 39
Ery. Mean Corpuscular Hemoglobin [fmol] MCH 40
Ery. Mean Corpuscular Volume [fL] MCV 41
Erythrocytes (Blood) [10^12/L] RBCB 42
Erythrocytes (Urine) [/HPF] RBCU 43
Ethanol ETHANOL 44
Ferritin [ug/L] FERRITIN 47
Follicle S timulating Hormone [IU/L] FSH 48
Gamma Glutamyl Transferase [U/L] GGT 49
Glucose (Blood) [mmol/L] GLUCB 50
Glucose (Urine) GLUCU 51
Granulocytes Band Form/Total Cells [%] GRANBCE 52
Hematocrit [L/L] HCT 53
Hemoglobin (Blood) [mmol/L] HGBB 54
Hemoglobin (Urine) [10^6/L] HGBU 55
Ketones [mmol/L] KETONES 56
Leukocytes (Blood) [10^9/L] WBCB 57
Leukocytes (Urine - Dipstick) [10^6/L] WBCUD 58
Leukocytes (Urine - Microscopy) [/HPF] WBCUM 59
Lipase [U/L] LIPASET 60
Lymphocytes (Blood) [10^9/L] LYMB 62
Lymphocytes (Blood Smear) [10^9/L] LYMBS 65
Lymphocytes Atypical/Leukocytes [%] LYMATLE 66
Lymphocytes/Leukocytes (Blood) [%] LYMLEB 68
Lymphocytes/Leukocytes (Blood Smear) [%] LYMLEBS 69
Macrocytes MACROCY 70
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Methadone METHDN 71
Methamphetamine METHAMPH 72
Microcytes MICROCY 73
Monocytes (Blood) [10^9/L] MONOB 75
Monocytes (Blood Smear) [10^9/L] MONOBS 78
Monocytes/Leukocytes (Blood) [%] MONOLEB 80
Monocytes/Leukocytes (Blood Smear) [%] MONOLEBS 81
Myelocytes [%] MYCY 82
Neutrophils (Blood) [10^9/L] NEUTB 84
Neutrophils (Blood Smear) [10^9/L] NEUTBS 87
Neutrophils/Leukocytes (Blood) [%] NEUTLEB 89
Neutrophils/Leukocytes (Blood Smear) [%] NEUTLEBS 90
Nitrite NITRITE 91
Opiate OPIATE 92
pH PH 93
Phencyclidine PCP 94
Platelets [10^9/L] PLAT 95
Poikilocytes POIKILO 96
Potassium [mmol/L] K 97
Protein [mg/L] PROT 98
Round Epithelial Cells [/HPF] EPIROCE 99
Smudge Cells/Leukocytes [%] SMDGCELE 100
Sodium [mmol/L] SODIUM 101
Specific Gravity SPGRAV 102
Tricyclic Antidepressants TRCYANDP 103
Urea Nitrogen [mmol/L] UREAN 104
Urobilinogen [umol/L] UROBIL 105
Yeast Cells [/HPF] YEAST 106
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8.2 Appendix II: Look Up Table
Pre fe rre d Te rm Pre fe rre d Te rm Code
Abdominal pain 10000081
Abdominal pain lower 10000084
Arthralgia 10003239
Axillary p ain 10048750
Body temperature increased 10005911
Chills 10008531
C-reactive protein increased 10006825
Decreased appetite 10061428
Diarrhoea 10012735
Discomfort 10013082
Dizziness 10013573
Fatigue 10016256
Feeling hot 10016334
Gastrointestinal disorder 10017944
Head discomfort 10019194
Headache 10019211
Hot flush 10060800
Influenza like illness 10022004
Injection site discolouration 10051572
Injection site discomfort 10054266
Injection site erythema 10022061
Injection site hypersensitivity 10022071
Injection site hypoaesthesia 10074586
Injection site pain 10022086
Injection site paraesthesia 10022088
Injection site reaction 10022095
Injection site swelling 10053425
Malaise 10025482
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Muscle tightness 10049816
Myalgia 10028411
Nausea 10028813
Neck pain 10028836
Procedural pain 10064882
Pyrexia 10037660
Vomiting 10047700
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8.3 Appendix I II: Methods to der ive key ADAE variables
ADAE Variables Derivation Method
TRTEMFL *if not missing Adverse start date/time and AE start date/time >= first im-
munization date/time and AE start date/time <= (last immunization date/time
+ 28 days), then TRTEMFL='Y';
*if missing Adverse start time and AE start date >= first immunization date
and AE start date <= (last immunization date + 28 days), then
TRTEMFL='Y';
*if not missing Adverse start date/time and AE start date/time > (last immun-
ization date/time + 28 days) but assessed as related to IMP by investigator then TRTEMFL='Y';
*if missing Adverse start time and AE start date > (last immuni zation date +
28 days) but assessed as related to IMP by investigator then TRTEMFL='Y';
*if AE present before immunization and worsened after first immunization,
then TRTEMFL='Y';
*if missing AE date or time and AE cannot be determined TEAE from the
above set rules, then TRTEMFL='Y';
PTDIAFL if (AEDECOD in ('Abdominal pain', ' Abdominal pain lower', ' Arthralgia', 'Chills', 'Decreased appetite', 'Diarrhoea', 'Discomfort', 'Fatigue', ' Feeling
hot', 'Gastrointestinal disorder', 'Headache', 'Hot flush', 'I nfluenza like illness',
'Injection site discomfort', 'Injection site erythema', 'Injection site hypersensi-tivity', 'Injection site pain', 'Injection site paraesthesia', 'Injection site reac-tion', 'Injection site swelling', 'Malaise', 'Muscle tightness', 'M yalgia', 'Nau-
sea', ' Pyrexia' , 'Vomiting', 'Axillary pain', 'Body temperature increased', 'C -
reactive protein increased', 'Dizziness', 'Head discomfort', 'Injection site dis-colouration', 'Injection site hypoaesthesia', 'Neck pain' ) and ((AENDT -
ASTDT)+ 1)<=7) then PTDIAFL='Y'.
AEEMREL If TRTEMFL='Y' and upcase(arel)='RELATED' then AEEMREL='Y'; else
AEEMREL='N'.
AEEMS If TRTEMFL='Y' and asevn in (3,4) then AEEMS='Y'; else AEEMS='N'.
AEEMSER If TRTEMFL='Y' and aeser='Y' then AEEMSER='Y'; else AEEMSER='N '.
AEEMSERR If TRTEMFL='Y' and aeser='Y' and upcase(arel)='RELATED' then AEEM-
SERR='Y'; else AEEMSERR='N'.
AEEMSREL If TRTEMFL='Y' and asevn in (3,4) and upcase(arel)='RELATED' then
AEEMSREL='Y'; else AEEMSREL='N'.
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ASEV Propcase(AE.AESEV) when AE.AESEV not missing ; else Prop-
case(AE.AETOXGR) when AE.AETOXGR is not missing. ASEV= ' ' when
both AE.AESEV and AE.AETOXGR missing.
TMINT1FL AE is Treatment -Emergent:
if ASTDTM >= PRIMDTM and (PRIMDTM <= ASTDTM <= (PRIMDTM + 7 days)) then TMINT1FL='Y';
if ASTDTM < PRIMDTM and Adverse Event worsened after Prime immun-
ization then TMINT1FL='Y';
if AE time missing and Date not missing and
(PRIMDT <= ASTDT <= (PRIMDT + 7)) then TMINT1FL='Y';
if missing AE Date/or time and AE cannot be determined with above set rules, then TMINT1FL='Y';
TMINT2FL AE is Treatment -Emergent:
Identify the minimum of duration - ((Prime to Boost) or (28 days from
Prime) - whatever comes first.
When Boost is missing, duration is 28 days from Prime.
if duration < 28 then: (Prime to Boost contribution)
if not missing AE start date/time and PRIMDTM <= ASTDTM <= BOIM-
DTM then TMINT2FL='Y';
if not missing AE start date/time and ASTDTM < PRIMDTM and Adverse
Event worsened after Prime immunization then TMINT2FL='Y';
if missing AE start time and PRIMDT <= ASTDT <= BOIMDT then
TMINT2FL='Y';
if missing AE start time and ASTDT < PRIMDT and Adverse Event wors-ened after Prime immunization then TMINT2FL='Y';
if duration = 28 then: (28 days from prime contribution)
if not missing AE start date/time and PRIMDTM <= ASTDTM <= (PRIM-
DTM + 28 days) then TMINT2FL='Y';
if not missing AE start date/time and ASTDTM < PRIMDTM and Adverse
Event worsened after Prime immunization then TMINT2FL='Y';
if missing AE start time and PRIMDT <= ASTDT <= (PRIMDT + 28) then
TMINT2FL='Y';
if missing AE start time and ASTDT < PRIMDT and Adverse Event wors-
ened after Prime immunization then TMINT2FL='Y';
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if missing AE Date/or time and AE cannot be determined with above set
rules, then TMINT2FL='Y';
TMINT3FL AE is Treatment -Emergent:
if ASTDTM >= BOIMDTM and (BOIMDTM <= ASTDTM <= (BOIMDTM
+ 7 days)) then TMINT3FL='Y';
if ASTDTM < BOIMDTM and Adverse Event worsened after boost immun-
ization then TMINT3FL='Y';
if AE time missing and Date not missing and Boost immunization date not missing and (BOIMDT <= ASTDT <= (BOIMDT + 7)) then TMINT3FL='Y';
if missing AE Date/or time and AE cannot be determined with above set rules, then TMINT3FL='Y';
TMINT4FL AE is Treatment -Emergent:
if ASTDTM >= BOIMDTM and (BOIMDTM <= ASTDTM <= (BOIMDTM + 28 days)) then TMINT4FL='Y';
if ASTDTM < BOIMDTM and Adverse Event worsened after boost immun-ization then TMINT4FL='Y';
if AE time missing and Date not missing and Boost immunization date not missing and (BOIMDT <= ASTDT <= ( BOIMDT + 28)) then
TMINT4FL='Y';
if missing AE Date/or time and AE cannot be determined with above set
rules, then TMINT4FL='Y';
TMINT5FL
AE is Treatment -Emergent:
if not missing AE Date/time, Prime/Boost immunization date/time and
ASTDTM >= PRIMDTM and (PRIMDTM <= ASTDTM <= (BOIMDTM +
28 days)) then TMINT5FL='Y';
if not missing AE Date/time, Prime/Boost immunization date/time and
ASTDTM < PRIMDTM and Adverse Event worsened on/after prime im-
munization and before/on (boost immunization + 28 days) then
TMINT5FL='Y';
if not missing AE and Prime immunization date/time and boost date/time missing and
ASTDTM >= PRIMDTM and (PRIMDTM <= ASTDTM <= (PRIMDTM +
28 days)) then TMINT5FL='Y';
if missing AE time and AE date available and
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ASTDT >= PRIMDT and (PRIMDT <= ASTDT <= (BOIMDT + 28)) then
TMINT5FL='Y';
if missing AE time and AE date available and boost immunization missing
and
ASTDT >= PRIMDT and (PRIMDT <= ASTDT <= (PRIMDT + 28)) then
TMINT5FL='Y';
if missing AE Date/or time and AE cannot be determined with above set
rules, then TMINT5FL='Y';
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8.4 Appendix I V: ADFACEVD Analysis Parameters
PARAM PARAMCD PARAMN
Arthralgia occurrence indicator OCARTHR 230
Arthralgia severity/intensity SEVARTHR 231
Chills occurrence indicator OCCHILLS 235
Chills severity/intensity SEVCHIL 236
Diarrhea occurrence indicator OCDIAR 210
Diarrhea severity/intensity SEVDIAR 211
Fatigue occurrence indicator OCFATIG 220
Fatigue severity/intensity SEVFATI 221
Fever occurrence indicator OCFEVER 250
Fever severity/intensity SEVFEVER 251
Headache occurrence indicator OCHEAD 215
Headache severity/intensity SEVHEAD 216
Loss of Appetite occurrence indicator OCLOA 240
Loss of Appetite severity/intensity SEVLOA 241
Malaise occurrence indicator OCMALAI 245
Malaise severity/intensity SEVMALAI 246
Myalgia occurrence indicator OCMYALG 225
Myalgia severity/intensity SEVMYALG 226
Nausea occurrence indicator OCNAUS 200
Nausea severity/intensity SEVNAUS 201
Pain at injection site occurrence indicator OCPIS 100
Pain at injection site severity/intensity SEVPIS 101
Redness occurrence indicator OCISR 110
Redness severity/intensity SEVREDN 111
Swelling occurrence indicator OCINS 115
Swelling severity/intensity SEVSWEL 116
Tenderness at injection site occurrence indicator OCTIS 105
Tenderness at injection site severity/intensity SEVTIS 106
Time from first to last arthralgia DURARTH 2303
Time from first to last arthralgia with grade >= 3 DURARTH3 2304
Time from first to last chills DURCHIL 2353
Time from first to last chills with grade >= 3 DURCHIL3 2354
Time from first to last diarrhea DURDIAR 2103
Time from first to last diarrhea with grade >= 3 DURDIAR3 2104
Time from first to last fatigue DURFATI 2203
Time from first to last fatigue with grade >= 3 DURFATI3 2204
Time from first to last fever DURFEVE 2503
Time from first to last fever with grade >= 3 DURFEVE3 2504
Time from first to last headache DURHEAD 2153
Time from first to last headache with grade >= 3 DURHEAD3 2154
090177e196784ab8\Final\Final On: 09-Mar-2021 15:49 (GMT)
FDA-CBER-2021-5683-0058199
Study BNT162- 01 Analysis Data Reviewer’s Guide
Time from first to last local or systemic reaction DURAR 3
Time from first to last local or systemic reaction with grade >= 3 DURAR3 4
Time from first to last local reaction DURLR 13
Time from first to last local reaction with grade >= 3 DURLR3 14
Time from first to last loss of appetite DURLOA 2403
Time from first to last loss of appetite with grade >= 3 DURLOA3 2404
Time from first to last malaise DURMALA 2453
Time from first to last malaise with grade >= 3 DURMALA3 2454
Time from first to last myalgia DURMYAL 2253
Time from first to last myalgia with grade >= 3 DURMYAL3 2254
Time from first to last nausea DURNAUS 2003
Time from first to last nausea with grade >= 3 DURNAUS3 2004
Time from first to last pain at injection site DURPIS 1003
Time from first to last pain at injection site with grade >= 3 DURPIS3 1004
Time from first to last redness DURISR 1103
Time from first to last swelling DURINS 1153
Time from first to last systemic reaction DURSR 23
Time from first to last systemic reaction with grade >= 3 DURSR3 24
Time from first to last tenderness at injection site DURTIS 1053
Time from first to last tenderness at injection site with grade >= 3 DURTIS3 1054
Time from first to last vomiting DURVOMI 2053
Time from first to last vomiting with grade >= 3 DURVOMI3 2054
Time to first arthralgia TTEARTH 2301
Time to first arthralgia with grade >= 3 TTEARTH3 2302
Time to first chills TTECHIL 2351
Time to first chills with grade >= 3 TTECHIL3 2352
Time to first diarrhea TTEDIAR 2101
Time to first diarrhea with grade >= 3 TTEDIAR3 2102
Time to first fatigue TTEFATI 2201
Time to first fatigue with grade >= 3 TTEFATI3 2202
Time to first fever TTEFEVE 2501
Time to first fever with grade >= 3 TTEFEVE3 2502
Time to first headache TTEHEAD 2151
Time to first headache with grade >= 3 TTEHEAD3 2152
Time to first local or systemic reaction TTEFAR 1
Time to first local or systemic reaction with grade >= 3 TTEFAR3 2
Time to first local reaction TTEFLR 11
Time to first local reaction with grade >= 3 TTEFLR3 12
Time to first loss of appetite TTELOA 2401
Time to first loss of appetite with grade >= 3 TTELOA3 2402
Time to first malaise TTEMALA 2451
Time to first malaise with grade >= 3 TTEMALA3 2452
Time to first myalgia TTEMYAL 2251
090177e196784ab8\Final\Final On: 09-Mar-2021 15:49 (GMT)
FDA-CBER-2021-5683-0058200
Study BNT162- 01 Analysis Data Reviewer’s Guide
Time to first myalgia with grade >= 3 TTEMYAL3 2252
Time to first nausea TTENAUS 2001
Time to first nausea with grade >= 3 TTENAUS3 2002
Time to first pain at injection site TTEPIS 1001
Time to first pain at injection site with grade >= 3 TTEPIS3 1002
Time to first redness TTEISR 1101
Time to first swelling TTEINS 1151
Time to first systemic reaction TTEFSR 21
Time to first systemic reaction with grade >= 3 TTEFSR3 22
Time to first tenderness at injection site TTETIS 1051
Time to first tenderness at injection site with grade >= 3 TTETIS3 1052
Time to first vomiting TTEVOMI 2051
Time to first vomiting with grade >= 3 TTEVOMI3 2052
Vomiting occurrence indicator OCVOMI 205
Vomiting severity/intensity SEVVOMI 206
090177e196784ab8\Final\Final On: 09-Mar-2021 15:49 (GMT)
FDA-CBER-2021-5683-0058201