Document text
Study C4591001 Clinical Study Data Reviewer’s Guide
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Clinical Study Data Reviewer’s Guide for
Sequencing Data Analysis
BLA Analysis for Participants ≥16 Years of Age
BioNTech SE and PFIZER INC.
Study C4591001
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FDA-CBER-2021-5683-1007493
Study C4591001 Clinical Study Data Reviewer’s Guide
This document is confidential Page 2 of 8 Clinical Data Reviewer ’s Guide Revision history
Version Summary of Major Change(s) and Impact Version Date
1.0 First approved version of Clinical Data Reviewer’s Guide for Sequencing
data Analysis 03-Jun-2021
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Clinical Study Data Reviewer’s Guide
Contents
Study C4591001 ................................ ................................ ................................ ................................ ................................ ................................ ......................... 1
Clinical Data Reviewer’s Guide Revision history ................................ ................................ ................................ ................................ ................................ ...... 2
1. Introduction ................................ ................................ ................................ ................................ ................................ ................................ ........................ 4
1.1 Purpose ................................ ................................ ................................ ................................ ................................ ................................ ....................... 4
1.2 Acronyms ................................ ................................ ................................ ................................ ................................ ................................ .................... 4
1.3 Study Data Standards and Dictionary Inventory ................................ ................................ ................................ ................................ ........................ 4
2. Protocol Description ................................ ................................ ................................ ................................ ................................ ................................ ........... 5
2.1 Protocol Number and Title ................................ ................................ ................................ ................................ ................................ ......................... 5
2.2 Protocol Design ................................ ................................ ................................ ................................ ................................ ................................ ........... 5
2.3 Trial Desi gn Datasets ................................ ................................ ................................ ................................ ................................ ................................ .. 5
3. Subject Data Description ................................ ................................ ................................ ................................ ................................ ................................ .... 5
3.1 Overview ................................ ................................ ................................ ................................ ................................ ................................ ..................... 5
3.2 Traceability Flow Diagram ................................ ................................ ................................ ................................ ................................ ......................... 6
3.3 Annotated CRFs ................................ ................................ ................................ ................................ ................................ ................................ .......... 6
3.4 SDTM Subject Domains ................................ ................................ ................................ ................................ ................................ ............................. 6
3.4.1 XB – Sequencing Data ................................ ................................ ................................ ................................ ................................ ........................ 7
4. Data Conformance Summary ................................ ................................ ................................ ................................ ................................ ............................. 7
4.1 Conformance Inputs ................................ ................................ ................................ ................................ ................................ ................................ .... 7
4.2 Issues Summary ................................ ................................ ................................ ................................ ................................ ................................ .......... 7
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This document is confidential Page 4 of 8 1. Introduction
1.1 Purpose
This document provides context for tabulation datasets and terminolo gy that benefit from additional explanation beyond the Data Definitions document (define.xml). In
addition, this document provides a summar y of SDTM conformance findings. This cSDRG is a supplement to the primary cSDRG previously submitted for the BLA and
cover s only the e fficacy sequencing data analyses in the blinded placebo -controlled follow -up period for the COVID -19 case data (cutoff date: 13Mar 2021)
1.2 Acronyms
Acronym Translation
COVID -19 Coronavirus Disease 2019
cSDRG Clinical Study Data Reviewer’s Guide
SDTM Study Data Tabulation Model
BLA Biologic s Licensing Application
1.3 Study Data Standards and Dictionary Inventory
Standard or Dictionary Versions Used
SDTM •SDTM v1.4
•SDTM -IG v3.2
Controlled Terminology CDISC SDTM Con trolled Terminology, 2020 -03-27
Data Definitions Define -XML v2.0
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Medications Dictio nary WHODD GLOBALV3Mar20, WHO DDE v202003 , SNOMED
2020 -09-01, UNII 2020 -08-18, NDF -RT 2020 -09-08
2. Protocol Description
2.1 Protocol Number and Title
Refer to the primary cSDRG .
2.2 Protocol Design
Refer to the primary cSDRG .
2.3 Trial Design Datasets
Are Trial Design datasets included in the submission? - Yes
Refer to the primary cSDRG for complete details of the trial design datasets
3. Subject Data Description
3.1 Overview
Are the submitted data taken from an ongoing study? Yes
Were the SDTM datasets used as sources for the analysis datasets? Yes
Do the submission datasets include screen failures? Yes
Refer to the primary cSDRG for further details
Were any domains planned, but not submitted because no data were collected? No
Are the submitted data a subset of collected data? No
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3.2 Traceability Flow Diagram
3.3 Annotated CRFs
Collected fields and pages that have not been tabulated have been annotated as "Not Submitted". Pfizer collects certain data elements to facilitate
operational processes including data cleaning and dynamically creating additional forms in the electronic data capture system. All fields and pages
that have been annotated as "Not Submitted" meet this criterion and are described below .
Explanation of data fields [Not Submitted]
Refer to the primary cSDRG for further details .
3.4 SDTM Subject Domains
Only the domains relevant to the sequencing data analysis are listed below . DM and EX have been included in the package for Pinnacle checks and
these domains are identical to the datasets included in the BLA esub package, for the list of complete domains refer to the primary cSDRG.
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RELREC
XB - Sequencing Data X
3.4.1 XB – Sequencing Data
The XB domain is a custom domain and is similar to the MB domain . XB was created to support the sequencing data which is a distinct analysis
separate from the primary analysis . Sequencing data dataset consists of one record per microbiology specimen finding per t ime point per visit per
subject .
4. Data Conformance Summary
4.1 Conformance Inputs
Was a validator used to evaluate conformance? Yes
If yes, specify the version(s) of the validation rules: Pinn acle 21 Enterprise version 4. 2.0
Validation Engine version 2010 .1
Were sponsor -defined validation rules used to evaluate conformance? No
Were the SDTM datasets evaluated in relation to define.xml? Yes
Was define.xml evaluated? Yes
Provide any additional compliance evaluation information :
4.2 Issues Summary
The issues for DM and EX are not included, o nly XB domain issues are listed below . Refer to the primary cSDRG for the issue summary of all the
domains that are part of the primary submission .
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ID Diagnostic Message FDA
Severity Dataset Count
(Issue
Rate) Explanation
SD1082 Variable length is too
long for actual data Error XB 1 (5.00%) According to FDA technical conformance guide section 3.3.3: The
allotted length for each column containing character (text) data should be
set to the maximum length of the variable used across all datasets in the
study except for suppqual datasets. Pinnacle 21 provides false positive
information since it only checks the length of the variable within the data
set.
SD1203 XBDTC date is after
RFPENDTC Error XB 2 (0.27%) At the time of data extraction, study is still ongoing and RFPENDTC is
derived as the maximum of date of disposition, Subject Visits, date of
death. Therefore, for ongoing subjects may not yet include completion
date of the current study phase where individual dates from that phase
may already be reported.
CT2002 XBMETHOD value
not found in 'Method'
extensible codelist Warning XB 1146
(100.00%) New terms were added to extensible codelist Method (C85492) for the
study protocol needs:
• Next generation sequence
CT2002 XBSPEC v alue not
found in 'Specimen
Type' extensible
codelist Warning XB 1146
(100.00%) New terms were added to extensible codelist Specimen Type (C78734)
for the study protocol needs:
• NASAL_SWAB
• NASAL_SWAB_SELF
CT2002 EPOCH value not
found in 'Epoch'
extensible codelist Warning XB 279
(24.35%) New term s were added to extensible codelist EPOCH (C99079) for the
study protocol needs:
•VACCINATION
•OPEN LABEL FOLLOW -UP
•REPEAT SCREENING 1
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