Evaluation of the Clinical Performance of an Investigational Real-Time Colorectal Polyp Clinical Decision Support Device (CDSD)
Conditions: Polyp, Colorectal, Colonoscopy
Sponsor: Olympus Corporation of the Americas

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                                                                                                                 Protocol # OCA 2019-GI-03 
Version # 2.0 (AUG 31 2020) 
 
 
 
 
 
Evaluation of the Clinical Performance of an Investigational Real-Time 
Colorectal Polyp Clinical Decision Support Device (CDSD) 
 
Protocol # OCA 2019-GI-03 
 
 
CLINICAL INVESTIGATION PLAN 
 
 
 
 
 
Sponsored By 
Olympus Corporation of the Americas (OCA) 
 
 
 
 
 
 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
 
Do not copy or distribute without written permission from Olympus. 
 
 
 
 

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                                                                                                                 Protocol # OCA 2019-GI-03 
Version # 2.0 (AUG 31 2020) 
 
Contact Information 
Role 
Contact  
Clinical Contact 
Jeremy Bolt 
Senior Manager, Clinical Affairs 
Olympus Corporation of the Americas 
118 Turnpike Road 
Southborough, MA 01772 
Jeremy.bolt@olympus.com 
(508) 579-8495 
 
 
Coordinating Principal 
Investigator 
Douglas Rex, MD 
Indiana University Medical Center 
Indianapolis, IN 
 
 
 

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                                                                                                                 Protocol # OCA 2019-GI-03 
Version # 2.0 (AUG 31 2020) 
 
Original Release: FEB 18 2020 
Current Version: 2.0 
 
Revision History 
Version Number 
Release Date 
Section 
Change 
Reason for Change 
1.0 
FEB 18 2020 
N/A 
N/A 
Initial Release 
2.0 
AUG 31 2020 
Multiple 
 
Incorporate FDA 
feedback on Statistical 
Analysis Plan (sample 
size re-calculation, 
adoption of bootstrap 
methodology, treatment 
of normal tissue 
pathology results and 
recuts, additional 
endpoint regarding 
discordant unaided and 
aided results, etc.) 
 
Minor update to 
exclusion criteria 
regarding bowel prep 
based on principal 
investigator clinical 
experience 
 
Other minor content and 
administrative updates 
Incorporated feedback from 
FDA Pre-submission 
Q181327/S003 
 
 
 
 

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                                                                                                                 Protocol # OCA 2019-GI-03 
Version # 2.0 (AUG 31 2020) 
 
 
 
 
 
 
Sponsor Protocol Approval Page 
  
STUDY TITLE: 
Evaluation of the Clinical Performance of an 
Investigational Real-Time Colorectal Polyp Clinical 
Decision Support Device (CDSD) 
 
PROTOCOL NUMBER: 
Protocol # OCA 2019-GI-03 
VERSION NUMBER: 
2.0 (AUG 31 2020) 
 
 
We, the undersigned, have read and approve the protocol specified above and agree on its 
content. 
Haytham Gareer, MD 
Vice President, Clinical Affairs 
 
  
Date: 
Jeremy Bolt  
Senior Manager, Clinical Affairs 
  
  
Date: 

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Protocol # OCA 2019-GI-03 
Version # 2.0 (AUG 31 2020) 
Investigator Protocol Approval Page 
 
Evaluation of the Clinical Performance of an Investigational Real-Time 
Colorectal Polyp Clinical Decision Support Device (CDSD) 
 
Protocol # OCA 2019-GI-03 
 
Protocol Version 2.0 (AUG 31 2020) 
 
I hereby agree to participate in the above noted study sponsored by Olympus. (here in after 
protocol provided by the Study Sponsor in accordance with applicable local regulations, and 
in accordance with the conditions imposed by the reviewing Institutional Review Board 
(IRB).  I agree to supervise all use of the study devices and to ensure appropriate informed 
consent is obtained from all subjects prior to inclusion in this study. 
I understand that this investigation will be monitored by the Study Sponsor and/or a designee 
employed by the Study Sponsor. This monitoring will involve periodic inspection of my 
investigational site and ongoing review of the data that are submitted by me to the Study 
Sponsor.   
I am aware that the Study Sponsor reserves the right to discontinue this investigation at any 
time. 
I understand this study protocol and trial results are confidential, and I agree not to disclose 
any such information to any person other than a representative of the Study Sponsor, the 
IRB/EC, or regulatory authorities without the prior written consent of the Study Sponsor. 
 
Accepted by: 
 
 
 
_________________________________       _________________________ 
Principal Investigator  
 
 
  Date 
 
 
______________________________________________________________ 
Printed Name  

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Protocol # OCA 2019-GI-03 
Version # 2.0 (AUG 31 2020) 
Protocol Synopsis 
Evaluation of the Clinical Performance of an Investigational Real-Time 
Colorectal Polyp Clinical Decision Support Device (CDSD) 
Study 
Objective(s) 
The study objective is to establish the efficacy of the colorectal polyp 
CDSD in clinical use. 
Planned 
Indication(s) 
for Use  
The colorectal polyp Clinical Decision Support Device is intended to 
support authorized healthcare professionals in increasing histological 
prediction accuracy of physician-identified diminutive (  5mm) 
polyps during colonoscopy for documentation and comparison with 
pathology.  
 
The device does not mark, highlight, or d
specific location in the original image. The device is not intended to 
replace histopathological sampling as a means of diagnosis. 
Test Device 
The investigational device consists of software residing on a 
dedicated computer enabling display of a polyp histology prediction 
(Adenoma or Non-Adenoma) in the Picture-in-Picture area of the 
endoscopic screen during colonoscopy procedures when Narrow 
Band Imaging (NBI) is engaged. The CDSD-aided endoscopist 
makes a final prediction of histology considering CDSD output. 
Control Device Unaided endoscopist prediction of polyp histology using NBI. 
Study Design 
Prospective, single arm, multicenter study 
Planned 
Number of 
Subjects 
A minimum of 2,400 subjects will be enrolled in order to obtain 
predictions on at least 1,918 diminutive polyps.  It is anticipated that 
the study will take up to 6 months to complete. 
Investigational 
Sites 
Up to seven investigational sites in the USA will be utilized. 
Co-Primary 
Endpoint(s) 
Sensitivity and Specificity of CDSD-aided endoscopist predictions  
compared with unaided NBI prediction on the same polyp. 
Additional 
Endpoints 
1. Number, proportion, unaided NBI prediction and pathology result 
of diminutive polyps detected by the endoscopist and confirmed by 
pathology for which CDSD does not return a prediction. 

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Protocol # OCA 2019-GI-03 
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Evaluation of the Clinical Performance of an Investigational Real-Time 
Colorectal Polyp Clinical Decision Support Device (CDSD) 
2. Sensitivity, specificity, NPV, PPV of unaided endoscopist 
prediction using white light compared with pathology. 
3. Sensitivity, specificity, NPV, PPV of unaided endoscopist 
prediction using NBI compared with pathology.  
4. Sensitivity, specificity, NPV, PPV of CDSD prediction compared 
with pathology. 
5. Sensitivity, specificity, NPV, PPV of CDSD-aided endoscopist 
prediction compared with pathology. 
6. Number, proportions and pathology results for diminutive polyps 
with discordant unaided predictions using NBI and aided 
predictions with CDSD. 
 
Method of 
Assigning 
Subjects to 
Treatment 
Consecutive subjects presenting for colonoscopy and meeting the 
pre-procedure entrance criteria will be consented and screened.  
Subjects meeting all the entrance criteria will be enrolled and 
undergo colonoscopy per the standard of care with the added use of 
CDSD. 
After detection of a polyp by the endoscopist, the user will make 
three histological predictions (adenoma or non-adenoma): 
1) using white light 
2) using NBI 
3) using CDSD 
 
Visit Schedule 
1. Screening (Clinic Visit) 
a. Informed consent 
b. Pre-procedural entrance criteria 
2. Baseline (Clinic Visit) 
a. Demographics 
b. Relevant medical history 
3. Procedure (Clinic Visit) 
a. Colonoscopy procedure 
b. Procedural entrance criteria 

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Protocol # OCA 2019-GI-03 
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Evaluation of the Clinical Performance of an Investigational Real-Time 
Colorectal Polyp Clinical Decision Support Device (CDSD) 
c. Unaided endoscopist prediction using white light 
d. Unaided endoscopist prediction using NBI and confidence 
level (high or low) 
e. CDSD prediction 
f. CDSD-aided endoscopist prediction and confidence level 
(high or low) 
4. Immediate Post Procedure Evaluation (Lab results only) 
a. Pathological results 
5. End of Study 
a. End of study will be reached after final pathology results 
have been obtained (typically within one to two weeks of 
the procedure). 
 
Study Duration results are obtained. Study enrollment is anticipated to take up to 6 
months to complete. 
Key Patient 
Inclusion 
Criteria 
1. 
 18 years of age 
2. Willing and able to provide informed consent 
3. Subjects undergoing colonoscopy  
Key Patient 
Exclusion 
Criteria 
1. Polyposis syndromes including Familial Adenomatous 
Polyposis Syndrome 
2. Inflammatory Bowel Disease 
3. Hereditary Non Polyposis Colorectal Cancer 
4. Severe coagulopathy 
5. Subjects scoring less than 6 on the Boston Bowel Prep Score. 
6. No diminutive polyps detected during colonoscopy 
 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
The co-primary effectiveness endpoint is the sensitivity and specificity 
of CDSD-aided endoscopist prediction. 

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The hypothesis for Sensitivity is: 
H0Sn:Sn CDSD-aided  
 CDSD-unaided 
H1Sn: Sn CDSD-aided  >  Sn CDSD-unaided  
 
The hypothesis for Specificity is: 
H0Sp:Sp CDSD-aided  
 CDSD-unaided 
H1Sp:Sp CDSD-aided  >  Sp CDSD-unaided 
The overall hypothesis tested is that the CDSD-aided endoscopist 
predictions of polyp histology will have superior sensitivity and 
specificity as compared with the unaided endoscopist predictions of 
histology on the same polyps.  
H0: H0Sn or H0Sp 
H1:  H1Sn and H1Sp 
 
Statistical Test 
Method 
Bootstrap resampling 95% confidence intervals for the difference 
between CDSD aided and unaided sensitivity and specificity, with 
bootstrap resampling performed first at the endoscopist level, then at the 
patient level. 
Sample Size 
Parameters 
Based on a review of the literature, without CDSD, the operator 
sensitivity is presumed to be 88% and the specificity is presumed to be 
58% across all operators1 6. The operator sensitivity with CDSD is 
presumed to be 92% and the specificity with CDSD is presumed to be 
73% across all operators based on validation testing. In order to 
demonstrate the primary endpoint with 80% power and one-sided 
significance level of 2.5% a minimum of 2400 subjects and 40 
endoscopists are required. Assuming 52% of subjects will have one or 
more diminutive polyps7, 1.81 diminutive polyps per subject having at 
least one diminutive polyp7 and an adenoma prevalence of 58%7 yields a 
minimum requirement of 1918 polyps. 
 
 
 

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Table of Contents
INTRODUCTION ................................................................................................................13
DEVICE DESCRIPTION......................................................................................................13
STUDY OBJECTIVES .........................................................................................................17
STUDY ENDPOINTS ...........................................................................................................17
STUDY DESIGN .................................................................................................................17
Scale and Duration................................................................................................20
Treatment Assignment..........................................................................................20
Justification for the Study Design........................................................................21
SUBJECT SELECTION........................................................................................................21
Study Population and Eligibility..........................................................................21
Entrance Criteria ..................................................................................................21
SUBJECT ACCOUNTABILITY.............................................................................................22
Point of Enrollment...............................................................................................22
STUDY METHODS .............................................................................................................22
Data Collection ......................................................................................................22
Informed Consent .................................................................................................22
Screening/Enrollment ...........................................................................................23
Colonoscopy Procedure ........................................................................................23
Post-Procedure ......................................................................................................23
Study Completion..................................................................................................24
Source Documents.................................................................................................24
Local Laboratory Documentation .......................................................................24
STATISTICAL CONSIDERATIONS ......................................................................................24
Endpoints ...............................................................................................................24
General Statistical Methods .................................................................................28
DATA MANAGEMENT.......................................................................................................29
Data Collection, Processing, and Review............................................................29

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Data Retention.......................................................................................................29
AMENDMENTS ..................................................................................................................30
DEVIATIONS .....................................................................................................................30
DEVICE/EQUIPMENT ACCOUNTABILITY .........................................................................30
COMPLIANCE....................................................................................................................31
Statement of Compliance......................................................................................31
Investigator Responsibilities ................................................................................31
Institutional Review Board ..................................................................................32
Sponsor Responsibilities.......................................................................................33
Insurance................................................................................................................33
MONITORING....................................................................................................................34
POTENTIAL RISKS AND BENEFITS ...................................................................................34
Risks Associated with the Study Device(s)..........................................................34
Anticipated Benefits..............................................................................................34
Risk to Benefit Rationale......................................................................................34
SAFETY REPORTING.........................................................................................................34
Reportable Events by investigational site to Olympus ......................................34
Olympus Device Deficiencies................................................................................35
INFORMED CONSENT........................................................................................................35
SUSPENSION OR TERMINATION .......................................................................................36
Premature Termination of the Study ..................................................................36
Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval ................................................................................................................36
Requirements for Documentation and Subject Follow-up................................37
Criteria for Suspending/Terminating a Study Site............................................37
PUBLICATION POLICY......................................................................................................37
BIBLIOGRAPHY.................................................................................................................38
Abbreviations ........................................................................................................40

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Table of Figures 
Figure 2-1: System Overview ................................................................................................. 14 
Figure 2-2: Graphical User Interface of CDSD ...................................................................... 15 
Figure 5-1: Procedure Flow .................................................................................................... 18 
 
Table of Tables 
Table 2-1: CDSD Hardware Specification ............................................................................. 14 
Table 2-2: Non-Investigation Devices Required/Recommended ........................................... 17 
Table 5-1: NBI International Colorectal Endoscopic (NICE) Classification ......................... 19 
Table 8-1: Data Collection Schedule ...................................................................................... 22 
Table 9-1: Sample 2x2 Table for Paired Adenoma Predictions with NBI (Reference Standard 
Positive) ............................................................................................................... 25 
Table 9-2: Sample 2x2 Table for Paired Non-Adenoma Predictions with NBI (Reference 
Standard Negative) .............................................................................................. 25 
Table 9-3: Assumptions for Proportions of Predictions for Adenomas (Sensitivity, Reference 
Standard Positive) with CF-HQ190 ..................................................................... 27 
Table 9-4: Assumptions for Proportions of Predictions for Adenomas (Sensitivity, Reference 
Standard Positive) with PCF-H190 ..................................................................... 27 
Table 9-5: Assumptions for Proportions of Predictions for Non-Adenomas (Specificity, 
Reference Standard Negative) with CF-HQ190 .................................................. 28 
Table 9-6: Assumptions for Proportions of Predictions for Non-Adenomas (Specificity, 
Reference Standard Negative) with PCF-H190 ................................................... 28 
Table 21-1: Abbreviations ...................................................................................................... 40 
 

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Introduction
Screening colonoscopy is considered the gold standard for colorectal cancer detection and 
prevention in the United States. Central to screening colonoscopy is the detection of 
adenomatous lesions. Adenomas are considered neoplastic lesions and their removal during 
colonoscopy is thought to disrupt the adenoma-carcinoma progression8. Their presence also 
influences the probability that an average-risk individual will develop colon cancer and so 
the number and size of adenomas detected during colonoscopy are a critical part of the 
-polypectomy colon cancer surveillance interval9. One 
hallmark of adenomas and advanced neoplastic lesions is their enrichment with capillaries 
compared with normal colon mucosa and non-neoplastic polyps10
Imaging (NBI) is an endoscopic visualization method and adjunctive tool, cleared via 510(k) 
(K131780) in which broad spectrum white light illumination is filtered into bands of violet 
and blue light11,12. Preferential absorption of this light by oxy-hemoglobin in red blood cells 
residing in capillaries and vessels of the mucosa leads to their accentuation under NBI 
observation. 
Over the last decade researchers have validated a handful of classification systems using NBI 
to accurately differentiate colorectal polyps as adenomatous or non-adenomatous based on 
color, presence and structure of vessels and mucosal surface patterns13.  The NBI 
International Colorectal Endoscopic (NICE) Classification is one such system that was 
specifically created for simple characterization of diminutive (
5mm) and small (< 10mm)
polyps with non-magnifying endoscopes commonly available in Western nations14 and 
experienced endoscopists have reached high levels of diagnostic accuracy in visual 
assessments relative to pathological analysis7,15 21. Despite this, application of NBI for real-
time polyp characterization by community-level and non-expert endoscopists have yielded 
mixed results for performance 1,4,5,22, possibly due to variation in endoscopist skill, attention 
to detail or motivation.
Characterizing diminutive colorectal polyps as adenomatous and non-adenomatous, the two 
major classes of colorectal lesions, remains a clinical challenge for many practicing 
endoscopists. An adjunctive tool such as CDSD may aid in this distinction by increasing the 
number of accurate predictions relative to ground truth pathological analysis. The proposed 
study seeks to establish the effectiveness of CDSD as an adjunctive tool to assist 
endoscopists in the assessment of diminutive colorectal polyps.
Device Description
The investigational device consists of clinical decision support software (CDS) hosted on a 
dedicated, non-networked, medical accessory computer (the colorectal polyp Clinical 
Decision Support Device
The Device 
connects directly to the Olympus CV-190 Video Processor (non-investigational) and sits on 
the open bottom shelf of the medical cart while in use. See Figure 2-1 and Table 2-1 for 
details.

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Figure 2-1: System Overview 
 
 
Table 2-1: CDSD Hardware Specification 
Dimensions 
 
Processor 
Intel i7 
Memory 
16GB DDR4 
Hard Drive 
Solid State Drive, Enterprise Grade 
GPU 
nVidia Quadro P4000 
Capture Card 
HD-SDI input/output 
USB Ports 
2x Front/ 4x Rear 
Operating System 
Windows 10 IOT, 64 bit 
 
The Device connects to the Olympus CV-190 Video Processor through two HD-SDI cables, 
enabling the receipt of the endoscopic signal from the CV-
output to the CV-190 for display in the Picture-in-Picture (PiP) region of the endoscopic 
monitor.  
The software composing the Device contains two modules:  
 
 
 
 

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2.1.1 User Interface Module  
The CDS continuously receives the raw (unfiltered) endoscopic video stream from the CV-190 
video processor, and integrates the data from the AI module into the final information 
displayed by the UI module. This information is presented as both a text output and progress 
bar in the PiP region of the monitor alongside the raw video output. The presented text output 
-
 prediction 
repeatability is not achieved, too variable over consecutive frames or no polyp is present in the 
video stream that is identifiable to the AI module. The progress bar illustrates model prediction 
repeatability and is color-coded to identify suspected adenoma/non-adenoma. Figure 2-2 
depicts these different outputs. 
Figure 2-2: Graphical User Interface of CDSD 
Empty Bar 
 NBI is not engaged, OR 
 NBI is engaged but the software 
cannot classify the polyp or no polyp 
is present 
Filling Bar 
 The software is classifying a polyp 
Result: Non-Adenoma 
 The 
software 
has 
repeatedly 
classified the suspected polyp and 
has returned a result of Non-
Adenoma. 

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Result: Adenoma
 The 
software 
has 
repeatedly 
classified the suspected polyp and 
has returned a result of Adenoma. 
 
 
The information of the investigational device does not obfuscate the primary endoscopic video 
arly identified as 
-2) to ensure the endoscopist does not mistake it for 
the primary endoscopic video.  
2.1.2 Artificial Intelligence Module 
The AI module is composed of a static AI model, trained on raw endoscopic videos (video 
recordings) originating from unaltered recordings of colorectal polyps, specifically of 
data as input (full frame, no segmentation), and outputs two data streams:  
(1) Classification of video frames into white light mode versus Olympus CV-190 
NBI mode, and  
(2) 
-
 
Information from the AI module is presented to the operator, via the User Interface module 
described in section 2.1.1 only when the Olympus CV-190 processor is engaged in the NBI 
mode by the operator.  
The investigational Device connects to and is used with the Olympus EVIS EXERA III, 
which includes the CV-190 Video Processor (CV-190). The EVIS EXERA III system was 
last cleared via 510(k) K131780. During the clinical study, the EVIS EXERA III system will 
be used within its cleared indication for use. 
Further, table 2-2 provides a complete listing of non-investigational devices needed or 
recommended for use in the clinical study.  
 
 

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Table 2-2: Non-Investigation Devices Required/Recommended 
Device *
Manufacturer
Description
Required or 
Recommended
CV-190
Olympus
Endoscopic video processor
Required
CLV-190
Olympus
Endoscopic light source
Required
OEV-262
Olympus
Endoscopic video monitor
Recommended
One or more of the following colonoscopes:
CF-HQ190L
Olympus
Colonoscope
Required 
PCF-H190(D)L
Olympus
Colonoscope
Required
Study Objectives
The study objective is to establish the efficacy of the colorectal polyp CDSD in clinical use.
Study Endpoints
Co-Primary Endpoint:
Sensitivity and Specificity of CDSD-aided endoscopist predictions compared with unaided 
prediction on the same polyp.
Secondary Endpoints:
1.
Number, proportion unaided NBI prediction and pathology result of diminutive polyps 
detected by the endoscopist and confirmed by pathology for which CDSD does not return a 
prediction.
2.
Sensitivity, specificity, NPV, PPV of unaided endoscopist prediction using white light.
3.
Sensitivity, specificity, NPV, PPV of unaided endoscopist prediction using NBI.
4.
Sensitivity, specificity, NPV, PPV of CDSD prediction.
5.
Sensitivity, specificity, NPV, PPV of CDSD-aided endoscopist prediction.
6.
Number, proportions and pathology results for diminutive polyps with discordant unaided 
predictions using NBI and aided predictions with CDSD.
Study Design
The study shall be a prospective, single arm, multicenter study. Endoscopists comprising a 
range of clinical experience will be invited to participate in the study at each site. All 

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participating endoscopists will receive an overview of the NICE classification to guide their 
unaided and CDSD-aided assessments as well as instruction on the use of CDSD.   
 
For each participating endoscopist, consecutive subjects presenting for colonoscopy and 
meeting the pre-procedure entrance criteria will be consented and screened.  Consented 
subjects meeting all the entrance criteria will be enrolled and undergo colonoscopy per the 
standard of care with the added use of CDSD. CDSD-unaided and CDSD-aided predictions 
will be compared with the ground truth of histopathology. Presuming at least 40 endoscopists 
participate, each endoscopist will make approximately 60 predictions on diminutive polyps 
through the course of the study. 
 
 
Figure 5-1: Procedure Flow 
 
During the procedure, the endoscopist will insert the colonoscope to the cecum as per 
standard of care. Examination will be under white light illumination. Typically during 
withdrawal, but also during insertion at the discretion of the endoscopist, identified lesions 

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will have their location, size and shape documented. The endoscopist will inspect the lesions 
and estimate the size of lesion (diameter in mm) using a device such as the tip of a biopsy 
forceps or snare catheter tip as is common practice. Diminutive size is defined as a diameter 
5mm. For diminutive polyps, an initial histology prediction will be made in white light as 
-
NBI will 
be engaged and the endoscope tip will be steadied with the lesion centered. The endoscopist 
will be blinded to the CDSD result. The endoscopist will make a second prediction of polyp 
-
-
1). NICE Type 1 will be defined as Non-Adenoma and NICE Type 2 will be defined as 
Adenoma. T
prediction. 1,15,16,23. See Table 5-1 for a description of the NICE classification and criteria 
used to predict diminutive polyp histology. 
 
 
Table 5-1: NBI International Colorectal Endoscopic (NICE) Classification 
NICE Classification 
Type 1 
Type 2 
Color 
Same or lighter than 
background 
Browner relative to background 
(verify color arises from 
vessels) 
Vessels 
None, or isolated lacy vessels 
may be present coursing across 
the lesion 
Brown vessels surrounding 
white structures 
Surface Pattern 
Dark or white spots of uniform 
size, or homogeneous absence 
of pattern 
Oval, tubular or branched white 
structures surrounded by brown 
vessels 
Predicted Histology 
(Human or CDSD) 
Non-Adenoma 
Adenoma 
 
 
After making their prediction using NBI alone, the endoscopist or coordinator will enable PiP 
to allow the endoscopist to observe the CDSD result. The CDSD result shall be recorded as 
1) Adenoma, 2) Non-adenoma, or 3) No prediction after system stabilization. The 
endoscopist considers their initial prediction and the output of the device to make a final 
-
will make a determination of their co
If 
CDSD does not return a prediction this does not indicate that no polyp is present. More 
likely, this output is due to the module not being able to make a clear adenoma/non-adenoma 
assessment based on the training the model has received. Based on software validation 
testing, this is expected to occur in approximately 11-16% of the polyps.  In cases that this 
l 
make a final prediction without the aid of CDSD. 
 

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Polyps will be biopsied or resected as per the standard of care and placed in a separate 
specimen jar or polyp trap chamber and uniquely labeled as per standard procedure. The 
exam will continue and the steps above are repeated for each identified diminutive lesion. At 
the end of the procedure, polyp specimens are sent to pathology for review. The pathologist 
is blinded to the endoscopist predictions and CDSD prediction.
The diagnosis will be rendered by the pathologist
characterization, and the pathology report will be reviewed by the endoscopist. A CDSD-
aided or CDSD-unaided prediction of Adenoma will be rendered as a True Positive when the 
conventional a
tubular adenoma), tubulovillous 
adenoma, villous adenoma, traditional serrated adenoma (TSA), adenoma with high grade 
dysplasia or cancer. A CDSD-aided or unaided prediction of non-adenoma will be rendered 
as a True Negative when the pathological diagnosis is hyperplastic polyp, sessile serrated 
polyp (SSP), inflammatory polyp, lymphoid aggregate/follicle, granulation tissue or normal 
colonic mucosa. Diminutive polyps that are lost following resection or destroyed during 
pathology prior to diagnosis will be excluded from the analysis due to lack of ground truth 
pathology results.
In cases where the CDSD-aided endoscopist prediction and the pathology result differs, a 
recut and reanalysis of the tissue block will be conducted. In such cases, the second 
successful pathology reading will be recorded and used as the histopathological ground truth.
Scale and Duration
A minimum of 2,400 subjects will be enrolled in order to obtain predictions on at least 1,918 
diminutive polyps.  It is anticipated that the study will take up to 6 months to complete.
Treatment Assignment
For each participating endoscopist, consecutive subjects presenting for colonoscopy and 
meeting the pre-procedure entrance criteria will be consented and screened.  Subjects 
meeting all the entrance criteria will be enrolled and undergo colonoscopy according to the 
standard of care with the added use of CDSD.
During the procedure, subjects found to meet any of the exclusion criteria will be excluded 
from the study. CDSD will be applied to all endoscopist-identified diminutive polyps in all 
subjects. Pathology will be blinded to all predictions. See Figure 5-1 for details.
5.2.1
Target Lesions
Diminutive ( 5mm) colorectal polyps identified during colonoscopy will be considered 
target lesions. 

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Justification for the Study Design
This study design was chosen to follow current standard of care endoscopy procedures with 
the exception of introduction of CDSD
Pathology remains the gold standard methodology for diagnosis in this study.  The study 
aims to demonstrate that CDSD is capable of increasing the sensitivity and specificity of 
endoscopist predictions for diminutive polyp histology. The single arm design was chosen to 
evaluate the incremental improvement in predictive accuracy relative to the standard of care 
while controlling for variability in polyp presentation by using a matched pair design.  
Inclusion of endoscopists comprising a range of experience is intended to reflect real-life 
clinical practice and potential increased benefit to non-expert users. Blinding allows for 
independence of assessments, and comparison of results without bias.
Subject Selection 
Study Population and Eligibility 
Subjects who provide informed consent and meet all of the inclusion criteria and none of the 
exclusion criteria will be enrolled in this study.
Entrance Criteria
6.2.1
Inclusion Criteria
Subjects who meet all of the following criteria may be given consideration for inclusion in 
this clinical study, provided no exclusion criterion is met. 
1.
2.
Willing and able to provide informed consent
3.
Subject scheduled for colonoscopy
6.2.2
Exclusion Criteria
Subjects who meet any one of the following criteria will be excluded from this clinical study.
1.
Polyposis syndromes including Familial Adenomatous Polyposis (FAP) Syndrome
2.
Inflammatory Bowel Disease (IBD)
3.
Hereditary Non Polyposis Colorectal Cancer (HNPCC)
4.
Severe coagulopathy
5.
Subjects with a cumulative score of 6 or less on the Boston Bowel Prep Score
6.
No diminutive polyps detected during colonoscopy

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Subject Accountability
Point of Enrollment
Existing family history and other standard-of-care screening tests and questions may be used 
to determine subject eligibility for recruitment prior to the colonoscopy procedure. Following 
signing of the informed consent form (ICF), subjects will be defined as being enrolled in the 
study, however; subjects may subsequently be excluded from the study based on findings 
during the procedure consistent with exclusion criteria listed in Section 6.  Consented 
subjects who fail the procedural entrance criteria will be considered screening failures, and 
the reason for exclusion will be recorded.  Subjects who meet all entrance criteria including 
those evaluated during the colonoscopy procedure will be considered the Intent to Treat 
(ITT) population for this study.
Study Methods
Data Collection
Table 8-1: Data Collection Schedule
Procedure/Assessment
Screening / 
Enrollment
Procedure
Post- procedure
(Lab results 
only)
Informed consent
X
Inclusion / Exclusion 
X
X
Demographics
X
Medical history
X
Colonoscopy / CDSD
X
Pathology assessment
X
Follow-up pathology assessment
X (as needed)
Device deficiencies assessment
X
X: Required Procedure/Assessment
Informed Consent
All subjects taking part in this clinical study must undergo the informed consent process. 
Subjects must be allowed adequate time to review the consent, raise questions, and make a 
voluntary decision to participate in the clinical study. Each subject must sign and date the 
IRB approved ICF before any clinical study-related procedures are performed. A copy of 
signed ICF
clinical study begins with the signing and dating of the ICF. 

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8.2.1
Post-Consent Eligibility Validation
Exclusion criteria such as poor bowel prep and absence of diminutive polyps will not be 
known until after the start of the procedure.  Consented subjects who fail exclusion criteria 
during the procedure will be considered screening failures and excluded from the statistical 
analysis. 
Screening/Enrollment
Consecutive subjects presenting for colonoscopy will be considered for participation.  
Existing family history and other standard-of-care screening tests and questions may be used 
to determine subject eligibility for recruitment prior to the colonoscopy procedure.  Subjects 
meeting the pre-procedural entrance criteria will be consented prior to the colonoscopy 
procedure.  Demographic and relevant medical history data will be collected.  Subjects may 
still be excluded from the study during the colonoscopy procedure assessment if they no 
longer meet entrance criteria.
Colonoscopy Procedure
The colonoscopy procedure will proceed as per standard of care with the exception of use of 
CDSD.  The following information will be collected during this visit:
Colonoscopy indication
Endoscopist
Colonoscope model used
Procedure date
Length of procedure (scope in to scope out) including cecal intubation time and 
withdrawal time
Procedural entrance criteria
Unaided physician prediction using white light
Unaided physician prediction and confidence level using NBI
CDSD prediction
CDSD aided physician prediction and confidence level
Number, size, shape and location of all identified polyps
Post-Procedure
Lab results will be collected for all specimens sent to pathology, including secondary lab 
results in cases where a recut/re-analysis of specimen is requested by the endoscopist and 

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performed.  Diagnosis based on pathology will be recorded as well as prescribed surveillance 
interval.
Study Completion
procedure. Data collection shall end following review of the pathology report for any 
specimens resected or biopsied during the procedure. In cases where pathology re-evaluation 
is requested, data collection shall end once all subsequent pathology re-evaluations are 
complete and secondary pathology reports are reviewed by the investigators.
Source Documents
Source documents are the subject records maintained at the study site. In most cases, the 
source documents
chart. In some cases, the 
source documents may be electronic. In both cases, the information captured in the CRF must 
match the information in the chart or electronic source document. The Investigator agrees to 
make source documents (hard copy or electronic) available for monitoring by the Sponsor 
and/or their representatives.
Local Laboratory Documentation
Local laboratories for the clinical sites will be used as per standard practice.  Appropriate 
certifications and documentation records will be collected for the study file.
Statistical Considerations
Endpoints
9.1.1
Primary Endpoint
The co-primary effectiveness endpoint is the sensitivity and specificity of CDSD-aided 
endoscopist prediction.
9.1.1.1
Hypotheses
A 2x2 table for accuracy of paired predictions with NBI is constructed for both adenomas 
(Sn, histology reference standard positive) and non-adenomas (Sp, histology reference 
standard negative) (Tables 9-1 and 9-2).

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Table 9-1: Sample 2x2 Table for Paired Adenoma Predictions with NBI (Reference 
Standard Positive) 
 
CDSD-unaided Prediction 
 
Positive 
Negative 
Total 
CDSD-aided 
Prediction 
Positive 
a 
b 
a+b 
Negative 
c 
d 
c+d 
 
Total 
a+c 
b+d 
a+b+c+d 
 
Table 9-2: Sample 2x2 Table for Paired Non-Adenoma Predictions with NBI (Reference 
Standard Negative) 
 
CDSD-unaided Prediction 
 
Positive 
Negative 
Total 
CDSD-aided 
Prediction 
Positive 
m 
n 
m+n 
Negative 
p 
q 
p+q 
 
Total 
m+p 
n+q 
m+n+p+q 
 
 
In order to test the effect of CDSD, individual hypotheses for sensitivity and specificity will 
be evaluated based on 2x2 tables of paired predictions for adenomas and non-adenomas, 
respectively. The hypothesis for Sensitivity is: 
H0Sn: Sn CDSD-aided  Sn CDSD-unaided  or  
  
 
H1Sn: Sn CDSD-aided > Sn CDSD-unaided  or  
 > 
 
 
The hypothesis for Specificity is: 
H0Sp: Sp CDSD-aided  Sp CDSD-unaided  or  
  
 
H1Sp: Sp CDSD-aided > Sp CDSD-unaided  or  
 > 
 
The overall hypothesis tested is that the CDSD-aided endoscopist predictions of polyp 
histology will have superior sensitivity and specificity as compared with the unaided 
endoscopist predictions of histology on the same polyps.  
 

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H0: H0Sn or H0Sp 
H1:  H1Sn and H1sp 
 
9.1.1.2 Sample Size  
In order to demonstrate the primary endpoint with 80% power and one-sided significance 
level of 2.5% a minimum of 40 endoscopists and approximately 2400 subjects are required. 
Assuming 85% of subjects have adequate bowel preparation, 52% of subjects with adequate 
bowel preparation have one or more diminutive polyps, 1.81 diminutive polyps per subject 
having at least one diminutive polyp and a 58% adenoma prevalence7 yields a minimum 
requirement of 1918 polyps.  
9.1.1.3 Statistical Methods 
The 95% confidence intervals for the differences between CDSD-aided and CDSD-unaided 
sensitivity and specificity are estimated using bootstrap resampling with resampling 
performed first at the endoscopist level and then at the patient level. The null hypothesis is 
rejected if both lower bounds of the confidence intervals are greater than 0. 
Sn CDSD-aided - Sn CDSD-unaided > 0 
Sp CDSD-aided - Sp CDSD-unaided > 0 
The assumptions of the statistical model used to establish the sample size are: 
1. There are at a minimum 40 endoscopists participating in the study and each 
endoscopist makes approximately 60 predictions, 
2. For each endoscope (CF-HQ190 and PCF-H190) and for each class of diminutive 
polyp (adenoma and non-adenoma) there is an intra-cluster correlation coefficient of 
0.05 for predictions made by the same endoscopist5, 
3. 
 
4. There is no correlation between predictions made by the same operator across 
endoscope models (CF-HQ190 and PCF-H190), 
5. The distribution of adenomas and non-adenomas within subjects with more than one 
diminutive polyp was modelled and is described in the statistical analysis plan, 
6. The values from the range of possible values for the discordant pairs (b, c, n and p) 
that are used to calculate sample size are reported in Tables 9-3, 9-4, 9-5 and 9-6), 
7. Without CDSD, the operator sensitivity is presumed to be 88% and the specificity is 
presumed to be 58% across all operators for all colonoscopes1 6. The operator 
sensitivity with CDSD is presumed to be 92% and specificity with CDSD is 
presumed to be 75% across all operators when using the CF-HQ190 colonoscope 
(benchtop testing data). The operator sensitivity with CDSD is presumed to be 91% 
and the specificity with CDSD is presumed to be 72% across all operators when using 
the PCF-H190 colonoscope (benchtop testing data). Combined, the operator 

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sensitivity with CDSD is presumed to be 92% and the specificity with CDSD is 
presumed to be 73% across all operators, 
8. The prediction rate for CDSD with CF-HQ190 is 89% and the prediction rate for 
CDSD with the PCF-H190 is 84% (benchtop testing data), 
9. The proportion of subjects examined with the PCF-H190 will be 50%, 
10. The proportion of subjects that present with adequate bowel preparation will be 
85%24, the proportion of patients with diminutive polyps will be 52%7, there will be 
1.81 diminutive polyps per subject having diminutive polyps7, the overall prevalence 
of adenomas will be 58%7, 
11. The proportion of predictions with and without CDSD that will be assessed as normal 
tissue by pathology is estimated to be approximately 15%. 
 
 
A simulation analysis was performed in which a dataset is generated at each step following 
the assumptions above. To account for intra-cluster correlation at the endoscopist level, for 
each endoscope and each class of diminutive polyps, the proportions of accurate and non-
accurate predicions are sampled following a Dirichlet distribution, as described in Gönen25. 
At each simulation step, bootstrap resampling based 95% confidence intervals for the 
differences between CDSD-aided and CDSD-unaided sensitivity and specificity are 
calculated. Bootstrap resampling is performed first at the endoscopist level and then at the 
patient level. The power is calculated as the number of simulation steps where the lower 
bound of both confidence intervals is greater than 0. 
 
Table 9-3: Assumptions for Proportions of Predictions for Adenomas (Sensitivity, 
Reference Standard Positive) with CF-HQ190 
 
CDSD-unaided Prediction 
 
Positive 
Negative 
Total 
CDSD-aided 
Prediction 
Positive 
0.8411 
0.0859 
0.9270 
Negative 
0.0365 
0.0365 
0.073 
 
Total 
0.8776 
0.1224 
1.00 
 
Table 9-4: Assumptions for Proportions of Predictions for Adenomas (Sensitivity, 
Reference Standard Positive) with PCF-H190 
 
CDSD-unaided Prediction 
 
Positive 
Negative 
Total 
CDSD-aided 
Prediction 
Positive 
0.8301 
0.0749 
0.905 
Negative 
0.0475 
0.0475 
0.095 
 
Total 
0.8776 
0.1224 
1.00 
 
 
 

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Table 9-5: Assumptions for Proportions of Predictions for Non-Adenomas (Specificity, 
Reference Standard Negative) with CF-HQ190
CDSD-unaided Prediction
Positive
Negative
Total
CDSD-aided 
Prediction
Positive
0.124
0.124
0.248
Negative
0.299
0.453
0.752
Total
0.423
0.577
1.00
Table 9-6: Assumptions for Proportions of Predictions for Non-Adenomas (Specificity, 
Reference Standard Negative) with PCF-H190
CDSD-unaided Prediction
Positive
Negative
Total
CDSD-aided 
Prediction
Positive
0.1415
0.1415
0.283
Negative
0.2815
0.4355
0.717
Total
0.423
0.577
1.00
9.1.2
Secondary Endpoints
1.
Number, proportion, unaided NBI prediction and pathology result of diminutive polyps 
detected by the endoscopist and confirmed by pathology for which CDSD does not return a 
prediction.
2.
Sensitivity, specificity, NPV, PPV of unaided endoscopist prediction using white light 
compared with pathology.
3.
Sensitivity, specificity, NPV, PPV of unaided endoscopist prediction using NBI compared 
with pathology. 
4.
Sensitivity, specificity, NPV, PPV of CDSD prediction compared with pathology.
5.
Sensitivity, specificity NPV, PPV of CDSD-aided endoscopist prediction compared with 
pathology.
6.
Number, proportions and pathology results for diminutive polyps with discordant unaided 
predictions using NBI and aided predictions with CDSD.
General Statistical Methods
9.2.1
Analysis Sets
Intention to Treat (ITT) analysis will be performed on all subjects meeting the entrance 
criteria. The primary endpoint will be assessed by ITT analysis on polyp level data.

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9.2.2
Subgroup Analyses
Subgroup analyses of interest include impact of colonoscopy indication, impact of 
colonoscope used, impact of endoscopist confidence on sensitivity and specificity, impact of 
endoscopist experience on level of confidence in prediction, impact of endoscopist 
experience on frequency with which CDSD returns a result (i.e. influence of endoscope 
handling) and agreement with pathology as well as unaided and CDSD aided performance 
segmented by Paris Classification.  Additional subgroup analyses may be performed as 
appropriate.
9.2.3
Additional Analyses
In cases where the CDSD-aided endoscopist prediction and the pathology result differs, a 
recut and reanalysis of the tissue block will be conducted. In such cases, the second 
successful pathology reading will be recorded and used as the histopathological ground truth.
Data Management
Data Collection, Processing, and Review
Subject data will be recorded in a limited access secure electronic data collection system 
(EDC). The clinical database will reside on a production server hosted by the EDC System. 
All changes made to the clinical data will be captured in an electronic audit trail and 
available for review by the sponsor or its representative. The associated software and 
database have been designed to meet regulatory compliance for deployment as part of a 
validated system compliant with laws and regulations applicable to the conduct of clinical 
studies pertaining to the use of electronic records and signatures. Database backups are 
performed regularly.
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes.
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the EDC system and will 
be issued to the site for appropriate response. Site staff will be responsible for resolving all 
queries in the database.
Data Retention
The Principal Investigator or his/her designee or Investigational site will maintain, at the 
investigative site, all essential study documents and source documentation that support the 
data collected on the study subjects in compliance with ICH/GCP guidelines.  Documents 
must be retained for at least 2 years after the last approval of a marketing application or until 
at least 2 years have elapsed since the formal discontinuation of the clinical investigation of 

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the product. These documents will be retained for a longer period of time by agreement with 
Olympus or in compliance with other local regulations.
The Principal Investigator or his/her designee will take measures to ensure that these 
essential documents are not accidentally damaged or destroyed. If for any reason the 
Principal Investigator or his/her designee withdraws responsibility for maintaining these 
essential documents, custody must be transferred to an individual who will assume 
responsibility and Olympus must receive written notification of this custodial change. Sites 
are required to inform Olympus in writing where paper or electronic files are maintained in 
case files are stored off site and are not readily available.
Amendments 
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. IRB approval of the revised 
protocol must be obtained prior to implementation.
Deviations
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB of any deviation from the investigational plan to protect the 
life or physical well-being of a subject in an emergency, and those deviations which affect 
the scientific integrity of the clinical investigation. Such notice shall be given as soon as 
possible, but no later than 5 working days after the emergency occurred, or per prevailing 
local requirements, if sooner than 5 working days. 
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor. Sites may also be required to 
report deviations to the IRB, per local guidelines and government regulations. 
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor.
Device/Equipment Accountability
The study Devices/equipment shall be securely maintained, controlled, and used only in this 
clinical study. 
The sponsor shall keep records to document the physical location of all study 
Devices/equipment from shipment of study Devices from Olympus or designated 
facility/equipment to the investigation sites until return or disposal.
Records shall be kept by clinical sites to document the physical location and conditions of 
storage of all study Devices/equipment. 
The principal investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the study Devices/equipment, which shall include the 
following:

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Date of receipt
Identification of each study Device/piece of equipment (batch number, serial number or 
unique code)
Expiry date, as applicable
Date or dates of use
Subject identification
Date of return (and number) of unused, expired, or malfunctioning study 
Devices/equipment, if applicable.
Compliance
Statement of Compliance
This study will be conducted in accordance with 21 CFR 812 and 814.20 part 56 and part 50, 
ISO 14155: Clinical Investigation of Medical Devices for Human Subjects Good Clinical 
Practice, the relevant parts of the ICH Guidelines for Good Clinical Practices, ethical 
principles that have their origins in the Declaration of Helsinki, and pertinent individual 
country laws and regulations. The study shall not begin until the required approval/favorable 
opinion from the IRB has been obtained. Any additional requirements imposed by the IRB
shall be followed, if appropriate. 
Investigator Responsibilities
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Trial Agreement, the clinical investigation plan, 
ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB, and prevailing local and/or country 
laws and/or regulations, whichever affords the greater protection to the subject.
Prior to beginning the study, sign the Clinical Trial Agreement and comply with the 
Investigator responsibilities as described in such Agreement.  
Prior to beginning the study, sign the Protocol Signature page documenting his/her 
agreement to conduct the study in accordance with the protocol.
Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results.
Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation.

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Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements.
Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports.
Record, report to Sponsor, and assess every observed device deficiency.
Maintain the device accountability records and control of the Device, ensuring that the 
study Device is used only by authorized/designated users and in accordance with this 
protocol and instructions/directions for use.
Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s).
Allow and support regulatory authorities and the IRB when performing auditing 
activities.
Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB requirements.
Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required.
Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study.
Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation.
Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable.
14.2.1 Delegation of Authority  
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training and adequate supervision of those to whom tasks are delegated. The 
investigator is accountable for regulatory violations resulting from failure to adequately 
supervise the conduct of the clinical study. 
Institutional Review Board
The protocol and informed consent document must have the approval of a properly 
constituted committee ("Institutional Review Board") responsible for approving clinical 

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trials.  The signed IRB approval letter must identify the documents approved (i.e., list the 
Investigator's name, the protocol title, and date of approval, and informed consent 
document). A copy of the approval of the protocol (or permission to conduct the study) and
ICF, must be received by the sponsor before recruitment of subjects into the study and 
shipment of investigational product/equipment. Prior approval must also be obtained for 
other materials related to subject recruitment or which will be provided to the subject.
Annual IRB approval and renewals will be obtained throughout the duration of the study as 
of approval must be provided to the sponsor. 
Sponsor Responsibilities
All information and data sent to Olympus concerning subjects or their participation in this 
study will be considered confidential by Olympus. Only authorized Olympus personnel or an
Olympus representative including, but not limited to Contract Research Organization (CRO) 
will have access to these confidential records. Authorized regulatory personnel have the right 
to inspect and copy all records pertinent to this study. Study data collected during this study 
may be used by Olympus for the purposes of this study, publication, and to support future 
research and/or other business purposes. All data used in the analysis and reporting of this 
study will be without identifiable reference to specific subject name.
h information confidential in accordance with 
conduct this research, as well as for additional purposes, such as overseeing and improving 
the performance of its device, new medical research and proposals for developing new 
medical products or procedures, and other business purposes. Information received during 
the study will not be used to market to subjects; subject names will not be placed on any 
mailing lists or sold to anyone for marketing purposes. 
14.4.1 Role of Olympus Representatives
Olympus personnel can provide technical support to the investigator and other health care 
personnel (collectively HCP) as needed during procedures. Support may include HCP 
training, addressing HCP questions, or providing clarifications to HCPs concerning the 
operation of Olympus equipment/devices.
In addition, Olympus personnel may perform certain activities to ensure study quality.  These
activities may include the following.
Observing testing or medical procedures to provide information relevant to protocol 
compliance
Reviewing collected data and study documentation for completeness and accuracy
Insurance 
Where required by local/country regulation, proof and type of insurance coverage, by 
Olympus for subjects in the study will be obtained.

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Monitoring
On site and/or remote monitoring may be performed during the study to assess continued 
compliance with the protocol and applicable regulations. In addition, the Sponsor verifies 
that study records are adequately maintained, that data are reported in a satisfactory manner 
with respect to timeliness, adequacy, and accuracy, and that the Principal Investigator 
continues to have sufficient staff and facilities to conduct the study safely and effectively. 
The Principal Investigator/institution guarantees direct access to original source documents 
by Olympus personnel, their designees, and appropriate regulatory authorities.
The study may also be subject to a quality assurance audit by Olympus or its designees, as 
well as inspection by appropriate regulatory authorities. It is important that the Principal 
Investigator and relevant study personnel are available during on-site monitoring visits or 
audits and that sufficient time is devoted to the process.
Potential Risks and Benefits
Risks Associated with the Study Device(s) 
The study Device has no interaction with the subject, therefore there is no risk of Device-
related adverse events.  The study Device may fail to operate and/or show a prediction, 
however, in these cases the procedure and post-procedure care will proceed as per standard 
practice. It is anticipated that the use of CDSD may slightly lengthen the procedure time but 
it is not expected to have significant impact on the subject.
Anticipated Benefits
Subjects may receive no benefit from participation in this study.  It is possible that in some 
cases, pathological results may be reconsidered based on CDSD prediction, in which case 
adenoma may be diagnosed when it otherwise might not have been.
Risk to Benefit Rationale
There is no risk to subjects from participation in this study, with the exception of potential 
loss of confidentiality.  Appropriate measures will be taken by the clinical sites and Sponsor 
to ensure confidentiality is protected including de-identification of study data collected and 
reported by the Sponsor.  Given that use of the CDSD does not present new risks for the 
subjects, and may provide potential benefit, the risk ratio is considered to be acceptable.
Safety Reporting
Reportable Events by investigational site to Olympus
The CDSD is a minimal risk adjunctive tool to be used in conjunction with standard 
colonoscopy. As CDSD has no interaction with the subject, adverse events are not 

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anticipated to occur in the study and no safety reporting will be required.  Any device 
deficiencies will be recorded as per section 17.2 below.
Olympus Device Deficiencies
All Device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and inadequacy in the information supplied by the manufacturer) 
will be documented and reported to Olympus within 3 days of the clinical site becoming 
aware of the event. If possible, the Device(s) should be returned to Olympus for analysis. 
Instructions for returning the study Device(s) will be provided. If it is not possible to return 
the Device, the investigator should document why the Device was not returned and the final 
disposition of the Device. Device failures and malfunctions should also be documented in the 
Informed Consent
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any study Devices, study-
required procedures and/or testing, or data collection. 
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, IRB approval, FDA requirements, as 
applicable. The ICF must be accepted by Olympus or its delegate (e.g. CRO), and approved 
Olympus will provide a study-specific template of the ICF to investigators participating in 
this study. The ICF template may be modified to meet the requirements of the investigative 
The ICF must be in a language understandable to the subject and if needed, Olympus will 
assist the site in obtaining a written consent translation. Translated consent forms must also 
have IRB approval prior to their use.  Privacy language shall be included in the body of the 
form or as a separate form as applicable.  
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines:
be conducted by the Principal Investigator or designee authorized to conduct the process, 
include a description of a
decision to participate throughout the clinical study,
avoid any coercion of or undue influence of subjects to participate,
use native language that is non-technical and understandable to the subject or his/her 
legal representative,

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provide ample time for the subject to consider participation and ask questions if 
necessary,
ensure important new information is provided to new and existing subjects throughout the 
clinical study.
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form. 
Failure to obtain subject consent will be reported to the IRB and FDA as required.
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB. The new version of the ICF must be approved by the 
IRB. Acceptance by Olympus is required if changes to the revised ICF are requested by the 
ct population to be re-consented.
Suspension or Termination
Premature Termination of the Study
Olympus reserves the right to terminate the study at any stage but intends to exercise this 
right only for valid scientific or administrative reasons and reasons related to protection of 
subjects.  Investigators, associated IRB, and regulatory authorities, as applicable, will be 
notified in writing in the event of study termination.
19.1.1 Criteria for Premature Termination of the Study
Possible reasons for premature study termination include, but are not limited to, the 
following.
An enrollment rate far below expectation that prejudices the conclusion of the study. 
A decision on the part of Olympus to suspend or discontinue development of the Device.
Termination of Study Participation by the Investigator or Withdrawal of IRB
Approval
Any investigator, or IRB may discontinue participation in the study or withdrawal approval 
of the study, respectively, with suitable written notice to Olympus. Investigators, associated 

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IRBs, and regulatory authorities, as applicable, will be notified in writing in the event of 
these occurrences.
Requirements for Documentation and Subject Follow-up
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Olympus. The IRB and 
regulatory authorities, as applicable, will be notified. 
In the event an IRB terminates participation in the study, participating investigators, 
associated IRBs, and regulatory authorities, as applicable, will be notified in writing. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible.
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to Olympus.
Criteria for Suspending/Terminating a Study Site
Olympus reserves the right to stop the inclusion of subjects at a study site at any time after 
the study initiation visit if no subjects have been enrolled  for a period beyond 1 month after 
site initiation, or if the site has multiple or severe protocol violations/noncompliance without 
justification and/or fails to follow remedial actions.
In the event of termination of site participation, all study Devices and testing equipment, as 
applicable, will be returned to Olympus. The IRB and regulatory authorities, as applicable, 
will be notified. 
Publication Policy
Olympus requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a Olympus study or its results. Olympus will submit 
study results for publication (regardless of study outcome) following the conclusion or 
termination of the study. Olympus adheres to the Contributorship Criteria set forth in the 
Uniform Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, Olympus personnel 
may assist authors and investigators in publication preparation provided the following 
guidelines are followed.
All authorship and contributorship requirements as described above must be followed.
Olympus involvement in publication preparation should be discussed with the 
Coordinating Principal Investigator(s) at the onset of the project.
The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission. 

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Kang, H. Y. et al. Comparison of Narrow Band Imaging and Fujinon Intelligent Color 
Enhancement in Predicting Small Colorectal Polyp Histology. Dig. Dis. Sci. 60, 2777 2784 
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Gono, K. et al. Appearance of enhanced tissue features in narrow-band endoscopic imaging. J. 
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Gono, K. Narrow band imaging: Technology basis and research and development history. 
Clinical Endoscopy 48, 476 480 (2015).
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McGill, S. K. S. K., Evangelou, E., Ioannidis, J. P. A. J. P. a, Soetikno, R. M. & Kaltenbach, 
T. Narrow band imaging to differentiate neoplastic and non-neoplastic colorectal polyps in 
real time: a meta-analysis of diagnostic operating characteristics. Gut 62, 1704 1713 (2013).
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Hewett, D. G. et al. Validation of a simple classification system for endoscopic diagnosis of 

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small colorectal polyps using narrow-band imaging. Gastroenterology 143, 599-607.e1 
(2012). 
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Kaltenbach, T. et al. Real-time optical diagnosis for diminutive colorectal polyps using 
narrow-band imaging: the VALID randomised clinical trial. Gut 64, 1569 1577 (2015). 
16. 
Rex, D. K. Narrow-band imaging without optical magnification for histologic analysis of 
colorectal polyps. Gastroenterology 136, 1174 1181 (2009). 
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Repici, A. et al. Accuracy of narrow-band imaging in predicting colonoscopy surveillance 
intervals and histology of distal diminutive polyps: Results from a multicenter, prospective 
trial. Gastrointest. Endosc. 78, 106 114 (2013). 
18. 
Bade, K., MacPhail, M. E., Johnson, C. S., Kahi, C. J. & Rex, D. K. New colonoscope 
technology: impact on image capture and quality and on confidence and accuracy of 
endoscopy-based polyp discrimination. Endoscopy 46, 172 178 (2014). 
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Ikematsu, H. et al. Usefulness of narrow-band imaging with dual-focus magnification for 
differential  diagnosis of small colorectal polyps. Surg. Endosc. 29, 844 850 (2015). 
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confidence optical diagnosis of colorectal polyps. Endosc. Int. open 3, E140-5 (2015). 
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polypectomy in community practice. Endoscopy 47, 808 814 (2015). 
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Vleugels, J. L. A. et al. Effects of Training and Feedback on Accuracy of Predicting 
Rectosigmoid Neoplastic Lesions and Selection of Surveillance Intervals by Endoscopists 
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Hewett, D. G., Huffman, M. E. & Rex, D. K. Leaving distal colorectal hyperplastic polyps in 
place can be achieved with high accuracy by using narrow-band imaging: An observational 
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Abbreviations
Abbreviations are shown in Table 21-1.  
Table 21-1: Abbreviations
Abbreviation/Acronym
Term
AI
CDSD
CFR
CRF/eCRF
CRO
Artificial Intelligence
Clinical Decision Support Device
Code of Federal Regulations
Case Report Form / Electronic Case Report Form
Contract Research Organization
EDC
FAP
FDA
GCP
Electronic Data Collection
Familial Adenomatous Polyposis
Food & Drug Administration
Good Clinical Practice
HCP
HNPCC
IBD
Health Care Professional
Hereditary Non Polyposis Colorectal Cancer
Inflammatory Bowel Disease
ICF
Informed Consent Form
ICH
ICMJE
IRB
ISO
ITT
OCA
NBI
NICE
NPV
PiP
PPV
SSP
TN
TP
UI
WHO
International Council for Harmonization
International Committee of Medical Journal Editors
Institutional Review Board
International Organization for Standardization
Intention To Treat
Olympus Corporation of the Americas
Narrow Band Imaging
NBI International Colorectal Endoscopic [Classification]
Negative Predictive Value
Picture-in-Picture
Positive Predictive Value
Sessile Serrated Polyp
True Negative (as confirmed by pathology)
True Positive (as confirmed by pathology)
User Interface
World Health Organization