Randomized Multi-Center Study Comparing No Drainage to Preoperative Biliary Drainage Using Metal Stents in Patients With Resectable Pancreatic or Periampullary Cancer
Phase: NA
Conditions: Pancreatic Carcinoma
Sponsor: Boston Scientific Corporation

 
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Randomized Multi-Center Study Comparing No Drainage to Preoperative Biliary 
Drainage Using Metal Stents in Patients  
with Resectable Pancreatic or Periampullary Cancer 
 
Preoperative Biliary Drainage RCT 
 
 
 
CLINICAL PROTOCOL 
 
E7059 
Current Version: October 20, 2014 
NCT01774019 
 
 
 
 
 
 
 
 
 
Sponsored By 
Boston Scientific Corporation 
100 Boston Scientific Way 
Marlborough, MA 01752-1234 
USA 
 
 
 
 
 
 
 
 
 

Confidential 
 
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  Preoperative Biliary Drainage RCT Protocol  
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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. 

 
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Do not copy or distribute without written permission. 
Investigator’s Signature Page 
 
STUDY TITLE: 
Randomized Multi-Center Study Comparing No Drainage to 
Preoperative Biliary Drainage Using Metal Stents in Patients 
with Resectable Pancreatic or Periampullary Cancer 
STUDY CENTER: 
_____________________________________________ 
(Print name of study center) 
 
PROTOCOL VERSION: 
AD 
 
 
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 (if applicable) 
Print name: 
 
 
 
 
 
Date 
 

 
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Protocol Synopsis 
 
Full Title 
Randomized Multi-Center Study Comparing No Drainage to 
Preoperative Biliary Drainage Using Metal Stents in Patients with 
Resectable Pancreatic or Periampullary Cancer 
Short Title 
Preoperative Biliary Drainage RCT 
Objective(s) 
To demonstrate that preoperative biliary drainage using self-expanding 
metal stents (SEMS) does not negatively impact overall surgical 
outcomes in patients undergoing pancreaticoduodenectomy for treatment 
of pancreatic or periampullary cancer. 
Test Device 
Devices: 
WallFlex Biliary RX Fully Covered stent  
Note: WallFlex Biliary RX Uncovered stents may be used in some 
cases as outlined in the protocol 
Cleared Indications:  
The WallFlex Biliary stents are indicated for use in the palliative 
treatment of biliary strictures produced by malignant neoplasms and relief 
of malignant biliary obstruction prior to surgery 
Note: The WallFlex Biliary FC stent is also indicated for the 
treatment of benign biliary strictures per CE Mark or other local 
regulations 
Study Design 
• Prospective, multi-center, randomized, post-market (on label)  
• Patients will be block randomized at baseline in a 1:1 ratio between 
Group 1: No Pre-Operative Biliary Drainage and Group 2: Pre-
Operative Biliary Drainage with a SEMS.   
Planned 
Number of 
Subjects 
294 total number of subjects:  
• Group 1: 147 
• Group 2: 147  
Planned 
Number of 
Centers  
Up to 20 sites world-wide 
Primary 
Endpoint 
Serious pre-operative, operative and post-operative adverse events to 120 
days post randomization or to 30 days post-surgery, whichever comes last 

 
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Secondary 
Endpoints 
1. Adverse events: rate, severity, seriousness, relatedness to stent or 
endoscopic or surgical procedure, impact on time of surgery, 
length of hospitalization and ICU stay  
2. Time to surgery  
3. Curative Intent Surgery details pertaining to intraoperative 
assessment of resectability, surgical resection and reconstruction 
techniques   
4. Intraoperative blood loss and blood transfusions, duration of 
surgery 
5. Biliary obstructive symptoms assessment (Week 2, 
surgery/transition to palliation, 30 day post-operative follow up 
and 120 day follow up) 
6. Improvement of LFT levels as relative to baseline (Week 2, 
surgery/transition to palliation, 30 day post-operative follow up 
and 120 day follow up) 
7. Stent placement success: ability to deploy the stent in satisfactory 
position across the stricture (Group 2) 
8. Stent removal success: successful SEMS removal, either en bloc 
at time of surgery or endoscopically prior to surgery without stent 
removal related SAEs   
9. Number, type, reason and timing of biliary re-interventions 
10. Number and duration of hospital and ICU admissions  
Follow-up 
Schedule and 
Assessments 
• Screening: Count all consecutive patients seen at investigational site 
presenting with biliary obstructive symptoms and suspicion of 
pancreatic cancer, distal common bile duct cholangiocarcinoma or 
peri-ampullary cancer. Of those, a subset will be invited to participate 
in trial: Informed Consent (enrollment) and Eligibility Criteria 
Assessment  
• Baseline Visit (Day 0): Demographics, Medical History, Tumor 
Diagnosis, Staging and Characteristics, Assessment of Biliary 
Obstructive Symptoms, Laboratory Tests, Randomization  
• Stent Placement Procedure Visit (Group 2 only, Day 0):  Stent 
Details, Procedure Details, Adverse Events (AEs) 
• Pre-Operative Visit (Week 2):  Assessment of Biliary Obstructive 
Symptoms, Laboratory Tests, AEs  
Group 1 (No Pre-Operative Biliary Drainage): Patients will undergo 
resection per institutional standard of practice.  Time to surgery is not 
to exceed 4 weeks unless there is a need to delay planned surgery due 
to a complication, biliary obstructive symptoms, decline in patient 

 
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physiologic status, or other factors that preclude surgery.  
Group 2 (Pre-Operative Biliary Drainage with a SEMS):  Patients 
will undergo resection after resolution of jaundice is achieved 
(defined as Bilirubin below 100mol per liter), or at 4 weeks, 
whichever comes first.  
• Biliary Reintervention Visit (as needed):  Timing, Reason for 
Biliary Reintervention, Type of Biliary Reintervention,  AEs 
Group 1 patients who fail their treatment algorithm by requiring 
biliary drainage prior to surgery will receive a study SEMS. 
Group 2 patients who require re-stenting or placement of a stent for a 
new stricture, will receive a study SEMS. 
• Curative Intent Surgery: Assessment of Biliary Obstructive 
Symptoms, Laboratory Tests, Operative Details, Stent Removal, 
Blood Loss,  Intra- and Post-Operative Transfusion, Post-Operative 
Course, Specimen Pathology, AEs 
• Transition to Palliative Management Visit (as needed): 
Assessment of Biliary Obstructive Symptoms, Laboratory Tests, AEs 
• Post-Operative Follow up Visit (30 days Post-Surgery, if 
applicable): Assessment of Biliary Obstructive Symptoms, 
Laboratory Tests, AEs 
• Long Term Follow-up Visit (120 days--150 days post 
randomization):   Assessment of Biliary Obstructive Symptoms, 
Laboratory Tests, AEs   
Patients who undergo surgery as planned will be evaluated at 30 days 
post-surgery and will be followed up to 120 days after randomization. 
Patients with delay in planned surgery may require follow up longer 
than 120 days to allow for a 30 day post-surgery follow up visit but 
follow up is not to exceed 150 days post-randomization.  
Patients with a delay in planned surgery whose rescheduled surgery is 
unable to occur within 120 days will be followed up to 120 days after 
randomization. 
Patients who do not undergo surgery as planned due to conversion to 
palliative management or patient choice will be followed up to 120 
days after randomization.  If patient’s course of treatment requires 
placement of a biliary stent, stenting will be done per standard of care 
at each institution.  If a metal stent is required, a study WallFlex 
Biliary FC stent will be placed.    
Key Inclusion 
1. Age 18 or older 

 
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Criteria 
2. Willing and able to comply with the study procedures and provide 
written informed consent to participate in the study 
3. Diagnosis of probable pancreatic cancer, distal common bile duct 
(CBD) cholangiocarcinoma and other periampullary cancers 
(histology not required) 
4. Biliary obstructive symptoms or signs 
5. Bilirubin level at/above 100 μmol per liter (5.8 mg/dL) 
6. Distal biliary obstruction consistent with pancreatic cancer, distal 
CBD cholangiocarcinoma or other periampullary malignancy 
7. Location of distal biliary obstruction is such that it would allow 
the proximal end of a stent to be positioned at least 2 cm from the 
hilum 
8. Patients deemed as resectable by pancreatic protocol CT or MRI  
9. Surgical candidate per pancreatobiliary surgeon after multi-
disciplinary discussion  
10. Surgery intent within 4 weeks 
11. Endoscopic and surgical treatment to be provided by same team 
Key Exclusion 
Criteria 
1. Biliary strictures caused by confirmed benign tumors  
2. Biliary strictures caused by malignancies other than pancreatic, 
cancer, distal CBD cholangiocarcinoma and other periampullary 
cancers 
3. Surgically altered biliary tract anatomy, not including prior 
cholecystectomy  
4. Neoadjuvant chemotherapy for current malignancy 
5. Palliative indication due to reasons other than surgical candidate 
status 
6. Previous biliary drainage by ERCP/PTC 
7. Patients for whom endoscopic techniques are contraindicated 
8. Participation in another investigational trial within 90 days 
9. Pregnancy  
Primary 
Statistical 
Hypothesis 
A literature search of preoperative biliary drainage with self-expanding 
metal stents in patients with pancreatic or periampullary cancer yielded 
eight articles with 305 patients.1-8 
A meta-analysis of the probability for pre-operative, operative and peri-
operative complications was performed.   A rate of 24.2% [95% CI: 13.2%, 

 
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37.2%] was calculated using the eight articles. 
Statistical testing will be performed to determine if the rate of complications 
for the Pre-Operative Biliary Drainage with SEMS group is non-inferior 
to the No Pre-Operative Biliary Drainage group.  The null hypothesis is 
that the complication rate is inferior in the Pre-Operative Biliary Drainage 
with SEMS versus the No Pre-Operative Biliary Drainage group: 
𝐻𝑜: 𝜋𝑡𝑒𝑠𝑡−𝜋𝑐𝑜𝑛𝑡𝑟𝑜𝑙 ≥∆  (Inferior) 
 
𝐻𝑎: 𝜋𝑡𝑒𝑠𝑡−𝜋𝑐𝑜𝑛𝑡𝑟𝑜𝑙 < ∆  (Non-inferior) 
 
where 𝜋𝑡𝑒𝑠𝑡  and 𝜋𝑐𝑜𝑛𝑡𝑟𝑜𝑙 are the probabilities of having pre-operative, 
operative and peri-operative complications in the Pre-Operative Biliary 
Drainage with SEMS arm and No Pre-Operative Biliary Drainage arm 
respectively, and ∆ is defined as the non-inferiority margin. 
 
The sample size was calculated for a one-sided 0.050 exact Farrington-
Manning test using StatXact 9®. If the P value from the exact Farrington-
Manning test is <0.05 then the Pre-Operative Biliary Drainage with 
SEMS group will be considered non-inferior to the No Pre-Operative 
Biliary Drainage group. The expected probability of complications in the 
Pre-Operative Biliary Drainage with SEMS arm and No Pre-Operative 
Biliary Drainage arm is 37.2%, which was taken from the upper limit of 
the 95% CI from the meta-analysis described above and from the only 
available Level 1 study comparing no drainage to preoperative stenting in 
which the complication rate was reported to be 39% in the no drainage 
arm.9 The non-inferiority margin (∆) is 15%.  Given these assumptions 
and a one-sided 5% significance level, 2 x 132 = 264 subjects will 
provide 80% power to reject the null hypothesis, that the Pre-Operative 
Biliary Drainage with SEMS group is inferior to the No Pre-Operative 
Biliary Drainage group.  
To compensate for possible loss of subjects after enrollment and complete 
assessment of inclusion/exclusion criteria, an additional 10% of subjects 
will be enrolled, for a total of 2 x 147 = 294 subjects. 
 

 
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TABLE OF CONTENTS 
1. 
INTRODUCTION ................................................................................................................. 12 
1.1. Pancreatic and Periampullary cancer .................................................................. 12 
1.2. Treatment of Pancreatic/Periampullary Cancer................................................. 12 
1.3. Biliary Drainage in Patients with Pancreatic/Periampullary Cancer ............... 13 
2. 
PRIMARY OBJECTIVE ........................................................................................................ 13 
3. 
DESIGN .............................................................................................................................. 13 
3.1. Scale, Duration and Investigators ......................................................................... 13 
3.2. Treatment Assignment........................................................................................... 14 
4. 
ENDPOINTS ........................................................................................................................ 16 
4.1. Primary Endpoint .................................................................................................. 16 
4.2. Secondary Endpoints ............................................................................................. 16 
5. 
SUBJECT SELECTION ......................................................................................................... 16 
5.1. Study Population and Eligibility ........................................................................... 16 
5.2. Inclusion Criteria ................................................................................................... 16 
5.3. Exclusion Criteria .................................................................................................. 17 
6. 
STUDY DEVICES ................................................................................................................ 17 
7. 
STUDY VISITS .................................................................................................................... 19 
7.1. Visit Schedule ......................................................................................................... 19 
7.2. Screening ................................................................................................................. 21 
7.3. Baseline Visit (Day 0)—Office Visit...................................................................... 21 
7.4. Stent Placement Procedure Visit (Group 2 subjects only)—Office Visit (may 
occur during Baseline visit) ................................................................................... 21 
7.5. Pre-Operative Visit (Week 2 +/-  3 days)—Telephone or Office Visit .............. 22 
7.6. Biliary Reintervention Visit (Group 1 or 2) —as needed ................................... 22 
7.7. Curative Intent Surgery—Office Visit (within 4 weeks, or delayed surgery by 
120 days post-randomization) ............................................................................... 22 
7.8. Transition to Palliative Management Visit (if applicable)—Telephone or 
Office Visit .............................................................................................................. 23 

 
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7.9. Post-Operative Follow-up Visit (30 days Post-Surgery +/- 7 days, if 
applicable)—Telephone or Office Visit ................................................................ 23 
7.10. Long Term Follow-up Visit (120 days—150 days post randomization +/- 14 
days)—Telephone or Office Visit .......................................................................... 24 
7.11. Study Completion ................................................................................................... 24 
8. 
STATISTICAL CONSIDERATIONS ....................................................................................... 24 
8.1. Hypothesis ............................................................................................................... 24 
8.2. Sample Size ............................................................................................................. 25 
8.3. Analysis Populations .............................................................................................. 25 
8.3.1. 
Enrolled Cohort ......................................................................................... 25 
8.3.2. 
Intent-to-Treat Cohort ................................................................................ 25 
8.3.3. 
Per-Protocol Cohort ................................................................................... 26 
8.4. Data Analyses ......................................................................................................... 26 
8.4.1. 
Baseline Data ............................................................................................. 26 
8.4.2. 
Post-Procedure Endpoints .......................................................................... 26 
8.4.3. 
Subgroup Analyses .................................................................................... 26 
8.4.4. 
Justification of Pooling .............................................................................. 26 
8.4.5. 
Multivariable Analyses .............................................................................. 27 
8.4.6. 
Changes to Planned Analyses .................................................................... 27 
9. 
POTENTIAL RISKS AND BENEFITS .................................................................................... 27 
9.1. Anticipated Adverse Device Effects with Use of WallFlex Biliary Stent .......... 27 
9.2. Anticipated Adverse Events in Patients Without Pre-Operative Biliary 
Drainage .................................................................................................................. 28 
9.3. Anticipated Surgical Adverse Events ................................................................... 28 
9.4. Risk Minimization Actions .................................................................................... 29 
9.5. Anticipated Benefits ............................................................................................... 29 
9.6. Risk to Benefit Rationale ....................................................................................... 29 
10. SAFETY REPORTING .......................................................................................................... 29 
10.1. Definitions and Classification ............................................................................... 29 
10.2. Relationship to Study Device(s) ............................................................................ 31 
10.3. Investigator Reporting Requirements .................................................................. 32 
10.3.1. Serious Adverse Events ............................................................................. 32 
10.3.2. Adverse Events .......................................................................................... 32 
10.3.3. Device Failures, Malfunctions, and Product Nonconformities ................. 32 

 
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10.4. Boston Scientific Device Deficiencies .................................................................... 32 
10.5. Reporting to Regulatory Authorities / IRBs / ECs / Investigators .................... 33 
11. BIBLIOGRAPHY .................................................................................................................. 33 
12. APPENDICES:  SPONSOR REQUIRED PROTOCOL SECTIONS ............................................. 35 
12.1. Data Management .................................................................................................. 35 
12.1.1. Data Collection, Processing, and Review .................................................. 35 
12.1.2. Data Retention ........................................................................................... 36 
12.2. Amendments ........................................................................................................... 36 
12.3. Deviations ................................................................................................................ 36 
12.4. Device/Equipment Accountability ........................................................................ 36 
12.5. Compliance ............................................................................................................. 37 
12.5.1. Statement of Compliance ........................................................................... 37 
12.5.2. Investigator Responsibilities ...................................................................... 37 
12.5.3. Delegation of Responsibility ..................................................................... 39 
12.6. Institutional Review Board/ Ethics Committee ................................................... 39 
12.7. Sponsor Responsibilities ........................................................................................ 39 
12.8. Insurance ................................................................................................................. 40 
12.9. Monitoring .............................................................................................................. 40 
12.10. 
Informed Consent .................................................................................... 40 
12.11. 
Committees ............................................................................................... 41 
12.11.1. Safety Monitoring Process ......................................................................... 41 
12.12. 
Suspension or Termination ..................................................................... 42 
12.12.1. Premature Termination of the Study .......................................................... 42 
12.12.2. Criteria for Premature Termination of the Study ....................................... 42 
12.12.3. Termination of Study Participation by the Investigator or Withdrawal of 
IRB/ EC Approval ..................................................................................... 42 
12.12.4. Requirements for Documentation and Subject Follow-up ........................ 42 
12.12.5. Criteria for Suspending/Terminating a Study Center ................................ 43 
12.13. 
Publication Policy .................................................................................... 43 
12.14. 
Definitions of complication criteria (per van der Gaag article): ......... 44 
 

 
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1. Introduction 
1.1. Pancreatic and Periampullary cancer 
Pancreatic cancer is the fourth leading cause of cancer death in the US and worldwide with 
217,000 new cases/year and 213,000 deaths worldwide.10, 11   Relative 1-year and 5-year 
survival rates are 26% and 6% respectively.11 
Pancreatic tumors are usually asymptomatic until the disease is advanced.  Presenting 
symptoms may include weight loss, jaundice, pain, nausea, dyspepsia and depression.12 
Diagnosis and staging is usually achieved with a pancreas protocol CT, a triphasic cross-
sectional imaging with thin slices using multidetector CT13-16which allows for an assessment 
of the vascular invasion of the tumor, a major factor in determining resectability. In patients 
where CT is not possible or contraindicated, MRI with contrast can be used to diagnose and 
stage pancreatic cancer.17  Pancreas protocol MRI has been emerging as an equivalent 
alternative to CT.18  Endoscopic ultrasound (EUS) can be used complementary to CT to 
provide additional vascular invasion information or to evaluate periampullary masses.19, 20 
Although histologic diagnosis is not necessary before surgical treatment, a biopsy can be 
taken using fine-needle aspiration with either EUS-guidance (preferred) or CT-guidance.18    
Diagnostic staging laparoscopy is also utilized, and is mostly valuable when there is a need to 
rule out sub-radiologic metastases (especially for body and tail lesions).21, 22  
Based on results from imaging studies described above, patients with pancreatic cancer can 
be divided into four prognostic subgroups (Stages I-IV) to allow for choice of proper 
treatment course.  These groups are based on local tumor resectability status and presence or 
absence of distant disease as defined by the tumor-node-metastasis (TNM) staging system of 
the American Joint Commission on Cancer (AJCC).23 Patients in whom the primary tumor 
can be removed are classified as localized resectable (Stages I and II), and patients whose 
tumors are unresectable are classified as locally advanced (Stage III) and metastatic (Stage 
IV).24 
Criteria for resectability vary but usually include the absence of distant metastases and no 
tumor involvement of major arteries; in cases of venous invasion of the tumor, there must be 
a suitable segment of portal vein (above) and superior mesenteric vein (below) the site of 
venous involvement to allow for venous reconstruction.25  
1.2. Treatment of Pancreatic/Periampullary Cancer 
The only potential curative treatment option for patients with resectable 
pancreatic/periampullary cancers is curative-intent-surgery (CIS) by 
pancreaticoduodenectomy (Whipple procedure)26 with a long-term survival rate of 20% and a 
median survival of 12-20 months.24 Only 15-20% of patients presenting with pancreatic 
cancer have potentially resectable tumors.27   
Most pancreatic cancers arise in the head of the pancreas and often cause bile duct 
obstruction resulting in jaundice, while body and tail lesions are insidious in their 
development and usually far advanced when detected.  Therefore most patients who are 

 
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candidates for CIS have tumors in the head of the pancreas.28 The most common type of 
pancreatic cancer is adenocarcinoma, originating from the pancreatic duct cells24 and 
accounting for over 90% of pancreatic malignancies.12 
1.3. Biliary Drainage in Patients with Pancreatic/Periampullary Cancer 
Biliary obstruction associated with pancreatic/periampullary cancer occurs in up to 70% of 
patients.29  Hyperbilirubinemia resulting from biliary obstruction adversely affects liver, 
cardiovascular and renal function,26 and the subsequent cholestasis which is thought to impair 
immune response and clotting1 may negatively impact the outcome of CIS.  Preoperative 
biliary drainage potentially reverses these factors and could result in improved outcome of 
pancreaticoduodenectomy.26 
Preoperative biliary decompression has traditionally been achieved with plastic stents, 
however, these stents have been associated with high complication rates and relatively low 
success rates in preoperative management of biliary obstruction.1-3, 9, 30    
In recent publications, SEMS have been shown to be superior to plastic stents for 
preoperative biliary drainage in pancreatic cancer1 because of longer patency achieved by a 
greater stent diameter,31 fewer ERCP procedures, and fewer episodes of 
cholangitis/cholestasis due to stent occlusion while awaiting surgery (15% using SEMS vs 
93% using plastic stents).2   
2. Primary Objective 
The primary objective is to demonstrate that preoperative biliary drainage using SEMS does 
not negatively impact overall surgical outcomes in patients undergoing 
pancreaticoduodenectomy for treatment of pancreatic or periampullary cancer. 
3. Design  
3.1. Scale, Duration and Investigators 
This is a post-market (on label), prospective, multi-center, randomized, non-blinded study.   
Patients will be followed for 120 days after randomization.  Only patients who experience a 
delay in their planned surgery due to factors such as but not limited to complications, biliary 
obstructive symptoms, patient physiologic status, etc. may be followed up to 150 days to 
allow for a 30 days post-surgery follow up visit. 
There will be up to 20 participating centers world-wide with anticipated enrollment of 294 
patients, 147 per group.    
At each investigational center, there will be one principal investigator (PI) and at least one 
Co-PI.  At a minimum, there will be one gastroenterologic endoscopist and one 
pancreaticobiliary surgeon among the investigators.  Although more than two investigators 
per center are allowed, it is encouraged that the number be kept small. 
 
 

 
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3.2. Treatment Assignment 
Patients will be randomized at baseline in equal proportions of 1:1 ratio between Group 1 and 
Group 2 as follows: 
• Group 1: No pre-operative biliary drainage (patients will not receive a stent)  
• Group 2: Pre-operative biliary drainage with a SEMS 
Block randomization through an online database system will be used.  Randomization will be 
stratified by study center.  
Figure 1 below provides an overview of various patient management scenarios in the form of 
a study flow chart. 
 
 

 
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4. Endpoints 
4.1. Primary Endpoint 
Serious pre-operative, operative and post-operative adverse events to 120 days post 
randomization or to 30 days post-surgery, whichever comes last 
4.2. Secondary Endpoints 
1. Adverse events: rate, severity, seriousness, relatedness to stent or endoscopic or 
surgical procedure, impact on time of surgery, length of hospitalization and ICU stay  
2. Time to surgery  
3. Curative Intent Surgery details pertaining to intraoperative assessment of 
resectability, surgical resection and reconstruction techniques   
4. Intraoperative blood loss and blood transfusions, duration of surgery 
5. Biliary obstructive symptoms assessment (Week 2, surgery/transition to palliation, 30 
day post-operative follow up and 120 day follow up) 
6. Improvement of LFT levels as relative to baseline (Week 2, surgery/transition to 
palliation, 30 day post-operative follow up and 120 day follow up) 
7. Stent placement success: ability to deploy the stent in satisfactory position across the 
stricture (Group 2) 
8. Stent removal success: successful SEMS removal, either en bloc at time of surgery or 
endoscopically prior to surgery without stent removal related SAEs   
9. Number, type, reason and timing of biliary re-interventions 
10. Number and duration of hospital and ICU admissions 
5. Subject Selection  
5.1. Study Population and Eligibility  
All consecutive patients seen at an investigational site presenting with biliary obstructive 
symptoms with suspicion of pancreatic cancer, periampullary cancer or distal CBD 
cholangiocarcinoma will be counted. Of those, a subset will be invited to participate in trial 
and is considered enrolled after signing the study specific Informed Consent Form (ICF). A 
screening log will be maintained to document the assessment of eligibility criteria provided 
in Section 5.2 and Section 5.3. 
5.2. Inclusion Criteria 
Subjects who meet all of the criteria listed below may be given consideration for inclusion in 
this clinical investigation, provided no exclusion criterion (see Section 5.3) is met. 

 
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1. Age 18 or older 
2. Willing and able to comply with the study procedures and provide written informed 
consent to participate in the study 
3. Diagnosis of probable pancreatic cancer, distal common bile duct (CBD) 
cholangiocarcinoma and other periampullary cancers (histology not required) 
4. Biliary obstructive symptoms or signs 
5. Bilirubin level at/above 100mol per liter (5.8 mg/dL) 
6. Distal biliary obstruction consistent with pancreatic cancer, distal CBD 
cholangiocarcinoma or other periampullary malignancy 
7. Location of distal biliary obstruction is such that it would allow the proximal end of a 
stent to be positioned at least 2cm from the hilum 
8. Patients deemed as resectable by pancreatic protocol CT or MRI  
9. Surgical candidate per pancreatobiliary surgeon after multi-disciplinary discussion  
10. Surgery intent within 4 weeks 
11. Endoscopic and surgical treatment to be provided by same team 
 
5.3. Exclusion Criteria  
Subjects who meet any one of the following criteria will be excluded from this clinical study. 
1. Biliary strictures caused by confirmed benign tumors  
2. Biliary strictures caused by malignancies other than pancreatic cancer, distal CBD 
cholangiocarcinoma and other periampullary cancers 
3. Surgically altered biliary tract anatomy, not including prior cholecystectomy  
4. Neoadjuvant chemotherapy for current malignancy 
5. Palliative indication due to reasons other than surgical candidate status 
6. Previous biliary drainage by ERCP/PTC 
7. Patients for whom endoscopic techniques are contraindicated 
8. Participation in another investigational trial within 90 days 
9. Pregnancy 
6. Study Devices 
The WallFlex Biliary RX Fully Covered stent will be the default choice for treatment of 
patients in Group 2.  A WallFlex Biliary RX Uncovered stent may be used at the joint 

 
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discretion of the endoscopic and surgical investigators for documented reasons related to the 
ductal anatomy, namely stricture involving the cystic duct confluence, low cystic duct 
confluence, or other anatomic considerations to be specified.    
The WallFlex Biliary RX Fully Covered and the WallFlex Biliary RX Uncovered Stent 
Systems are indicated for use in the palliative treatment of biliary strictures produced by 
malignant neoplasms and relief of malignant biliary obstruction prior to surgery; the 
WallFlex Biliary RX Fully Covered Stent System is also indicated for treatment of benign 
biliary strictures, per CE Mark or other local regulations. For a detailed description of the 
WallFlex Biliary Stent Systems, please reference the Directions for Use (DFU) included in 
each device package.  
Investigators should use the WallFlex Biliary RX Fully Covered and Uncovered Stent 
Systems in accordance with the DFUs. 
Study devices are labeled on the box and inner pouch and contain information including but 
not limited to:  device name and dimensions, lot number, expiration date, name of legal 
manufacturer, and investigational use statement. Device labeling will be provided in local 
language(s) as per national regulations. 
Study devices will be available in the following dimensions: 
 
WallFlex Biliary 
RX Stent 
Diameter 
Length 
Delivery 
System 
Diameter 
Guidewire 
Diameter 
Uncovered 
8 mm 
10 mm 
40, 60, 80 
40, 60, 80 
8 Fr 
.035” 
Fully Covered 
8 mm 
10 mm 
60, 80mm 
40, 60, 80mm 
8.5 Fr 
.035” 
 
Stent placement should be such that the proximal end of the stent is minimum 2 cm from the 
hilum.  Performing a biliary or pancreatic sphincterotomy or enlarging a prior 
sphincterotomy will be done at the discretion of the endoscopist. 
In case of a failed stent placement due to a device event, a new attempt to place a stent will 
be made.  If a stent placement is not possible due to non-device related reasons (such as 
inability to cannulate the CBD or reach the papilla, extensive tumor growth at site of papilla, 
etc.), interventional radiologic (IR) access is allowed and, where possible, should be 
associated with placement of a study stent over a transhepatically inserted guide-wire in a 
"rendez-vous" procedure.  Percutaneous transhepatic cholangiograpy (PTC) and a subsequent 
internal drainage with a stent placement may be done at the same time (one-stage procedure), 
or PTC with external drainage may be performed 2 -3 days before stent insertion (two-stage 
procedure) per standard of practice.  If access to the biliary tree or endoscopic placement of 
the study stent through a “rendez-vous” procedure fails and patient requires percutaneous 
transhepatic biliary drainage (PTBD), then the patient will exit the study. 

 
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7. Study Visits 
7.1. Visit Schedule 
The schedule of observations and assessments to take place during the study is outlined in 
Table 1 below.

                                                     
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Table 1.  Study Event Schedule 
 
Study Visit 
Screening 
Baseline/ Stent 
Placement 
Procedure 
Pre-Operative 
Visit 
Week 2† 
Biliary 
Reintervention 
(if applicable) 
Curative 
Intent Surgery 
Transition to 
Palliative 
Treatment Visit 
(if applicable) 
30 Days Post-Op 
Follow up Visit 
(if applicable) 
Long Term 
Follow up Visit 
120 Days* 
 
Window 
N/A 
N/A 
±3 d 
N/A 
N/A 
N/A 
±7 d 
±14 d 
ICF 
X 
 
 
 
 
 
 
 
Eligibility Criteria 
Assessment 
X 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
Medical History 
 
X 
 
 
 
 
 
 
Assessment of Biliary 
Obstructive Symptoms 
 
X 
X 
 
X 
X 
X 
X 
Laboratory Tests 
 
X 
X 
 
X 
X 
X 
X 
Tumor Diagnosis, Staging 
& Characteristics 
 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
Stent Details 
 
X  
 
X  
(if applicable) 
 
 
 
 
Procedure Details 
 
X  
 
X  
(if applicable) 
 
 
 
 
Operative Details 
 
 
 
 
X 
 
 
 
Specimen Pathology 
 
 
 
 
X 
 
 
 
Stent Removal 
 
 
 
X  
(if applicable) 
X  
(if applicable) 
 
 
 
Adverse Events 
X  (as applicable) 
Protocol Deviations 
X  (as applicable) 
* Visit may occur up to 150 days post-randomization;  † Visit may be conducted in the office or via telephone with liver function tests drawn and sent from local clinic/hospital.

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7.2. Screening  
• Informed Consent 
• Eligibility Criteria Assessment  
No study-specific testing will be conducted until the subject has signed the study specific 
informed consent form (ICF).  
Informed consent must be obtained for all subjects who are potential study candidates. 
Subjects will be asked to sign the ICF before any study-specific tests or procedures are 
performed. The ICF is study-specific and must be approved by the Institutional Review 
Board (IRB)/Ethics Committee (EC) at each center. Study personnel should explain that even 
if a subject agrees to participate in the study and signs the study specific ICF, the screening 
process may demonstrate that the subject is not a suitable candidate for the study.  
7.3. Baseline Visit (Day 0)—Office Visit 
• Demographics 
• Medical History  
• Tumor Diagnosis, Staging and Characteristics 
o Diagnostic modality 
o Tumor stage 
o Location and size of mass 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Tests   
o Serum albumin level 
o Alkaline phosphatase  
o Total Bilirubin  
o Gamma GT  
o SGOT (AST—optional) and SGPT (ALT)  
o Normal Ranges 
• Randomization into Group 1 or Group 2  
7.4. Stent Placement Procedure Visit (Group 2 subjects only)—Office Visit (may 
occur during Baseline visit) 
• Stent Details (including stent choice) 

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• Procedure Details (including sphincterotomy information) 
• Adverse Events (AEs) 
7.5. Pre-Operative Visit (Week 2 +/-  3 days)—Telephone or Office Visit 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Tests   
o Serum albumin level 
o Alkaline phosphatase  
o Total Bilirubin  
o Gamma GT  
o SGOT (AST—optional) and SGPT (ALT)  
• AEs 
7.6. Biliary Reintervention Visit (Group 1 or 2) —as needed 
• Timing 
• Reason for Biliary Reintervention 
• Type of Biliary Reintervention (including SEMS placement or removal) 
• Adverse Events (AEs) 
7.7. Curative Intent Surgery—Office Visit (within 4 weeks, or delayed surgery by 
120 days post-randomization) 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Tests   
o Serum albumin level 
o Alkaline phosphatase  
o Total Bilirubin  
o Gamma GT  

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o SGOT (AST—optional) and SGPT (ALT)  
• Operative details:  
o Exploration 
o Resection (including SEMS removal) 
o Reconstruction 
• Blood Loss 
• Intra and Post-Operative Transfusion 
• Post-Operative Course 
• Specimen Pathology (including margin status) per World Health Organization 
(WHO) classification system 
• AEs 
7.8. Transition to Palliative Management Visit (if applicable)—Telephone or Office 
Visit 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Tests   
o Serum albumin level 
o Alkaline phosphatase  
o Total Bilirubin  
o Gamma GT  
o SGOT (AST—optional) and SGPT (ALT)  
• AEs 
7.9. Post-Operative Follow-up Visit (30 days Post-Surgery +/- 7 days, if 
applicable)—Telephone or Office Visit 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Tests   
o Serum albumin level 

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o Alkaline phosphatase  
o Total Bilirubin  
o Gamma GT  
o SGOT (AST—optional) and SGPT (ALT)  
• AEs 
7.10. Long Term Follow-up Visit (120 days—150 days post randomization +/- 14 
days)—Telephone or Office Visit 
• Assessment of Biliary Obstructive Symptoms 
o Right Upper Quadrant Pain 
o Fever/Chills 
o Jaundice 
o Itching 
o Dark urine 
o Pale stools 
o Nausea/Vomiting 
• Laboratory Tests   
o Serum albumin level 
o Alkaline phosphatase  
o Total Bilirubin  
o Gamma GT  
o SGOT (AST—optional) and SGPT (ALT)  
• AEs 
7.11. Study Completion 
Each subject will be followed for 120 days from the time of randomization. In cases where 
patients experience a delay of planned surgery, the long term follow up can be extended up to 
150 days post randomization to allow for completion of a Follow-up Visit at 30 days after 
surgery. 
A subject will be considered lost to follow-up if the subject remains unresponsive to 
communication after three documented attempts by study staff. 
8. Statistical Considerations 
8.1. Hypothesis 
Statistical testing will be performed to determine if the rate of complications for the Pre-
Operative Biliary Drainage with SEMS group is non-inferior to the No Pre-Operative Biliary 
Drainage group. The null hypothesis is that the complication rate is inferior in the Pre-
Operative Biliary Drainage with SEMS versus the No Pre-Operative Biliary Drainage group: 
 
Ho: πtest −πcontrol  ≥∆  (Inferior) 

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Ha: πtest −πcontrol  < ∆  (Non-inferior) 
 
where πtest  and πcontrol are the probabilities of having pre-operative, operative and peri-
operative complications in the Pre-Operative Biliary Drainage with SEMS arm and No Pre-
Operative Biliary Drainage arm respectively, and ∆ is defined as the non-inferiority margin. 
8.2. Sample Size  
A literature search of preoperative biliary drainage with self-expanding metal stents in 
patients with pancreatic or periampullary cancer yielded 8 articles with 305 patients.21-24, 27-31 
The following meta-analysis of the probability for pre-operative, operative and post-
operative complications was done:  
• A rate of 24.2% [95% CI: 13.2%, 37.2%] was calculated using the 8 articles. 
 
The sample size was calculated for a one-sided 0.050 exact Farrington-Manning test using 
StatXact 9®. If the P value from the exact Farrington-Manning test is <0.05 then the Pre-
Operative Biliary Drainage with SEMS group will be considered non-inferior to the No Pre-
Operative Biliary Drainage group. The expected probability of complications in the Pre-
Operative Biliary Drainage with SEMS arm and No Pre-Operative Biliary Drainage arm is 
37.2%, which was taken from the upper limit of the 95% CI from the meta-analysis described 
above and from the only available Level 1 study comparing no drainage to preoperative 
stenting in which the complication rate was reported to be 39% in the no drainage arm.9 The 
non-inferiority margin (∆) is 15%.  Given these assumptions and a one-sided 5% significance 
level, 2 x 132 = 264 subjects will provide 80% power to reject the null hypothesis, that the 
Pre-Operative Biliary Drainage with SEMS group is inferior to the No Pre-Operative Biliary 
Drainage group.  
To compensate for possible loss of subjects after enrollment and complete assessment of 
inclusion/exclusion criteria, an additional 10% of subjects will be enrolled, for a total of 2 x 
147 = 294 subjects. 
8.3. Analysis Populations 
8.3.1. Enrolled Cohort 
A subject is considered “enrolled” after signing the study-specific ICF.  Subjects who sign 
the ICF but subsequently do not meet one or more of the eligibility criteria provided in 
Section 5.2 and Section 5.3 will be considered screen failures and excluded from the study. 
8.3.2. Intent-to-Treat Cohort 
This cohort consists of those “enrolled” subjects who meet all inclusion/exclusion criteria 
and are subsequently randomized.  

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8.3.3. Per-Protocol Cohort 
The per-protocol cohort is a subset of the ITT subjects who are treated per protocol after 
randomization (Group 1 no stent, and Group 2 received a study stent) and no major protocol 
deviations (ICH E9 definitions). 
8.4. Data 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).  
The distribution of prognostic factors between patients with and without data will be 
examined. Statistical models that account for censored data will be employed in appropriate 
circumstances, e.g. for time-to-event outcomes. Sensitivity analyses will be conducted to 
assess the impact of missing data on the interpretation of the results, e.g. a tipping point 
analysis.  
 
8.4.1. Baseline Data 
Baseline data will be summarized.  Subject demographics, clinical history, risk factors, LFTs, 
tumor diagnosis, and obstruction symptoms will be summarized using descriptive statistics 
(e.g., mean, standard deviation, n, minimum, maximum) for continuous variables and 
frequency statistics for discrete variables.  
  
8.4.2. Post-Procedure Endpoints 
Post-procedure information will be collected at regularly scheduled follow-up examinations 
as detailed in the clinical study event schedule and will be summarized using descriptive 
statistics for continuous variables (e.g., mean, standard deviation, n, minimum, maximum) 
and frequency tables or proportions for discrete variables.  
8.4.3. Subgroup Analyses 
The subgroup analyses will include tabulating the primary endpoint and select secondary 
endpoints by gender.  
8.4.4. Justification of Pooling 
The analyses will be presented using pooled data across institutions. An analysis of the 
poolability will be made using logistic regression for binary outcomes, analysis of covariance 
for continuous outcomes, or proportional hazards regression for time-to-event outcomes, to 
assess differences between study institutions and to justify pooling data across institutions. 

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8.4.5. Multivariable Analyses 
Univariate and multivariate analyses will be performed to assess possible predictors of the 
primary endpoint. Possible predictors may include any but not limited to 
demographic/baseline data and medical history data. Factors from the univariate model with 
p≤0.20 will also be modeled multivariately using a stepwise procedure in a generalized linear 
model or Cox Proportional Hazards model. The significance thresholds for entry and exit into 
the model will be set to p<0.10. 
8.4.6. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in a Statistical Analysis Plan approved prior to performing the analyses.  
9. Potential Risks and Benefits 
9.1. Anticipated Adverse Device Effects with Use of WallFlex Biliary Stent 
As per the commercial DFU included with the study devices, the potential complications 
associated with the use of the WallFlex Biliary FC and UC Stent may include, but are not 
limited to:   
• Pain 
• Bleeding 
• Fever 
• Nausea 
• Vomiting 
• Infection 
• Inflammation 
• Recurrent obstructive jaundice 
• Stent occlusion 
• Tumor overgrowth around ends of stent 
• Tumor ingrowth through the stent 
• Mucosal hyperplasia 
• Cholangitis 
• Cholecystitis* 
• Pancreatitis 
• Bile duct or duodenum ulceration 
• Perforation of duodenum or bile duct 
• Stent migration 
• Death (other than that due to normal disease progression) 
• Stent misplacement 
• Perforation of the gallbladder due to the stent covering the cystic duct* 
• Stent fracture 

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• Hepatic abscess 
 
*Note: In a small clinical trial of this device, two out of four (50%) subjects who had 
a stent placed across the cystic duct developed cholecystitis. One of these subjects 
suffered a perforated gallbladder due to the stent covering the cystic duct, requiring a 
drain to be placed. 
 
As per the commercial DFU included with the study devices, potential complications 
associated with stent removal during an ERCP procedure include, but are not limited to:  
• Pain 
• Bleeding 
• Fever 
• Nausea 
• Vomiting 
• Infection 
• Inflammation 
• Recurrent obstructive jaundice 
• Mucosal hyperplasia 
• Cholangitis 
• Cholecystitis 
• Pancreatitis 
• Ulceration of duodenum or bile duct 
• Perforation of duodenum or bile duct 
• Death (other than that due to normal disease progression) 
• Impaction to the common bile duct wall 
9.2. Anticipated Adverse Events in Patients Without Pre-Operative Biliary Drainage 
• Severe jaundice 
• Cholangitis 
9.3. Anticipated Surgical Adverse Events  
• Pancreaticojejunostomy leakage  
• Delayed gastric emptying   
• Biliary leakage  
• Gastro/-duodenojejunostomy leakage  
• Intra-abdominal abscess formation  
• Wound infection  
• Portal Vein Thrombosis  
• Cholangitis   
• Hemorrhage  
• (Emergency) (re)laparotomy   

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• Pneumonia 
• Myocardial infarction  
• Mortality  
9.4. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol.  The latter may facilitate inter-center communications regarding 
serious AEs. 
9.5. Anticipated Benefits 
Subjects may not receive any benefit from participating in this study but this study may 
provide a future benefit to medical science and other patients.  To date there is no broadly 
accepted standard of practice pertaining to pre-operative drainage of patients as defined by 
the inclusion and exclusion criteria of the study. 
9.6. Risk to Benefit Rationale 
Based on prior BSC’s clinical studies and collected reports in literature to-date, the risk-to-
benefit ratio is within reason for forseeable risks. However, literature reports do not always 
capture all side effects. Observation and follow up of subjects is required as outlined in the 
protocol. 
10. Safety Reporting 
10.1.  Definitions and Classification 
Adverse event definitions are provided in Table 10.1-1.  
Table 10.1-1: 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 

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Table 10.1-1: Adverse Event Definitions 
Term 
Definition 
related to the investigational device  
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.  
Note: For SAE reporting requirements see the information 
below for SADE.  
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. 
Device Deficiency 
A device deficiency is any inadequacy of a medical device with 

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Table 10.1-1: Adverse Event Definitions 
Term 
Definition 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 
12/2010 
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 (see Table 10.1-1 for AE 
definitions).  
Any AE experienced by the study subject after informed consent, whether during or 
subsequent to the procedure, must be recorded in the eCRF. 
Refer to Section 9 for the known risks associated with the study device(s). 
Adverse events that occur during the course of the study will be evaluated against a list of 
pre-specified complication criteria as defined in Section 12.14.  Determination of whether an 
AE meets the definition of a pre-specified complication will be made by study physicians. 
10.2. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device as related or 
unrelated. See criteria in Table 10.2-2:  
Table 10.2-2: Criteria for Assessing Relationship of Study Device to Adverse Event 
Classification 
Description 
Unrelated 
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. 
Related 
• 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. 
• There is a strong relationship to investigational product, or recurs on 
re-challenge, and another etiology is unlikely. 

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Table 10.2-2: Criteria for Assessing Relationship of Study Device to Adverse Event 
Classification 
Description 
• There is no other reasonable medical explanation for the event. 
10.3.  Investigator Reporting Requirements 
Investigators will be required to report all SAEs and ADEs. 
10.3.1.  Serious Adverse Events  
These events should be reported to the Global Safety Office and/or Project Manager within 2 
business days of first becoming aware of the event. Events should be documented in the 
eCRF and all relevant source documentation for the event should be provided to the Global 
Safety Office, as applicable. 
10.3.2.  Adverse Events  
Device-related events should be reported to the Global Safety Office and/or Project Manager 
within 10 business days of first becoming aware of the event. Unrelated AEs will not be 
collected. 
10.3.3.  Device Failures, Malfunctions, and Product Nonconformities 
These events should be reported to Project Manager and/or Global Safety Office within 1 
business day of first becoming aware of the event. Events should be documented in the 
eCRF. 
10.4.  Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and labeling errors) will be documented and reported to BSC. If 
possible, the device(s) should be returned to BSC for analysis. Instructions for returning the 
investigational device(s) will be provided. If it is not possible to return the device, the 
investigator should document why the device was not returned and the final disposition of the 
device.  
Device 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. 

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10.5.  Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating investigators 
and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB/EC and regulatory authorities 
of SAEs as required by local procedure.   
11. Bibliography 
1. Decker C, Christein JD, Phadnis MA, Wilcox CM, Varadarajulu S. Biliary metal 
stents are superior to plastic stents for preoperative biliary decompression in 
pancreatic cancer. Surg Endosc. 2011 Jul;25(7):2364-7. Epub 2011 Mar 4. 
2. Wasan SM, Ross WA, Staerkel GA, Lee GH.  Use of Expandable Metallic Biliary 
Stents in Resectable Pancreatic Cancer. Am J Gastroenterol. 2005;100:2056–2061. 
3. Mullen JT, Lee JH, Gomez HF, Ross WA, et al.  Pancreaticoduodenectomy After 
Placement of Endobiliary Metal Stents.  J Gastrointest Surg 2005;9:1094–1105. 
4. Sanders MK, El Hajj II, Slivka A, et al  Placement of Self-Expanding Metal Biliary 
Stents (SEMS) in Patients with Resectable Pancreatic Cancer [Abstract].  Gastrointest 
Endosc 2009; 69(5)  
5. Kahaleh M, Brock A, Conaway MR, et al. Covered self−expandable metal stents in 
pancreatic malignancy regardless of resectability: a new concept validated by a 
decision analysis.  Endoscopy 2007 Apr;39(4):319-24 
6. Pop GH, Richter JA, Sauer B, et al. Bridge to surgery using partially covered self-
expandable metal stents (PCMS) in malignant biliary stricture: an acceptable 
paradigm?  Surg Endosc 2011 Feb;25(2):613-8 
7. Lawrence C , Howell DA, Conklin DE, et al. Delayed pancreaticoduodenectomy for 
cancer patients with prior ERCP-placed, nonforeshortening, self-expanding metal 
stents: a positive outcome, Gastrointest Endosc 2006 May;63 (6): 804-807 
8. Singal AK, Ross WA, Guturu P, et al.  Self-Expanding Metal Stents for Biliary 
Drainage in Patients with Resectable Pancreatic Cancer: Single-Center Experience 
with 79 Cases.  Dig Dis Sci 2011 Jul 13. [Epub ahead of print] 
9. van der Gaag NA, Rauws EAJ, van Eijck CHJ, et al. Preoperative Biliary Drainage 
for Cancer of the Head of the Pancreas.  N Engl J Med 2010;362:129-37. 
10. Hariharan D, Saied A, Kocher HM.  Analysis of mortality rates for pancreatic cancer 
across the world. HPB (Oxford). 2008; 10(1): 58–62.  
11. American Cancer Society. Cancer Facts and Figures 2012. Atlanta: American Cancer 
Society; 2012. 
12. NCCN Clinical Guidelines in Oncology Pancreatic Adenocarcinoma Version 2.2011, 
NCCN.org 

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13. Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan 
DC. Pretreatment assessment of resectable and borderline resectable pancreatic 
cancer: expert consensus statement. Ann Surg Oncol. 2009 Jul;16(7):1727-33. Epub 
2009 Apr 24. 
14. Wong JC, Lu DS. Staging of pancreatic adenocarcinoma by imaging studies. Clin 
Gastroenterol Hepatol. 2008 Dec;6(12):1301-8. Epub 2008 Sep 27. Review. 
15. House MG, Yeo CJ, Cameron JL, Campbell KA, Schulick RD, Leach SD, Hruban 
RH, Horton KM, Fishman EK, Lillemoe KD. Predicting resectability of 
periampullary cancer with three-dimensional computed tomography. J Gastrointest 
Surg. 2004 Mar-Apr;8(3):280-8. 
16. Olivié D, Lepanto L, Billiard JS, Audet P, Lavallée JM. Predicting resectability of 
pancreatic head cancer with multi-detector CT. Surgical and pathologic correlation. 
JOP. 2007 Nov 9;8(6):753-8. 
17. Schima W, Ba-Ssalamah A, Goetzinger P, Scharitzer M, Koelblinger C. State-of-the-
art magnetic resonance imaging of pancreatic cancer. Top Magn Reson Imaging. 
2007 Dec;18(6):421-9. Review. 
18. NCCN Clinical Guidelines in Oncology Pancreatic Adenocarcinoma Version 2.2012, 
NCCN.org 
19. Rösch T, Braig C, Gain T, Feuerbach S, Siewert JR, Schusdziarra V, Classen M. 
Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. 
Comparison with conventional sonography, computed tomography, and angiography. 
Gastroenterology. 1992 Jan;102(1):188-99. 
20. Varadarajulu S, Wallace MB. Applications of endoscopic ultrasonography in 
pancreatic cancer. Cancer Control. 2004 Jan-Feb;11(1):15-22. Review. 
21. Ahmed SI, Bochkarev V, Oleynikov D, Sasson AR. Patients with pancreatic 
adenocarcinoma benefit from staging laparoscopy. J Laparoendosc Adv Surg Tech A. 
2006 Oct;16(5):458-63. 
22. Warshaw AL, Gu ZY, Wittenberg J, Waltman AC. Preoperative staging and 
assessment of resectability of pancreatic cancer. Arch Surg. 1990 Feb;125(2):230-3. 
23. Katz MH, Hwang R, Fleming JB, Evans DB. Tumor-node-metastasis staging of 
pancreatic adenocarcinoma. CA Cancer J Clin. 2008 Mar-Apr;58(2):111-25. Epub 
2008 Feb 13. Review. 
24. Edge SB, Byrd DR, Compton CC, et al., eds. Exocrine and endocrine pancreas.  
AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 241-9.  
25. Tseng JF, Tamm EP, Lee JE, et al. Venous resection in pancreatic cancer surgery. 
Best Pract Res Clin Gastroenterol. 2006;20(2):349–364. 
26. Bonin EA, Baron TH. Preoperative biliary stents in pancreatic cancer. J Hepatobiliary 
Pancreat Sci. 2011 Sep;18(5):621-9. Review. 

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27. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. The Lancet 2004; 363 
(9414):1049-1057.  
28. Gumbs AA, Rodriguez Rivera AM, Milone L, Hoffman JP. Laparoscopic 
pancreatoduodenectomy: a review of 285 published cases. Ann Surg Oncol. 2011 
May;18(5):1335-41. Epub 2011 Jan 5. Review. 
29. Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617. 
30. Boulay BR, Gardner TB, Gordon SR.  Occlusion rate and complications of plastic 
biliary stent placement in patients undergoing neoadjuvant chemoradiotherapy for 
pancreatic cancer with malignant biliary obstruction.  J Clin Gastroenterol 2010 
Jul;44(6):452-5. 
31. Moss AC, Morris E, Leyden J, MacMathuna P. Malignant distal biliary obstruction: a 
systematic review and meta-analysis of endoscopic and surgical bypass results. 
Cancer Treat Rev. 2007 Apr;33(2):213-21. Epub 2006 Dec 8. Review.  
12. Appendices:  Sponsor Required Protocol Sections 
12.1. Data Management 
12.1.1.  Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server. All changes made to the clinical data 
will be captured in an electronic audit trail and available for review by Boston Scientific 
Corporation (BSC) or its representative. The associated software and database have been 
designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the EDC system and will 
be issued to the site for appropriate response. Site staff will be responsible for resolving all 
queries in the database. 

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12.1.2.  Data 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 
the last approval of a marketing application or until at least 2 years have elapsed since the 
formal discontinuation of the clinical investigation of the product. These documents will be 
retained for a longer period of time by agreement with BSC or in compliance with other local 
regulations. It is BSC’s responsibility to inform the Investigator when these documents no 
longer need to be maintained. The Investigator will take measures to ensure that these 
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 BSC must receive 
written notification of this custodial change.  
12.2.  Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/FDA/CA) of the revised protocol must be obtained prior to implementation. 
12.3.  Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC of any deviation from the investigational plan to protect 
the life or physical well-being of a subject in an emergency, and those deviations which 
affect the scientific integrity of the clinical investigation. Such notice shall be given as soon 
as possible, but no later than 5 working days after the emergency occurred, or per prevailing 
local requirements, if sooner than 5 working days.  
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor using the Protocol Deviation 
EDC CRF. Sites may also be required to report deviations to the IRB/EC, 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. 
12.4.  Device/Equipment Accountability 
There are no investigational devices used in this study. The WallFlex Biliary Fully Covered 
and Uncovered Stent Systems are available for commercial use in the geographic areas in 
which this clinical study is taking place; therefore, there is no requirement for device 

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accountability for the purposes of this study. Device lot information must be maintained in 
the subject’s medical record and recorded on the appropriate case report form.  
Any individual country/region requirements that depart from the aforementioned will be 
implemented on a case-by-case basis. 
12.5.  Compliance 
12.5.1.  Statement of 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. The study will not begin until the required approval/favorable 
opinion from the EC and/or regulatory authority has been obtained, if appropriate. Any 
additional requirements imposed by the EC or regulatory authority shall be followed,                     
if appropriate. 
12.5.2.  Investigator Responsibilities 
The Principal Investigator of an investigational center is responsible for ensuring that the 
study is conducted in accordance with the Clinical Study Agreement, the investigational 
plan/protocol, ISO 14155, ethical principles that have their origins in the Declaration of 
Helsinki, any conditions of approval imposed by the reviewing IRB/EC, and prevailing local 
and/or country laws and/or regulations, whichever affords the greater protection to the 
subject. 
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. 

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• 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 BSC, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE. 
• Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies that 
could have led to a SADE, if required by the national regulations or this protocol or by 
the IRB/EC, and supply BSC with any additional requested information related to the 
safety reporting of a particular event. 
• Maintain the device accountability records and control of the device, ensuring that the 
investigational device is used only by authorized/designated users and in accordance with 
this protocol and instructions/directions for use. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
monitor and respond to questions during monitoring visits. 
• Allow and support regulatory authorities and the IRB/EC when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with this protocol and local 
IRB/EC 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 Informed Consent Form 
(ICF). 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the investigational device when it is used/operated by the subject. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together with 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 

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• 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. 
• Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
12.5.3.  Delegation of Responsibility 
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.  
12.6.  Institutional Review Board/ Ethics Committee 
Prior to gaining Approval-to-Enroll status, the investigational center will provide to the 
sponsor documentation verifying that their IRB/EC is registered or that registration has been 
submitted to the appropriate agency, as applicable according to national/regulatory 
requirements.   
A copy of the written IRB/EC and/or competent authority approval of the protocol (or 
permission to conduct the study) and Informed Consent Form, must be received by the 
sponsor before recruitment of subjects into the study and shipment of investigational 
product/equipment. Prior approval must also be obtained for other materials related to subject 
recruitment or which will be provided to the subject. 
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by local/country or IRB/EC requirements. Copies of the Investigator’s reports 
and the IRB/EC continuance of approval must be provided to the sponsor.  
12.7.  Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC. Only authorized BSC personnel or a BSC 
representative will have access to these confidential records. Authorized regulatory personnel 
have the right to inspect and copy all records pertinent to this study. Study data collected 
during this study may be used by BSC 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. 

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Boston Scientific will keep subjects’ health information confidential in accordance with all 
applicable laws and regulations.  Boston Scientific 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.  
12.8.  Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 
12.9.  Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the monitor verifies that study records are 
adequately maintained, that data are reported in a satisfactory manner with respect to 
timeliness, adequacy, and accuracy and that the Investigator continues to have sufficient staff 
and facilities to conduct the study safely and effectively. The Investigator/institution 
guarantees direct access to original source documents by BSC personnel, their designees and 
appropriate regulatory authorities. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Investigator and 
relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
12.10. 
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 Ethics Committee and/or Regulatory authority body, as applicable. The ICF must be 
approved by the center’s IRB/EC, or central IRB, if applicable. 
Boston Scientific 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 IRB/EC.  Any modification requires approval from BSC prior to use of 
the form.  The ICF must be in a language understandable to the subject and if needed, BSC 
will assist the center in obtaining a written consent translation. Translated consent forms 
must also have IRB/EC approval prior to their use.  Privacy language shall be included in the 
body of the form or as a separate form as applicable.   

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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 will be reported by BSC to the applicable regulatory body 
according to their requirements (e.g., FDA requirement is within 5 working days of learning 
of such an event). Any violations of the informed consent process must be reported as 
deviations to the sponsor and local regulatory authorities (e.g. IRB/EC), 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 IRB/EC. The new version of the ICF must be approved by the IRB/EC. 
Boston Scientific approval is required if changes to the revised ICF are requested by the 
center’s IRB/EC. The IRB/EC will determine the subject population to be re-consented. 
12.11. 
Committees 
12.11.1.  Safety Monitoring Process  
An independent data review (IDR) board comprised of physician experts in surgery and 
gastroenterological endoscopy not participating in the clinical study and with no affiliation 
with BSC, will provide external oversight and review for potential safety concerns.  

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During the course of the clinical study, the IDR board will periodically review aggregate 
accumulating safety data to monitor for the incidence of major adverse events and other 
trends. 
Any IDR recommendations for clinical study modification or termination because of 
concerns over subject safety or issues relating to data monitoring or quality control will be 
submitted in writing to BSC for consideration.  
12.12. 
Suspension or Termination 
12.12.1.  Premature Termination of the Study 
Boston Scientific Corporation reserves the right to terminate the study at any stage but 
intends to exercise this right only for valid scientific or administrative reasons and reasons 
related to protection of subjects.  Investigators, associated IRBs/ECs, and regulatory 
authorities, as applicable, will be notified in writing in the event of study termination. 
12.12.2.  Criteria for Premature Termination of the Study 
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.  
• A decision on the part of Boston Scientific to suspend or discontinue development of the 
device. 
12.12.3.  Termination of Study Participation by the Investigator or Withdrawal of IRB/ 
EC Approval 
Any investigator, or IRB/ EC in the Preoperative Biliary Drainage RCT Study may 
discontinue participation in the study or withdrawal approval of the study, respectively, with 
suitable written notice to Boston Scientific. Investigators, associated IRBs/ECs, and 
regulatory authorities, as applicable, will be notified in writing in the event of these 
occurrences. 
12.12.4.  Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating centers by Boston Scientific. 
The IRB/EC and regulatory authorities, as applicable, will be notified. Detailed information 
on how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 

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Detailed information on how enrolled subjects will be managed thereafter will be provided 
by Boston Scientific. 
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 Boston Scientific. 
The investigator must return all documents and investigational product to Boston Scientific, 
unless this action would jeopardize the rights, safety, or welfare of the subjects. 
12.12.5.  Criteria for Suspending/Terminating a Study Center 
Boston Scientific Corporation 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/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of investigator participation, all study devices and testing 
equipment, as applicable, will be returned to BSC unless this action would jeopardize the 
rights, safety or well-being of the subjects. The IRB/EC and regulatory authorities, as 
applicable, should be notified. All subjects enrolled in the study at the center will continue to 
be followed per protocol. The Principal Investigator at the center must make provision for 
these follow-up visits unless BSC notifies the investigational center otherwise. 
12.13. 
Publication Policy 
In accordance with the Corporate Policy on the Conduct of Human Subject Research, BSC 
requires disclosure of its involvement as a sponsor or financial supporter in any publication 
or presentation relating to a BSC study or its results. In accordance with the Corporate Policy 
for the Conduct of Human Subject Research, BSC will submit study results for publication 
(regardless of study outcome) following the conclusion or termination of the study. Boston 
Scientific Corporation 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, BSC 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. 
• BSC involvement in the publication preparation and the BSC Publication Policy should 
be discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  

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12.14. 
Definitions of complication criteria (per van der Gaag article): 
Specific PBD (ERCP, PTC) related: 
o Acute pancreatitis  Abdominal pain and a serum concentration of pancreatic 
enzymes (amylase or lipase) three or more times the upper limit of normal, that 
required more than one night of hospitalization 
o Acute cholecystitis  No suggestive clinical or radiographic signs of acute 
cholecystitis before the procedure and if emergency cholecystectomy is subsequently 
required 
o Perforation  Retroperitoneal or bowel-wall perforation documented by any 
radiographic technique or direct visual evidence 
o Stent Occlusion Recurring obstructive jaundice with necessary stent replacement 
Specific surgery related: 
o Pancreaticojejunostomy leakage Drain output of any measurable volume of fluid on 
or after postoperative day 3 with an amylase content greater than 3 times the serum 
amylase activity, graded according to clinical course (ISGPS grade A, B, C), or direct 
visual evidence of defect at anastomosis 
o Delayed gastric emptying  Gastric stasis requiring nasogastric intubation for 10 days 
or more, or the inability to tolerate a regular (solid) diet on or before the fourteenth 
postoperative day, not due to sequelae of intra-abdominal complications (i.e. abscess, 
anastomotic leakage) 
o Biliary leakage Bilirubin in abdominal drain or dehiscence found at laparotomy 
o Gastro/-duodenojejunostomy leakage Conclusive radiographic or direct visual 
evidence of a defect of the anastomosis 
o Intra-abdominal abscess formation Intra-abdominal fluid collection with positive 
cultures identified by ultrasonography or computed tomography, associated with 
persistent fever and elevations of white blood cells 
o Wound infection Requiring intervention otherwise considered as minor complication 
o Portal Vein Thrombosis Conclusive radiologic evidence of thrombosis 
Following either procedure: 
o Cholangitis  Elevation in temperature more than 38°C, thought to have a biliary 
cause, without concomitant evidence of acute cholecystitis, requiring intervention 
o Hemorrhage Bleeding after the index procedure requiring transfusion of ≥4 units of 
packed cells within a 24-hour period, or leading to relaparotomy/intervention 
o (Emergency) (re)laparotomy  Any (other) reason following either preoperative 
biliary drainage or another surgical procedure 
o Pneumonia Pulmonary infection with radiological confirmation and requiring 
antibiotic treatment 
o Mortality In-hospital death, due to protocol complications or any cause, including 
progression of disease, within the study period