Clinical trial NCT02757898
Conditions: Anemia
Keywords: Red Blood Cell (RBC) transfusion Biotin labeled red blood cells
Sponsor: Emory University
Start date: 2017-01-11; Completion date: 2018-11-13
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this research is to study how red blood cells (RBCs) survive in a person's circulation, and how that survival may be different in red blood cells that are donated and stored prior to being transfused. Investigators will study this by collecting blood samples from participants, "labeling" RBCs with a naturally occurring vitamin, biotin. The RBCs will then be re-infused back into the participant and blood samples will be taken weekly for 10 weeks to assess the number of labeled cells in the samples.

Detailed description:
The purpose of this research is to study how red blood cells (RBCs) survive in a person's circulation, and how that survival may be different in red blood cells that are donated and stored prior to being transfused.

In this study, blood is collected from healthy subjects, processed into packed red blood cell units, and either immediately afterwards or 40-42 days later the packed red blood cells are labeled with biotin. The biotin-labeled red blood cells are then re-infused back to the donor (autologous transfusion). Blood samples are then taken from the subject every week for up to 70 days (10 weeks) to track survival of the labeled red blood cells.

This study also seeks to demonstrate that biotin-labeled RBCs can be safely transfused back to autologous subjects without any adverse reactions. All participants will be followed to watch for the development of antibodies against biotin-labeled RBCs.

Arms: arm 1: Blood will be drawn from participants and labeled with biotin before being re-infused back to the participant. Blood samples will be obtained weekly over 10 weeks.
Interventions: intervention 1: Biotin-Labeled Red Blood Cells (RBCs)
Intervention descriptions: intervention 1: 500 mL of blood will be drawn from each participant. The blood will be processed into a packed RBC unit.

For participants 1 and 2, the RBCs will be labeled with biotin at three pre-defined concentrations of biotin labeling reagent (2, 6, 18 µg/mL of RBCs) and the labeled RBCs will be re-infused into the participant on the same day of collection.

For participants 3 through 8, the RBCs will be stored at 2-6 C for 40-42 days before being labeled with three pre-defined concentrations of biotin labeling reagent (2, 6, 18 µg/mL of RBCs) and re-infused into the participant.

Participants will have a 5 mL blood sample drawn within a few minutes of the re-infusion, the day after the re-infusion and then weekly for 70 days (10 weeks) to track the survival of the infused biotin labeled RBCs.

Protocol documents:
Prot_SAP_000.pdf: 
RBC Survival Validation in Adult Humans Under Condition of Normal RBC Survival
NCT02757898
December 12, 2018


Protocol version:  2
Version date: December 12, 2018
    Page 
1
1
RBC SURVIVAL VALIDATION IN ADULT HUMANS UNDER CONDITIONS 
OF NORMAL RBC SURVIVAL
SUBMITTED BY:
John D. Roback, MD PhD
Associate Professor, Pathology and Laboratory Medicine
Director, Center for Transfusion and Cellular Therapies
Emory University School of Medicine
FUNDING:
National Institutes of Health, R01 HL095479-06:  Adverse effects of RBC transfusions: 
A unifying hypothesis. 2014 –2018.
National Institutes of Health Program Project Grant, 2 P01 HL 086773-06A1:  
Mechanisms and interventions addressing serious hazards of transfusion and cellular 
therapies. 2015 – 2020. 
SPONSOR:
John D. Roback, MD PhD


Protocol version:  2
Version date: December 12, 2018
    Page 
2
2
Study Summary:
Study phase:  Phase I
Duration of study:  1-2 years
Methodology: Blood is collected from healthy subjects, processed into packed red blood cell 
units, and either immediately afterwards or 40-42 days later the packed red blood cells are 
labeled with biotin.  The biotin-labeled red blood cells are then transfused back to the donor 
(autologous transfusion), and subsequently blood samples are taken from the subject for up to 
154 days (22 weeks) to track survival of the labeled red blood cells.  
Study Site:  Emory University Hospital 
Approximate number of subjects:  8
Investigator’s affiliation:  Department of Pathology and Laboratory Medicine, Emory University 
School of Medicine
Background Information / Significance:
Name of drug:  “biotinylated red blood cells (b-RBCs)” 
Active ingredients:  Biotin (that is covalently attached to human adult and red blood cells).
Pharmacological class:  Water soluble B group vitamin.
Structural formula:  We will utilize sulfo-NHS “short chain” biotin (MW=443.43) in a reaction with 
the amino groups on RBC surface proteins as shown in the following reaction diagram:  
Formulation:  Indicated as “Biotinylated Protein” in the reaction diagram above. 
Dosage:  The concentration of sulfo-NHS short chain biotin to be used in each labeling reaction 
will range from 2-18 g / mL of packed RBCs. Previous results suggest that these 
concentrations of biotin will produce RBCs with (on average) 25 – 250 pmol of biotin / mL of 
packed RBCs.  Thus, a study in which 3 aliquots of b-RBCs are infused (25 mL each; labeled 
with 2, 6 or 18 g / mL of packed RBCs) will result in the transfusion of approximately 8.8 nmol 
of biotin (3.8 g).  As a point of reference, this amount is well below the recommended daily 
intake (RDI) of biotin for adults of 100 g; a typical multivitamin contains about 30 g of biotin.  
Thus, this dosage should be safe. 
Route of administration:  Intravenous.
Summary of results from prior clinical studies and clinical data to date:  There is no known 
toxicity of biotin in doses vastly exceeding those we propose [1, 2]. Daily doses up to 200 mg 
orally and up to 20 mg intravenously have been given to newborn infants to treat biotin-
responsive inborn errors of metabolism and acquired biotin deficiency.  No toxicity at these 
doses under these conditions has been reported [3-5].  
Based on the growing number of published reports using biotinylated RBCs for measuring RBC 
volume and RBC survival in humans [6-10], the use of biotinylated RBCs is becoming 


Protocol version:  2
Version date: December 12, 2018
    Page 
3
3
increasingly accepted as a safe and effective method for determining RBC volume and survival. 
Biotinylated RBCs have been used to study RBC volume and RBC survival in humans since 
1988 [1].  Since that time, there have been no definitive risks of biotinylated RBCs noted in 
studies in adults in which a total of 96 individuals have been studied [1, 6, 9, 11-16].  In addition 
to these studies in adults, we are aware of 139 newborn infants in the first months of life who 
have been studied with biotinylated red cells also for measurement of red cell volume and red 
cell survival [7, 10, 17, 18].  With the exception of one previous paper [6], none of the other 
reports described any safety problems with biotinylated RBCs.  In the paper by Cordle et al, 
15% of the adult subjects developed antibodies to biotinylated RBCs.  In none of these adult 
subjects were antibodies to biotin per se identified.  Moreover, the antibodies to biotinylated 
RBCs were transient and did not affect RBC survival, a finding which is supported by a study of 
biotinylated RBCs administered to adult baboons [19].  
Risks and benefits to study subjects: There will be no specific benefits to the 8 subjects to be 
studied with this protocol.
The risks are those that may be seen with blood collections and blood transfusions.  These 
include: feeling queasy, throwing up, chills or feeling cold, fainting, feeling light in the head, 
seizures, discomfort around the needle, bruising, infection, swelling around the needle site, 
blood loss, and red cell destruction.  Other risks could include skin rashes and hives. Since only 
a small amount of blood will be drawn, these risks are probably minimal.  
Transfusion recipients may also potentially get a blood infection when they are transfused with 
the biotinylated red blood cells, although we take a large number of precautions in the lab when 
we label the RBCs to minimize the chances of this problem, which would be a very rare 
occurrence.  
Many volunteers and patients in other centers have participated in a similar study, and they 
have not noted any of these adverse effects.  The main risk they did observe was the 
occasional development of an immune response to the biotin label on the RBCs; in the same 
way that transfusion recipients develop antibodies against alloantigens on transfused RBCs, 
these recipients can also form antibodies against the novel antigen formed by biotin, the 
crosslinker, and the crosslinked target on the RBCs [20].  There appear to be no adverse effects 
of these antibodies by themselves (eg, no effects of recipient biotin levels or function of biotin-
dependent processes). Furthermore, the risk of developing these antibodies appears to be 
reduced when using lower doses of biotin for labeling (eg, < 18 g/mL such as we propose in 
this protocol).  Nonetheless, under the very specific case where study subjects who have 
developed these antibodies are later transfused with additional biotin-labeled RBCs, the b-RBCs 
in the second transfusion are eliminated from the recipient’s circulation with accelerated 
kinetics.  Because of these occurrences, the FDA requires that recipients be tested for the 
presence of anti-biotin antibodies following their first transfusion of biotin-labeled RBCs, and that 
the subset of recipients who make anti-biotin antibodies be eliminated from future studies where 
biotin-labeled RBCs are transfused. 
Description of the population to be studied:  Healthy adult volunteers.  
Description and justification for the dosing regimen and treatment period:  In this study the 
non-radioactive, multi-biotin-labeling method for labeling RBCs for use in studies of RBC 
survival will be validated in normal, non-anemic adult volunteers.  The dosing regimen and 
treatment period are based on published studies from Dr. Widness’ group at the Unversity of 
Iowa and their collaborators [9, 14, 20-25] previously developed.  Autologous RBCs that are 
collected, processed into packed RBC units, and then either not stored or stored under 
refrigerated conditions for 40-42 days, will be labeled with up to 3 separate densities of biotin (2, 
6 and 18 g per mL RBC), and re-infused into the donor.  Our hypothesis in this experiment is 
that we at Emory will be able to recreate the effective methodology for tracking RBC survival 
pioneered by the Iowa group.  Specifically, we will be able to measure RBC survival of up to 3 
populations of autologous RBCs in normal adult volunteers using a non-radioactive biotin 


Protocol version:  2
Version date: December 12, 2018
    Page 
4
4
labeling methodology.  We anticipate that RBC survival of the three biotinylated RBC 
populations will agree with one another (and with published determinations using the standard 
51Cr method).  These measures of RBC survival will be conducted in 8 normal adult volunteers 
studied under normal, non-anemic, steady state conditions during the 154days (22 weeks) 
following transfusion.  Following completion of these studies, and after validating the 
methodology, we will be in a position to pursue novel studies in which quantification of 
transfused RBC storage will be an important endpoint.  
Compliance:  The clinical study will be conducted in compliance with the protocol, SOPs, and 
the federal, state and local regulations including requirements within the approved FDA IND.  
Objectives / Rationale / Research Question:  Our research group and collaborators at Emory 
study diverse aspects of blood banking and transfusion medicine in order to improve the clinical 
efficacy and safety of RBC transfusion practice. Within this area of investigation, we have a 
number of ongoing and anticipated studies that would benefit from the use of biotinylated RBCs 
to track survival of banked RBCs after infusion:  (1) We are NIH-funded to identify biomarkers 
that can predict survival of transfused RBCs.  Thus, we would like to compare predictions of 
RBC survival after transfusion, which we make using these potential biomarkers, with actual 
RBC survival after transfusion determined by labeling RBCs with biotin, infusing them into 
recipients, and then collecting post-transfusion samples for flow cytometric quantitation of in 
vivo RBC survival (this IND application specifically covers these studies).  (2) For anemic 
patients with antibodies against RBCs, in particular either auto-antibodies or broadly reactive 
allo-antibodies of indeterminate specificity, we would like to develop methods for an “in vivo 
crossmatch” where small aliquots of donor RBCs that appear to be least-incompatible in vitro 
(using a standard Coombs crossmatch) are each labeled at different biotin densitites and are 
then infused simultaneously to determine, in vivo, which donor RBCs survive the longest; the 
remaining unit from that donor will then be transfused (to be the subject of a future IND 
application).  (3) Addtionally, we would like the ability to study endogenous RBC survival in 
healthy volunteers and patients (for example, those with sickle cell disease) by drawing a small 
amount of blood, labeling the RBCs with biotin, and then re-infusing that blood back into the 
donor to track their endogenous RBC survival (to be the subject of a future IND application).  
In order to pursue these and other important clinical transfusion studies we need to first validate 
the biotin-labeling procedure in human subjects at Emory. This is the goal of the present 
protocol.
The Research Hypothesis is: We will be able to use biotin-labeling to track RBC survival in 
volunteers, and the methodology will be validated for later studies by achieving both the Primary 
and Secondary Objectives (below).   
The Primary Objective is:  To confirm that we can label RBCs with biotin, at up to 3 different 
densities, and then distinguish the differentially labeled RBCs from one another both after 
labeling and subsequently after they have been transfused back to the donor, allowed to 
circulate, and then re-identified in phlebotomy samples.   
The Secondary Objective is:  To demonstrate that b-RBCs can be safely transfused back to 
autologous subjects without any adverse reactions (other than possibly the development of 
antibodies against biotin-labeled RBCs).  
Clinical Study Design:
Primary endpoints: Determination of the length of time biotin-labeled RBCs can be detected 


Protocol version:  2
Version date: December 12, 2018
    Page 
5
5
following infusion; determine the length of time that differentially labeled RBCs can be 
distinguished from one another after transfusion.  
Secondary endpoints:  Measure the occurrence of adverse effects, including development of 
anti-biotin-RBC antibodies.
Information needed to answer the research question:  Samples of peripheral blood collected at 
designated times after transfusion of biotinylated RBCs.  
Study design:  Single-arm study.
Intervention:  The intervention is transfusion and subsequent tracking of autologous biotinylated 
RBCs (b-RBCs; the investigational product).  Specifically, the steps include:  collection of blood 
from the subject (up to 500 mL), processing of blood into a packed RBC unit (of the type used 
for transfusion), storing the unit at 2-6C for 40-42 days (or, in some cases, not storing the unit at 
all), withdrawing blood from the unit under sterile conditions, sterilely labeling aliquots of this 
blood with up to 3 pre-defined concentrations of biotin labeling reagent (2, 6, 18 g / mL of 
RBCs), re-infusing the b-RBCs back to the recipient, and then taking serial blood samples from 
the recipient (typically, weekly for up to 154 days) to track the survival of the infused b-RBCs.  
Although under ideal circumstances the subject would agree to participate for the maximal study 
duration of 112 days (from day of blood collection through maximum blood storage period [42 
days] and then, after receiving transfusion of b-RBCs on day 42, for another 154 days of weekly 
blood collections) the subject may elect to discontinue their participation at any time.
There is no randomization for this study.  The first 2 donors will not have their blood stored after 
collection; they will receive transfusion of b-RBCs on the same day blood was collected in order 
to more rapidly and specifically test the biotin-labeling and post-transfusion detection 
procedures.  The next 6 donors will more closely approximate the protocol for future studies in 
which blood is collected and stored under standard blood bank conditions prior to biotinylation 
and transfusion. All confidential information will be stored in locked cabinets.
As described above, the risks are those that may be seen with other studies in which blood 
collections and blood transfusions are performed.  These include: feeling queasy, throwing up, 
chills or feeling cold, fainting, feeling light in the head, seizures, discomfort around the needle, 
bruising, infection, swelling around the needle site, blood loss, and red cell destruction.  Other 
risks could include skin rashes and hives. Since only a small amount of blood will be drawn, 
these risks are probably minimal.  Transfusion recipients may also potentially get a blood 
infection when they are transfused with the biotinylated red blood cells, although we take a large 
number of precautions in the lab when we label the RBCs to minimize the chances of this 
problem, which would be a very rare occurrence.  
An additional possible risk specific to transfusion of b-RBCs is the occasional development of an 
immune response to the biotin label on the RBCs.  Since the initial studies performed using b-
RBCs in the early-1990’s, the biotinylation protocol has been optimized; recent evidence 
suggests that the risks of making these antibodies can be reduced through the use of lower 
concentrations of biotin during the labeling reaction (eg, < 18 g/mL, as we propose to use in 
these studies). Should a study participant develop these antibodies, there appear to be no 
adverse effects of the antibodies by themselves (eg, no effects of recipient biotin levels or 
function of biotin-dependent processes). Nonetheless, the FDA requires that recipients be 
tested for the presence of anti-biotin antibodies following their first transfusion of biotin-labeled 
RBCs, and that the subset of recipients who make anti-biotin antibodies be eliminated from 
future studies where biotin-labeled RBCs are transfused. 
The study subjects will experience no specific benefits during the course of this study.  
However, we may learn things about blood transfusion by performing these studies that may 
one day improve the outcomes of patients that require blood transfusion.  


Protocol version:  2
Version date: December 12, 2018
    Page 
6
6
Inclusion and Exclusion Criteria of the Subjects:
Inclusion Criteria: Adult subjects of 18-65 years of age will be considered for enrollment;  
subjects will be enrolled without preference to gender, race or ethnic background. The subjects 
must be in good health.   
Exclusion Criteria:  Anemia (Hb < 8 g/dL), chronic diseases (diabetes, heart or lung disease, 
hypertension [if poorly managed], peripheral vascular disease), ongoing consumption of biotin 
or raw egg supplements, a history of bleeding disorder or evidence of anemia on initial 
screening will be excluded.  Any subjects who are pregnant or plan to become pregnant will be 
excluded.  
Informed Consent Process:  We plan to recruit subjects from our existing registry of 
transfusion research donors. Most of these donors have previously consented to participate in 
multiple transfusion research studies, which include studies in which they donate blood and also 
studies in which they are transfused with blood.  Either Dr. Roback or Ms. Shannon Bonds will 
present the study to potential subjects, describing the procedures (blood draw, transfusion of 
their autologous blood after it has been labeled with biotin, and subsequent small volume blood 
draws to track circulation of b-RBCs).  Compensation will also be described (up to $40 for the 
initial donation, $10 for transfusion of b-RBCs, and then $5 for each sample of post-transfusion 
blood we draw over a total of 154 days post-transfusion).  The subjects will be instructed that 
they can withdraw from the study at any time. The subjects will then have an opportunity to ask 
any questions, after which they will have the opportunity to review and sign the consent.  
Procedures:
Interventions: Collection of up to 500 mL blood; preparation of the b-RBC investigational product 
(labeled using concentrations of either 2, 6 or 18 g/mL biotin reagent); IV infusion of up to 75 
mL packed RBCs (25 mL of pRBC at each of the 3 labeling densities), and sequential blood 
draws (< 5 mL each) to track b-RBC survival over the course of up to 154 days.   
Medications:  the only restriction is the use of biotin or raw egg-containing supplements which 
by block or otherwise inhibit our ability to accurately quantify b-RBCs.  All other medications 
may be taken during the study.  
Compliance:  as the investigational product will be administered is by study team, there are not 
expected to be any compliance issues.  
Adverse Events:
Definition of adverse events and anticipated types of adverse events: For the purposes of this 
study, we define adverse events as those events that the subject encounters (during the blood 
collection, during the transfusion, or following the transfusion) which cause pain, discomfort, 
other morbidities, or mortality.  Anticipated adverse events during blood collection include: 
feeling queasy, throwing up, fainting, feeling light in the head, seizures, discomfort around the 
needle, and bruising.  Adverse events that might occur during transfusion include skin rash, 
hives, fever, chills or feeling cold, infection, swelling around the needle site, and red cell 
destruction. Possible adverse events that may occur following transfusion include the detection 
of a new antibody against biotin-labeled RBCs. 


Protocol version:  2
Version date: December 12, 2018
    Page 
7
7
Plan for collection of adverse events:  Subjects will be monitored closely during the blood 
collection and transfusion procedures by staff trained to detect these adverse events.  If such 
events occur, they will be entered into the case report forms (CRFs).  The detection of 
antibodies against biotinylated RBCs will be based on testing performed on each sample 
collected following transfusion;  these results will likewise be entered into the CRFs.  
Follow-up treatment: Follow-up is dependent on the adverse event, and can range from 
elevating the legs and applying a cold compress to the back of the neck (fainting and light 
headedness) to hospitalization (infection or red cell destruction).   
Data and Safety Monitoring Plan:
Meeting reporting requirements: All adverse events will be collected on each volunteer. We 
will report adverse events to the IRB as required by IRB P&P and as part of regular progress 
reports. In addition, we will submit IND safety reports as required by FDA regulations and 
report Serious Adverse Events to the FDA as part of the IND progress reports.
Plan for reviewing data for safety:  Given that other investigators have performed similar 
studies using b-RBC infusion with no safety problems, we believe this single-site clinical trial 
presents only minimal risks. As such, we propose that the PI (Dr. Roback) will monitor data 
and safety, ensuring participants’ safety on a daily basis. Monitoring will occur in real-time 
(or within 1-2 hours of the occurrence of any adverse events). Thus, initially we will not use 
an independent Safety Officer (SO) or Data and Safety Monitoring Board (DSMB). Should 
unexpected risks or problems occur, we will either appoint an SO or DSMB to review study 
records. In addition, we will arrange for an impartial observer with knowledge of clinical trials to 
assess the study for data quality and protocol compliance both mid-way through the study 
(after 4 subjects have completed the study) as well as at the conclusion of the study.  This 
observor will also monitor the study to ensure protocol compliance as well as accuracy and 
completeness of documentation.
Data Collection, Monitoring and Access:
Overview: All data will be collected, stored and analyzed in consultation with Kirk Easley from 
Biostatistics. Mr. Easley is a co-investigator on one of the grants supporting this study (National 
Institutes of Health Program Project Grant, 2 P01 HL 086773-06A1:  Mechanisms and 
interventions addressing serious hazards of transfusion and cellular therapies. 2015 – 2020), 
where his specific charge is to direct a Biostatistics and Data Management Core.
IT resources:  The Information Technology (IT) Department of the Rollins School of Public 
Health is a state-of-the-art desktop and server infrastructure that supports over 2500 users. 
From the ground up, it was designed to be modular and expandable so as to give the School 
the greatest computing capability, flexibility and growth potential.  The server environment is 
based on a combination of UNIX and Windows 8 and can be divided into a number of service 
areas: The DataFax application runs on a dedicated Unix server that also runs statistical 
software SAS.  Firebird server specification: A Unix Solaris X series server with 8 cores of 2.4 
GHZ processors speed, 36 GB RAM Memory, 2 TB RAID 5 disk space, 1 Sun E series tape 
library tape drive; 2 modems (with one additional modem in reserve) are connected to phone 
lines with roll over capability. A Linux cluster server with 8 nodes for parallel computing with 
statistical software (SAS and S-Plus) will be used for analysis in the Roback program project. 
Cluster specifications: Four R710 , two R720 and one R810 running Linux Operating System; 
102 cores , 2.2 GHZ processors, 640 GB total memory, 500 TB disk space on an EMC VNX 
5700 storage array and data domain secure backup solution. The servers are housed in the 


Protocol version:  2
Version date: December 12, 2018
    Page 
8
8
locked computer room within a secured network operating center (NOC) of the Rollins School of 
Public Health with 24x7 monitoring, and environmental sensors and climate controls. The 
servers are accessible by staff within the RSPH building via the school’s network which consists 
of ATM, FDDI and Ethernet hardware running TCP/IP. The staff have PC computers which 
interface to the server using X-ming. Professional system administrators maintain and operate 
the servers and are responsible for ensuring performance, uptime and system maintenance, 
including security and application-layer patching. In addition, their services comply with Emory 
University Information security practices and controls.
The core of our computer services is provided by high performance computing cluster. Storage 
is provided through our SAN (storage area network) over a fiber channel network, with 54 
terabytes of RAID-protected HIPAA-compliant storage local on the cluster. The server hosts 
analysis and programming tools including: SAS, SPlus, Fortran 77/90, C, C++, Java, R, 
MATLAB and IMSL. The application environments are 64 bit and parallel computing enabled 
when the product supports the capability. Services are provided to the desktop using the X 
Windows  and Sun Grid Engine interfaces. The files systems are GFS2 based for efficiency and 
stability. Our researchers also have access to a central cluster computer called Ellipse, which 
has 1024 CPUs and is a high-memory computing environment.  We also supply through our 
Citrix frame 10 open use high end computing desktops. 1,024 CPU environment, high memory 
nodes.
They also run a number of database services that range from SQLServer 2000-2008 and also 
an instance of Oracle 10g that are provided across both the VM windows environments and the 
LInux systems.  These databases are used to services a number of application systems across 
our administrative and research needs. Database accounts are available for any faculty as 
requested. Web-based access to databases is provided by Adobe ColdFusion application 
server, which runs on a 440 MHZ Sun Ultra 10 with 512 MG of main system memory and 9 GB 
of mirrored disk space.
The RSPH network consists of Fast Ethernet hardware running TCP/IP. Gigabit Ethernet 
provides high-speed transmission to each of 10 floors and across the RSPH campus buildings 
and all the other buildings across campus. Ethernet provides high speed (100 Mbps) access to 
most desktop computers and peripheral devices. The network terminates at over 2500 
locations. The RSPH network is connected to the Emory Campus backbone via a 1gigabyte 
Ethernet connection, making campus services and wide area network services readily available. 
We also have an extensive wireless network providing “N” class connections and speeds that 
cover all of our buildings and the nearby external areas. This network has guest services as well 
as secure services for our faculty and staff. Our voice communications are connected into a 
Unified Communications system that provides phones through VOIP and are integrated with our 
Email systems for VMail access. All of the secured services inside our firewalls including 
network storage and other services can be access through our VPN firewall authenticated 
specifically to Emory faculty, staff, and students.
Currently, the computers for data access and analysis are at least an I7 CPU configuration with 
8GB of RAM memory, and have CD/DVD-RW and 20” or higher flat panel monitors standard 
with 500 gigs local diskspace and 64 bit Windows. Our Apple Mac environments are generally 
iMac configurations or Powerbook laptops with at least 4 gigs of memory. All of our desktop and 
laptop systems are connected to our network storage array that provides both highly secure and 
open storage areas. The network storage array is around 255TB of useable space and 
subdivided between a secure areas and an open access area. Our student computing 
environments are provided through our RSPHDesktop environment. This is a Citrix based virtual 
desktop environment that provides over 40 plus applications to our students and is accessible 
from any place they can get on a network and open a browser. We also supply through our 
Citrix frame 10 open use high end computing desktops. These are available for out for 
researchers to access an equivalent of the analytical desktop computer through a browser 


Protocol version:  2
Version date: December 12, 2018
    Page 
9
9
interface. This provides access to our full series of applications to a field deployed faculty 
member or one in temporary need of a high performance desktop environment in house. All 
desktop computers are configured based on best practices in industry as well as those outlined 
in NIST SP 800-69 Guidance for Securing Microsoft Windows XP Systems for IT Professionals: 
A NIST Security Configuration Checklist. All Windows machines have anti-virus software 
installed with updated virus signatures as well as the latest Microsoft XP Professional updates. 
The desktops required authentication from the Emory Active Directory to gain access to network 
services. In addition to the LINUX server used for reporting and analysis, there will be various 
applications that are PC-based. These include various MS files for word processing and 
graphics etc that are useful to share among the staff. The RSPH maintains a Windows NT 
based PC network. All shared PPG applications will be stored on a network drive.
Information security: The Rollins School of Public Health (RSPH) information technology 
environment is a HIPAA covered entity and complies with HIPAA and Emory information 
security and privacy policies and practices. In compliance with these policies and practices, 
RSPH aligns with the National Institute of Standards and Technology (NIST) special 
publications (800 series) for identifying, assessing, and managing information security risk 
within a technology environment. Drawing on federal and industry best practices, RSPH has 
implemented a series of multi-layered security controls to protect the integrity, reliability, and 
confidentiality of data. A sample of the key security controls includes:

An annual risk assessment of all RSPH information technology assets with their level of
risk, potential impact, probability, and controls evaluated based on NIST SP 800-30 Risk
Management Guide for Information Technology Systems.

RSPH and Emory network are protected by firewalls and intrusion detection devices.
Rules on these devices are set to deny all traffic by default and "allows" are written as
exceptions. These devices are updated as appropriate through Emory University's
change management process and evaluated to ensure they provide the appropriate level
of protection based on the sensitivity level of the data.

Servers are housed within a secured network operating center (NOC). The NOC has
environmental controls (fire, water, temperature), is accessible only through a two-factor
authorization system (key card and passcode), and is accessible only by authorized
information technology personnel. In the event of a power outage, the NOC devices will
draw UPS power then from a backup generator.

All servers are configured based on RSPH and Emory University best practices. Only
authorized, trained system administrators have administrative privileges on the servers.
System administrators monitor security mailing lists and sites and patch/update systems
based on priority of the patch. All servers are periodically scanned for vulnerabilities and
any identified vulnerabilities are assessed and managed.

All information technology personnel go through background checks before gaining
access to administrative privileges. At point of termination with Emory, all information
technology personnel's administrative privileges are removed.

Protected health information (PHI) data and the services that manage them are stored
on separate network and server infrastructure with limited access and additional security
controls.
Data are backed up daily. Backups are stored in a tiered structure for disaster recovery
purposes and include local, off-site, and out-of-state storage. Data stored off-site are
encrypted to prevent compromise and can only be retrieved by authorized personnel.

Data written to any RSPH file servers are checked with server-based anti-virus software.
Access to data is verified with a local single point of contact within each department
before any access control is granted. Principle Investigators are required to review
access control lists each year to ensure continued accuracy.

All RSPH desktops are configured based on best practices in industry as well as those
outlined in NIST SP 800-69 Guidance for Securing Microsoft Windows XP Systems for


Protocol version:  2
Version date: December 12, 2018
    Page 
10
10
IT Professionals: A NIST Security Configuration Checklist. All Windows machines have 
anti-virus software installed with updated virus signatures as well as the latest Microsoft 
XP Professional updates. The desktops required authentication from the Emory Active 
Directory to gain access to network services. 

Security policies are created and reviewed through the Woodruff Health Sciences Center
HIPAA committee, the Emory University Technology Infrastructure and Policy
committee, and, local policies, through the RSPH Information Technology Advisory
committee.
A full back up is performed every week with incremental backups nightly. Thus there is a 24 
hour window of redundancy of our files. Also we use Raid 5 to protect the primary data drives 
that are backed up to a secondary set of drives and then moved to tape as the final backup. The 
tapes are encrypted and moved out of state for disaster recovery protection.
Statistical Methods:
Statistical methods:  Circulating RBC volume and and RBC survival will be determined by flow 
cytometry as previously described [26-28] with the following modifications.  The binding of 
fluorescent-tagged streptavidin to the biotinylated RBCs is terminated at 10 min by addition of 
1 mL of 10 nM biotin in washing buffer to prevent cross-linkage of the heavily biotinylated RBCs 
with biotin binding sites on tetrameric streptavidin.  Each population of biotinylated RBCs will be 
discretely enumerated using a histogram relating number of RBCs to the log of fluorescent 
intensity.  For this analysis, up to six windows will be set separately by flowing separate 
samples of unlabeled blood and each of the different biotin density populations.  For each 
population of biotinylated RBCs, “% biotinylated” will be calculated by dividing the number in 
that population by the number of total cells (biotinylated plus unlabeled).  A standard curve will 
be constructed by sequential in vitro dilutions of each population into autologous normal RBCs. 
Initially, a simple paired t-test will be used to identify significant differences in cirulating b-RBC 
concentrations between different time point.  Additionally, we are discussing more detaield 
analyses with Mr. Easley.  
Number of subjects:  8 adults
Sample size rationale:  Sample size was determined based on conversations with Dr. Jack 
Widness’ group at University of Iowa, who pioneered this methodology.  Rather than using a 
power analysis, since this is just a single-site single-arm study directed at validating the 
biotinylation methodology in our laboratory, the proposed recruitment of 8 subjects is based on 
Dr. Widness’ estimate of how many repetitions of the procedure we should perform prior to 
moving onto the second phase of the study (not included herein), which is turn was based on 
his experience in working with the FDA to receive IND approvals for clinical trials with b-RBCs.    
Bibliography:
1.
Cavill, I., et al., The measurement of the total volume of red cells in man: a non-
radioactive approach using biotin. British Journal of Haematology, 1988. 70: p. 491-493.
2.
Hudson, I.R.B. and E. al, Biotin labeling of RBCs in the measurement of red cell volume
in preterm infants. Pediatr Res, 1990. 28: p. 199-202.


Protocol version:  2
Version date: December 12, 2018
    Page 
11
11
3.
Mock, D.M., Biotin, in Modern Nutrition in Health and Disease, M.E. Shils, et al., Editors.
2005, Lippincott Williams & Wilkens: Baltimore, MD. p. 498-506.
4.
McMahon, R.J., Biotin in metabolism and molecular biology. Annual Review of Nutrition,
2002. 22: p. 221-239.
5.
Zempleni, J., Biotin, in Present Knowledge in Nutrition. 2001, International Life Sciences
Institute: Washington, D.C. p. 241-252.
6.
Cordle, D.G., et al., Antibodies provoked by the transfusion of biotin-labeled red cells.
Transfusion, 1999. 39(10): p. 1065-9.
7.
Mock, D., et al., Hematocrit correlates well with circulating red blood cell volume in very
low birth weight infants. Pediatric Research, 2001. 50: p. 525-531.
8.
Cordle, D., et al., Antibodies provoked by the transfusion of biotin-labeled red cells.
Transfusion, 1999. 39: p. 1065-1069.
9.
Mock, D.M., et al., RBCs labeled at two biotin densities permit simultaneous and
repeated measurements of circulating RBC volume. Transfusion, 2004. 44(3): p. 431-7.
10.
Strauss, R.G., et al., Circulating RBC volume, measured with biotinylated RBCs, is
superior to the Hct to document the hematologic effects of delayed versus immediate
umbilical cord clamping in preterm neonates. Transfusion, 2003. 43(8): p. 1168-72.
11.
Franco, R.S., et al., Time-dependent changes in the density and hemoglobin F content
of biotin-labeled sickle cells. J Clin Invest, 1998. 101(12): p. 2730-40.
12.
Franco, R.S., et al., The survival characteristics of dense sickle cells. Blood, 2000.
96(10): p. 3610-7.
13.
Kumpel, B.M., et al., Comparison of flow cytometric assays with isotopic assays of
(51)chromium-labeled cells for estimation of red cell clearance or survival in vivo.
Transfusion, 2000. 40(2): p. 228-39.
14.
Mock, D.M., et al., Measurement of circulating red cell volume using biotin-labeled red
cells: validation against 51Cr-labeled red cells. Transfusion, 1999. 39(2): p. 149-55.
15.
Russo, V., et al., Studies with biotinylated RBC: (1) use of flow cytometry to determine
posttransfusion survival and (2) isolation using streptavidin conjugated magnetic beads.
Adv Exp Med Biol, 1992. 326: p. 101-7.
16.
Yasin, Z., et al., Phosphatidylserine externalization in sickle red blood cells: associations
with cell age, density, and hemoglobin F. Blood, 2003. 102(1): p. 365-70.
17.
Aladangady, N., et al., Infants' blood volume in a controlled trial of placental transfusion
at preterm delivery. Pediatrics, 2006. 117(1): p. 93-8.
18.
Hudson, I.R.B., et al., Biotin labeling of red cells in the measurement of red cell volume
in preterm infants. Pediatric Research, 1990. 28: p. 199-202.
19.
Valeri, C.R., et al., Comparison of radioisotope methods and a nonradioisotope method
to measure the RBC volume and RBC survival in the baboon. Transfusion, 2003. 43: p.
1366-1373.
20.
Mock, D.M., et al., Accelerated removal of antibody-coated red blood cells from the
circulation is accurately tracked by a biotin label. Transfusion, 2012. 52(5): p. 1097-105.
21.
Mock, D.M., et al., Measurement of red cell survival using biotin-labeled red cells:
validation against 51Cr-labeled red cells. Transfusion, 1999. 39(2): p. 156-62.
22.
Cohen, R.M., et al., Red cell life span heterogeneity in hematologically normal people is
sufficient to alter HbA1c. Blood, 2008. 112(10): p. 4284-91.
23.
Mock, D.M., et al., Red blood cell volume can be independently determined in vitro using
sheep and human red blood cells labeled at different densities of biotin. Transfusion,
2009. 49(6): p. 1178-85.
24.
Mock, D.M., et al., Red blood cell (RBC) volume can be independently determined in
vivo in humans using RBCs labeled at different densities of biotin. Transfusion, 2011.
51(1): p. 148-57.
25.
Mock, D.M., et al., Red blood cell (RBC) survival determined in humans using RBCs
labeled at multiple biotin densities. Transfusion, 2011. 51(5): p. 1047-57.


Protocol version:  2
Version date: December 12, 2018
    Page 
12
12
26.
Mock, D., et al., Measurement of circulating red cell volume using biotin-labeled red
cells: validation against 51Cr-labeled red cells. Transfusion, 1999. 39: p. 149-155.
27.
Mock, D., et al., RBCs labeled at two biotin densities permit simultaneous and repeated
measurements of circulating RBC volume. Transfusion, 2004. 44: p. 431-437.
28.
Mock, D.M., et al., Measurement of circulating red blood cell volume using biotin labeled
red cells: Validation against 51Cr labeled red cells. Transfusion, 1999. 39: p. 149-155.
Revision Dates:
3/29/16
Last Review Date:
3/29/16
Approval Signatures: 
Effective Date:
John D. Roback, MD PhD
3/29/16

ICF_001.pdf: 
RBC SURVIVAL VALIDATION IN ADULT HUMANS UNDER CONDITIONS OF NORMAL RBC 
SURVIVAL
NCT02757898 
February 01, 2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 1 of 8
Version Date: 12/12/2018
IRB Form 01292016
You Are Being Asked to Be in a Research Study
What Is a Research Study?
The main purpose of research studies is to gain knowledge. This knowledge may be used to 
help others. Research studies are not intended to benefit you directly, though some might.  
Do I Have to Do This?
No. Being in this study is entirely your choice.  If you decide to join this study, you can 
change your mind later on and withdraw from the research study. 
Taking part in a study is separate from medical care. The decision to join or not join the 
research study will not affect your status as a patient.  
What Is This Document?
This form is an informed consent document. It will describe the study risks, procedures, and 
any costs to you.
This form is also a HIPAA Authorization document. It will describe how your health information 
will be used and by whom.
Signing this form indicates you are willing to take part in the study and allow your health 
information to be used.
What Should I Do Next?
1. Read this form, or have it read to you.
2. Make sure the study doctor or study staff explains the study to you.
3. Ask questions (e.g., time commitment, unfamiliar words, specific procedures, etc.)
4. If there will be medical treatment, know which parts are research and which are
standard care.
5. Take time to consider this, and talk about it with your family and friends.
IRB00085954
IRB Approved
2/1/2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 2 of 8
Version Date: 12/12/2018
IRB Form 01292016
Emory University
Consent to be a Research Subject / HIPAA Authorization 
Title:  Transfusion of biotinylated RBCs
Principal Investigator:  John D. Roback, MD PhD
Sponsor:  
Investigator-Sponsor:  John D. Roback, MD PhD
Study-Supporter:  National Heart, Lung and Blood Institute (NHLBI) / NIH
Introduction
You are being asked to be in a medical research study. This form is designed to tell you everything you need to think 
about before you decide if you want to be a part of the study.  It is entirely your choice.  If you decide to take part, you 
can change your mind later on and withdraw from the research study. The decision to join or not join the research 
study will not cause you to lose any medical benefits.  If you decide not to take part in this study, your doctor will 
continue to treat you.
Before making your decision:
•
Please carefully read this form or have it read to you
•
Please listen to the study doctor or study staff explain the study to you
•
Please ask questions about anything that is not clear
You can take a copy of this consent form, to keep. Feel free to take your time thinking about whether you would like to 
participate. You may wish to discuss your decision with family or friends. Do not sign this consent form unless you have 
had a chance to ask questions and get answers that make sense to you.  By signing this form you will not give up any 
legal rights.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. law. This Web site 
will not include information that can identify you. At most the Web site will include a summary of the results. You can 
search this Web site at any time.
What is the purpose of this study?
The Emory University Center for Transfusion and Cellular Therapies (CTCT) studies various aspects of blood, including 
blood donation and blood transfusion. The purpose of this research is to study how red blood cells (RBCs) survive in a 
person’s circulation, and how that survival may be different in red blood cells that are donated and stored prior to being 
transfused. 
In this study we would like to collect a sample of your blood, take it to the laboratory to add a small “label” to the RBCs, 
then inject your RBCs back into your circulation.  After this transfusion, we will draw a few additional blood samples 
from you and count how many labeled cells are in those samples.  Any samples we collect from you are identified only 
with a code number.  The label we will use is biotin, which is a naturally occurring vitamin that most people eat large 
IRB00085954
IRB Approved
2/1/2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 3 of 8
Version Date: 12/12/2018
IRB Form 01292016
amounts of every day.  This type of labeling, which is for investigational purposes,  has been used for many years and 
has been shown to be very safe even when used in very young babies. We anticipate that over the course of this study 
we will enroll 8 people in this study.  
What will I be asked to do?
A health history will be done before you donate to see if you are eligible to participate in this study.  If you are pregnant 
or planning to become pregnant you will not be eligible to participate.
If you are eligible, we will draw up to 500 milliliter of blood from you (1/2 liter); this is the amount of blood you would 
normally donate if you were a blood donor.  That blood will be taken to the laboratory, where it will be processed into 
packed red blood cells.  In some cases, the packed red blood cell unit will be stored for 40-42 days in the refrigerator; 
you will be asked to return on day 40-42 to receive transfusions of your stored blood.  In other cases, after we process 
your blood into packed red blood cells, we will transfuse it back to you on the same day.  
In either case, prior to transfusing the blood back to you, we will perform a simple 2-3 hour procedure to add biotin to 
the outside of the RBCs in your blood sample.  After the labeling procedure is performed, we will inject the blood back 
into your arm.  Then, within a few minutes we will draw a 5 milliliter sample of blood from you (1 teaspoon).  You will 
then be completed for that day.  We ask that you come back the next day to have another 5 milliliter blood sample 
drawn, and do the same thing once a week for approximately the next 22 weeks.  Should you have to miss occasional 
blood draws over those 22 weeks, please let us know; even under these circumstances you may still be an acceptable 
volunteer for this study.  
The process to donate blood for this project is the same as when a lab collects blood for testing or for use in transfusion. 
A sterile needle will be placed into one of your veins and blood will be collected in a sterile tube.  After the blood is 
collected, we will remove the needle and hold pressure.  A bandage will be applied to stop further bleeding.  The 
bandage should be left on 1- 2 hours after you donate.  The process for donating blood will last about 30 minutes.  We 
will briefly check you and you will be free to go.
While you are in the study, you should not use biotin or raw-egg-containing supplements.
After You Have Donated:
•
Do not leave until a staff member releases you.
•
If you feel faint or dizzy, either lie down or sit down with your head between your knees.
•
Drink an extra 1- 2 cups of fluids over the next four hours.
•
If you were given an elastic pressure bandage and it becomes too tight, loosen it up and re-wrap it.
•
Bandages should be kept dry and can be removed after 1-2 hours.  You should not have to put on another 
bandage.
•
If there is bleeding from the needle site, apply pressure and raise your arm until the bleeding stops.
•
If you have any questions or problems about the donation, please call Shannon Bonds, RN, at 
If you participate in the full study, and depending on the results we find in your blood, you may be asked whether you 
want to participate in a follow-up study. It will be your choice as to whether to participate or not. If you are interested, 
you will be presented with a separate consent at that time.
IRB00085954
IRB Approved
2/1/2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 4 of 8
Version Date: 12/12/2018
IRB Form 01292016
Who owns my study information and samples?
If you join this study, you will be donating your samples and study information.  You will not receive any compensation if 
your samples or information are used to make a new product. If you withdraw from the study, data and samples that 
were already collected may be still be used for this study.  
What are the possible risks and discomforts?
Many volunteers and patients in other centers have participated in a similar study, and they have not noted any adverse 
effects.  The main risk is that you may develop an immune response to the biotin label on your RBCs.  We will be 
monitoring regularly for this response.  While there have not been any cases of people having adverse effects from the 
development of this antibody response, we will not be able to accept you for future studies that involve injection of your 
biotin-labeled RBCs.    
The risks for giving blood may include feeling queasy, throwing up, chills or feeling cold, fainting, feeling light in the 
head, seizures, discomfort around the needle, bruising, infection, swelling around the needle site, blood loss, and red 
cell destruction.  Other risks could include skin rashes and hives.  Since you will only be giving a small amount of blood 
these risks are probably minimal.  You may potentially get a blood infection when we transfuse your blood back to you, 
although we take a large number of precautions in the lab when we label your RBCs with biotin to minimize the chances 
of this problem, which would be a very rare occurrence.  
There may be side effects from the study or procedures that are not known at this time.  
It is possible that the researchers will learn something new during the study about the risks of being in it.  If this 
happens, they will tell you about it. Then you can decide if you want to continue to be in this study or not.  You may be 
asked to sign a new consent form that includes the new information if you decide to stay in the study.
Will I benefit directly from the study? 
This study is not designed to benefit you directly. This study is designed to learn more about how RBCs survive in 
circulation. The study results may be used to help others in the future.
Will I be compensated for my time and effort?
There are no costs to you for being a part of this study.  You will receive between $5 and $40 when we collect the first 
sample of blood (depending on the volume we collect); $10 when we inject that blood back into you; and then $5 when 
we take another blood sample a few minutes later.  Thus, on the first day of the study, if you go through with all 3 of 
these procedures, you will receive $20 - $55.  You will receive $5 each time you return to donate blood.  If you do not 
finish the study, we will compensate you for the visits you have completed. You will get up to $170 total, if you complete 
all study visits. 
What are my other options?
Participation in this study is voluntary. You do not have to participate in this study. 
How will you protect my private information that you collect in this study?
Emory will keep any research records that it creates private to the extent that this is required to do so by law.  
Whenever possible, a study number, rather than your name, will be used on study records.  Your name and other 
IRB Approved
2/1/2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 5 of 8
Version Date: 12/12/2018
IRB Form 01292016
identifying information will not appear when we present or publish the study results. Study records can be opened by 
court order.  
They also may be provided in response to a subpoena or a request for the production of documents. 
Storing and Sharing your Information
Your samples, genomic data and health information will be stored and shared with other researchers. The samples and 
information will be available for any research question, such as research to understand what causes certain diseases (for 
example heart disease, cancer, or psychiatric disorders), development of new scientific methods, or the study of where 
different groups of people may have come from.
Medical Record
Information from the study, including your signed consent form, will not go into your Emory Healthcare medical record. 
If you have never been an Emory Healthcare patient, you do not have one.   
Tests and procedures done at non-Emory places may not become part of your Emory medical record. Also, if you decide 
to be in this study, it is up to you to let your other health providers know. 
In Case of Injury
If you get ill or injured from being in the study, Emory will help you to get medical treatment.   Emory and the sponsor 
have not, however, set aside any money to pay you or to pay for this medical treatment. The only exception is if it is 
proven that your injury or illness is directly caused by the negligence of an Emory or sponsor employee.  “Negligence” is 
the failure to follow a standard duty of care. 
If you become ill or injured from being in this study, your insurer will be billed for your treatment costs.  If you do not 
have insurance, or if your insurer does not pay, then you will have to pay these costs.  
If you believe you have become ill or injured from this research, you should contact Dr. Roback at telephone number 
 You should also let any health care provider who treats you know that you are in a research study. 
Costs
There will be no costs to you for participating in this study, other than basic expenses like transportation. You will not be 
charged for any of the research activities.
Withdrawal from the Study
You have the right to leave a study at any time without penalty.  
The researchers also have the right to stop your participation in this study without your consent for any reason, especially if 
they believe it is in your best interest or if you were to object to any future changes that may be made in the study plan.
Authorization to Use and Disclose Protected Health Information
IRB00085954
IRB Approved
2/1/2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 6 of 8
Version Date: 12/12/2018
IRB Form 01292016
The privacy of your health information is important to us.  We call your health information that identifies you, your 
“protected health information” or “PHI.”  To protect your PHI, we will follow federal and state privacy laws, including the 
Health Insurance Portability and Accountability Act and regulations (HIPAA).  We refer to all of these laws as the “Privacy 
Rules.”  Here we let you know how we will use and disclose your PHI for the main study and for any optional studies in 
which you may choose to participate.
PHI that Will be Used/Disclosed:  
The PHI that we will use or share for the main research study includes:
•
Medical information about you including your medical history and present/past medications.
Purposes for Which Your PHI Will be Used/Disclosed:
We will use and share your PHI for the conduct and oversight of the research study.  We will use and share your 
PHI to provide you with study related treatment and for payment for such treatment.  We will also use and 
share your PHI to conduct normal business operations.  We may share your PHI with other people and places 
that help us conduct or carry out the study, such as laboratories, data management centers, data monitors, 
contract research organizations, Institutional Review Boards (IRBs)and other study sites. If you leave the study, 
we may use your PHI to determine your health, vital status or contact information. We will use and disclose your 
Use and Disclosure of Your Information That is Required by Law:  
We will use and disclose your PHI when we are required to do so by law. This includes laws that require us to 
report child abuse or abuse of elderly or disabled adults. We will also comply with legal requests or orders that 
require us to disclose your PHI. These include subpoenas or court orders.  
Authorization to Use PHI is Required to Participate:
By signing this form, you give us permission to use and share your PHI as described in this document. You do not 
have to sign this form to authorize the use and disclosure of your PHI.  If you do not sign this form, then you may 
not participate in the research study or receive research-related treatment.  You may still receive non-research 
related treatment.  
People Who will Use/Disclose Your PHI:
The following people and groups will use and disclose your PHI in connection with the research study:
•
The Principal Investigator and the research staff will use and disclose your PHI to conduct the study and 
give you study related treatment.
•
Emory may use and disclose your PHI to get payment for study related treatment and to run normal 
business operations. 
•
The Principal Investigator and research staff will share your PHI with other people and groups to help 
conduct the study or to provide oversight for the study.
•
Dr. John Roback is the Sponsor of the study.  The Sponsor may use and disclose your PHI to make sure 
the research is done correctly and to collect and analyze the results of the research.  The Sponsor may 
disclose your PHI to other people and groups like study monitors to help conduct the study or to provide 
oversight for the study.  
•
The following people and groups will use your PHI to make sure the research is done correctly and 
safely:
o
Emory offices that are part of the Human Research Participant Protection Program and those 
that are involved in study administration and billing.  These include the Emory IRB, the Emory 
Research and Healthcare Compliance Offices, and the Emory Office for Clinical Research. 
IRB00085954
IRB Approved
2/1/2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 7 of 8
Version Date: 12/12/2018
IRB Form 01292016
o
Government agencies that regulate the research including:  Office for Human Research 
Protections; Food and Drug Administration.
o
Public health agencies.
o
Research monitors and reviewer.
o
Accreditation agencies.
Expiration of Your Authorization
Your PHI will be used until this research study ends.
Revoking Your Authorization
If you sign this form, at any time later you may revoke (take back) your permission to use your information.  If you want 
to do this, you must contact Shannon Bonds, RN at: 
At that point, the researchers would not collect any more of your PHI.  But they may use or disclose the information you 
already gave them so they can follow the law, protect your safety, or make sure that the study was done properly and 
the data is correct.  If you revoke your authorization you will not be able to stay in the study. 
Other Items You Should Know about Your Privacy
Not all people and entities are covered by the Privacy Rules.  HIPAA only applies to health care providers, health care 
payers, and health care clearinghouses.  If we disclose your information to people who are not covered by the Privacy 
Rules, including HIPAA, then your information won’t be protected by the Privacy Rules.  People who do not have to 
follow the Privacy rules can use or disclose your information with others without your permission if they are allowed to 
do so by the laws that cover them
To maintain the integrity of this research study, you generally will not have access to your PHI related to this research 
until the study is complete.  When the study ends, and at your request, you generally will have access to your PHI that 
we maintain in a designated record set.  A designated record set is data that includes medical information or billing 
records that your health care providers use to make decisions about you. If it is necessary for your health care, your 
health information will be provided to your doctor. 
We may remove identifying information from your PHI.  Once we do this, the remaining information will not be subject 
to the Privacy Rules.  Information without identifiers may be used or disclosed with other people or organizations for 
purposes besides this study.  
IRB00085954
IRB Approved
2/1/2023


Study No.: «ID»
Emory University IRB
IRB use only
Document Approved On: «ApproveDate»
Page 8 of 8
Version Date: 12/12/2018
IRB Form 01292016
Contact Information
Contact Shannon Bonds, RN at 
:
•
if you have any questions about this study or your part in it,
•
if you feel you have had a research-related injury or a bad reaction to the study drug, or
•
if you have questions, concerns or complaints about the research
Contact the Emory Institutional Review Board at 
 or 
•
if you have questions about your rights as a research participant.
•
if you have questions, concerns or complaints about the research.
•
You may also let the IRB know about your experience as a research participant through our Research Participant
Survey at http://www.surveymonkey.com/s/6ZDMW75.
Consent and Authorization
TO BE FILLED OUT BY SUBJECT ONLY
Please print your name, sign, and date below if you agree to be in the main study. By signing this consent and 
authorization form, you will not give up any of your legal rights. We will give you a copy of the signed form to keep.
Name of Subject 
Signature of Subject (18 or older and able to consent)
Date              Time
TO BE FILLED OUT BY STUDY TEAM ONLY
__________________________________________________________
Name of Person Conducting Informed Consent Discussion
Signature of Person Conducting Informed Consent Discussion
Date              Time
IRB00085954
IRB Approved
2/1/2023