A Multi-center Study on the Efficacy and Safety of Artificial Intelligence-assisted Navigation System for Biliopancreatic Endoscopic Ultrasonography
Phase: NA
Conditions: Pancreatic Cancer
Sponsor: Renmin Hospital of Wuhan University

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A single-center study on the efficacy and safety of
Artificial Intelligence-assisted navigation system for
pancreatic endoscopic ultrasonography
Short Title：Endoangel Study
NCT
-
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..........................................8
5.
Purpose and overall design......................................................................................................... 9
5.1.
Purpose............................................................................................................................9
5.2.
Overall design................................................................................................................. 9
6.
Study process.............................................................................................................................. 9
6.1.
Summary of Study Process.............................................................................................9
6.2.
Enrollment.......................................................................................................................9
6.2.1.
Informed Consent............................................................................................. 10
6.2.2.
Patient Selection............................................................................................... 10
6.2.3.
Subject identification number...........................................................................11
6.3.
Treatment Description...................................................................................................11
6.3.1.
Patient Screening Assessments.........................................................................11
6.3.2.
Pre-procedure Management..............................................................................11
6.3.3.
Intraprocedure Management.............................................................................11
6.3.4.
Post-procedure Management............................................................................ 12
6.4.
Suspension and withdrawal.......................................................................................... 12
6.4.1.
Pre-procedure....................................................................................................12
6.4.2.
Intraprocedure...................................................................................................12
6.4.3.
Replacement......................................................................................................12
6.5.
Randomization and Blinding........................................................................................ 13
6.5.1.
Randomization Implementation....................................................................... 13
6.5.2.
Blinding Implementation and Protection..........................................................13
6.5.3.
Unblinding........................................................................................................ 13
6.6.
Concomitant Therapy and Medication......................................................................... 14
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..............................................................................................................15
7.4.
Expected and trial-related adverse events.................................................................... 15
7.5.
Risk minimization.........................................................................................................16
7.6.
Related benifits............................................................................................................. 16
7.7.
Overall feasibility analysis............................................................................................16

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8.
Statistical Analysis Plan............................................................................................................16
8.1.
Statistical Analysis Plan................................................................................................16
8.2.
Methods.........................................................................................................................16
8.3.
Hypothetical test........................................................................................................... 16
8.4.
Sample Size Calculation............................................................................................... 17
8.5.
Statistical analysis set................................................................................................... 17
9.
Device Description.................................................................................................................... 17
10. Abbreviation..............................................................................................................................17
11. References.................................................................................................................................19
12. Informed Consent Form............................................................................................................21

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1.
Summary
Title：
A single-center study on the efficacy and safety of Artificial
Intelligence-assisted navigation system for pancreatic endoscopic
ultrasonography
Short Title：
EndoAngel Study
Trial number：
EA-19-003
Research system
EndoAngel
Expected effect：
ENDOANGEL's intended use is to effectively improve the
quality of EUS scanning for physicians, enhance the cognitive
ability of endoscopists in endoscopic ultrasound images, and
reduce the missed diagnosis of lesions.
Primary Endpoint：
Missed scanning rate of adjacent important anatomical structures
in pancreatic endoscopic ultrasonography
Secondary Endpoints:
1.Pancreatic lesions detection rate;
2.Cholangiopancreatic duct lesions detection rate
3.The average number of scanning in the pancreatic standard
station of endoscopic ultrasonography
4.Detection rate of lesions in different pancreatic standard
stations of endoscopic ultrasonography
5.Missed scanning rate of adjacent vital anatomical structures in
different pancreatic standard stations of endoscopic
ultrasonography
6.Mean scanning time in different pancreatic standard stations of
endoscopic ultrasonography
Trail design：
Prospective, single-center, randomized controlled trial
Participants：
Male and female subjects aged 18 years or older will require a endoscopic
ultrasonography,
and
voluntarily
provide
endoscopic
ultrasonography
imaging data and sign an informed consent form.
Sample size：
285 samples needed to be enrolled
Study Process：
Subjects who met all inclusion criteria and did not meet all exclusion criteria
were included in the study before endoscopic ultrasonography. All included
subjects signed an informed consent form. Subjects will be randomized prior
to the start of the examination to either an Endoangel-assisted experimental
group or a control group without Endoangel assistance. The operating
physician completed the endoscopic ultrasonography according to the
presence or absence of AI prompt. The recorder shall record the number of
adjacent important structures, the number of standard stations, the operation
time and the lesion detection etc. Follow-up will be performed for one week
after the end of examination. The end time of follow-up is the end time of
study. And the results are sent to an independent data analysis team for
review.

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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 EUS（d 0）Follow up (d 1-14)
Informed Consent
X
Basic characteristics
X
Medical
history/surgical
history
X
Inclusion/Exclusion
Criteria
X
Random
X
Endoscopic
Ultrasonography
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
Experimental group
Endoscopists perform endoscopic
ultrasonography of the pancreas with the
aid of Endoangel
Sign the Informed Consent
Quit
No
Yes
The recorder shall record the number of adjacent important structures, the number of
standard stations, the operation time and the lesion detection etc.
Follow-up.Research completed
Control group
Endoscopists perform endoscopic
ultrasonography of the pancreas without
the aid of Endoangel
Randomization

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2.
Introduction
Pancreatic cancer is a malignant tumor of the digestive system with insidious onset, rapid
progression and very poor prognosis[1, 2]. According to the latest cancer data in China in 2020
released by the International Agency for Research on Cancer (IARC) of the World Health
Organization, there are about 120,000 new cases of pancreatic cancer in China, with a mortality
rate close to 100%, which seriously endangers the national health[3, 4]. Early diagnosis of
pancreatic cancer can be achieved by surgical resection with a 5-year survival rate of 58% [5],
Once advanced pancreatic cancer develops, patient survival is 7.2%[6]. As a rapidly developing
deadly cancer, missed diagnosis of pancreatic cancer may have extremely serious consequences
for patients.How to improve the diagnostic rate of early pancreatic cancer is an urgent problem to
be solved.
EUS(endoscopic ultrasonography) is considered one of the most sensitive modalities for
pancreatic cancer detection. It has a much higher diagnostic accuracy than MRI and CT for the
diagnosis of pancreatic cancer, especially early pancreatic cancer < 1 cm in diameter (EUS-FNA
95.6% vs CT 77.4%, MRI 76.2%)[7-9]. EUS is the modality of choice for the early diagnosis of
pancreatic tumors[10]. To avoid a missed diagnosis of the pancreatic cancer, the continuity and
integrity of EUS needs to be ensured as much as possible. But EUS is highly operator-dependent
and the learning curve is steep, and the quality of the examination is highly dependent on the
operator's technique[11-13]. Therefore, it is necessary to develop a system that can effectively
assist the full scanning of EUS.
The station approach in pancreatic EUS has been established as the standard scanning
procedure[14-15]. The principle of completing the station approach is to find the anatomical
landmarks of this station[16-17], Such as organs (kidney, spleen), blood vessels (such as splenic
artery, splenic vein, portal vein), ducts (pancreatic duct, bile duct), etc.The scanning of these
anatomical landmarks is the basis for an accurate assessment of the entire pancreas。
At the same time, the type of pancreatic lesions and the development of the course have
abnormal imaging findings of different anatomical structures[18-19]. For example, ultrasound
images of pancreatic cancer will show vascular invasion, deformation of the biliopancreatic duct,
and metastasis of adjacent organs[20]. The guidelines clearly require that the choice of surgical
approach for pancreatic cancer needs to be based on the degree of invasion of the cancer to
adjacent important anatomical structures, to maximize the volume sparing of functional pancreatic
parenchyma[21]. Complete anatomical scanning can assist in the diagnosis of pancreatic lesions
and guide patient treatment and prognosis.
In recent years, artificial intelligence (AI) has been successfully applied in multiple medical
fields[22-24]. At present, there have been studies of AI-based endoscopic ultrasonography for the
identification of pancreatic lesions[25-27], However, there are no studies of AI-based navigation
system for pancreatic endoscopic ultrasonography. Previously, we have successfully developed a
standard station scanning navigation system for the pancreas and bile ducts. This system can
improve the recognition accuracy of endoscopists for standard stations and enhance the cognitive
ability of endoscopic ultrasonography images[28-29].

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Based on the previous, we constructed a deep learning-based pancreatic scanning navigation
system in EUS, which can assist in identifying important anatomical structures adjacent to the
pancreas in real time. and verify its auxiliary performance for endoscopists in clinical practice. In
order to improve the quality of EUS and reduce the missed diagnosis of pancreatic lesions.
3.
Patient Selection
Male and female subjects aged 18 years or older will require a endoscopic ultrasonography,
and voluntarily provide endoscopic ultrasonography imaging data and sign an 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.
3.1. 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)
EUS 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.
3.2. 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)
A history of Upper Gastrointestinal surgery.
6)
Patients with anatomical abnormalities of the upper gastrointestinal tract due to advanced
neoplasia
7)
Patients in whom the presence of clearly defined vital anatomical structures cannot be
observed
8)
Researchers believe that the patient is not suitable to participate in the trial.

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3.3. Definition of enrollment
After participants signed informed consent, they were randomized before the endoscopic
ultrasonography. The randomization time was the enrollment time, and was recorded in CRF.
4.
Endpoints
4.1. Primary Endpoint
1) Missed scanning rate of adjacent important anatomical structures in pancreatic endoscopic
ultrasonography：
It was calculated by dividing the number of important anatomy that is not scanned in the actual
EUS pancreas by the number of EUS.
4.2. Secondary Endpoints
1)
Pancreatic lesions detection rate: It was calculated by dividing the total number of patients
being detected pancreatic lesions by the number of EUS.
2)
Cholangiopancreatic duct lesions detection rate: It was calculated by dividing the total
number of patients being detected cholangiopancreatic duct lesions by the number of EUS.
3)
The average number of scanning in the pancreatic standard station of endoscopic
ultrasonography: It was calculated by dividing the total number of scanning in the
pancreatic standard station by the number of EUS.
4)
Detection rate of lesions in different pancreatic standard stations of endoscopic
ultrasonography: It was calculated by dividing the number of patients with pancreatic
lesions and Cholangiopancreatic duct lesions in the different standard stations by the
number of EUS.
5)
Missed scanning rate of adjacent vital anatomical structures in different pancreatic
standard stations of endoscopic ultrasonography: It was calculated by dividing the number
of important anatomy that is not scanned in the different standard stations by the number
of EUS.
6)
Mean
scanning
time
in
different
pancreatic
standard
stations
of
endoscopic
ultrasonography: It was calculated by dividing the total scanning time by the number of
EUS.
4.3. 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

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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.
5.
Purpose and overall design
5.1. Purpose
The purpose of this study is to develope the Endoangel with real-time pancreatic scanning
navigation system in EUS. It can assist in identifying important anatomical structures adjacent to
the pancreas in real time. and verify its auxiliary performance for endoscopists in clinical practice.
In order to improve the quality of EUS and reduce the missed diagnosis of pancreatic lesions.
5.2. Overall design
This is a prospective, single-center, randomized controlled trial study.
6.
Study process
6.1. 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 EUS will be collected
• If the patient is enrolled, he will be randomized
• EUS 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.
6.2. Enrollment
Only after patients signed the informed consent, can the research-related procedures be conducted.

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6.2.1. 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,
• 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.
6.2.2. Patient Selection
All patients who underwent EUS, 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.

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It is desirable to be able to collect complete data for all enrolled patients, without those
withdrawal from the study.
6.2.3 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.
6.3 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.
6.3.1 Patient Screening Assessments
1）History
2）Physical examination
3）Hematuria pregnancy test (if required)
6.3.2 Pre-Procedure Managements
1）Fasting for 6 hours and water deprivation for 2 hours before examination
2）Routine stomach preparation.
3）Psychological counseling.
4）Performing routine anesthesia for painless gastroscopy patients.
6.3.3 Intraoperative Managements
1）Patient position: lateral position with appropriate restraint.
2）Insertion route: according to the actual situation of the subject, usually through the esophagus
3）Routine observation

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6.3.4 Post-operative Managements
1）Postoperative routine nursing
2）Subjects were observed to wake up
3）Patients without pancreatic lesions and other lesions were followed up until the patient
woke up and left the endoscopic room.
4）Patients with pancreatic lesions and other lesions detected should be followed up for 7 days
after the EUS.
5）Record complications (if any).
6.4 Suspension and withdrawal
Patients who were screened and confirmed to be eligible for the study, signed the informed
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.
6.4.1Pre-Procedure
In any time during the study period, even before EUS, participants could withdraw their
informed consent whenever necessary. Researchers can withdraw participants before surgery
according to safety considerations in the inclusion and exclusion criteria.
6.4.2 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）Unable to complete EUS due to obstruction or other reasons
6.4.3 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 EUS
examination will not subsequently be replaced by other subjects.

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6.5 Randomization and Blinding
6.5.1 Randomization Implementation
Randomization is conducted according to the study protocol, and the random contents are
implemented in an electronic system block-randomized manner (n = 4; experimental group/control
group = 1). Randomization prior to EUS to decide whether to use EndoAngel. The researchers
randomized the random results generated by the electronic system, and the generated random
results were stored in the research center. The random time (accurate to minute), random person,
subject number and acronym were recorded in the corresponding positions of the electronic
system.
6.5.2 Blinding Implementation and Protection
Subjects and evaluators are blinded according to the protocol.
Randomization results will be kept confidential to the subjects in general. Randomization
results are not reflected in inpatient history and other subject access documents. During and after
the examination, study personnel should take care not to talk to the subject about the results of the
randomization to avoid unnecessary unblinding
The assessors are blinded, and the data analysis team and pathologists could not obtain the
randomization results from the medical history data.
6.5.3 Unblinding
Uncovering or breaking the blindness means displaying the randomized results to the subjects
or evaluators. Researchers should protect the blind method as far as possible. Uncovering the
randomized results of a single subject may lead to the leakage of the randomized results of other
subjects. Any leakage of the randomized results will have a significant impact on statistical
analysis. In general, it is prudent to deal with the disclosure of blind law. In the following cases, it
is possible to consider the disclosure of blind law:
1) endangering the safety of subjects: For example, in some serious adverse events, subjects need
to know the randomized results to inform other physicians to take appropriate emergency
treatment.
2) Threatening the safety of the assessor: When the assessor is facing potential safety hazards, he
needs to know the randomization results.
3) Compliance: For reasons of partial compliance, in certain circumstances, if the research
instruments and cases involved in unexpected adverse events are needed, the results of
randomization should be made public to the relevant departments or the public.
5) Other management reasons.

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6.6 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.
7.
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.
7.1. Selection of endpoints
1、The primary outcome of the study are the Missed scanning rate of adjacent important
anatomical structures in pancreatic endoscopic ultrasonography.
The
secondary
outcomes
of
this
study
were:
1.Pancreatic
lesions
detection
rate;
2.Cholangiopancreatic duct lesions detection rate; 3.The average number of scanning in the
pancreatic standard station of endoscopic ultrasonography; 4.Detection rate of lesions in different
pancreatic standard stations of endoscopic ultrasonography; 5.Missed scanning rate of adjacent
vital anatomical structures in different pancreatic standard stations of endoscopic ultrasonography;
6.Mean scanning time in different pancreatic standard stations of endoscopic ultrasonography.
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).
7.2. Definition of participants
Patients were included according to the indications and contraindications described in the use

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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.
7.3. 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.
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.
7.4. 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

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the incidents of diagnosis and treatment.
7.5. 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.
7.6. Related benifits
Subjects will be randomly assigned to an experimental group or a control group. And
experimental subjects may increase the detection of pancreatic lesions and other lesions.
7.7. 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.
8.
Statistical Analysis
8.1. Statistical Analysis Plan
Data management and statistical analysis were implemented by Renmin Hospital Wuhan
University.
8.2. 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.
8.3. Hypothetical test
The main assumptions are:
1. The use of EndoAngel can reduce the missed scanning rate of adjacent important anatomical
structures in pancreatic endoscopic ultrasonography.
2. The use of EndoAngel can improve the the detection rate of Pancreatic lesions.

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8.4. Sample Size Calculation
We mainly studied the effect of EndoAngel on the the quality of EUS scanningfor
physicians.Therefore, data collection and analysis were conducted for the main effect. It is
expected that a total of 285 subjects will be enrolled. Assuming the missed scanning rate of
adjacent important anatomical structures in experimental group is 8%, the missed scanning rate of
adjacent important anatomical structures in control group is 20%. Bilateral significance level 5%
(alpha =5%), assurance 80% (beta =20%), shedding rate 10%, Expected to enroll 285 patients in
total.
8.5. 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.
9.
Device Description
EndoAngel
Version: EA 2301
10. 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

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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
EUS
Endoscopic ultrasonography
超声内镜
EUS-FNA
Endoscopic Ultrasound Guided Fine Needle Aspiration
超声内镜引导下细针穿刺活检

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11. References
[1]
Henrikson N B, Aiello B E, Blasi P R, et al. Screening for Pancreatic Cancer: Updated Evidence
Report and Systematic Review for the US Preventive Services Task Force[J]. JAMA,
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[2]
Kamisawa T, Wood L D, Itoi T, et al. Pancreatic cancer[J]. Lancet, 2016,388(10039):73-85.
[3]
Chen Q, Zheng R S, Zhang S K, et al. [Cancer incidence and mortality of kidney and unspecified
urinary organs in China, 2015][J]. Zhonghua Zhong Liu Za Zhi, 2020,42(12):1001-1006.
[4]Cancer incidence and mortality statistics worldwide and by region. Available:
https://gco.iarc.fr/today/data/factsheets/cancers/13-Pancreas-fact-sheet.pdf
[5]
Egawa S, Toma H, Ohigashi H, et al. Japan Pancreatic Cancer Registry; 30th year anniversary:
Japan Pancreas Society[J]. Pancreas, 2012,41(7):985-992.
[6]
Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled
analysis of 17 population-based cancer registries[J]. Lancet Glob Health, 2018,6(5):e555-e567.
[7]
Jin Z D, Cai Z Z, Li Z S, et al. [The clinical value of endoscopic ultrasonography in early
diagnosis of pancreatic tumor][J]. Zhonghua Nei Ke Za Zhi, 2007,46(12):984-987.
[8]
Harinck F, Konings I C, Kluijt I, et al. A multicentre comparative prospective blinded analysis of
EUS
and
MRI
for
screening
of
pancreatic
cancer
in
high-risk
individuals[J].
Gut,
2016,65(9):1505-1513.
[9]
Singhi A D, Koay E J, Chari S T, et al. Early Detection of Pancreatic Cancer: Opportunities and
Challenges[J]. Gastroenterology, 2019,156(7):2024-2040.
[10] Dimastromatteo J, Brentnall T, Kelly K A. Imaging in pancreatic disease[J]. Nat Rev
Gastroenterol Hepatol, 2017,14(2):97-109.
[11] Cote G A, Smith J, Sherman S, et al. Technologies for imaging the normal and diseased
pancreas[J]. Gastroenterology, 2013,144(6):1262-1271.
[12] DeWitt J, Devereaux B, Chriswell M, et al. Comparison of endoscopic ultrasonography and
multidetector computed tomography for detecting and staging pancreatic cancer[J]. Ann Intern
Med, 2004,141(10):753-763.
[13]C. F. Dietrich, "Endoscopic Ultrasound : An Introductory Manual and Atlas," Stuttgart: TIS, vol. 2nd
ed, 2011.
[14] Wani S, Wallace M B, Cohen J, et al. Quality indicators for EUS[J]. Gastrointest Endosc,
2015,81(1):67-80.
[15] Irisawa A, Yamao K. Curved linear array EUS technique in the pancreas and biliary tree: focusing
on the stations[J]. Gastrointest Endosc, 2009,69(2 Suppl):S84-S89.
[16] Palazzo
L.
How
to
perform
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pancreaticobiliary
area[J].
Minerva
Med,
2014,105(5):371-389.
[17] Wani S, Keswani R N, Petersen B, et al. Training in EUS and ERCP: standardizing methods to
assess competence[J]. Gastrointest Endosc, 2018,87(6):1371-1382.
[18] Bonmati E, Hu Y, Gibson E, et al. Determination of optimal ultrasound planes for the initialisation
of image registration during endoscopic ultrasound-guided procedures[J]. Int J Comput Assist
Radiol Surg, 2018,13(6):875-883.
[19] Kann P H. Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine

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Pancreas[J]. Front Horm Res, 2016,45:46-54.
[20] Rana
S
S,
Bhasin
D
K.
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ultrasound
and
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divisum[J].
Pancreas,
2014,43(1):141-153.
[21] Brugge W R. The role of EUS in the diagnosis of cystic lesions of the pancreas[J]. Gastrointest
Endosc, 2000,52(6 Suppl):S18-S22.
[22] Ting D, Pasquale L R, Peng L, et al. Artificial intelligence and deep learning in ophthalmology[J].
Br J Ophthalmol, 2019,103(2):167-175.
[23] Ching T, Himmelstein D S, Beaulieu-Jones B K, et al. Opportunities and obstacles for deep
learning in biology and medicine[J]. J R Soc Interface, 2018,15(141).
[24] Richards B A, Lillicrap T P, Beaudoin P, et al. A deep learning framework for neuroscience[J]. Nat
Neurosci, 2019,22(11):1761-1770.
[25] Saftoiu A, Vilmann P, Dietrich C F, et al. Quantitative contrast-enhanced harmonic EUS in
differential
diagnosis
of
focal
pancreatic
masses
(with
videos)[J].
Gastrointest
Endosc,
2015,82(1):59-69.
[26] Kuwahara T, Hara K, Mizuno N, et al. Usefulness of Deep Learning Analysis for the Diagnosis of
Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas[J]. Clin Transl
Gastroenterol, 2019,10(5):1-8.
[27] Marya N B, Powers P D, Chari S T, et al. Utilisation of artificial intelligence for the development
of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune
pancreatitis[J]. Gut, 2020.
[28] Zhang J, Zhu L, Yao L, et al. Deep learning-based pancreas segmentation and station recognition
system in EUS:
development and validation of a useful training tool (with video)[J].
Gastrointest Endosc, 2020,92(4):874-885.
[29] Chen M, Wang J, Xiao Y, et al. Automated and real-time validation of gastroesophageal varices
under esophagogastroduodenoscopy using a deep convolutional neural network: a multicenter
retrospective study (with video)[J]. Gastrointest Endosc, 2021,93(2):422-432.

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Informed Consent Form
“A single-center study on the efficacy and safety of Artificial
Intelligence-assisted navigation system for pancreatic
endoscopic ultrasonography”
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 “A single-center study on the efficacy and
safety
of
Artificial
Intelligence-assisted
navigation
system
for
pancreatic
endoscopic
ultrasonography”. During this study, we will use a new EUS-assisted system which do not
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
Pancreatic cancer is a malignant tumor of the digestive system with insidious onset, rapid
progression and very poor prognosis. According to the latest cancer data in China in 2020 released
by the International Agency for Research on Cancer (IARC) of the World Health Organization,
there are about 120,000 new cases of pancreatic cancer in China, with a mortality rate close to
100%, which seriously endangers the national health. Early diagnosis of pancreatic cancer can be
achieved by surgical resection with a 5-year survival rate of 58%, Once advanced pancreatic
cancer develops, patient survival is 7.2%. As a rapidly developing deadly cancer, missed diagnosis
of pancreatic cancer may have extremely serious consequences for patients.How to improve the
diagnostic rate of early pancreatic cancer is an urgent problem to be solved.
EUS(endoscopic ultrasonography) is considered one of the most sensitive modalities for
pancreatic cancer detection. It has a much higher diagnostic accuracy than MRI and CT for the
diagnosis of pancreatic cancer, especially early pancreatic cancer < 1 cm in diameter (EUS-FNA
95.6% vs CT 77.4%, MRI 76.2%). EUS is the modality of choice for the early diagnosis of

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pancreatic tumors. To avoid a missed diagnosis of the pancreatic cancer, the continuity and
integrity of EUS needs to be ensured as much as possible. But EUS is highly operator-dependent
and the learning curve is steep, and the quality of the examination is highly dependent on the
operator's technique. Therefore, it is necessary to develop a system that can effectively assist the
full scanning of EUS.
The station approach in pancreatic EUS has been established as the standard scanning
procedure. The principle of completing the station approach is to find the anatomical landmarks of
this station, Such as organs (kidney, spleen), blood vessels (such as splenic artery, splenic vein,
portal vein), ducts (pancreatic duct, bile duct), etc.The scanning of these anatomical landmarks is
the basis for an accurate assessment of the entire pancreas。
At the same time, the type of pancreatic lesions and the development of the course have
abnormal imaging findings of different anatomical structure. For example, ultrasound images of
pancreatic cancer will show vascular invasion, deformation of the biliopancreatic duct, and
metastasis of adjacent organs. The guidelines clearly require that the choice of surgical approach
for pancreatic cancer needs to be based on the degree of invasion of the cancer to adjacent
important anatomical structures, to maximize the volume sparing of functional pancreatic
parenchyma. Complete anatomical scanning can assist in the diagnosis of pancreatic lesions and
guide patient treatment and prognosis.
In recent years, artificial intelligence (AI) has been successfully applied in multiple medical
fields. At present, there have been studies of AI-based endoscopic ultrasonography for the
identification of pancreatic lesions, However, there are no studies of AI-based navigation system
for pancreatic endoscopic ultrasonography. Previously, we have successfully developed a standard
station scanning navigation system for the pancreas and bile ducts. This system can improve the
recognition accuracy of endoscopists for standard stations and enhance the cognitive ability of
endoscopic ultrasonography images.
Based on the previous, we constructed a deep learning-based pancreatic scanning navigation
system in EUS, which can assist in identifying important anatomical structures adjacent to the
pancreas in real time. and verify its auxiliary performance for endoscopists in clinical practice. In
order to improve the quality of EUS and reduce the missed diagnosis of pancreatic lesions.
2.Who can participate in the study
1)Male or female aged 18 or above;
2)EUS 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.
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)A history of Upper Gastrointestinal surgery.

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6)Patients with anatomical abnormalities of the upper gastrointestinal tract due to advanced
neoplasia
7)Patients in whom the presence of clearly defined vital anatomical structures cannot be observed
8)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 EUS routinely, fasting for at least 6 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. If you are assigned to the
experimental group, the endoscopists will be assisted by EndoAngel, which can assist in
identifying important anatomical structures adjacent to the pancreas in real time. If you are
assigned to the control group, the endoscopist performs the examination routinely without special
prompts. You are equally likely to be in the above two groups
5.Benefits
You will be randomized into the experimental group and the control group. The endoscopists
in the experimental group will be assisted by EndoAngel, which can assist in identifying important
anatomical structures adjacent to the pancreas in real time. Patients who have access to the EUS
with EndoAngel will likely have a better view of the lesion, a higher exam quality, 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 EUS 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 EUS process, your EUS 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

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laboratory and physical examination if your doctor deems it necessary.
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：A single-center study on the efficacy and safety
of Artificial Intelligence-assisted navigation system for pancreatic endoscopic
ultrasonography
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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