Clinical Utility of a Non Endoscopic Device EsoCheck and Biomarker EsoGuard as Alternative to Endoscopy for Screening for Barrett's Esophagus in At Risk Population (ASBE) A Randomized Controlled, Virtual Patient Trial
Phase: NA
Conditions: Barrett Esophagus
Sponsor: Lucid Diagnostics, Inc.

 
 
 
 
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ASBE study 
 
Clinical Utility of a Non endoscopic Device EsoCheck and 
Biomarker EsoGuard as Alternative to Endoscopy for Screening 
for Barrett’s Esophagus in At Risk Population (ASBE) 
A Randomized Controlled, Virtual Patient Trial 
 
 
 
Principal Investigator:  
Victoria T. Lee MD 
Vice President Medical Affairs Lucid Diagnostics 
 
 
 
 
 
 
Study sponsor:  
 
Lucid Diagnostics 
 
 
 
 
360 Madison Avenue 
 
 
 
 
Floor 25 
New York, NY 10017 
 
Version: 1  
Date: 03/6/2023 
 
 

 
 
 
 
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TABLE OF CONTENTS 
1. 
PROTOCOL SYNOPSIS .............................................................................................................................. 3 
2. 
INTRODUCTION AND SCOPE ................................................................................................................... 4 
3. 
TRIAL DESIGN .......................................................................................................................................... 4 
4. 
STUDY OBJECTIVES ................................................................................................................................. 6 
Primary objective ........................................................................................................................................ 6 
Secondary objective.................................................................................................................................... 6 
5. 
STUDY POPULATION ............................................................................................................................... 6 
Inclusion criteria ......................................................................................................................................... 6 
6. 
STUDY PROCEDURES ............................................................................................................................... 6 
6.1 Round 1 Control .................................................................................................................................... 7 
6.2 Round 2 Intervention ............................................................................................................................ 7 
7. 
STATISTICAL ANALYSES ........................................................................................................................... 8 
7.1 
Case Selection ................................................................................................................................. 8 
7.2 
Power Justification ......................................................................................................................... 8 
7.3 
Statistical formulation and statistical analysis plan of the objectives .......................................... 8 
8. 
ETHICAL CONSIDERATIONS ..................................................................................................................... 9 
9. 
REFERENCES .......................................................................................................................................... 10 
  
 
 

 
 
 
 
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1. PROTOCOL SYNOPSIS 
Title 
Clinical Utility of a Non endoscopic Device EsoCheck and Biomarker EsoGuard as Alternative 
to Endoscopy for Screening for Barrett’s Esophagus in At Risk Population (ASBE) 
A Randomized Controlled, Virtual Patient Trial 
Rationale
 
 
A randomized controlled virtual patient trial is a means of obtaining clinical utility data for 
reimbursement.  
This trial will obtain clinical utility data on EsoGuard® (EG) a biomarker assay (laboratory 
developed test/LDT), and EsoCheck® (EC), an FDA cleared, non-endoscopic esophageal cell 
collection device, which when used in combination has been identified by the AGA and ACG 
as a reasonable, non-endoscopic alternative for screening of Barrett’s Esophagus (BE) and 
esophageal adenocarcinoma (EAC).  
Study 
objectives 
Primary objective 
To determine the impact of EsoCheck/EsoGuard on health care provider’s decision for 
endoscopy referral  
Secondary objective 
To determine the impact of EsoCheck/EsoGuard on health care provider’s patient risk 
assessment for BE  
Study 
design 
A Randomized Controlled, Virtual Patient Trial. 
Eligible participants will sign the IRB approved ASBE participant Informed Consent Form 
(ICF). 
The participants complete two rounds of questions concerning the assessed risk for BE and 
upper endoscopy referral of 6 patient cases (clinical vignettes).  
Per round, there will be 3 different questionnaires consisting of 6 clinical vignettes (A/B/C). 
Participants will be randomized to questionnaire A, B or C according to the randomization 
scheme. 
Study 
population 
Primary care physicians and other physicians whose scope of practice includes disease 
screening, and/or diagnosis and management of patients with esophageal disease.  
• At least 80% of the overall study population will be primary care physicians, family 
medicine physicians, and other general practitioners; 
• ≤20% will be other types of physicians/specialists. 
Number of 
participants Minimum of 100. Around 200 will be invited to participate. 
Expected 
duration of 
accrual 
Approximately 3, but up to 6 months. 

 
 
 
 
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2. INTRODUCTION AND SCOPE 
EsoCheck® (EC) is an FDA cleared, non-endoscopic cell collection device designed to sample cells 
from a targeted region of the esophagus; EsoGuard® (EG) is a laboratory developed test (LDT) 
performed in a Clinical Laboratory Improvement Amendment (CLIA) certified and College of 
American Pathologists (CAP) accredited lab that utilizes set of genetic assays and algorithms 
which examines the presence of cytosine methylation at 31 different genomic locations on the 
vimentin (VIM) and Cyclin-A1 (CCNA1) genes. Using EsoCheck and EsoGuard in combination may 
offer an accurate, lower cost, minimally invasive, non-endoscopic, approach to screen for BE with 
and without dysplasia, and for esophageal adenocarcinoma (EAC), as compared with the current 
gold standard, namely diagnostic upper endoscopy of the esophagus plus biopsies.  
EsoCheck/EsoGuard has been clinically validated in a developmental study published in 2018 and 
shown to have a >90% sensitivity and >90% specificity in non-endoscopic detection of BE or EAC 
(Moinova 2018). EsoCheck administration is a simple, non-endoscopic, office-based procedure 
that can be performed by a variety of healthcare providers including physicians, nurse 
practitioners, physician assistants, nurses and others. It allows for planned, point-of-care 
screening of the at-risk patient population to provide a convenient and early datum for providers 
to assist in medical decision making.  
Non endoscopic minimally invasive cell-collection devices like EsoCheck/EsoGuard may be 
considered as an acceptable alternative to upper endoscopy or as an option to screen for BE as 
mentioned in the 2022 American College of Gastroenterology (ACG) and American 
Gastroenterological Association (AGA) guidelines for screening in Barrett’s Esophagus (Shaheen 
2022; Muthusamy 2022). 
A randomized controlled virtual patient trial is a means of obtaining clinical utility data for 
reimbursement (Peabody 2019). 
 
AIM 
This prospective randomized, controlled, virtual, patient study aims to assess the impact of 
EsoCheck/EsoGuard on health care provider’s decision for upper endoscopy referral.  
 
3. TRIAL DESIGN 
This will be a prospective randomized, controlled, virtual, patient study to measure the impact of 
EsoCheck/EsoGuard on health care provider’s decision for upper endoscopy referral.  
Around 200 US physicians will be asked to participate in this study and at least 100 will be 
enrolled. 

 
 
 
 
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Physicians eligible for participation are those whose scope of practice includes preventative care 
and disease screening – namely screening of BE, such as primary care physicians, family medicine 
physicians, and general practitioners; physicians whose scope of practice include diagnosis and 
management of esophageal disease may also participate. 
• At least 80% of the overall study population will be primary care primary care physicians, 
family medicine physicians, and general practitioners; 
• ≤20% will be other physicians/specialists. 
Eligible participants will sign the IRB approved ASBE participant Informed Consent Form (ICF). 
The participants will complete two rounds of questions concerning the assessed risk for BE and 
decision for endoscopy referral of 6 patient cases (clinical vignettes). Per round, there will be 3 
different questionnaires consisting of 6 clinical vignettes (A/B/C). Participants will be randomized 
to questionnaire A, B or C according to the randomization scheme. The link to the online 
questionnaires will be sent by email. The questionnaires should be completed within 
approximately ten (10) business days, and no more than twenty (20) business days after receiving 
the link. After the first round has been completed, an EsoCheck/EsoGuard educational 
information package and the second round of 6 clinical vignettes including EsoGuard results will 
be sent. 
 
Flowchart 
 
 

 
 
 
 
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4. STUDY OBJECTIVES 
This study has the following objectives: 
Primary objective 
To determine the impact of EsoCheck/EsoGuard on health care provider’s decision for upper 
endoscopy referral.  
Secondary objective 
To determine the impact of EsoCheck/EsoGuard on health care provider’s patient risk assessment 
for BE. 
 
5. STUDY POPULATION 
Inclusion criteria  
1. Board-certified physicians whose scope of practice includes preventative care and disease 
screening, and/or those whose scope of practice include diagnosis and management of 
esophageal disease (examples include but are not limited to primary care physicians/ 
general practitioners, family medicine physicians, gastroenterologists, and foregut 
surgeons);   
2. Have between 1 to 40 years of post-residency clinical experience within their field of 
practice; 
3. Have an active panel (whether as part of a group practice, or individually) of over 1000 
patients with an adult patient load of more than 50%. 
 
6. STUDY PROCEDURES 
The participants will complete two rounds of questions concerning the assessed risk for BE and 
upper endoscopy referral of 6 patient cases (clinical vignettes). Per round, there will be 3 
different questionnaires consisting of 6 clinical vignettes (A/B/C). Participants will be randomized 
to questionnaire A, B or C according to the randomization scheme. 
The link to the online questionnaires will be sent by email. The questionnaires should be 
completed within approximately ten (10) business days, and no more than twenty (20) business 
days after receiving the link. 

 
 
 
 
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After the first round has been completed, an EsoCheck/EsoGuard information package and the 
second round of 6 clinical vignettes including EsoGuard results will be sent. 
6.1 Round 1 Control  
The control round consists of 8 virtual patient cases (clinical vignettes). The 3 questionnaires 
(A/B/C) will consist of 6 clinical vignettes with the same risk profile as in the intervention round 
with a different description and in a different order. 
The following baseline and self-assessment questions will be asked: 
• 
Location of practice 
• 
Type of practice 
• 
Number of MDs associated with the practice 
• 
Years of practice 
• 
Proportion of patients covered by Medicare/Commercial insurance (<50% Medicare/>50% 
commercial; 50/50; >50% Medicare/<50% commercial) 
• 
Estimate of number of GERD patients seen per week (<10; 10-20; ≥20) 
• 
Rate your knowledge of Barrett’s Esophagus (BE), esophageal adenocarcinoma (EAC), and 
associated risk factors (1 = not knowledgeable at all; 2 = not very knowledgeable; 3 = somewhat 
knowledgeable; 4 = very knowledgeable;  5 = expert) 
• 
Rate your knowledge of the options and indications for BE screening (1 = not knowledgeable 
at all; 2 = not very knowledgeable; 3 = somewhat knowledgeable; 4 = very knowledgeable;  5 = expert) 
• 
Rate the frequency in which you refer your GERD patients for endoscopic BE screening, as 
part of your standard practice (<20%; 20-40%; 40-60%; 60-80%; ≥80%) 
The following questions will be asked per clinical vignette: 
1. What level of risk for BE (and/or EC) do you think this patient has? 
• Low 
• Intermediate 
• High 
2. Do you refer this patient for upper endoscopy? 
• Yes, I would refer this patient for endoscopy 
• No, I would not refer this patient for endoscopy 
6.2 Round 2 Intervention  
The intervention round consists of 8 EsoGuard patient cases (clinical vignettes) (3 positive and 5 
negative for EsoGuard). The 3 questionnaires (A/B/C) will have the same 5 negative EsoGuard 
cases, and 1 (different) positive EsoGuard case per questionnaire. 
The following questions will be asked per clinical vignette: 

 
 
 
 
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1. What level of risk for BE (and/or EC) do you think this patient has? 
• Low 
• Intermediate 
• High 
2. Do you refer this patient for upper endoscopy? 
• Yes, I would refer this patient for endoscopy 
• No, I would not refer this patient for endoscopy 
3. Did the EsoGuard result influence your decision to refer or not refer the patient for upper 
endoscopy? 
• Yes; the EsoGuard result had an impact on my decision   
• No; the EsoGuard result had no impact on my decision   
The following self-assessment questions will be asked of each participant at the end of round two 
(scale 1 very low to 5 high): 
• 
Rate your understanding of EsoCheck/EsoGuard and its indications?  
• 
How likely are you to use EsoCheck/EsoGuard for BE screening in your own practice?  
• How likely are you to refer this technology to others or use in their practices?  
7. STATISTICAL ANALYSES 
7.1 Case Selection  
The enrollment period is expected to be 3-6 months. Around 200 primary care physicians and 
other physicians whose scope of practice includes disease screening, and/or diagnosis and 
management of patients with esophageal disease in the United States will be invited and a 
minimum of 100 will participate.  
7.2 Power Justification  
No data exist regarding the expected endoscopy referral rate for patients at risk for BE with an 
EsoGuard test result by primary care physicians. It is expected that if at least 100 providers 
participate and complete both rounds the objectives can be met. Previous randomized 
controlled, virtual patient trials enrolled between 81 and 202 participants (Peabody, 2019).  
7.3 Statistical formulation and statistical analysis plan of the objectives 
Primary objective: To determine the impact of EsoCheck/EsoGuard on health care provider’s 
decision for upper endoscopy referral.  

 
 
 
 
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The impact will be measured by assessing the change in the percentage/rate of virtual patient 
cases who will be referred for endoscopy in the intervention round compared to the control 
round.  
Statistics summarizing the agreement between the EsoGuard result (positive or negative) and the 
health care provider’s decision (referral or no referral deemed necessary) include:  
• positive agreement; percentage of EsoGuard positive virtual patient cases that were referred 
for endoscopy  
• negative agreement; percentage of EsoGuard negative virtual patient cases that were not 
referred for endoscopy  
• positive predictive value (PPV); percentage of referred virtual patient cases that are EsoGuard 
positive  
• negative predictive value (NPV); percentage of non-referred virtual patient cases that are 
EsoGuard negative  
• percentage of concordance  
The participant-reported impact of EsoGuard results on their clinical decision making will be 
measured by assessing the proportion of patient cases in round 2 for which the provider 
answered the question, “Did the EsoGuard result influence your decision to refer or not refer the 
patient for upper endoscopy”, with, “Yes; the EsoGuard result had an impact on my decision”   
divided by all patient cases in round 2.  
The provided answers will also be reported in a table with counts and percentages. 
Secondary objective: To determine the impact of EsoCheck/EsoGuard on health care provider’s 
patient risk assessment for BE. 
The impact will be measured by assessing the change in the provider’s virtual patient risk 
assessment for BE in the intervention round compared to the control round. 
The provided answers will be reported in a table with counts and percentages. 
 
The baseline and self-assessment questions, Round 1 Control, and Round 2 Intervention, will be 
reported in a table with counts and percentages. 
8. ETHICAL CONSIDERATIONS 
All participants must be appropriately informed about the participation in this study and sign an 
IRB approved consent form. Data will be collected for this research project in accordance with 
applicable laws and guidelines.  
The protocol has been written and the study will be conducted according to the ICH Harmonized 
Tripartite Guideline for Good Clinical Practice.  
 

 
 
 
 
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9. REFERENCES 
1. Moinova HR, LaFramboise T, Lutterbaugh JD, Chandar AK, Dumot J, Faulx A, Brock W, De 
la Cruz Cabrera O, Guda K, Barnholtz-Sloan JS, Iyer PG, Canto MI, Wang JS, Shaheen NJ, 
Thota PN, Willis JE, Chak A, Markowitz SD. Identifying DNA methylation biomarkers for 
non-endoscopic detection of Barrett's esophagus. Sci Transl Med. 2018 Jan 
17;10(424):eaao5848.  
2. Shaheen NJ, Falk GW, Iyer PG, Souza RF, Yadlapati RH, Sauer BG, Wani S. Diagnosis and 
Management of Barrett's Esophagus: An Updated ACG Guideline. Am J Gastroenterol. 
2022 Apr 1;117(4):559-587.  
3. Muthusamy VR, Wani S, Gyawali CP, Komanduri S; CGIT Barrett’s Esophagus Consensus 
Conference Participants. AGA Clinical Practice Update on New Technology and 
Innovation for Surveillance and Screening in Barrett's Esophagus: Expert Review. Clin 
Gastroenterol Hepatol. 2022 Dec;20(12):2696-2706.e1.  
4. Peabody J, Tran M, Paculdo D, Valdenor C, Burgon T, Jeter E. Establishing Clinical Utility 
for Diagnostic Tests Using a Randomized Controlled, Virtual Patient Trial Design. 
Diagnostics (Basel). 2019 Jun 29;9(3):67.