Prospective Randomized Trial to Compare the Clinical Efficiency (Adenoma Detection Rate) of G-EYE™ HD Colonoscopy With Standard HD Colonoscopy
Phase: NA
Conditions: Adenoma, Polyps, Colorectal Cancer
Sponsor: Smart Medical Systems Ltd.

 
            
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Smart Medical Systems Ltd. 
 
 
Study Protocol 
 
 
Study protocol number: G-EYE™ 15505, 
Rev. 01 
Protocol Date: July 9, 2013 
 
 
 
Project:  
Prospective randomized trial to compare the 
clinical efficiency (Adenoma Detection Rate) of 
G-EYE™ HD colonoscopy with Standard 
Colonoscopy 
 
 
 
 
This protocol and related documents are the sole property of Smart Medical Systems 
Ltd. and contain confidential and proprietary information. No unpublished 
information contained herein may be disclosed without the prior written approval of 
Smart Medical Systems Ltd. 

 
            
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SPONSOR STATEMENT OF COMPLIANCE 
 
The sponsor of this study, Smart Medical Systems Ltd., manufacturer of the 
investigational device, legally represented by Gadi Terliuc - Chief Executive Officer, 
states the following: 
 
a) 
to assume responsibility related to the clinical investigation; 
b) 
that the treatments used to perform the clinical study are adequate for 
the device under investigation; 
c) 
that the clinical study, as for the responsibility of the manufacturer, 
will be conducted in conformity with: 
annex X of the Council Directive 93/42/EEC concerning medical devices, Declaration 
of Helsinki, and the applicable parts of the ICH/GCP guidelines, the UNI EN ISO 
14155:2011 standards, MEDDEV 2.7/3 and following revisions or other analogous 
internationally recognized standards, to be specified, and only after the approval, by 
the competent Ethics Committee, of the investigational protocol, the informed consent 
and the documentation required by the above mentioned standards; 
 
 
Signature: ___________________________ Date: __________________ 
 

 
            
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INVESTIGATOR AGREEMENT 
 
Prior to participation in this study, a written approval must be obtained from the 
Ethics Committee, and copy should be provided to the Sponsor, Smart Medical 
Systems Ltd., or their authorized representatives, along with the Ethics Committee 
approved Informed Consent Form.  
 
 
The Principal Investigator must also: 
 
Conduct the study in accordance with the study protocol, the Investigator 
Agreement, the Declaration of Helsinki, Good Clinical Practices, international 
harmonized standards for clinical investigation of medical devices (ISO 
14155, Clinical investigation of medical devices for human subjects), the laws 
and regulations of the countries where the study will take place, applicable 
FDA regulations, and conditions of approval imposed by the reviewing IRB or 
FDA, indemnity/insurance requirements and any other applicable regulations.   
 
Supervise all testing of the device involving human subjects 
 
Agree to participate in an appropriate training program as part of the study 
initiation. 
 
Assure that informed consent is obtained from each subject prior to 
enrollment, using the Ethics Committee approved form.   
 
Assure that the study is not commenced until Ethics Committee approval has 
been obtained. 
 
Provide all required data and agree to source document verification of study 
data with subject’s medical records.   
 
Allow staff of the Sponsor and its authorized representatives, as well as 
representatives from regulatory agencies, to review, inspect and copy any 
documents pertaining to this clinical investigation. 
 
Provide accurate financial disclosure information to allow the sponsor to 
submit a complete and accurate certification or disclosure statement as 
required by the FDA. This information shall be updated if any relevant 
changes occur during the course of the investigation and for 1 year following 
completion of the study. 
  
 
The Principal Investigator (PI) may delegate one or more of the above functions to an 
associate or sub-investigator.  However, the PI retains overall responsibility for proper 
conduct of the study, including obtaining and documenting subject informed consent, 
compliance with the study protocol, and the collection of all required data. 
 
Investigator Signature  
I have read and understand the contents of the clinical protocol.  I agree to follow and 
abide by the guidelines set forth in this document.  
 
Principal Investigator Signature: ___________________ 
Date: ____________ 
 

 
            
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Table of Contents 
1.  
STUDY PROTOCOL SYNOPSIS .......................................................................................... 5 
2.  
LIST OF ABBREVIATIONS  ................................................................................................. 6 
3.  
INTRODUCTION 
 ................................................................................................. 6 
4.  
BACKGROUND 
 ................................................................................................. 6 
5.  
DEVICE DESCRIPTION 
 ................................................................................................. 9 
6.  
RISKS AND BENEFITS 
 ............................................................................................... 10 
7.  
STUDY CONDUCT 
 ............................................................................................... 11 
8. 
STATISTICAL CONSIDERATIONS .................................................................................. 17 
9. 
ADVERSE EVENTS 
 ............................................................................................... 17 
10. 
STUDY MONITORING 
 ............................................................................................... 26 
11. 
REGULATORY AND HEALTH AUTHORITY AUDITS ................................................ 26 
12. 
RECORD RETENTION 
 ............................................................................................... 27 
13. 
PROTOCOL MODIFICATIONS ......................................................................................... 27 
14. 
PUBLICATION POLICY 
 ............................................................................................... 27 
15. 
SUBJECT CONFIDENTIALITY ......................................................................................... 27 
16. 
SUBJECT / STUDY DISCONTINUATION ........................................................................ 28 
17. 
DEVICE ACCOUNTABILITY............................................................................................. 29 
18. 
DATA MANAGEMENT 
 ............................................................................................... 29 
19. 
APPENDIXES 
 ............................................................................................... 31 
20. 
REFERENCES 
 ............................................................................................... 31 
APPENDIX A 
 ............................................................................................... 34 
APPENDIX B 
 ............................................................................................... 35 

 
            
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1. STUDY PROTOCOL SYNOPSIS 
Smart Medical Systems Ltd.  Clinical Study Protocol No. G-EYE 15600, Rev 01 
 
Sponsor: 
Smart Medical Systems Ltd. 
10 Hayetsira St., Ra'anana 43663, Israel. 
Tel: +972 9 7444321 
Fax: +972 9 7444543 
Title: 
Comparative evaluation of G-EYE™ Colonoscopy vs. Standard 
Colonoscopy  
The 
Device: 
The NaviAid™ G-EYE System is intended for the optical visualization, 
diagnosis and endoscopic treatment in the gastrointestinal tract. It is also 
intended for positioning of the endoscope in the gastrointestinal tract.  
Study 
design: 
Multicenter, two-arm, randomized , open-label  study  
Number of 
subjects: 
Total of 1000 patients, 500 patients in each group 
Timing: 
Patients will be followed in a short term scheduled visit, or via phone call 
within 48 - 72 hours post-procedure 
Study 
objective: 
The purpose of this study is to compare the adenoma detection rate of G-
EYE™ high definition colonoscopy with that of standard high definition 
colonoscopy  
Study 
endpoint: 
Primary endpoint - G-EYE™ colonoscopy detection rate of adenomas and 
serrated lesions compared to the standard colonoscopy detection rate of the 
same.  
Secondary endpoints – polyp and adenoma detection, procedure times and 
safety. 
Inclusion 
Criteria 
 
1. Patients over 50 years old 
2. Referred to colonoscopy for screening, following positive FOBT 
testing, change of bowel habits or for surveillance colonoscopy 
(history of adenoma resection). 
3. The patient must understand and provide written consent for the  
procedure.  
Exclusion 
Criteria 
 
1. Subjects with inflammatory bowel disease;  
2. Subjects with a personal history of polyposis syndrome;  
3. Subjects with suspected chronic stricture potentially precluding 
complete colonoscopy;  
4. Subjects with diverticulitis or toxic megacolon;  
5. Subjects with a history of radiation therapy to abdomen or pelvis;  
6. Pregnant or lactating female subjects; 
7. Subjects who are currently enrolled in another clinical 
investigation. 
8. Subjects with current oral or parenteral use of anticoagulants  
9. Subjects with recent (within the last 3 mounts) coronary ischemia 
or CVA (stroke) 
10. Any patient condition deemed too risky for the study by the 

 
            
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Smart Medical Systems Ltd.  Clinical Study Protocol No. G-EYE 15600, Rev 01 
 
investigator 
11. Previous colonic surgery (except for appendectomy)   
2. LIST OF ABBREVIATIONS 
ADR = Adenoma Detection Rate 
AE = Adverse Event 
BBPS = Boston Bowel Preparation Scale 
CIP = Clinical Investigation Plan (protocol) 
eCRF = Electronic Case Report Form 
EC = Ethics Committee 
PDR = Polyp Detection Rate 
SAE = Severe Adverse Event 
 
3. INTRODUCTION 
This document is a clinical research protocol and the described study will be 
conducted in compliance with the protocol, Good Clinical Practices standards and 
associated regulations, and all applicable research requirements. 
 
4. BACKGROUND 
Colorectal cancer (CRC) is the second leading cause of cancer in the US and europe, 
with more than 140,000 new cases and over 50,000 deaths annually in the USA 
alone.1,2,3 While being extremely lethal in its advanced stages, exhibiting a five-year 
survival rate of less than 10%,2 it is by far a most preventable cancer by early 
detection. Over 90% of the CRC incidents develop over years from polyps that grow 
in the colon.2 Timely detection and removal of these polyps prevent the disease.  
Colonoscopy is the major GI endoscopy procedure, and is in particular the gold-
standard method for CRC screening, as it enables detection and real-time removal of 
pre-cancerous polyps during the examination.  
It is well known that lesions are missed during routine colonoscopy. A meta-analysis 
of 6 studies by Van Rijn et al.4, in which subjects went through two colonoscopies in 
the same day, reported an overall 22% polyp miss rate. A clinical study by Rex et 
al.,5 which performed same-day, back-to-back colonoscopy on 183 subjects, reported 
an overall adenoma (pre-cancerous polyp) miss rate of 24%. A back-to-back same-
day colonoscopy study in 286 subjects by Heresbach et. al.6 reported miss rate during 
the first colonoscopy of 28% polyps and 20% adenomas. The polyp missing effect 
and its consequences are well demonstrated when comparing actual colorectal cancer 
incidents to past colonoscopies performed in these CRC subjects. Postic et. al.7 
compared resected colon specimens with the results of colonoscopies performed 

 
            
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within 5 months prior to surgery and reported that 23.3% of the lesions in the 
resected specimens were missed during these colonoscopies. Pabby et. al.8 reported 
that 23% of subjects in whom colon cancer developed, went within 30 month prior to 
the CRC incident through colonoscopy in which no polyp was found in the cancer 
area of the colon. 
An apparently leading cause of missed polyps during colonoscopy is attributed to 
polyps that are located behind austral folds in the colon, and are therefore hidden 
from the conventional, forward-viewing endoscope optics. It was demonstrated that 
occasional straightening of austral folds during colonoscopy, by a plastic cap 
mounted on the endoscope tip, increases polyp detection yield. While such 
mechanical stretching of colon folds is not systematic and not circumferential, it does 
have a positive effect on polyp detection rate. A 6,185 patient study by Westwood et. 
al.9 reported a miss-rate of 12.2% in the cap-assisted colonoscopy group vs. 28.6% 
miss rate in the standard colonoscopy group, implying a positive effect of cap 
employment on polyp detection rate. In contrast, another study performed by Tee et. 
al.10 in 400 subjects, reported that there was no significant polyp detection rate 
difference detection standard colonoscopy and cap-assisted colonoscopy (31.3% vs. 
32.8%, respectively). Recently, a rearward viewing device was introduced for use 
during colonoscopy with standard endoscopes. The device – the Third Eye 
Retroscope (TER) (Avantis Medical, Sunnyvale, CA), is a disposable optical 
instrument which is passed through the instrument channel of a standard endoscope, 
and folds forwardly of the endoscope optics to provide retrograde viewing which is 
inspected in parallel to the endoscope’s forward viewing image. This technique is 
aimed to allow inspection of the proximal surface of austral folds, which is not in the 
line-of-sight of the endoscope’s forward-viewing optics, thereby allowing detection 
of polyps that are located behind such folds. Few clinical studies were performed to 
evaluate the ability of TER to detect additional polyps, beyond standard colonoscopy. 
Triadafilopoulos et. al.11 performed a 24 patient study and reported additional 11.8% 
increase in polyp diagnostic yield using the TER. In this study, the endoscope was 
advanced in the colon to the cecum, and TER was employed during endoscope 
withdrawal. DeMarco et. al.12 performed a 298 patient study with similar 
comparison, which demonstrated 13.2% and 11% increase in detection of polyps and 
adenomas, respectively, by using TER. A similar study by Waye et. al.13 in 249 
subjects reported 14.8% and 16% TER-related increase in detection of polyps and 
adenomas, respectively. Leufkens et. al.14 performed a tandem (back-to-back) study 
in 349 subjects, investigating the TER-related second pass net increase in polyp 
detection, and reported respective TER-related increase in polyp and adenoma 
detection of 23.2% and 29.8%. 
Overall, 5 major reasons can be detailed for missing polyps during colonoscopy: 
1. Polyps that are hidden behind folds in the colon, and are thus not in the line-
of-sight of the endoscope's optics. 
2. Polyps that are in the endoscope optics line-of-sight, but are masked by the 
colon's topography and natural folds, and are thus un-noticed. 
3. Shallow polyps which do not extend much beyond the mucosa surface. 

 
            
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4. Polyps located in an unscreened portion of the colon, due to incomplete 
colonoscopy. 
5. Endoscope slippage during withdrawal, causing a portion of the colon that was 
pleated over the endoscope during advancement to be released in an 
uncontrolled manner and thus to remain unscreened, unless endoscope is re-
advanced to inspect this portion. 
 
The NaviAid™ G-EYE™ system presents a new and unique concept that overcomes 
all 5 items listed above, providing an overall solution to the two endoscopy key 
challenges of limited detection/treatment yield and limited operation range. 
 
The NaviAid™ G-EYE™ system is aimed to create a comprehensive change of 
practice in the methodology, yield and range of concurrent GI endoscopy, while 
maintaining the existing practice, visualization technique and endoscopy room 
process flow. 
 
The NaviAid™ G-EYE™ endoscope comprises a standard endoscope onto which a 
unique balloon is permanently integrated, at its bending section. The NaviAid™ G-
EYE™ balloon is controlled by the NaviAid™ SPARK2C inflation system. The  
NaviAid™ G-EYE™ system components are presented in figure 1. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A major attribute of the NaviAid™ G-EYE™ system is its Controlled Withdrawal™ 
technique of the endoscope, with the balloon moderately inflated is to expand and 
stretch the intestinal lumen during endoscope withdrawal. The balloon-endoscope 
system encompassing this controlled withdrawal method, will broadly improve 
endoscopy performance technique, clinical practice and diagnostic/therapeutic yield, 
by providing the following effects: 
1. It straightens intestinal folds, thereby allowing detection and treatment of 
hidden lesions and polyps that were previously located behind these folds. In 
contrast to rearward-viewing optics, this solution does not detect the lesion in 
its rearward location, but rather brings the lesion towards the forward-viewing 
optics of the endoscope. A major advantage of this approach is that once the 
lesion is brought forwardly of the endoscope optics, it can be readily treated, 
Figure 1: The NaviAid™ G-EYE™ system, (a) SPARK2C 
inflation system, and (b) permanently integrated reusable 
balloon on standard endoscope’s bending section 
(a)
 
(b)
 

 
            
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eliminating the need to manipulate the endoscope to be positioned facing the 
lesion.  
1. The local stretching of the colon (or other portion of the GI tract) creates a 
smoother and more visually uniform background against which polyps and 
other lesions can more readily be seen by the physician and thus creates 
enhanced visual contrast between polyps and the interior of the colon. 
2. This stretching causes polyps and other pathologies to protrude inwardly from 
the colon walls to an extent which is enhanced. Specifically, it provides 
enhanced visibility and access to shallow polyps. 
3. The smooth engagement of the moderately inflated balloon with the colon (or 
other portion of the GI tract) provides the operator with full control over the 
withdrawal process, allowing thorough and continuous investigation of the 
colon, and very importantly – preventing endoscope slippage in the colon. As 
mentioned in reason 5 above, endoscope slippage may occur during 
withdrawal, when a portion of the colon, which was pleated over the 
endoscope during advancement, is released in an uncontrolled manner. Unless 
the endoscope is reinserted to inspect it, such a portion remains unscreened, 
adversely affecting detection yield.    
4. Once a polyp or other lesion is detected, the endoscope’s balloon can be 
readily inflated to anchoring pressure providing endoscope stabilization in the 
bowel during treatment. This attribute can be highly valuable when 
performing complex or time/effort consuming intervention, such as removing 
a shallow polyp, multiple polyp removal, suturing, clip application, ERCP 
sessions, and a variety of other interventions. In terms of impact on 
endoscopic intervention practice, the stabilization effect can be dramatic, 
substantially reducing operation time, failure rate, patient risk and sedation 
exposure level, and physician’s required interventional experience and skills.  
5. DEVICE DESCRIPTION 
Smart Medical Systems Ltd. Is an ISO 13485:2003+AC:2007, company that designs, 
develops and manufactures the G-EYE™ system. The NaviAid™ G-EYE™ system is 
CE and AMAR approved. ISO 13485:2003+AC:2007, CE and AMAR certificates are 
provided is appendix B. 
The NaviAid™ G-EYE™ system is intended for the optical visualization, diagnosis 
and endoscopic treatment in the gastrointestinal tract. It is also intended for complete 
positioning of the endoscope in the gastrointestinal tract.  
 
The NaviAid™ G-EYE™ system is comprised of a standard endoscope which is 
mounted with an integral re-used balloon and a second balloon that may be inserted 
through the instrument channel of the endoscope (either the NaviAid™ AB or 
NaviAid™ ABC) during procedure to enable deep or challenging intestinal 
advancement. The NaviAid™ G-EYE™ may also be used without a balloon catheter 
for performing controlled withdrawal and endoscope stabilization. The air supply and 

 
            
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control system – the NaviAid™ SPARK2C controls the inflation and deflation of the 
relevant balloon. 
 
 
5.1 Device Intended Use 
The G-EYE System is intended for the optical visualization, diagnosis and endoscopic 
treatment in the gastrointestinal tract. It is also intended for complete positioning of 
the endoscope in the gastrointestinal tract.  
 
6. RISKS AND BENEFITS 
The NaviAid™ G-EYE™ system is designed according to international standards for 
medical devices. Compliance with these standards ensures that the device can be used 
safely in human beings. All patient-contact materials are biocompatible and comply 
with ISO 10993. This study is intended to evaluate the performance of the NaviAid™ 
G-EYE™ system.  
 
Smart Medical Systems Ltd. Is an ISO 13485:2003+AC:2007 that designs, develops, 
manufactures the NaviAid™ G-EYE™ system.  
Smart Medical Systems Ltd. is a company that follows application and compliance 
with the risk management standard ISO 14971:2007(E), the company performed 
biocompatibility and biological testing according to ISO 10993. The device was found 
to be biocompatible. An extensive design verification & validation bench tests in 
accordance with essential requirements listed in the Medical Device Directive (MDD 
93/42/EEC). 
 
Special considerations have been taken during the design of the device to ensure that 
it is safe and reliable.  
 
Refer to the Investigator’s Brochure for complete details regarding testing, 
specifications, design etc.  
 
6.1 Anticipated Clinical Benefits 
Previous studies indicate that the NaviAid™ G-EYE™ system enables the 
performance of Controlled Withdrawal™ during colonoscopy while straightening 
intestinal folds and enhancing diagnostic yield. Patients participating in this trial may 
benefit from potentially increased detection rate obtained by performing the 
NaviAid™ G-EYE™ procedure not 
available when performing standard 
colonoscopy.  
 

 
            
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6.2 Anticipated Adverse Events and Contraindications 
Possible complications that may result from the procedure are similar to those relevant to 
standard endoscopy and include, but may not be limited to: perforation, hemorrhage and 
septicemia/infection. 
 
Contraindications include those specific to the endoscopy procedure. Relative 
contraindications include the following:  
 
Bowel obstruction  
 
Concomitant Coumadin use  
 
Diverticulitis  
 
Recent (within the last 3 months) coronary ischemia or CVA (stroke).  
 
In each of the above cases, it is not recommended to use the NaviAid™ G-EYE™ 
system. Final decision will be based on the actual case and the physician’s decision. 
 
All these risks can be reduced significantly when the device is operated by a qualified 
person that is experienced with similar procedures, and according to the product IFU. 
 
7. STUDY CONDUCT 
This study will be performed in accordance with the Declaration of Helsinki,  
the Israeli MOH guidelines, European Union’s Medical Device Directive (93/42/EEC 
art.15) and local Member States transpositions. The study will be conducted in 
agreement with the guidelines for conducting a Clinical Investigation as outlined in 
the European Harmonized Standard, EN ISO 14155:2011(E), and in accordance with 
the principles of ICH GCP.  
 
7.1 Study Objective 
The purpose of this study is to compare the ADR obtained by performing G-EYE™ 
colonoscopy vs. the ADR obtained by performing standard colonoscopy. The study 
will enroll 1000 subjects. 
7.2 Study Endpoints 
Primary endpoint - G-EYE™ colonoscopy detection rate of adenomas and serrated 
lesions (combined), compared to the standard colonoscopy detection rate of the same. 
Secondary endpoints - comparison of polyp and adenoma detection, length of procedure 
and safety. 
7.3 Subject Selection 
In order to be included in this study, subjects will have to fulfill all the inclusion 
criteria and none of the exclusion criteria. 

 
            
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7.3.1  Inclusion Criteria 
Any subject who meets all of the following criteria may be included in this study:  
1. Patients over 50 years old 
2. Referred to colonoscopy for screening, following positive FOBT testing, 
change of bowel habits or for surveillance colonoscopy (history of adenoma 
resection). 
3. The patient must understand and provide written consent for the procedure 
7.3.2 Exclusion Criteria 
Any subject who meets any of the following criteria will not be included in this 
study:  
1. Subjects with inflammatory bowel disease;   
2. Subjects with a personal history of polyposis syndrome;  
3. Subjects with suspected chronic stricture potentially precluding complete 
    colonoscopy;  
4. Subjects with diverticulitis or toxic megacolon;  
5. Subjects with a history of radiation therapy to abdomen or pelvis;  
6. Pregnant or lactating female subjects; 
7. Subjects who are currently enrolled in another clinical investigation.  
8. Subjects with routine oral or parenteral use of anticoagulants  
9. Subjects with recent (within the last 3 mounts) coronary ischemia or CVA 
(stroke) 
10. Any patient condition deemed too risky for the study by the investigator  
11. Previous colonic surgery (except for appendectomy)  
 
 
7.4 Study Design 
This is a multicenter, two-arm, randomized, open-label  study intended to compare the 
detection rate obtained by performing G-EYE™ high definition colonoscopy vs. the 
detection rate obtained by performing high definition standard colonoscopy.  
The study will enroll 1000 subjects. 
Consecutive adult subjects who were referred for elective colonoscopy will be asked 
to enroll into this randomized clinical study if the candidate meets the study inclusion 
and exclusion criteria.  
Subjects will sign informed consent form and undergo randomization.  
7.5 Randomization Process 
Subjects will be randomized to one of two groups. Group A, the “Study Group,” and 
Group B, the “Control Group.”  
Group A: Subjects will undergo a G-EYE™ colonoscopy. 
Group B: Subjects will undergo a standard colonoscopy.  
 

 
            
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All subjects will be randomized at the time of informed consent. Randomization will 
take place at the study site under the direction of the investigating physician or the 
clinical study coordinator. Details on the randomization method are described in the 
statistical section (section 8). 
  
The investigator will inform the patient of the Group designation prior to the start of 
the procedure. 
 
7.6 Study Procedures 
 
 All subjects will undergo routine bowel preparation according standard protocol 
for each institution.  
 The subject will undergo colonoscopy in accordance with the randomization 
process.  
 Standard colonoscopy will be performed using Pentax endoscope of EC-3890i 
series. 
 G-EYE™ colonoscopy will be performed using G-EYE™ colonoscope which is 
based on Pentax EC-3890i series.  
 When performing standard colonoscopy, the endoscopist and facility staff will 
follow their usual practice. 
 When performing the G-EYE™ colonoscopy, the endoscopist and facility staff 
will conduct the exam according to the NaviAid™ G-EYE™ system Instructions 
For Use (IFU). 
 During intubation and withdrawal, investigator will use standard clinical practice 
and will observe the video display.  
 No Buscopan will be used during the procedure. 
 All polyps detected during intubation will be removed; irrespective of size, color 
or subjective interpretation, with the possible exception of very small (<2 mm) 
polyps or clusters of rectal polyps and that – in the judgment of the endoscopists – 
are not clinically significant. Such lesions will be treated according to the 
endoscopists’ standard practice with methods that the endoscopists consider to be 
in the best interest of their subjects. Possible approaches include a) removing all 
such lesions, b) removing one or more lesions for histological evaluation and 
leaving the rest behind or c) leaving all of the lesions in place. These lesions will 
be excluded whether removed or not.  
 Intubation time is defined as the duration of the time from the entry of the 
colonoscope into the anal verge to the time when the colonoscope arrives in the 
cecum, as determined by the investigator.  

 
            
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 Investigator will record bowel preparation using the Boston Bowel Preparation 
Scale Score method15. Total score (0-9) will be obtained by adding the scores for 
individual evaluation of right, mid and left colon. Score in each segment should be 
≥2 (2 or 3) to be acceptable. If score of either segment is <2 (0 or 1), then the 
patient should be either excluded from the study or re-scheduled to a different 
session. If patient is rescheduled than he/she will not be re-randomized. 
 Intubation time, withdrawal time and total procedure time will be measured using 
time displayed on the monitor, on a wall clock or on a watch. Pause times will be 
measured by recording the time at the beginning of each therapeutic intervention 
and the time when intubation resumes. An acceptable alternative is to use a 
stopwatch to determine the time intervals, in which case the stopwatch will be 
stopped at the beginning of a pause and re-started as the procedure resumes.  
 Withdrawal time is defined as the duration of the time from initiation of cecal 
inspection to the time when the colonoscope is withdrawn from the anus.  
 During withdrawal, pause times will be measured by recording the time at the 
beginning of each therapeutic intervention and the time when intubation resumes. 
An acceptable alternative is to use a stopwatch to determine the time intervals, in 
which case the stopwatch will be stopped at the beginning of a pause and re-
started as the procedure resumes.  
 Polyps observed during insertion will not be removed or marked with biopsies or 
color. 
 Polyp size will be measured by comparison to an open biopsy forceps 
 All polyps detected during withdrawal will be removed (except for complicated 
polipectomies – see below), irrespective of size, color or subjective interpretation, 
with the possible exception of very small (<2mm) polyps or clusters of rectal 
polyps as described above.  
 After detection of a polyp, chromoendoscopy (e.g. NBI) can be used for polyp 
characterization. 
 Images of detected polyps will be taken in 3 states: iScan1, iScan2, after removal. 
Complicated polypectomies can be performed in a different session. The detection 
of the lesion will be noted in the files, and the histology results will be taken from 
the polypectomy phase. Such cases should be noted in the study files. 
 Withdrawal times should be targeted to a minimum of 6 minutes. Withdrawal 
times of less than 5 minutes will be regarded as a violation of the protocol.  
 All removed polyps have to be clearly marked and sent to histology.  
 Patients will be followed up in either short term scheduled visit (for instance 
following histology results) or via telephone call within 48 - 72 hours post-
procedure, to assess safety. Follow up during either phone call or visit will be 
noted in patient study files. 

 
            
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7.7 Data Collection 
 Data will be collected using a computer based application. Non-identifiable 
patient information will be uploaded to web base database (i.e eCRF). 
 If the procedure cannot be completed, the endoscopist will record the reason on 
the eCRF.  
 Patient's demographics and medical history will be collected. 
 The standard treatment and care provided to all subjects, alongside the application 
of the investigational device will be performed and recorded on the appropriate 
study eCRF.  
 Data collection will also include investigator identification, device identification 
data and usage of the device, relevant concomitant medication. 
 Data collection will also include time to cecum, withdrawal time, total procedure 
time, polyp size, polyp location, polyp histology, any other finding (including 
mass, bleeding, stricture, inflammation etc.), images of polyps, , etc. 
 All data will be documented on the eCRF’s, together with the occurrence of any 
adverse events during the device usage. 
 Any complication attributed to the device will be recorded.  
 All serious adverse events/complications will be reported immediately (within 48 
hours) to the study sponsor/monitor, sponsor, EU representative and to the Ethics 
Committee (in accordance to European and national law). 
 
7.8 Deviations from study protocol 
Any deviations from the study protocol should be notified to the sponsor and 
documented on study deviation forms. 
 
7.9 Informed Consent 
Written informed consent must be obtained from each study subject. The subject will 
be asked to read the informed consent form and to sign the form to indicate consent to 
participate in the study.  
The investigator will explain carefully to the subject the research nature of the study. 
The scope and aims of the research will be described together with known or 
foreseeable benefits, risks and discomforts that subjects may experience. Appropriate 
alternative treatments will be discussed so that the subject may determine whether or 
not he or she wishes to participate in the study.  The subject must understand that 
throughout the study his or her participation remains voluntary and protected by the 
Declaration of Helsinki.  The investigator is responsible for obtaining written (or 

 
            
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witnessed) informed consent from potential subjects prior to study entry.  Subjects 
will be given time to read the informed consent and ask any questions before being 
asked to sign the form.  The informed consent (approved by the sponsor and the 
Ethics Committee) must be signed and dated by the subject and the investigator. One 
copy of the signed consent will be given to the subject, a second copy will be sent to 
the referral investigator and the original will be retained by the investigator.  
Subjects may withdraw their consent to participate in the study at any time without 
prejudice. The investigator may withdraw a subject if, in his clinical judgment, it is in 
the best interest of the subject or if the subject cannot comply with the protocol. 
Attempts should be made to complete any examinations and the sponsor must be 
notified of all withdrawals.  
Should a protocol amendment be made, the subject's consent form may be revised to 
reflect the changes of the protocol. It is the responsibility of the investigator to ensure 
that an amended informed consent is approved or reviewed by the EC, and that it is 
signed by all subjects subsequently entered in the study and those currently in the 
study, if affected by the amendment.   
   7.10 Investigative Center Selection Criteria 
The investigative site will meet the following selection criteria prior to inclusion in 
this study: 
 Experience with colonoscopy 
 Clinical research study experience and resources that demonstrate good 
compliance with study requirements and timely, complete documentation of 
subject follow-up.   
 All investigative center personnel involved in this study must agree to allow 
sufficient time for comprehensive training in the use of the investigational 
device. 
 Sufficient subject volume to meet enrollment timeframe. 
 
7.11 Ethics Committee  
The clinical protocol for this study must be reviewed and approved by the Ethics 
Committee (EC) at the institution(s) where the study will be conducted. The sponsor 
shall provide any additional information or assistance that may be requested. Should 
the EC suggest changes to the clinical protocol to conform to institutional rules or 
local regulations, these changes may be incorporated in a modification of this protocol 
with approval from the sponsor. A copy of the written EC approval must be provided 
to the sponsor prior to the beginning of the study. 
 
Other investigator responsibilities relative to the EC include the following: 
1. 
During the conduct of the study, the investigator will submit progress reports to 
the EC as required, and request re-review and approval of the study at least once 
a year; 

 
            
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2. 
The investigator will report immediately to the EC of any unexpected serious 
adverse events that occur during the study, and provide the sponsor with a copy 
of the correspondence; 
3. 
If the sponsor notifies about serious adverse events reported in other studies 
using this device, the investigator must report that information to the EC; 
4. 
As required, the investigator must obtain approval from the EC for protocol 
amendments and for revisions to the consent form or subject recruitment 
advertisements; 
5. 
The investigator should provide the EC with any other information it requests 
before or during conduct the study; 
6. 
The investigator must maintain a file of study-related information that includes 
all correspondence with the EC; 
7. 
The investigator must notify EC when study is completed (i.e. after the last 
study visit of the final study subject); 
8. 
After study completion (within 12 months is recommended) the investigator 
should provide the EC with a final report on the study. The recommended 
components of a final report are as follows; dates of study start and completion, 
number of subjects enrolled/treated, number of subjects who discontinued 
participation early and reason why, itemization and discussion of any serious 
adverse event. 
 
 
 
 
 
 
8. STATISTICAL CONSIDERATIONS 
8.1 Study Design and Objectives: 
This is a multicenter, two-arm, randomized, open-label  study intended to compare the 
detection rate obtained by performing G-EYE™ colonoscopy vs. the detection rate 
obtained by performing standard colonoscopy.  
8.2 Study Endpoints: 
8.2.1 Primary Performance Endpoint: 
The primary performance measure will be the detection rate of adenomas and 
serrated lesions combined (DR) which is defined as the percentage of subjects 
with at least one relevant lesion found, in each of the study groups. 

 
            
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8.2.2 Secondary Endpoints 
Secondary endpoints include: 
 Time to reach cecum,  
 Withdrawal (of device) time,  
 Total procedure time,  
 Number of polyps, 
 Number of adenomas  
 Other findings (including mass, bleeding, stricture, inflammation etc.) 
8.2.3 Safety Endpoints 
 Incidences of known complications that may result from the procedure are 
similar to those relevant to standard endoscopy and include, but may not 
be limited to: perforation, hemorrhage and septicemia/infection. 
 All adverse events and complications 
8.3 Study hypothesis: 
Null Hypothesis:  Psc = PG-EYE 
Alternative Hypothesis: Psc ≠ PG-EYE 
Where Psc is the ADR in subjects who undergo standard colonoscopy, and PG-EYE is the DR in 
subjects who undergo G-EYE™ colonoscopy. 
 
8.4 Sample size estimation 
A sample size is calculated to test the above described null hypothesis with 80% 
power at a 5% level of significance. From the literature it is known that the adenoma 
detection rate is 24%. If we power this study to detect a 35% increase in the DR with 
the G-EYE™ colonoscopy then 450 subjects will be required per study group, for a 
total sample size of 900 subjects. To allow for a potential 10% drop out rate we will 
enroll 500 patients in each group, for a total of 1000 subjects. 
8.5 Randomization: 
After a subject meets the eligibility criteria, he/she will be equally allocated (with a 
1:1 ratio) to one of the following 2 treatment groups based on a randomization scheme 
with blocks stratified by center:  
 Group A: Subjects will undergo a G-EYE™ colonoscopy. 

 
            
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 Group B: Subjects will undergo a standard colonoscopy.  
The randomization scheme will be prepared by the study statistician using the SAS 
(version 9.3.) random number procedure. 
 
8.6 Blinding: 
NR to open label study. 
 
8.7 Data Analysis Sets: 
8.7.1 Intent to Treat (ITT) analysis set: 
The ITT analysis set will consist of all subjects randomized. In accordance with the 
ITT principle, all subjects randomized who were found eligible for the study will be 
kept in their originally assigned treatment group. 
8.7.2 Per protocol (PP) analysis set: 
The per-protocol analysis set will consist of all subjects who complete the study 
without major protocol violations; a list of protocol violations that are considered 
major will be prepared before statistical analysis is performed. 
8.7.3 Statistical Analysis of analysis sets: 
The ITT analysis set will serve as the main set for performance and safety 
assessments. 
The primary performance assessment will also be performed on the PP analysis set 
8.8 Statistical Analysis: 
8.8.1 General Considerations 
 
Statistical analyses will be performed using SAS® v9.3 or higher (SAS Institute, Cary 
NC, USA). 
Baseline demographic and other baseline characteristics, together with safety analyses 
will be performed on all enrolled subjects. Baseline values are defined as the last valid 
value prior to treatment. 
Study results will be presented in tables and graphs when relevant. Continuous 
variables will be summarized by a mean, standard deviation, minimum, median and 
maximum, and categorical variables by a count and percentage 
The required significance level of findings will be 5%. All statistical tests will be two-
sided.  If statistical tests are performed nominal p-values will be presented. Where 

 
            
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confidence limits are appropriate, a two-sided 95% confidence interval will be 
constructed, unless stated otherwise. 
For comparison of means (continuous variables), the two-sample t-test or the 
Wilcoxon rank sum test will be used as appropriate.  For comparison of proportions 
(categorical variables), the Chi-squared test or Fisher’s exact test will be used as 
appropriate. 
 
8.8.2 Demographic and Other Baseline Variables 
 
Demographic and baseline condition related characteristics will be tabulated. 
Continuous variables such as age will be summarized by a mean, standard deviation, 
minimum, median and maximum, and categorical variables by a count and 
percentage. 
 
8.8.3 Disposition of Subjects 
 
Device tolerability will compare between the treatment groups, the number and 
percent of subjects who fail to complete the study and the number and percent of 
subjects who fail to complete the study because of Adverse Events will be presented.  
 
8.8.4 Performance Analyses 
 
A count and percentage of subjects with adenomas with each of the study devices will 
be presented, together with 95% exact confidence intervals. The null hypothesis will 
be tested using a chi-squared test, 
Secondary endpoints will be summarized by descriptive statistics per study group; the 
groups will be compared according to data type as described in the general methods 
section. 
Kaplan-Meier curves of the time to cecum, withdrawal time, total procedure time in 
each of the study groups will be presented and compared using the Log-Rank test.  
 
8.8.5 Safety Analysis 
 
Tables displaying the frequency and incidence of AEs will be presented by treatment 
group, an odds ratio and 95% confidence interval will be presented as well. 
Adverse events (AEs) will also be presented by seriousness, severity and relation to 
device by study group.  
 
8.8.6 Pooling 
 

 
            
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Subgroup analysis of the primary efficacy endpoints by center will be used to evaluate 
the poolability of the results. The ADR  by center interaction will be tested with 
Fisher’s exact test using a significance level of 10%. If the interaction is found 
significant, the reasons for these interactions will be further explored and rationalized. 
This evaluation may include demographic features, symptoms at presentation, clinical 
and treatment history, and center comparability in the features found to be associated 
with the primary efficacy variable. Sites with a small amount of subjects (<10) will be 
pooled together for this analysis by geographical location. 
 
8.8.7 Handling of Missing Data 
 
The study outcome will not be evaluated for patients who drop out or do not have data 
available for the analysis.  Nevertheless a sensitivity analysis will be performed using 
a worst case scenario model where subjects who have dropped out or do not have the 
study evaluation available are considered as not detected. 
 
8.8.8 Interim Analysis 
 
No interim analyses are planned for this study. 
9. ADVERSE EVENTS 
9.1 
Reporting requirements 
Timely and complete reporting of Adverse Events (AE) and safety assessment allows: 
 Protection of safety of study subjects. 
 Greater understanding of the overall safety profile of the study treatment. 
 Appropriate modification of study protocols and improvement in study 
design and procedures. 
 Adherence to regulatory requirements 
The definitions and reporting requirements adopted in this study are derived from 
the current International standard on clinical investigations: ISO 14155:2011 and 
MEDDEV 2.7.3. 
 

 
            
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9.2 
Definitions: 
Adverse Events (AE) 
AE is defined as any untoward medical occurrence in a subject. This definition does 
not imply that there is a relationship between the adverse event and the device under 
investigation.  An AE can therefore be any unfavorable and unintended sign, 
symptom, laboratory observations or disease temporally associated with the use of the 
investigational product, whether or not related to the investigational product. The 
following should be reported as AE: 
 Untoward medical conditions or signs or symptoms that were absent before 
starting study treatment. 
 Untoward medical conditions or signs or symptoms present before starting 
study treatment and worsen (increase severity or frequency) after starting 
study treatment. 
 Abnormal laboratory value or test. 
 Clinical signs or symptoms that require therapy. 
Device Related Adverse Events 
Device Related Adverse Events are defined as any untoward medical occurrence not 
present at baseline which is suspected of being related to the investigational device.  
Device-Related AE’s MUST also be reported by the investigator to the sponsor within 
24 hours of investigator's awareness of the event. The reporting should then be 
followed up by written notification within 5 days, using the appropriate form in the 
study file. 
 
 
Device Deficiency  
Device Deficiency is defined as Inadequacy of a medical device related to its identity, 
quality, durability, reliability, safety or performance, such as malfunction, misuse or 
use error and inadequate labeling and when occurred it is regarded as a reportable 
event.  
 
Adverse Device Effect (ADE) 
ADE is defined as any untoward and unintended response to a medical device. This 
definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use or the deployment of the device, and any event that is a result of a 
user error.  Therefore, some adverse device effects may be related to device failure, 
malfunction or misuse. 
 
Device failures, Malfunctions and Misuse 
Investigators are instructed to report all possible device failures, malfunctions or 
misuse observed during the course of the trial. These incidents will be documented in 
the case report form provided as follows: 

 
            
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Device Failure - A device failure has occurred when the device is used in compliance 
with the Instructions for Use, but does not perform as described in the Instructions for 
Use and also negatively impacts treatment of the study subject. 
Device Malfunction - A device malfunction occurs when an unexpected change to 
the device that is contradictory to the Instructions for Use is observed, which may or 
may not affect device performance. 
Device Misuse - Any use of the investigational device by the investigator that is 
contradictory to the application described in the Instructions for Use will be 
categorized as device misuse. 
Unanticipated Adverse Device Effect (UADE) 
An Unanticipated Adverse Device Effect (UADE) is defined as any serious adverse 
effect on health or safety or any the life-threatening problem or death caused by or 
associated with the use of the investigational device that was not previously identified 
in the Investigational Plan or Instructions for Use in its nature, frequency or severity. 
UADEs may also include other serious problems associated with the device that affect 
the rights or welfare of study subjects.   
 
Serious Adverse Events (SAE) 
A SAE is an adverse event that: 
1.     Led to a death, 
2.     Led to a serious deterioration in the health of the subject that: 
        a.     Resulted in a life-threatening illness or injury 
        b.     Resulted in a permanent impairment of a body structure or a body function 
        c.     Required in-patient hospitalization or prolongation of existing 
                hospitalization 
d. Resulted in medical or surgical intervention to prevent permanent 
impairment to body structure or a body function. 
  3.       Led to fetal distress, fetal death or a congenital abnormality or birth defect. 
 
Serious Adverse Device Effect (SADE) 
A Serious Adverse Device Effect is an adverse event caused by or associated with the 
use of the investigational device that has resulted in any of the consequences 
characteristic of a serious adverse event or that might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made 
or if circumstances had been less opportune. 
 
Unexpected Serious Adverse Device Effect (USADE)  
An Unanticipated Adverse Device Effect (UADE) is defined as any serious adverse 
effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan or 

 
            
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application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
9.3 
Documentation 
Adverse events must be listed on the appropriate eCRF page. All AEs will be 
characterized by the following criteria:    
 Intensity or Severity 
 Relatedness 
 Outcome 
 Treatment or Action Taken 
 
Intensity or Severity 
The following categories of the intensity of an adverse event are to be used:  
Mild - Awareness of a sign or symptom that does not interfere with the patient’s usual 
activity or is transient, resolved without treatment and with no sequelae. 
Moderate - Interferes with the patient’s usual activity and/or requires symptomatic 
treatment. 
Severe - Symptom(s) causing severe discomfort and significant impact of the 
patient’s usual activity and requires treatment. 
 
Relatedness 
The investigator will use the following definitions to assess the relationship to the 
device: 
Not related - The cause of the AE is known and the event is not related to any aspect 
of study participation. 
Possibly related - There is a reasonable possibility that the event may have been 
caused by study participation.  
The AE has a timely relationship to the study procedure(s); however, follows no 
known pattern of response, and an alternative cause seems more likely or there is 
significant uncertainty about the cause of the event.  
Probably related - It is likely that the event was caused by study participation. 
The AE has a timely relationship to the study procedure(s) and follows a known 
pattern of response; a potential alternative cause, however, may explain the event. 
Related - A related event has a strong temporal relationship and an alternative cause 
is unlikely. 
 
Outcome 
The clinical outcome of the AE or SAE will be characterized as follows: 
Death - The SAE eCRF must be completed for this outcome 
Recovered without sequelae - The patient returned to baseline status 

 
            
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Ongoing - Patient did not recover and symptoms continue; 
Recovered with sequelae - The patient has recovered but with clinical sequelae from 
the event 
Unknown - The patient outcome is unknown 
 
Treatment or Action taken 
The treatment or action taken after the occurrence of an AE or SAE will be reported 
as: 
Interventional Treatment - Surgical, percutaneous or other procedure 
Medical Treatment - Medication dose reduction/interruption or discontinuation, or 
medication initiated for event 
None - No action is taken 
9.4 
Expedited Reporting of Serious Adverse Events 
All adverse events occurring since the start of the study procedure must be recorded in 
the Case Report Form. Any Serious Adverse Event, must be reported to Smart 
Medical Systems Ltd. within 24 hours of knowledge, to the following contact person: 
  
Name: Adva Yoselzon 
Tel:  +972-9-7444321  
Fax:  +972-9-7444543                           
E-mail: ayoselzon@smartmedsys.com 
 
The reporting should then be followed up by written notification within 5 days, using 
the Serious Adverse Event form in the study file.  
In accordance with European regulations, all investigators will be notified of the 
occurrence of serious unexpected AEs, if such AEs are associated with the use of the 
study device (i.e., if there is a reasonable possibility that the AE may have been 
caused by the device and are thus deemed significant new adverse effects or risks with 
respect to the investigational device). The investigator must inform the relevant 
Medical Ethics Committee according the applicable national procedures. 
 
It is also the responsibility of the investigator to inform the representative of the 
appropriate local Ethics Committee, within 24 hours of investigator's awareness of the 
event. A copy of the report cover letter will be filed with the subject’s medical file. 
 
9.5 
         Follow-Up of Unresolved Events 
All serious adverse events should be followed until they are resolved or the subject’s 
participation in the study ends.  
 

 
            
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9.6 
Anticipated Adverse Events 
Possible complications that may result from the procedure are similar to those relevant to 
standard endoscopy and include, but may not be limited to: perforation, hemorrhage and 
septicemia/infection. 
 
10. STUDY MONITORING  
Study monitoring activities will include study initiation visits, interim site monitoring 
visits and close-out visit.  The study initiation visit enables the study monitor and/or 
sponsor to review thoroughly the study protocol and case report forms with the 
investigator's staff, in order to assure that the investigator understands the Clinical 
Study Protocol, including records and reports, has sufficient background, facilities, 
subject load, time, and willingness to comply with the study requirements; submits the 
Clinical Study Protocol to the Ethics Committee for review and approval, maintains 
all correspondence, the Clinical Study Protocol, and all required records on file; and 
submits required reports, assumes responsibility for the investigation at her/his 
institution, which may include supervision of some tasks; and has sufficient 
experience with the study population. 
Interim site monitoring visits will be scheduled depending on the rate of subject 
enrollment. During the interim site monitoring visits the following treatments will be 
followed; the monitor will review the case report forms of each subject in the study to 
make certain that the data provided are accurate and obtained in the manner specified 
in the protocol.  The subjects' clinical records will be reviewed to confirm that the 
case report form data is consistent with the investigator clinical records, the 
background data and concurrent medication are documented in the case report forms, 
and that there is an accurate account of the use of the study device in the treatment.   
The site Study Regulatory binder and other study documents will be reviewed.  The 
subjects' clinical records will be reviewed to determine whether recording of adverse 
events has been omitted in the case report forms.  If this is found to be so, the case 
report forms will be returned to the investigator and corrected to include this 
information. During the course of the study, the monitor shall be available to discuss, 
in person or by telephone, questions regarding adverse effects, removal of subjects 
from the study, conduct of the study, etc.  At the completion or termination of this 
study a close-out visit will be conducted. 
  
11. REGULATORY AND HEALTH AUTHORITY AUDITS 
The European Union’s authorities and/or the Food and Drug Administration (FDA) 
and/or the local state health authorities may request access to all study records, 
including source documents for inspection. The investigator and hospital staff are 
requested to cooperate with these audits. The investigator must notify the sponsor of 
any health authority audit as soon as notification of such audit is made. A 
representative or designee of the sponsor may also conduct similar audits and may be 
present during health authority audit. 

 
            
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12. RECORD RETENTION  
It is required that a copy of all records (e.g., informed consent documents, source 
documents, safety reports, study device dispensing record, etc.) which support case 
report forms for this study, be retained in the files of the responsible investigator for a 
minimum of five (5) years following notification by the sponsor that all investigations 
(not merely the investigator's portion) are completed, terminated and/or discontinued.  
If the principal investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person 
who will accept the responsibility. Smart Medical Systems Ltd. must be notified in 
writing of the name and address of the new custodian. 
13. PROTOCOL MODIFICATIONS 
An amendment to the protocol may be proposed by an investigator. The amendment 
will be prepared and approved by the sponsor according to the sponsor’s relevant 
SOP. The amendment must be submitted to the EC. When applicable, the 
amendment’s implementation will take place only once approved by the EC. 
If for any unexpected reasons, there is any requirement to deviate from the treatments 
stated above, the protocol deviation should be discussed with a Smart Medical 
Systems Ltd. representative.  
 
14. PUBLICATION POLICY 
All information concerning this study that was not previously published is considered 
confidential information. This confidential information shall remain the sole property 
of Smart Medical Systems Ltd.; it shall not be disclosed to others without written 
consent of Smart Medical Systems Ltd. and shall not be used except in the 
performance of this study. 
Any investigator involved with this study is obligated to provide the Sponsor with 
complete test results and all data derived from the study. 
 
15. SUBJECT CONFIDENTIALITY 
The subject’s name and personal data will remain confidential and will not be 
published in any way. However, the sponsor’s monitor or representative and 
regulatory representatives, auditors and inspectors may have access to medical files in 
order to verify authenticity of data collected. 

 
            
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16. SUBJECT / STUDY DISCONTINUATION (DROP OUT CRITERIA) 
Subjects should be removed from the study whenever considered necessary for their 
welfare or when the subject expresses a desire to withdraw from the study. Non-
compliance with the protocol, the occurrence of a Serious Adverse Event or any 
medical condition that, in the opinion of the investigator, warrants discontinuation 
from the study for the safety of the subject, may necessitate discontinuing a subject. If 
a subject is discontinued, the reason must be entered on the case report form and 
signed by the investigator. In case of any questionable situation, the study monitor or 
Smart Medical Systems Ltd. personnel should be consulted. When a subject is 
removed from the study as a result of Serious Adverse Event, a final physical 
examination must be performed. Subjects removed from the study because of an 
adverse event will be followed-up until the adverse event has been resolved. 
 
In the case that the occurrence of adverse events is greater than anticipated, the 
clinical investigation will be suspended; in such a case, a safety committee will be 
arranged to decide if the study could be continued. The Ethics Committee will be 
notified and the results of the safety committee discussions will be brought for the EC 
review and decision. 
 
Smart Medical Systems Ltd., reserves the right to discontinue any study for 
administrative reasons at any time, such as, but not limited to a decision to 
discontinue further clinical investigation with the device, improper conduct of the 
study by the investigator, inability to obtain the number of subjects required by the 
protocol, etc.  Reimbursements for reasonable expenses will be made if such an action 
is necessary. 
In the following cases, subjects will be withdrawn from the study: 
 Technical error or device malfunction 
 Inadequate bowel preparation (score <2 in one or more colon segments, 
according to BBPS). In such case patient can also be rescheduled for a 
secondary session. In such case patient will not be re-randomized. 
 Any medical condition revealed during the examination that might require 
cease of treatment for medical reasons or affect study outcome 
 Patient having more than 20 polyps 
 
The following cases will be considered as screening failure and will also be 
withdrawn from the study: 
 Polyposis that was revealed during the examination 
 Bowel obstruction 
 Any medical condition deemed too risky by the investigator 
 
  

 
            
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17. DEVICE ACCOUNTABILITY  
Complete traceability records will be kept of all devices during the study. The 
NaviAid™ G-EYE™ system and relevant accessories will be provided by Smart 
Medical Systems Ltd., bearing required labeling. Device number will be documented 
in the center log. 
 
Each clinical investigator will be responsible for the safe storage with restricted 
access of the investigational materials in their possession, thereby preventing use of 
any materials by any persons not participating in the study. 
After completion of the study, all devices must be returned in their original package to 
Pentax Europe GmbH. 
 
All investigators will be responsible for using the products according to the IFU and 
protocol and maintaining product inventory and records. 
 
18. DATA MANAGEMENT 
18.1 Data handling procedure – Data review and Queries resolution 
 
18.1.1 eCRF 
 An Electronic Case Report Form (eCRF) will be completed for each subject 
enrolled into the clinical study, to record and transmit all information collected 
in the study. The Investigator will review, approve and electronically sign/date 
each completed eCRF; the Investigator’s signature serving as attestation of the 
Investigator’s responsibility for ensuring that all clinical and laboratory data 
entered on the eCRF are complete, accurate and authentic.   Access to the 
eCRF will be given by Smart Medical Systems to the PI through an dedicated 
iPad application. 
 It is the responsibility of the investigator to ensure that eCRFs are legible and 
completely filled in. 
 Errors must be corrected. History of changes including who performed the 
change and date of change will be kept in the study database. An investigator 
or any personnel signature authorized by the investigator is required to 
personally sign each eCRF on the appropriate pages to verify that the 
investigator has reviewed and concurs with the recorded data. No other person 
is permitted to sign for the investigator. The signature must be made at the 
time that the eCRF is reviewed by the investigator signing the eCRF.  
Patients will be identified only by ID number. 
 If an assessment is not done or not known or otherwise unavailable, indicate 
this by writing “"Unknown"in the respective answer field of the eCRF. If the 
question is irrelevant (e.g. not applicable to the subject), indicate this by 
writing “N/A” (Not Applicable) in the respective answer field of the eCRF. 

 
            
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 It is anticipated that relevant sections of the eCRF will be completed by the 
investigator or designee within 24 hours of the last data becoming available, 
but in no case later than 5 days. Similarly, when a subject completes a study, it 
is anticipated that all relevant eCRF pages will be completed within 24 hours 
of the last data becoming available, but in no case later than 5 days. 
18.1.2 Source documents are the clinical findings and observations, laboratory and 
test data, and other information contained in Source Documents.  Source 
Documents are the original records (and certified copies of original records); 
including, but not limited to, hospital medical records,  physician or office 
charts, physician or nursing notes, subject diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, x-
rays, etc.  Information recorded on the eCRF may be considered as Source 
Data only when Data is collected for trial purposes 
18.1.3 For each Subject identifier code (patient code) will be given by the PI based 
on serial number.  This code will be applied on documentation relating to each 
subject, namely, eCRF, Informed Consent form and CDs.   Also, this will also 
be used for transferring, reporting processing and analysis of data.  The 
investigator's iPad will include Subject identification list with the personal 
information of each Subject and will be accessible using a personal username 
and password. When printed, the list will be kept in closed envelop to protect 
subjects’ confidentially. 
18.1.4 Subject name or other directly identifiable information will not appear on any 
reports, publications, or other disclosures of clinical study outcomes.  
18.1.5 The PI will update the database upon receipt of new information for each 
patient.   The CRA will issue query form when unclear information and/or 
significant deviation lab result or other information from previous visit occur. 
18.1.6 The Study Coordinator will deal with the query form requirements no later 
than two weeks from date of query receipt and will send the query resolution 
to the CRA.  Should new information becomes available the Study 
Coordinator will update the database accordingly. 
 
 
18.2 Data retention 
 
18.2.1 Smart Medical Systems and Investigator will maintain records in accordance 
with Good Clinical Practice guidelines; to include: 
 Clinical protocol, including copies of submitted Safety Reports and Annual 
Reports  
 Ethics Committee correspondence (including approval notifications) related to 
the clinical protocol; including copies of adverse event reports and annual or 
interim reports. 
 Current and past versions of the EC-approved clinical protocol and 
corresponding EC-approved consent form(s). 
 Financial disclosure information (i.e., for the Sponsor-Investigator agreement 
and for sponsor-hospital agreement  

 
            
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 Curriculum vitae of the Investigation team.  
 Certificates of required training namely, physician training and protocol 
requirement training.  
 Listing of printed names/signatures. (i.e., for the Sponsor-Investigator and for 
all sub-investigators who will be involved in the administration of the study 
drugs and/or the evaluation of research subjects [i.e., who will contribute 
significantly to the study data])  
 Laboratory certification information 
 Instructions 
for 
Use 
on-site 
preparation 
and 
handling 
of 
the  
G-EYE™ system and other study-related materials (i.e., if not addressed in the 
clinical protocol). 
 Site Signature Log 
 Signed informed consent forms  
 Completed Case Report Forms; signed and dated by the Investigator  
 Source Documents or certified copies of Source Documents §  Monitoring 
visit reports  
 Copies of Smart Medical Systems -Investigator correspondence (including 
notifications of safety information) to sub-investigators 
 Subject screening and enrollment logs   
 Subject identification code list 
 Investigational device accountability records. 
 Final clinical study report 
 
 
19. APPENDIXES LIST 
A. Compliance with ISO 14155:2011(E) annex A 
B. Certificates-ISO 13485:2003+AC:2007, CE and AMAR  
 
 
20. REFERENCES 
1. Davila RE, Rajan E, Baron TH, Adler DG, Egan JV, Faigel DO, Gan SI, Hirota 
WK, Leighton JA, Lichtenstein D, Qureshi WA, Shen B, Zuckerman MJ, 
VanGuilder T, Fanelli RD;, American Society for Gastrointestinal Endoscopy 
Guideline: Colorectal Cancer Screening and Surveillance, Gastrointestinal 
Endoscopy 2006 Apr;63(4):546-57 (PMID: 16564851) 
2. Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, Dash 
C, Giardiello FM, Glick S, Levin TR, Pickhardt P, Rex DK, Thorson A, Winawer 
SJ; Screening and Suveillance for the Early Detection of Dolorectal Dancer and 
Adenomatous Polyps, 2008:A Joint Guideline from the American Cancer Sociaty, 
the US Multi-Society Task Force on Colorectal Cancer and the; American College 
of Radiology, CA Cancer J Clin. 2008 May-Jun;58(3):130-60 (PMID: 18322143) 

 
            
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3. Gregory S. Cooper, Amitabh Chak, Siran Koroukian, The Polyp Detection Rate of 
Colonoscopy:A National Study of Medicare Beneficiaries, The American Journal 
of Medicine 2005 Dec;118(12):1413 (PMID: 16378787) 
4. Jeroen C van Rijn, Johannes B Reitsma, Jaap Stoker, Patrick M Bossuyt, Sander J 
van Deventer and Evelien Dekker, Polyp miss rate determined by tandem 
colonoscopy: a systematic review, American Journal of Gastroenterology 2006 
Feb;101(2):343-50 (PMID:16454841) 
5. Rex DK, Cutler CS, Lemmel GT, Rahmani EY, Clark DW, Helper DJ, Lehman 
GA, Mark DG, Colonoscopic Miss Rates of Adenomas Determined byBack-to-
Back Colonoscopies, Gastroenterology. 1997 Jan;112(1):24-8 (PMID:8978338) 
6. D.Heresbach, 
T.Barrioz, 
M.G. 
Lapalus,D.Coumaros, 
P.Bauret, 
P.Potier, 
D.Sautereau, 
C.Boustiere, 
J.C.Grimaud, 
C.Barthelemt, 
J.See, 
I.Serraj, 
P.N.D'Halluin, B.Branger, T.Ponchon,  Miss rate for colorectal neoplastic polyps: 
a prospective multicenter study of back-to-back video colonoscopies, Endoscopy 
2008 Apr;40(4):284-90 (PMID:18389446) 
7. Georges Postic, David Lewin, Charles Bickerstaff and Michael B Wallace, 
Colonoscopic miss rates determined by direct comparison of colonoscopy with 
colon resection specimens, American Journal of Gastroenterology 2002 
Dec;97(12):3182-5 (PMID:12492208) 
8. Ajay Pabby, Robert E. Schoen, Joel L. Weissfeld, Randall Burt, James W. 
Kikendall, Peter Lance, Moshe Shike, Elaine Lanza, Arthur Schatzkin, Analysis of 
colorectal cancer occurrence during surveillance colonoscopy in the dietary Polyp 
Prevention 
Trial, 
Gastrointestinal 
Endoscopy 
2005 
Mar;61(3);392-4 
(PMID:15758908) 
9. Westwood DA, Alexakis N, Connor SJ, Transperent cap-assisted colonoscopy 
versus standard adult colonoscopy: a sustemic review and meta-analysis, Dis. 
Colon Rectum 2012 Feb;55(2) 218-25 (PMID:22228167) 
10. Tee HP, Corte C, Al-Ghamdi H, Prakoso E, Darke J, Chettiar R, Rahman W, 
Davison S, Griffin SP, Selby WS, Kaffes AJ, Prospective randomized controlled 
trail evaluating cap-assisted colonoscopy vs standard colonoscopy, World J 
Gastroenterology 2010 Aug 21;16(31);3905-10 (PMID:20712051) 
11.  Triadafilopoulos G, Li J, A pilot study to assess the safety and efficacy of the 
Third Eye retrograde auxiliary imaging system during colonoscopy, Endoscopy 
2008 Jun;40(6):478-82.( PMID:18543136) 
12. DeMarco DC, Odstrcil E, Lara LF, Bass D, Herdman C, Kinney T, Gupta K, Wolf 
L, Dewar T, Deas TM, Mehta MK, Anwer MB, Pellish R, Hamilton JK, Polter D, 
Reddy KG, Hanan I., Impact of experience with a retrograde-viewing device on 
adenoma detection rates and withdrawal times during colonoscopy: the Third Eye 

 
            
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Retroscope study group, Gastrointestinal Endoscopy. 2010 Mar;71(3):542-50 
(PMID:20189513) 
13. Waye JD, Heigh RI, Fleischer DE, Leighton JA, Gurudu S, Aldrich LB, Li J, 
Ramrakhiani S, Edmundowicz SA, Early DS, Jonnalagadda S, Bresalier RS, 
Kessler WR, Rex DK, A retrograde-viewing device improves detection of 
adenomas in the colon: a prospective efficacy evaluation, Gastrointestinal 
Endoscopy 2010 Mar;71(3):551-6 (PMID:20018280) 
14. Leufkens AM, DeMarco DC, Rastogi A, Akerman PA, Azzouzi K, Rothstein RI, 
Vleggaar FP, Repici A, Rando G, Okolo PI, Dewit O, Ignjatovic A, Odstrcil E, 
East J, Deprez PH, Saunders BP, Kalloo AN, Creel B, Singh V, Lennon AM, 
Siersema PD; Effect of a retrograde-viewing device on adenoma detection rate 
during colonoscopy: the TERRACE study, Gastrointestinal Endoscopy 2011 
Mar;73(3):480-9 (PMID:21067735) 
15. E.J. Lai, A.H. Calderwood, G. Doros, O.K. Fix, B.C. Jacobson: The Boston 
Bowel Preparation Scale: A valid and reliable instrument for colonoscopy-
oriented research, Gastrointest Endosc. 2009 March; 69(3 Pt 2): 620–625.  
 

 
            
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APPENDIX A 
COMPLIANCE WITH ISO 14155:2011(E) ANNEX A 
Page/section in protocol  
ISO section 
9-14/4 
Introduction (A.1.1) 
1 
Identification of the CIP (A.1.2) 
7/1 
Sponsor details (A.1.3) 
Will be supplied in separate 
document 
Investigators details (A.1.4) 
7-8/2 
Synopsis (A.1.5) 
14-17/5 
Identification and description of the IP (A.2) 
12 
Justification for the study design (A.3) 
17-19/6 
Risks and benefits (A.4) 
19/7.1 
Objectives of CIP (A.5) 
21/7.4 
Design of clinical investigation – general (A.6.1) 
20/7.3 
Design of clinical investigation – subjects (A.6.3) 
22-24/7.6 
Design of clinical investigation – procedures 
(A.6.4) 
35/10 
Design of clinical investigation – monitoring plan 
(A.6.5) 
28/8 
Statistical considerations (A.7) 
39-42/18 
Data Managment (A.8) 
37/13 
Amendments to the CIP (A.9) 
25/7.8 
Deviations from the CIP (A.10) 
39/17 
Device Accountability (A.11) 
2 
Statement of compliance (A.12) 
25/7.9 
Informed consemt process (A.13) 
28-35/9 
AE (A.14) 
NA 
Volnerable population 
38/16 
Suspemsion or premature termination (A.16) 
37/14 
Publication policy (A.17) 
NA 
Bibliography 
 
 
 
 
 
 
 
 
 
 
 

 
            
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APPENDIX B (DOCUMENTS WILL BE ADDED) 
 
 
ISO 13485:2007+AC:2007 Certificate 
 

 
            
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CE Certificate