Development and Validation of an Artificial Intelligence-assisted Strategy Selection System for Colonoscopy Cleaning
Conditions: Colorectal Adenoma
Sponsor: Renmin Hospital of Wuhan University

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Development and Validation of an Artificial
Intelligence-assisted Strategy Selection System for
Colonoscopy Cleaning
Short Title：EndoAngel Study
NCT
NCT04444908
Trial number
EA-19-003
Protocol version
1.1
Version date
Dec 12, 2019
Country
China
Device
EndoAngelTM
Principal investigator
Professor HonggangYu
Address
No. 99, Zhangzhidong Road, Wuchang District, Wuhan,
Hubei.

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Content
1.
Summary..................................................................................................................................... 4
1.1.
Time and event table.......................................................................................................5
1.2.
Flow chart....................................................................................................................... 5
2.
Introduction.................................................................................................................................6
3.
Patient Selection..........................................................................................................................7
3.1.
Inclusion Criteria............................................................................................................ 7
3.2.
Exclusion Criteria........................................................................................................... 7
3.3.
Definition of enrollment................................................................................................. 8
4.
Endpoints.....................................................................................................................................8
4.1.
Primary endpoint.............................................................................................................8
4.2.
secondary endpoints........................................................................................................8
4.3.
Safety evaluation endpoints and other secondary endpoints..........................................9
5.
Purpose and overall design......................................................................................................... 9
5.1.
Purpose............................................................................................................................9
5.2.
Overall design................................................................................................................. 9
6.
Study process............................................................................................................................ 10
6.1.
Summary of Study Process...........................................................................................10
6.2.
Enrollment.....................................................................................................................10
6.2.1.
Informed Consent............................................................................................. 10
6.2.2.
Patient Selection................................................................................................11
6.2.3.
Subject identification number...........................................................................11
6.3.
Treatment Description...................................................................................................11
6.3.1.
Patient Screening Assessments.........................................................................12
6.3.2.
Pre-procedure Management..............................................................................12
6.3.3.
Intraprocedure Management.............................................................................12
6.3.4.
Post-procedure Management............................................................................ 12
6.3.5..
Specimen handling procedure.......................................................................... 12
6.4.
Suspension and withdrawal.......................................................................................... 12
6.4.1.
Pre-procedure....................................................................................................13
6.4.2.
Intraprocedure...................................................................................................13
6.4.3.
Replacement......................................................................................................13
6.5.
Concomitant Therapy and Medication......................................................................... 13
7. Basis of study protocol and risk/benefit analysis..................................................................... 14
7.1.
Selection of endpoints...................................................................................................14
7.2.
Definition of participants..............................................................................................14
7.3.
Adverse events..............................................................................................................14
7.4.
Expected and trial-related adverse events.................................................................... 15
7.5.
Risk minimization.........................................................................................................15
7.6.
Related benifits............................................................................................................. 16
7.7.
Overall feasibility analysis............................................................................................16
8.
Statistical Analysis Plan............................................................................................................16
8.1.
Statistical Analysis Plan................................................................................................16
8.2.
Methods.........................................................................................................................16

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8.3.
Hypothetical test........................................................................................................... 16
8.4.
Sample Size Calculation............................................................................................... 16
8.5.
Statistical analysis set................................................................................................... 17
9.
Device Description.................................................................................................................... 17
10. Abbreviation..............................................................................................................................17
11. References.................................................................................................................................18
11. Informed Consent Form............................................................................................................19

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1.
Summary
Title：
Development and Validation of an Artificial Intelligence-assisted
Strategy Selection System for Colonoscopy Cleaning
Short Title：
EndoAngel Study
Trial number：
EA-19-003
Research system
EndoAngel
Expected effect：
ENDOANGEL's intended use is to assist doctors in identifying
patients who require a second colonoscopy, thus avoiding missed
adenomas and excessive washing time costs due to subjective
factors and poor decision-making. It can improve the quality of
endoscopy and the detection rate of digestive tract lesions.
Primary Endpoint：
1.Adenoma detection rate (ADR);
2.Boston Bowel Preparation Score of intestinal segment in
artificial intelligence system;
Secondary Endpoints:
1.Polyp detection rate (PDR);
2.Mean number of adenomas per procedure (MAP);
3.Mean number of polyps per procedure (MNP);
4.The detection rate of large, small and micro - small adenoma
and the average number of detection;
5.The detection rate and average number of polyps in large, small
and microsized polyps;
6.Adenoma detection rate (ADR) of different location
7.Mean number of adenomas per procedure (MAP) of different
location
8.Scope-forward time;
9.withdrawal time;
10.Cecal intubation rate;
11.Boston Bowel Preparation Score of endoscopists;
Trail design：
prospective, single group, observational, single-cente
Participants：
Male and female subjects aged 18 years or older will require a colonoscopy,
and voluntarily provide endoscopic imaging data and sign an informed
consent form.
Sample size：
200 samples were collected to explore the sample distribution, and then
calculate the sample size according to the sample distribution.
Study Process：
Subjects who met all inclusion criteria and did not meet all exclusion criteria
were included in the study before colonoscopy. During the colonoscopy, the
endoscopists need to remain in the same without withdrawal while flushing
the bowel. The biopsied patients are followed up for one week. the
non-biopsied patients are followed up at the end of their colonoscopy , and
the results are sent to an independent data analysis team for review. We will
collect the patients' video and exclude the clips of irrigation, biopsy, and

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observation of polyp. Then the EndoAngel evaluates the Boston Bowel
Preparation Scale of the ascending colon, transverse colon and descending
colon, and calculates the proportion of 1 Score.
Security
Safety incidents shall be evaluated and reported according to the quality
management measures for clinical trials of medical devices
1.1. Time and Event Tables
Events
Screening period （d
-30~-1）
The day of
colonoscopy（d 0）
Follow up (d 1-14)
Informed Consent
X
Basic characteristics
X
Medical
history/surgical
history
X
Inclusion/Exclusion
Criteria
X
Colonoscopy
X
Concomitant
treatment
X
X
Concomitant
medication
X
X
Adverse Events
X
X
Research completed
X
1.2. Flow chat
Meeting the Inclusion and not
meeting exclusion Criteria？
Screening
The endoscopists need to remain in the same without withdrawal while flushing the bowel
Sign the Informed Consent
Quit
No
Yes
EndoAngel’s evaluate
Exclude the clips of irrigation, biopsy, and observation of polyp of patients’ videos
Research completed

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Follow-up Time: The biopsied patients are followed up for one week. the non-biopsied patients
are followed up at the end of the study
2.Introduction
Colorectal disease as a common human disease seriously affects the health of human life.
With the aging of the population, the change of diet structure and the aggravation of
environmental pollution, the incidence of colorectal diseases, such as colon cancer, Colon Polyp
and inflammatory bowel disease, has gradually increased1-2.
Colonoscopy is the simplest and most widely available screening procedure for colorectal
cancer(CRC) prevention and early detection2. Colonoscopy can clearly observe the small changes
in the terminal ileum and the colorectal, such as erosion, ulcers, bleeding, congestion, edema,
polyps, early cancer, and so on. Colonoscopy can biopsy the lesion site for pathological
examination, to histologically qualitative the characterization of mucosal lesions, such as
inflammation, polyp nature, the degree of differentiation of cancer, and so on. It is helpful to
understand the severity of the lesion and guide the formulation of the correct treatment plan or
judgment of treatment effect. Colonoscopy can also be the minimally invasive endoscopic
treatment of colorectal polyps, early cancer, bleeding, foreign bodies and other diseases.
Because the quality of bowel preparation affects the colonoscopy's ability to detect
adenomas and polyps, adequate bowel preparation is necessary to ensure optimal use of
colonoscopy in CRC prevention3. Almost all clinical guidelines recommend adequate bowel
preparation before colonoscopy4-6. However, up to one third of colonoscopies have been found to
show inadequate bowel preparation, which is estimated to increase the cost of colonoscopies by
12% to 22%. And there are 20% of patients’ bowel is not adequately prepared. When the
patient's bowel preparation is inadequate, the difficulty of flushing may lead to missed detection
of adenomas7-9. so doctors need to accurately identify such patients and tell them to have a
second colonoscopy after a full bowel cleanse10. However, the evaluation of intestinal cleanliness
is decided by doctors subjectively, and there is no objective and effective scoring standard to
guide the patients to accept the second colonoscopy.
Deep learning is an important breakthrough in the field of artificial intelligence in the past
decade. It has great potential in extracting tiny features in image analysis and image classification.
In 2017, the journal Nature published a paper showing that using artificial intelligence to diagnose
skin diseases can reach the level of experts11. Subsequently, in the field of digestive endoscopy,
more and more studies began to apply artificial intelligence to assist doctors to find polyps and
improve the detection rate of polyps and adenomas.Urban, G. team used artificial intelligence to
identify polyps with 95% sensitivity12. Misawa, M team used artificial intelligence to identify
polyps with 90% sensitivity13. The purpose of our research group is to develop the EndoAngel
with real-time intestinal cleanliness assessment. It can derive a decision curve for bowel
cleanliness based on the relationship between the percentage of bowel segments with a Boston
score of 1 and the detection rate of missed adenomas. It can help endoscopists to identify patients
who need a second colonoscopy, to avoid the detection of missed adenomas and the high cost of
cleaning time caused by the wrong decision-making. At the same time, artificial intelligence is in

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the preliminary research stage in the field of digestive endoscopy, our research results are
expected to provide new ideas in improving the detection rate of colonoscopic adenomas.
2.
Patient Selection
Male and female subjects aged 18 years or older will require colonoscopy. And they
voluntarily provide endoscopic imaging data and sign informed consent form.
Patients not meeting the inclusion criteria or meeting exclusion criteria will not be considered
for participation in the study. Patients who met all criteria and singed informed consent may be
excluded from the study due to:
• Endoscopists’ professional advices/medical reasons (only under very limited conditions to avoid
researcher bias).
• Withdraw informed consent.
2.1. Inclusion criteria
All patients meeting the following criteria will be considered for participation in the study:
1)
Male or female aged 18 or above;
2)
Colonoscopy is needed to further clarify the characteristics of digestive tract diseases;
3)
Patients able to give informed consent were eligible to participate.
4)
Able and willing to comply with all study process.
5)
No intestinal organic disease.
2.2. Exclusion criteria
All patients meeting the following criteria will not be considered for participation in the study:
1)
Has participated in other clinical trials, signed informed consent and was in the follow-up
period of other clinical trials.
2)
Has participated in clinical trials of the drug and is in the elution period of the experimental
drug or control drug.
3)
Drug or alcohol abuse or psychological disorder in the last 5 years.
4)
Patients in pregnancy or lactation.
5)
Known polyposis syndromes.
6)
Gastrointestinal Bleeding.
7)
A history of inflammatory bowel disease, colorectal cancer and colorectal surgery.
8)
A history of colorectal surgery.
9)
Patients with a contraindication for biopsy.
10) Previous history of allergy to ingredient of bowel cleanser.
11) Patients with intestinal obstruction or perforation, toxic megacolon, Colectomy, heart failure
(Grade III or IV) , severe cardiovascular disease, severe liver failure or renal insufficiency,
etc. .

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12) Patients with poor bowel preparation that are unable to reach their blindness.
13) Researchers believe that the patient is not suitable to participate in the trial.
2.3. Definition of enrollment
After participants signed informed consent, they were regarded as enrolled. The sign time
was the enrollment time, and was recorded in CRF.
3.
Endpoints
3.1. Primary Endpoint
1) The adenoma detection rate (ADR)：
ADR was calculated by dividing the total number of patients being detected adenomas by the
number of colonoscopies.
2) Cleanliness assessment of different intestinal segment in the artificial intelligence system
The artificial intelligence system evaluates the Boston Bowel Preparation score of the ascending
colon, transverse colon and descending colon in real-time, and calculates the proportion of 1 Score
3.2. Secondary Endpoints
1)
The polyp detection rate (PDR): PDR was calculated by dividing the total number of patients
being detected polyps by the number of colonoscopies.
2)
The mean number of polyps per patient (MNP). MNP was calculated by dividing the total
number of polyps by the number of colonoscopies.
3)
The mean number of adenomas per patient (MAP). MAP was calculated by dividing the total
number of adenomas by the number of colonoscopies.
4)
PDR of different sizes. It was calculated by dividing the number of patients with polyps that
large (≥10 mm), small (6-9 mm) and diminutive (≤5 mm) by the number of patients
undergoing colonoscopy.
5)
MNP of different sizes. It was calculated by dividing the number of polyps that large (≥10
mm), small (6-9 mm) and diminutive ≤5 mm) by the number of patients undergoing
colonoscopy.
6)
ADR of different sizes. It was calculated by dividing the number of patients with adenomas
that large (≥10 mm), small (6-9 mm) and diminutive≤5 mm) by the number of patients
undergoing colonoscopy.
7)
MAP of different sizes. It was calculated by dividing the number of adenomas that large
( ≥10 mm), small (6-9 mm) and diminutive ≤5 mm) by the number of patients
undergoing colonoscopy.

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8)
ADR of different location. It was calculated by dividing the number of patients with
adenomas detected in the rectum, sigmoid colon, descending colon, transverse colon,
ascending colon, ileocecal region etc. by the Total number of patients undergoing
colonoscopy.
9)
MAP of different location. It was calculated by dividing the number of adenomas detected in
the rectum, sigmoid colon, descending colon, transverse colon, ascending colon, ileocecal
region etc. by the Total number of patients undergoing colonoscopy.
10) Scope-forward time. The time is taken to go from the the rectum to the ileocecal region.
11) Withdrawal time. The time is taken to finish the examination from the beginning of the
ileocecal region.
12) Cecal intubation rate. It was calculated by dividing the number of colonoscopies that get to
the ileocecal region by the total number of colonoscopies.
13) Boston Bowel Preparation Score of endoscopists. Endoscopists evaluate the different
intestinal segment according Boston Bowel Preparation Scale(BBPS)
3.3. Safety evaluation endpoints and other secondary endpoints
Adverse events shall be determined according to the definition in the code for the quality
management of adverse events of medical devices.The following types of adverse events should
be recorded and calculated in the hospital history and CRF. According to the CRF table, the
occurrence time, starting and ending time, intervention measures and treatment results should be
filled in when recording. The severity should be referred to the previous literature and CTCAE 5.0
standard.
4.
Purpose and overall design
4.1. Purpose
The purpose of this study is to develope the Endoangel with real-time intestinal cleanliness
assessment. It can derive a decision curve for bowel cleanliness based on the relationship between
the percentage of bowel segments with a Boston score of 1 and the detection rate of missed
adenomas. To assist endoscopist in identifying patients who require a second colonoscopy, thus
avoiding missed adenomas and excessive washing time costs due to subjective factors and poor
decision-making. It can improve the quality of endoscopy and the detection rate of digestive tract
lesions.
4.2. Overall design
This is a prospective, single group, observational, single-centel study.

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5.
Study process
5.1. Summary of Study Process
• If the patient meets the inclusion criteria, the patient is invited to participate in the study and then
the informed consent procedure for the clinical trial is applied.
• Assess patients’ eligibility based on the inclusion/exclusion criteria.
• If the patient meets the inclusion/exclusion criteria, information prior to endoscopy will be
collected.
• A colonoscopy is performed after informed consent. Any intraoperative adverse events are
recorded on the CRF for submission and subsequent analysis.
• Follow-up will be performed from the postoperative to the study completion, as detailed in the
time and event table.
5.2. Enrollment
Only after patients signed the informed consent, can the research-related procedures be conducted.
5.2.1. Informed Consent
According to the Helsinki Declaration, patients are not allowed to participate in the study
without adequate informed consent. The principal investigator is responsible for ensuring that no
patient was enrolled in the study without adequate informed consent. Failure to obtain informed
consent and failure to document this process is considered a violation of the Helsinki Declaration
and the study protocol.
All informed consent documents (ICDs) must be approved by ethics. Patient’s informed
consent requires documentary record on the informed consent by himself in his primary language.
The investigator or trained designated person performs a preliminary screening to determine
if the patient generally meets the eligibility criteria for the study. If yes, the investigator or trained
designee should recommend the patient to participate in the study. If the patient agrees to
participate, they will need to sign an informed consent document.
The investigator or trained designated person should confirm that the subject understands the
following points in the study:
• the purpose of research,
• potential risks or adverse events,
• Potential risks or adverse events directly related to participating the research,
• The likelihood of failure,
• Research requirements include follow-up visits,

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• All rights of the subject as a participant in the clinical study.
After explaining the purpose of the study, the investigator or trained designee should answer
any questions from the subject. If the subject agrees to participate, his or her wishes must be
recorded by signing and dated on the EC-approved ICF, and the document should be signed and
dated by the patient receiving the informed consent.
After successful completion of the informed consent process, the investigator or trained
designated person will assess the eligibility of patients based on the protocol.
5.2.2. Patient Selection
All patients who underwent colonoscopy, agreed to use EndoAngel and generally meet the
study requirements were screened based on the inclusion/exclusion criteria. Patients who passed
the screening were enrolled and recorded in the subject screening and enrollment tables. There is
no bias in the choice of the enrolled subjects. The date of screening, the results (enrolled or not),
and the primary reason for not selecting subjects (such as not meeting inclusion criteria, or not
interested in participating in the study) will be recorded.
After the patients are enrolled, the research center should complete the preoperative study
data collection.
It is desirable to be able to collect complete data for all enrolled patients, without those
withdrawal from the study.
5.2.3. Subject identification number
Patients were numbered after signing informed consent.
The subject number begins with EA as a fixed number and is numbered starting from 0001 at
the time of signing the informed consent. For example, the first patient who signed the informed
consent was EA0001, and the second one was EA0002.
Once the subject identification number is assigned, the number is not reusable.
5.3. Treatment Description
This section applies to individuals who have signed an approved informed consent and have
been identified as eligible to participate in this study on the basis of the inclusion and exclusion
criteria. This section introduces the preoperative, surgical and postoperative management of
subjects in detail.

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5.3.1. Patient Screening Assessments
1）History
2）Physical examination
3）Hematuria pregnancy test (if required)
5.3.2. Pre-Procedure Managements
1）Fasting for 14 hours and water deprivation for 2 hours before examination
2）Routine bowel preparation.
3）Psychological counseling.
4）Performing routine anesthesia for painless enteroscopy patients.
5.3.3. Intraoperative Managements
1）Patient position: lateral position with appropriate restraint.
2）Insertion route: according to the actual situation of the subject, usually through the anus
3）Routine observation
5.3.4. Post-operative Managements
1）Postoperative routine nursing
2）Subjects were observed to wake up
3）Patients without polyps and other lesions were followed up until the patient woke up and left
the endoscopic room.
4）Patients with polyps and other lesions detected but no biopsy was taken during the operation
should be followed up until the patient received polypectomy and other treatments, and the
follow-up period should be within 7 days after the colonoscopy.
5）Record complications (if any).
5.3.5. Specimen handling procedure
5.4. Suspension and withdrawal
Patients who were screened and confirmed to be eligible for the study, signed the informed

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consent and completed the randomization were considered as enrolled. If serious program
deviation, withdrawal, or death occurs, the subject study is considered to be suspended. If the
subject
discontinues
the
study
after
obtaining
informed
consent,
the
data
before
the
discontinuation will still be included in the study-related analysis.
5.4.1. Pre-Procedure
In any time during the study period, even before colonoscopy, participants could withdraw
their informed consent whenever necessary. Researchers can withdraw participants before surgery
according to safety considerations in the inclusion and exclusion criteria.
5.4.2. Intraprocedure
For safety reasons, the investigator may have the subject quit during the procedure. For
example, the patient is not suitable for receiving the instrument for the study or the endoscopists
do not use the specified instrument for any reason. If the following serious cases occur, please
withdraw during the operation:
1）Perforation
2）Bleeding
3）Allergy to narcotic drugs
4）Poor intestinal cleanliness
5）Unable to complete colonoscopy due to obstruction or other reasons
5.4.3. Replacement
Subject will be deemed to have commenced the study upon completion of the informed
consent process, and any subject who has been discontinued prior to or during the endoscopic
examination will not subsequently be replaced by other subjects.
5.5. Concomitant therapy and medication
The concomitant treatment and concomitant medication were recorded from the time the
subject signed the informed consent to the time the study was completed. Concomitant treatment
and concomitant medication should be recorded in the CRF, or a clear copy of the form available
from the research center should be kept in the CRF as research data to identify other factors
affecting the end of the study. When recording the concomitant treatment and concomitant
medication, the indications and the starting and ending time of use should be clearly defined, and
the corresponding types of adverse events should be indicated for the treatment measures to cope
with adverse events. When using a copy of the study center form, the investigator should sign the
copy and indicate the date of review to confirm that the document is a study document.

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6.
Basis of study protocol and risk/benefit analysis
EndoAngel is used to provide assistant to monitor the operation of endoscopists, which will
not provide diagnosis. Doctors make their own diagnosis on the basis of EndoAngel's results. The
security of the software and the improvement of endoscopic physician's diagnosis and treatment
level have also been confirmed in the previous feasibility study. And the patients in this study
carry out the diagnosis and treatment according to the conventional treatment measures, which are
formulated in accordance with the standard medical treatment procedures and do not increase the
risk of the subjects.
6.1. Selection of endpoints
The primary outcome of the study are the adenoma detection rate (ADR) and Cleanliness
assessment of different intestinal segment in artificial intelligence system.
The secondary outcomes of this study were: 1.Polyp detection rate (PDR);2.Mean number of
adenomas per procedure (MAP); 3.Mean number of polyps per procedure (MNP);4.The detection
rate of large, small and micro - small adenoma and the average number of detection;5.The
detection rate and average number of polyps in large, small and microsized polyps;6.Adenoma
detection rate (ADR) of different location;7.Mean number of adenomas per procedure (MAP) of
different location;8.Scope-forward time;9.withdrawal time;10.Cecal intubation rate;11.Boston
Bowel Preparation Score of endoscopists;
Adverse events in safety indicators shall be judged in accordance with relevant regulations,
and serious adverse events shall be recorded and reported in accordance with regulations.
Other evaluations are detailed in the Case Report Form (CRF).
6.2. Definition of participants
Patients were included according to the indications and contraindications described in the use
plan. Because of practical reasons (such as younger patients, participation in a number of clinical
studies, alcohol/drug dependence patients, and other factors that may affect the completion and/or
reliability of gastroscopy) and ethical reasons (whether informed consent can be completed, etc.),
the entry and discharge criteria have been reduced.
6.3. Adverse events
The relevant definitions of adverse events are as follows:
Adverse Events (AE): Any adverse medical event, unexpected disease or injury, or adverse
clinical manifestations (including abnormal laboratory findings) that occur in a subject, user or
other person, whether or not associated with medical devices.

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Serious Adverse Events (SAE): Adverse Events with the following information:
- causing death.
- leading to severe deterioration of the health of the subjects, including
- leading to life-threatening diseases or injuries,
- Causing impairment of body structure or function.
- Need hospitalization or extended hospitalization
- lead to hospitalization and preventive medical or surgical intervention
- Permanent damage to body structure or function
- Fetal distress, fetal death or congenital abnormalities or congenital defects.
Note: Hospitalization for existing conditions, or surgery required in the program, without
serious deterioration of health status, is not considered a serious adverse event. Purposeful
hospitalization, such as economic or reimbursement reasons, is not considered a serious adverse
event.
Unexpected adverse device response (UADE): refers to adverse events related to medical
devices that were not previously identified in the current version of the risk analysis report in
terms of nature, severity or incidence. The definition includes any event caused by insufficient or
inadequate description of the use or deployment of the device. This definition includes any event
caused by a user's error.
6.4. Expected and trial-related adverse events
Previous studies have shown that the expected adverse events are basically the same as the
complications of conventional endoscopic diagnosis and treatment.
The instrument used in this experiment is a medical software which is not in contact with
human body. There is no difference between the experimental operation and the routine operation.
The intervention measures (such as randomized process) in the experiment may slightly increase
the incidents of diagnosis and treatment.
6.5. Risk minimization
In this study, when there are bugs in the software, doctors can still operate under their own
judgment without affecting conventional diagnostic and treatment measures, greatly reducing the
risk of the test.

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6.6. Related benifits
Subjects will be randomly assigned to an experimental group or a control group. And
experimental subjects may increase the detection of polyps and other lesions.
6.7. Overall feasibility analysis
EndoAngel is an independent system including both software and computer hardware, which
can monitor image data 24 hours a day. The system is not invasive. The overall operability is
strong.
7.
Statistical Analysis
7.1. Statistical Analysis Plan
Data management and statistical analysis were implemented by Renmin Hospital Wuhan
University.
7.2. Methods
Continuous variables should be described by number of subjects, mean, standard deviation,
median, minimum and maximum.The classification variables are summarized by frequency and
percentage.
7.3. Hypothetical test
The main assumptions are:There is a correlation curve between intestinal cleanliness score and the
detection rate of adenoma.The use of EndoAngel can assess the intestinal cleanliness score in real
time,and give a decision whether the patients need second colonoscopy
7.4. Sample Size Calculation
The primary endpoint was the detection rate of Adenomas and the percentage of 1 score to
get a correlation curve. In order to calculate the sample size more accurately, we prepare to collect
200 colonoscopies to explore the sample distribution, and then calculate the sample size according
to the sample distribution.

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7.5. Statistical analysis set
All patients who met the inclusion and exclusion criteria were considered eligible for
recruitment.
The two analysis sets in this study are defined as follows:
• The full analysis set (FAS) population analysis set will contain all eligible cases and shedding
cases, but does not include culling cases.
• The Compliance (PP) population analysis set will include all subjects in the FAS analysis set
with no significant deviation from the program.
Intention-to-treat and conformity analysis sets should be used to analyze the primary efficacy
endpoints. The main analysis will be based on the PP analysis set. FAS analysis was regarded as
supportive analysis.
8.
Device Description
EndoAngel
Version: EA 2301
9.
Abbreviations
Abbreviations
Full Name
Chinese
AE
Adverse Event
不良事件
CFDA
China Food and Drug Administration
国家食品药品监督管理总局
CNDA
China National Drug Administration
国家食品药品监督管理总局
CRF
Clinical Record File
病例报告表
CTCAE
Common Terminology Criteria for Adverse Events
不良事件常规评价标准
EC
Ethical Committee
伦理委员会
ICD
Informed Consent Document
知情同意文件
ICF
Informed Consent Form
知情同意书
ITT
Intention to Treat
意向治疗分析集
PP
Per Protocol
符合方案集
SAE
Serious Adverse Event
严重不良事件
CRC
Colorectal cancer
结肠癌
MNP
the Mean Number of Polyps per Procedure
平均每例肠镜发现的息肉个数
MAP
the Mean Number of Adenomas per Procedure
平均每例肠镜发现的腺瘤个数
PDR
Polyp Detection Rate
息肉发现率
ADR
Adenoma Detection Rate
腺瘤检出率
BBPS
Boston Bowel Preparation Scale
波士顿肠道评分量表

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10. References
1
Hosokawa,O. et al. Difference in accuracy between gastroscopy and colonoscopy for detection
of cancer. Hepatogastroenterology 2007;54:442-4.
2
Bisschops,R. et al. Performance measures for upper gastrointestinal endoscopy: a European
Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative. Endoscopy
2016;48:843-64.
3
Rutter,MD. et al. Quality in gastrointestinal endoscopy. Endoscopy 2014;46:526-8.
4
Gado,AS. et.al. Quality assurance in gastrointestinal endoscopy: An Egyptian experience.
Arab journal of gastroenterology : the official publication of the Pan-Arab Association of
Gastroenterology 2016;17:153-8.
5
Faigel DO. Quality, competency and endosonography. Endoscopy 2006;38 Suppl 1:S65-9.
6
Malheiro,R. et al. Methodological quality of guidelines in gastroenterology. Endoscopy
2014;46:513-25.
7
Chokshi, RV. et al. Prevalence of missed adenomas in patients with inadequate bowel
preparation on screening colonoscopy. Gastrointest Endosc, 2012. 75(6): p. 1197-203.
8
Froehlich, F. et al. Impact of colonic cleansing on quality and diagnostic yield of colonoscopy:
the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study.
Gastrointest Endosc, 2005. 61(3): p. 378-84
9
Kaminski, MF. et al. Quality indicators for colonoscopy and the risk of interval cancer. N
Engl J Med, 2010. 362(19): p. 1795-803.
10
Liu, Y.L. et al. Gallbladder stones and gallbladder polyps associated with increased risk of
colorectal adenoma in men. J Gastroenterol Hepatol, 2018. 33(4): p. 800-806.
11
Esteva, A. et al. Dermatologist-level classification of skin cancer with deep neural networks.
Nature 2017; 542: 115-118
12
Urban, G. et al. Deep Learning Localizes and Identifies Polyps in Real Time With 96%
Accuracy in Screening Colonoscopy. Gastroenterology 2018; 155: 1069-1078
13
Misawa, M. et al. Artificial Intelligence-Assisted Polyp Detection for Colonoscopy: Initial
Experience. Gastroenterology 2018; 154: 2027-2029

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Informed Consent Form
“Development and Validation of an Artificial
Intelligence-assisted Strategy Selection System for Colonoscopy
Cleaning”
Informed Consent Form for clinical study subjects
Informed Consent Form:Information page
Release date: 1.1,12 December 2019
Principal investigator: Yu Honggang
Dear sir / Madam,
We will invite you to participate in a clinical study “ Development and Validation of an
Artificial Intelligence-assisted Strategy Selection System for Colonoscopy Cleaning”. During this
study, we will collect your colonoscopy video for analysis by a new colonoscopy-assisted system
to derive your score of bowel preparation, Doesn’t interfere the physician's original observations
and procedures.
Before you decide whether to participate in the study, please read the following as carefully
as possible to help you understand the study and why it was conducted, the procedure and duration
of the study, the potential benefits or risks of participating in the study. If you wish, you can
discuss it with your family or friends, or ask your doctor for an explanation to help you make a
decision
1.Background and Purpose
Colorectal disease as a common human disease seriously affects the health of human life.
With the aging of the population, the change of diet structure and the aggravation of
environmental pollution, the incidence of colorectal diseases, such as colon cancer, Colon Polyp
and inflammatory bowel disease, has gradually increased.
Colonoscopy is the simplest and most widely available screening procedure for colorectal
cancer(CRC) prevention and early detection. Colonoscopy can clearly observe the small changes
in the terminal ileum and the colorectal, such as erosion, ulcers, bleeding, congestion, edema,
polyps, early cancer, and so on. Colonoscopy can biopsy the lesion site for pathological
examination, to histologically qualitative the characterization of mucosal lesions, such as
inflammation, polyp nature, the degree of differentiation of cancer, and so on. It is helpful to
understand the severity of the lesion and guide the formulation of the correct treatment plan or

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judgment of treatment effect. Colonoscopy can also be the minimally invasive endoscopic
treatment of colorectal polyps, early cancer, bleeding, foreign bodies and other diseases.
Because the quality of bowel preparation affects the colonoscopy's ability to detect adenomas
and polyps, adequate bowel preparation is necessary to ensure optimal use of colonoscopy in CRC
prevention. Almost all clinical guidelines recommend adequate bowel preparation before
colonoscopy. However, up to one third of colonoscopies have been found to show inadequate
bowel preparation, which is estimated to increase the cost of colonoscopies by 12% to 22%. And
there are 20% of patients’ bowel is not adequately prepared. When the patient's bowel
preparation is inadequate, the difficulty of flushing may lead to missed detection of adenomas. so
doctors need to accurately identify such patients and tell them to have a second colonoscopy after
a full bowel cleanse. However, the evaluation of intestinal cleanliness is decided by doctors
subjectively, and there is no objective and effective scoring standard to guide the patients to accept
the second colonoscopy.
Deep learning is an important breakthrough in the field of artificial intelligence in the past
decade. It has great potential in extracting tiny features in image analysis and image classification.
In 2017, the journal Nature published a paper showing that using artificial intelligence to diagnose
skin diseases can reach the level of experts. Subsequently, in the field of digestive endoscopy,
more and more studies began to apply artificial intelligence to assist doctors to find polyps and
improve the detection rate of polyps and adenomas.Urban, G. team used artificial intelligence to
identify polyps with 95% sensitivity. Misawa, M team used artificial intelligence to identify
polyps with 90% sensitivity. The purpose of our research group is to develop the EndoAngel with
real-time intestinal cleanliness assessment. It can derive a decision curve for bowel cleanliness
based on the relationship between the percentage of bowel segments with a Boston score of 1 and
the detection rate of missed adenomas. It can help endoscopists to identify patients who need a
second colonoscopy, to avoid the detection of missed adenomas and the high cost of cleaning time
caused by the wrong decision-making. At the same time, artificial intelligence is in the preliminary
research stage in the field of digestive endoscopy, our research results are expected to provide new
ideas in improving the detection rate of colonoscopic adenomas.
2.Who can participate in the study
1)Male or female aged 18 or above;
2)Colonoscopy is needed to further clarify the characteristics of digestive tract diseases;
3)Patients able to give informed consent were eligible to participate.
4)Able and willing to comply with all study process.
5)No intestinal organic disease.
3.Who can not participate in the study
1)Has participated in other clinical trials, signed informed consent and was in the follow-up period
of other clinical trials.
2)Has participated in clinical trials of the drug and is in the elution period of the experimental drug
or control drug.
3)Drug or alcohol abuse or psychological disorder in the last 5 years.
4)Patients in pregnancy or lactation.
5)Known polyposis syndromes.
6)Gastrointestinal Bleeding.
7)A history of inflammatory bowel disease, colorectal cancer and colorectal surgery.

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8)A history of colorectal surgery.
9)Patients with a contraindication for biopsy.
10)Previous history of allergy to ingredient of bowel cleanser.
11)Patients with intestinal obstruction or perforation, toxic megacolon, Colectomy, heart failure
(Grade III or IV) , severe cardiovascular disease, severe liver failure or renal insufficiency, etc. .
12)Patients with poor bowel preparation that are unable to reach their blindness.
13)Researchers believe that the patient is not suitable to participate in the trial.
4.What would you need to do
Patients need to prepare for colonoscopy routinely, fasting for at least 14 hours and water
deprivation for at least 2 hours before the procedure. Patients undergoing painless operation
receive general anesthesia, while patients undergoing general operation do not need it.The doctor
will be assisted by EndoAngel, which will be able to evaluate intestinal cleanliness according
BBPS.
5.Benefits
Patients who have access to the colonoscopy with EndoAngel will likely have a better view
of the lesion, more accurate recommendations for interval colonoscopy, and more comprehensive
disease information.
6.Adverse events
The adverse events are basically the same as the complications of conventional endoscopic
diagnosis and treatment.Participation in this study does not increase other additional risks.
7.Related fees
Routine colonoscopy for your clinical examination items, the cost of your own. Participation
in this study does not involve additional testing and does not increase the cost of your care.
8.Personal Information
During the colonoscopy process, your endoscopic electronic images and case information
will be collected and preserved in the hospital. Your doctor, the researcher, will be given access to
this electronic information for scientific research. Your personal identity will not be disclosed in
any public report of the results of the relevant research and development. We will do everything
within the law to protect the privacy of your personal medical data.
9.For more information
You can ask any question about this study at any time.
Your doctor will give you his or her phone number so that he or she can answer your
questions
Your doctor will keep you informed if there is any important new information during the
course of the study that may affect your willingness to continue participating in the study.
10.Participation and withdrawal are voluntary
Participation in the study is entirely up to you. You may refuse to participate in the study or
withdraw from the study at any time during the course of the study. You will not be discriminated
against or retaliated against for refusing to participate in the study. Your medical treatment and
entitlements will not be affected.
Your doctor or researcher may suspend your participation at any time in the best interest of
you.
If you withdraw from the study for any reason, you may also be required to undergo a
laboratory and physical examination if your doctor deems it necessary.

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If you choose to participate in this study, we hope that you can adhere to the completion of
the entire research process.
11.Others
Participation in this study is up to you. You can discuss it with your family or friends before
making a decision.
Before you decide to participate in the study, ask your doctor as many questions as you can
about the study until you have a complete understanding of it.
Thank you for reading this. If you decide to participate in the study, please tell your doctor, he or
she will arrange for you to participate in all matters related to the study. Please keep this
information.

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Informed Consent Form:Information page
Name of Clinical Research Project：Development and Validation of an Artificial
Intelligence-assisted Strategy Selection System for Colonoscopy Cleaning
Research physician commitment:
As a research physician, I confirmed that I had clearly explained to the subject
the details of this trial, including their rights and possible benefits and risks, and gave
them a signed copy of my informed consent.
Name：＿＿＿＿＿＿＿
Date;＿＿＿＿＿＿＿
Contact：＿＿＿＿＿＿＿
Subject commitment:
I have read and understood the introduction to this study on the informed consent
page, and have had the opportunity to ask questions. I understand the research
physician's explanation.
I am aware of the risks and benefits of participating in this study. I am aware that
participation in the study is voluntary, and I am sure that there has sufficient time to
consider and volunteer for the trial. I can always ask my doctor for more information,
and I can always withdraw from the study without discrimination or retaliation, and
without prejudice to medical benefits and entitlements.
I also knew that if I dropped out of the study, I would tell my doctor and
complete the physical and chemical tests. If I need to take any other medication for
my illness, I will consult with my doctor in advance or tell him the truth afterwards.
I agree□or refuse□Use my medical records for any other study.
I agree to participate in the study and promised to follow the doctor's advice to
the best of my ability. I will receive a signed and dated copy of the Informed Consent
Form.
Name：＿＿＿＿＿＿＿
Date;＿＿＿＿＿＿＿
Contact：＿＿＿＿＿＿＿

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