A Single-Site Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
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Sponsor: Sanguine Biosciences

 
 
 
 
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     PROTOCOL 
 
 
TITLE: 
A Single-Site Tissue Repository Providing 
Annotated Biospecimens for Approved Investigator-
directed Biomedical Research Initiatives 
PROTOCOL NUMBER:  
PRINCIPAL INVESTIGATOR:  
SPONSOR: 
 
 
 
VERSION: 
 
 
IRB APPROVAL DATE: 
SAN-BB-02 
 
Houman Hemmati, M.D., Ph.D. 
 
Sanguine Biosciences, Inc. 
318 Bear Hill Road, Suite 1 
Waltham, MA 
02451 
 
 
1.0 
 
 
31Dec2021
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
 
The document is property of Sanguine BioSciences, Inc. The document contains confidential 
information and intellectual property solely intended for the recipient (clinical investigator). The 
document must not be used for any other reason or disclosed to any other party. Any other use of 
this document is strictly prohibited unless written consent from Sanguine BioSciences, Inc. 

 
 
 
 
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PROTOCOL SIGNATURE PAGE 
 
Statement of Compliance: 
 
The trial will be conducted in accordance with the International Conference on Harmonisation 
Good Clinical Practice (ICH GCP), and all applicable laws and regulations including the 
following United States Code of Federal Regulations (CFR). The CFR’s applicable to clinical 
studies (§ 45 CFR Part 46, § 21 CFR Part 50, and § 21 CFR Part 56).  
 
As Principal Investigator, I will assure that no deviation from, or changes to the protocol will take 
place without prior agreement from the Sponsor, and documented approval from the Institutional 
Review Board (IRB), except where necessary to eliminate an immediate hazard(s) to the study 
participant. All personnel involved in the conduct of this study have completed human subject 
protection and ICH GCP training.  
 
The protocol, informed consent form(s) (ICFs), recruitment materials, and all participant 
materials will be submitted to the IRB for review and approval. Approval of both the protocol 
and the consent form is obtained before any participant is enrolled. Any amendment to the 
protocol will require review and approval by the IRB before the changes are implemented to the 
study. In addition, all changes to the consent form will be IRB-approved; a determination will be 
made regarding whether a new consent needs to be obtained from participants who have already 
provided consent, using a previously approved consent form.  
 
The information contained herein is confidential, and the proprietary property of Sanguine 
BioSciences, Inc., and any unauthorized use or disclosure of such information without the prior 
written authorization of Sanguine BioSciences, Inc. is expressly prohibited. 
 
 
 
 
 
 
Investigator Signature: _____________________________________   Date: ______________ 
 
 
 
 
 
 
Investigator Print Name: ________________________________________________________     
 

 
 
 
 
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TABLE OF CONTENTS 
 
 
1   PROTOCOL SYNOPSIS 
5 
2   BACKGROUND & RATIONALE 
9 
2.2   Biomedical Research Methods and Diagnostic Markers 
10 
2.3   Study Rationale 
11 
3   STUDY OBJECTIVES & PURPOSE 
11 
4   STUDY DESIGN 
13 
4.1   Study Design Rationale 
13 
4.2   Description of the Study 
14 
4.3   Compliance with Laws and Regulations 
15 
5   STUDY METHODS 
15 
5.1   Sample Size 
15 
5.2   Participation Criteria 
15 
5.2.1   Health Condition Group 
16 
5.2.2   Exceptive Condition Group 
16 
5.2.3   Control Group 
17 
5.3   Patient Procedures 
18 
5.3.1   Recruitment 
18 
5.3.1.1   Online Recruitment 
19 
5.3.2   Potential Participant Inclusion/Exclusion Screening 
19 
5.3.3   Potential Participant Cohort Placement 
19 
5.3.4   Informed Consent 
19 
5.3.5   Biospecimen Collection 
20 
5.3.6   Control Group 
21 
5.3.7   Optional Biospecimen Collection 
21 
5.3.8   Patient surveys, questionnaires, and PROs 
22 
5.3.9   Recovery Time 
22 
5.3.10   Collection of Protected Health Information (PHI) 
22 
5.4   Confidentiality/De-identification Process 
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5.5   Direct Access to Source Data/Documents 
22 
5.6   Sample Processing and Storage 
22 
5.7   Biospecimen & Data Distribution Procedures 
23 
5.8   Study Termination 
23 
5.9   Patient-Initiated Withdrawal 
24 
5.10   Investigator-Initiated Withdrawal 
24 
6   RISK/BENEFIT ASSESSMENT 
24 
6.1   Potential Risks 
24 
6.2   Risk Classification 
24 
6.3   Protection Against Risks 
25 
6.4   Potential Benefits 
25 
7   ETHICAL CONSIDERATIONS 
26 
7.1   Online Recruitment 
26 
7.2   Informed Consent Form 
26 
7.3   Potential Collection from Subjects with Infectious Diseases 
27 
7.4   De-identifying Protected Health Information Under the Privacy Rule and Disclosure 
of Data 
27 
7.5   Regulatory Compliance 
28 
7.6   Principal Investigator 
28 
8   RECORD RETENTION 
28 
9   FINANCIAL OBLIGATION & COMPENSATION 
28 
9.1   Financial Obligation of the Subjects 
28 
9.2   Financial Compensation for Participation 
28 
10   INTELLECTUAL PROPERTY 
29 
11   APPENDIX A – WORKS CITED 
30 
13   APPENDIX B – SUBJECT SAFETY PROCEDURE FLOW 
32 
14   APPENDIX C – EXAMPLE OF DATA COLLECTED 
33 
16   APPENDIX D  – POST-VISIT SURVEY 
34 
17   APPENDIX E – ABBREVIATIONS 
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1   PROTOCOL SYNOPSIS 
 
SPONSOR: Sanguine Biosciences, Inc. 
STUDY TITLE: 
A Single-Site Tissue Repository Providing Annotated Biospecimens for Approved Investigator-
directed Biomedical Research Initiatives 
PROTOCOL NUMBER: SAN-BB-02 
PRIMARY OBJECTIVE:  
To collect, preserve, and/or distribute annotated biospecimens and associated medical data to 
institutionally approved, investigator-directed biomedical research to discover and develop new 
treatments, diagnostics, and preventative methods for specific and complex conditions. 
STUDY DESIGN: 
● A single-site, cross-sectional study 
● Biological tissue samples will be collected from study participants, processed, and preserved in 
the biorepository’s cryogenic core biobank (hereinafter, “biobank”) until a research study 
requests a sample. 
● If a sample does not require processing, the sample may be delivered directly to the requesting 
researchers or designated third parties. 
● Health information will be collected via self-report and medical record review to obtain a detailed 
clinical history of the participant’shealth. This information includes but is not limited to 
demographic and lifestyle information, current medications and comorbidities, date of diagnosis, 
condition-related treatment history, current disease characteristics, diagnostic reports, and family 
medical history. 
● Sanguine will implement a software-as-a-service (SaaS) provider of electronic signature 
technology and transaction management solutions or a hardcopy of the informed consent form 
(ICF). Participants may electronically sign the ICF and authorization of release of information 
using an electronic device. The Sponsor may alternatively provide the participant the option 
of completing hardcopy documents if they so desire. In addition to the Principal Investigator 
(PI), approved study staff can also administer and sign the ICF and will address all of the 
participant’s queries regarding the ICF and study design. 
● All participants biospecimens, if processed, will be stored and distributed by blinded personnel to 
the participants direct identifiers. 

 
 
 
 
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DURATION OF PARTICIPANT PARTICIPATION: 
● This study requires the collection of a tissue sample, which is considered active participation. 
Study enrollment and the sample collection take about one hour or more to complete depending 
on the number and types of samples collected. Therefore, active participation will be about one 
hour and may be up to two hours. 
● Inactive participation lasts as long as a participants samples and data remain at the biobank. 
There is no limit on the length of time samples and data may be stored. The samples may remain 
indefinitely at the biobank or until the participant decides to withdraw their participation from 
the study. 
STUDY POPULATIONS: 
Health Condition Group: 
  Health Condition Group Inclusion Criteria: 
● Persons 18 to 85 years of age at the date of informed consent. 
● If presenting with a history of a specific condition, the diagnosis is confirmable in the medical 
record or may be confirmed using other forms of verification including self-reporting. 
● Understands the procedures and requirements of the study by providing written informed 
consent (or verbal assent if a legally authorized representative will sign the ICF), including 
consent for authorization for protected health information disclosure. 
 
  Health Condition Group Exclusion Criteria: 
● Persons younger than 18 years of age or older than 85 years of age at the date of informed 
consent.  
● Receipt of blood products 30 days before the study blood draw. 
● Receipt of an investigational (unapproved) drug 30 days before the study blood draw. 
● A confirmable diagnosis of any medical condition that would increase potential phlebotomy 
risks. Such medical conditions include: 
o Severe or untreated cardiovascular diseases;  
o Bleeding disorders; 
o Late-stage chronic kidney disease; and/or 
o Conditions associated with chronic anemia.  
o Stage 3 and 4 cancers 
● Pregnancy 
● Has donated a unit of blood within the last 2 months at the date of informed consent. 

 
 
 
 
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Exceptive Condition Group: 
  Exceptive Condition Group Inclusion Criteria: 
● Persons 18 to 85 years of age at the date of informed consent 
● If presenting with a history of a specific condition, the diagnosis is confirmable in the 
medical record. 
● A confirmable diagnosis of any medical condition that would increase potential 
phlebotomy risks. Such medical conditions include: 
o Severe or untreated cardiovascular diseases; (including a stroke or myocardial 
infraction within the last 2 months) 
o Bleeding disorders; 
o Late-stage chronic kidney disease;  
o Splenomegaly; 
o Pregnancy; and/or 
o Conditions associated with chronic anemia.  
● Understands the procedures and requirements of the study by providing written 
informed consent (or verbal assent if a legally authorized representative will sign the 
ICF), including consent for authorization for protected health information disclosure. 
 
  Exceptive Condition Group Exclusion Criteria: 
● Persons younger than 18 years of age or older than 85 years of age at the date of 
informed consent.  
● Receipt of blood products 30 days before the study blood draw. 
● Receipt of an investigational (unapproved) drug 30 days before the study blood draw. 
● Has donated a unit of blood within the last 2 months at the date of informed consent. 
 
Control Group: 
  Control Group Inclusion Criteria: 
● Persons 18 to 85 years of age at the date of informed consent. 
● Understands the procedures and requirements of the study by providing written informed
consent (or verbal assent if a legally authorized representative will sign the ICF), includi
consent for authorization for protected health information disclosure. 

 
 
 
 
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  Control Group Exclusion Criteria: 
● Persons younger than 18 years of age or older than 85 years of age at the date of 
informed consent.  
● Receipt of blood products 30 days before the study blood draw. 
● Receipt of an investigational (unapproved) drug 30 days before the study blood draw. 
● A confirmable diagnosis of any medical condition that would increase potential 
phlebotomy risks. Such medical conditions include: 
o Severe or untreated cardiovascular diseases;  
o Bleeding disorders; 
o Late-stage chronic kidney disease; and/or 
o Conditions associated with chronic anemia.  
● Pregnancy 
● Requires a Legally Authorized Representative (LAR) for the study informed consent.  
● Has donated a unit of blood within the last 2 months at the date of informed consent. 
STUDY OUTCOMES 
The study’s objective is to provide quality and standardized biospecimen collections to the 
biomedical community to facilitate future personalized medical care. 
SAMPLE SIZE CONSIDERATIONS 
The number of participants to be enrolled in this study is 20,000. The reason for 20,000 
participants is that the Sponsor anticipates that over 2 years of the study, at least 50% of the 
participants will discontinue study participation. Because this study aims to establish a tissue 
biorepository for future therapeutic and diagnostic research endeavors, the Sponsor requires 
accrual and maintenance of a large enough biospecimen cohort for research clients to obtain 
statistically significant results. Therefore, the Sponsor believes that this sample size will 
provide the required sample diversity and volume to achieve statistically significant results 
despite participation attrition. 

 
 
 
 
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2   BACKGROUND & RATIONALE 
To collect, preserve, and/or distribute annotated biospecimens and associated medical data to 
institutionally approved, investigator-directed biomedical research to discover and develop new 
treatments, diagnostics, and preventative methods for specific and complex conditions. 
Biomedical research has utilized biorepository specimens for decades. Starting as small, private 
tissue collections, investigators analyzed small cohorts of samples to validate an anticipated 
molecular or genetic aberration specific to a particular disease. In recent years, advances in 
molecular and genetic research techniques have extended the ceiling of biomedical research 
potential allowing large volumes of samples, genes, and molecules surrounding a disease to be 
analyzed quickly and cost-effectively.1 One major factor now governing translational research is 
the availability of quality biospecimens to deliver quality results.  
The National Cancer Institute surveyed over 700 investigators regarding their research experience 
with biobank specimens. Over 60% of researchers surveyed considered the specimens to be under-
annotated, 47% stated the quality was questionable.2 This led to 60% of researchers questioning 
their findings and over 80% were forced to limit the scope of their proposed research.2 It is evident 
that the quality of research conducted using biobank specimens would be greatly enhanced by 
standardized collection and storage processes assuring the uniform quality of the material to be 
studied. 
Another factor hindering the clinical applicability and impact of biomedical research findings is 
the limited volume and diversity of available samples for analysis. Traditional institutionally 
established biobank collections are restricted by regional location and the population.3 Such 
biobanks are also limited to collect specimens from people seeking medical care.3 Analyzing 
molecular patterns present within these collections limits the applicability of investigational 
findings. 
A third issue limiting the scope of current molecular and genetic research methods is the sheer 
complexity of health conditions, both etymologically and in terms of therapeutic efficacy. 
Researchers have exhausted the effects of one to a few genes on a disease state. When mutated, a 
single gene can trigger a rare inherited disorder such as Huntington’s disease, which is an 
increasingly infrequent discovery. Many diseases are increasingly viewed as complex conditions 
affected by numerous genes of varying influence. In oncology alone, there are more than 100 
known types of cancer, mostly named after the organs they were first located and the type of cells 
from which they originate.4 Yet, these common pathological designations are rapidly becoming 
less definitive as molecular markers become more clinically relevant in the era of personalized 
medicine. The National Comprehensive Cancer Network (NCCN) has more than forty molecular 
biomarkers for clinical practice to characterize six of the most common types of malignancies.5 
The NCCN has designated an entire task force to vet the increasing number of potential markers 
for clinical   use. 
Molecular markers can be diagnostic, prognostic, or predictive and are revolutionizing cancer 
treatment through the elucidation of genetic factors, which can influence a participant’s specific 
therapeutic course. Cancer is comprised of hundreds of distinct molecular diseases. The ability to 
molecularly distinguish cancer types independent of routine gross and microscopic inspection 
holds the potential for discovering therapeutic similarities between well-documented and 

 
 
 
 
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uncommon types of cancer. This may increase participant outcomes for rare forms of cancer. An 
example of this is imatinib; a drug approved by the FDA to treat leukemia. Researchers discovered 
molecular similarities between leukemia and gastrointestinal stromal tumors (GIST), making 
tumors responsive to imatinib.6 This molecular correlation proved correct in clinical trials, and 
imatinib was FDA-approved to treat GIST. 
Cancer is one of many fields exploring genetic and molecular variability between disease subtypes 
and individuals. Autoimmune, metabolic, cardiovascular, and most other common and rare health 
conditions are influenced by genetic predisposition and environmental and comorbid factors.7 
Common conditions such as atherosclerosis or diabetes mellitus are caused by deficiencies in 
multiple genes combined with diet or lifestyle habits. Because each gene contributes a small 
amount to overall risk, varying signals are emitted, confounding efforts to associate it with a 
specific disease state. Therefore, researchers need to study the genetic profiles of many people, 
incorporating phenotypic and health data to maximize clinical impact. In addition to the molecular 
complexity of the pathophysiology of health conditions, treating diseases can be just as complex. 
It is well known that standards of treatment do not consistently work from participant to 
participant. Therefore, to more effectively treat participants, physicians must understand the 
genetic complexity associated with certain medical conditions and the individual.  To decipher the 
genetic web that governs certain conditions, researchers must study a large and diverse cohort of 
genetic material to arrive at statistically significant results. 
 
2.2   Biomedical Research Methods and Diagnostic Markers 
Biological research methods such as genetics and proteomics are beginning to develop a powerful 
influence in developing new medicines and diagnostics, which is an emerging area of biomarker 
development. Biomarkers are substances that can be found in the body when cancer is present. The 
classic tumor marker is a protein that can be found in the blood at increased levels when a certain 
type of cancer is present. Systemic Lupus Erythematosus can be detected from values of 
biomarkers present within a person’s blood. In recent years, doctors have begun to develop newer 
types of biomarkers using different types of biological and genetic material. Bioinformaticians and 
molecular biologists have deemed this field of biomarker discovery using the suffix “omics.” 
Examples of omics include genomics, proteomics, metabolomics, and pharmacogenomics. 
The study of patterns of DNA changes (or mutations) is called genomics.8 We know that most 
health conditions have changes in DNA that direct the function of cells. By looking for DNA 
aberrations in blood samples, scientists may find complex genetic patterns that characterized 
certain health conditions. Pharmacogenomics analyzes an individual’s response to certain drugs 
by looking at their genes.8 Such analysis will help physicians choose the optimal treatment course 
for each participant maximizing drug efficacy while simultaneously minimizing adverse effects, 
truly personalizing medicine. 
Another approach, called proteomics, looks at the patterns of all the proteins in the blood instead 
of looking at individual protein levels.9 New testing equipment allows researchers to look at 
thousands of proteins at one time. It is unlikely that such a test would be used in the clinic, but it 
may help researchers narrow down which protein levels are important in a certain disease state. 
This information could then be used to develop a diagnostic test looking only at these important 
proteins. Alternatively, treatment may be developed to target these proteins affecting the 

 
 
 
 
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pathophysiology of a condition or to test the efficacy of a certain therapy used in a case. These 
new testing methods are still in the early stages of development. Very few are in routine use at this 
time. 
Metabolomics studies the chemicals and molecules created during specific cellular processes 
(metabolites).10 Metabolomic profiles can capture a cell’s physiology at a specific time. 
Metabolites are much smaller than proteins. Therefore, metabolomics allows researchers to view 
a broader range of chemicals within the molecular spectrum.10 Working together with proteomics, 
researchers can put together a complete picture of cellular pathways utilized by health conditions. 
The omics field of biomarker discovery is but one new field currently explored by biomedical 
researchers. The concept of statistically analyzing a vast amount of data for patterns within whole 
populations is also an expanding area of interest for a couple of reasons. Such studies can be 
performed remotely on an electronic dataset by multiple investigators without depleting the 
physical biospecimen. Potential research studies for which Sanguine BioSciences, Inc., will 
provide biospecimens are not limited to the types of research discussed above. Instead, the purpose 
of the above discussion is to elucidate potential areas of future research to which biobank samples 
may be provided. 
 
2.3   Study Rationale 
The availability of high-quality biospecimens to use in such studies dictates the quality of scientific 
results achieved and remains a significant roadblock to the standardization of results in biomedical 
research. Following the accepted international best biorepository practices, Sanguine Biosciences, 
Inc. will provide superior biospecimen collection and processing to the research community. By 
following these practices, specimens will be a consistent grade to promote viable and reproducible 
scientific results. The primary purpose of SAN-BB-02 is to collect, preserve and/or distribute 
quality biospecimens with associated health data (annotations) to researchers. Not only will this 
study physically accomplish this task, but Sanguine Biosciences, Inc., will also establish an 
electronic DNA database. Through physical and electronic biospecimen collection, this study will 
create a shared research infrastructure for a large population of investigators, thus allowing them 
access to physical biospecimens, electronic genetic material, and associated health data. This dual 
method of biospecimen availability allows studies to fully explore their research initiatives with a 
direct emphasis on clinical impact. 
Sanguine Biosciences, Inc., is a steward of health information, physical and electronic, biological 
and subjective, and provides a direct resource of molecular data for researchers via biological 
tissue collections and electronic genetic library. Sanguine BioSciences, Inc., will source potential 
participants using different public spheres to collect a diverse genetic and epigenetic cohort 
allowing for potential population-based investigations to discern general molecular trends in 
multifactorial conditions. Such wide-range studies can only be qualitatively accomplished by 
comparing a large condition-specific population against a diverse control population where 
biospecimen integrity is standardized across all samples. The core competency of this study is 
providing such samples to the research community to ensure quality results. Through valid 
population-based studies, personalized medicine can truly come into focus in the clinic. 
Individuals can be compared against molecular trends within a population to be diagnosed and 
treated according to molecular disposition instead of gross, histological, or clinical standards of 

 
 
 
 
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care currently in use. 
 
3  STUDY OBJECTIVES & PURPOSE 
The primary study objective is to collect, preserve, and/or distribute annotated biospecimens and 
associated medical data to institutionally approved, investigator-directed biomedical research to 
discover and develop new treatments, diagnostics, and preventative methods for specific and 
complex conditions. 
To further study genotypic and phenotypic characteristics of specific and complex health 
conditions, the Sponsor may establish its biorepository to facilitate viable experimental results by 
supplying the research community with consistent, high-quality specimens. Sanguine BioSciences, 
Inc. (hereinafter, Sanguine) may collect biospecimens from health conditions participants and 
controls participants. Peripheral blood mononuclear cells (PBMC), serum, DNA/RNA, protein, 
and other blood portions may be extracted from blood samples and stored for future research. Other 
biospecimens that may be donated and stored include but are not limited to saliva, sputum, urine, 
hair, skin, nail clippings, stool, and semen. Demographically matched control samples may be 
collected to give researchers a baseline to compare against health condition samples. Control 
donors are considered participants who have not been clinically diagnosed with a medical 
condition. 
Eventually, Sanguine may develop participant-derived induced pluripotent stem cells (iPS cells) 
to develop disease-specific cell lines that can be expanded in culture for research and development 
purposes only. The cells that we would obtain from participants blood do not divide in culture, and 
therefore will be available to a limited number of researchers. However, one can genetically 
transform those cells to divide. These cells are very similar to embryonic stem cells (cells that 
divide and transform into all types of cells – like nerve cells, skin cells, etc.)—allowing more of 
the participants cells to researchers working in specific conditions. The advantage of iPS cells – 
which are very similar to embryonic stem cells – is that they are not derived from human embryos, 
eliminating the ethical concern. By providing these samples to researchers, Sanguine will facilitate 
the pre-clinical analysis and correlation of genotypes with phenotypes (such as clinical outcomes). 
The Sanguine biorepository may store biospecimens extracted from blood samples donated from 
control and health condition donors for unspecified future biological and biomedical research. The 
information gathered from this future research potentially include, but is not limited to: 
● DNA/RNA/protein mutation analysis; 
● DNA methylation analysis; 
● Protein to DNA/RNA binding analysis; and/or 
● Gene/protein expression analysis. 
The additional information may help improve participant care by developing new diagnostics and 
therapies. The information will also help physicians understand how and why specific treatments 
behave differently in different participants, leading to individualized drug therapy for participants 
in the future. 
Sanguine may also extend the biobank to include an electronic genetic database composed of 

 
 
 
 
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partial and whole sequences of the participants DNA and RNA. Such a library would allow more 
researchers to utilize the biobank samples than possible through traditional physical biobanking 
means. 
4   STUDY DESIGN 
4.1   Study Design Rationale 
Researchers with institutionally approved study initiatives may request and analyze the 
biospecimens, genetic material, and health data collected in this study to better understand specific 
health problems.  
The information from this unspecified future biological and biomedical research may facilitate 
developing new diagnostic tools and personalized treatments for specific health conditions. Such 
conditions may be acute or chronic, specific or complex, prevalent or rare. Many health conditions 
overlap with each other clinically and genetically, necessitating in-depth molecular 
characterization of these conditions to diagnose and treat sufferers of such conditions successfully. 
Sanguine will facilitate these research endeavors by providing samples of standard quality 
collected during this study to research institutions. 
The biobank may potentially collect biospecimens from rare populations such as elderly 
participants up to 85 years old. As the American population ages, the Sponsor feels that research 
on the aging process and conditions and diseases that disproportionately affect the elderly becomes 
increasingly important. 
Other rare and underrepresented populations in research from which the study aims to collect 
include participants with infectious diseases, including, but not limited to, HIV/AIDS and hepatitis 
subjects. Because this is a potential population from which biospecimens may come, special 
training, consideration, and safety will be performed by study staff handling such specimens. Since 
it is considerably more dangerous to handle specimens with bloodborne pathogens present, many 
biorepository studies neglect to collect these populations. Unfairly neglected and under-
represented within many biorepository cohorts, the Sanguine’s biobank wishes to collect and store 
quality infectious specimens to help advance biomedical research of such diseases. 
The study may require a tissue collection and/or a participant survey for participation. Most tissue 
collected will come from a blood draw; up to 100mL for the health condition group, 60mL for the 
exceptive condition group, and up to 180mL for the control group (if determined safe for the 
participant). Participant surveys may involve participant reported outcomes (PROs) or custom 
participant surveys. 
Drawing up to 100mL for the health condition group will allow the biobank to collect enough 
blood from isolating several sub-products from the whole blood, such as serum, plasma, peripheral 
blood mononuclear cells (PBMCs), and genetic material (DNA/RNA), which are commonly used 
in biomedical research. A blood draw will provide biological tissue to research and expose 
participants to minimal risk.11 A blood draw allows participants flexibility in scheduling the draw, 
either at a site or in the comfort of their home. 
Due to a potential increase of phlebotomy risks for people with certain medical conditions such as 
cardiovascular diseases, bleeding disorders and late-stage kidney problems, the exceptive 
condition group will have only up to 60mL drawn to minimize these risks. 

 
 
 
 
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The study aims to collect biological tissue from multiple populations to support and advance 
biomedical research. Drawing a large volume of blood from healthy donors will provide more 
control biosamples for researchers (posing minimal risk to the participant). Allowing the study 
efforts to concentrate on collecting samples from various populations to service more research 
fields.  
The control group may have up to 180mL of blood drawn for the study if determined that the 
participants health will not compromise their safety during the draw. The amount of 180mL is 
about one-third of the blood drawn during a blood donation and is considered by the Department 
of Health and Human Safety (HHS) to pose minimal risk to the participant. The study would like 
to have the potential to draw up to 180mL if the health of the participant allows this amount 
biological tissue to be collected from one appointment. Since the major risk and discomfort from 
venipuncture comes from being stuck with the needle, the study believes that a one-time blood 
draw of a larger volume would be potentially more comfortable for a healthy individual versus 
undergoing multiple venipunctures.   
Participant health will be assessed prior to phlebotomy to determine maximum blood draw volume 
for all cohorts.  
For all research requests that are not covered within this protocol, independent protocol 
amendments addressing the procedural changes may be drafted to address and minimize possible 
study risks. A medical practitioner will review the procedural amendments for safety assessment 
and submit to the IRB for review. 
 
4.2   Description of the Study 
This protocol is for a single-site, biospecimen collection study in adult participants. Participants 
will sign an informed consent (or provide verbal assent if a legally authorized representative will 
sign the consent) before the biospecimen collection(s). In addition to the Principal Investigator 
(PI), trained study staff (e.g., research coordinators,and phlebotomists) can screen a potential 
participant to determine their study eligibility and can administer and sign the Informed Consent 
Form (ICF) with the participant and address all of their questions regarding the ICF and study 
design.  
As a next step, a research coordinator will set up a potential enrollment appointment with a 
contracted mobile phlebotomist.  Health condition, exceptive condition, and control participants 
will be recruited by one or any of the following resources, but not limited to:  
● Use of online marketing where potential participants receive study information from the 
Sanguine’s website or online participant referral program;  
● In the site investigators (or PI’s) clinic; and/or 
● Through community advocacy programs. 
● Participant Referral 
In all cases, potential participants will not be contacted by Sanguine study staff before agreeing to 
Sanguine’s Privacy Policy, available online, or by contacting Sanguine directly via phone or email.  
Participants who have agreed to participate and who have signed the ICF for Study SAN-BB-02 
(or given assent if a legally authorized representative will sign the ICF) will be eligible to 

 
 
 
 
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participate in this biorepository study. A signed ICF will be obtained from those participants who 
choose to participate. After obtaining the informed consent for this study, a professional 
phlebotomist, nurse practitioner, physician, or other qualified health professional will collect 
specified tissue samples. Blood samples will be drawn, and minimal risk tissue collection 
procedures may be performed at the participant’s home, workplace (in a private setting), other 
private settings, or selected clinics.  
 
Blood samples, serum, plasma, PBMCs, and other blood portions may be processed. Additionally, 
DNA and/or RNA may be extracted from the collected blood samples by Sanguine. Other 
biospecimens that may be donated will be stored in whole or delivered directly to requesting 
researchers and/or designated third parties. Biospecimens will be stored in Sanguine’s biobank 
indefinitely or until they are exhausted. 
The participant’s biospecimens will be annotated with self-report or medical review health 
information. The biospecimens and the linked clinical data will be de-identified. End users will 
not have any access to unique participant identifiers. 
Participants may be asked to complete a participant survey either in tandem with the biospecimen 
collections or following a separate, variable schedule that can be customized depending on need.  
 
4.3  Compliance with Laws and Regulations 
This study will be conducted in accordance with applicable U.S. Food and Drug Administration 
(FDA) and Department of Health and Human Services (DHHS) regulations, the International 
Conference on Harmonization (ICH) E6 Guideline for Good Clinical Practice (GCP), and 
applicable local, state, and federal laws. The Sponsor is responsible for personnel regulatory 
education in standard operating procedures and educational materials and training. The Office of 
Human Research Protection (OHRP) provides guidance on ethical and regulatory issues 
encountered in biomedical human participant’s research. Sanguine strives to adhere to OHRP 
guidelines and compliance with DHHS Code of Federal Regulations (CFR) Title 45, Part 46 (45 
CFR 46). 
Laboratory compliance is consistent with national good laboratory practices and follows the 
International Society of Biological and Environmental Repositories (ISBER) best practice.  
 
5  STUDY METHODS 
5.1  Sample Size 
The number of participants to be enrolled in this study is 20,000. The reason for 20,000 participants 
is that the Sponsor anticipates that over2 years of the study, at least 50% of the participants will 
discontinue study participation. Because this study aims to establish a tissue biorepository for 
future therapeutic and diagnostic research endeavors, the Sponsor requires accrual and 
maintenance of a large enough biospecimen cohort for research clients to obtain statistically 
significant results. Therefore, the Sponsor believes that this sample size will provide the required 
sample diversity and volume to achieve statistically significant results despite participation 
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Sanguine anticipates collecting biospecimens not only from participants with known health 
conditions but also from control participants with no known health conditions. These control 
biospecimens may be requested for comparison against other condition-specific biospecimens 
stored in the biobank. The total population of control participants is undetermined but will be 
included in the 20,000 total study participants. 
 
5.2   Participation Criteria 
Eligibility and applicable participant medical history will be overseen by a medical doctor 
throughout the course of the study to assess participant safety. About 85% of research requests can 
be completed by the protocol procedures, herein. Some research requests cannot be fulfilled using 
the procedures discussed below. These requests will be submitted to the IRB as an amendment to 
this protocol.  A medical doctor will review these exceptional collection requests to assess 
participant safety. 
 
5.2.1   Health Condition Group 
Health Condition Group Inclusion Criteria: 
● Persons 18 to 85 years of age at the date of informed consent. 
● If presenting with a history of a specific condition, the diagnosis is confirmable in the 
medical record. 
● Understands the procedures and requirements of the study by providing written informed 
consent (or verbal assent if a legally authorized representative will sign the ICF), including 
consent for authorization for protected health information disclosure. 
Health Condition Group Exclusion Criteria: 
● Persons younger than 18 years of age or older than 85 years of age at the date of informed 
consent.  
● Receipt of blood products 30 days before the study blood draw. 
● Receipt of an investigational (unapproved) drug 30 days before the study blood draw. 
● A confirmable disease of any medical condition that would increase potential phlebotomy 
risks. Such medical conditions include:  
o Severe or untreated cardiovascular diseases;  
o Bleeding disorders; 
o Late-stage chronic kidney disease; and/or 
o Conditions associated with chronic anemia.  
● Pregnancy 
● Has donated a unit of blood within the last 2 months at the date of informed consent. 
5.2.2   Exceptive Condition Group 
Exceptive Condition Group Inclusion Criteria: 
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● If presenting with a history of a specific condition, the diagnosis is confirmable in the        
 medical record. 
● A confirmable diagnosis of any medical condition that would increase potential phlebotomy  
risks. Such medical conditions include: 
o Severe or untreated cardiovascular diseases (including a stroke or myocardial  
o infraction within the last 2 months) 
o Bleeding disorders; 
o Late-stage chronic kidney disease;  
o Splenomegaly;  
o Pregnancy; and/or 
o Conditions associated with chronic anemia.  
● Understands the procedures and requirements of the study by providing written informed 
consent (or verbal assent if a legally authorized representative will sign the ICF), including 
consent for authorization for protected health information disclosure. 
Exceptive Condition Group Exclusion Criteria: 
● Persons younger than 18 years of age or older than 85 years of age at the date of informed 
consent.  
● Receipt of blood products 30 days before the study blood draw. 
● Receipt of an investigational (unapproved) drug 30 days before the study blood draw. 
● Has donated a unit of blood within the last 2 months at the date of informed consent. 
 
5.2.3   Control Group 
Control Group Inclusion Criteria: 
● Persons 18 to 85 years of age at the date of informed consent. 
● Understands the procedures and requirements of the study by providing written informed 
consent (or verbal assent if a legally authorized representative will sign the ICF), including 
consent for authorization for protected health information disclosure. 
 
Control Group Exclusion Criteria: 
● Persons younger than 18 years of age or older than 85 years of age at the date of informed 
consent.  
● Receipt of blood products 30 days before the study blood draw. 
● Receipt of an investigational (unapproved) drug 30 days before the study blood draw. 
● A confirmable diagnosis of any medical condition that would increase potential 
phlebotomy risks. Such medical conditions include: 
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o Bleeding disorders; 
o Late-stage chronic kidney disease; and/or 
o Conditions associated with chronic anemia.  
● Pregnancy 
● Requires a Legally Authorized Representative (LAR) for the study informed consent.  
● Has donated a unit of blood within the months at the date of informed consent. 
 
5.3  Participant Procedures 
The components of this study include: 
1. Participant recruitment 
2. Pre-consent Inclusion/Exclusion Screening 
a. Collection of demographic data 
b. Collection of self-report health history 
 
3. Cohort Placement 
a. Health Condition Group 
b. Exceptive Condition Group 
c. Control Group 
4. Study enrollment and Informed Consent process 
5. Biospecimen Collection 
a. Blood draw by a certified medical professional. Medical history considered. 
b. Minimal risk biospecimen collection 
c. Biospecimens that require a clinical procedure and are considered more than 
minimal risk 
i. Participant signs procedure-specific ICF 
ii. Procedures performed by trained medical professionals such as physicians 
and nurses and at study-approved sites 
6. Participant surveys, questionnaires, and PROs 
7. Recovery time assessment by the study staff depending on the type of specimen 
collected, medical history, and health of the individual.  
8. Data is securely stored through electronic and physical means. 
 
Please see Appendix C for participant safety workflow. 
 
5.3.1   Recruitment 
Participants may be recruited through identification by a study site investigator (e.g, PI) verbal 
referral by study participants, web-based media, or community advocacy events. 
 
Potential participants must consent to be contacted either by opting in to the Privacy Policy online 
or contacting Sanguine directly via email or phone. The signup process captures direct participant 
identifiers such as: 
● Name 
● Email address 

 
 
 
 
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● Telephone number 
● Residential address 
● Date of birth 
● Sex 
● Ethnicity 
● Have you been diagnosed with a medical condition? Yes/No 
● Have you participated in a clinical trial in the past 30 days? Yes/No 
By submitting this information, a health profile is generated within Sanguine’s database. This 
information is securely captured, and a research coordinator will contact the potential participant 
for the next steps in study participation. The initial contact call will consist of an introduction to 
the study and inclusion/exclusion evaluation. The screening process is described in more detail in 
section 4.3.2. 
 
5.3.1.1   Online Recruitment 
Participants may be recruited online through patient advocacy websites, social websites such as 
Craigslist, Sanguine Bioscience’s Facebook page, and Sanguine’s website. The Sanguine website 
provides information to potential participants about the Sanguine biobank through its website, 
explaining study objectives and participation requirements. Participants may also receive updates 
regarding condition-specific current active biospecimen collections. 
Participants can also refer friends and family to participate in the biobank study. Current 
participants can enroll on Sanguine’s website. The referral recruitment method is initiated and 
controlled solely by study participants.  
All potential participants recruited/referred to Sanguine’s biobank study must consent to be 
contacted, permitting study staff to contact them. Through the successful completion of study 
procedures and referral, participants may be awarded points.  
 
5.3.2   Potential Participant Inclusion/Exclusion Screening 
From the screening process, study staff will determine if the potential participant can enroll in the 
study or not. After the potential participant has signed up, a study staff member will contact the 
potential participant to introduce the study and evaluate participant inclusion/exclusion. During 
this process, direct participant identifiers will be collected. Data collected include but are not 
limited to a physical address, date of birth, and general medical history associated with a specific 
condition. Please see Appendix D for an example of medical information collected. 
 
5.3.3   Potential Participant Cohort Placement 
After the screening process, trained study staff will review the self-reported medical history to 
determine cohort placement. If the participant does not report any medical conditions or 
remarkable medical history, they will be placed in the control cohort. If the participant has reported 
a medical condition that could potentially increase the presentation of risks associated with 
phlebotomy, such as bleeding disorders, severe or untreated cardiovascular diseases, late-stage 
chronic kidney diseases, pregnancy, or splenomegaly, the participant will be placed in the 
exceptive condition cohort. This cohort identification is designed to distinguish participants who 
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in the health condition group. If a participant does not meet inclusion/exclusion criteria, they will 
be notified that they cannot participate in this study. 
 
5.3.4   Informed Consent 
The informed consent process will occur either at the Sponsor site or in the comfort of the 
participant’s home, where trained study staff will explain the ICF, study design, participation 
requirements, and reasonable risks. Participants will be encouraged to ask questions regarding the 
ICF, study design, and what is being asked of them. The study staff will assess the participants 
understanding of the entire informed consent, including but not limited to the voluntary nature of 
study participation, their ability to withdraw from the study at any time, and participation 
requirements. After signing the ICF, participants will get a copy of the signed ICF for their records. 
If the participant is unable to give informed consent, a legally authorized representative (LAR) 
may sign the ICF, in addition to the participant’s verbal assent. Trained study staff will decide 
whether a LAR may or may not be used. 
Participants requiring LARs include but are not limited to participants with mental health 
disorders, genetic disorders such as Huntington’s disease, and neurological conditions such as 
Alzheimer’s disease.  
For this study, a legally authorized representative may include: 
1. An agent pursuant to an advanced health care directive; 
2. A spouse, or 
3. A child having the authority to make health care decisions. When possible, the participant 
will be involved in the informed consent process and provide assent to the best of their 
ability.  
 
Since Sanguine acts as a Sponsor and as a site, there will be two scenarios for participant 
consenting and data transfer: 
1. As a site, Sanguine will implement a software-as-a-service (SaaS) provider of electronic 
signature technology and transaction management solutions, so participants electronically 
sign the ICF and authorize the release of medical records using a tablet or computer from 
the comfort of their home or through a secure website. 
2. Alternatively, if the participant prefers, physical ICFs and information release 
authorization may be completed using hardcopy documents. 
 
5.3.5   Biospecimen Collection 
Biospecimen collection will occur either at a study-approved clinic, in the comfort of the 
participant’s home, at the participant’s workplace (in a private setting), or in other private settings. 
Participation requires at least one type of tissue collection described below. Biospecimens are 
collected as a donative gift from the participant to the Sponsor. 
 
5.3.5.1 Blood Collection 
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95% of biospecimen requests. Blood will generally be collected by venipuncture from a medical 
professional certified in phlebotomy. Participants may also be asked to provide a microsample of 
blood via fingerstick. Fingerstick samples will be collected on a blood card, such as a dried blood 
spot (DBS) card, or into a microtainer. Researchers may use the blood cards for specific testing of 
biomarkers or isolating genetic material.  
Blood collection volumes are dependent on which cohort the participant is placed and self-reported 
medical data (see Table 1). Blood may be collected every 7 days, but the total volume collected 
during a 6-week period may not exceed the Table 1 volumes. Maximum blood collection volumes 
in Table 1 may be collected at one time  
 
Table 1: Maximum Blood Collection Volume by Cohort 
Cohort 
Blood Draw Volume (mL) 
Health Condition 
≤100mL  
Exceptive Condition 
≤60mL 
Control 
≤180mL  
The maximum blood collection volume within a 6-week period by cohort. 
 
Participants within the health condition and control groups who weigh less than 110 pounds and/or 
are older than 85 years old will have a maximum collection volume of 75mL within a 6-week 
period. 
 
Before the phlebotomy procedure, a Sanguine designated phlebotomist will assess the participants 
health by asking questions like, “Do you feel healthy today?” and noting any physical symptoms 
that may require the blood draw to be aborted. The phlebotomist then decides if the blood draw 
can continue as scheduled. The blood draw appointment follows phlebotomy best practices set 
forth by the College of American Pathology (CAP) and the World Health Organization (WHO). 
Venipuncture is attempted no more than 3 times. After a third failed attempt, the blood draw is 
canceled. After the blood draw, the phlebotomist will remain with the participant until the wound 
has successfully clotted and/or the participant reports that they feel well enough to resume light 
activities. 
 
5.3.6   Control Group 
Each participant’s health history will be collected before the blood draw to determine the health 
and safety of each participant during the venipuncture procedure. The participant’s self-reported 
medical history is reviewed by trained study staff to assess any medical history that would place a 
participant at increased risk during a blood collection. 
If the participant qualifies for the control group and a researcher has requested the maximum blood 
volume to be collected, the study staff must assess the health of the participant to determine if they 
are healthy enough to undergo a 180mL blood draw. The following questions are asked to the 
participant to assess the s safety during the 180mL blood draw: 
 
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1. Is the participant’s weight ≥110lbs? 
2. Is the participant younger than 85 years old? 
3. Does the participant have difficulties with blood draws (e.g., hard stick)? 
 
5.3.7   Optional Biospecimen Collection 
Participants may be asked to donate other biospecimens such as saliva, stool, urine, sputum, semen, 
hair, nail clippings, skin cells from a skin or swab or skin taping strips, cells from the mouth via 
buccal swab, and respiratory mucosa or nasal samples from a nasal or nasopharyngeal swab. The 
collection methods of these biospecimens are considered no more than minimal risk to the 
participant. 
Participant facing visit guides may be created for any required self-collections. This documentation 
will be approved by the IRB for approval prior to any applicable collection taking place.  
 
5.3.8   Participant surveys, questionnaires, and PROs 
Participants may be asked to complete a survey, questionnaire, or PRO, either in conjunction 
with a biospecimen collection or following a separate, variable schedule.  
Sanguine sends a single question, non-study specific survey to participants post-screen, and post-
scheduled appointment for feedback on their experience.  
 
5.3.9   Recovery Time 
Depending on how much blood is drawn, pertinent health history (including current medications), 
and other tissue donation procedures performed, the phlebotomist and/or study staff will determine 
how much time a participant will need to recover from the procedure. Steps to recovery include 
hydration, a snack, and a period of rest before performing strenuous activities or heavy lifting. 
Phlebotomists will remain with the participant after the phlebotomy procedure to ensure proper 
clotting and the participant feels well-enough to perform daily activities. 
After the visit is completed, Sanguine will send a post-visit survey to the participants for feedback 
on their experience. Refer to Appendix D for a survey example. 
 
5.3.10   Collection of Protected Health Information (PHI) 
Participants will have their protected health information collected in two ways: self-reported data 
and a thorough review of their medical records. Upon enrollment, participants will be asked to 
authorize the release of their health information. Participants who deny this authorization may 
affect their enrollment within the biobank study. Upon receiving this authorization, study staff will 
request medical data from the appointed healthcare provider. This data will be secured by physical, 
electronic, and administrative means. 
The biobank has security measures to protect the participant’s PHI and are discussed in Section 6 
and Section 7.  
 
5.4   Confidentiality/De-identification Process 

 
 
 
 
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The research on the biospecimens will be performed without the use of the participant’s names, 
pictures, address, or any government-issued identification numbers (such as social security 
number) or any other direct identifiers as stated in the Health Insurance Portability and 
Accountability Act (HIPAA). Participants will be randomly assigned a unique participant 
identifier. This number will be used to identify the participant on all documents. 
 
5.5   Direct Access to Source Data/Documents 
The investigator and/or institutions involved in this study will agree to allow trained employees  
from Sanguine direct access to all source data and documents, including the participants complete 
medical records. Access must also be granted to authorized auditors, IRB reviewers, and all 
applicable regulatory bodies, as necessary.  
 
5.6   Sample Processing and Storage 
Sanguine follows the International Society for Biological and Environmental Repositories 
(ISBER) and NCI repository best practices to assure quality biospecimen processing and storage. 
Guidelines for these best practices have been adapted to Sanguine’s specific laboratory space and 
personnel and are specified in applicable lab procedures. In accordance with these guidelines and 
to assure quality, each type of biospecimen extracted and processed on behalf of the Sponsor 
follows 
a 
specific 
standard 
operating 
procedure.  
 
Biospecimens extracted and processed by Sanguine for storage and redistribution to researchers 
include, but are not limited to, serum, plasma, PMBC’s, DNA, and RNA. Biospecimens are stored 
in cryogenic containers. To control biospecimen quality the cryogenic containers are constantly 
monitored for temperature oscillations, which are recorded electronically. In the future, the 
biobank may store dehydrated samples at ambient temperature as approved and accepted by 
biorepository storage practices. As a part of the biorepository protocol, specimens will remain at 
Sanguine indefinitely or until they are distributed to an approved research study. 
Detailed sample collection and shipping documentation will be provided to each site by Sanguine. 
Samples collected may be shipped overnight directly to the requesting researcher and/or 
designated third party, dropped off same-day to the requesting researcher, or shipped overnight to 
one of Sanguine’s processing labs. Shipments may be frozen, ambient, or refrigerated. The lab 
verifies incoming samples before processing begins. All direct participant identifiers are blinded 
to the laboratory staff and researchers. Parent samples will be labeled with the unique participant 
identifier, as specified in the applicable lab procedures. 
All procedures for collecting, handling, storing, and shipping biobank materials are specified in 
the biorepository standard operating procedures or specific study documentation. Sanguine 
follows the International Society for Biological and Environmental Repositories (ISBER) and NCI 
repository best practices to assure quality biospecimen processing and storage. 
 
5.7   Biospecimen & Data Distribution Procedures 
Sanguine will provide quality biospecimens to institutionally approved pre-clinical and clinical 
investigator-led studies for diagnostic, therapeutic, and preventative research. Once the Sponsor 
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ship the requested biospecimens at either room temperature, refrigerated, or cryogenically to the 
client. The Sponsor will deliver the associated, redacted health information to the client either 
electronically or physically. Third parties receiving annotated biospecimens or access to the 
electronic biospecimen library must agree to Sanguine’s terms and conditions and/or complete a 
Materials Transfer Agreement to minimize risks associated with the transfer of biospecimens and 
health information. Third parties must agree to use biospecimens for research purposes as specified 
in the informed consent and agree not to seek out the identity of participants.  
The Sponsor will also provide potential client investigators with access to available de-identified 
biospecimens and clinical information (de-identified DNA sequences and associated de-identified 
electronic medical records and participants’ self-reported but de-identified information) through a 
data tracking application.  
● 
 
5.8   Study Termination 
Participants will be considered inactively involved in SAN-BB-02 indefinitely or for as long as 
their biospecimens and data remain stored within the biobank. A participants participation may be 
terminated partially or completely. 
Guidelines for these best practices have been adapted to Sanguine’s laboratory partners and 
personnel and are specified in Sanguine’s SOPs.  
 
5.9   Participant-Initiated Withdrawal 
Participants have the right to withdraw from the study at any time. There is no penalty if the 
participant decides to end his/her participation. For a participant to withdraw from the study, a 
written or verbal request must be made to Sanguine’s study staff. Participants do not need to give 
a reason for changing their minds. Biospecimens and health data may be handled after withdrawal 
in two ways: 
 
1. No Longer Interested. The study no longer has contact with the participant, and the 
authorization for the release of information expires. The biobank still has permission to use 
all biospecimens and data stored within the biobank at the time of withdrawal. 
2. No Longer Interested - Destroy Remaining Samples/Data. The study no longer has 
contact with the participant, and the authorization for the release of information expires. 
All samples and data remaining in the biobank are destroyed. 
If it is not clear how the participant wants the samples and information handled from your written 
request, the Sponsor will treat the withdrawal as “No Longer Interested.” 
 
The biobank cannot recall samples and data that have already been given to third-party researchers. 
 
5.10   Investigator-Initiated Withdrawal 
The site investigator or Sponsor may remove a participant from the study at any time and for any 
reason. Since the biobank does not provide medical treatment or health care, there will be no 
penalty imposed upon the participant. Reasons for which the PI or site investigator may terminate 
a participant’s enrollment may include but are not limited to: the participant does not follow study 
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6   RISK/BENEFIT ASSESSMENT 
6.1   Potential Risks 
Potential risks associated with this study include physical and data-related risks. 
Physical risks are those associated with venipuncture. At the time of the blood draw, the participant 
may experience a small amount of pain associated with introducing the needle into the skin, 
bruising at the venipuncture site, and a small risk of light-headedness or feeling faint, which are 
commonly associated with blood draws in general. There may also be slight discomfort or skin 
irritation due to hair sampling or skin taping.  
This biorepository study is a study where biospecimens and associated medical data are stored 
indefinitely. Therefore, the main data-related risk is a breach of privacy. Though rare and 
unforeseen, a participant’s private health information or identifiable information may become 
available outside the study. If a participant’s insurance provider or employer becomes aware of the 
participant’s study enrollment or experimental results associated with their specimens, the 
insurance provider or employer may participant the participant to health discrimination. 
 
6.2   Risk Classification 
The risk for the participant is minimal. There will be no additional discomfort to the participant 
beyond that ordinarily encountered during the performance of routine phlebotomy. Optional 
biospecimen donations are also considered a minimal risk and are collected via non-invasive 
means.  
Some optional study procedures are considered more than minimal risk. If participation in such 
procedures is requested, an addendum to the ICF will be reviewed by the participant before the 
procedure is conducted. This addendum will describe all potential risks associated with these 
procedures. 
 
6.3   Protection Against Risks 
Physical risks associated with venipuncture will be minimized by utilizing experienced 
phlebotomists, nurse practitioners, or physicians to draw the blood samples. If the participant 
suffers a research-related injury, medical expenses will not be covered by the Sponsor. Study 
participants are not precluded from seeking to collect compensation for injury related to 
malpractice, fault, or blame on those involved in the research. 
All efforts will be made to minimize data-related risks through several levels of protection. First, 
potential participants are made aware of the potential risks outlined within the ICF during the 
informed consent process. At the time of potential participant s consent to be contacted either by 
opting in to the Privacy Policy online or contacting Sanguine directly via email or phone, the 
participant is given a unique participant identifier, which does not utilize any of his/her direct 
identifiers (e.g., birth date, zip code, or social security number) as outlined in HIPAA. So, the 
participant is identified within the study only by this study ID. Biospecimens are processed and 
stored with sample-specific identification, which is electronically linked to the study ID. 
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with the participant’s direct identifiers unless one has administrative access to the linking list 
portion of the database. Sanguine is guided by the 45 CFR 160 and 164, also known as the Security 
Rule within HIPAA, to protect participants’ privacy and confidential information. 
Sanguine uses honest brokers to collect linking information of participants with study identifiers. 
Such honest brokers are participant to privacy policies and procedures created by Sanguine that 
adhere to applicable privacy regulations. Access to participant identifiers is physically restricted 
via password-protected levels within the study database. All physical private health identifiers are 
destroyed following HIPAA regulations. In addition, the study database is electronically monitored 
and records all information accessed by each study member. The study may seek a Certificate of 
Confidentiality (Certificate) to provide an extra layer of privacy protection to study participants. 
A Certificate may be sought by any research study that collects private health information and is 
awarded by the National Institute of Health (NIH) to protect human participant s in research against 
compulsory legal demands. It is possible participants diagnosed with an infectious disease may 
participate in the biobank. PHI protection for this population is considered of the utmost 
importance to discourage any potential health or social discrimination. All employees handling 
PHI will be trained regarding the importance of such sensitive information.   
 
6.4   Potential Benefits 
As a biorepository, this study aims to collect, store and distribute biospecimens for future research 
endeavors. Therefore, this study may not offer direct or immediate personal benefit to study 
participants. However, participant biospecimens utilized in future research may lead to new 
diagnostic and therapeutic techniques, which will benefit future participants with similar diseases. 
 
7   ETHICAL CONSIDERATIONS 
7.1   Online Recruitment 
Participants can refer friends and family to Sanguine’s IRB-approved studies through 
the Sponsor’s website. The refer-a-friend recruitment method is initiated and controlled by 
participants. The Sponsor stores no contact information regarding third parties. Therefore, a third 
party voluntarily decides to contact Sanguine or not. Sanguine does store participant referral 
information and provides compensation for referrals. Sanguine personnel can contact potential 
participants only if the potential participant s provide consent to be contacted either by opting in 
to the Privacy Policy online or contacting Sanguine directly via email or phone. This policy 
highlights the participant’s right to voluntary participation. 
After a successful referral, Sanguine may make a monetary donation to the participant’s nonprofit 
organization of choice. Sanguine’s donation to nonprofit organizations on behalf of participants 
who successfully refer friends and family is innocuous. Since Sanguine’s IRB-approved protocol 
does not provide treatment options for participants and is considered minimal risk, participants do 
not feel obligated or dependent upon the study or study staff for healthcare management. 
Therefore, such a donation would not be considered ethically negligent and does not create undue 
influence by the Sponsor. 
 
7.2   Informed Consent Form 
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or his/her designees must obtain a signed ICF for each participant and healthy donor participant. 
The Sponsor will retain the signed ICF. A copy of the signed ICF is given to each participant for 
their records. 
The collection and blood processing/storing sites and the PI’s Sponsor designees will comply with 
the study protocol and be responsible for the administration of the ICF and for acting in accord 
with HIPAA requirements. The biospecimens collection site is responsible for the accuracy and 
completeness of the data submitted and for making medical records and source documents 
available to the study Sponsor. 
Sanguine research coordinators treat the informed consent as a process and not as a single event, 
carefully explaining all aspects of the study to each participant in language readily understood by 
the participant. The risks and benefits of participating in this study will be explained to each 
potential participant before entering the study. Participants will be made aware that their 
participation is entirely voluntary, and they may withdraw from the study at any time without 
penalty or repercussions. As a biorepository study, participants must understand their annotated 
samples will remain stored at Sanguine indefinitely or until a client requests them. In addition, the 
participant has the option of being re-contacted by the Sponsor to participate in other research 
studies. This preference is recorded on the ICF.  
Sanguine or a designee is responsible for adequate training of the biospecimen collection site 
personnel and for monitoring these sites as required.  
The Sponsor trains Sanguine research coordinators to explain and answer questions regarding the 
study to ensure the participant is fully informed about what is being asked of them.  
 
The Sponsor allows study staff, directly and indirectly, involved with this biobank study and their 
family and friends to enroll and participate in the study. Since this study does not include any type 
of medical intervention or health care and active participation in the study is expected to be about 
one hour—or as long as it takes to complete the ICF process and the required biospecimen 
collection—undue influence or coercion of this population is minimal. All protected health 
information stored within the biobank database is treated with the same respect and care as all 
other participants. No unauthorized study staff may have access to this information, and 
employment status will not be influenced by information collected under this study as required by 
the Genetic Information Nondiscrimination Act (GINA). 
 
7.3   Potential Collection from Participants with Infectious Diseases 
People with infectious diseases are considered a vulnerable population for human participant’s 
research because of multiple social, medical, and psychological issues. The biobank will consider 
these issues when recruiting and enrolling such participants. This study does not offer any medical 
intervention, and therefore, the Sponsor believes the risk of coercion or dependence upon the study 
staff will be minimal. The biobank’s main risk is the privacy of all participants, and therefore, the 
privacy risks for participants with infectious diseases are already a top concern for the study. 
 
7.4   De-identifying Protected Health Information Under the Privacy Rule and 
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Ethical issues of protection of privacy are the biobank’s primary concern. The biorepository 
purpose is to supply the pre-clinical and clinical research community with quality biospecimens to 
promote therapeutic and diagnostic development. The repository provides well-characterized 
specimens annotated with relevant medical data derived from protected health information to 
facilitate good research. A prevailing concern regarding the inadvertent disclosure of such private 
information to employers or insurance providers exposes research participant s to potential 
discrimination. Health discrimination may include denial of healthcare coverage or even 
workplace retribution. Anonymizing samples would best protect participant s’ identifying 
information but would severely limit the utility of experimental results. Therefore, to maximize 
study benefits and minimize participant risk, the Sponsor will make every effort to protect private 
health information. 
Several laws are in effect to protect research participants and their privacy. GINA legally protects 
Americans from genetic discrimination, allowing them to pursue genetic testing for clinical or 
research purposes freely. This act is an important step to address the potential risks of storing 
genetic information. Still, research entities should look to themselves to ensure maximum efforts 
are applied to protect participant identifying information. To manage the information collected for 
sample annotation in the study database, the Sponsor has implemented a data breach notification 
system as specified in the Health Information Technology for Economic and Clinical Health 
(HITECH) Act. Sanguine adheres to the Office of Human Research Protection (ORHP) guidelines 
to best protect our study participants. Sanguine is also pursuing the award of an NIH Certificate of 
Confidentiality (Certificate) to further protect participant privacy from legal requests. A Certificate 
is a study-specific barrier to disclosure. 
Health Insurance Portability and Accountability Act (HIPAA) defines policies and guidelines for 
maintaining participant privacy and confidentiality; specifically, the Security Rule outlines 
administrative, electronic, and physical barriers of protection against disclosure. Before seeking to 
release this health information to the Sponsor’s clients, including clinical research organizations, 
research institutions, pharmaceutical, and biotechnology companies, the Sponsor must determine 
that the information no longer contains direct identifiers by removing specific pieces of 
information from each record that could directly identify a participant. Since the Sponsor does not 
participate in medical treatment or any therapeutic or diagnostic facet of healthcare, Sanguine is 
not considered a covered entity under the Privacy Rule. Therefore, Sanguine is not required by law 
to remove the 18 elements specified in HIPAA to comply with the Safe Harbor part of the Privacy 
Rule. The Sponsor does remove as many as possible to assure privacy protection while maintaining 
research relevance. The only one of the 18 elements the Sponsor currently does not redact is the 
treatment date to provide a complete health history to researchers. 
 
7.5   Regulatory Compliance 
This study will be conducted according to applicable requirements outlined in the FDA Code of 
Federal Regulations Title 21 and the ICH E6 Good Clinical Practice. The Sponsor is responsible 
for personnel regulatory education in standard operating procedures, educational materials, and 
training. ORHP provides guidance on ethical and regulatory issues encountered in biomedical 
human participant’s research. 
Sanguine strives to adhere to OHRP guidelines and is therefore compliant with the Health and 

 
 
 
 
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Human Services Code of Federal Regulations Title 45, Part 46 (45 CFR 46). 
Laboratory compliance is consistent with national good laboratory practices and follows the 
International Society of Biological and Environmental Repositories (ISBER) best practices. 
Though the Sponsor site does not process tissue for clinical use, the Sanguine laboratory partner 
labs look to Clinical Laboratory Improvement Amendments (CLIA) for operations and quality 
standards guidance. 
 
7.6   Principal Investigator 
The PI, together with any designated sub-investigators, has the overall responsibility for the 
conduct and compliance of this biospecimens collection study according to this protocol and 
GCP. 
 
8   RECORD RETENTION 
Sanguine requires that all study-related documentation be retained and stored in Sanguine’s database 
indefinitely. 
 
9   FINANCIAL OBLIGATION & COMPENSATION 
9.1   Financial Obligation of the Participants 
The participant s will not incur any financial obligations. 
 
9.2   Financial Compensation for Participation 
The participants will be monetarily compensated, and Sanguine may also donate an equal 
amount on their behalf to a nonprofit organization of their choosing. 
 
Although the research results, including donated biospecimens, may be patentable or have 
commercial value, the study participant will have no legal or financial interest in any commercial 
development resulting from the research. 
 
10   INTELLECTUAL PROPERTY 
All inventions and discoveries, including without limitation identification of markers and 
therapeutic drugs and all information and results from such discoveries, whether patentable or not, 
arising from this study or this protocol, shall be the property of the client investigator that procured 
associated samples and participant data from the Sponsor. 
All rights, title, and interest in such discoveries and inventions, whether patentable or not, and all 
intellectual property rights therein shall be assigned to the client investigator that procured 
associated samples and participant data from the Sponsor. 
All donated (remaining) samples are solely the property of Sanguine to be used solely in 
accordance with this protocol and the informed consent form. 
 

 
 
 
 
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11   APPENDIX A – WORKS CITED 
 WORKS CITED 
 
1. Coppola L, Cianflone A, Grimaldi AM, et al. Biobanking in health care: evolution and future 
directions. J Transl Med. 2019;17(1):172. Published 2019 May 22. doi:10.1186/s12967-019-
1922-3 
2. Massett HA, Atkinson NL, Weber D, et al. Assessing the need for a standardized cancer 
HUman Biobank (caHUB): findings from a national survey with cancer researchers. J Natl 
Cancer Inst Monogr. 2011;2011(42):8-15. doi:10.1093/jncimonographs/lgr007 
3. Swede H, Stone CL, Norwood AR. National population-based biobanks for genetic 
research. Genet Med. 2007;9(3):141-149. doi:10.1097/gim.0b013e3180330039 
4. National Cancer Institute. What is cancer? National Cancer Institute website. Accessed July 
21, 2021. https://www.cancer.gov/about-cancer/understanding/what-is-cancer 
5. Febbo P, Ladanyi M, Aldape K, et al. NCCN Task Force Report: Evaluating the Clinical 
Utility of Tumor Markers in Oncology. JNCCN. 2011; 9(5). Published 2011 November. 
https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.734.4398&rep=rep1&type=pdf 
6. Din OS, Woll PJ. Treatment of gastrointestinal stromal tumor: focus on imatinib 
mesylate. Ther Clin Risk Manag. 2008;4(1):149-162. doi:10.2147/tcrm.s1526 
7. Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Del Cañizo-Gómez FJ. Type 2 
diabetes and cardiovascular disease: Have all risk factors the same strength?. World J 
Diabetes. 2014;5(4):444-470. doi:10.4239/wjd.v5.i4.444 
8. National Institutes of Health (US); Biological Sciences Curriculum Study. NIH Curriculum 
Supplement Series [Internet]. Bethesda (MD): National Institutes of Health (US); 2007. 
Understanding Human Genetic Variation. Available from: 
https://www.ncbi.nlm.nih.gov/books/NBK20363/ 
9. Graves PR, Haystead TA. Molecular biologist's guide to proteomics. Microbiol Mol Biol 
Rev. 2002;66(1):39-63. doi:10.1128/MMBR.66.1.39-63.2002 
10. Liu X, Locasale JW. Metabolomics: A Primer. Trends Biochem Sci. 2017;42(4):274-284. 
doi:10.1016/j.tibs.2017.01.004 
11. Kiechle, F. L. (2010). An Introduction to Phlebotomy, 13th Ed. Northfield, Illinois: College 
of American Pathologists. 
 
 

 
 
 
 
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13   APPENDIX B – PARTICIPANT SAFETY PROCEDURE FLOW 
 
 

 
 
 
 
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14   APPENDIX C – EXAMPLE OF DATA COLLECTED 
 
 
 

 
 
 
 
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15   APPENDIX D –VISIT SURVEY EXAMPLES 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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16   APPENDIX E – ABBREVIATIONS 
 
CFR 
Code of Federal Regulations 
DNA 
Deoxyribonucleic acid 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GINA 
Genetic Information Nondiscrimination Act 
HHS 
Health and Human Services 
HIPAA 
Health Insurance Portability and Accountability Act 
HITECH 
Health Information Technology for Economic and Clinical Health 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
iPS cells 
Induced pluripotent stem cells 
IRB 
Institutional Review Board 
ISBER 
International Society of Biological and Environmental Repositories 
LAR 
Legally Authorized Representative 
mL 
Milliliter 
NIH 
National Institute of Health 
OHRP 
Office of Human Research Protection 
PBMC 
Peripheral blood mononuclear cells 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PROs 
Patient reported outcomes 
RNA 
Ribonucleic acid 
WHO 
World Health Organization