Document text
Data Fitness Findings Report
IND27034
BioNTech SE and Pfizer , November 2020
Findings Notes
BNT162 -01
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
Document / Standard Version Notes
annotated CRF Seems fine
SDTM Implementation
Guide SDTM -IG v3. 2
SDTM Controlled
Terminology 2020-03-27
SDTM define.xml V2.0 Seems fine
Medications Dictionary WHODRUG GLOBAL
B3 March 1, 2020
Medical Events
Dictionary
(MedDRA) V23.0
SDTM Reviewer ’s Guide PhUSE template Seems fine
From cSDRG : Data cutoff date of 13Aug2020 is applied by comparing XXDTC or XXSTDC from respective SDTM domains. Apart from data
cutoff this esub is limited to cohorts described in the section 2.3.1 of cSDRG.
FDA-CBER-2021-5683-1060075
C4591001 -ia-efficacy ( Phase 2/3 Interim Analysis )
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.
Document / Standard Version Notes
annotated CRF Seems fine
SDTM Implementation
Guide SDTM -IG v3.2
SDTM Controlled
Terminology 2020-03-27
SDTM define.xml V2.0 Seems fine
Medications Dictionary WHODD
GLOBALV3Mar20,
WHO DDE v202003
Medical Events
Dictionary
(MedDRA) V23.1
SDTM Reviewer’s Guide PhUSE template Seems fine
From cSDRG: The IA efficacy analysis data with a cutoff of 4NOV2020 was included in this submission. In addition, a subject cutoff to
exclude phase 1 subjects was also applied to the data. Only subjects in Phase 2/3 that had informed consent date after 27JUL2 020 were
included.
ADaM folder contains: adc19ef, adsl, adsympt
FDA-CBER-2021-5683-1060076
C4591001 -safety -fa-eff (Final Efficacy/EUA Safety Analysis )
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.
Document / Standard Version Notes
annotated CRF Seems fine
SDTM Implementation
Guide SDTM -IG v3.2
SDTM Controlled
Terminology 2016 -12-16
SDTM define.xml V2.0 Seems fine
Medications Dictionary GLOBALB3Mar19
Medical Events
Dictionary
(MedDRA) V21.1
SDTM Reviewer’s Guide PhUSE template Seems fine
From cSDRG: The final analysis data with a cutoff of 14NOV2020 was included in this submission. Screen failure data was also dropped
as part of the cutoff process. Details about the cutoff algorithm applied to the SDTM data :
All records with ASTDT <= &cutoff are included. In addition,
If .<ASTDT <= &cutoff and AEENDT > cutoff date, then - AEENDTC and AEENDY is set to missing
- AEENRTPT = ‘ONGOING’
- AEENTPT = ‘Last Subject Encounter’
- AEOUT = ‘NOT RECOVERED/NOT RESOLVED’
end;
else if AESTDTC = ‘ ‘ and AEENDTC ne ‘ ‘and AENDT <=
&cutoff then the record is included.
If AESTDTC and AEENDTC are both missing then the record
is included.
DROP ASTDT and AENDT
ADaM folder contains: adae, adc19ef, adcevd, adds, adfacevd, admh, adsl, adsympt, adva
FDA-CBER-2021-5683-1060077
Data Issues
Missing MedDRA coding data
• Study c4591001- ia-efficacy:
aedecod aeptcd aellt aelltcd aehlt aehltcd aehlgt aehlgtcd aebodsys aebdsycd aesoc aesoccd Freq
populated null null null null null null null null null null null 97
populated populate
d populate
d populate
d populate
d populated populated populated populated populated populated populated 16670
• Study c4591001- safety -fa-eff
aedecod aeptcd aellt aelltcd aehlt aehltcd aehlgt aehlgtcd aebodsys aebdsycd aesoc aesoccd Freq
populated null null null null null null null null null null null 89
populated populate
d populate
d populate
d populate
d populate
d populated populated populated populated populated populated 20228
• Note: For both studies, AEDECOD = ‘Uncoded’ when the rest of the MedDRA levels are null . In ADAE (for study c4591001- safety -
fa-eff), for these uncoded records, AEDECOD values are a copy of AETERM, but upper cased, and two @ symbols attached. For
example, AETERM ‘Injection site pain’ has ADAE.AEDECOD = ‘INJECTION SITE PAIN@@’
• cSDRG explanation: Study was ongoing at the time of data cutoff therefore some AE terms were not yet coded in MedDRA.
These terms were set to 'Uncoded' in AE dataset for transparency. These terms will be coded for the final reporting event for
this study once the study is completed.
Subjects have multiple D ISPOSITION EVENT records for the same EPOCH and DSSTDTC
• Studies c4591001- ia-efficacy and c4591001- safety -fa-eff
• Need to use SUPPDS.DSPHASE to distinguish whether its VACCINATION or FOLLOW -UP or SCREENING
• Example of just a few out of many subjects in c4591001- safety -fa-eff:
usubjid dsseq dsterm dsdecod dscat epoch dsstdtc dsstdy suppds.dspha
se
C4591001 1005 10051308 5 busy work schedule WITHDRAWAL BY
SUBJECT DISPOSITION
EVENT VACCINATION 10/19/2020 1 FOLLOW -UP
C4591001 1005 10051308 4 busy work schedule WITHDRAWAL BY
SUBJECT DISPOSITION
EVENT VACCINATION 10/19/2020 1 VACCINATION
C4591001 1005 10051308 1 COMPLETED COMPLETED DISPOSITION
EVENT VACCINATION 10/19/2020 1 SCREENING
C4591001 1013 10131017 5 SUBJECT WITHDREW
CONSENT FROM
STUDY. WITHDRAWAL BY
SUBJECT DISPOSITION
EVENT SCREENING 7/30/2020 1 FOLLOW -UP
FDA-CBER-2021-5683-1060078
C4591001 1013 10131017 4 SUBJECT CHANGED
HIS DECISION AND
WAS RANDOMIZED INTO SYSTEM. WITHDRAWAL BY
SUBJECT DISPOSITION
EVENT SCREENING 7/30/2020 1 VACCINATION
C4591001 1013 10131017 1 COMPLETED COMPLETED DISPOSITION
EVENT SCREENING 7/30/2020 1 SCREENING
Subjects have AE records with AEACN = DRUG WITHDRAWN but no ADVERSE EVENT record in DS
• Study BNT162- 01 – see report “ IND27034 - BNT162- 01 - AEACN is DRUG WITHDRAWN but no ADVERSE EVENT record in DS.xlsx ”
• Study c45 91001- ia-efficacy – see report “ IND27034 - c4591001- ia-efficacy - AEACN is DRUG WITHDRAWN but no ADVERSE
EVENT reco rd in DS.xlsx ”
• Study c4591001- safety -fa-eff – see report “ IND27034 - c4591001- safety -fa-eff - AEACN is DRUG WITHD RAWN but no ADVERSE
EVENT record in DS.xlsx ”
Subjects have multiple baseline records in VS
• Study BNT162 -01 – 40 records, 5 subjects – see report “ IND27034 - BNT1 62-01 - Multiple baseline records in VS.xlsx ”
Subjects have multiple baseline records in LB
• Study BNT162 -01 – 100 records, 5 subjects – see report “ IND27034 - BNT162- 01 - Multiple baseline records in LB.xlsx ”
Reactogenicity events in CE with a duration of at least 7 days, but aren’t in the AE domain
• Study BNT162- 01 – 13 records
usubjid ceterm cestdtc ceendtc
BNT162 -01-276-01-0003 Injection site reaction - Tenderness 5/19/2020 5/26/2020
BNT162 -01-276-01-0005 Fatigue 5/15/2020 5/22/2020
BNT162 -01-276-01-0010 Fatigue 4/24/2020 5/2/2020
BNT162 -01-276-01-0010 Headache 4/25/2020 5/2/2020
BNT162 -01-276-01-0010 Injection site reaction - Pain 4/25/2020 5/2/2020
BNT162 -01-276-01-0010 Injection site reaction - Tenderness 4/25/2020 5/2/2020
BNT162 -01-276-01-0010 Malaise 4/25/2020 5/2/2020
BNT162 -01-276-01-0010 Myalgia 4/25/2020 5/2/2020
BNT162 -01-276-01-0019 Headache 5/20/2020 5/27/2020
FDA-CBER-2021-5683-1060079
BNT162 -01-276-02-0156 Injection site reaction - Tenderness 7/23/2020 7/30/2020
BNT162 -01-276-02-0160 Fatigue 6/29/2020 7/7/2020
BNT162 -01-276-02-0160 Headache 6/30/2020 7/7/2020
BNT162 -01-276-02-0160 Malaise 6/30/2020 7/7/2020
DDDTC date is after RFPENDTC
• Study c4591001- ia-efficacy - 1 records (33.33%)
USUBJID DDTEST DDORRES DDDTC RFPENDTC Last Disposition
date DSDECOD
C4591001 1162 11621327 PRIMARY CAUSE OF
DEATH atherosclerotic
disease 9/24/2020 9/13/2020 9/13/2020 DEATH
• Study c4591001- safety -fa-eff - 3 records (50%)
USUBJID DDTEST DDORRES DDDTC RFPENDTC Last Disposition
date DSDECOD
C4591001 1066 10661350 PRIMARY CAUSE OF
DEATH myocardial infarction 11/10/2020 11/3/2020 11/3/2020 DEATH
C4591001 1081 10811194 PRIMARY CAUSE OF
DEATH Cause is currently
unknown. Detail will
be updated once the death certificate has
been received 11/11/2020 11/1/2020 11/1/2020 DEATH
C4591001 1162 11621327 PRIMARY CAUSE OF
DEATH atherosclerotic
disease 9/24/2020 9/13/2020 9/13/2020 DEATH
EXSTDTC /EXENDTC date is after RFPENDTC
• Study c4591001- ia-efficacy - 25 records (0.03%)
USUBJID EXTRT EXSTDTC RFPENDTC
C4591001 1013 10131358 Placebo 2020 -10-06T14:32:00 9/21/2020
C4591001 1013 10131622 BNT162b2 2020 -10-28T15:20:00 10/19/2020
C4591001 1019 10191178 BNT162b2 2020 -10-08T12:09:00 9/30/2020
C4591001 1024 10241117 Placebo 2020 -10-16T16:10:00 10/7/2020
FDA-CBER-2021-5683-1060080
C4591001 1028 10281292 Placebo 2020 -10-30T09:15:00 10/29/2020
C4591001 1044 10441116 Placebo 2020 -10-29T10:11:00 10/5/2020
C4591001 1044 10441165 BNT162b2 2020 -10-19T10:40:00 10/6/2020
C4591001 1044 10441214 BNT162b2 2020 -10-30T10:18:00 10/22/2020
C4591001 1072 10721037 Placebo 2020 -10-07T12:34:00 9/9/2020
C4591001 1084 10841481 Placebo 2020 -11-02T11:25:00 10/29/2020
C4591001 1088 10881045 BNT162b2 2020 -10-26T10:53:00 9/8/2020
C4591001 1088 10881080 Placebo 2020 -10-12T16:44:00 9/11/2020
C4591001 1088 10881139 BNT162b2 2020 -10-15T14:05:00 9/21/2020
C4591001 1092 10921175 Placebo 2020 -11-04T09:30:00 9/9/2020
C4591001 1097 10971118 Placebo 2020 -10-15T09:49:00 10/13/2020
C4591001 1098 10981209 Placebo 2020 -10-15T14:36:00 10/13/2020
C4591001 1107 11071189 Placebo 2020 -10-07T13:04:00 9/22/2020
C4591001 1109 11091408 BNT162b2 2020 -10-07T15:49:00 9/22/2020
C4591001 1128 11281353 Placebo 2020 -10-19T10:00:00 10/5/2020
C4591001 1141 11411096 BNT162b2 2020 -10-13T13:23:00 9/24/2020
C4591001 1156 11561193 BNT162b2 2020 -10-21T15:14:00 10/20/2020
C4591001 1226 12261684 BNT162b2 2020 -10-16T13:05:00 10/2/2020
C4591001 1226 12261821 Placebo 2020 -10-22T08:53:00 10/8/2020
C4591001 1226 12262353 Placebo 2020 -10-23T11:25:00 10/20/2020
C4591001 1247 12471092 Placebo 2020 -10-29T12:07:00 10/20/2020
• Study c4591001- safety -fa-eff - 18 records (0.02%)
USUBJID EXTRT EXSTDTC RFPENDTC
C4591001 1013 10131544 BNT162b2 2020 -11-04T13:47:00 10/5/2020
C4591001 1013 10131622 BNT162b2 2020 -10-28T15:20:00 10/19/2020
C4591001 1013 10131738 BNT162b2 2020 -11-11T15:27:00 11/5/2020
C4591001 1024 10241117 Placebo 2020 -10-16T16:10:00 10/7/2020
C4591001 1028 10281292 Placebo 2020 -10-30T09:15:00 10/29/2020
C4591001 1044 10441116 Placebo 2020 -10-29T10:11:00 10/5/2020
FDA-CBER-2021-5683-1060081
C4591001 1044 10441214 BNT162b2 2020 -10-30T10:18:00 10/22/2020
C4591001 1056 10561232 Placebo 2020 -11-04T12:40:00 10/7/2020
C4591001 1079 10791143 Placebo 2020 -11-06T15:33:00 9/9/2020
C4591001 1079 10791264 BNT162b2 2020 -11-04T13:48:00 9/30/2020
C4591001 1088 10881045 BNT162b2 2020 -10-26T10:53:00 9/8/2020
C4591001 1120 11201299 BNT162b2 2020 -10-19T13:48:00 10/12/2020
C4591001 1122 11221052 Placebo 2020 -11-13T13:15:00 10/30/2020
C4591001 1123 11231345 Placebo 2020 -11-05T09:46:00 11/2/2020
C4591001 1156 11561193 BNT162b2 2020 -10-21T15:14:00 10/20/2020
C4591001 1226 12261797 BNT162b2 2020 -11-06T12:36:00 10/7/2020
C4591001 1226 12262083 Placebo 2020 -11-07T09:18:00 10/27/2020
C4591001 1247 12471092 Placebo 2020 -10-29T12:07:00 10/20/2020
cSDRG explanation: “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 pha se
where individual dates from that phase may already be reported.”
DSSTDTC is before RFICDTC
• Study c4591001- ia-efficacy - 4 records (0%)
USUBJID DSDECOD DSSTDTC SUB:RFICDTC SUPPDS.DSPHASE
C4591001 1161 11611011 COMPLETED 8/1/2020 8/19/2020 SCREENING
C4591001 1161 11611011 RANDOMIZED 8/1/2020 8/19/2020
C4591001 1213 12131020 RANDOMIZED 11/2/2020 11/3/2020
C4591001 1213 12131021 RANDOMIZED 11/2/2020 11/3/2020
• Study c4591001- safety -fa-eff - 3 records (0%)
USUBJID DSDECOD DSSTDTC SUB:RFICDTC SUPPDS.DSPHASE
C4591001 1097 10971003 PROTOCOL
DEVIATION 8/17/2020 8/19/2020 FOLLOW -UP
C4591001 1161 11611011 COMPLETED 8/1/2020 8/19/2020 SCREENING
FDA-CBER-2021-5683-1060082
C4591001 1161 11611011 RANDOMIZED 8/1/2020 8/19/2020
cSDRG explanation: “At the time of data extraction study is still ongoing and data cleaning is still occurring. Updated data will be
included for future reporting events and at study completion.”
Value for LBSTNRHI is less than value for LBSTNRLO
• Study c4591001- ia-efficacy - 1 records (0.06%)
o cSDRG explanation: “Subject C4591001 1047 10471252 has one record where LBTESTID=BILI with LBSTHRHI=1.7 and LBSTNRLO=17.1. Data is reported as collected. At the time of data extraction study is still ongoing and data cleaning is
still occurring. Updated data will be included for future reporting events and at study completion.”
• Study c4591001- safety -fa-eff - 12 records (0.06%)
o cSDRG explanation: “Data is reported as collected. At the time of data extraction s tudy is still ongoing and data cleaning
is still occurring. Updated data will be included for future reporting events and at study completion.”
study usubjid lbtestcd lbstresu lbstnrlo lbstnrhi lbspec
C4591001 -ia-efficacy C4591001 1047 10471252 BILI umol/L 17.1 1.7 BLOOD
C4591001 -safety -fa-eff C4591001 1082 10821143 LYM 10^9/L 1.5 0.7 BLOOD
C4591001 -safety -fa-eff C4591001 1110 11101357 CD4 10^9/L 0.49 0.174 BLOOD
C4591001 -safety -fa-eff C4591001 1194 11941073 CD4 10^9/L 0.453 0.157 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041152 CD4 10^9/L 0.3 0.17 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041154 CD4 10^9/L 0.3 0.17 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041162 CD4 10^9/L 0.2 0.17 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041164 CD4 10^9/L 0.3 0.17 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041165 CD4 10^9/L 0.393 0.149 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041176 CD4 10^9/L 0.3 0.17 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041216 CD4 10^9/L 0.3 0.17 BLOOD
C4591001 -safety -fa-eff C4591001 1204 12041233 CD4 10^9/L 0.49 0.174 BLOOD
C4591001 -safety -fa-eff C4591001 1246 12461073 CD4 10^9/L 0.358 0.126 BLOOD
MHSTDTC date is after RFSTDTC (which typically means it should be an AE, not MH)
• Study c4591001- ia-efficacy - 2 records (0%)
• Study c4591001- safety -fa-eff - 3 records (0%)
FDA-CBER-2021-5683-1060083
cSDRG explanation: “At the time of data extraction study is still ongoing and data cleaning is still occur ring. Updated data will be
included for future reporting events and at study completion.”
STUDYID USUBJID MHTERM MHDECOD MHSTDTC RFSTDTC
C4591001 -ia-efficacy C4591001 1110 11101299 prostatectomy Prostatectomy 10/1/2020 2020 -09-
24T11:27:00
C4591001 -ia-efficacy C4591001 4444 44441233 Ahmed valve tube
shortening Glaucoma surgery 9/23/2020 2020 -09-
21T20:30:00
C4591001 -safety -fa-eff C4591001 1007 10071418 Bone spur removal Bone lesion excision 11/5/2020 2020 -10-
22T14:15:00
C4591001 -safety -fa-eff C4591001 1095 10951180 Atrial Septal Defect Atrial septal defect 11/5/2020 2020 -08-
31T12:08:00
C4591001 -safety -fa-eff C4591001 1133 11331285 RIGHT HAND
TENOLYSIS Tenolysis 9/11/2020 2020 -08-
27T13:30:00
FDA-CBER-2021-5683-1060084