125742 S1 M1 financial cert bias

Pfizer Documents (PHMPT/FDA)

Pfizer Bla Submission

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PFIZER CONFIDENTIAL  
Page 1  BNT162b2                  1.3.4 Financial Certification and Disclosure
       
1.3.4 FINANCIAL CERTIFICATION AND DISCLOSURE – BIAS STATEMENT 
Protocol Number: C4591001  
Study Title:  A Phase 1/2/3, Placebo -Controlled , Randomized , Observer -Blind, Dose-
Finding  Study To Evaluate  The Safety , Tolerability , Immunogenicity, And Efficacy Of 
SARS -COV -2 RNA V accine  Candidates Against  COVID -19 In Healthy Individuals   
STEPS TAKEN TO MINIMIZE THE POTENTIAL FOR BIAS  
The above -referenced trial was conducted according to ICH Good Clinical Practices. The 
study was co nducted according to Pfizer SOPs .   
Other processes used to minimize potential bias are as follows:  
•The facilit ies performing the safety and efficacy evaluations w ere determined to be
acceptable based on appropriate certification or historical performance and/or
qualifications and credentials.
•Electronic diaries were  used to collect patient reported outcomes, to ensure real time
completion of outcomes questionnaires.
•Subjects were allocated randomly to vaccine group  through use of an Interactive
Response System .
•An independent external data monitoring committee  (DMC) , operating under a
written charter, reviewed unblinded safety data on a weekly basis during Phase 2/3
and was responsible for the review of the efficacy interim analysis.
•Ongoing accrual of protocol -defined cases was monitored in a blinded manner  and,
when sufficient cases were available, the unblinded analysis was performed by a
limited number of individu als who are not involved in ongoing conduct of the study
(statistical team supporting the DMC) .
•Microbiological confirmation of cases by Polymerase Chain Reaction ( PCR) was
performed by individuals blinded to treatment allocation in a central laboratory.
•An independent unblinded submissions team separate from the study team , operating
under a written charter , analyzed defined endpoints for regulatory submissions (EUA,
MAA).  Analyses were stored on restricted sites. Access to the restricted sites was
govern ed by charter and tracked.
•Investigator trial  sites were monitored frequently .
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BNT162b2                   1.3.4 Financial  Certification   and  Disclosure 
PFIZER CONFIDENTIAL  
Page 2  •The validity of the data collected during the study was confirmed by standard
monitoring procedures.
•During the course of  processing, analyzing and reporting data from clinical trials,
Pfizer applied procedures (e.g., querying data through electronic edit checks and
clinical reviews) designed to ensure that errors were eliminated.
•Appropriate statistical methods were employe d by use of an approved statistical
analysis plan.
•The study report was reviewed by the Sponsor’s Quality Control Group.
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BNT162b2                  1.3.4 Financial Certification and Disclosure 
CONFIDENTIAL 
Page 3  1.3.4 FINANCIAL CERTIFICATION AND DISCLOSURE – BIAS STATEMENT 
Protocol number: BNT162 -01 
Study 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 and immunocompromised adults   
STEPS TAKEN TO MINIMIZE THE POTENTIAL FOR BIAS  
The clinical study  BNT162 -01 is being  conducted according to I CH Good Clinical 
Practices, relevant regulatory guidance, and BioNTech  SOPs . The study is still ongoing 
clinically.  
The study has an open -label exploratory design and does not include testing of a formal 
statistical hypothesis.  
Other processes used to minimize potential bias are as follows:  
•The contract research organization ( CRO ) conducting the  study was qualified
according to the sponsor’s standard operating procedures (SOPs) in cooperation with
the sponsor’s quality assurance department.
•Study sites  were monitored frequently and the validity of the data collected during the
study was confirmed according to BioNTech  SOPs .
•Data verification was performed on the data in the database using computerized
checks looking for missing data, inconsistencies, an d incorrect values. A manual
review of the data was also performed. If necessary, data clarification forms were
generated and transmitted to the site. The investigator was requested to confirm or
make corrections or enter additional or missing data as requ ired. Further data quality
control measures were defined in the data validation plan. In addition, a reconciliation
of reportable adverse events between the global drug safety and clinical databases as
well as a reconciliation of other non -CRF data were pe rformed.
•Appropriate statistical methods were employed by use of an approved statistical
analysis plan  according to BioNTech  SOPs.
•The study report was reviewed and subjected to quality control checks according to
BioNTech  SOPs.
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