Partnership to Establish a Practice Based Network to Assess for Head and Neck Cancers Using a Low-Cost Portable Flexible Nasopharyngoscope - Optimization Phase
Phase: NA
Conditions: Head and Neck Cancer, Oral Cancer
Sponsor: Duke University

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 ____________________________________________________________________________________________ 
 
Partnership to Establish a Practice Based Network to Assess 
for Head and Neck Cancers Using a Low-cost Portable 
Flexible Nasopharyngoscope – Optimization Phase 
NIDCR Protocol Number: 22-136-E   
NIDCR Grant Number:  R01 DE028555 
Principal Investigator:  Walter Lee, MD 
Grantee Institution: Duke University Medical Center 
NIDCR Program Official:  Amanda Melillo, PhD 
Draft or Version Number:  8.0 
 March 13, 2023 
 
NCT04905134 
 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
i 
STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the International Council for 
Harmonisation guidelines for Good Clinical Practice (GCP) (ICH E6) and the Code of 
Federal Regulations on the Protection of Human Subjects (45 CFR Part 46). National 
Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
ii 
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: 
 
Signed:  
 
Date:  
 
Name: Walter Tsong Lee 
Title: PI 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
iii 
TABLE OF CONTENTS 
PAGE 
STATEMENT OF COMPLIANCE ................................................................................................. I 
SIGNATURE PAGE .................................................................................................................... II 
TABLE OF CONTENTS ............................................................................................................. III 
LIST OF ABBREVIATIONS ........................................................................................................ V 
PROTOCOL SUMMARY .......................................................................................................... VII 
1 
KEY ROLES AND CONTACT INFORMATION ................................................................... 1 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ......... 4 
2.1 
Background Information .......................................................................................... 4 
2.2 
Rationale ................................................................................................................ 4 
2.3 
Potential Risks and Benefits ................................................................................... 5 
2.3.1 
Potential Risks ............................................................................................ 5 
2.3.2 
Potential Benefits ........................................................................................ 5 
3 
OBJECTIVES AND OUTCOME MEASURES ..................................................................... 6 
3.1 
Primary ................................................................................................................... 7 
3.2 
Secondary .............................................................................................................. 7 
4 
STUDY DESIGN ................................................................................................................ 8 
5 
POPULATION .................................................................................................................. 10 
5.1 
Participant Inclusion Criteria ................................................................................. 10 
5.2 
Participant Exclusion Criteria ................................................................................ 10 
5.3 
Strategies for Recruitment and Retention ............................................................. 10 
5.4 
Participant Withdrawal or Discontinuation from Study Procedures/Intervention..... 11 
5.4.1 
Reasons for Participant Withdrawal or Discontinuation from Study 
Procedures/Intervention ............................................................................ 11 
5.4.2 
Handling of Participant Withdrawals from Study or Participant 
Discontinuation of Study Intervention ........................................................ 11 
5.5 
Premature Termination or Suspension of Study .................................................... 11 
6 
STUDY INTERVENTION .................................................................................................. 12 
6.1 
Study Procedural Intervention(s) Description ........................................................ 12 
6.2 
Administration of Procedural Intervention .............................................................. 12 
6.3 
Procedures for Training of Clinicians on Procedural Intervention .......................... 12 
6.4 
Assessment of Clinician and/or Participant Compliance with Study Procedural 
Intervention ........................................................................................................... 13 
7 
STUDY SCHEDULE ......................................................................................................... 14 
7.1 
Screening ................................................................ Error! Bookmark not defined. 
7.2 
Enrollment ............................................................................................................ 14 
8 
STUDY PROCEDURES/EVALUATIONS ......................................................................... 15 
8.1 
Study Procedures/Evaluations .............................................................................. 15 
9 
ASSESSMENT OF SAFETY ............................................................................................ 16 
9.1 
Specification of Safety Parameters ....................................................................... 16 
9.1.1 
Unanticipated Problems ............................................................................ 17 
9.1.2 
Adverse Events ......................................................................................... 17 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
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Based on NIDCR Interventional Protocol Template v5.0–20190311 
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9.1.3 
Serious Adverse Events ............................................................................ 17 
9.2 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 18 
9.3 
Characteristics of an Adverse Event ..................................................................... 18 
9.3.1 
Relationship to Study Intervention ............................................................. 18 
9.3.2 
Expectedness ............................................................................................ 18 
9.3.3 
Severity of Event ....................................................................................... 19 
9.4 
Reporting Procedures ........................................................................................... 19 
9.4.1 
Unanticipated Problem Reporting .............................................................. 19 
9.4.2 
Serious Adverse Event Reporting .............................................................. 20 
9.5 
Halting Rules ........................................................................................................ 20 
10 
STUDY OVERSIGHT ....................................................................................................... 21 
11 
CLINICAL SITE MONITORING ........................................................................................ 22 
12 
STATISTICAL CONSIDERATIONS .................................................................................. 25 
12.1 
Study Hypotheses ................................................................................................. 25 
12.2 
Sample Size Considerations ................................................................................. 25 
12.2.1 Safety Review ........................................................................................... 25 
12.2.2 Efficacy Review ......................................................................................... 25 
12.3 
Final Analysis Plan ............................................................................................... 25 
13 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................. 28 
14 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................................ 29 
15 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................. 30 
15.1 
Ethical Standard ................................................................................................... 30 
15.2 
Institutional Review Board .................................................................................... 30 
15.3 
Informed Consent Process ................................................................................... 30 
15.4 
Exclusion of Women, Minorities, and Children (Special Populations) .................... 31 
15.5 
Subject Confidentiality .......................................................................................... 31 
16 
DATA HANDLING AND RECORD KEEPING ................................................................... 33 
16.1 
Data Management Responsibilities ....................................................................... 33 
16.2 
Data Capture Methods .......................................................................................... 33 
16.3 
Types of Data ....................................................................................................... 33 
16.4 
SCHEDULE AND CONTENT OF REPORTS ........................................................ 33 
16.5 
Study Records Retention ...................................................................................... 34 
16.6 
Protocol Deviations ............................................................................................... 34 
17 
PUBLICATION/DATA SHARING ...................................................................................... 35 
18 
LITERATURE REFERENCES .......................................................................................... 36 
HTTP://WWW.WCRF.ORG/CANCER_STATISTICS/WORLD_CANCER_STATISTICS.PHP ... 37 
SUPPLEMENTAL MATERIALS ................................................................................................ 39 
POST-PROCEDURAL SURVEY BY CLINICIAN WHO PERFORMED THE SCOPE EXAM ..... 39 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
v 
LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
CCSG 
Cancer Center Support Grant 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DCI 
Duke Cancer Institute 
DSMB 
Data and Safety Monitoring Board 
DUHS 
Duke University Hospital System 
ENT 
Ears Nose and Throat 
FDA 
Food and Drug Administration 
FNS 
Flexible Nasopharyngoscope 
FWA 
Federal-wide Assurance 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HNC 
Head and Neck Cancer 
HLD 
High Level Disinfection 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
IRB 
Institutional Review Board 
iRIS 
Electronic IRB software system 
MOP 
Manual of Procedures 
N 
Number (typically refers to participants) 
NIDCR 
National Institute of Dental and Craniofacial Research, NIH, 
Department of Health and Human Services 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PO 
Program Official, NIDCR, NIH 
PRMC 
Protocol Review and Monitoring Committee 
PRMS 
Protocol Review and Monitoring System 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOC 
Standard of Care 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
vi 
SOC 
Safety Oversight Committee 
SOP 
Standard Operating Procedure 
SC 
Study Coordinator 
US 
United States 
 
 
 
 
 
 
 
 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
vii 
PROTOCOL SUMMARY 
 
Title: 
Partnership to Establish a Practice Based Network to 
Assess for Head and Neck Cancers Using a Low-Cost 
Portable Flexible Nasopharyngoscope – Optimization 
Phase 
Précis: 
The optimization phase of this study will be conducted at Duke 
University.  The implementation phase will be done in Vietnam 
and conducted under a separate protocol. During optimization, 
direct comparison between the standard flexible 
nasopharyngoscope scope used in the US. with the new 
mobile flexible nasopharyngoscope (FNS) will be done to 
optimize the FNS design to be noninferior to the standard of 
care (SOC) exam. Any patient who meets clinical indication for 
a nasopharyngoscope exam is eligible for the study. If consent 
is given the subject will first undergo the “SOC” scope 
endoscopy. Then the FNS exam will be performed using the 
mobile device. A post-procedure survey will then be 
administered and completed by both the provider and subject. 
Post-procedure data will be collected in three areas: technical 
assessment (i.e.  image, lighting, and steering), physician 
feedback (i.e.  ease of use, image quality), and subject 
feedback (i.e. perceived pain). Data collected during 
optimization will inform of final adjustments needed to the 
mobile FNS device before it is used to conduct the 
implementation phase in Vietnam.  A protocol amendment will 
be submitted to include details about the implementation phase 
in Vietnam before study activities begin there.  
 
Objectives: 
Optimize the low cost FNS by comparing to SOC scopes at Duke 
University Medical Center 
We will compare the use and reliability of the FNS scope to 
SOC scopes available at Duke University Medical Center. This 
will include image quality to see structures, lighting, and 
steering mechanism. Key objectives include ease of use, 
image quality, and perceived pain. The technical and 
subjective feedback will optimize the device to gain efficiencies 
and improve tolerability. Success is considered to be that the 
FNS is overall non-inferior to the current SOC scopes. 
 
The expected outcome is to have an optimized FNS scope for 
production and widespread implementation and use   

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
viii 
 
 
 
Population: 
Up to 50 subjects 18 years or older who meet clinical criteria to 
undergo a SOC endoscopic exam 
Phase or Stage: 
N/A 
Number of Sites: 
1 site  
Description of 
Intervention: 
The FNS is used for assessment of the entire upper 
aerodigestive tract by Ear, Nose, and Throat (ENT) doctors or 
otolaryngologists and is part of SOC in the USA. This scope is 
inserted through the nasal passages into the pharynx, enabling 
a full view of all areas at risk for Head and Neck Cancer 
(HNC). Study participation ends once the post intervention 
survey is completed. 
Study Duration: 
3 months 
Subject 
Participation 
Duration: 
About 30 minutes 
Estimated Time to 
Complete 
Enrollment: 
2 months 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
ix 
 
 
Recruitment: Adult subjects that will undergo SOC endoscopy at the Head and Neck 
Surgery and Communication Sciences clinic at Duke will be approached by their 
treating physician if they would be interested in participating in this study.  If they are 
interested, the study team will approach them to review the written consent form.  Once 
signed, the SOC procedure will take place followed by the study scope procedure.  The 
physician will complete their portion of the post procedure survey and assess for 
adverse effects. The subject will complete a single question on the survey focused on 
comparing the pain from both procedures.  
 

1 KEY ROLES AND CONTACT INFORMATION 
Principal 
Investigator:   
Walter T. Lee MD, MHS 
Professor & Chief of Staff, Department of Head and Neck 
Surgery & Communication Sciences 
Co-Director, Head and Neck Program, Duke Cancer Institute  
Chief, Division of Head and Neck Surgical Oncology 
Duke University Medical Center 
40 Duke Medicine Circle, Room 4075B 
Box 3805 
Durham NC 27710 
Phone:  919-613-6407 
Fax:  919-681-6881 
Email: walter.lee@duke.edu  
NIDCR Program 
Official: 
Amanda Melillo, Ph.D. 
Chief, Integrative Biology & Infectious Diseases Branch 
Director, Oral Opportunistic Pathogens & Viral Disease 
Program 
National Institute of Dental and Craniofacial Research 
(NIDCR), NIH (https://www.nidcr.nih.gov/) 
6701 Democracy Blvd., MSC 4878; Bethesda, MD 20892-4878 
Phone: (301) 529-7217; FAX: (301) 480-8319; 
emailamanda.melillo@nih.gov 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
2 
Clinical Site 
Investigators: 
  
Russel R. Kahmke, MD, MMCi, FACS 
Assistant Professor of Surgery 
Department of Head and Neck Surgery & Communication 
Sciences 
Division of Plastic, Maxillofacial, & Oral Surgery, 
Department of Surgery 
Duke University Health System 
40 Duke Medicine Circle 
Box 3805 
Durham, NC 27710 
Phone: (919) 684-6357 
Email: russel.kahmke@duke.edu  
 
Daniel Rocke, MD, JD, FACS 
Associate Professor 
Department of Head and Neck Surgery & Communication 
Sciences 
Duke University Medical Center 
40 Duke Medicine Circle 
Box 3805 
Durham, NC 27710 
Phone: (919) 681-3841 
daniel.rocke@dm.duke.edu 
 
  
Institutions: 
Duke University Medical Center 
DUMC Box 3805  
Durham, NC 27710 
Walter Lee, MD 
Ph: 919 681 8449 
Email: walter.lee@duke.edu 
 
Vivo Surgical Private Limited 
67 Ayer Rajah Crescent #01-01/02 
Singapore 139950 
Phone: +65 66770395 
Kevin Koh, MD, CEO and Founder 
kevinkoh@vivo-surgical.com  
 
 
 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
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Other Key 
Personnel: 
Leah Zullig, PhD 
Associate Professor 
Department of Population Health Sciences 
Duke University Medical Center 
215 Morris St. 
Durham, NC 27701 
Ph: 919 668 0300 
leah.zullig@duke.edu 
 
Maragatha Kuchibhatla, PhD 
Professor of Biostatistics and Bioinformatics 
Duke University Medical Center 
Duke Box 3003,  
Durham, NC 27710 
Ph: 919 660 7526 
Email: maggie.kuchibhatla@duke.edu  

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
4 
2 INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
2.1 
Background Information 
Head and neck cancers (HNC) are the 6th most common cancers worldwide, with an 
incidence of 550,000 patients/year and a mortality rate of 356,000 patients/year 
(International; Jemal et al., 2011). Most HNC occur in the upper aerodigestive tract, 
which includes nasopharyngeal, tonsil, tongue, hypopharyngeal and larynx (voicebox) 
cancers (Figure 1).  
 
 
Proper examination of the head and neck region 
without specialized equipment and devices makes 
HNC difficult to diagnose at earlier stages.  
 
A critical tool that has improved the examination of the 
areas where HNC can present is the FNS. The FNS is 
used for assessment of the entire upper aerodigestive 
tract by Ear, Nose, and Throat (ENT) doctors or 
otolaryngologists and is part of SOC in developed 
countries. This scope is inserted through the nasal 
passages into the pharynx, enabling a full view of all 
areas at risk for HNC. Furthermore, it allows for 
assessment of function of this area (e.g. vocal cord 
movement) that can provide important information for early 
detection of cancers. Currently, FNS systems at tertiary 
medical centers in the US cost around $10,000 and are 
large and heavy, limiting their use to a single room. Figure 
2 shows an example of a currently available system that 
includes a monitor, scope, light source, image processor, 
and printer.  
 
 
 
 
This study seeks to develop a low cost FNS scope that can be used in low resource 
settings.  The hope is that with an affordable device, this will improve the ability to 
screen for HNC.   The optimization phase will compare this new prototype with standard 
SOC scopes used at Duke University. 
 
2.2 
Rationale 
 
There is a rising global incidence of HNC in LMICs. Specifically, Vietnam has one of the 
highest incidences of HNC and the healthcare system is not meeting this need. Local 
provincial/district hospitals often lack scopes that provide adequate evaluations for 
patients. National/central hospitals have proper equipment for examinations, but are 
Figure 2: FNS System 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
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overburdened by patients, many of which could have been cared for and treated locally 
if they could have been examined properly at local hospitals. A low cost FNS would 
significantly improve the ability of ENT doctors at these local hospitals to properly 
examine patients. Furthermore, training and equipping users at the district/provincial 
hospitals with this scope could improve clinical decisions as to which patients can be 
locally treated vs. referred. This could result in refocusing patient care burden at 
national specialty hospitals to conditions that truly need tertiary care (i.e. advanced 
HNC), rather than conditions that could be addressed at provincial/district hospitals.   
 
Based on preliminary work, we have collected feedback from physicians on how to 
improve on our basic prototype. This includes providing consistent image quality to 
visualize the structures in the upper aerodigestive tract as well as improve lighting.  
Furthermore, the diameter of the scope is to be decreased to improve scope insertion 
and patient comfort. These factors are being incorporated into the first prototype to be 
used in this current clinical study.  The goal is to optimize the low-cost scope as 
compared to the current SOC scope used at Duke.  
2.3 
Potential Risks and Benefits 
2.3.1 
Potential Risks 
The SOC scope exam is done through the nasal cavity.  Risks for the SOC include stiff 
neck, sore throat, temporary perceived difficulty breathing, bleeding, and minor damage 
to the lining of the airway. These are all considered very rare and self- limiting. 
  
The risks to the subjects using the FNS include stiff neck, sore throat, temporary 
perceived difficulty breathing, bleeding, and minor damage to the lining of the airway. 
These are all considered very rare and self- limiting. 
2.3.2 
Potential Benefits 
There are potential benefits to large parts of the developing world, if an affordable, 
easily portable scope proves clinically acceptable. There may be benefit for earlier 
detection of cancer or other lesions using the FNS in settings in which no scope device 
is available. 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
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3 OBJECTIVES AND OUTCOME MEASURES 
OBJECTIVES: 
 
We will collect user feedback and reliability of the low-cost FNS scope as compared 
with the currently used SOC scope procedure.  Collection of technical issues with the 
low cost FNS prototypes will also include steering, lighting, video, fogging, image 
capture. 
 
 Key objectives include comparisons between the SOC scope and FNS: 
 
Primary 
Ease of use   
 
 
 
 
Compared with the first scope, how easy was the second scope to use?  
Very Hard  Harder   same      Easier  Very Easy 
1   
2 
   3 
        4  
5 
  
. 
Secondary 
1) Image Quality 
Rate the video quality of the first scope:     
   (Poor) 1  2  3  4  5  (Excellent) 
 
Rate the video quality of the second scope:   
   (Poor) 1  2  3  4  5  (Excellent) 
 
2) Perceived pain by subjects 
 
 
 
Did you experience more, the same, or less pain/discomfort with the second scope 
compared with the first scope?       
                      
     much more  about the same  much less 
 
1 
 
2 
 
3                    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
13 March 2023 
 
 
Based on NIDCR Interventional Protocol Template v5.0–20190311 
7 
 
 
OUTCOME MEASURES 
3.1 
Primary 
Objective 
Brief 
Description/Justification 
of Outcome Measure 
Outcome Measured 
By  
Time Frame 
Assess ease of 
use by end users 
between the SOC 
scope and FNS 
We are comparing the ease 
of use between the FNS to 
the SOC scope. This will 
impact the design 
considerations and 
modification for the 
prototype optimization. 
Compared with the first 
scope, how easy was 
the second scope to 
use?  
Very Hard   1  
Harder      2 
 
Same          3 
Easier    4 
Very Easy   5 
Up to 2 months 
3.2 
Secondary 
Objective 
Brief Description/ 
Justification of Outcome 
Measure 
Outcome Measured By  Time Frame 
Assess image 
quality and subject 
pain  
Comparison of image quality 
between the SOC scope and 
FNS as well as subject 
perception of pain between 
the two exams will help to 
inform modifications needed 
for prototype optimization. 
image quality of each 
scope: 
rated 1(poor) to 5 
(excellent) 
  
perceived pain by 
subjects between 
scopes: 
Much More           1 
About the same   2  
Much Less       3 
 
up to 2 months 
 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
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Based on NIDCR Interventional Protocol Template v5.0–20190311 
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4 STUDY DESIGN 
The Optimization Phase (Phase 1) Due to new regulatory restrictions in Vietnam, the 
optimization phase for Aim 1 will now be conducted at Duke University.   This will allow 
us to obtain data from subjects and providers that will be helpful in determining if 
additional adjustments or improvements are needed to the FNS prototype. Direct 
comparison between the current approach using available SOC flexible scopes with the 
new approach using the low cost FNS will be made. Potential eligible subjects being 
seen in the Duke Head and Neck Surgery and Communication Sciences clinic meeting 
clinical indication for a SOC scope exam will be approached for the study. If consent is 
given, the subject will first undergo the “SOC” scope endoscopy. Then the FNS exam 
will be performed using the prototype. A post-procedure survey will then be 
administered and completed by both the provider and subject. Post-procedure data will 
be collected in three areas: technical assessment, physician feedback, and subject 
feedback. 
 
The entire study procedure after consent takes about 5 minutes: ~one minute for the 
SOC scope procedure, ~one minute to change to the FNS scope, ~one minute for the 
FNS procedure, ~one minute to complete the study survey. We will have at least two 
low cost FNS to use. To allow for high level disinfection (HLD) between use, we will 
recruit 2 study participants in the morning clinic session, and 2 in the afternoon for a 
total of 4 participants per day.    
 
Data will be collected using REDCap on a tablet to enable real time data collection. 
REDCap is a browser-based survey data collection platform. The data input tablet will 
be password protected and coded. Data will be stored in the REDCap database. Data 
will be collected after each FNS scope procedure and will include a technical 
assessment from the physician. This assessment includes ease of use, and quality of 
the image. Finally, the subjects will use a numeric scale to assess and compare pain 
experience between the two scope procedures. Collection of adverse events will also be 
via REDCap at this time. 
 
The study participation is completed on the scope when survey information is collected. 
Data collection for each FNS prototype will involve a cohort of up to 50 subjects.  
 
This technical and subjective feedback from subjects and providers will be used to 
optimize the device during the Optimization Phase. Each outcome measure as 
described in Section 3.1 and 3.2 will be compared between the SOC scope to the low 
cost FNS and used as a basis for modifications.  For example, if the low-cost FNS 
image quality is noted to have lower ratings compared to the SOC scope due to 
inadequate lighting, modifications will be made to increase the light output for the next 
prototype.  
 
The goal is to modify the prototype so that the outcome measures from the low cost 
FNS meet or exceed the outcome measures from the SOC scope. If this is the case, no 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
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Based on NIDCR Interventional Protocol Template v5.0–20190311 
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further prototypes will need to be performed for the optimization phase. Thus, the 
threshold for success will be noninferiority of the FNS compared to the SOC scope. 
 
In addition to survey feedback, the FNS will have capacity to capture anonymized 
images of the upper aerodigestive tract such as the oropharynx, larynx, and 
nasopharynx. These will be collected and stored to a centralized image library. There 
will be no link to the subject, thus preventing loss of confidentiality.  
 

Partnership to establish a practice-based network to assess for head and neck 
cancers using a low-cost portable flexible nasopharyngoscope - Optimization 
Version 8.0 
IRB Protocol Pro00102912 
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Based on NIDCR Interventional Protocol Template v5.0–20190311 
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5        POPULATION 
5.1 
Participant Inclusion Criteria 
To be eligible to participate in this study, an individual must meet all of the following 
criteria: 
• Willing and able to provide signed and dated written informed consent  
• Willing to comply with all study procedures and be available for the duration of 
the study  
• Male or female, aged 18 or older 
• Patients who clinically meet clinical criteria for SOC scope examination of the 
upper aerodigestive tract. This includes signs and symptoms such as dysphagia, 
nasal obstruction, neck mass, throat pain, and hoarseness.  
5.2 
Participant Exclusion Criteria 
An individual who meets any of the following criteria at baseline will be excluded from 
participation in this study: 
• Withdrawal of consent during the study duration 
• Subjects who have complications from the SOC exam  
• Anyone unable to undergo the SOC exam 
5.3 
Strategies for Recruitment and Retention 
Optimization Phase: Based on our prior work, 20 patients are seen daily per provider 
within the HNC Clinic at Duke University. We have 2 full time surgeons and 2 part time 
surgeons that see patients.  About 50% of these patients require a SOC scope 
procedure. It is estimated that up to 50% of these patients would be willing to participate 
in this study. Thus, our target of having up to 50 subjects to assess each scope 
prototype version in order to make improvements focused on the stated outcomes is 
feasible and can be accomplished within 2-3 weeks.  Participating HNC providers will be 
trained on the study and use of device prior to start of subject recruitment.  
 
Potential subjects will be identified by their HNC provider during a SOC visit. The 
provider will ascertain interest in study participation. If a potential subject expresses 
interest then a member of the study team will review eligibility and conduct the consent 
process prior to the SOC scope exam and start of study activities. If the subject is not 
able to tolerate or has complications from the SOC scope exam then he/she will be 
considered a screen failure.  

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5.4 
Participant Withdrawal or Discontinuation from Study 
Procedures/Intervention 
5.4.1 
Reasons for Participant Withdrawal or Discontinuation from Study 
Procedures/Intervention 
Subjects are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue an individual’s participation in an intervention or 
withdraw an individual from the study if: 
• The participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation. 
• Inability to complete the FNS exam (i.e., bilateral nasal obstruction preventing 
passing of the flexible FNS) 
5.4.2 
Handling of Participant Withdrawals from Study or Participant 
Discontinuation of Study Intervention 
The reason for withdrawal will be solicited from the subject if they choose to stop the 
investigational scope exam and this will be recorded in the REDCap database. 
Replacement participants will be recruited until enrollment is complete. Data that is 
already collected will be included in the analysis and not destroyed.   
5.5 
Premature Termination or Suspension of Study 
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 to the investigator, 
funding agency (NIDCR), and regulatory authorities. The principal investigator will also 
promptly inform the IRB and NIDCR and will provide the reason(s) for the termination or 
suspension.  
Circumstances that may warrant termination include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to participants. 
• Insufficient adherence to protocol requirements.   
• Data that are not sufficiently complete and/or evaluable.  
• Determination of futility. 

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6 STUDY INTERVENTION 
6.1 
Study Procedural Intervention(s) Description 
A low-cost, mobile, FNS that could be used in low-resource settings was designed in 
2011 by the PI and collaborators. The FNS is used for assessment of the entire upper 
aerodigestive tract by Ear, Nose, and Throat (ENT) doctors or otolaryngologists and is 
part of SOC in developed countries. This scope is inserted through the nasal passages 
into the pharynx, enabling a full view of all areas at risk for HNC.  
 
This study will test a low cost FNS prototype based on one used in preliminary work 
(Figure 4). It has a self-contained monitor as well as replaceable batteries. There is an 
LED light in the articulating tip.  
The new prototype will be built by Vivo Surgical and addresses many of the barriers to 
the implementation of the technology, and in consideration of aspects identified by 
physicians as being of particular importance. All modified and updated prototypes will 
be submitted to the IRB at Duke, Approval for use will be required prior to any clinical 
use. 
 
 
 
 
The protective sheath covering developed under the supplemental grant will be used 
once it is ready for use (refer to separate COVID19 sheath sub-study document).  
6.2 
Administration of Procedural Intervention 
The FNS will be used only by medical providers in Head and Neck Surgery at Duke. 
This procedural intervention will be only administered during a clinic visit. The 
participation is considered complete once the subject leaves the clinic visit. The actual 
duration of the FNS procedural intervention is estimated to last about 1 minute.   
6.3 
Procedures for Training of Clinicians on Procedural Intervention 
Training will occur prior to the recruitment of subjects and initiation of study activities. 
Training sessions, led by the PI – Dr. Walter Lee will include details on the operation, 
cleaning, and care of the scopes. The clinicians for the optimization phase are faculty 
and are familiar with using a flexible scope.   
 
 
 
Figure 4: FNS prototype with LED lighted articulating tip and attached user monitor. 

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6.4 
Assessment of Clinician and/or Participant Compliance with Study 
Procedural Intervention 
 
The 9 steps of the intervention FNS protocol are below.  
1. Confirm understanding of procedure and subject consent. Confirm newly 
disinfected scope is being used. 
2. Lubricate the FNS tip with gel and wipe FNS tip as needed to obtain clear image. 
Check mobility of FNS tip. 
3. Place scope into nares with direct vision then look at screen. 
4. Insert through nasal cavity being careful not to apply pressure on the nasal 
septum. 
5. Assess nasal cavity, nasopharynx. Document any clinical findings per routine 
care practices. 
6. Direct tip to make bend at nasopharynx and have subject breathe through the 
nose. This relaxes soft palate and opens airway. 
7. Assess oropharynx by having subject protrude tongue.  Assess larynx and 
hypopharynx by having subject phonate and sniff and swallow. Document and 
clinical findings per routine care practices. 
8. Straighten tip and withdraw scope.  
9. Immediately send scope for HLD per SOP.  Complete study survey questions 
and assessment of SAE. 
 
 

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7 STUDY SCHEDULE 
7.1 
Enrollment/Baseline 
• Obtain and document consent from participant on study consent form. 
• Verify inclusion/exclusion criteria.   
• Administer the SOC scope then FNS study intervention.  
• Administer post procedural surveys:  
o Provider survey 
o Subject survey 

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8 STUDY PROCEDURES/EVALUATIONS 
8.1 
Study Procedures/Evaluations 
The Study procedure includes the following: 
AIM 1:  
FNS scope procedure 
 
 
Post procedure survey 
The FNS procedure has been described in section 6.4. 
All surveys will be recorded via REDCap. This will be immediately completed by a study 
investigator and also the subject (as indicated). 
(Surveys can be found under supplemental materials section of the protocol) 

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9  ASSESSMENT OF SAFETY 
This study involves optimization of a low cost FNS.  This is considered a 
nonsignificant risk investigational device by the FDA (21 CFR 874.4760  -  Class 
II device). The risks are rare and include: stiff neck, sore throat, temporary loss of 
voice, temporary perceived difficulty breathing, bleeding, and minor damage to 
the lining of the airway.  These are all self-limiting.  
Prior to use in subjects, all study investigators will demonstrate competency in 
the FNS exam and study procedures.  Only certified ENT surgeons listed as key 
personnel with the IRB will be performing the FNS exam. Manual HLD will be 
performed with Revital-Ox RESERT, a 2% Accelerated Hydrogen Peroxide 
solution, per manufacture instructions for use 
After each study FNS procedure, the study investigator will record any observed 
adverse events. If there are adverse events, the subject will be observed until 
stabilization of the event has occurred. These are recorded real time to the 
REDCap database.  If there are AE or unanticipated problems (UPs), the PI 
(WTL) will be notified via email.   
The optimization phase of this study will be conducted at Duke University 
Medical Center and will require safety monitoring and oversight. The Duke study 
team will review safety information in real time as data are collected, as well as a 
monthly basis.  Adverse events will be reported as outlined in the sections below.    
9.1 
Specification of Safety Parameters 
Unanticipated problems (UPs) will be recorded in the data collection system (REDCap) 
and must be reported to the IRB and NIDCR in accordance with Duke IRB-defined 
timeline for reporting policy. An Adverse Event must be reported to the IRB if it: (i) is 
more likely than not related to study activities; and (ii) represents a new risk; and (iii) is 
unanticipated. In addition, an expected event that is occurring at a frequency or intensity 
greater than originally anticipated must be reported to the IRB.   
UPs include incidents, experiences, and outcomes that are not adverse events, as well 
as a subset of adverse events. This study will follow Duke IRB policy for reporting other 
events to the IRB.  
All serious adverse events (SAEs) that are also determined to be UPs will be reported 
to NIDCR and the IRB concurrently, for assessment by the NIDCR Medical Monitor.  
Determining whether a particular adverse event is unexpected by virtue of an 
unexpectedly higher frequency can only be done through an analysis of appropriate 
data on all subjects enrolled in the research. If the investigator determines that an 
adverse event is not an unanticipated problem, but the NIDCR Medical Monitor 
subsequently determines that the adverse event does represent an unanticipated 
problem (for example, due to an unexpectedly higher frequency of the event), the 
NIDCR Medical Monitor will report this determination to the investigator, and such 
reports must be promptly submitted by the investigator to the IRB.   

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9.1.1 
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. 
 
9.1.2 
Adverse Events 
An adverse event is any untoward or unfavorable medical occurrence in a human 
subject, including any symptom temporally associated with the subject’s participation in 
the research, whether or not considered related to the subject’s participation in the 
research. 
9.1.3 
Serious Adverse Events  
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 
• 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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9.2 
Time Period and Frequency for Event Assessment and Follow-Up 
The PI and/or study team will record all events occurring any time after informed 
consent is obtained until the subject leaves the clinic. Subjects will only be allowed to 
leave the clinic once resolution of the event or patient stabilization occurs. This is 
adequate for the following reasons: 1) trained physicians skilled with endoscopic 
examinations are present to conduct the procedure and observe patients, 2) incidence 
of adverse events is rare, and 3) direct visualization of the placement of the scope will 
occur, thus preventing adverse events. 
9.3 
Characteristics of an Adverse Event 
Each event will be recorded on an appropriate case report form that includes 
assessment of the characteristics defined below. These characteristics, along with the 
frequency of an event’s occurrence, will be considered in determining if the event is a 
UP. 
9.3.1 
Relationship to Study Intervention 
To assess relationship of an event to study intervention the following guidelines are 
used: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention, and/or 
b. There is a temporal relationship between the intervention and event onset 
and/or 
c. The event abates when the intervention is discontinued, and/or 
d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event 
onset, and/or 
b. An alternate etiology has been established. 
9.3.2 
Expectedness  
The Study PI and/or study-appointed, clinically/medically responsible individual will 
determine whether an AE is expected or unexpected. An AE will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent with the 
risk information previously described for the intervention.     
 

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9.3.3 
Severity of Event 
The following scale will be used to grade adverse events: 
1. Mild: no intervention required 
2. Moderate: minimal, local, or non-invasive intervention indicated 
3. Severe: significant symptoms requiring invasive intervention; subject seeks 
medical attention 
9.4 
Reporting Procedures 
9.4.1 
Unanticipated Problem Reporting  
Incidents or events that meet the OHRP criteria for unanticipated problems require the 
creation and completion of an unanticipated problem report form. OHRP recommends 
that investigators include the following information when reporting an adverse event, or 
any other incident, experience, or outcome as an unanticipated problem to the IRB: 
• appropriate identifying information for the research protocol, such as the title, 
investigator’s name, and the IRB project number; 
• a detailed description of the adverse event, incident, experience, or outcome;  
• an explanation of the basis for determining that the adverse event, incident, 
experience, or outcome represents an unanticipated problem;  
• a description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the unanticipated problem. 
To satisfy the requirement for prompt reporting, unanticipated problems will be reported 
using the following timeline:   
• Immediately (within 24 hours) upon learning of an unanticipated study-related 
death, study personnel will notify the IRB via phone or e-mail by providing a brief 
summary of the event. Then, within 1 week (five business days), study personnel 
will send to the IRB a Safety Event submission in the eIRB. 
• All unanticipated problems should be reported to appropriate institutional officials 
(as required by an institution’s written reporting procedures), the supporting 
agency head (or designee), and OHRP within one month of the IRB’s receipt of 
the report of the problem from the investigator. 
All unanticipated problems will be reported to NIDCR concurrently with reporting to the 
IRB. These reports will be made to NIDCR’s centralized reporting system via the 
CROMS contractor. Additional reporting instructions can be found in the MOP. 

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9.4.2 
Serious Adverse Event Reporting  
The study’s clinically responsible individual will complete a Serious Adverse Event Form 
and submit via fax or email within the following timelines:   
• For a reportable serious adverse event, study personnel will notify the IRB within 
five business days of the investigator becoming aware of the event. Study 
personnel will send a Safety Event submission in the eIRB. 
• For any other problem or event requiring prompt reporting to the IRB, within ten 
business days of the investigator becoming aware of the event, study personnel 
will send to the IRB a Safety Event submission in the eIRB. 
All SAEs will be followed until resolution or stabilization.  
9.5 
Halting Rules 
Subsequent review of serious, unexpected, and related AEs by the Medical Monitor, 
Data and Safety Monitoring Board (DSMB), IRB, the sponsor(s), or relevant local 
regulatory authorities may also result in suspension of further study 
interventions/administration of study product at a site. The study sponsor(s) retain the 
authority to suspend additional enrollment and study interventions/administration of 
study product for the entire study, as applicable. 
Examples of findings that might trigger a safety review are the number of SAEs overall, 
the number of occurrences of a particular type of SAE, severe AEs/reactions, or 
increased frequency of events. 

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10 STUDY OVERSIGHT 
Dr. Lee, Dr. Koh and Dr. Tan will have monthly meetings to assess progress and FNS 
feedback from end users.  
The Advisory Board for this project is comprised of leaders in biomedical engineering, 
global health, and device development. The role of the advisory board will include 
advising regarding optimizing the prototype within the specified time period of 3 months.  
Dr. Walter Lee (PI, Duke University), and Kevin Koh (Vivo Surgical) will have formal 
meetings with the advisory board twice per year. 
In addition to the PI’s responsibility for oversight, study oversight will be under the 
direction of the Specialized Technology and Devices for Head and Neck Cancers 
(STAND) Data and Safety Monitoring Board (DSMB), who is composed of members 
with expertise in Head and Neck Squamous Cell Carcinoma and imaging, 
bioethics/health policy, practice-based research, and biostatistics. The DSMB will meet 
regularly, at an interval to be determined, to assess safety and efficacy data, study 
progress, and data integrity for the study.  Per instructions given by the DSMB, safety 
reports will include the grades of adverse events and a summary of changes to the 
protocol, if there are any.  The first DSMB safety report will be submitted three months 
following the start of the study.  If safety concerns arise, more frequent meetings may 
be held. The DSMB will operate under the rules of an NIDCR-approved charter that will 
be approved at the organizational meeting of the DSMB. At this time, most data 
elements that the DSMB needs to assess will be clearly defined. The DSMB will provide 
recommendations to the NIDCR.   

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11 CLINICAL SITE MONITORING 
The sponsor-investigator or principal investigator (PI), and Duke Cancer Institute (DCI), 
through the PRMS and PRMC, will monitor this clinical research study. For internal 
review, the sponsor-investigator or PI will continuously monitor and tabulate adverse 
events. The study team will make reports to the Duke University Hospital System 
(DUHS) Institutional Review Board (IRB). If an unexpected frequency of Grade III or IV 
events occur, depending on their nature, action appropriate to the nature and frequency 
of these adverse events (AE) will be taken. This may require a protocol amendment or 
potentially study closure. The study sponsor-investigator or PI will also continuously 
monitor study conduct, data, and safety to ensure: 
• Interim analyses occur as scheduled. 
• Stopping rules for toxicity and/or response are met. 
• Risk/benefit ratio is not altered to subject detriment. 
• Appropriate internal AE and outcomes monitoring is performed. 
• Over-accrual does not occur. 
• Under-accrual is addressed with appropriate amendments or actions. 
• Data are being appropriately collected in a reasonably timely manner. 
PRMS protocol review begins with the PRMC. PRMC new protocol reviews focus on 
scientific relevance, study design, biostatistical input adequacy, protocol prioritization, 
feasibility of study completion within a reasonable time frame and trial risk assessment. 
The sponsor-investigator or PI will abide by PRMC risk level assessment. PRMC also 
conducts annual scientific progress reviews on protocols open to enrollment and 
focuses on protocol prioritization, accrual, and scientific progress. The PRMC conducts 
reviews at the time of IRB annual renewals and maintains documentation in iRIS. 
During the initial PRMC approval, the PRMC determines the monitoring risk level and 
frequency which will be commensurate with the type and level of intervention, phase, 
endpoints, degree of risk, size, and protocol complexity. The DCI monitoring team will 
conduct formal, independent monitoring according to the risk level and the PRMC 
monitoring plan until the study is closed to enrollment or subjects are no longer 
receiving study drug or other interventions that are more than minimal risk.  
The DCI has determined this study to be “moderate risk/complexity”. Moderate Risk is 
defined as “Behavioral intervention, complex observational or sample/tissue or blood 
collection studies deemed more than minimal risk. These studies require a physical 
intervention with a participant”.     
Per the DCI’s Data and Safety Monitoring Plan (DSMP), moderate risk studies undergo 
the following: A minimum of 10% of records to be reviewed every 6 months. Review 
may be more frequent based on findings in initial study review, enrollment, or at the 
request of the DCI Safety Oversight Committee or School of Medicine Clinical Quality 
Management Program.  

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Findings from monitoring visits, unexpected frequency of serious and/or unexpected 
toxicities, or other concerns may prompt additional monitoring. DUHS and DCI 
Leadership, PRMC, DCI Safety Oversight Committee (SOC), a sponsor, an investigator, 
or the IRB may also request additional monitoring visits.  
The DCI monitoring team reviews informed consent adequacy, eligible patient 
enrollment, protocol-specified procedures and treatment implementation, data collection 
adequacy, and adverse event monitoring and reporting appropriateness. The DCI 
monitoring team presents final monitoring reports to the DCI SOC highlighting safety 
concerns and unresolved issues. The SOC, at a convened meeting, assigns an overall 
rating of satisfactory, marginal, or unsatisfactory to reflect the overall data quality, 
regulatory, consent, eligibility, study conduct, and AE reporting. Corrective action plans 
(CAPs) are developed, implemented, and evaluated as indicated. The SOC will notify 
the sponsor-investigator or PI and DUHS IRB when significant safety concerns are 
identified. 
The SOC in conjunction with the DCI monitoring team conducts data and safety 
monitoring for DUHS sponsor-investigator or PI Phase I and II, therapeutic 
interventional oncology studies that do not have an independent Data Safety Monitoring 
Board (DSMB). These reviews occur at a minimum annually and possibly more 
frequently based on risk level. The SOC safety reviews include safety, data accuracy, 
enrollment status, stopping rules if applicable, accrual, toxicities, reference literature, 
and interim analyses as the sponsor-investigator provides. The SOC, at a convened 
meeting, assigns a “satisfactory” rating when adequate accrual with lack of excessive 
toxicity is present.  
Clinical site monitoring is conducted to ensure that the rights of human subjects are 
protected, that the study is implemented in accordance with the protocol and/or other 
operating procedures, and that the quality and integrity of study data and data collection 
methods are maintained.  In addition, monitoring for this study will be performed by 
NIDCR’s Clinical Research Operations and Management Support (CROMS) contractor. 
The monitor will evaluate study processes and documentation based on NIDCR 
standards and the International Conference on Harmonisation (ICH), E6: Good Clinical 
Practice guidelines (GCP). 
Details of documented in a Clinical Monitoring Plan (CMP) developed by the CROMS 
contractor, in collaboration with the NIDCR Office of Clinical Trials and Operations 
Management (OCTOM) and the NIDCR Program Official. The CMP will specify the 
frequency of monitoring, monitoring procedures, the level of clinical site monitoring 
activities (e.g., the percentage of subject data to be reviewed), and the distribution of 
monitoring reports.  Some monitoring activities may be performed remotely, while others 
will take place at the study site(s).  Staff from the CROMS contractor will conduct 
monitoring activities and provide reports of the findings and associated action items in 
accordance with the details described in the CMP.  Documentation of monitoring 
activities and findings will be provided to the site study team, the study PIs, OCTOM, 

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and the NIDCR. The NIDCR reserves the right to conduct independent audits as 
necessary. 
 
 

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12 STATISTICAL CONSIDERATIONS 
12.1 
Study Hypotheses 
The study hypothesis is that a low cost FNS can be non-inferior to the SOC scope in 
terms of ease of use, image quality, and perceived pain.  
12.2 
Sample Size Considerations 
 
Aim 1 is aimed at optimizing the FNS for its optimal functioning as explained in the 
recruitment described above.  
 
Fixing alpha at 0.05, power at 80%, a sample size of 37 produces a two-sided 95% 
confidence interval with a width equal to 0.2 when the sample proportion of success is 
0.9. The lower and upper confidence interval for this success rate of 0.9. is 0.76 and 
0.96 respectively (PASS 16, 2018).  Hence at the end of testing on 37 subjects, if the 
proportion who answer good outcomes as described in scenario 1 is between 0.76 and 
0.96, phase one of the study is a success.   
 
Power Analysis and Sample Size Software (2018). NCSS, LLC. Kaysville, Utah, USA, 
ncss.com/software/pass). 
 
12.2.1 Safety Review 
A review of adverse events will be done by the PI weekly. This will be done through 
review of the survey data.  More frequent review may need to occur if SAE's will be 
identified and reported to the IRB within 5 days as stated in section 9.4.2 
12.2.2 Efficacy Review 
This study is an optimization study and seeks to optimize a low cost FNS for clinical 
use.  
12.3 
Final Analysis Plan 
Statistical Analysis – Aim 1: Optimization Phase. 
1. Outcome 1 (Primary): The primary outcome is ease of use comparison between 
the FNS to the SOC scope (score of 1 – 5, with 1 being very hard and 5 being 
very easy). 
2. Outcome 2 (Secondary): Quality of the image (image quality score range 1-5, 
with 1 being poor and 5 being excellent). 
3. Outcome 3 (Secondary): Perceived pain between the FNS to the SOC scope 
(pain score range of 1 – 3, with 1 being much more and 3 being much less). 
 
Scenario 1:  

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Success of this first phase 1 (Aim 1) after evaluating 37 subjects is defined as - (1) at 
least 90% response of ease of use of second scope compared to first score to range 
from same to excellent (3 to 5); and (2) 90% responding to better video quality of 
second scope compared to first (score ranging from same to excellent (3 to 5); and (3) 
90% responding to pain score of same or much less (2 or 3); In short, this phase is a 
success if 90% respond to same to excellent/much less on all 3 of the outcomes. 
Scenario 2: If the rate is between 50 to < 90% for any three outcomes in a sample from 
37, then the plan is to proceed recruiting more subjects until 50 are recruited. At 50 
subjects, if in scenario 1 then phase 1 is a success and phase 1 is complete; if not, fine 
tune the prototype.  
Scenario 3: If the rate is < 50% for any one of the 3 outcomes described above, then 
the plan is to proceed to fine tuning the prototype. 
 
The primary outcome of ease of use of scope as reported by the physicians, will be 
examined between the two different scopes, at the simplest level, using paired Z-test if 
the scores (or transformed scores) are normally distributed or by using Wilcoxon test if 
the scores are non-normal.  
 
The analysis for secondary outcomes of the change in the quality of the videos and pain 
will each be examined using paired Z-test, if the change (or transformed scores) is 
normally distributed or by Wilcoxon test if the change is non-normal. Assumptions of each 
of these tests will be examined. The significance of each of the outcomes will be examined 
at alpha = 0.05 The reliability of this instrument (using intra-class-correlation (ICC)) will 
be first assessed by using the data from the first 50 subjects. If ICC is < 0.9, we will include 
training component and necessary adjustment for the physicians. 
 
See diagram below 

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13 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Source documents will include signed consent forms kept at the local study site, as well 
as the REDCap database which is web based.  Study staff will maintain appropriate 
research records for this study, in compliance with ICH E6, Section 4.9 and regulatory 
and institutional requirements for the protection of confidentiality of participants. Study 
staff will permit authorized representatives of NIDCR 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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14 QUALITY CONTROL AND QUALITY ASSURANCE 
PHI will be collected and stored on subjects enrolled at Duke. All potential subjects 
who are approached about study participation will be entered in a screening log. 
Those who agree to participate by providing written informed consent will be entered 
in the enrollment log and assigned a unique study ID number. Identifiers such as 
name, medical record number and date of study visit will be included in the 
enrollment log and the REDCap database.  If electronic consent is obtained then 
email address will also be collected. Quality reviews will be done by the PI and study 
team on a weekly basis, and per the independent internal monitor as outlined in the 
CQMP.  The PI and Study Coordinator (SC) will be responsible for correcting 
procedures that are not in compliance with protocol and quality control issues 
(correcting errors in data entry).  
A kick-off meeting will be conducted to train study staff on the protocol and use of 
FNS device prior to start of study activities. 
The Industry partner will assess the quality of the scopes prior and during usage.  
The industry partner will provide adequate support for repair or replacement as 
needed. 

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15 ETHICS/PROTECTION OF HUMAN SUBJECTS 
15.1 
Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the 
principles set forth in The Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research, as drafted by the US National Commission 
for the Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 
1979) and codified in 45 CFR Part 46 and/or the ICH E6, the Declaration of Helsinki, 
and the International Ethical Guidelines for Biomedical Research Involving Human 
Subjects (2002).  
15.2 
Institutional Review Board 
Review and approval of this protocol and the associated informed consent documents 
and recruitment materials by an appropriate IRB registered with the OHRP will be 
obtained.  Duke University Health System IRB will be the IRB of record for the 
optimization phase. The FWA number assigned to Duke’s IRB is FWA00009025, 
expiring 2/11/2027. 
The protocol, informed consent form(s), and all participant materials will be submitted to 
the IRB for review and approval. Approval of both the protocol and the consent form(s) 
must be obtained before any participant is enrolled.  Amendments to the protocol will 
require review and approval by the IRB and NIDCR before the changes are 
implemented in the study.   
15.3 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to 
participate in the study and continues throughout study participation. Written informed 
consent will be obtained by paper or electronic consent. An oral explanation of the study 
will be given to the potential subjects, and they will be asked to also read and sign the 
consent from. A copy will be provided to them. If electronic consent is obtained then an 
electronic copy will be automatically sent to the participants email address.  Consent 
forms will be IRB-approved, and the participant is required to be able to read and review 
the document.  The investigator or designee will explain the research study to the 
participant and answer any questions that may arise. The participant will sign the 
informed consent document prior to any study-related assessments or procedures.  
Participants will be given the opportunity to discuss the study with their surrogates or 
think about it prior to agreeing to participate. They may withdraw consent at any time 
during the course of the study. The rights and welfare of the participants will be 
protected by emphasizing to them that the quality of their clinical care will not be 
adversely affected if they decline to participate in this study. 
 
The consent process will be documented in the electronic health record.   

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15.4 
Exclusion of Women, Minorities, and Children (Special Populations) 
There are no exclusionary criteria for the study population based on sex/gender, race, 
or ethnic background. As this is a focused device study on a new low-cost FNS, there is 
no scientific reason to exclude any subject by sex/gender, race of ethnic group, or 
pregnancy status. We are excluding children as head and neck cancers are very rare in 
this population. 
15.5 
Subject Confidentiality 
Subject confidentiality is strictly held in trust by the investigators, study staff, and the 
study sponsor(s) and their agents.  
The study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the study 
sponsor. 
The study monitor or other authorized representatives of NIDCR may inspect all study 
documents and records required to be maintained by the investigator, including but not 
limited to source documents and survey responses for the study participants. The 
clinical study site will permit access to such records. 
Certificate of Confidentiality  
To further protect the privacy of study participants, the Secretary, Health and Human 
Services (HHS), has issued a Certificate of Confidentiality (CoC) to all researchers 
engaged in biomedical, behavioral, clinical, or other human subjects research funded 
wholly or in part by the federal government. Recipients of NIH funding for human 
subjects research are required to protect identifiable research information from forced 
disclosure per the terms of the NIH Policy (https://humansubjects.nih.gov/coc/index). As 
set forth in 45 CFR Part 75.303(a) and NIHGPS Chapter 8.3, recipients conducting NIH-
supported research covered by this Policy are required to establish and maintain 
effective internal controls (e.g., policies and procedures) that provide reasonable 
assurance that the award is managed in compliance with Federal statutes, regulations, 
and the terms and conditions of award. It is the NIH policy that investigators and others 
who have access to research records will not disclose identifying information except 
when the participant consents or in certain instances when federal, state, or local law or 
regulation requires disclosure. NIH expects investigators to inform research participants 
of the protections and the limits to protections provided by a Certificate issued by this 
Policy. 
NIH Data Sharing Policies  
As described in section 17, it is NIH policy that the results and accomplishments of the 
activities that it funds should be made available to the public (see 
https://grants.nih.gov/policy/sharing.htm). PIs and funding recipient institutions will 

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ensure that all mechanisms used to share data include proper plans and safeguards to 
protect the rights and privacy of individuals who participate in NIH-sponsored research.  

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16 DATA HANDLING AND RECORD KEEPING 
The investigators are responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported. All source documents should be completed in a 
neat, legible manner to ensure accurate interpretation of data. The investigators will 
maintain adequate case histories of study participants, including accurate case report 
forms (CRFs), and source documentation. 
16.1 
Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff 
under the supervision of the investigator. All source documents must be reviewed by the 
study team and data entry staff, who will ensure that they are accurate and complete. 
Unanticipated problems and adverse events must be reviewed by the investigator or 
designee.   
16.2 
Data Capture Methods 
The team will work with the research staff to develop a REDCap EDC that meets the 
data collection needs for the project. Data being collected for this project does not 
include identifiable information. The data will be stored in a HIPAA Compliant EDC. A 
member of the Clinical Data Management Team will have access to the data as outlined 
above for the duration of the project in order to oversee data security and data integrity 
on behalf of the Department and the Study Team.  
16.3 
Types of Data 
Data containing PHI will be stored locally in the Duke REDCap database and the 
electronic screening/enrollment logs; PHI will include name, medical record number, 
email address, and date of visit. Survey data will include health care providers 
assessment of the prototype’s 1) Ease of use and 2) quality of images. This will also 
include assessment of adverse events.  
 
Furthermore, subjective pain comparison between the SOC and prototype scopes will 
be collected from the subject and study investigator via a tablet.  
Data review and reports will occur at least twice a year or more frequently based on the 
final CQMP plan approved by the Duke School of Medicine’s Office of Clinical Research 
from site visits by the independent medical monitor. Protocol and data review will occur 
during internal monitoring per the CQMP guidance document. Reporting enrollment 
schedule to the NIDCR will be determined by NIDCR and NIDCR appointed DSMB. 
 
16.4 
SCHEDULE AND CONTENT OF REPORTS 
Data review and reports will occur at least twice a year from clinical site monitoring 
activities, as described under protocol section 11. Protocol and data review will also 
occur prior to DSMB reporting. The specific schedule or reporting will be determined by 
NIDCR and the NIDCR appointed DSMB.  

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16.5 
Study Records Retention 
Study records will be maintained for a minimum of six years following the completion of 
the study (closure with the IRB), or a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending, or contemplated 
marketing applications in an ICH region, or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product (whichever 
is longer). These documents should be retained for a longer period, however, if required 
by local regulations. No records will be destroyed without the written consent of the 
sponsor, if applicable. It is the responsibility of the sponsor to inform the investigator 
when these documents no longer need to be retained. 
16.6 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol or Good 
Clinical Practice requirements. The noncompliance may be on the part of the 
participant, 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. 
All deviations from the protocol must be addressed in study participant source 
documents and promptly reported to NIDCR and the IRB, according to their 
requirements. 

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17 PUBLICATION/DATA SHARING  
This study will comply with all applicable NIH Data Sharing Policies. See 
https://grants.nih.gov/policy/sharing.htm for policies and resources. 
NIH Public Access Policy 
The NIH Public Access Policy requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to PubMed Central immediately upon acceptance 
for publication. This ensures that the public has access to the published results of NIH 
funded research.  

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18 LITERATURE REFERENCES 
Abendstein, H., Nordgren, M., Boysen, M., Jannert, M., Silander, E., Ahlner-Elmqvist, M., 
Bjordal, K. (2005). Quality of life and head and neck cancer: a 5 year prospective study. 
Laryngoscope, 115(12), 2183-2192. doi:10.1097/01.MLG.0000181507.69620.14 
 
 
Bellmunt, A. M., Roberts, R., Lee, W. T., Schulz, K., Pynnonen, M. A., Crowson, M. G., Shin, J. 
J. (2016). Does an Otolaryngology-Specific Database Have Added Value? A Comparative 
Feasibility Analysis. Otolaryngol Head Neck Surg, 155(1), 56-64. doi:10.1177/0194599816651036 
 
Chapurin, N., Pynnonen, M. A., Roberts, R., Schulz, K., Shin, J. J., Witsell, D. L., Lee, W. T. 
(2017). CHEER National Study of Chronic Rhinosinusitis Practice Patterns: Disease 
Comorbidities and Factors Associated with Surgery. Otolaryngol Head Neck Surg, 156(4), 751-
756. doi:10.1177/0194599817691476 
 
Cheng, T.-M. (2014). Vietnam’s Health Care System Emphasizes Prevention And Pursues 
Universal Coverage. Health Aff (Millwood), 33(11), 2057-2063. doi:10.1377/hlthaff.2014.1141 
 
Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences. Hillsdale NJ: Lawrence 
Earlbaum. Crowson, M. G., Schulz, K., Parham, K., Vambutas, A., Witsell, D., Lee, W. T., 
Langman, A. (2016). Meniere's Disease: A CHEER Database Study of Local and Regional 
Patient Encounter and Procedure Patterns. Otolaryngol Head Neck Surg, 155(1), 15-21. 
doi:10.1177/0194599815617752 
 
Curran, G. M, Bauer, M., Mittman, B., Pyne, J. M., Stetler, C. (2012). Effectiveness-
implementation hybrid designs: combining elements of clinical effectiveness and implementation 
research to enhance public health impact. Med Care, 50(3), 217-26. doi: 
10.1097/MLR.0b013e3182408812. 
 
Esteva, A., Kuprel, B., Novoa, R. A., Ko, J., Swetter, S. M., Blau, H. M., & Thrun, S. (2017). 
Dermatologist-level classification of skin cancer with deep neural networks. Nature, 542(7639), 
115-118. doi:10.1038/nature 21056  
 
Ghafoorian, M., Karssemeijer, N., Heskes, T., van Uden, I. W. M., Sanchez, C. I., Litjens, G., 
Platel, B. (2017). Location Sensitive Deep Convolutional Neural Networks for Segmentation of 
White Matter Hyperintensities. Sci Rep, 7(1), 5110. doi:10.1038/s41598-017-05300-5 
 
Gibson, C. B. (2017). Elaboration, Generalization, Triangulation, and Interpretation On 
Enhancing the Value of Mixed Method Research. Organizational Research Methods, 20(2), 193-
223. doi.org/10.1177/1094428116639133 
 
Gupta, A., Keuskamp, D. (2018).Use and misuse of mixed methods in population oral health 
research: A scoping review. Community Dent Health. 30;35(2):109-118. doi: 
10.1922/CDH_4250Gupta10.  
 
 
Hanna, E. Y., Mendoza, T. R., Rosenthal, D. I., Gunn, G. B., Sehra, P., Yucel, E., & Cleeland, 
C. S. (2014). The symptom burden of treatment-naive patients with head and neck cancer. 
Cancer. doi:10.1002/cncr.29097 

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International, W. C. R. F. Cancer Statistics Worldwide. Retrieved from 
http://www.wcrf.org/cancer_statistics/world_cancer_statistics.php 
 
Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer 
statistics. CA Cancer J Clin, 61(2), 69-90. doi:10.3322/caac.20107 
 
Lawrentschuk, N., & Chamberlain, M. (2005). Sterile disposable sheath system for flexible 
cystoscopes. Urology, 66(6), 1310-1313. doi:10.1016/j.urology.2005.06.118 
 
Lê Quang Cường, L. N. K., Khương Anh Tuấn, Trần Thị Mai Oanh, Dương Huy Lương, Nguyễn 
Thị Minh Hiếu, Trịnh Ngọc Thành, Hoàng Thu Thủy, Nguyễn Thị Thắng et al. (2011). Study on 
current situation of overcrowding, under-crowding in hospitals at levels and recommended 
solutions for improvement.  
 
 
 
Lee, W. T., Witsell, D. L., Parham, K., Shin, J. J., Chapurin, N., Pynnonen, M. A., Schulz, K. 
(2016). Tonsillectomy Bleed Rates across the CHEER Practice Research Network: Pursuing 
Guideline Adherence and Quality Improvement. Otolaryngol Head Neck Surg, 155(1), 28-32. 
doi:10.1177/0194599816630523 
 
 
Ministry of Health, V. (2016). For People's Health Protection, Care and Promotion 2016-2020. Hanoi, 
Vietnam. 
 
NCCN National Pratice Guidelines in Oncology : Head and Neck Cancers. (2014). (2 ed.). 
NCCN.org.  
 
Osthus, A. A., Aarstad, A. K., Olofsson, J., & Aarstad, H. J. (2011). Head and neck specific 
Health Related Quality of Life scores predict subsequent survival in successfully treated head 
and neck cancer patients: a prospective cohort study. Oral Oncol, 47(10), 974-979. 
doi:10.1016/j.oraloncology.2011.07.010 
 
Parham, K., Chapurin, N., Schulz, K., Shin, J. J., Pynnonen, M. A., Witsell, D. L., Lee, W. T. 
(2016). Thyroid Disease and Surgery in CHEER: The Nation's Otolaryngology-Head and Neck 
Surgery Practice-Based Network. Otolaryngol Head Neck Surg, 155(1), 22-27. 
doi:10.1177/0194599815627641 
 
PASS,2016, NCSS 11 Statistical Software (2016). NCSS, LLC. Kaysville, Utah, USA, 
ncss.com/software/ncss 
 
Piker, E. G., Schulz, K., Parham, K., Vambutas, A., Witsell, D., Tucci, D., Lee, W. T. (2016). 
Variation in the Use of Vestibular Diagnostic Testing for Patients Presenting to Otolaryngology 
Clinics with Dizziness. Otolaryngol Head Neck Surg, 155(1), 42-47. 
doi:10.1177/0194599816650173 
 

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Powell, B. J., McMillen, J. C., Proctor, E. K., Carpenter, C. R., Griffey, R. T., Bunger, A. C., 
Glass, J. E., York, J. L. (2012). A compilation of strategies for implementing clinical innovations 
in health and mental health. Med Care Res Rev, 69(2),123-57. doi: 10.1177/1077558711430690. 
 
Powell, B. J., Waltz, T. J., Chinman, M. J., Damschroder, L. J., Smith J. L., Matthieu M. M., 
Proctor, E. K., Kirchner, J. E. (2015). A refined compilation of implementation strategies: results 
from the Expert Recommendations for Implementing Change (ERIC) project. Implement Sci, 12, 
10:21. doi: 10.1186/s13012-015-0209-1. 
 
 
Schroy, P. C., 3rd, Wilson, S., & Afdhal, N. (1996). Feasibility of high-volume screening 
sigmoidoscopy using a flexible fiberoptic endoscope and a disposable sheath system. Am J 
Gastroenterol, 91(7), 1331-1337. 
 
 
 
Vo, Q. T., Pham, D., Choi, K. J., Nguyen, U. T., Le, L., Shanewise, T., Lee, W. T. (2017). Solar-
powered hearing aids for children with impaired hearing in Vietnam: a pilot study. Paediatr Int 
Child Health, 1-6. doi:10.1080/20469047.2016.1276119 
 
 

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SUPPLEMENTAL MATERIALS 
Post-Procedural Survey By Clinician who performed the scope exam 
(Provider questions once the SOC and study FNS exams are completed): 
 
  
TECHNICAL ASSESSMENT OF FNS 
Were you able to complete the first scope procedure to your satisfaction?   
1=no  2=somewhat 3=yes 
 
Were you able to complete the second scope procedure to your satisfaction 
1=no  2=somewhat 3=yes 
 
Were you able to view all the structures of concern using first scope ?  Y/N   
If no, please explain: 
 
Were you able to view all the structures of concern using second scope ?  Y/N   
If no, please explain: 
 
 
Did the patient appear to have more, the same, or less discomfort with the second 
scope?       
                           much more   about the same   much less 
 
 
 
1 
 
2 
 
3    
If much more: please describe why: 
 
Were there technical issues with the second prototype scope?  Y/N  ( if Yes, please 
explain below) 
                  ____ steering 
 
       ____ lighting 
                  ____ video 
 
       ____ fogging 
 
       ____ image capture 
                  ____ other 
 
Ease of use: Aim 1:  
Compared with the first scope, how easy was the second scope to use?  
Very hard    Harder  same      Easier    Very easy 
1   
2 
3 
        4  
5 
 
If harder or very hard: please explain: 
 
Quality of Images: Aim 1 
 
Rate the video quality of the first scope:     
(Poor) 1  2  3  4  5   (Excellent) 

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Rate the video quality of the second scope:   
(Poor) 1  2  3  4  5  (Excellent) 
 
Did the subject experience an AE: Y / N 
 
 
If yes - please provide additional information below: 
Name of adverse event: __________________________________ 
 
Brief description of the problem or event:  
 
 
Severity of adverse event (using scale below): 
1. Mild: no intervention required 
2. Moderate: minimal, local, or non-invasive intervention indicated 
3. Severe: significant symptoms requiring invasive intervention; subject seeks 
medical attention 
 
 
Is the adverse event related to study procedure?    
1. If related, please specify: Possibly, Probably, or Definitely related 
a) 
The event is known to occur with the study intervention, and/or 
b) 
There is a temporal relationship between the intervention and event onset 
and/or 
c) 
The event abates when the intervention is discontinued, and/or 
d) 
The event reappears upon a re-challenge with the intervention. 
2. If not related, please specify if unlikely related or Not Related) 
a) 
There is no temporal relationship between the intervention and event 
onset, and/or 
b) 
An alternate etiology has been established. 
Is the problem/event unexpected?  Y/N 
  Does the event meet the definition of a serious adverse event?  Y/N  
 
If yes, check criteria below:  
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
1. Results in death 

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2. Is life-threatening (places the subject at immediate risk of death from the event 
as it occurred) 
3. Results in inpatient hospitalization or prolongation of existing hospitalization 
4. Results in a persistent or significant disability or incapacity 
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. 
 
 
Outcome of adverse event:     resolved or unresolved 
Date of resolution:  
 
For enrolled subjects 
Pain Comparison: Aim 1-secondary objective 
Did you experience more, the same, or less pain/discomfort with the second scope 
compared with the first scope?       
 
    much more  about the same   much less 
 
1 
 
2 
 
3   
 
 
 
 
 
 
 
 
 
 
 
 

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CONSENT FORM FOR PARTICIPATING IN RESEARCH 
Duke’s IRB approved consent form will be provided separately