Use of Esophageal String Test to Understand Symptoms, Inflammation, and Function in Eosinophilic Esophagitis
Phase: NA
Conditions: Eosinophilic Esophagitis
Sponsor: University of Colorado, Denver

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Use of Esophageal String Test to Understand 
symptoms, inflammation and function in Eosinophilic 
Esophagitis 
 
 
 
Sponsor:  
 
  
 
End Allergies Together (501(c)(3)) 
 
Investigator:   
 
 
Calies Menard-Catcher, MD 
Investigator Address:   
Children’s Hospital Colorado 
13123 East 16th Avenue 
Aurora, CO 80045 
 
 
 
Version:   
 
 
 
3.0 
Date:  
 
 
 
 
4/25/18 
COMIRB:  
 
 
 
17-0796 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Conference on Harmonisation 
guidelines for Good Clinical Practice (ICH E6), the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46), and the NIDCR Clinical Terms of Award.  All 
personnel involved in the conduct of this study have completed human subjects protection 
training.   
 
 

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SIGNATURE PAGE 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this study will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable US federal regulations and ICH guidelines. 
Principal Investigator or Clinical Site Investigator: 
Signature 
 
Date 
 
Print Name 
 
Title 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................. 2 
SIGNATURE PAGE..................................................................................................................... 3 
LIST OF ABBREVIATIONS ....................................................................................................... 6 
1 
INTRODUCTION:  BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE ................................................................................................................................. 9 
1.1 
Background Information ............................................................................................................... 9 
1.2 
Rationale ......................................................................................................................................... 9 
1.2.1 Potential Risks ......................................................................................................................... 10 
1.2.2 Potential Benefits .................................................................................................................... 11 
2 
OBJECTIVES ..................................................................................................................... 12 
2.1 
Study Objectives ......................................................................................................................... 12 
3 
STUDY DESIGN................................................................................................................. 13 
4 
STUDY ENROLLMENT AND WITHDRAWAL ............................................................. 14 
4.1        Subject Inclusion Criteria 
4.2 
Subject Exclusion Criteria .......................................................................................................... 14 
4.3 
Rationale for Study Population .................................................................................................. 15 
4.4 
Strategies for Recruitment and Retention ............................................................................... 15 
4.5 
Subject Withdrawal ..................................................................................................................... 15 
4.5.1 Reasons for Withdrawal ......................................................................................................... 15 
4.5.2 Handling of Subject Withdrawals .......................................................................................... 15 
4.6 
Premature Termination or Suspension of Study .................................................................... 15 
6 
STUDY PROCEDURES/ EVALUATIONS ..................................................................... 17 
7 
ASSESSMENT OF SAFETY ........................................................................................... 20 
7.1 
Specification of Safety Parameters .......................................................................................... 20 
7.1.1 Unanticipated Problems ......................................................................................................... 20 
7.1.2 Serious Adverse Events......................................................................................................... 20 
8 
PROTOCOL DEVIATIONS .............................................................................................. 22 
8.1 
Major Protocol Deviation (Protocol Violation) ......................................................................... 22 
8.2 
Non-Major Protocol Deviation ................................................................................................... 22 
8.3 
Reporting and Managing Protocol Deviations ........................................................................ 22 
9 
Ethics/Protection of Human Subjects ........................................................................ 23 
9.1 
The Belmont Report .................................................................................................................... 23 
9.2 
Institutional Review Board ......................................................................................................... 23 
9.3 
Informed Consent Process ........................................................................................................ 23 
9.3.1 Assent or Informed Consent Process (in Case of a Minor) .............................................. 23 
9.3.2 Consent of Non-English Speaking Subjects ....................................................................... 24 
9.4 
Participant Confidentiality .......................................................................................................... 24 
9.5 
Registration on ClinicalTrials.gov ............................................................................................. 25 
9.6 
Future Use of Stored Specimens and Other Identifiable Data ............................................. 25 
10 
STATISTICAL CONSIDERATIONS ........................................................................... 26 

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10.1 
Sample Size Considerations ..................................................................................................... 26 
10.1.1 
Technical feasibility ............................................................................................................ 26 
11 
Data Handling and Record keeping ........................................................................ 27 
11.1 
Data Entry ..................................................................................................................................... 27 
12 
SOURCE DocUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .... 28 
13 
QUALITY CONTROL AND QUALITY ASSURANCE ............................................. 29 
14 
PUBLICATION/DATA SHARING POLICY ............................................................... 30 
15 
LITERATURE REFERENCES .......................................... Error! Bookmark not defined. 
5 
 

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LIST OF ABBREVIATIONS 
{Please add all disease or study-specific abbreviations/acronyms in this section. Modify this list 
as needed for your particular study and remove abbreviations that are not used in the 
document.} 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CHCO 
Children’s Hospital Colorado 
CHOP 
Children’s Hospital of Philadelphia 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DSMO 
Data and Safety Monitoring Officer 
EOE 
Eosinophilic Esophagitis 
EREFS 
Endoscopic Reference System 
EST 
Esophageal String Test 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
MOP 
Manual of Procedures 
N 
Number (typically refers to participants) 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
OHSR 
Office of Human Subjects Research 
PEESS 
Pediatric Eosinophilic Esophagitis Symptom Scores 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
US 
United States 
 
 
 
 

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Title: 
Use of Esophageal String Test to understand symptoms, 
inflammation and function in eosinophilic esophagitis 
Overview: 
Presently, the only method available to monitor disease activity in 
Eosinophilic Esophagitis is endoscopy with pathological review of 
biopsies. The overall goal of this study is to determine the ability of 
the Esophageal String Test (EST), a minimally invasive capsule 
based technology, to measure disease activity in children with EoE. 
Objectives: 
Primary Aim: Do eosinophil proteins captured by the EST correlate 
with symptoms related to pediatric EoE? 
 
Secondary Aim 1: Do eosinophil proteins captured by the EST 
correlate with the markers of EoE pathogenesis? 
Secondary Aim 2: Do eosinophil proteins captured by the EST 
correlate with a measure of esophageal function? 
Population: 
40 subjects: males and females, ages 7-18 years old undergoing 
upper endoscopy for monitoring of EoE or for symptoms of 
esophageal dysfunction concerning for EoE 
Study Sites: 
Lead Site: Children’s Hospital of Colorado  
Recruitment Site: Children’s Hospital of Philadelphia  
Clinical Laboratory: University of Illinois, Chicago  
 
Site Principal 
Investigators 
Stephen Ackerman, PhD; University of Illinois, Chicago 
Amanda Muir, MD; Children’s Hospital of Philadelphia 
Study Duration: 
2 years 
Subject Participation 
Duration: 
1 month 
Estimated Time to 
Complete 
Enrollment: 
18 months 
 
 
 
 
 
 
 
 
 

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1 INTRODUCTION:  BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
1.1 Background Information 
Eosinophilic Esophagitis (EoE) is a chronic disease characterized by symptoms related 
to esophageal dysfunction and large numbers of eosinophils in the lining of the esophagus (1). 
An endoscopy is required to make the diagnosis, because a biopsy of the esophageal tissue 
needs to be examined under the microscope. Eosinophils contain a number of proteins that 
likely participate in their function. Eosinophil peroxidase, major basic protein, eosinophil cationic 
protein and eosinophil derived neurotoxin are four of the major proteins that are associated with 
the eosinophil’s function. 
The EST is a capsule filled with a 90cm nylon string. A trailing end of the string protrudes 
from one end of the capsule. This end is taped to the cheek and the capsule is swallowed. As 
the capsule travels to the small intestine, the string inside the capsule is dislodged, leaving a 
string that goes from the cheek to the small intestine. The capsule dislodges from the string and 
the string is left in place, in the mouth, esophagus, stomach and small intestine for an hour. 
During this time, the string rubs against the inside of the esophagus and collects eosinophil 
proteins. After one hour, the string is removed through the mouth and placed in preservative to 
save the eosinophil proteins. The fluid extracted from the string is analyzed in the laboratory for 
eosinophil proteins. In a previous study, we showed that the eosinophil proteins captured by the 
string correlated with the number of eosinophils and amount of eosinophil proteins in the tissue 
biopsy (2). In this proposal, we will measure eosinophil proteins contained in the EST and 
correlate that with esophageal symptoms, inflammatory proteins and function. 
1.2 Rationale 
Procurement of mucosal biopsies during sedated endoscopy is the only method to 
determine whether a child may have eosinophilic esophagitis (EoE). Counting esophageal 
eosinophils in the squamous epithelium remains key to establishing the diagnosis. To date, no 
blood, stool, breath or other peripheral sampling of eosinophil related biomarkers has been 
shown to correlate with mucosal eosinophilia in esophageal biopsies, thus leaving patients and 
families with the only option of undergoing this invasive, costly and time consuming procedure. 
Sedated upper endoscopy with biopsy is a safe procedure, but alternative methods that limit or 
eliminate exposure to anesthetic agents and address other problematic features are needed to 
obtain diagnostic samples. Although eosinophils are easy to count, variability exists with respect 
to reporting, and better biomarkers must be determined. In this regard, we, and others showed 
that effluents obtained from the esophageal lumen are reflective of esophageal eosinophilia. 
Katzka et al determined that the esophageal sponge is able to harvest mucosal scrapings to 
measure eosinophils (10). This approach is not suitable for children because of its size and 
tolerability. Our work documents that the Esophageal String Test (EST) can detect luminal 
biomarkers that reflect esophageal eosinophilic infiltration (2). This capsule based technology is 
well tolerated by children ages 7 years and up, and fluid adherent to the string has been shown 
to contain eosinophil granule proteins that correlate with esophageal eosinophilia and amounts 
of these proteins in biopsies. 
The overall goal of this study is to discover a less invasive fashion to make the EoE 
diagnosis and assess disease activity in children. Here, we will determine whether eosinophil 
granule proteins captured by the EST correlate with: a) EoE symptoms, b) EoE 
histopathological scores and inflammatory proteins and c) a new functional biometric, 
distensibility. In this proposal, we hypothesize that luminal eosinophilic granule proteins will 
correlate with symptoms, inflammatory proteins and distensibility.  

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1.2.1 
Potential Risks 
 The study involves greater than minimal risk with no prospect of direct benefit.  
 
Since the patient will be undergoing endoscopy/colonoscopy for diagnostic purposes 
regardless of this study, the benefits to the subject and society outweigh the minimal risks 
associated with the additional biopsies. The procedure will present the subject with an 
experience that is the same as that expected in the standard of care. Risks associated with 
endoscopy and colonoscopy with biopsy include perforation, hemorrhage and the risks of 
conscious sedation.  
 
While upper endoscopy with esophageal biopsy is greater than minimal risk, only those 
patients consenting for and receiving upper endoscopy with biopsy for evaluation of GI 
symptoms as recommended by their primary clinician as part of routine care will be approached 
for study. The additional biopsies for research purposes are therefore of minimal risk beyond 
routine clinical care.  
The safety of multiple biopsies is supported by studies on adult patients with Barrett’s 
esophagus that have shown that multiple esophageal biopsies (as many as 35 to 120 
esophageal biopsies in an individual patient) do not produce esophageal perforation or bleeding 
when performed by an experienced team of physicians, nurses, and technicians (48).  In 
addition, a recent NIH study demonstrated that obtaining multiple mucosal biopsies for research 
purposes during elective endoscopy is well tolerated and appears to have no more than minimal 
risk without appreciably increasing the risk of otherwise routine endoscopy (49).  Importantly, 
there was no statistically significant association between the number of biopsies, type of 
procedure, anatomic location of research biopsies, endoscopist, or the use of nonsteroidal anti-
inflammatory drugs and the risk of complications. 
A recent review of the incidence of perforation and other severe complications 
associated with upper endoscopy was performed at Children’s Hospital Colorado. In a 42 month 
period of study there were 8 documented episodes of perforation out of 8130 endoscopic 
procedures. In all 8 cases the patient had undergone an interventional endoscopic procedure (4 
esophageal dilations, 2 gastrojejunostomy placements, 1 foreign body removal and 1 
polypectomy). None of the perforations was the result of esophageal mucosal biopsies 
performed during diagnostic EGD. The incidence of perforation associated with pediatric 
gastrointestinal endoscopy performed by pediatric gastroenterologists is low. In the 3.5 year 
period of study, 5683 diagnostic EGD’s were performed here at CHCO. There were no 
documented complications resulting from esophageal mucosal biopsies, including bleeding 
requiring blood transfusion, tamponade, or cauterization. There were 5 diagnostic EGD’s 
(0.09%) which presented after endoscopy with symptoms concerning for upper GI bleeding 
(hematemesis/coffee ground emesis), 4 of which were referred to the ED, but none of whom 
required blood transfusion or additional intervention. 
EndoFLIP has been shown to be safe in adults and children without increased risk of 
bleeding or perforation. Parameters can be set to limit the degree of inflation permitted. 
EndoFLIP will add approximately an additional 10 minutes of sedation time to overall procedure.  
Allergic reaction to the gelatin in the capsule is the only associated risk with the EST. The 
EnteroTracker device contains a small metal ball to weigh down the string. Subjects should tell 
their providers they have swallowed the ball and xray should be ordered prior to undergoing an 
MRI after completed the study. The small ball should pass within 24-48 hours in healthy 
individuals.  
There are no differences in the risks to the experimental group (patients with eosinophilic GI 
diseases) and the control groups (other inflammatory diseases and those with normal 

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mucosae). No treatments will be administered. Specific procedures are in place to protect the 
patient including using the smallest biopsy forceps and smallest capsule indicated as well as 
automatic stoppage of EndoFLIP insufflation at set intrabag pressures and volumes. Risks are 
minimized by qualified investigators closely monitoring subjects, and appropriate use of 
inclusion/exclusion criteria. 
Patient confidentiality will be maintained.  Violation of privacy and loss of confidentiality 
are both risks to which research participants are exposed. The possibility of these risks 
increases when protected health information is collected 
Describe plan to minimize risk. We will minimize risk by excluding those patients at 
potential or theoretical increased risk of bleeding or perforation from esophageal mucosal 
biopsies (See exclusion criteria) and with the below mentioned stopping rules. EndoFLIP will 
only be performed by endoscopists trained in these tools to avoid unnecessary prolongation of 
procedure and anesthesia time.  
Stopping Rules. A subject will be able to discontinue the study any time after giving 
consent up until time of procedure. Subjects will need to be re-consented if ever undergoing 
repeat procedure. If, during the procedure, there is real or anticipated complication on the part 
of the physician(s) related to anesthesia or procedure, the research procedure will be stopped.  
Protocol stopping criteria include any grade 3 complication. 
 
1.2.2 
Potential Benefits 
No immediate benefits are available to the subject.  
Potential benefits to the subject are related to the long-term outcome of these studies. If the 
pathogenic mechanisms for GI inflammatory diseases can be further dissected, more specific 
diagnostic and appropriate therapeutic measures can be developed. Specifically, this study will 
expand the knowledge as to the role of eosinophils and eosinophil-derived granule proteins in 
gastrointestinal inflammation. In addition, these studies will provide the basis for future 
diagnostic criteria and treatments for certain GI inflammatory diseases.  
Treatment of EoE is in large part administered to prevent the development of esophageal 
stricture. However, we are extremely limited in the available clinical parameters to monitor 
disease progression in this regard. The overall aim of this proposal is to evaluate the 
association between patient reported symptoms, esophageal function and eosinophil activity 
using standard and investigative assessment tools. This data will advance our understanding of 
the relationship between patient reported symptoms, esophageal inflammation and esophageal 
function and provide novel information regarding the utility of potentially less invasive disease 
assessment tools. Second, there is the potential to gain further understanding of the 
pathogenesis of disease. Future studies will use tools identified here to define the natural history 
and measure response to treatment.  
 
Taken together, results from these studies will provide a rich assessment of the esophageal 
mucosa using a minimally invasive device, the EST. We anticipate that EST protein 
measurements will correlate with symptoms, inflammatory proteins and a functional biometric. 
We will take advantage of the robust resources and rich collaboration of three academic 
institutions to address these aims. 

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2 OBJECTIVES 
2.1 Study Objectives 
Specific Aim 1: Do eosinophil proteins captured by the EST correlate with symptoms related to 
pediatric EoE? 
Prior to children undergoing a standard of care endoscopy and biopsy, we will assess their 
symptoms with a validated score sheet (PEESS)(3). Then, they will swallow an EST and leave it 
in place for one hour. At the end of the hour, we will remove the EST and freeze it so that we 
can measure eosinophil proteins that stick to the EST at a later time. We will compare the 
symptoms score with the EST protein levels. Previous studies show variability in the correlation 
of symptoms with inflammation, but we anticipate that because the EST samples all of the 
esophagus, and not just a small piece, like the esophageal biopsy, the EST protein levels will 
correlate with symptoms (2). 
Specific Aim 2: Do eosinophil proteins captured by the EST correlate with the markers of EoE 
pathogenesis? 
In the same pediatric subjects described in Aim 1, we will obtain esophageal biopsies and 
measure the amount of inflammation in that tissue using 3 different specialized scoring systems 
(4-6). We will correlate these inflammation scores in the biopsy with the eosinophil protein levels 
from the EST. We anticipate that the inflammation scores from the tissue will correlate with the 
eosinophil protein levels on the ESTs. 
Specific Aim 3: Do eosinophil proteins captured by the EST correlate with a measure of 
esophageal function? 
In the same pediatric subjects described in Aim 1, we will perform EndoFLIP measurments 
during the endoscopy. The EndoFLIP is a slender probe covered by a smooth long balloon that 
is passed into the esophagus and slowly expanded with a salt solution (7). As the EndoFLIP is 
expanded, sensors inside the balloon identify pressure values that reflect how well the 
esophagus can stretch. Our early study shows that these readings can identify reduced 
distensibility in children with EoE (8). We will correlate distensibility measurements obtained by 
the EndoFLIP with the eosinophil protein levels from the EST. 

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3 STUDY DESIGN 
When children are scheduled to undergo an endoscopy, research assistants will contact 
the family to arrange for the EST to be performed within one week of the endoscopy as 
previously described (REF). Prior to swallowing the EST, the patient will complete the PEESS 
form to assess symptoms. The string will be left in place for 1 hour and then removed. The 
endoscopy and EREFs and EndoFLIP will be performed as previously described (2). 
Endoscopic severity: Endoscopic esophageal appearances will be scored using a validated EoE 
scoring system (EREFS). Five features of EoE will be scored: Edema (0-1), Rings (0-3) 
Exudates (0-2), Furrows (0-1), Stricture (0-1). Results will be reported as an inflammatory score 
(edema, exudates, furrows) and fibrostenotic score (rings, stricture). Functional Luminal Imaging 
Probe (FLIP): After endoscopic visualization, the FLIP, a 16 cm probe (Crospon) will be placed 
transorally and positioned 3 cm distal to the lower esophageal sphincter. Esophageal cross 
sectional areas and intrabag pressure will be measured during stepwise distensions beginning 
with 5 mL and increasing to a maximum of 70mL or intrabag pressure of 50 mmHg is achieved, 
whichever comes first. FLIP is FDA-approved without age restriction and its use has been 
approved by our IRBs previously. Primary results will be reported as distensibility plateau (mm). 
EST and biopsy samples: The EST will be placed in a labeled tube and frozen until 
analysis as below. Four mucosal biopsies will be obtained from the distal esophagus for protein 
(3) and histological (1 biopsy) analysis. Samples for protein analysis will be snap frozen for 
batch processing and assessment. Samples for histological analysis will be paraffin embedded 
and cut into 5μM sections for batch staining. 
 

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4 STUDY ENROLLMENT AND WITHDRAWAL 
Children with EoE or symptoms of esophageal dysfunction concerning for EoE, who are 7 Years 
of age and older, will be enrolled in this study at Children’s Hospital Colorado (CHCO) and 
Children’s Hospital of Philadelphia (CHOP). Most children 7 years and older can swallow 
capsules. Subjects will be identified by screening appointment schedules, a well-tested method 
used at both institutions. Informed consent and assent will be obtained. After endoscopy, 
subjects will be identified as: 1) EoE active or 2) EoE inactive or 3.) other-symptoms but normal 
histology or vice versa. EoE will be defined based on current diagnostic criteria as having 
clinical symptoms of esophageal dysfunction, >15 eos/HPF, and other causes of eosinophilia 
ruled out either by negative pH/impedance study or greater than 6 weeks of treatment with 
proton pump inhibitor prior to endoscopy (1). EoE active will be defined as having symptoms 
and abnormal histology. EoE inactive will be defined as being asymptomatic and <15 eos/HPF. 
“Other” patients will be analyzed separately based on clinical diagnoses. Subjects will be age 
and sex matched for data analysis. 
 
Participation of Minorities: Subjects will be recruited/enrolled without regard to racial/ethnic 
group.  
 
Participation of Children:  Children aged 7 years and older will be recruited/enrolled. 
4.1 
Subject Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria: 
• 
Provide signed and dated informed consent form. 
• 
Willing to comply with all study procedures and be available for the duration of the study. 
• 
Male or female, aged 7 to 18 years old, inclusive 
• 
Undergoing upper Endoscopy with biopsy for clinical care at CHCO or CHOP  
• 
Current or historical diagnosis of EoE, or suspected of having EoE 
4.2 
Subject Exclusion Criteria  
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
• 
Known connective tissue disease, other eosinophilic disorders 
• 
Past history of caustic ingestion, esophageal surgery or other esophageal injury 
• 
Known inflammatory bowel disease or esophageal motility disease (achalasia) 
• 
Unwilling or unable to swallow the EST 
• 
Oral or intravenous steroids in the preceding 60 days (not including swallowed topical 
fluticasone, budesonide, etc) 
• 
Pregnancy  
• 
Participation in a clinical study that may interfere with participation in this study  

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4.3  
Rationale for Study Population 
Based on prior experience with the EST in a similar population, one out of three subjects is 
unable to swallow the EST. In order to achieve the enrollment goal of 40 subjects completing all 
study procedures, 70 subjects would need to be consented at both CHCO and CHOP.  It is 
anticipated that 35 subjects would sign consent at CHCO in order to reach 20 subjects 
completing the study.  
4.4 Strategies for Recruitment and Retention 
Potential participants will be screened from the clinical schedules at CHCO and CHOP. 
Should this method of recruitment yield poor accrual, the study teams will pursue other methods 
of recruitment including, but not limited to: print advertisement, social media and email 
communications. Research coordinators will contact the parents of the subjects and explain the 
study at least one week prior to the scheduled endoscopy. Interested potential participants will 
be scheduled for consenting and completion of the EST procedure. If the EST procedure cannot 
be completed prior to the Endoscopy with EndoFLIP, then the consent will be completed prior to 
the upper endoscopy and the EST procedure will be scheduled within one week of the 
Endoscopy. Subjects will receive reminder telephone calls prior to all scheduled procedures.  
4.5 Subject Withdrawal 
Subjects may withdraw voluntarily from the study or the investigator may terminate a subject's 
participation. 
4.5.1 
Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request.  
An investigator may terminate a study subject’s participation in the study if: 
• 
Any medical condition, event or situation occurs such that continued participation in the 
study would not be in the best interest of the subject. 
• 
The subject meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation.   
4.5.2 
Handling of Subject Withdrawals 
Participation in research is always voluntary. A subject can decide to withdrawal from the study 
at any time. If the subject choses to withdrawal prior to completing any procedures, it will be 
recorded as such in the study Case Report Forms. If a subject withdraws after completing some 
of the procedures, the data collected for those procedures will be entered in the CRFs and the 
uncompleted procedures will be noted as not completed prior to withdrawal.  
4.6 Premature Termination or Suspension of Study 
It is understood that the study could be terminated prematurely based on poor accrual or prior to 
reaching recruitment goals, but at the end of the grant cycle.  
This study may be suspended or prematurely terminated if there is sufficient reasonable cause.  
Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party.  If the study is prematurely terminated or 

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suspended, the principal investigator will promptly inform the IRB and will provide the reason(s) 
for suspension or termination. 
Circumstances that may warrant termination include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects. 
• 
Insufficient adherence to protocol requirements. 
• 
Data that are not sufficiently complete and/or evaluable 
 
5 STUDY SCHEDULE 
Screening/ Consenting (Day -7 to 0) When children are scheduled to undergo an endoscopy, 
research assistants will review the child’s information for basic inclusion/exclusion criteria. They 
will then contact the family to discuss the study. The CRC will email or fax the consent form to 
families in order to provide ample opportunity to review the consent form. Families who agree to 
the study will be scheduled to consent for the study up to one week prior to the scheduled EGD 
or on the day of the EGD before the EGD scheduled time.  
  
Baseline Visit (Day 0):  All procedures can be completed in one day if the subject agrees. If so, 
the baseline visit will be the only visit for the subject. The baseline visit should be completed as 
follows: 
• 
Obtain Informed Consent 
• 
Obtain Subject Medical History and complete Study Inclusion/Exclusion criteria 
• 
Obtain subject’s height  
• 
Administer the PEESS  
• 
Administer EST device (subjects are allowed up to 8 ounces of water to assist in 
the swallowing of the EST) 
• 
After 1 hour, remove the EST and assess for adverse events 
• 
Accompany subject to procedure center for check in 
• 
Obtain biopsies during EGD 
• 
Perform EndoFLIP during EGD 
 
Follow Up Visit (Day 1-3):  Research Coordinators should contact subjects between 1-3 days 
after procedures are completed and assess for any adverse events.  
 

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6 STUDY PROCEDURES/ EVALUATIONS 
6.1  
Study Procedures 
When children are scheduled to undergo an endoscopy, research assistants will contact 
the family to arrange for the EST to be performed within one week of the endoscopy. Prior to 
swallowing the EST, the patient will complete the PEESS form to assess symptoms. The string 
will be left in place for 1 hour, removed. The EST will be removed from the subject at least 2 
hours before the scheduled upper endoscopy time to align with NPO guidelines for upper 
endoscopy. The endoscopy and EREFs and EndoFLIP will be performed per clinical guidelines 
and procedures for EndoFLIP (described below).  
 
Pediatric EoE Symptom Score (PEESS): PEESSv2.0 is a validated pediatric PRO that 
contains patient and parent proxy instruments that can be easily understood. Scoring is based 
on two domains that evaluate frequency and severity of the symptoms reported by the patient 
(see Appendix 1). PEESS Score v2.0 will be used to assess EoE symptoms. The PEESSv2.0 
Children and Teens Report (8-18) is intended for children ages 8-18 years old to complete 
independently. The PEESSv2.0 Parent Report for Children and Teens (2-18) is completed for all 
subjects by the parent.  
  
Endoscopic severity: Endoscopic esophageal appearances will be scored using a validated 
EoE scoring system (EREFS). Five features of EoE will be scored: Edema (0-1), Rings (0-3) 
Exudates (0-2), Furrows (0-1), Stricture (0-1). Results will be reported as an inflammatory score 
(edema, exudates, furrows) and fibrostenotic score (rings, stricture) (see Appendx 2). 
 
EST Satisfaction Survey: Following the string procedure, the subject and parent will be asked 
to complete a survey within 2-5 days of the endoscopy.  The survey will assess symptoms/side 
effects after the string and endoscopy procedures, and collect information on patient preference 
with string versus the endoscopy. 
 
Functional Luminal Imaging Probe (FLIP): After endoscopic visualization, the FLIP, a 16 cm 
probe (Crospon) will be placed transorally and positioned 3 cm distal to the lower esophageal 
sphincter. Esophageal cross sectional areas and intrabag pressure will be measured during 
stepwise distensions beginning with 5 mL and increasing to a maximum of 70 mL or intrabag 
pressure of 50mmHg is achieved, whichever comes first. To prevent unintended dilation of a 
stiff esophagus, infusion will stop and alarm message will sound if intrabag pressure exceeds 60 
mm Hg. Raw data will be exported to EndoFLIP Analytics and will be filtered to remove 
measurements during esophageal contractions and vascular and respiratory artifacts. A 
polynomial regression method to identify pressure to cross sectional area relationships will be 
used to determine outcomes, narrowest cross sectional area, and distensibility plateau. FLIP is 
FDA-approved without age restriction and its use has been approved by our IRBs previously. 
Primary results will be reported as distensibility plateau (mm). 
 
EST and biopsy samples: The EST will be placed in a labeled tube and frozen until analysis 
as below. Four mucosal biopsies will be obtained from the distal esophagus for protein (3 
biopsies) and histological (1 biopsy) analysis. Samples for protein analysis will be snap frozen 
for batch processing and assessment. Samples for histological analysis will be paraffin 
embedded and cut into 5μM sections for batch staining. 
 
6.2  
Lab Procedures 
 

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EST samples and corresponding biopsies will be shipped in 3 month intervals to Dr. 
Ackerman at the University of Illinois, Chicago. EST sample processing and analysis- EST 
samples will be thawed (previously harvested and frozen in extraction buffer with protease 
inhibitors) on ice and vortexed for 1 min at maximum vortex speed. Biomashers will be used to 
separate the string from the EST sample following manufacturer instructions to homogenize the 
sample, centrifuge the filter column (1min/13,400 rpm/+4°C) and collect the flow through. The 
EST eluates are aliquoted and stored at -80°C until used in biomarker assays. ELISAs for 
selected eosinophil biomarkers including MBP1 and CLC/Gal-10 (in house ELISAs at UIC), and 
commercial ELISAs for EPX and EDN will be performed as per manufacturer instructions (2). 
Measurement of non-eosinophil protein biomarkers including CCL24, CCL26, TSLP, Lox5, 
EMSY, IL-13, periostin and others will be done by commercial ELISAs and nanostring methods 
(2,16,17). Results will be reported as mass amount of protein/ml after adjusting for sample 
dilution factors. 
1.  Histopathological scores- Cut paraffin embedded samples will be assessed and scored 
for each of EoEHSS(4), EPX (5) and EMT (6) as previously described. 
2.  Data capture- PEESS survey results, FLIP results, histopathology and EREFs scores 
and molecular readouts will be loaded into the REDCAP study database after obtained. 
3. Data Analysis- In order to address our aims, we will perform the following correlation 
analyses. 
a. EST protein analyte concentration vs. PEESS scores 
b. EST protein analyte concentration vs. EREFS scores 
c. EST protein analyte concentration vs. EoEHSS scores 
d. EST protein analyte concentration vs. EPX scores 
e. EST protein analyte concentration vs. EMT scores 
f. EST protein analyte concentration vs. nano-string biomarkers 
g. EST protein analyte concentration vs. EndoFLIP numerical values 
Correlation of biomarkers from 1 hr ESTs with PEESS symptom score or histology scores. 
Analysis of variance or its non-parametric counterpart will be used to compare the differences in 
biomarkers between patients with different endoscopic appearance (e.g. Rings+/- Furrows + 
Stricture vs. Rings+/- Furrows vs. None of Rings, Furrows or Stricture). The semi partial 
correlation of biomarker level from string test with cross sectional area at 40 mmHg pressure, a 
metric of extensibility from FLIP test, will be examined using multiple linear regression (MLR) 
while adjusting for age of patient. MLR will also be used to examine the association of the 
outcomes with multiple biomarkers. No adjustment for comparisons of multiple outcomes will be 
applied in order to preserve some power for this study. 
 
  
6.3  
BioSpecimens Procedures 
 
 
 
1.   Purpose (if known) 
• 
Immunohistochemical analysis, bacterial DNA and RNA extraction and analysis, 
protein measurement, barrier function analysis or microbial culture and staining 
will be performed. Samples may undergo short-term culture in the lab prior to 
processing as above.  
2. Handling of specimens 
• 
Samples will be collected from endoscopy suite unfixed into a tube with 
physiological saline, will undergo short-term cultures in the lab and then either 
snap frozen or formalin fixed, stored in either a -80 freezer in a locked room until 
analysis is complete or in a slide box behind a locked office in a secure building 
until analyzed.  

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• 
All samples will be coded with indirect identifiers and records will be kept in a 
notebook locked in a cabinet behind locked door or in a password protected 
computer stored in a locked room. 
• 
Patient will be able to request destruction of sample. 
• 
Samples will be destroyed if subject withdraws consent for further participation. 
• 
The PI will have ownership of the specimens. 
• 
Portions of the sample will be sent to University of Illinois, Chicago for laboratory 
analysis.  

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7 ASSESSMENT OF SAFETY 
 
7.1 
Specification of Safety Parameters 
Due to the nature of the EST, expected adverse events in this study include gagging, vomiting 
or sore throat up to 24 hours following the procedure. Subjects who vomit the EST will be given 
the option to attempt the procedure again if they would like. We will contact subjects 24 -72 
hours after the EST procedure to assess for any unanticipated events.  
Safety monitoring for this study will focus on unanticipated problems involving risks to 
participants, including unanticipated problems that meet the definition of a serious adverse 
event.   
7.1.1 
Adverse Events 
An Adverse Event is any untoward medical occurrence in a patient or clinical investigation 
subject administered an investigational product and which does not necessarily have a causal 
relationship with this treatment.  
 
 
Immediate gagging and/or vomiting and sore throats 24 hours after the EST will be 
documented but these AEs are expected. All other adverse events will be documented and 
reviewed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. 
Study coordinators will contact subjects 2-3 days after the procedures to assess for AEs. The PI 
will determine causality as well as severity and all AEs will be reviewed on a quarterly basis by a 
DSMO.  
7.1.2 
Unanticipated Problems  
The Office for Human Research Protections (OHRP) considers unanticipated problems 
involving risks to subjects or others to include, in general, any incident, experience, or outcome 
that meets all of the following criteria: 
• 
unexpected in terms of nature, severity, or frequency given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved 
research protocol and informed consent document; and (b) the characteristics of the 
subject population being studied; 
• 
related or possibly related to participation in the research (possibly related means there 
is a reasonable possibility that the incident, experience, or outcome may have been 
caused by the procedures involved in the research); and 
• 
suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
7.1.3 
Serious Adverse Events  
For the purposes of this study, serious adverse events will be tracked if they meet the below 
criteria and are determined to be related to the research procedures.  

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A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• 
Results in death 
• 
Is life-threatening (places the subject at immediate risk of death from the event as it 
occurred) 
• 
Results in inpatient hospitalization or prolongation of existing hospitalization 
• 
Results in a persistent or significant disability or incapacity 
• 
Results in a congenital anomaly or birth defect 
An important medical event that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
the event may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. 
 

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8 PROTOCOL DEVIATIONS 
A protocol deviation is any noncompliance with the clinical study protocol, Good Clinical 
Practice, or Manual of Procedures requirements.  The noncompliance may be on the part of the 
subject, the investigator, or study staff.  As a result of deviations, corrective actions are to be 
developed by the study staff and implemented promptly. 
These practices are consistent with investigator and sponsor obligations in ICH E6: 
• 
Compliance with Protocol, Sections 4.5.1, 4.5.2, 4.5.3, and 4.5.4. 
• 
Quality Assurance and Quality Control, Section 5.1.1 
• 
Noncompliance, Sections 5.20.1 and 5.20.2. 
All deviations from the protocol must be addressed in study subject source documents and 
promptly reported to the local IRB, according to their requirements. 
8.1 Major Protocol Deviation (Protocol Violation)  
A Protocol Violation is a deviation from the IRB approved protocol that may affect the subject's 
rights, safety, or well-being and/or the completeness, accuracy and reliability of the study data.  
In addition, protocol violations include willful or knowing breaches of human subject protection 
regulations, or policies, any action that is inconsistent with the NIH Human Research Protection 
Program’s research, medical, and ethical principles, and a serious or continuing noncompliance 
with federal, state, local or institutional human subject protection regulations, policies, or 
procedures.  
 
8.2 Non-Major Protocol Deviation  
A non-major protocol deviation is any change, divergence, or departure from the study design or 
procedures of a research protocol that does not have a major impact on the subject's rights, 
safety or well-being, or the completeness, accuracy and reliability of the study data. 
 
8.3 Reporting and Managing Protocol Deviations 
The study site principal investigator has the responsibility to identify, document and report 
protocol deviations as directed by the study Sponsor.  However, protocol deviations may also be 
identified during study conduct review.  
Upon determination that a protocol deviation (major or minor) has occurred, the study 
staff will a) notify the site Principal Investigator, b) will complete a Protocol Deviation form. The 
Protocol Deviation form will document at a minimum the date PD occurred, the date PD 
identified, a description of event, whether the deviation resulted in SAE/AE, the signature of PI, 
report to local IRB, and documentation of a corrective action plan.  The DSMO may request 
discussion with the PI to determine the effect of the protocol deviation on the study participant 
and his/her further study participation, the effect of the protocol deviation on the overall study, 
and corrective actions.  The PI will complete and sign the Protocol Deviation form and submit it 

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to the local IRB, per IRB regulations.  Major protocol deviations will be reported to the DSMO. 
All deviations, major or minor will be collated submitted to local IRBs at annual review periods.  
9 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
9.1 
The Belmont Report 
In accordance with the National Institutes of Health’s federal wide assurance (FWA00005897): 
“This institution assures that all of its activities related to human subject research, regardless of 
funding source, will be guided by the ethical principles of The Belmont Report.”  Additionally, 
the investigator assures that all activities of this protocol will be guided by the ethical principles 
of The Belmont Report, 45 CFR 46 and all of its subparts (A, B, C and D). 
9.2 
Institutional Review Board 
A copy of the protocol, informed consent forms, assent form, any advertising/recruitment 
materials and other information to be completed by participants, such as survey 
instruments or questionnaires, will be submitted to the local IRBs for written approval. 
The investigator must submit and obtain approval from the IRB for all subsequent 
amendments to the protocol, informed consent documents and other study documentation 
referenced above. The investigator will be responsible for obtaining IRB approval of the 
annual Continuing Review throughout the duration of the study. 
The investigator will notify the IRB of serious adverse events and protocol violations. 
9.3 
Informed Consent Process 
Written informed consent will be obtained from each participant before any study-specific 
procedures or assessments are done and after the aims, methods, anticipated benefits, 
and potential hazards are explained.  The research study will be explained in lay terms to 
each potential research participant. The participant’s willingness to participate in the study 
will be documented in writing in a consent form, which will be signed by the participant with 
the date of that signature indicated.  The investigator will keep the original consent forms 
and signed copies will be given to the participants.  It will also be explained to the 
participants that they are free to refuse entry into the study and free to withdraw from the 
study at any time without prejudice to future treatment.  Written and/or oral information 
about the study in a language understandable by the participant will be given to all 
participants. 
Once the informed consent has been signed, the participant is considered enrolled in the 
study. 
9.3.1 Assent or Informed Consent Process (in Case of a Minor) 
All participants will receive a full oral explanation of the study, and informed consent will be 
obtained prior to participation. The consent form that is used for this study will be approved by a 
central IRB. Informed consent will be obtained by one of the investigators or his/her authorized 
delegate. All study staff receive training in the informed consent process. Prospective subjects 
are given time to read over the entire consent form in order to make their decision and are also 
given an opportunity to ask any questions concerning the study. They may request what they 
would like done with their material and clinical information when the study is completed, or if 
they should happen to withdraw from the study. They are then asked to check boxes indicating 

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the components of the study to which they will consent; for example, some individuals can 
participate in database entry but not consent for tissue procurement. If the child is over the age 
of assent (varies by institution), they are also asked to sign an assent form. A copy of the 
consent/assent form is given to the family so that they have the information regarding the study. 
Another copy is placed in their medical chart, and the third copy is kept in the research office.  
 
9.3.2 
Consent of Non-English Speaking Subjects 
 
As per, 45 CFR 46.117 (b)(2), we anticipate that no more than 3 subjects of Non-English 
speaking subjects of the same language will be enrolled. If a 4th subject is to be enrolled then a 
translation of the entire consent form will be provided. We will provide oral presentation of 
informed consent in conjunction with a short form stating that the elements of informed consent 
have been presented orally, for studies that will include non-English speaking subjects but not 
purposely recruit them. The translated consent form will be done according to the conditions 
stated above. A translator fluent in the subject’s language and English will read the consent 
summary to the subject or their representative.  A written summary of what is presented orally 
will be completed.  A witness to the oral presentation will be provided and the translator may 
serve in this role.  The subject or their representative and the witness (translator) will sign the 
Short Form.  The person obtaining consent as authorized under the protocol and the witness 
(translator) will sign the Consent Summary.  The subject will be given copies of the Short Form 
document and the Consent Summary.  We will answer the subject’s questions and assess 
comprehension in the subjects’ native language.  The subject or his/her representative will walk 
away with: (1) the short form written consent in the subject’s language; (2) the long standard 
consent in English; (3) a copy of the summary of the oral presentation. 
 
9.4 
Participant Confidentiality 
All of the practices will adhere to institutional and national policies regarding the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA).  
Following Health Insurance Portability and Accountability Act guidelines, a participant’s 
privacy and confidentiality will be respected throughout the observational study.  Each 
participant will be assigned a sequential identification number, and this number rather than a 
name will be used to collect, store, and report participant information.  Data reported in medical 
journals or scientific meetings will be presented in aggregate for participants as a whole.  No 
individual participant will be identified in any way. 
Participant confidentiality will be strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their agents.  This confidentiality is extended to cover testing of 
biologic samples in addition to the clinical information relating to participating subjects. 
Research samples will be labeled with code numbers so that direct identifiers will not be 
visible. All information concerning patient identification will be kept in protected storage areas, 
including password-protected computer files and locked files and/or offices. The Principal 
Investigator, primary researchers, and clinical research coordinator(s) will have access to the 
patient identifiers  
Some samples that are collected during an endoscopy and/or colonoscopy for research 
purposes may be frozen and shipped to other hospitals, institutions, and testing companies for 
analysis. Data may also be shared.  The data and/or samples will be coded with indirect 
identifiers per HIPAA and have no PHI associated with them. The data and/or samples will be 

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used in a collaborative relationship between institutions, or testing company receiving the data 
and/or samples. All of these samples will be shared under an MTA, or other applicable 
agreement 
9.5 Registration on ClinicalTrials.gov 
A description of this study will be available on http://www.ClinicalTrials.gov. 
 
9.6 Future Use of Stored Specimens and Other Identifiable Data 
All specimens will include a research study identifier but otherwise will be de-identified. 
Specimens remaining after study analysis will be stored for analysis in future related protocols. 
The use of these samples will be described in those protocols and requests will be routed 
through proper institutional and IRB channel for approval.    
 

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10 STATISTICAL CONSIDERATIONS 
No previous data exists for estimating the potential magnitude of correlation of biomarkers 
from the 1-hour EST with other outcome variables for this power analysis. We want to have 
sufficient power to detect a significant correlation if the true underlying correlation is 0.45 or 
greater, corresponding a medium to large effect size by Cohen’s operational cutoff. In this case, 
a sample of 40 is required to ensure 80% chance at 5% significance to detect significant 
correlation between a biomarker and an outcome variable. 
 
Correlation of each biomarker level from 1 hour string test with PEESS symptom score, 
EREFS histopathological score or luminal diameter measured by EndoFlip at 50 mmHg 
pressure will be analyzed using Spearman correlation analysis.  Wilcoxon rank sum test will be 
used to compare the difference in biomarker level between patients with different endoscopic 
appearance (e.g. Rings+/- Furrows + Stricture vs. Rings+/- Furrows vs. None of Rings, Furrows 
or Stricture).  Multiple linear regression (MLR) will be used to examine the above relationship 
while adjusting for other covariates such as age and gender of patients.  Log transformation will 
be used for biomarker in MLR. 
 
10.1 
 Sample Size Considerations 
Preliminary studies- With respect to evidence for completion of aims in this proposal, we feel 
that we have either published on our ability to both establish technical feasibility and scientific 
rationale as summarized below 
10.1.1 
 Technical feasibility 
a. Tolerability and performance of EST- (2) 
b. Ability of EST to capture luminal mediators - (2) 
c. Ability to perform EREFs- (20) 
d. Ability to assess pathological inflammation in tissue sections- (5) 
e. Tolerability and performance of EndoFLIP - (8) 
 
10.1.2 
Scientific rationale 
a. Luminal measurements correlate with mucosal inflammation - (2) 
b. EndoFLIP reflects differences in pediatric esophageal distensibility in EoE - (8) 
 

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11 DATA HANDLING AND RECORD KEEPING 
Data will be entered into a REDCap database developed and maintained in the University of 
Colorado REDCap system. REDCap is a secure web application designed to support data 
capture for research studies, providing user-friendly web-based case report forms, real-time 
data entry validation (e.g. for data types and range checks), audit trails and a de-identified data 
export mechanism to common statistical package 
All study coordinators and PIs will be required to complete the REDCap training platforms 
provided by the University of Colorado in order to obtain a username and password. Passwords 
should remain unique and confidential to the assigned team members.  
11.1 
Data Entry 
Data will be collected either electronically (i.e. via tablet/computer) or on paper CRFs at 
each site and entered into online electronic case report forms maintained by the DMCC. 
Participants will be given the option to complete questionnaires at home. The first recording 
of any information captured for the registry will be considered the source document, which 
may be, but is not limited to, a medical record, a laboratory or clinical report, a paper CRF, 
or an eCRF.  
 
 

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12 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical research study necessary for the reconstruction and evaluation of the 
study.  Examples of these original documents and data records include, but are not limited to, 
hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ memory aid 
or evaluation checklists, recorded data from automated instruments, audio recordings of data 
collection events, copies or transcriptions certified after verification as being accurate and 
complete, photographs or digital photo files, x-rays, and subject files and records kept at the 
pharmacy, at the laboratories, and medico-technical departments involved in the study.  If CRFs 
are used as source documents, it should be stated in this section what data will be collected on 
CRFs and what data will be collected from other sources. 
All source documents should be created and maintained according to Standard Operating 
Procedures of the individual sites. Source documents should be accurate, legible, 
contemporaneous, original and attributable and documentation for each subject should be 
maintained on site for the duration of the study.  
Study staff will maintain appropriate medical and research records for this study, in compliance 
with ICH E6, Section 4.9 and regulatory and institutional requirements for the protection of 
confidentiality of subjects.  Study staff may be asked to provide de-identified documents to the 
PI at CHCO for verification of data points and regulatory agencies to examine (and when 
required by applicable law, to copy) research records for the purposes of quality assurance 
reviews, audits, and evaluation of the study safety, progress and data validity.   

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13 QUALITY CONTROL AND QUALITY ASSURANCE 
This section will address the plans for local quality assurance and quality control.  
Quality Management is the overall process of establishing and ensuring the quality of 
processes, data, and documentation associated with clinical research activities.  It 
encompasses both quality control (QC), and quality assurance (QA) activities.   
Each site should have standard operating procedures (SOPs) and/or a quality management 
plan that describe:   
• 
How data will be evaluated for compliance with the protocol and for accuracy in relation 
to source documents.  
• 
The documents to be reviewed (e.g., CRFs, clinic notes, product accountability records, 
specimen tracking logs, questionnaires, audio or video recordings), who is responsible, 
and the frequency for reviews.   
• 
Who will be responsible for addressing quality assurance issues (correcting procedures 
that are not in compliance with protocol) and quality control issues (correcting errors in 
data entry).  
• 
Staff training methods and how such training will be tracked. 
• 
Training on the EST procedure will be provided by staff from CHCO via webinar and 
video training. Sites should maintain records of the training for all staff administering the 
EST.  
 
 
 

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14 PUBLICATION/DATA SHARING POLICY 
We will comply with all NIH guidelines of February 26, 2003 on data sharing as well as all 
subsequent policies and best practices that have evolved since this initial policy was released. 
Data sharing will be customized according to the type of data and setting in which it was 
collected. 
 
Human Subjects Trials 
Our projects that include human subjects have datasets stored in on-site secure databases. 
Before release of any information, the raw data is stripped of identifiers to uphold compliance 
with HIPAA and other governing agencies’ guidelines; and is published as subsets of the 
original dataset, rather than allowing access to the original database. All databases housing any 
personal health information (PHI) are constructed with appropriate security to prevent 
unauthorized access; and have defined user roles that restrict access to PHI to those authorized 
by the University of Colorado School of Medicine’s HIPAA Office for that project, and to the 
database administrator, a quality assurance auditor, and authorized go-betweens. When 
appropriate CCTSI Translational Informatics Core or the Children’s Clinical Research 
Organization will be responsible for the coordination of these databases. 
 
Laboratory-based Data 
Our laboratory will maintain the associated data within our laboratory. Requests for data are 
sent to the Technology Transfer Office of the University of Colorado. They will negotiate an 
appropriate data sharing agreement with the requesting investigator and institution. 
 
Data Generated by Shared Resources 
Each Shared Resource has established policies that have been reviewed and approved by 
GEDP Leadership that define the length of time service-generated data is stored and the 
security provisions in place to prevent unauthorized access to the data. Data is not released to 
researchers other than the originating investigator without prior written approval from the 
originating investigator.  
Biosamples: Access to biosamples and related data collected using federal funding is overseen 
by the PI and when appropriate by the GEDP Leadership team. 
 
Operational Procedures 
The Technology Transfer Office works closely with us to help protect our intellectual property. 
The office provides guidance on and formally negotiates data use agreements with requesting 
parties when appropriate. 
 
 
 
 
 
 
 

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15 LITERATURE REFERENCES 
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APPENDIX 1: PEESS 
 
 

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APPENDIX 2: EREFS 

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