A Multicenter, Prospective, Randomized Study on Endosonographic Evaluation of Pancreatic Cystic Lesions Using 22 G, 19 G, and Flexible 19 G Fine Needle Aspiration
Phase: NA
Conditions: Pancreatic Cystic Lesions
Sponsor: Boston Scientific Corporation

Confidential 
 
12 AUG 2016                                              
 
Boston Scientific 
 
FINAL                         
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 1 of 46 
 
 
 
Evaluation of PCLs Using Three EUS-FNA Needles 
 
NCT 01711294 
 
Clinical Protocol 
 
12 August 2016 

Confidential 
 
12 AUG 2016                                              
 
Boston Scientific 
 
FINAL                         
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 2 of 46 
 
 
A Multicenter, Prospective, Randomized Study on 
Endosonographic Evaluation of Pancreatic Cystic Lesions  
Using 22 G, 19 G, and Flexible 19 G Fine Needle Aspiration 
 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
 
 
CLINICAL PROTOCOL 
 
90869947/E7084 
12 August 2016 
 
 
 
 
 
 
 
 
 
 
 
Sponsored By 
Boston Scientific Corporation 
100 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. It should be held 
confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 

E7084 
 
Confidential 
12 AUG 2016 
                                                   Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 3 of 46 
Investigator’s Signature Page 
 
 
STUDY TITLE: 
A Multicenter, Prospective, Randomized Study on 
Endosonographic Evaluation of Pancreatic Cystic Lesions 
Using 22 G, 19 G, and Flexible 19 G Fine Needle Aspiration 
 
 
PROTOCOL VERSION 
AG 
STUDY CENTER: 
 
(Print name of study center) 
 
We, the undersigned, have read and understand the protocol specified above and agree on its 
content.  We agree to perform and conduct the study as described in the protocol.  In 
addition, when applicable, we agree to enlist sub-Investigators who also agree to perform and 
conduct the study as described in the protocol. 
 
 
_____________________________________                  
________________________ 
Principal Investigator (Print Name)  
 
 
Date 
 
 
 
_____________________________________                  
________________________ 
Co-Principal Investigator (Print Name) 
 
 
Date 
 
 
 
_____________________________________                  
________________________ 
Co-Principal Investigator (Print Name) 
 
 
Date 
 
 
 
_____________________________________                  
________________________ 
Co-Principal Investigator (Print Name) 
 
 
Date 
 
 

E7084 
 
Confidential 
12 AUG 2016 
                                                   Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 4 of 46 
Contact Information 
Role 
Contact  
Clinical Contact 
Nguyet Labenski 
Associate Project Manager 
Endoscopy  
Boston Scientific Corporation 
100 Boston Scientific Way 
Marlborough, MA 01752-1234 
Phone:  +1-508-683-4065 
Fax:  +1-508-683-5042 
Email:  nguyet.labenski@bsci.com 
 
Coordinating 
Principal 
Investigator 
Michael B. Wallace, MD, MPH 
Professor of Medicine 
Chair, Division of Gastroenterology 
Mayo Clinic 
4500 San Pablo Road  
Jacksonville, FL 32224 
Phone:  +1-904 953-7382 
Fax:  +1-904 953-6225 
Email:  Wallace.Michael@mayo.edu  
 
Original Release: April 13, 2012 
Current Version: August 12, 2016 
 
 
 
 
 
 
 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 5 of 46 
 
1. 
INTRODUCTION ................................................................................................................. 12 
2. 
PRIMARY OBJECTIVE ........................................................................................................ 12 
3. 
STUDY DESIGN .................................................................................................................. 12 
4. 
ENDPOINTS ........................................................................................................................ 14 
4.1. Primary Endpoint .................................................................................................. 14 
4.2. Secondary Endpoints ............................................................................................. 14 
5. 
SUBJECT SELECTION ......................................................................................................... 16 
5.1. Study Population and Eligibility ........................................................................... 16 
5.2. Inclusion Criteria ................................................................................................... 16 
5.3. Exclusion Criteria .................................................................................................. 16 
6. 
STUDY DEVICES ................................................................................................................ 17 
7. 
STUDY PROCEDURES ......................................................................................................... 17 
7.1. Antibiotic Treatment ............................................................................................. 17 
7.2. Needle Puncture and Aspirate Requirements ..................................................... 17 
7.3. Salvage Aspiration ................................................................................................. 18 
7.4. Post-Procedure Handling of Cyst Aspirate.......................................................... 18 
7.5. Adverse Event Assessment .................................................................................... 19 
8. 
STUDY VISITS .................................................................................................................... 19 
8.1. Visit Schedule and Data Collection ...................................................................... 19 
8.2. From Screening to Baseline ................................................................................... 20 
8.2.1. 
Screening and Informed Consent ............................................................... 20 
8.2.2. 
Enrollment ................................................................................................. 21 
8.2.3. 
Baseline ...................................................................................................... 21 
8.2.4. 
Randomization ........................................................................................... 21 
8.3. Procedure ................................................................................................................ 21 
8.3.1. 
Lesion Characteristics ................................................................................ 21 
8.3.2. 
EUS-FNA Procedure ................................................................................. 22 
8.4. Cytology and Chemistry Results .......................................................................... 22 
8.5. 30-Day Follow-up ................................................................................................... 22 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 6 of 46 
8.6. Long Term Clinical Follow-Up Chart Review .................................................... 23 
9. 
STATISTICAL CONSIDERATIONS ....................................................................................... 23 
9.1. Study Hypothesis and Sample Size Calculation .................................................. 23 
9.1.1. 
Primary endpoint considerations: .............................................................. 23 
9.1.2. 
Secondary endpoint c) considerations: ...................................................... 24 
9.2. Enrollment per Investigational Site ...................................................................... 25 
9.3. Data Analysis .......................................................................................................... 25 
10. POTENTIAL RISKS ............................................................................................................. 27 
10.1. Anticipated Adverse Effects .................................................................................. 27 
10.2. Definitions and Classification of Adverse Events ................................................ 27 
10.3. Relationship to Study Device(s) ............................................................................ 29 
10.4. Reporting Requirements to Sponsor .................................................................... 30 
10.4.1. Communication Method ............................................................................ 30 
10.4.2. Communication Timelines ......................................................................... 30 
10.5. Reporting Requirements to EC/IRB .................................................................... 30 
10.6. Return of Devices to Sponsor ................................................................................ 30 
10.7. Potential Risks and Benefits Associated with Study Participation .................... 31 
10.8. Safety Reviews ........................................................................................................ 31 
APPENDIX A: BIBLIOGRAPHY ........................................................................................ 32 
APPENDIX B: ADDITIONAL STUDY CONDUCT REQUIREMENTS ......................... 33 
B.1  COMPLIANCE ..................................................................................................................... 33 
B.2  ETHICS COMMITTEE/INVESTIGATIONAL REVIEW BOARD REVIEW ............................... 33 
B.3 INFORMED CONSENT ......................................................................................................... 33 
B.4 WITHDRAWAL OF CONSENT .............................................................................................. 35 
B.5 DATA MANAGEMENT ......................................................................................................... 35 
B.6 DOCUMENT RETENTION .................................................................................................... 35 
B.7 DEVIATIONS ....................................................................................................................... 36 
B.8 DEVICE ACCOUNTABILITY ................................................................................................ 36 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 7 of 46 
B.9 DEVICE FAILURES AND PRODUCT NONCONFORMITIES .................................................... 36 
B.10 LIST OF INVESTIGATOR RESPONSIBILITIES .................................................................... 37 
B.11 CONFIDENTIALITY ........................................................................................................... 38 
B.12 MONITORING ................................................................................................................... 38 
B.13 ENROLLMENT CONTROLS ............................................................................................... 39 
B.14 SUSPENSION OR TERMINATION ....................................................................................... 39 
B.15 PUBLICATION POLICY ...................................................................................................... 40 
APPENDIX C: STATISITICS AND DIAGNOSTIC ACURACY MEASURES ............... 41 
C.1 META-ANALYSIS OF NINE REFERENCES .......................................................................... 41 
C.2 SAMPLE SIZE CALCULATION ............................................................................................ 41 
C.3 DIAGNOSTIC ACCURACY MEASURES ............................................................................... 43 
 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 8 of 46 
Protocol Synopsis 
 
Full Title 
A Multicenter, Prospective, Randomized Study on Endosonographic 
Evaluation of Pancreatic Cystic Lesions Using 22 G, 19 G, and 
Flexible 19 G Fine Needle Aspiration 
Short Title 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
Primary 
Objective 
To document impact of EUS-FNA needle gauge and flexibility on 
effectiveness of pancreatic cystic lesions (PCL) aspiration, on ability to 
obtain sufficient material for standard diagnostic testing, and on 
diagnostic accuracy of EUS-FNA aspirate for differentiation of mucinous 
(pre-malignant) and non-mucinous cysts.   
Devices 
Name 
Expect™ Endoscopic Ultrasound Aspiration Needle 
Cleared Indication 
The Expect™ Needle is designed to sample targeted sub mucosal and 
extramural gastrointestinal lesions through the accessory channel of a 
curvilinear echoendoscope. 
Device Categories 
• Expect 22 gauge (22 G) 
• Expect 19 gauge (19 G) 
• Expect 19 gauge Flex (19 G Flex) 
Study Design 
Prospective, multi-center study 
Three arm randomized (19 G Flex, 22 G, 19 G) in 2:1:1 ratio with 
salvage.  Salvage procedure will use 19 G Flex for patients originally 
randomized to 19 G or 22 G standard needles, and will use 19 G or 22 G 
standard needle at investigator discretion for patients originally 
randomized to 19 G Flex needle. 
 
Phased 
• Phase I: 2 centers 
• Phase II: expanded to 7 to 12 centers 
Number of 
Subjects 
250 patients (121 in 19 G Flex arm, and 61 patients each in 22 G and 19G 
arm, rounded up) 
Number of 
Centers 
7 to 12 centers 
Primary 
Volume of aspirated cyst fluid as a function of estimated maximal volume 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 9 of 46 
Endpoint 
based on pre-aspiration EUS measure of cyst diameter (s) (% aspiration 
of total estimated volume) 
Secondary 
Endpoints 
Safety Endpoint 
a. Occurrence, severity and relatedness of adverse events to the needle 
and procedure 
Other Endpoints 
b. Extent of cyst aspiration as measured by reduction of maximal cyst 
diameter before and after FNA (converted to volume by standard 
geometric formulation)  
c. Successful echoendoscopic fine needle aspiration of PCL, defined as 
complete cyst aspiration or collection of aspirate adequate to perform 
two standard assays: cytology and carcinoembryonic antigen (CEA) 
d. Ability to reach and penetrate the PCL, stratified by route of access 
and PCL location 
e. Number of EUS-FNA needles and EUS-FNA needle passes used 
f. Time needed for aspiration for each pass and time from first needle 
pass in to last needle pass out 
g. Ease of needle passage in and out of echoendoscope and quality of 
needle visualization inside the cyst, categorized as Excellent, Very 
Good, Good, Fair, and Poor  
h. Accuracy of two EUS-FNA-based standard assays (cytology and 
CEA) as a diagnostic measure of disease state categorized as one of 
the following: serous cyst, mucinous cyst, intra papillary mucinous 
neoplasm (IPMN), or pseudocyst  
i. Post EUS-FNA patient management plan (clinical and/or imaging 
surveillance, percutaneous aspiration, surgical removal) 
j. Impact of EUS-FNA based assays on diagnosis 
k. Rate of cross-over to salvage arm  
Follow-up 
Schedule 
• Baseline:  Screening, Enrollment, Randomization, Demographics, 
Medical History, Lesion Location  
• Procedure:  Lesion Characteristics, EUS-FNA Procedure Details 
(including needle use and times), Aspirate Characteristics, Salvage 
Procedure (if needed), Adverse Events assessment (through discharge 
or approximately 2hrs post-procedure) 
• 30-Day Follow-up:  Adverse events, End of Study 
• Long Term Clinical Follow-Up Chart Review:  Assess patient 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 10 of 46 
status, Chart Review Details, Morphological Status, Cytopathological 
Status, Biochemical Status, Surgical Pathology  
Inclusion 
Criteria 
1. Pancreatic cystic lesion measuring 13mm or greater in largest 
diameter.  
2. Indicated for EUS evaluation of the PCL including EUS-FNA.   
3. Age 18 years of age or older. 
4. Willing and able to comply with the study procedures and provide 
written informed consent form to participate in the study. 
Exclusion 
Criteria 
1. Cysts in which FNA is not indicated based on review by the clinician, 
including potential concern of blood vessel location relative to the 
cyst. 
2. Requirement for anticoagulation using clopidogril, warfarin, or other 
long acting antiplatelet agents (with the exception of aspirin) that 
cannot be safely stopped according to institutional guidelines. 
3. Standard contraindications for EUS.  
4. Known pancreatic pseudocyst. 
5. Pregnancy. 
Statistical 
Methods and 
Sample Size  
The sample size of this study was computed based on the following 
assumptions on the primary endpoint, as well as for the secondary 
endpoint c): 
 
Primary endpoint considerations: 
• The volume of actual aspirated cyst fluid as a function of 
estimated maximal volume either in 19 G or 19 G Flex Arm is 
superior by at least 10% compared to the 22 G Arm, detected with 
90% conjunctive power, using multiple comparison Hochberg’s 
step up method. 
• Requires 50 patients in 19 G Flex Arm, and 25 patients each in 22 
G and 19 G Arms. 
 
Secondary endpoint c) considerations: 
• Superiority of EUS-FNA success rate in 19 G Flex Arm by 16% 
or more compared to both the success rate of the 19 G Arm and 
the 22 G Arm, detected with 80% conjunctive power, using 
multiple comparison Hochberg’s step up method. 
• Requires 121 patients  in 19 G Flex Arm, and 61 patients each in 
22 G and 19G Arm, rounded up 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 11 of 46 
The final sample size was considered to be the maximum of required 
sample sizes of the above stated two endpoints to make sure that the both 
endpoints are properly powered, namely 250 patients. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 12 of 46 
1. Introduction  
Endoscopic ultrasound fine needle aspiration (EUS-FNA) has become the reference standard 
for preoperative diagnosis of pancreatic cystic lesions (PCLs).1,2 Limitations of EUS-FNA 
persist however and include poor cytological yield, modest sensitivity to detection of 
malignancy of neoplastic cysts, and incomplete aspiration of cyst fluid which limits the 
ability to perform tumor marker and cytological testing.  Additionally, EUS-FNA may 
increase the risk of infectious complications compared to EUS without FNA.  Adverse events 
may include but are not limited to pancreatitis, infection, and bleeding.2, 3  Overall, however, 
EUS-FNA is considered a safe and effective procedure.   
Aspiration with a larger diameter needle, particularly in neoplastic cysts with viscous mucoid 
contents, may improve EUS-FNA diagnostic yield and hence favorably impact treatment 
decisions, assuming no unfavorable impact on procedural safety.  Traditionally, however, 
larger diameter EUS-FNA needles are stiffer than lower diameter EUS-FNA needles.  This 
makes their use difficult or even impossible in lesions requiring significantly flexed 
positioning of the echoendoscope.   
Qualitatively, the study hypothesis is based on the assumption that a larger diameter, yet 
flexible EUS-FNA needle may favorably combine lesion accessibility and viscous lesion 
aspiration.  More specifically, the suggestion is that the 19 G Flex EUS-FNA  needle 
combines lesion accessibility attributes of a 22 G standard EUS-FNA  needle and aspiration 
attributes of a 19 G standard EUS-FNA  needle.  Thus, the hypothesis is that the EUS-FNA 
19 G Flex needle will be superior to the EUS-FNA 22 G standard and 19 G standard needles 
for successful EUS-FNA procedures to assess PCLs.  A successful procedure requires lesion 
access or aspirate volume adequate for three widely accepted assays for the assessment of 
PCLs.  
The study design, accordingly, prescribes 3-way randomization with conjunctive superiority 
of performance of the 19 G Flex EUS-FNA  needle compared to both the 19 G standard and 
22 G standard EUS-FNA  needles.  A salvage procedure is offered in case access or complete 
aspiration of the PCL is not attained. 
2. Primary Objective 
To document impact of EUS-FNA  needle gauge and flexibility on effectiveness of PCL 
aspiration, on ability to obtain sufficient material for standard diagnostic testing, and on 
diagnostic accuracy of EUS-FNA aspirate for differentiation of mucinous (pre-malignant) 
and non-mucinous cysts.   
3. Study Design 
• Prospective 
• Multi-center 
• Three arm randomized: 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 13 of 46 
o Arm 1: 19 G Flex, Arm 2: 22 G, Arm 3: 19 G in a 2:1:1 ratio  
o Salvage to 19G or 22G at investigator discretion for Arm 1 failures, and to 19 G 
Flex for Arm 2 and 3 failures 
• Number of patients: 
o 250, namely 121 patients in 19 G Flex and 61 patients each in 22 G and 19 G arm, 
rounded up 
• Number of centers: 
o Phase I: 2 centers, 30 patients 
o Phase II: expanded to 7 to 12 centers, 220 patients 
The Phase I centers are at different locations overseen by one common Investigational 
Review Board (IRB).  The Lead Principal Investigator (Lead PI) is at one of these 
centers.  The small Phase I preamble to further expansion of the study will allow for 
further definition of data collection points in Case Report Forms (CRFs).  No formal 
analysis is planned for the Phase I data. 
• Anticipated study duration: 
o Patients will have a study Follow-up Visit up to 30 days post-EUS-FNA 
procedure and will exit the study. No further study visits will occur. 
o A retrospective Long Term Clinical Follow-Up Chart Review will be performed 
to collect up to 24 months of standard of care clinical information (if applicable).    
 
A flow chart illustrating the study design is provided in Figure 1 below. 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 14 of 46 
Figure 1 – Study Design Flow Chart 
 
 
Consecutive patients with Pancreatic 
Cystic Lesion (PCL)
Eligibility Criteria Met, 
Patient Enrollment & Randomization
Eligibility Criteria Not Met 
22G
19G
Flex
19G 
Repeat Attempt 
Salvage   
19 G Flex
Repeat Attempt 
Salvage       
 19 G/22 G
Repeat Attempt 
Salvage       
 19G Flex
Successful 
echoendoscopic 
FNA of PCL
Successful 
echoendoscopic 
FNA of PCL
Successful 
echoendoscopic 
FNA of PCL
EXIT
30 Day Follow up
30 Day Follow up
30 Day Follow up
30 Day Follow up
30 Day Follow up
30 Day Follow up
EXIT
EXIT
 
4. Endpoints 
4.1. Primary Endpoint 
Volume of aspirated cyst fluid as a function of estimated maximal volume based on pre-
aspiration EUS measure of cyst diameter (s) (% aspiration of total estimated volume). 
4.2. Secondary Endpoints 
Safety Endpoint 
a. Occurrence, severity and relatedness of adverse events to the needle and procedure.   
 
Other Endpoints 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 15 of 46 
b. Extent of cyst aspiration as measured by reduction of maximal cyst diameter before and 
after FNA (converted to volume by standard geometric formulation).  
c. Successful echoendoscopic fine needle aspiration of PCL, defined as complete cyst 
aspiration or collection of aspirate adequate to perform two standard assays: cytology and 
carcinoembryonic antigen (CEA). 
NOTES:  Endpoint c) success is defined as:  
• complete aspiration, defined as reaching a final cyst maximal diameter of less than 
5mm attained with a maximum of 3 needle passes; in the case of a multilocular cyst, 
complete aspiration of the largest locule is required, 
or 
• collection of aspirate adequate to perform two standard assays: cytology and CEA, 
attained with a maximum of 3 needle passes    
Total aspirate volume should be 3cc or more. In cases where less than 3cc of aspirate is 
obtained but cytology and CEA  assays can be adequately completed, the primary 
endpoint is considered to have been met.  Aspirate handling procedures are provided in 
Section 7.4 below. 
d. Ability to reach and penetrate the PCL, stratified by route of access and PCL location. 
e. Number of EUS-FNA needles and EUS-FNA needle passes* used.   
f. Time needed for aspiration for each pass and time from first needle pass in† to last needle 
pass out€.   
DEFINITIONS: 
*Needle pass -- from needle insertion through needle removal outside the cyst lumen, but 
not including needle repositioning within a single of multi-compartment cyst.   
Note: A maximum of 3 needle passes are allowed, after which the EUS-FNA procedure 
will be considered failed. 
†Time of first needle pass in -- time of the first needle puncture into the cyst lumen.   
€Time of last needle pass out -- time of removal of needle outside the cyst lumen at the 
end of the last fluid aspiration from a single or multi-loculated cyst, or after 10 seconds of 
failed attempt to aspirate fluid after the last needle re-repositioning in a single or multi-
compartment cyst. 
g. Ease of needle passage in and out of echoendoscope and quality of needle visualization 
inside the cyst, categorized as Excellent, Very Good, Good, Fair, and Poor.   
h. Accuracy of two EUS-FNA-based standard assays (cytology and CEA) as a diagnostic 
measure of disease state categorized as one of the following: serous cyst, mucinous cyst, 
intra papillary mucinous neoplasm (IPMN), or pseudocyst.     
 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 16 of 46 
NOTES:  
• Determination of disease state per EUS-FNA will be based on results from 
cytology and CEA and will follow published criteria.4 Definitions of the 
diagnostic accuracy measures are provided in Appendix C.3. 
• Samples that do not have both diagnostic assay results (cytology and CEA) will 
be labeled as Indeterminate. 
i. Post EUS-FNA patient management plan (clinical and/or imaging surveillance, 
percutaneous aspiration, surgical removal). 
j. Impact of EUS-FNA based assays on diagnosis. 
k. Rate of cross-over to salvage.  
5. Subject Selection  
5.1. Study Population and Eligibility 
All patients who are scheduled to undergo an EUS-FNA procedure of a PCL by a study 
Investigator will be offered the opportunity to enroll in the study (see Section 8.2 below).  A 
count of such consecutive patients will be kept at each participating center from the time the 
center is enrollment-ready to when enrollment is closed for the center.  Subjects will be asked 
to sign an Informed Consent form (ICF) before any study-specific tests or procedures are 
performed.  Pregnant women will be excluded as per routine clinical care. 
5.2. Inclusion Criteria 
1. Pancreatic cystic lesion measuring 13mm or greater in largest diameter.*  
2. Indicated for EUS evaluation of the PCL including EUS-FNA.  
3. Age 18 years of age or older. 
4. Willing and able to comply with the study procedures and provide written informed 
consent form to participate in the study. 
NOTE: * In a multilocular cyst, the largest locule should measure 13mm or greater in its 
largest diameter. 
5.3. Exclusion Criteria 
1. Cysts in which FNA is not indicated based on review by the clinician, including potential 
concern of blood vessel location relative to the cyst. 
2. Requirement for anticoagulation using clopidogril, warfarin, or other long acting 
antiplatelet agents (with the exception of aspirin) that cannot be safely stopped according 
to institutional guidelines.  
3. Standard contraindications for EUS.  

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 17 of 46 
4. Known pancreatic pseudocyst. 
5. Pregnancy. 
6. Study Devices 
Three versions of the Expect™ Endoscopic Ultrasound Aspiration Needle will be used in this 
study.  The Expect™ Needle is a market-approved device designed to sample targeted sub 
mucosal and extramural gastrointestinal lesions through the accessory channel of a 
curvilinear echoendoscope. 
Study devices are labeled on the box and inner pouch and include name of the legal 
manufacturer, device name and dimensions, lot number, and expiration date. Device labeling 
will be provided in local language(s) as per national regulations. 
For a detailed description of the Expect™ Endoscopic Ultrasound Aspiration Needle, please 
reference the Directions for Use (DFU) included in each device package.  
Devices with the specifications outlined in Figure 2 below will be used in the study: 
Figure 2 – Device Chart 
Device Name 
 
Delivery System 
Working Length  
Needle 
Size 
Needle 
Diameter 
Needle 
Length 
Expect™ Endoscopic 
Ultrasound Aspiration 
Needle 
137.5 cm to 
141.5 cm 
adjustable 
- 22 G 
- 19 G 
- 19 G Flex 
- 0.72 mm 
- 1.10 mm 
- 1.14 mm 
0 cm to 8 cm 
adjustable 
7. Study Procedures 
Endoscopic ultrasound will be performed using standard linear sector scanning EUS 
equipment (e.g., Olympus, Pentax, or Fujinon).  Study procedures will be followed as 
outlined in the sections below.    
7.1. Antibiotic Treatment 
All patients will be given broad spectrum antibiotics such as fluoroquinolone for at least 3 
days starting on the day of the EUS-FNA procedure.  
7.2.  Needle Puncture and Aspirate Requirements 
The following procedural rules will be followed: 
a. Initial needle puncture with stylet in place (with time stamp).  Remove stylet and apply 
10cc suction.  If no aspirate visible in syringe lumen after 5 seconds of suction: reposition 
needle and re-apply suction.  If no aspirate after 5 seconds of suction- lesion classified as 
FNA failure.  Switch to salvage method.  

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 18 of 46 
b. If aspirate visible within syringe lumen, hold suction until no additional material 
accumulated for 10 seconds.  If cyst completely collapses, note final time stamp.  If cyst 
is not completely collapsed, then repositioning is allowed until all cyst locules have been 
punctured, and no additional fluid is obtained for 10 seconds.  Note final time stamp.  If 
cysts is not completely collapsed after attempts, above, note final maximal and 
perpendicular diameter.  
c. In case of a multi-compartment, loculated lesion, all locules accessible with the same 
needle pass will be aspirated, with priority to the largest locule. In cases where a locule is 
positioned in front of another along the axis of the needle, the one most proximal to the 
needle tip should be fully aspirated before accessing the locules located in a more distal 
position. 
d. In the event that cyst components cannot be reached without repuncture, remove needle 
completely from cyst (note time stamp for pass completion).  Repuncture for pass 2 (or 
more) as needed until criteria (see “b” above) for complete aspiration or failure is met.  
e. If maximal cyst diameter is > 5mm after efforts described in “b” above, cyst aspiration is 
considered “failed.” Switch to salvage method (19 Flex, if first method was not 19 Flex).  
7.3. Salvage Aspiration  
In case of inability to access the PCL or to attain complete cyst aspiration, a salvage 
aspiration procedure, or a repeated attempt to aspirate the PCL with another needle, should 
be performed.   
Patients randomized to Arm 1 (19G Flex) should undergo a salvage procedure with a 22 G or 
19 G needle (needle choice at discretion of physician); patients randomized to Arm 2 (22 G) 
and Arm 3 (19 G) should undergo a salvage procedure with a 19 G Flex needle.  Salvage 
procedure will follow the needle puncture and aspirate requirements guidelines outlined in 
Section 7.2 above.   
7.4. Post-Procedure Handling of Cyst Aspirate 
a. Record final cyst maximum diameter and perpendicular diameter.   
b. Record total volume of cyst aspiration by suctioning all material, including what is in the 
needle lumen, into the syringe, inverting it, and removing air. 
- 
If sample volume is > 3cc, send 2cc to chemistry laboratory for CEA. Send remainder 
to cytology lab.  
- 
If sample volume is < 3cc, divide the sample into two aliquots guided by volumetric 
requirements of the local cytology and chemistry labs.  
- 
Sequential portions of the aspirate will be used for the two assays as follows:  
o First aliquot (preferably at least 1cc) – Cytology 
o Second aliquot (preferably at least 1cc) – CEA  
o All remaining fluid is to be added to the first aliquot and sent for cytology 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 19 of 46 
- 
In case the total aspirate volume is insufficient to satisfy local cytology and chemistry 
lab requirements, then the aliquot order outlined above should be used to prioritize 
which subset of assays will be performed.  
- 
In cases in which the aspirate volume is more than 1 cc but less than 3 cc, the first cc 
should be sent for cytology and the remainder should be sent for CEA.  Some 
laboratories may have the ability to perform CEA assays on less than 1 cc of fluid for 
assay.   
- 
In cases in which the aspirate volume is less than 1 cc, the aspirate will nevertheless 
be sent for cytology. 
7.5. Adverse Event Assessment 
• Immediate Adverse Event assessment: Assessment for immediate complications during 
the procedure and prior to discharge (approximately 2hrs post-procedure) or planned 
hospital observation transfer will be done and will be recorded on the Adverse Event (AE) 
CRF.  
• Delayed Adverse Event assessment:  Assessment for delayed complications will be done 
by telephone at 30 days (± 5 days) and will be recorded on the AE CRF.  If a scheduled 
office visit is made during the same time window, it may substitute for the telephone call.  
If surgery or other major intervention (e.g., ERCP, other invasive biopsy) is performed 
prior to 30 days, events will be censored at the date of the procedure.  
Adverse event details including definitions, types, and reporting requirements are provided in 
Section 10. 
8. Study Visits 
8.1. Visit Schedule and Data Collection 
The visit and data collection schedule is outlined in Figure 3 below. 
  
 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 20 of 46 
Figure 3 – Visit and Data Collection Schedule 
Procedure/Assessment 
Screening, 
Enrollment, 
Baseline 
Procedure 
30 
Day 
Follow
-up 
Visit 
(± 5 
days) 
Long Term 
Clinical 
Follow-Up  
Chart 
Review (Up 
to 24 
months 
from 
Procedure) 
ICF 
X 
 
 
 
Eligibility Criteria Assessment  
X 
 
 
 
Demographics 
X 
 
 
 
Medical History 
X 
 
 
X 
Lesion Location 
X 
 
 
X 
Randomization  
X 
 
 
 
Lesion Characteristics 
 
X 
 
X 
EUS-FNA Procedure Details 
(including Needle Use and Times) 
 
X 
 
 
Aspirate Characteristics 
 
X 
 
 
Salvage EUS-FNA Procedure (if 
applicable) 
 
X 
 
 
Adverse Events Assessment 
 
X 
X 
 
Additional Fluid Testing Results 
(if applicable) 
 
 
 
X 
Surgical Pathology (if applicable) 
 
 
 
X 
8.2. From Screening to Baseline 
8.2.1. Screening and Informed Consent 
On an all-comer basis, Investigators will keep a count of the number of patients to whom 
study participation was offered (see also Section 5.1 above).  No study-specific testing will 
be conducted before the subject has signed an Informed Consent Form (ICF).  The ICF is 
study-specific and must be approved by the study Institutional Review Board (IRB)/Ethics 
Committee (EC) (see also Appendix B.2 below).  Study personnel should explain that even 
if a subject agrees to participate in the study and signs the ICF, the inclusion/exclusion 
criteria may demonstrate that the subject is not a suitable candidate for the study.    

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 21 of 46 
8.2.2. Enrollment 
Patients who signed the ICF, met all inclusion criteria, and met none of the exclusion criteria 
will be considered enrolled.  A Screen Failure/Enrolled Log will be maintained of patients 
who signed the ICF but did not satisfy enrollment criteria.   
Only enrolled patients will be randomized and count toward the enrollment ceiling.     
8.2.3. Baseline 
Patient information will be collected on the Baseline CRF pertaining to: 
• Demographics 
• Medical History 
• Lesion Location (head/uncinate, body, tail) 
8.2.4. Randomization 
Enrolled patients will be assigned to the 19G Flex, 22 G or 19 G Arm in a 2:1:1 ratio by 
randomization schedules which will be computer-generated using a pseudo-random number 
generator.  An Interactive Web Response System (IWRS) will be utilized.   
Randomization will be stratified (block randomization) by the following strata: 
• Investigational center 
• PCL location:  head/uncinate, other 
8.3. Procedure 
8.3.1. Lesion Characteristics 
The following lesion characteristics will be assessed by EUS prior to the start of the FNA 
procedure and will be recorded on the Procedure CRF: 
a. Cyst size (maximal diameter, and cross-sectional diameter)  
NOTE:  In the case of a multilocular cyst, size will be measured both as the aggregate 
size of all cyst locules and the long and short perpendicular axis of the largest locule. 
b. Number of locules (1, 2, 3, 4, 5, 6-10, > 10) 
c. Presence of visible mucin (floating, or mobile filling defects) 
d. Presence of mural nodule (non-mobile filling defect) and size  
e. Presence of solid components 
f. Presence of distinct PCL wall 
g. Connectivity to pancreatic duct 
h. Maximal pancreatic duct diameter 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 22 of 46 
An EUS image of the patient’s PCL will be saved during the procedure. 
8.3.2. EUS-FNA Procedure 
The EUS-FNA procedure will be carried out in line with the guidelines provided in Section 7 
above, and the following data will be collected and recorded on the Procedure CRF: 
a. Route of access (gastric, duodenal, esophageal) 
b. Ease of insertion of EUS-FNA needle through echoendoscope 
c. Ability to reach target lesion   
d. Ability to penetrate into target lesion 
e. Quality of needle visualization 
f. Number of needle passes 
g. Ease of removal of EUS-FNA needle from echoendoscope 
h. Aspirate characteristics and adequacy of aspirate volume to perform two assays (cytology 
and CEA) 
i. Adverse Event assessment during procedure and through 2 Hours Post-Procedure or 
discharge from endoscopy unit 
8.4. Cytology and Chemistry Results 
The results of cyst aspirate cytology and CEA assessments will be provided by the cytology 
and chemistry labs and will be recorded on the Cytology and Chemistry Results CRF.  
Results will be categorized as follows4 and will be used for determination of Disease State 
per EUS-FNA: 
• Cytology 
o Bland PAS + 
o Mucinous 
o Pigmented histiocytes 
• CEA (ng/mL) 
o < 0.5 
o > 0.5 and < 200 
o > 200 
8.5. 30-Day Follow-up 
The post-procedure 30-day Follow-up Visit will be conducted over the telephone.  The visit 
window allows for this visit to occur anytime from 25 days to 35 days post procedure.  
Patients will be assessed for potential adverse events that might have occurred from 
discharge until 30 days post-procedure.  AE information will be recorded on the Adverse 
Event CRF. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 23 of 46 
End-of-Study information including information about loss to follow-up or any other 
circumstances that might have led to the patient’s study participation ending will be collected 
on the End of Study CRF.  A subject will be considered lost to follow-up after 3 documented 
attempts of contact by study staff.   
Protocol deviations will also be documented throughout the study. 
 
8.6. Long Term Clinical Follow-Up Chart Review  
After completion of the 30-day Follow-up Visit, a retrospective Long Term Clinical Follow-
Up Chart Review will be performed to collect up to 24 months of standard of care clinical 
information (if applicable). There are no office or telephone visits required. The Investigator 
or study coordinator will review the hospital charts to assess patient status and extract PCL 
characteristic pertaining to Morphological Status, Cytopathological Status, Biochemical 
Status, and Surgical Pathology.  No new Adverse Event information will be captured after 
the 30 Day Post Procedure. 
 
9. Statistical Considerations 
9.1. Study Hypothesis and Sample Size Calculation 
Sample size was calculated based on assumptions for the primary endpoint as well as for 
secondary endpoint c): 
9.1.1. Primary endpoint considerations: 
The study hypothesis states that for either of the 19 G Flex and 19 G Arms, the volume of 
actual aspirated cyst fluid as a ratio (%) of estimated maximal volume is superior by at least 
10% compared to that of the 22 G Arm. 
The study investigators provided the following experience-based estimate of the primary 
endpoint (aspirate volume as % of max volume based on EUS image of the cyst): 
Figure 4 – Hypothesis Generating References (Primary Endpoint) 
Site Investigator 
Mean Volume Ratio 
(%) for 19G and 
19Flex needles 
Mean Volume Ratio 
(%) for 22G needles 
Investigator 1 
80% 
50% 
Investigator 2 
90% 
70% 
Investigator 3 
90% Unilocular cysts, 
50% Multi-locular 
80% 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 24 of 46 
cysts, 
80% Blended mean 
Investigator 4 
90% 
90% 
Investigator 5 
90%  
50% 
Investigator 6 
85% 
65% 
 
From the above table, bootstrap method with 10,000 resamples yielded an estimated mean of 
67.44% and standard deviation of 15.29% for 22G, and a mean of 85.9% and standard 
deviation of 4.67% for 19G/19G Flex. 
The assumption was made that the mean of the “control group”, namely the 22G arm, will be 
67% with a standard deviation of 15.29%. 
 Two null hypotheses are made: 
• H01 : Mean volume ratio of 19 G Flex Arm and  22 G Arm are the same 
• H02 : Mean volume ratio of 19 G Arm  and  22 G Arm are the same 
The alternative hypothesis is: 
• H1 : Mean volume ratio of 19 G Flex/19G Arm is superior to 22 G Arm 
If 50 patients are enrolled in the 19 G Flex Arm and 25 patients each in the 19 G and 22 G 
Arm, the study will have 90% conjunctive power to detect the rejection of both null 
hypotheses to demonstrate superiority of the mean volume ratio of 19 G Flex Arm and 19 G 
Arm to that of 22 G Arm by 10% or more.  Thus, a minimum of 100 patients 
(50+25+25=100) are required. 
9.1.2. Secondary endpoint c) considerations: 
The study hypothesis states that the EUS-FNA 19 G Flex needle is superior to the EUS-FNA 
22 G standard and 19 G standard needles in the secondary endpoint c) measure, which 
requires access or adequate aspirate volume for two standard assays expected from successful 
EUS-FNA procedures in PCL assessment indications.   
To create a quantitative hypothesis for the study, a meta-analysis was completed of nine 
literature reports of EUS-FNA success levels in this indication, using standard, non-flexible 
EUS-FNA needles.  The following references outlined in Figure 5 were used: 
Figure 5 – Hypothesis Generating References (Secondary Endpoint c) 
Reference 
Success ratio 
Success Rate 
(1) Brugge 
109/112 
97.3% 
(3) Al-Haddad 
31/37 
83.8% 
(5) Larsen 
132/251 
52.6% 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 25 of 46 
(6) Khalid 
76/113 
67.3% 
(7) Sawhney 
84/100 
84.0% 
(8) Rogart 
75/107 
70.1% 
(9) Hong 
60/69 
87.0% 
(10) de Jong 
80/128 
62.5% 
(11) Repak 
38/38 
100% 
 
This yields a success rate point estimate of 75% with 95% CI [67% - 90%] (see Appendix 
C.1 for details). 
The assumption was made that the success level of both “control groups”, namely the 22 G 
arm and the 19 G Arm, will be 75%.   
Two null hypotheses are made: 
• H01 : Success rate of 19 G Flex Arm and  22 G Arm are the same 
• H02 : Success rate of 19 G Flex Arm  and  19 G Arm are the same 
The alternative hypothesis is: 
• H1 : Success rate of 19 G Flex Arm is superior to both 22 G Arm and 19 G Arm 
If 121 patients are enrolled in the 19 G Flex Arm and 61 patients each in the 19 G and 22 G 
Arm, the study will have 80% conjunctive power to detect the rejection of both null 
hypotheses to demonstrate superiority of the success rate of 19 G Flex Arm to that of both 
other arms by 16% or more.   Thus, a minimum of 243 patients (121+61+61=243) are 
required. 
Details of the sample size calculation are provided in Appendix C.2.   
9.2. Enrollment per Investigational Site 
A total of 250 patients will be enrolled in this trial at 7 to 12 investigational sites.  To avoid 
that enrollment be too heavily biased towards one site, an enrollment maximum by site will 
be instituted per clinical study agreement between each investigational site and the Sponsor.  
Enrollment controls are discussed in Appendix B.13.     
9.3. Data Analysis 
The Intent-to-treat (ITT) cohort will consist of all randomized patients, namely patients who 
signed the ICF, met all eligibility criteria (see note below), were randomized to one of three 
study arms, and experienced echoendoscope insertion and attempted EUS-FNA procedure.  
Subjects in this cohort, independent of whether EUS-FNA was successful or not, will be 
counted towards the enrollment ceiling.  Any adverse events occurring or resulting from a 
treatment attempt will be collected.       
NOTE:   

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 26 of 46 
Exclusion criteria #1 may be documented after a patient was randomized and the EUS 
procedure was started.  In such cases, the patient will be excluded from the study and no 
longer be a part of the ITT cohort. 
The Modified Intent-to-treat population will consist of ITT population with salvage, namely 
the patients with 19G + Salvage, 22G + Salvage, and 19G Flex+ Salvage. 
 
The per-protocol (PP) cohort will consist of the subset of the ITT patients in whom the target 
lesion could be reached and EUS-FNA yielded any aspirate, used the assigned needle, and 
there were no major protocol deviations.  All endpoints will be analyzed for the ITT and PP 
study populations, for all patients and stratified by EUS-FNA needle type (by randomization 
arm).    
Justification for pooling of data from all study sites will be assessed using standard 
poolability tests. 
Multivariate analyses will be carried out to assess potential correlations between the primary 
endpoint and PCL location, PCL size, route of access (duodenal, esophageal, or gastric), 
needle used, and number of locules.  
The following analyses are planned: 
• Informal interim analysis after study completion of approximately 30 subjects (Phase 
I) to assure that the data structure is robust for data analyses; no decisions pertaining 
to enrollment will be made based on findings of this interim analysis.  
• Informal interim analysis after study completion of approximately 100 subjects (30 
Phase I + 70 Phase II) to finalize endpoint programs and validate them for end of 
study data analysis; no decisions pertaining to enrollment will be made based on 
findings of this interim analysis.  
• Formal final analysis after study completion of all subjects (30 Phase I + 220 Phase 
II). 
A statistical analysis plan will be in place prior to enrollment.  Changes to the plan or 
additional analyses conducted will be identified as ad hoc analyses. 
All statistical analyses will be done using The SAS System software, version 8 or higher 
(Copyright © 2000 SAS Institute Inc., SAS Campus Drive, Cary, North Carolina 27513, 
USA. All rights reserved). Subject demographics, medical history, risk factors, pre- and post- 
procedure characteristics, and outcome variables will be summarized using descriptive 
statistics for continuous variables (mean, standard deviation, number of observations, 
minimum and maximum) and frequency statistics (percent of conformers, number of 
conformers, number of observations) for discrete variables.  

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 27 of 46 
10. Potential Risks 
10.1. Anticipated Adverse Effects  
As per the commercial DFU included with the study devices, the potential complications 
associated with the use of the Expect Needle may include, but are not limited to:   
• Bleeding 
• Perforation 
• Pancreatitis 
• Infection 
• Peritonitis 
• Inflammation 
• Aspiration 
• Fever 
• Allergic Reaction to Medication 
• Hypotension 
• Respiratory Depression or Arrest 
• Cardiac Arrhythmia or Arrest 
• Tumor Seeding 
10.2. Definitions and Classification of Adverse Events  
Adverse event definitions provided below are extracted from References ISO 14155-2011 
and MEDDEV 2.7/3 12/2010 as indicated.  
Figure 6 - Adverse Event Definitions 
Term 
Definition 
Adverse Event 
(AE) 
 
Ref: ISO 14155-
2011 
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal lab findings) in subjects, 
users or other persons, whether or not related to the investigational 
medical device. This includes events related to: 
• The investigational medical device or comparator 
• The procedures involved (study-required) 
For users/other persons, this definition is restricted to events related to 
the investigational device  
Note: In this study, reported AEs will include unanticipated events 
such as unplanned hospital admission or overnight observation, 
laboratory or radiological investigation which confirms pancreatitis, 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 28 of 46 
Figure 6 - Adverse Event Definitions 
Term 
Definition 
bleeding, or perforation, or any other event deemed by the Investigator 
to be unanticipated and attributable to the EUS-FNA procedure. 
Adverse Device 
Effect (ADE) 
 
Ref: ISO 14155-
2011 
Adverse event related to the use of an investigational medical device: 
• This includes adverse events resulting from insufficient or 
inadequate instructions for the use, deployment, implantation, 
installation or operation, or any malfunction of the investigational 
medical device. 
• This includes any event resulting from use error or from intentional 
misuse of the investigational medical device. 
Serious Adverse 
Event (SAE) 
 
Ref: ISO 14155-
2011 
An adverse event that: 
• Led to death 
• Led to a serious deterioration in the health of the subject that either 
resulted in: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, 
or 
o in-patient hospitalization or prolonged hospitalization (of an 
existing hospitalization), or 
o medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
• Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
Note: Planned hospitalization for a pre-existing condition, or a 
procedure required by the protocol, without serious deterioration in 
health, is not considered a serious adverse event.  
Serious Adverse 
Device Effect 
(SADE) 
 
Ref: ISO 14155-
2011 
An adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Note: All SAEs that could have led to a SADE if suitable action had 
not been taken or if circumstances had been less fortunate shall be 
reported as required by the local IRB/EC, national regulations, or the 
protocol. If applicable, see MEDDEV 2.7/3 12/2010 for reporting 
timeline requirements. 
Unanticipated 
Serious Adverse 
Device Effect 
(USADE) 
A serious adverse device effect which by its nature, incidence, 
severity, or outcome has not been identified in the current version of 
the risk analysis report. 
Note: An anticipated serious adverse device effect (ASADE) is an 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 29 of 46 
Figure 6 - Adverse Event Definitions 
Term 
Definition 
 
Ref: ISO 14155-
2011 
effect which by its nature, incidence, severity or outcome has been 
identified in the risk analysis report. 
Device Deficiency 
 
Ref: ISO 14155-
2011 
 
Ref: MEDDEV 
2.7/3 12/2010 
A device deficiency is any inadequacy of a medical device with 
respect to its identity, quality, durability, reliability, safety or 
performance. 
Note: Device deficiencies include malfunctions, use errors, and 
inadequate labeling. 
Note: All device deficiencies that could have led to a SADE if suitable 
action had not been taken or if circumstances had been less fortunate 
shall be reported as required by the local IRB/EC, national regulations, 
or the protocol. If applicable, see MEDDEV 2.7/3 12/2010 for 
reporting timeline requirements. 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
 
Underlying diseases are not reported as AEs unless there is an increase in severity or 
frequency during the course of the investigation. Death should not be recorded as an AE, but 
should only be reflected as an outcome of a specific SAE.  
Reporting requirements are provided in Section 10.4 below. 
Refer to Section 10.1 above for the known risks associated with the study device(s) and 
EUS-FNA procedure. 
10.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study devices as related or 
unrelated using criteria outlined below. 
• AE Unrelated to Study Device:   
o The adverse event is determined to be due to a concurrent illness or effect of 
another device/drug and is not related to the investigational product. 
• AE Related to Study Device:   
o The adverse event is determined to be potentially related to the investigational 
product, and an alternative etiology is equally or less likely compared to the 
potential relationship to investigational product. 
o There is a strong relationship to investigational product, or recurs on re-
challenge, and another etiology is unlikely. 
o There is no other reasonable medical explanation for the event. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 30 of 46 
Unrelated AEs will not be documented. 
10.4. Reporting Requirements to Sponsor 
10.4.1. Communication Method  
Reporting of adverse events and device deficiencies or malfunctions as outlined by category 
and as applicable during the entire duration of the study, from signing of the ICF through 
completion of an end-of-study report, should be made by entering pertinent information into 
the associated study data base fields.  In case access to the electronic case report forms is not 
possible, the Investigator or site study staff members should contact the Sponsor Global 
Safety Office and Sponsor Project Manager by e-mail.  If e-mail communications are also 
impossible, then one of these Boston representatives should be contacted by telephone.  
Contact information for the Sponsor Global Safety Office and Sponsor Project Manager will 
be provided and kept up to date by Sponsor at all times.  
Upon receipt of these communications, associated source documentation may be requested 
by the Sponsor Global Safety Office and Sponsor Project Manager.   
10.4.2. Communication Timelines  
The following should be reported to Sponsor within 2 business days: 
• All Serious Adverse Events (SAEs), whether related to the EUS-FNA  devices and/or 
procedure or not  
• Device Deficiencies, Failures, Malfunctions, and Product Nonconformities that led to 
any Adverse Event (AE) or Serious Adverse Event (SAE).   
The following should be reported to Sponsor within 10 business days: 
• All non-serious Adverse Events (AEs) related to the EUS-FNA  devices and/or 
procedure 
• Device Deficiencies, Failures, Malfunctions, and Product Nonconformities that did 
not lead to an Adverse Event (AE) or Serious Adverse Event (SAE). 
10.5. Reporting Requirements to EC/IRB 
The Principal Investigator is responsible for informing the EC/IRB of AEs and SAEs as 
required by local procedure.  These reporting requirements may vary from one EC/IRB to 
another.   
The Sponsor is responsible for reporting AE and SAE information to participating 
Investigators as required by local procedures at individual Investigational sites.  
10.6. Return of Devices to Sponsor 
All device deficiencies (including but not limited to failures, malfunctions, product 
nonconformities, and labeling errors) will be documented and reported to the Sponsor as 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 31 of 46 
detailed in Section 10.4 above.  If possible, the device(s) related to an observed device 
deficiency should be returned to the Sponsor for analysis.  Instructions for returning the 
investigational device(s) are provided in Appendix B.9.   
10.7. Potential Risks and Benefits Associated with Study Participation 
Patients enrolled in this study were scheduled to undergo a EUS-FNA procedure for 
assessment of a PCL.  The EUS-FNA procedures in this study are performed per DFU and 
standard of practice.  The EUS-FNA needles are commercially available devices.  Thus, there 
is no known added risk resulting from undergoing the EUS-FNA procedure in this study 
compared to outside of this study. 
 
Patients randomized to the standard 19 G or 22 G EUS-FNA needles and in whom the PCL 
could not be accessed or complete cyst aspiration cannot be attained, will receive a second 
attempt at adequate PCL aspiration using the marketed, novel 19 G Flex EUS-FNA needle 
design.  Thus, in a subset of patients, there is an added potential benefit to undergoing the 
EUS-FNA procedure in this study compared to outside of this study.  
10.8. Safety Reviews 
On a pre-established frequency, listings of all device and/or procedure related adverse events 
and of all serious adverse events will be reviewed by the Sponsor.  Incidence of key types of 
adverse events will be statistically compared to pre-established safety thresholds.  These 
thresholds will be based on literature reports of these types of adverse events and will also be 
guided by an ASGE guideline12 on complications associated with EUS.   
Thresholds will be established for:  
• Pancreatitis 
• Infection 
• Hemorrhage  
The Sponsor will capture frequency of safety reviews and of the three above-mentioned 
thresholds in a Safety Plan placed on file prior to first patient enrollment.    
 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 32 of 46 
APPENDIX A: BIBLIOGRAPHY 
1. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, Centeno BA, Szydlo T, Regan 
S, Fernandez del Castillo C, Warshaw AL, The Investigators of the CPC Study; 
Diagnosis of Pancreatic Cystic Neoplasms: A Report of the Cooperative Pancreatic 
Cyst Study  Gastroenterology 2004; 126: 1330-1336 
2. Sakamoto H, Kitano M, Kamata K, El-Masry M, Kudo M; Diagnosis of pancreatic 
tumors by endoscopic Ultrasonography  World J Radiol 2010; 2(4): 122-134 
3. Al-Haddad M, Gill KRS, Raimondo M, Woodward TA, Krishna M, Crook JE, 
Skarvinko LN, Jamil LH, Hasan M, Wallace MB; Safety and efficacy of cytology 
brushing versus standard fine-needle aspiration in evaluating cystic pancreatic 
lesions: a controlled study  Endoscopy 2010; 42: 127-132 
4. Brugge WR; The use of EUS to diagnose cystic neoplasms of the pancreas  GIE 
2009; 69: S 203-9  
5. Larsen MC, Binmoeller KF, Shaw RE, Jaffee IM, Shah JN; Factors Affecting 
Diagnostic Yield of EUS-FNA of Pancreatic Cystic Lesions  GIE 2010; 71: AB282 
(T1456) 
6. Khalid A, Zahid M, Finkelstein SD, LeBlanc JK, Kaushik N, Ahmad N, Brugge WR, 
Edmundowicz SA, Hawes RH, McGrath KM; Pancreatic cyst fluid DNA analysis in 
evaluating pancreatic cysts: a report of the PANDA study  GIE 2009; 69: 1095-102  
7. Sawhney MS, Devarajan S, O’Farrel P, Cury MS, Kundu R, Vollmer CM, Brown A, 
Chuttani R, Pleskow DK; Comparison of carcinoembryonic antigen and molecular 
analysis in pancreatic cyst fluid  GIE 2009; 69: 1106-110 
8. Rogart JN, Loren DE, Singu BS, Kowalski TE; Cyst wall puncture and aspiration 
during EUS-guided fine needle aspiration may increase the diagnostic yield of 
mucinous cysts of the pancreas  J Clin Gastroenterol 2011; 45(2): 164-9 
9. Hong S-KS, Loren DE, Rogart JN, Siddiqui AA, Sendecki JA, Bibbo M, Coben RM, 
Meckes DP, Kowalski TE; Targeted cyst wall puncture and aspiration during EUS-
FNA increases the diagnostic yield of premalignant and malignant pancreatic cysts  
GIE 2012; 75(4): 775-82  
10. de Jong K, Poley JW, van Hooft JE, Visser M, Bruno MJ, Fockens P; Endoscopic 
ultrasound-guided fine-needle aspiration of pancreatic cystic lesions provides 
inadequate material for cytology and laboratory analysis: initial results from a 
prospective study  Endoscopy 2011; 43(7): 585-90 
11. Repak R, Rejchrt S, Bartova J, Malirova E, Tycova V, Bures J; Endoscopic 
ultrasonography (EUS) and EUS-guided fine-needle aspiration with cyst fluid 
analysis in pancreatic cystic neoplasms  Hepatogastroenterol 2009; 56(91-92): 629-
35   
12. Jacobson BC, The ASGE Standards of Practice Committee; ASGE guideline: 
complications of EUS  GIE 2005; 61: 8-12   

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 33 of 46 
APPENDIX B: ADDITIONAL STUDY CONDUCT REQUIREMENTS 
This section provides additional details on items that are mentioned or described more 
succinctly in the main body of the protocol above.  These sections are included per Sponsor 
protocol template requirements.  
B.1  Compliance 
This study will be conducted in accordance with relevant sections of the International 
Standard (ISO) 14155: Clinical Investigation of Medical devices for Human Subjects – Good 
Clinical Practice, the relevant parts of the ICH Guidelines for Good Clinical Practices, ethical 
principles that have their origins in the Declaration of Helsinki, and pertinent individual 
country laws and regulations.  
B.2  Ethics Committee/Investigational Review Board Review 
The study will not begin until the required approval from the EC or IRB has been obtained.  
Approval needs to be gained for the protocol and the ICF.  
Prior to gaining approval to participate in the study, the investigational center will provide to 
the Sponsor documentation verifying that their EC/IRB meets applicable requirements.  This 
typically consists of a detailed list of members of the EC/IRB, including their titles and roles.    
A copy of the written EC/IRB approval of the protocol and ICF must be received by the 
Sponsor before recruitment of subjects into the study and shipment of investigational 
product/equipment.  
Annual EC/IRB approval renewals will be obtained throughout the duration of the study as 
required by local/country or EC/IRB requirements. Copies of the Investigator’s reports and 
the EC/IRB continuance of approval must be provided to the Sponsor.  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate EC/IRB approvals of 
the revised protocol must be obtained prior to implementation. 
B.3 Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
all subjects or their legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and 
local EC/IRB and/or Regulatory authority body, as applicable. The ICF must be approved by 
the EC/IRB as described in Section B.2 above. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 34 of 46 
The Sponsor will provide a study-specific template of the ICF to Investigators participating 
in this study. The ICF template may be modified to meet the requirements of the 
investigative center’s EC/IRB.  Any modification requires approval from the Sponsor prior to 
use of the form.  The ICF must be in a language understandable to the subject and if needed, 
the Sponsor will assist the center in obtaining a written consent translation. Translated 
consent forms must also have EC/IRB approval prior to their use.  Privacy language shall be 
included in the body of the form or as a separate form as applicable.   
The process of obtaining Informed Consent shall: 
• be conducted by the Principal Investigator or designee authorized to conduct the process,  
• include a description of all aspects of the clinical study that are relevant to the subject’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout the 
clinical study. 
The ICF shall always be signed and personally dated by the subject or legal representative 
and by the Investigator or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the center and a copy of the signed and dated document and 
any other written information must be given to the person signing the form.  
Failure to obtain subject consent and any violations of the informed consent process must be 
reported as deviations to the Sponsor and to the EC/IRB, as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 
an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the protocol, a change in Principal Investigator, administrative changes, or following 
annual review by the EC/IRB. The new version of the ICF must be approved by the EC/IRB.  
Sponsor approval is required if changes to the revised ICF are requested by the center’s 
EC/IRB. The EC/IRB will determine the subject population to be re-consented. 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 35 of 46 
B.4 Withdrawal of Consent 
Patients have the right to withdraw from study participation at any time.  
If a subject withdraws from the clinical investigation, the reason(s) shall be reported. If such 
withdrawal is due to problems related to investigational device safety or performance, the 
Investigator shall ask for the subject’s permission to follow his/her status/condition outside of 
the clinical study.   
While study withdrawal is discouraged, subjects may withdraw from the study at any time, 
with or without reason, and without prejudice to further treatment. Additional data may no 
longer be collected after the point at which a subject has been withdrawn from the study or 
withdraws consent. Withdrawn subjects will not be replaced. All open adverse events should 
be closed or documented as ongoing. Data collected up to the point of subject withdrawal 
may still be used. 
B.5 Data Management 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  All changes made to the clinical data will be captured in an electronic audit trail and 
available for review by the Sponsor or its representative.  Database backups are performed 
regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs). Changes to data previously submitted to the Sponsor require a new 
electronic signature by the Investigator acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies.  Manual and/or automatic queries will be created in the EDC system and will 
be issued to the site for appropriate response.  Site staff will be responsible for resolving all 
queries in the database. 
B.6 Document Retention 
The Investigator will maintain, at the investigative site, in original format all essential study 
documents and source documentation that support the data collected on the study subjects in 
compliance with ICH/GCP guidelines.  Documents must be retained for at least 2 years after 
completion of the study.  The Sponsor will also retain study documents for 2 years after 
completion of the study, defined as the date on which a final study report is issued.  The 
Investigator will take measures to ensure that essential documents are not accidentally 
damaged or destroyed.  If for any reason the Investigator withdraws responsibility for 
maintaining these essential documents, custody must be transferred to an individual who will 
assume responsibility and the Sponsor must receive written notification of this custodial 
change.  

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 36 of 46 
B.7 Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An Investigator shall notify the 
Sponsor and the reviewing EC/IRB of any deviation from the investigational plan to protect 
the life or physical well-being of a subject in an emergency, and those deviations which 
affect the scientific integrity of the clinical investigation. Such notice shall be given as soon 
as possible, but no later than 5 working days after the emergency occurred, or per prevailing 
local requirements, if sooner than 5 working days.  
All deviations from the investigational plan, with the reason for the deviation, must be 
documented and reported to the Sponsor using the EDC Protocol Deviation CRF in the 
database.  Sites may also be required to report deviations to the EC/IRB, per local guidelines 
and government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including notification, center re-training, or 
discontinuation) will be put into place by the Sponsor. 
B.8 Device Accountability 
There are no investigational devices used in this study.  The Expect™ Endoscopic 
Ultrasound Aspiration Needle is available for commercial use in the geographical areas in 
which this clinical study is taking place, and therefore no requirements for device 
accountability exist for this study.  Any country/region requirements that depart from the 
aforementioned will be implemented on a case-by-case basis.  
Device Lot information must be maintained in the subject’s medical record and recorded on 
the Procedure CRF. 
B.9 Device Failures and Product Nonconformities 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and labeling errors) will be documented and reported to the 
Sponsor. If possible, the device(s) should be returned to the Sponsor for analysis. Instructions 
for returning the investigational device(s) will be provided by the Sponsor. If it is not 
possible to return the device, the Investigator should document why the device was not 
returned and the final disposition of the device. Device failures and malfunctions should also 
be documented in the subject’s medical record.  
Device deficiencies, failures, malfunctions, and product nonconformities are not to be 
reported as adverse events. However, if there is an adverse event that results from a device 
failure or malfunction, that specific event would be recorded on the appropriate eCRF. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 37 of 46 
B.10 List of Investigator Responsibilities 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Investigator Agreement and Protocol Signature 
page documenting his/her agreement to conduct the study in accordance with the 
protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the center team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
Sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event and observed device deficiency. 
• Report to the Sponsor, per the protocol requirements, all SAEs and device deficiencies 
that could have led to a SADE. 
• Report to the EC/IRB any SAEs and device deficiencies that could have led to a SADE, 
if required by the national regulations or this protocol or by the EC/IRB, and supply the 
Sponsor with any additional requested information related to the safety reporting of a 
particular event. 
• Maintain the device accountability records as needed.   
• Allow the Sponsor to perform monitoring and auditing activities, and be accessible to the 
monitor and respond to questions during monitoring visits. 
• Ensure that informed consent is obtained in accordance with this protocol and local 
EC/IRB requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the ICF. 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 38 of 46 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
When specific tasks are delegated by an Investigator, included but not limited to conducting 
the informed consent process, the Investigator is responsible for providing appropriate 
training and adequate supervision of those to whom tasks are delegated. The Investigator is 
accountable for regulatory violations resulting from failure to adequately supervise the 
conduct of the clinical study.  
B.11 Confidentiality 
All information and data sent to the Sponsor concerning subjects or their participation in this 
study will be considered confidential by the Sponsor.  Only authorized Sponsor personnel or 
a Sponsor representative will have access to these confidential records.  Study data collected 
during this study may be used by the Sponsor for the purposes of this study, publication, and 
to support future research and/or other business purposes.  All data used in the analysis and 
reporting of this study will be without identifiable reference to specific subject name. 
The Sponsor will keep subjects’ health information confidential in accordance with all 
applicable laws and regulations.  The Sponsor may use subjects’ health information to 
conduct this research, as well as for additional purposes, such as overseeing and improving 
the performance of its device, new medical research and proposals for developing new 
medical products or procedures, and other business purposes. Information received during 
the study will not be used to market to subjects; subject names will not be placed on any 
mailing lists or sold to anyone for marketing purposes.  
B.12 Monitoring 
Regular on site monitoring by the Sponsor will not be planned during the study, but 
occasional visits by the Sponsor may be conducted as a measure of quality assurance.  
However, the study database will be monitored to ensure that data are reported in a 
satisfactory manner with respect to timeliness, adequacy, and accuracy.  Sites will be queried 
in the case of any missing, incomplete or inconsistent data.  
The Investigator/institution guarantees direct access to original source documents by Sponsor 
personnel and their designees if required during a monitoring visit or quality assurance audit. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 39 of 46 
B.13 Enrollment Controls 
The Sponsor Project Manager will have responsibility to make every effort possible to avoid 
over-enrollment.  To that end, the Sponsor Project Manager will keep all participating centers 
informed of enrollment status on a regular basis.  An enrollment ceiling will be established 
for each center as well as for the study as a whole.   
When an investigational site is within 3 patients of its enrollment ceiling, the Sponsor Project 
Manager will ask that the site contact him/her PRIOR to each new patient enrollment.    
When overall enrollment of the study is within 15 patients of the enrollment ceiling, the 
Sponsor Project Manager will ask that each site contact him/her PRIOR to each new patient 
enrollment.  Alerts will be sent to all enrolling sites after each new enrollment starting when 
overall enrollment of the study is within 5 patients of the enrollment ceiling.   
When the last patient is enrolled, all investigational sites will immediately be notified of with 
an “Enrollment complete.  Stop Enrollment” message by the Sponsor Project Manager.     
B.14 Suspension or Termination 
The Sponsor reserves the right to terminate the study at any stage but intends to exercise this 
right only for valid scientific or administrative reasons and reasons related to protection of 
subjects.   Investigators and associated ECs/IRBs will be notified in writing in the event of 
study termination. Possible reasons for premature study termination include, but are not 
limited to, the following: 
• The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study. 
Any Investigator or EC/IRB in this study may discontinue participation in the study or 
withdraw approval of the study, respectively, with suitable written notice to the Sponsor.  
Investigators and associated ECs/IRBs will be notified in writing in the event of these 
occurrences. 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating centers by the Sponsor. The 
ECs/IRBs will be notified.  Detailed information on how enrolled subjects will be managed 
thereafter will be provided.  
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by the Sponsor. 
In the event an Investigator terminates participation in the study, study responsibility will be 
transferred to a co-Investigator, if possible.  In the event there are no opportunities to transfer 
Investigator responsibility, detailed information on how enrolled subjects will be managed 
thereafter will be provided by the Sponsor. 
The Investigator must return all documents and investigational product to the Sponsor, unless 
this action would jeopardize the rights, safety, or welfare of the subjects. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 40 of 46 
The Sponsor reserves the right to stop the inclusion of subjects at a study center at any time 
after the study initiation visit if no subjects have been enrolled for a period beyond 2 months 
after center initiation, or if the center has multiple or severe protocol violations/non-
compliance without justification and/or fails to follow remedial actions. In the event of 
termination of Investigator participation, the EC, as applicable, should be notified.  
B.15 Publication Policy 
In accordance with the Corporate Policy on the Conduct of Human Subject Research, the 
Sponsor requires disclosure of its involvement as a Sponsor or financial supporter in any 
publication or presentation relating to a Sponsor study or its results.  In accordance with the 
Corporate Policy for the Conduct of Human Subject Research, the Sponsor will submit study 
results for publication (regardless of study outcome) following the conclusion or termination 
of the study.  The Sponsor adheres to the Contributorship Criteria set forth in the Uniform 
Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org).  In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, Sponsor personnel 
may assist authors and Investigators in publication preparation provided the following 
guidelines are followed. 
• All authorship and contributorship requirements as described above must be 
followed. 
• Sponsor involvement in the publication preparation and the Sponsor Publication 
Policy should be discussed with the Coordinating Principal Investigator(s) at the 
onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding 
publication content, review, approval, and submission.  
 
 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 41 of 46 
APPENDIX C: STATISITICS AND DIAGNOSTIC ACURACY 
MEASURES 
C.1 
Meta-Analysis of Nine References 
Based on published success rates in references 1, 3, 5, 6, 7, 8, 9, 10 and 11 as provided in 
Figure 5 in Section 9.1 above: 
 
  proportion   95%-CI % 
W(fixed) %W(random) 
1     0.9732  [0.9237; 0.9944]     11.72      11.31 
2     0.8378  [0.6799; 0.9381]      3.94      10.41 
3     0.5259  [0.4621; 0.5890]     26.14      11.59 
4     0.6726  [0.5779; 0.7579]     11.83      11.32 
5     0.8400  [0.7532; 0.9057]     10.48      11.25 
6     0.7009  [0.6048; 0.7856]     11.20      11.29 
7     0.8696  [0.7668; 0.9386]      7.26      11.01 
8     0.6250  [0.5351; 0.7090]     13.38      11.37 
9     1.0000  [0.9075; 1.0000]      4.05      10.44 
 
Number of trials combined: 9  
 
                      
 proportion   95%-CI   z  p.value 
Fixed effect model       0.7393  [0.7111; 0.7665] NA       -- 
Random effects model     0.8038  [0.6746; 0.9066] NA       -- 
C.2 
Sample Size Calculation 
Primary endpoint considerations: 
Two null hypotheses are made: 
• H01 : Mean volume ratio of 19 G Flex Arm and 22 G Arm are the same 
• H02 : Mean volume ratio of 19 G Arm and 22 G Arm are the same 
The alternative hypothesis is: 
• H1 : Mean volume ratio of 19 G Flex/19G Arm is superior to 22 G Arm 
Superiority by 10% or more is deemed clinically significant.  Statistical power of 90% is 
chosen using the multiple comparison Hochberg’s method.  Test results are shown below, 
resulting in the requirement for 50 patients for 19 G Flex Arm and 25 patients each for 19 G 
and 22G Arm. 
 
Hypothesis: 
 
𝐻𝑖: 𝜇𝑖−𝜇0 ≤0 Versus 𝐾𝑖: 𝜇𝑖−𝜇0 > 0 for i=1,2. 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 42 of 46 
 
Design Parameters: 
 
One-sided Type I Error=0.05 
Multiple comparison procedure= Hochberg’s step up 
Total Sample required=100 
Rejection region=Right tail 
 
Treatment parameters: 
 
Arm 
Mean volume ratio 
Standard Deviation 
Sample size per 
group 
22G 
67 
15.29 
25 
19G 
77 
4.67 
25 
19GFlex 
77 
4.67 
50 
 
Overall: 
Global (reject any𝐻𝑖): 0.912 
Conjunctive (reject all 𝐻𝑖): 0.901 
 
Secondary endpoint c) considerations: 
 
It is the desire of this study to demonstrate superiority of the EUS-FNA 19 G Flex needle 
over two other needles: 
• One offering the same needle diameter, but without added needle flexibility, namely 
the standard 19 G needle 
• One offering better needle flexibility via a reduced needle diameter, namely the 
standard 22 G needle 
 
Superiority by 16% or more is deemed clinically significant.  Statistical power of 80% is 
chosen using the multiple comparison Hochberg’s method.  Test results are shown below, 
resulting in the requirement for 121 patients for 19 G Flex arm and 61 patients each for 19 G 
and 22G arm. 
 
Hypothesis: 
 
𝐻𝑖: 𝜋𝑖−𝜋0 ≤0 Versus 𝐾𝑖: 𝜋𝑖−𝜋0 > for i=1,2 
 
Design Parameters: 
 
One-sided Type I Error=0.05 
Multiple comparison procedure= Hochberg’s step up 
Total Sample required=243 
Rejection region=Right tail 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 43 of 46 
 
Treatment Parameters: 
 
Arm 
Response rate 
Sample size per 
group 
19GFlex 
0.91 
121 
19G 
0.75 
61 
22G 
0.75 
61 
 
Overall: 
Global (reject any 𝐻𝑖): 0.947 
Conjunctive (reject all 𝐻𝑖): 0.808 
C.3 
Diagnostic Accuracy Measures 
Diagnostic accuracy is defined in terms of “disease state” and the following three disease 
state categories will be used in this study in order to assess diagnostic accuracy of EUS-FNA: 
• “Disease State per EUS-FNA”:  This measure is derived from the results of the cytology 
and chemistry assays of the cyst aspirate.  Cysts will be classified as serous cyst, 
mucinous cyst, IPMN, or pseudocyst based on the table below. 4  If any of the aspirate 
assays are not performed or the results from the two aspirate-based assays do not follow 
the table below, then the Disease State per EUS-FNA will be classified as Indeterminate.  
The Disease State per EUS-FNA will be recorded on the Cytology and Chemistry Results 
CRF. 
 
Disease State per 
EUS-FNA 
Cytology 
Cyst Fluid CEA 
(ng/mL) 
Serous 
Bland PAS +* 
< 0.5 
Mucinous 
Mucinous 
> 200 
IPMN 
Mucinous 
> 200 
Pseudocyst 
Pigmented histiocytes 
< 200 
* This cytological assay might be replaced by another cytological assay as needed 
 
In order to assess the accuracy of EUS-FNA-based standard assays (cytology and CEA) as a 
diagnostic measure of disease state, the Disease State per EUS-FNA measure will be 
compared to a reference diagnosis. The reference diagnostic standard will be diagnosis from 
a surgical specimen histology, the true gold standard for cases that evolve to surgical 
resection within the 30 day follow-up time of the protocol.  For cases that do not progress to 
surgery within 30 days of the EUS-FNA procedure, the reference diagnostic standard will be 
a composite diagnosis by a consensus board.  The consensus board will consist of 3 to 5 
Investigators who will be blinded to the type of needle used. The diagnosis of disease state 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 44 of 46 
will be based solely on baseline medical history and EUS and cross sectional imaging of the 
cyst.  Information regarding aspirate characteristics and results from aspirate tests will not be 
provided to the consensus board.  Diagnoses will be rendered at a separate Investigators 
Meeting or virtual meeting. 
 
• “Disease State per Histology”: This is the reference diagnostic standard. This measure is 
derived from the histology results of the surgical specimen in cases that progress to 
surgery within 30 days.  Cysts will be classified as follows: serous cyst, mucinous cyst, 
IPMN, pseudocyst, or Indeterminate.  As described above, this measure will serve as the 
gold standard for assessing diagnostic accuracy. 
 
• “Disease State per Consensus Board”:  This is the surrogate for the reference diagnostic 
standard. This measure is derived by the consensus board as described above.  Cysts will 
be classified as follows: serous cyst, mucinous cyst, IPMN, pseudocyst, or 
Indeterminate.  The classification will be based on baseline medical history and EUS 
and cross sectional imaging.  Medical history will include, but not be limited to presence 
or absence of prior necrotizing pancreatitis, trauma or other potential cause of 
pseudocyst.  Imaging will pertain to cyst location and cyst appearance.   
 
Degree of correlation between Disease State per EUS-FNA and Disease State per 
Consensus Board or per Histology is illustrated below.   
Total number of patients enrolled is sum of all entries, namely  
TOTAL = A + B + C + ….  + S + T+ U + V + W + X + Y. 
PCL Type 
Serous  
per 
Consensus 
Board 
or Histology 
Mucinous  
per 
Consensus 
Board 
or Histology 
IPMN  
per 
Consensus 
Board 
or Histology 
Pseudocyst 
Per 
Consensus 
Board 
or Histology 
Indeterminate 
per 
Consensus 
Board 
or Histology 
Serous  
per EUS-FNA  
A 
E 
F 
G 
U 
Mucinous  
per EUS-FNA  
K 
B 
H 
I 
V 
IPMN  
per EUS-FNA  
L 
M 
C 
J 
W 
Pseudocyst 
Per EUS-FNA  
N 
O 
P 
D 
X 
Indeterminate 
Per EUS-FNA  
Q 
R 
S 
T 
Y 
 

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 45 of 46 
Degree of correlation between Disease State per EUS-FNA and Disease State per 
Consensus Board or per Histology: 
• [A+B+C+D+Y] / [TOTAL] 
Diagnostic accuracy for Serous Cysts: 
• Sensitivity  
= [A] / [A+K+L+N+Q] 
• Specificity  
= [B+C+D+H+I+J+M+O+P+R+S+T+V+W+X+Y] / 
[B+C+D+E+F+G+H+I+J+M+O+P+R+S+T+U+V+W+X+Y] 
• Positive Predictive Value (PPV)  
= [A] / [A+E+F+G+U] 
• Negative Predictive Value (NPV)  
= [B+C+D+H+I+J+M+O+P+R+S+T+V+W+X+Y] / 
[B+C+D+H+I+J+K+L+M+N+O+P+Q+R+S+T+V+W+X+Y]  
• Overall Accuracy 
= [A+ B+C+D+H+I+J+M+O+P+R+S+T+V+W+X+Y] / [TOTAL] 
Diagnostic accuracy for Mucinous Cysts: 
• Sensitivity  
= [B] / [B+M+O+E+R] 
• Specificity  
= [A+C+D+Y+F+G+J+L+N+P+Q+S+T+U+W+X] / 
[A+C+D+F+G+H+I+J+K+L+N+P+Q+S+T+ U+W+X+Y+V] 
• Positive Predictive Value (PPV)  
= [B] / [B+H+I+K+V] 
• Negative Predictive Value (NPV)  
= [A+C+D+F+G+J+L+N+P+Q+S+T+Y+U+W+X] / 
[A+C+D+E+F+G+J+L+M+N+O+P+Q+R+S+T+U+W+X+Y] 
• Overall Accuracy 
= [A+B+C+D+F+G+J+L+N+P+Q+S+T+U+W+X+Y] / TOTAL  
Diagnostic accuracy for IPMN: 
• Sensitivity  
= [C] / [C+F+H+P+S] 
• Specificity  

E7084 
 
Confidential 
12 AUG 2016                                                  
Boston Scientific 
 
FINAL 
Randomized Evaluation of PCLs Using Three EUS-FNA Needles 
90869947 Rev/Ver. AG 
 
 
Page 46 of 46 
= [A+B+D+E+G+I+K+N+O+Q+R+T+U+V+X+Y] / 
[A+B+D+E+G+I+J+K+L+M+N+O+Q+R+T+U+V+X+Y+W] 
• Positive Predictive Value (PPV)  
= [C] / [C+J+L+M+W] 
• Negative Predictive Value (NPV)  
= [A+B+D+E+G+I+K+N+O+Q+R+T+U+V+X+Y] / 
[A+B+D+E+F+G+H+I+K+N+O+P+Q+R+S+T+U+V+X+Y] 
• Overall Accuracy 
= [A+B+C+D+E+G+I+K+N+O+Q+R+T+U+V+X+Y] / TOTAL 
Diagnostic accuracy for Pseudocysts (in principle excluded from study, but a few cases 
may not have been identified at baseline as such): 
• Sensitivity  
= [D] / [D+G+I+J+T] 
• Specificity  
= [A+B+C+E+F+H+K+L+M+Q+R+S+U+V+W+Y] / 
[A+B+C+E+F+H+K+L+M+N+O+P+Q+R+S+U+V+W+Y+X] 
• Positive Predictive Value (PPV)  
= [D] / [D+N+O+P+X] 
• Negative Predictive Value (NPV)  
= [A+B+C+E+F+H+K+L+M+Q+R+S+U+V+W+Y] / 
[A+B+C+E+F+G+H+I+J+K+L+M+Q+R+S+T+U+V+W+Y+X]   
• Overall Accuracy 
= [A+B+C+D+E+F+H+K+L+M+Q+R+S+U+V+W+Y] / TOTAL