Prospective Monitoring of BNT162b2 Second Vaccination Booster for Prevention of the COVID-19 Infection in Health Care Workers (HCW)
Conditions: Coronavirus Infections
Sponsor: Soroka University Medical Center

 
 
 
Prospective monitoring of BNT162b2 second vaccination booster for prevention of 
the COVID-19 infection in health care workers (HCW) 
 
 
Clinical Research Center and Infectious Disease Institute 
Soroka University Medical Center, 
Be'er-Sheva, Israel 
 
 
 
Protocol SCRC22001 
Version 1.4 
 May 2, 2022 
 
 
 
 
 
 
 
 
 
 
 
 

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1 
 Signature Page 
Study Title: 
Prospective monitoring of BNT162b2 second vaccination booster for 
prevention of the COVID-19 infection in health care workers (HCW) 
Protocol Version: Version 1.4 
Protocol Date: 
May 2, 2022 
Investigator’s Responsibility 
Prior to participation in the trial, as the site principal investigator I understand that I must 
obtain written approval from my local Ethics Committee and other regulatory bodies 
according to the local regulation.   
 As the site Principal Investigator, I must also: 
1. 
Ensure that the trial is not commenced until approvals have been obtained. 
2. 
Ensure that written informed consent is obtained from each subject prior to any data 
collection using the most recent EC approved Subject Informed Consent Form. 
3. 
Provide all required data and reports and agree to source document verification of 
trial data with subject’s medical records. 
4. 
Allow EC and/or regulatory bodies representatives, to inspect and copy any 
documents pertaining to this clinical investigation. 
Investigator Signature  
I have read and understand the contents of the trial protocol and agree to abide by the 
requirements set forth in this document.  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
Investigator’s Name  
 
 
 
Institution 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Investigator’s Signature 
 
 
 
 Date 

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2 
Protocol Summary 
OBJECTIVE 
Primary Objective 
Examine the protection against any type of COVID-19 infection as 
confirmed by PCR testing or positive serology for N antigen during 
the follow up period.  
Secondary Objectives 
Evaluate the impact of a fourth dose on: 
1. Symptomatic COVID 19 infection 
2. COVID 19 infection requiring hospitalization  
3. Antibody levels including IgG, IgA, IgM, binding and neutralizing 
activity and the avidity of the antibodies. 
STUDY DESIGN 
Prospective observational registry 
OUTCOMES  
Primary Outcome 
COVID-19 infection as confirmed by PCR testing or positive 
serology for N antigen during the follow up period. We hypothesize 
that booster of BNT162b2 vaccine in healthcare workers (HCW) will 
lower the rates of the COVID-19 infection as compared to HCW 
choosing not to receive the second booster. 
Secondary Outcomes 
1. Symptomatic COVID 19 infection 
2. COVID 19 infection requiring hospitalization  
3. Levels of binding and neutralizing activity and avidity of the 
antibodies 
4. Composite endpoint of serious adverse events during 14 days 
following the booster vaccination 
SAMPLE SIZE 
CONSIDERATIONS 
We aim to enroll up to 1000 subjects. The following assumptions 
were used to estimate the power of the analysis.  
• 
The proportion of the HCW choosing to receive the second 
booster is 60% 
• 
The expected monthly infection rate of 2.5% in the non-
vaccinated group 
• 
Expected monthly infection rate of 1.0% in the treatment group 
• 
Median follow-up until switching to the booster administration in 
the non-vaccinated group (15%) of 4 months 
• 
Type I error (α) = 0.025 (one-sided) 
• 
Log-rank test 
• 
Enrollment period of 1 month 
• 
Lost to follow-up of 10% 
An evaluable sample size of 1000 subjects provides 80.0% power 
to reject the null hypothesis, signifying the booster strategy is 
superior to the comparison group at 6 months post-vaccination.   
INCLUSION CRITERIA 
1. Able to provide written informed consent. 
2. Healthcare worker in one of the Clalit Health Services Medical 
centers and is at least 18 years of age. 
3. Completed three doses of BNT162b2 according to MOH 
guidelines. 
4. Third dose was given at least 4 months prior to enrollment. 

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EXCLUSION CRITERIA 
1. History of COVID-19 infection. 
2. History of being treated or is currently being treated for any type 
of Malignancies or other co-morbid conditions that may result in 
protocol non-compliance. 
3. Currently or in the past three months was treated with any type 
of Immune suppression medication (including chemotherapy, 
immunomodulatory drugs, biological agents that affect the 
immune system, any immunosuppressive drug such as 
corticosteroids). 
4. Received in the past 4 months monoclonal antibodies of any 
type. 
STUDY PROCEDURES 
Screening and Enrollment 
The following will take place at this visit: 
• 
Confirmation of eligibility and informed consent will be signed.  
• 
Demographics and medical history will be recorded.  
• 
COVID-19 questionnaire regarding exposure and 
symptoms. 
• 
Blood draw of three 5 ml vials, for antibody testing. 
• 
Blood drawn for PBMC and antibody testing: 
o Will be ONLY at Soroka Medical Center. 
o 150 subjects will be selected randomly. Subjects 
participating in this part will have 30 ml (3 vials of 9 ml and 1 
vial of 3 ml) of blood drawn for PBMC and antibody testing. 
Others will have blood draw of three 5 ml vials, for antibody 
testing. 
• 
A nasal and mouth swab will be performed for IgA, IgG and IgM 
levels testing  
Visit 2 –6  
• 
COVID-19 questionnaire regarding exposure and 
symptoms. Blood draw of 3 vials of 5 ml for antibody testing,  
• 
Blood drawn for PBMC and antibody testing: 
o Will be ONLY at Soroka Medical Center. Subjects who were 
not part of the PBMC group and are willing to participate, 
will be asked again to sign inform consent. 
o Subjects participating in this part will have 30 ml (3 vials of 9 
ml and 1 vial of 3 ml) of blood drawn for PBMC and antibody 
testing. Others will have blood draw of three 5 ml vials, for 
antibody testing. 
• 
A nasal and mouth swab will be performed for IgA, IgG and IgM 
levels testing  
• 
Adverse events following vaccination and changes in 
medications (chronic and/or Immune suppression medication) 
will be collected 

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LABORATORY TESTING 
 
• 
From each HCW at each visit the following tests will be 
performed: 
• 
The Platelia SARS-CoV-2 Total Ab assay by Bio rad, is a semi-
quantitative in vitro diagnostic test, in a one-step antigen 
capture format, for the detection of IgM/IgA/IgG antibodies to 
the SARS-CoV-2 in human serum and plasma (EDTA, heparin, 
ACD or citrate) specimens. This assay will be performed at 
SMC virology laboratory (head-Prof. Yonat Shemer). 
• 
Antibody profiling of blood and nasal samples will be tested 
using antigen microarrays, this will be performed by using chip 
antigen microarrays spotted with various coronavirus antigens, 
as well as antigens of other common respiratory pathogens. 
This assay will be performed at Prof. Tomer Hertz laboratory at 
Ben-Gurion University of the Negev.  
• 
On select samples from each visit neutralization assays for 
SARS-CoV-2 virus variants will be performed. Each sample 
selected will be tested for its ability to inhibit infection of target 
ACE2-expressing cells by reporter pseudoviruses that express 
the spike protein of either Delta or Omicron Variant of Concern. 
This assay will be performed at Dr. Ran Taube laboratory at 
Ben-Gurion University of the Negev. 
• 
Blood samples for PBMC’S will be stored at Prof. Hertz's 
laboratory at Ben-Gurion University of the Negev for future 
research.  
DATA TO CAPTURE 
The following data will be collected: 
• 
Demographic data: age, sex, country of birth, healthcare 
profession, direct contact with covid subjects in working 
capacity. 
• 
Detailed medical history, including but not limited to past illness 
with COVID, malignancy, diabetes, renal failure, heart disease, 
hypertension, history of stroke, rheumatological illness. 
• 
Current medications used and medications used for more than 
one week in the past three months. 
• 
Any adverse event during the study as a result of vaccination. 
DATA MANAGEMENT 
AND ANALYSIS 
The study will be overseen and managed by the Soroka Clinical 
Research Center. 
 

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Table of Contents 
1 
Signature Page ............................................................................................................ 2 
2 
Protocol Summary ........................................................................................................ 3 
3 
Abbreviations and Definitions ....................................................................................... 8 
4 
Background .................................................................................................................. 9 
5 
Methods ..................................................................................................................... 10 
5.1 
Working Hypothesis ................................................................................................... 10 
5.2 
Objectives .................................................................................................................. 10 
5.2.1 
Primary Objective ....................................................................................................... 10 
5.2.2 
Secondary Objectives ................................................................................................ 10 
5.3 
Schedule of Events .................................................................................................... 10 
5.4 
Flow chart .................................................................................................................. 11 
5.5 
Study Population ........................................................................................................ 11 
5.5.1 
Inclusion Criteria ........................................................................................................ 11 
5.5.2 
Exclusion Criteria ....................................................................................................... 11 
5.5.3 
Withdrawal/Discontinuation Criteria ............................................................................ 12 
5.6 
Enrollment .................................................................................................................. 12 
5.7 
Subject Screening ...................................................................................................... 12 
5.8 
Study Procedures ....................................................................................................... 13 
5.8.1 
Screening and Enrollment .......................................................................................... 13 
5.8.2 
Visit 2 –6 .................................................................................................................... 13 
5.9 
Laboratory testing ...................................................................................................... 14 
5.10 
Study Duration ........................................................................................................... 14 
5.11 
Data to Capture .......................................................................................................... 14 
5.11.1 
Required Data ............................................................................................................ 14 
5.11.2 
Data Collection ........................................................................................................... 14 
6 
Statistical Considerations and Analysis Plan .............................................................. 16 
7 
Adverse Events .......................................................................................................... 18 
7.1 
Adverse Event Definition ............................................................................................ 18 
7.1.1 
Adverse Event ............................................................................................................ 18 
7.1.2 
Treatment Related Adverse Event .............................................................................. 18 
7.1.3 
Serious Adverse Event ............................................................................................... 18 
7.2 
Anticipated Adverse Event ......................................................................................... 18 
8 
Ethical and Regulatory Considerations ....................................................................... 19 
8.1 
Subject Confidentiality ................................................................................................ 19 
8.2 
Sources of Materials ................................................................................................... 19 
8.3 
Maintaining Records ................................................................................................... 19 
8.4 
Site Record Retention Policy ...................................................................................... 19 

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8.5 
Informed Consent and Ethics Committee ................................................................... 19 
8.6 
Protocol Deviation ...................................................................................................... 20 
9 
References ................................................................................................................. 21 
 
 
 

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3 
Abbreviations and Definitions 
Abbreviation 
Term 
AE 
Adverse Event 
COVID-19 
Corona Virus Disease 
CRF 
Case report form 
EC 
Ethics Committee 
EOS 
End of Study 
HCW 
Health care worker of clalit health care 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
MOH 
Ministry of Health 
PBMC 
Peripheral blood mononuclear cell 
PCR 
Polymerase chain reaction 
SAE 
Serious adverse event 
SARS-CoV-2 
Severe acute respiratory syndrome- corona Virus-2 
SMC 
Soroka Medical Center 
Soroka CRC 
Soroka Clinical Research Center 
 
 

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4 
Background 
The SARS-CoV-2 virus causes severe respiratory illness and is an ongoing global 
pandemic. On December 12, 2020 the FDA approved Pfizer’s BioNTech vaccine 
BNT162b2 which is a messenger RNA type of vaccine for use. This vaccine has shown in 
numerus studies the ability to induce a strong immune response and provide both humeral 
and cellular protection against wild type, alpha and delta variants of SARS-CoV2 virus.  
In Israel the national vaccine operation began in mid-December 2020 which included 2 
initial doses three weeks apart. In August 2021 a first booster (3rd dose) was provided to 
enhance protection and due to reports of reduced immune response and clinical 
protection. Several studies have demonstrated that over time there is a decay in the 
antibody levels, and with them reduced protection.  
Recently a new variant of concern has been identified (Omicron) and is causing a surge of 
infections worldwide. There is lack of knowledge regarding the effectiveness of the current 
schedule of vaccine against this new variant and whether a second booster (4th dose) will 
provide higher levels of clinical protection against this variant, currently the ministry of 
health is considering recommendations for a fourth dose for HCW.  
The purpose of this study is to examine whether a fourth dose of vaccination will provide 
better protection against infection and clinical disease. 
 
 

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5 
Methods 
5.1 
Working Hypothesis 
In HCW, receiving a second booster (fourth dose) of BNT162b2 vaccine will lower the 
rates of the COVID-19 infection compared to controls. 
5.2 
Objectives 
5.2.1 
Primary Objective 
Examine the protection against any type of COVID-19 infection as confirmed by PCR 
testing or positive serology for N antigen during the follow up period.  
5.2.2 
Secondary Objectives 
Evaluate the impact of a fourth dose on: 
1. Symptomatic COVID 19 infection 
2. COVID 19 infection requiring hospitalization  
3. Antibody levels including IgG, IgA, IgM, binding and neutralizing activity and the avidity 
of the antibodies. 
5.3 
Schedule of Events 
Visit number 
 
1 
2 
3 
4 
5 
6 
Time point (± 2 week) 
Enrollment Month 1 Month 2 Month 3 Month 4 Month 5 Month 6 
Informed Consent 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
X 
 
 
 
 
 
 
Demographics and 
Medical History 
X 
 
 
 
 
 
 
Blood samples* 
X 
X 
X 
X 
X 
X 
X 
Nasal and mouth 
Swab** 
X 
X 
X 
X 
X 
X 
X 
Questionnaire  
X 
X 
X 
X 
X 
X 
X 
Adverse events 
X 
X 
X 
X 
X 
X 
X 
* Antibody levels including IgG, IgA, IgM, binding and neutralizing activity and the avidity of the 
antibodies. Serum separation and freezing at each site. Only at Soroka medical blood will be 
drawn for PBMC testing in addition to antibodies testing.  
** Antibody levels including IgG, IgA, IgM 
 
 

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5.4 
Flow chart 
 
Subjects in the control group who are vaccinated after inclusion in the study with a fourth 
dose will be switched to the vaccinated arm and followed from that point as boosted. 
5.5 
Study Population 
The study population will be screened at each participating medical center 
The study population will be enrolled according to the following inclusion and exclusion 
criteria. 
5.5.1 
Inclusion Criteria 
1. Able to provide written informed consent. 
2. Healthcare worker in one of the Clalit Health Services medical centers and is at least 
18 years of age. 
3. Completed three doses of BNT162b2 according to MOH guidelines. 
4. Third dose was given at least 4 months prior to enrollment. 
5.5.2 
Exclusion Criteria 
1. History of COVID-19 infection. 
2. History of being treated or is currently being treated for any type of Malignancies or 
other co-morbid conditions that may result in protocol non-compliance. 
3. Currently or in the past three months was treated with any type of Immune suppression 
medication (including chemotherapy, immunomodulatory drugs, biological agents that 
affect the immune system, any immunosuppressive drug such as corticosteroids). 
Screening of 
HCW 
Recived 
4th dose
Followed 
monthly for 6 
months
Control group
Followed 
monthly for 6 
months
Exlcuded

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4. Received in the past 4 months monoclonal antibodies of any type. 
5.5.3 
Withdrawal/Discontinuation Criteria 
All subjects should be encouraged to remain in the study through the entire follow up. 
However, if a subject decides to discontinue study participation, the reason for 
discontinuation must be recorded in the medical record and the Case Report Form (CRF). 
Subjects who discontinue participation prematurely will be included in the analysis of 
results (as appropriate) but they will not be replaced in the enrollment of total study 
subjects. 
Every attempt must be made to have all subjects complete the follow up visit schedule. A 
subject will not be considered lost-to-follow up unless all efforts to obtain compliance are 
unsuccessful.  
Discontinuation in the study will be if the antibody result at enrollment visit shows the 
participant already had the disease. 
5.6 
Enrollment 
Prior to participation in this study, the Investigator must obtain written approvals from the 
ethics committee and other local regulatory bodies as appropriate approval for the protocol 
and the informed consent form. Failure to obtain a signed and hand dated informed 
consent prior to the procedure constitutes a protocol violation, which is reportable to the 
EC.  
The Investigator will obtain an approval from the ethics committee to recruit and sign 
participants on informed consent form by study research members (such as study 
coordinators, research assistant, study investigator and etc.) with GCP certificate.       
5.7 
Subject Screening 
Screening will be performed at each participating medical center; an email or other 
medical communication will be sent out to the employees of each participating medical 
center with a short description of the study and invite them to learn more of the study and 
be screened.  
HCW who fulfills all the inclusions and none of the exclusion criteria will be approached 
and offered participation in the study by a study research member. A study research 
member will explain the purpose, procedures and intent of the study to each potential 

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participant. Interested HCW will be asked to provide written consent prior to performing 
any study procedure. 
5.8 
Study Procedures 
5.8.1 
Screening and Enrollment 
The following will take place at this visit: 
• Confirmation of eligibility and informed consent will be signed.  
• Demographics and medical history will be recorded.  
• COVID-19 questionnaire regarding exposure and symptoms. 
• Blood draw of three 5 ml vials, for antibody testing. 
• Blood drawn for PBMC and antibody testing: 
o Will be at ONLY at Soroka Medical Center. 
o 150 subjects will be selected randomly. Subjects participating in this part will have 
30 ml (3 vials of 9 ml and 1 vial of 3 ml) of blood drawn for PBMC and antibody testing. 
Others will have blood draw of three 5 ml vials, for antibody testing. 
• A nasal and mouth swab will be performed.  
5.8.2 
Visit 2 –6  
• 
COVID-19 questionnaire regarding exposure and symptoms. Blood draw of three vials 
of 5 ml for antibody testing,  
• Blood drawn for PBMC and antibody testing: 
o Will be at ONLY at Soroka Medical Center. Subjects who were not part of the PBMC 
group and are willing to participate, will be asked again to sign inform consent.  
o Subjects participating in this part will have 30 ml (3 vials of 9 ml and 1 vial of 3 ml) of 
blood drawn for PBMC and antibody testing. Others will have blood draw of three 5 
ml vials, for antibody testing. 
• A nasal and mouth swab will be performed.  
• Adverse events following vaccination and changes in medications (chronic and/or 
Immune suppression medication) will be collected  

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5.9 
Laboratory testing 
From each HCW at each visit the following tests will be performed: 
• The Platelia SARS-CoV-2 Total Ab assay by Bio rad, is a semi-quantitative in vitro 
diagnostic test, in a one-step antigen capture format, for the detection of IgM/IgA/IgG 
antibodies to the SARS-CoV-2 in human serum and plasma (EDTA, heparin, ACD or 
citrate) specimens. This assay will be performed at SMC virology laboratory (head-
Prof. Yonat Shemer). 
• Antibody profiling of blood and nasal and mouth samples will be tested using antigen 
microarrays, this will be performed by using chip antigen microarrays spotted with 
various coronavirus antigens, as well as antigens of other common respiratory 
pathogens. This assay will be performed at Prof. Tomer Hertz laboratory at Ben-Gurion 
University of the Negev.  
• On select samples from each visit neutralization assays for SARS-CoV-2 virus variants 
will be performed. Each sample selected will be tested for its ability to inhibit infection 
of target ACE2-expressing cells by reporter pseudoviruses that express the spike 
protein of either Delta or Omicron Variant of Concern. This assay will be performed at 
Dr. Ran Taube laboratory at Ben-Gurion University of the Negev. 
• Blood samples for PBMC’S will be stored at Prof. Hertz's laboratory at Ben-Gurion 
University of the Negev for future research.  
5.10 
Study Duration 
The subject will participate for 6 months from the initial consent.  
We expect that enrollment to the study will be for a period of 1 months.  
5.11 
Data to Capture 
5.11.1 Required Data 
All required data for this study will be collected via paper and or electronic case report 
forms (eCRF). 
5.11.2 Data Collection  
The final set of CRFs is designed to accommodate the specific features of the trial design. 
Modification of CRFs will only be made if deemed necessary by Soroka CRC. The CRFs 
will be filled out manually by the study personal and or will be collected through the 
computer services database. 

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The following data will be collected: 
• 
Demographic data: age, sex, country of birth, healthcare profession, direct contact 
with covid subjects in working capacity. 
• 
Detailed medical history, including but not limited to past illness with COVID, 
malignancy, diabetes, renal failure, heart disease, hypertension, history of stroke, 
rheumatological illness.  
• 
Current medications used and medications used for more than one week in the past 
three months. 
• 
Any adverse event during the study as a result of vaccination. 
 
 

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6 
Statistical Considerations and Analysis Plan 
In this prospective observational registry we aim to assess the rates of the COVID-19 
infection as confirmed by PCR testing or positive serology for N antigen during the follow 
up period. We hypothesize that booster of BNT162b2 vaccine in healthcare workers 
(HCW) will lower the rates of the COVID-19 infection as compared to HCW choosing not to 
receive the second booster. 
We aim to enroll up to 1000 subjects. The following assumptions were used to estimate 
the power of the analysis.  
• The proportion of the HCW choosing to receive the second booster is 60% 
• The expected monthly infection rate of 2.5% in the non-vaccinated group 
• Expected monthly infection rate of 1.0% in the treatment group 
• Median follow-up until switching to the booster administration in the non-vaccinated 
group (15%) of 4 months 
• Type I error (α) = 0.025 (one-sided) 
• Log-rank test 
• Enrollment period of 1 month 
• Lost to follow-up of 10% 
An evaluable sample size of 1000 subjects provides 80.0% power to reject the null 
hypothesis, signifying the booster strategy is superior to the comparison group at 6 months 
post-vaccination.   
 
All statistical analyses will be performed using Statistical Analysis System (SAS) for 
Windows (version 9.4 or higher, SAS Institute Inc. Cary, NC) or other widely accepted 
statistical or graphical software.  In general, data for all study patients will be combined 
and presented. Individual data will be presented in patient listings. 
Descriptive statistics will be used to present the data and to summarize the results.  
Categorical variables will be presented using frequency distributions and cross tabulations 
with numbers and percent per group. Continuous variables will be summarized by 
presenting the number of observations (N), mean, 95% confidence interval of the mean, 
standard deviation, median, minimum, and maximum values. 

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The primary outcome will be analyzed within the paradigm of the survival analysis, i.e. log-
rank test for the univariate analysis. Since it is possible that those who chose not to be 
vaccinated will differ in a number of characteristics, we will utilize Cox regression models 
with time dependent variable (timing of the booster) with the adjustment for the potential 
confounders. The confounders will be identified by the DAG approach. In addition different 
approaches to approximate the counterfactual world assumption such as propensity score 
adjustment will be considered.  
The following subgroup analysis will be performed: stratified by age, gender, immune 
status, medical center, timing of the booster (before and after the current wave peak).    
 
 

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7 
Adverse Events 
7.1 
Adverse Event Definition 
7.1.1 
Adverse Event 
Any undesirable experience (sign, symptom, illness, abnormal laboratory value, or other 
medical event) occurring to a subject, that is considered related to the investigational 
treatment regimen prescribed as part of the clinical protocol, predefined in the clinical 
protocol and/or Instructions For Use, that is identified or worsens during a clinical study. 
7.1.2 
Treatment Related Adverse Event  
A treatment related adverse event is defined as any adverse event, for which a causal 
relationship between the treatment and the event is at least a reasonable possibility, i.e., 
the relationship cannot be excluded.  
7.1.3 
Serious Adverse Event 
A serious adverse event as one when the subject outcome is one of the following: Death, 
Life-threatening, Hospitalization (initial or prolonged), Disability - significant, persistent, or 
permanent change, impairment, damage or disruption in the subject's body function/ 
structure, physical activities or quality of life, Congenital anomaly or requires intervention 
to prevent permanent impairment or damage. 
Since this is an observational registry study, SAEs will not be reported to the EC, but will 
be included in the statistical analysis. 
All side effects as a result of vaccination will be reported to Ministry of Health.   
7.2 
Anticipated Adverse Event 
In this study we do not anticipate adverse event. However, adverse event as a result from 
blood drawn and nasal and mouth swabbing can occur, such as: pain, hematoma, and 
discomfort in the sampling area 
 
 

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8 
Ethical and Regulatory Considerations 
8.1 
 Subject Confidentiality 
Subject confidentiality will be maintained throughout the study in a way that assures that 
data can always be tracked back to the source data. For this purpose, a unique subject 
identification code will be used that allows identification of all data reported for each 
subject.  
Data relating to the study might be made available to third parties (for example in case of 
an audit performed by regulatory authorities) provided the data are treated confidentially 
and that the subject’s privacy is guaranteed. 
8.2 
 Sources of Materials 
Research material obtained from study participants includes medical information, blood 
specimens, and nasal samples obtained for laboratory analysis.   
All of the data obtained for this study will be obtained prospectively. 
Copies of data obtained as part of the study will be retained by the clinical research center, 
with appropriate source documentation, on all subjects that sign informed consent. The 
data utilized in this study are described above and consist of information from medical 
records, or study-specified measures and interventions.  
8.3 
 Maintaining Records  
The principal investigator will maintain copies of all study-related correspondence, 
regulatory documents, data, shipment of sample logs, adverse events and other records 
related to the clinical study.  
8.4 
 Site Record Retention Policy  
All core laboratories and clinical sites will maintain study records until the principal 
investigator notifies them and the reviewing regulatory authorities that research is 
completed or terminated under the clinical investigation in compliance with national law. 
Record retention dates will be provided to study sites by the principal investigator at the 
onsite closeout visit. 
8.5 
Informed Consent and Ethics Committee 
All subjects must provide written informed consent in accordance with the local clinical 
site’s EC. A signed Informed Consent must be obtained from each subject prior to 

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commencing screening/baseline evaluations. One copy of the Informed Consent document 
will be given to the subject and another retained by the Investigator. 
8.6 
Protocol Deviation  
Any incident in which the investigator or site personnel did not conduct the study according 
to the clinical protocol or the investigator agreement.  
Protocol deviations are classified to three categories:  
• 
Major deviation: Any deviation from subject inclusion and or exclusion criteria or 
subject informed consent procedures. 
• 
Critical finding: any deviation that can affect the wellbeing of the participant, or the 
reliability of the data collected is compromised. 
• 
Minor deviation: Deviation from a clinical protocol requirement such as 
incomplete/inadequate testing procedures, follow-ups performed outside specified 
time windows, etc.  
 
 

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9 
References 
 
• 
Barda N, Dagan N, Cohen C, Hernán MA, Lipsitch M, Kohane IS, et al. Effectiveness of a third 
dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: 
an observational study. Lancet. 2021 Dec 4;398(10316):2093-2100. 
 
• 
Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 
Vaccine. N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577 
 
• 
Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide 
Mass Vaccination Setting. N Engl J Med. February 2021. doi:10.1056/NEJMoa2101765 
 
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