Directional Lead: Investigation of Rotational Current Steering, Ease of Use of Clinical Effects Map, and Therapeutic Outcomes of Deep Brain Stimulation
Phase: NA
Conditions: Parkinson Disease
Sponsor: Boston Scientific Corporation

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THESE DOCUMENTS ARE THE PROPERTY OF BOSTON SCIENTIFIC CORP. AND SHALL NOT BE REPRODUCED, 
DISTRIBUTED, DISCLOSED OR USED FOR MANUFACTURE OR SALE OF APPARATUS WITHOUT THE EXPRESS WRITTEN 
CONSENT OF BOSTON SCIENTIFIC CORP. 
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DIRECT-DBS Study-Specific Protocol 
91127016 Rev/Ver. AB  
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Directional Lead: Investigation of Rotational Current Steering, Ease of Use 
of Clinical Effects Map, and Therapeutic Outcomes of Deep Brain 
Stimulation 
DIRECT-DBS 
 
CLINICAL INVESTIGATION PLAN 
 
A4150 
 
Sponsored By 
Boston Scientific Corporation 
Neuromodulation 
25155 Rye Canyon Loop 
Valencia, CA 91355 
 
United States of America 
 
 
International Representative 
Boston Scientific Limited 
Ballybrit Business Park, 
Galway, Ireland 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol 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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Contact Information 
Role 
Contact  
Clinical Contact 
Nic Van Dyck 
Director International Clinical Operations 
Boston Scientific Corporation  
Gaetano Martinolaan 50 
6629 GS Maastricht 
Netherlands  
+ 31 (0)43 356 8328 
VanDycKN@bsci.com 
Coordinating Principal 
Investigator 
Prof. Jens Volkmann 
Neurologische Klinik und Poliklinik 
Universitätsklinikum Würzburg 
Josef-Schneider-Str. 11 
97080 Würzburg 
GERMANY 
Coordinating 
Co-Principal 
Investigator 
Prof. Stéphane Chabardes 
Clinique de Neurochirurgie, 
Pôle TCCR CHU MICHALLON, BP 217 
38043 Grenoble 
France  
 
 
 

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Original Release: February, 05, 2016 
Current Version: February, 25, 2016 
 
Revision History 
Revision Number 
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for Change 
AA 
05Feb2016 
90702637 
Rev./Ver. 
AF 
All 
N/A 
Initial Release 
AB 
25Feb2016 
90702637 
Rev./Ver. 
AF 
8.1 
Increased maximum 
number of sites to 4 
Flexibility in study 
execution 
AB 
25Feb2016 
90702637 
Rev./Ver. 
AF 
11.6 
Removed 
specification of the 
side to be tested 
Choice of side left to 
Investigator 
Judgement 
 
 

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2. Protocol Synopsis 
Directional Lead: Investigation of Rotational Current Steering, Ease of Use of Clinical 
Effects Map, and Therapeutic Outcomes of Deep Brain Stimulation 
DIRECT-DBS STUDY 
Study 
Objective(s) 
The primary objective is to characterize the programming effects of 
Boston Scientific Vercise™ PC System using the DBS Directional Lead 
for bilateral STN DBS for the treatment of Parkinson’s disease in acute 
and chronic settings. 
The exploratory objectives are to evaluate the directional marker, 
changes in impedance over time, collect induced field potentials and to 
explore sensitivity to current steering settings. In addition, to assess use 
and usefulness of the Vercise™ Navigator Steering mode controls and 
Clinical Effects Scores capture in the Directional Lead Clinical Effect 
Maps on the Vercise™ Programmer. 
Test Device 
Boston Scientific Neuromodulation (BSN) Vercise™ PC System with 
BSN Directional Lead 
Control Device 
None; each patient will serve as their own control 
Study Design 
Prospective, multi-center, open label study with double-blinded 
exploratory and crossover phases 
Planned 
Number of 
Patients 
Up to 12 randomized patients 
Planned 
Number of 
Investigational 
Sites / 
Count11ries 
Up to 4 sites in the EU 
Primary 
Endpoint 
Collected data will be used to guide product development and to build 
early experience to define the best practice for programming 
Additional 
Endpoints 
• 
Amplitude (mA) of first limiting stimulation induced side effect 
threshold during intra-operative testing  

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Directional Lead: Investigation of Rotational Current Steering, Ease of Use of Clinical 
Effects Map, and Therapeutic Outcomes of Deep Brain Stimulation 
DIRECT-DBS STUDY 
• 
Amplitude (mA) difference between efficacy threshold for full 
control of rigidity and first limiting stimulation induced side effect 
threshold, i.e. “therapeutic window”, for all evaluated settings at 
Programming Visits – Day 1, 2 and 3  
• 
UPDRS III Scores for selected settings at Programming Visits – Day 
1, 2 and 3 and at Randomization, Crossover, Release, and 1 Year 
Follow Up Visits 
• 
Kinesia ONE scores for selected settings at Programming Visits – 
Day 1, 2 and 3 and at Randomization, Crossover, Release, and 1 
Year Follow Up Visits 
• 
PDQ-39 Scores at Randomization, Crossover, Release, and 1 Year 
Follow Up Visits 
• 
Kinesia 360 motor diary scores during Crossover Arms 1 and 2    
Method of 
Assigning 
Patients to 
Treatment 
Eligible patients who consent to participation and have met all of the 
inclusion and none of the exclusion criteria will undergo implant and 
intraoperative testing.  After 3 months of omnidirectional (Ring Mode) 
stimulation, the patient will undergo 3 Programming Visits.  Patients are 
then randomized in an equal distribution to best Ring Mode settings or 
best Unrestricted settings for 4 weeks, followed by crossover to the 
opposite programming method for 4 additional weeks. After this, 
patients are followed up to one year post implant where programming 
can be further optimized 
Follow-up 
Schedule 
• Screening (prior to implant) 
• Implant  
• 3 Programming Visits (up to 7 days prior to Randomization Visit) 
• Randomization Visit (90  ± 30 days post first lead placement)  
• Crossover Visit (28 ± 7 days post Randomization Visit) 
• Release Visit (56 ± 7 days post Randomization Visit) 
• 1-Year Follow Up Visit (365 ± 30 days post first lead placement) 
The overall study will be considered complete when the last patient not 
lost to follow up completes the 1 Year Follow Up Visit 

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Directional Lead: Investigation of Rotational Current Steering, Ease of Use of Clinical 
Effects Map, and Therapeutic Outcomes of Deep Brain Stimulation 
DIRECT-DBS STUDY 
Study Duration The entire study will take less than 2 years to complete. 
Each patient will be enrolled for approximately 1 year. 
Key Inclusion 
Criteria 
IC1. Candidate for Vercise™ PC DBS with bilateral implant of BSN 
DBS Directional Leads in STN, and meets: 
• Diagnosis of bilateral idiopathic PD with the presence of 
rigidity and at least one (1) of the following: resting tremor or 
bradykinesia. 
• UPDRS III score of >25 in the meds OFF condition 
• Medication must improve PD symptoms by ≥30%, as measured 
by UPDRS subset III score 
IC2. Willing and able to comply with all visits, including required 
travel, and with study related procedures 
IC3. Meets all requirements of Vercise™ PC Local Directions For 
Use (DFU) 
IC4. Able to understand the study requirements and the treatment 
procedures and provides written informed consent before any 
study-specific tests or procedures are performed  
Key Exclusion 
Criteria 
EC1. Any significant psychiatric problems, including unrelated 
clinically significant depression as determined by the investigator 
EC2. Any current drug or alcohol abuse as determined by the 
investigator 
EC3. Any history of recurrent or unprovoked seizures 
EC4. Any significant medical condition that is likely to interfere with 
study procedures or likely to confound evaluation of study 
endpoints, including any terminal illness with survival <12 
months 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
NONE 
Statistical Test 
Method 
Descriptive statistics will be employed in post-hoc analysis 

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Directional Lead: Investigation of Rotational Current Steering, Ease of Use of Clinical 
Effects Map, and Therapeutic Outcomes of Deep Brain Stimulation 
DIRECT-DBS STUDY 
Sample Size 
Parameters 
Sample size not determined in prospective manner 
3. Table of Contents 
2. 
PROTOCOL SYNOPSIS .........................................................................................................4 
3. 
TABLE OF CONTENTS .........................................................................................................7 
3.1. Table of Figures .....................................................................................................10 
3.2. Table of Tables ......................................................................................................10 
4. 
INTRODUCTION ................................................................................................................11 
5. 
DEVICE DESCRIPTION ......................................................................................................12 
5.1. Medical Equipment Description ..........................................................................12 
6. 
STUDY OBJECTIVES .........................................................................................................13 
7. 
STUDY ENDPOINTS ...........................................................................................................13 
8. 
STUDY DESIGN .................................................................................................................13 
8.1. Scale and Duration ................................................................................................13 
8.2. Treatment Assignment .........................................................................................14 
8.2.1. 
Treatment and Control ..............................................................................14 
8.3. Justification for the Study Design ........................................................................15 
9. 
PATIENT SELECTION ........................................................................................................15 
9.1. Study Population and Eligibility ..........................................................................15 
9.2. Inclusion Criteria ..................................................................................................15 
9.3. Exclusion Criteria .................................................................................................16 
10. PATIENT ACCOUNTABILITY .............................................................................................16 
10.1. Point of Enrollment ...............................................................................................16 
10.2. Withdrawal ............................................................................................................16 
10.3. Enrollment Controls .............................................................................................17 

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11. STUDY METHODS .............................................................................................................17 
11.1. Data Collection ......................................................................................................17 
11.2. Study Candidate Screening ..................................................................................20 
11.3. Informed Consent .................................................................................................20 
11.4. Screening/Baseline Visit .......................................................................................20 
11.5. Implant Visit (Day 0) ............................................................................................20 
11.6. Programming Visits 1, 2 and 3 .............................................................................21 
11.6.1. Programming Visit 1 .................................................................................21 
11.6.2. Programming Visit 2 .................................................................................21 
11.6.3. Programming Visit 3 .................................................................................21 
11.7. Randomization Visit (90 ± 30 days post first lead placement) ..........................21 
11.8. Crossover Visit (28 ± 7 days post Randomization visit) ....................................21 
11.9. Release Visit (56 ± 7 days post Randomization visit) .........................................22 
11.10. 
1 Year Follow Up Visit (365 ± 30 days post first lead placement) ......22 
11.11. 
Study Completion ...................................................................................22 
11.12. 
Source Documents ..................................................................................22 
12. STATISTICAL CONSIDERATIONS ......................................................................................23 
12.1. Endpoints ...............................................................................................................23 
12.1.1. Primary Endpoint ......................................................................................23 
12.1.2. Hypotheses ................................................................................................23 
12.1.3. Sample Size ..............................................................................................23 
12.1.4. Statistical Methods ....................................................................................23 
12.1.5. Exploratory Endpoints ..............................................................................23 
12.2. General Statistical Methods .................................................................................24 
12.2.1. Analysis Sets .............................................................................................24 
12.2.2. Control of Systematic Error/Bias ..............................................................24 
12.2.3. Number of Patients per Investigative Site ................................................24 
12.3. Data Analyses ........................................................................................................24 
12.3.1. Interim Analyses .......................................................................................24 
13. DATA MANAGEMENT .......................................................................................................24 
13.1. Data Collection, Processing, and Review ............................................................24 
13.1.1. Electronic Transmission ...........................................................................24 
13.1.2. Kinesia System .........................................................................................24 

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13.1.3. Brain Imaging Data ...................................................................................25 
13.2. Data Retention .......................................................................................................25 
14. AMENDMENTS ..................................................................................................................25 
15. DEVIATIONS .....................................................................................................................25 
16. DEVICE/EQUIPMENT ACCOUNTABILITY .........................................................................26 
17. COMPLIANCE ....................................................................................................................26 
17.1. Statement of Compliance ......................................................................................26 
17.2. Investigator Responsibilities ................................................................................26 
17.2.1. Delegation of Responsibility ....................................................................28 
17.3. Ethics Committee ..................................................................................................28 
17.4. Sponsor Responsibilities .......................................................................................29 
17.4.1. Role of Boston Scientific Representatives ...............................................29 
17.5. Insurance ................................................................................................................30 
18. MONITORING ....................................................................................................................30 
19. POTENTIAL RISKS AND BENEFITS ...................................................................................30 
19.1. Anticipated Adverse Events .................................................................................31 
19.2. Anticipated Adverse Device Effects .....................................................................31 
19.3. Risks Associated with the Study Device(s) ..........................................................31 
19.4. Risks associated with Participation in the Clinical Study .................................31 
19.5. Possible Interactions with Concomitant Medical Treatments ..........................32 
19.6. Risk Minimization Actions ...................................................................................32 
19.7. Anticipated Benefits ..............................................................................................32 
19.8. Risk to Benefit Rationale ......................................................................................32 
20. SAFETY REPORTING .........................................................................................................33 
20.1. Reportable Events by investigational site to Boston Scientific .........................33 
20.2. Definitions and Classification ..............................................................................33 
20.3. Relationship to Study Device(s) ...........................................................................36 
20.4. Investigator Reporting Requirements .................................................................39 
20.5. Boston Scientific Device Deficiencies ...................................................................40 
20.6. Reporting to Regulatory Authorities / ECs / Investigators ...............................40 

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20.7. Subject Death Reporting ......................................................................................41 
21. INFORMED CONSENT ........................................................................................................41 
22. COMMITTEES ...................................................................................................................43 
22.1. Safety Monitoring Process ....................................................................................43 
23. SUSPENSION OR TERMINATION ........................................................................................43 
23.1. Premature Termination of the Study ..................................................................43 
23.1.1. Criteria for Premature Termination of the Study ......................................43 
23.2. Termination of Study Participation by the Investigator or Withdrawal of EC 
Approval ................................................................................................................43 
23.3. Requirements for Documentation and Patient Follow-up ................................44 
23.4. Criteria for Suspending/Terminating a Study Site ............................................44 
24. PUBLICATION POLICY ......................................................................................................44 
25. REIMBURSEMENT AND COMPENSATION FOR PATIENTS .................................................45 
25.1. Patient Reimbursement ........................................................................................45 
25.2. Compensation for Patient’s Health Injury .........................................................45 
26. BIBLIOGRAPHY .................................................................................................................45 
27. ABBREVIATIONS AND DEFINITIONS .................................................................................47 
27.1. Abbreviations ........................................................................................................47 
27.2. Definitions ..............................................................................................................48 
 
3.1. Table of Figures 
Figure 8.1-1: DIRECT-DBS Study Design ............................................................................ 14 
 
3.2. Table of Tables 
Table 9.2-1: Inclusion Criteria ................................................................................................ 16 
Table 9.3-1: Exclusion Criteria ............................................................................................... 16 
Table 11.1-1: Data Collection Schedule ................................................................................. 18 
Table 11.12-1: Source Documentation Requirements ............................................................ 23 
Table 20.2-1: Safety Definitions ............................................................................................. 33 

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Table 20.3-1: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 37 
Table 20.4-1: Investigator Reporting Requirements ............................................................... 39 
Table 27.1-1: Abbreviations ................................................................................................... 47 
Table 27.2-1: Definitions ........................................................................................................ 48 
4. Introduction 
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects 2.0 million 
Europeans (1). The prevalence of PD is estimated at 0.3% of the overall population in 
industrialized countries and advances to 1% by age 60 and 4% in the highest age groups (2). 
The hallmark signs of PD include movement disorders such as bradykinesia, resting tremors, 
and muscle rigidity (3).  
The motor symptoms of PD are associated with a dopamine deficiency resulting from the 
degradation of dopaminergic neurons in the substantia nigra pars compacta. At present there 
is no cure for PD; treatment is focused on medical management of motor symptoms. Medical 
therapy has been primarily focused on restoring dopamine levels through the administration 
of levodopa, dopamine agonists, or monoamine oxidase B inhibitors. Current standards for 
patient care recommend levodopa as first line therapy for the symptomatic control during the 
early, uncomplicated stages of PD (4, 5).  Unfortunately, chronic treatment with levodopa 
frequently leads to significant side effects, especially dyskinesias and motor fluctuations (6).  
Previously, for patients who had reduced response to medical therapy, pallidotomy 
(destruction of the globus pallidus) and thalamotomy (destruction of the thalamus) were the 
only available surgical treatment options. In the 1990s, high-frequency deep brain 
stimulation (DBS) was demonstrated to be effective in reducing the motor complications of 
patients with PD (7). Since that time numerous case studies and trials have substantiated 
these early findings. In addition, three recent large, multicenter, randomized trials have 
demonstrated the efficacy of the therapy (8-10). Currently, DBS of the subthalamic nuclei 
(STN) is recommended as a therapeutic option for appropriate PD patients (5, 11). 
This study will compare various program settings for the bilateral stimulation of the STN 
using the BSC implantable Vercise™ PC DBS System for the treatment of levodopa-
responsive, moderate to severe idiopathic PD. The Vercise™ PC System is capable of 
delivering stimulation similar to other commercially available DBS systems.  However, the 
Vercise™ PC System combined with the directional lead also features an expanded 
parameter range when compared to commercially available conventional cylindrical 
electrodes, including the ability to shape stimulation in the plane orthogonal to the long axis 
of the lead, and at settings that utilize independent current sources for multiple contacts 
(“current steering”). 

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5. Device Description 
The Boston Scientific Vercise™ DBS System received CE mark approval in September 2012 
for treatment of Parkinson’s disease, in September 2013 for treatment of intractable primary 
and secondary dystonia and in July 2014 for Essential Tremor. The directional lead, 
Vercise™ PC system and programming system received CE mark in September 2015 
The implantable portion of the Vercise™ PC System includes leads for bilateral stimulation 
and extensions that allow the leads to be extended to reach the Implantable Pulse Generator 
(IPG) near the clavicle. The electrode array is placed into the brain, typically targeting the 
subthalamic nucleus (STN) or Globus Pallidus (GPi). The directional leads can provide 
stimulation in a ring mode (equally around the lead) or in a directional mode (away from the 
center of the lead). Once the leads are placed, they are typically secured using physician’s 
standard lead fixation technique. A SureTek™ Burr Hole Cover may be used. Since the leads 
are often placed under the scalp for some time before being connected to lead extensions or 
IPG, lead boots will be provided to cover the proximal ends of the leads during this period.   
Surgical tools for the Vercise™ PC System include a tunneler. A lead stop (which may be 
attached to the lead to allow the lead to be located at the appropriate depth in the tissue 
during its initial placement) will also be provided.   
External devices including a Clinician Programmer, programming wand and Remote Control 
will also be provided for patient/physician use. During implant, the positioning of the lead(s) 
may be checked using macrostimulation provided by a Vercise™ PC External Trial 
Stimulator (ETS). 
A copy of the device labeling and DFU will be provided in local language(s) as required per 
national regulations. 
5.1. Medical Equipment Description 
Kinesia ONE 
Commercial, tablet-based system created by Great Lakes NeuroTech (GLNT) which assesses 
tremor, bradykinesia, hypokinesia, and dysrhythmia in an automated fashion via a patient-
worn, finger mounted motion sensor.  
Kinesia 360 
Commercial tablet-based motor diary system created by Great Lakes NeuroTech (GLNT) 
which assesses tremor, dyskinesia and mobility during the day in an automated fashion via 
patient-worn sensors and a mobile app to continuously measure Parkinson’s disease.  
The Kinesia ONE system is used in the hospital environment while the Kinesia 360 system is 
used by the patient at home. 

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6. Study Objectives 
The primary objective of this exploratory study is to characterize the programming effects of 
Boston Scientific Vercise™ PC System using the DBS Directional Lead for bilateral STN 
DBS for the treatment of Parkinson’s disease in an acute and chronic setting. 
The exploratory objectives of this study are to evaluate the directional marker, changes in 
impedance over time, collect induced field potentials, and to explore sensitivity to current 
steering settings. In addition we will assess use & usefulness of the Vercise™ Navigator 
Steering mode controls, and Clinical Effects Scores capture in the Directional Lead Clinical 
Effect Maps on the Vercise™ Programmer. 
7. Study Endpoints 
Collected data will be used to guide product development and to build early experience to 
define the best practice for programming. 
Exploratory endpoints are: 
• 
Amplitude (mA) of stimulation induced side effect threshold during intra-operative 
testing.  
• 
Amplitude (mA) difference between efficacy threshold for control of rigidity and first 
limiting stimulation induced side effect threshold, i.e. “therapeutic window”, for all 
evaluated settings at Programming Visits – Day 1, 2 and 3  
• 
UPDRS III Scores for selected settings at Programming Visits – Day 1, 2 and 3 and at 
Randomization, Crossover, Release, and 1 Year Follow Up Visits 
• 
Kinesia ONE scores for selected settings at Programming Visits – Day 1, 2 and 3 and at 
Randomization, Crossover, Release, and 1 Year Follow Up Visits 
• 
PDQ-39 Scores at Randomization, Crossover, Release, and 1 Year Follow Up Visits 
• 
Kinesia 360 motor diary scores during Crossover Arms 1 and 2    
8. Study Design 
Prospective, multi-center, open label, study with double-blinded exploratory and crossover 
phases. 
8.1. Scale and Duration 
The study will be conducted at up to 4 international centers.  Up to 12 patients will be 
randomized.  Follow-up of each patient will continue for one year after first lead placement.  
The study may require up to two years to complete.   

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Figure 8.1-1: DIRECT-DBS Study Design 
 
8.2. Treatment Assignment 
Eligible patients who consent to participation and have met all of the inclusion and none of 
the exclusion criteria will undergo implant and intraoperative testing.  After 3 months of 
omnidirectional (Ring Mode) stimulation, the patient will undergo 3 Programming Visits.  
Patients are then randomized in an equal distribution to best Ring Mode settings or best 
Unrestricted settings for 4 weeks, followed by crossover to the opposite programming 
method for 4 additional weeks. After this, patient is followed up to one year post implant 
where programming can be further optimized. 
8.2.1. Treatment and Control 
Each patient will serve as their own control during Crossover Phase. Symptom comparisons 
will be made across time and across different stimulation settings.  
Study 
Completion 
28 days  
Screening/Baseline 
Written Informed Consent 
Randomization Visit 
(90 ± 30 days)   
Ring Mode 
Vercise™  Implant 
Day 0:  Day of 1
st Lead Placement   
Long Term Follow 
Up 
Programming Visits  
1, 2, 3 (up to 1 week 
prior to Randomization) 
1 Year Follow Up Visit (365 ±  
30  Days) 
Unrestricted 
Settings 
Crossover Visit (28 ± 7 days 
post Randomization)   
Release Visit (56 ± 7 days 
post Randomization)   
Unrestricted 
Settings 
Ring Mode 
90 days  
28 days  

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8.3. Justification for the Study Design 
The study design is a prospective, multi-center, open label, study with double-blinded 
exploratory phase and un-blinded crossover phase with a blinded evaluator, characterizing 
the programming effects of Boston Scientific Vercise™ PC System using the DBS 
Directional Lead for bilateral STN DBS for the treatment of Parkinson’s disease in an acute 
and chronic setting. 
A multi-center design will minimize the impact on treatment outcome that may potentially 
result from differences in patient selection, regional differences in the patient demographic, 
and differences in investigator technique and patient management. 
The study will include multiple instances of randomization, where the patient will receive 
stimulation parameters from a preset list in a random order. Randomization will minimize 
bias due to order of presentation of stimulation settings.  A double blind (patient and 
neurologist assessor) will minimize bias that might impact subjective outcome measures. The 
programmer will remain un-blinded to provide appropriate care for each patient’s 
programming variables. 
The crossover phase requires that the patient is programmed with each of Ring Mode and 
Unrestricted programming settings for an equal amount of time, in a random order.  In this 
way, patients can each serve as their own control.  In order to minimize bias that might 
impact subjective outcome measures, the physician responsible for evaluating these arms will 
be blinded. 
9. Patient Selection  
9.1. Study Population and Eligibility  
Up to 12 randomized patients may be included in the study.  
Patients will generally be recruited from physician’s practice and will be eligible to receive 
Deep Brain Stimulation to treat their Parkinson disease using the commercially-approved 
BSC Vercise™ PC System per local DFU. 
9.2. Inclusion Criteria 
Patients who meet all of the following criteria (see Error! Reference source not found.) 
may be given consideration for inclusion in this clinical investigation, provided no exclusion 
criterion (see Section 9.3) is met.  

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Table 9.2-1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria 
IC1. Candidate for Vercise™ PC DBS with bilateral implant of BSN DBS Directional 
Leads in STN, and meets: 
• 
Diagnosis of bilateral idiopathic PD with the presence of rigidity and at least one (1) of 
the following: resting tremor or bradykinesia. 
• 
UPDRS III score of >25 in the meds OFF condition 
• 
Medication must improve PD symptoms by ≥30%, as measured by UPDRS subset III 
score. 
IC2. Willing and able to comply with all visits, including required travel, and with study 
related procedures. 
IC3. Meets all requirements of Vercise™ PC Local Directions For Use (DFU). 
IC4. Able to understand the study requirements and the treatment procedures and provides 
written informed consent before any study-specific tests or procedures are performed. 
 
9.3. Exclusion Criteria 
Patients who meet any one of the following criteria (Error! Reference source not found.) 
will be excluded from this clinical study. 
Table 9.3-1: Exclusion Criteria 
Clinical 
Exclusion 
Criteria 
EC1. Any significant psychiatric problems, including unrelated clinically significant 
depression as determined by the investigator. 
EC2. Any current drug or alcohol abuse as determined by the investigator. 
EC3. Any history of recurrent or unprovoked seizures. 
EC4. Any significant medical condition that is likely to interfere with study procedures or 
likely to confound evaluation of study endpoints, including any terminal illness with 
survival <12 months. 
 
10. Patient Accountability 
10.1. Point of Enrollment 
A patient will be considered enrolled in this study after he/she signs and dates the informed 
consent form (ICF). No study-related procedures or assessments can take place until the 
informed consent form is signed.  
10.2. Withdrawal 
All patients enrolled in the clinical study (including those withdrawn from the clinical study 
or lost to follow-up) shall be accounted for and documented. If a patient 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 
patient’s permission to follow his/her status/condition outside of the clinical study.   

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Reasons for withdrawal could include but are not limited to 
• 
physician discretion,  
• 
patient choice to withdraw consent; in case of patients under the age of 18 years old, 
parent/guardian choice to withdraw consent will be considered a valid reason for 
withdrawal. 
• 
patient’s failure to meet inclusion or not meet exclusion criteria after enrollment but 
prior to system implant,  
• 
failure to receive a BSC DBS system, 
• 
lost to follow-up, or  
• 
death.   
While study withdrawal is discouraged, patients may withdraw from the study at any time, 
with or without reason, and without prejudice to further treatment. 
All applicable case report forms (CRFs) up to the point of patient withdrawal and an “End of 
Study” form must be completed.  Any patient deemed “lost to follow-up” should have a 
minimum of three documented attempts to contact him/her prior to completion of the “End of 
Study” form.   
Additional data may no longer be collected after the point at which a patient has been 
withdrawn from the study or withdraws consent, for whatever reason.  All open adverse 
events should be closed or documented as unresolved.  Data collected up to the point of 
patient withdrawal may be used and analyzed. 
Patients withdrawn after completing the implant procedure will be replaced and will not be 
included in the site’s overall total for randomized patients. 
10.3. Enrollment Controls 
Enrollment will remain open until one of the following events occurs: 
• 
The maximum of 12 patients are randomized 
• 
The study is terminated at any time, at the Sponsor’s discretion. 
Enrollment controls will be implemented per the Enrollment Communication Plan developed 
for this study. 
11. Study Methods 
11.1. Data Collection 
The data collection schedule is shown in Table 11.1-1.

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Table 11.1-1: Data Collection Schedule 
 
 
Procedure/Assessment 
Screening
/Baseline 
Implant 
Visit 
(Day 0) 
Program. 
Visit 1 
(up to 7 
days 
prior to 
Randomi
zation 
Visit) 
Program. 
Visit 2 
(up to 6 
days 
prior to 
Randomi
zation 
Visit) 
Program. 
Visit 3 
(up to 5 
days 
prior to 
Randomi
zation 
Visit) 
Randomi
zation 
Visit 
(90±30 
days) 
Crossover 
Visit  
(28±7 
days post 
Randomiz
ation 
Visit) 
Release 
Visit 
(56±7 
days 
post 
Random
ization 
Visit) 
1 Year 
Follow Up 
(365±30 
days) 
Unscheduled 
Visits 
Informed consent form, including 
signatures and dates 
X 
 
 
 
 
 
 
 
 
 
Side effect thresholds (amplitude 
and effect) 
 
X 
X 
X 
 
 
 
 
 
 
Full rigidity control threshold 
(amplitude) 
 
 
X 
X 
 
 
 
 
 
 
Clinical Effects Scores 
 
 
O 
O 
O 
O 
O 
O 
O 
O 
Electrode impedances 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Brain Imaging (If done per 
Standard of Care) 
X 
X 
* 
* 
* 
* 
* 
* 
* 
* 
MER 
 
O 
 
 
 
 
 
 
 
 
Surgical  Plan 
 
O 
 
 
 
 
 
 
 
 
Induced Field Potentials 
 
O 
O 
O 
O 
O 
O 
O 
O 
O 
Clinician Programmer Reports 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinician Programmer Database 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
UPDRS III 
X 
 
X 
X 
X 
X 
X 
X 
X 
O 
PDQ-39 
X 
 
 
 
 
X 
X 
X 
X 
O 
Motor assessments 
 
 
X 
X 
X 
X 
X 
X 
X 
O 
Motor assessments  
 
 
 
 
 
 
X 
X 
 
 

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Procedure/Assessment 
Screening
/Baseline 
Implant 
Visit 
(Day 0) 
Program. 
Visit 1 
(up to 7 
days 
prior to 
Randomi
zation 
Visit) 
Program. 
Visit 2 
(up to 6 
days 
prior to 
Randomi
zation 
Visit) 
Program. 
Visit 3 
(up to 5 
days 
prior to 
Randomi
zation 
Visit) 
Randomi
zation 
Visit 
(90±30 
days) 
Crossover 
Visit  
(28±7 
days post 
Randomiz
ation 
Visit) 
Release 
Visit 
(56±7 
days 
post 
Random
ization 
Visit) 
1 Year 
Follow Up 
(365±30 
days) 
Unscheduled 
Visits 
Motor diary 
 
 
 
 
 
 
X 
X 
 
 
Directional Lead Implant 
questionnaire 
 
O 
 
 
 
 
 
 
 
 
Directional Lead Programming  
questionnaire 
 
 
 
 
O 
 
 
 
 
 
Adverse events assessment 
 
* 
* 
* 
* 
* 
* 
* 
* 
* 
 
 
X = required; O = optional but recommended; * = required if new

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11.2. Study Candidate Screening 
All interested patients will undergo screening during which their eligibility for the study will 
be determined. 
11.3. Informed Consent 
Written Informed Consent must be obtained for all patients who are potential study 
candidates.  Patients will be asked to sign the Informed Consent form before any study-
specific tests or procedures are performed, including any adjustments of medications that are 
made specifically for study eligibility purposes. The context of the study must be fully 
explained to the patient in language that is easily understood by the patient. The patients must 
also be given the opportunity to ask questions and have those questions answered to their 
satisfaction. The Informed Consent form is study specific and must be approved by the study 
Independent Ethics Committee (IEC). Study personnel should explain that even if a patient 
agrees to participate in the study and signs an ICF, certain diagnostic or screening procedures 
might demonstrate that the patient is not eligible to continue participation.  
11.4. Screening/Baseline Visit 
Screening and baseline visit can be done during the same hospitalization, provided patient 
gave consent before any study specific testing. UPDRS III and PDQ-39 will be collected as 
well as Kinesia ONE testing. Brain imaging, as done per center’s standard of care for 
surgical and targeting planning, will be collected.    
11.5.  Implant Visit (Day 0) 
The Vercise™ PC and directional lead surgical implant will be done according to center’s 
standard of care and applicable DFUs. If the surgical implant is done in several day stages, 
the date of the first lead placement shall be considered as day 0 for the study timeline.  
The main goal of the intraoperative stimulation testing is to establish stimulation-induced 
side effect thresholds to be compared against chronic programming and to determine the 
intraoperative sensitivity of these thresholds to directional current steering. 
During the intraoperative testing, the side effect thresholds will be determined for the 
individual and combination of the segments of some or all of the segmented electrodes on the 
directional leads. The physician evaluator will be blinded only to the programming 
fractionalizations used, but will not be blinded to any other element (e.g. hemisphere, 
orientation of marker), including amplitude of stimulation (current, in mA). Pulse width and 
frequency will be fixed. The details of the measurement procedures are described in the 
Manual of Operations.   
 
Upon intraoperative data collection, the surgical procedure is completed per center’s standard 
of care and the study visits will resume after approximately 3 months.  

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In the interim, the patient follow up and device programming occurs according to center’s 
standard of care, with the exception that programming is limited to Ring Mode 
fractionalizations. Data will be collected from any unscheduled programming visits which 
occur. 
11.6. Programming Visits 1, 2 and 3 
The Programming Visits, not to occur on simultaneous days, take place in the 7 days prior to 
the Randomization Visit (90 ± 30 days post first lead implantation).  
At the beginning of each test visit, the patient must be in a practically defined Meds OFF and 
Stim OFF state. All testing shall be done unilaterally. At the end of each visit, patient may 
resume their meds and DBS therapy per physician discretion. 
The data collected includes, but is not limited to: efficacy and stimulation induced side effect 
amplitude thresholds, impedances, UPDRS III and Kinesia ONE system scores. The details 
of the measurement procedures are described in the Manual of Operations.  
11.6.1. Programming Visit 1 
Personnel needed: blinded evaluator and non-blinded operator 
Goal: obtain the best Position of stimulation along one lead, in Ring Mode 
11.6.2. Programming Visit 2 
Personnel needed: blinded evaluator and non-blinded operator 
Goal: obtain the best setting of directional stimulation on one lead using Position found 
during Day 1. 
11.6.3. Programming Visit 3 
Personnel needed: non-blinded evaluator and non-blinded operator 
Goal: obtain the best clinical outcome possible (under Programming Visit conditions) 
11.7. Randomization Visit (90 ± 30 days post first lead placement) 
A UPDRS III assessment is performed, as well as the full battery of Kinesia ONE tests. The 
patient is also assessed using the PDQ-39 questionnaire. Assessments are performed with 
stim ON, meds ON, at the time of best ON. The patient is programmed according to 
randomization and educated again on the use of the Kinesia 360 system to be used at home. 
11.8. Crossover Visit (28 ± 7 days post Randomization visit) 
A UPDRS III assessment is performed by a blinded evaluator, as well as the full battery of 
Kinesia ONE tests. The patient is also assessed using the PDQ-39 questionnaire. 
Assessments are performed with stim ON, meds ON, at the time of best ON. The patient is 

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programmed according to randomization and, if needed, educated again on the use of the 
Kinesia 360 system to be used at home. 
11.9. Release Visit (56 ± 7 days post Randomization visit) 
A UPDRS III assessment is performed by a blinded evaluator, as well as the full battery of 
Kinesia ONE tests. The patient is also assessed using the PDQ-39 questionnaire. 
Assessments are performed with stim ON, meds ON, at the time of best ON. The patient is 
programmed according to standard of care. 
11.10. 
1 Year Follow Up Visit (365 ± 30 days post first lead placement) 
A UPDRS III assessment is performed, as well as the full battery of Kinesia ONE tests. The 
patient is also assessed using the PDQ-39 questionnaire. Assessments are performed with 
stim ON, meds ON, at the time of best ON. 
11.11. 
Study Completion 
Each patient’s participation in the study will be considered complete upon completion of the 
1 Year Follow Up Visit.  
11.12. 
Source Documents 
Error! Reference source not found. summarizes all source data requirements for this 
protocol.  Where copies of the original source document as well as printouts of original 
electronic source documents are retained, these shall be signed and dated by a member of the 
investigational site team with a statement that it is a true reproduction of the original source 
document. 
 
 

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Table 11.12-1: Source Documentation Requirements 
Requirement 
Disposition 
Hospital records or clinical and office charts 
including the evidence of but not limited to 
inclusion/exclusion criteria, informed consent, 
procedures, and assessment of adverse events 
Retain at center 
Clinician programmer printouts for 
programming information about trialed settings, 
clinical responses, and impedance 
measurements. 
Retain at center 
Brain imaging performed per standard of care  
Retain at center 
Clinical evaluations (e.g. UPDRS III, Kinesia) 
Retained on a cloud-based server (paper copy 
retained at the center) 
 
12. Statistical Considerations 
12.1. Endpoints 
12.1.1. Primary Endpoint 
Due to the exploratory nature of the study no prospectively defined, formal statistical 
methods will be employed.  
12.1.2. Hypotheses 
No formal hypotheses has been defined. 
12.1.3. Sample Size  
The sample size has not been determined in prospective manner. 
12.1.4.  Statistical Methods  
Descriptive statistics will be employed in post-hoc analysis 
12.1.5. Exploratory Endpoints 
A number of exploratory endpoints are included in this study to explore the effect of 
treatment on additional outcomes. The exploratory endpoints are intended to generate 
hypotheses for future study. Consequently, no correction for multiple testing will be 
performed for the exploratory endpoints. All exploratory endpoints will be clearly identified 
as such in study reports. 

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12.2. General Statistical Methods 
12.2.1. Analysis Sets 
All exploratory endpoints will be analyzed on both intent-to-treat and a per-protocol basis.  
Full definitions of the analysis set will be provided in the Statistical Analysis Plan. 
12.2.2. Control of Systematic Error/Bias 
Selection of patients will be made from the Investigator's usual patient load. All patients 
meeting the inclusion/exclusion criteria and having signed the Informed Consent Form will 
be eligible for participation in the study. The reasons for exclusion, for subjects who sign an 
informed consent form but are not implanted, will be indicated. Patients who reach 
Randomization Visit will be randomly allocated into the two arms of the Crossover Phase of 
the study, minimizing the systematic error.  
12.2.3. Number of Patients per Investigative Site 
There are no restrictions to the number of patients enrolled per investigative site. The 
enrollment will be competitive until the maximum number of patients in the study is reached. 
12.3. Data Analyses 
All data analysis will be performed using standard methods and tools, with appropriate 
validation when needed.  
12.3.1. Interim Analyses  
No formal interim analyses are planned for the purpose of stopping this study early for 
declaring effectiveness or futility. Handling of drop-outs and missing data will depend on 
their frequency and the nature of the outcome measure.  
13. Data Management 
13.1. Data Collection, Processing, and Review 
13.1.1. Electronic Transmission 
The questionnaires/forms collected on paper will be transmitted from the site via fax or email 
and stored on the secure server. 
13.1.2. Kinesia System 
Exploratory data related to PD symptoms may be collected using the Kinesia quantitative 
assessment system from Great Lakes NeuroTechnologies. The Kinesia system is a patient-
worn motion sensor for the quantitative assessment of tremor and bradykinesia. Real-time 

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motion sensor data and clinical response questionnaires may be captured and transferred to a 
secure server for review, storage and analysis. 
13.1.3. Brain Imaging Data 
Brain imaging data taken per standard of care will be transmitted electronically for storage 
via burned CD or flash drive and stored on a secure server. 
13.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain, at the 
investigative site, all essential study documents and source documentation that support the 
data collected on the study patients 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 country/regional/local regulations.  
The Principal Investigator or his/her designee will take measures to ensure that these 
essential documents are not accidentally damaged or destroyed. If for any reason the 
Principal Investigator or his/her designee 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. Sites are 
required to inform Boston Scientific in writing where paper or electronic files are maintained 
in case files are stored off site and are not readily available.  
14. Amendments  
If a protocol revision is necessary which affects the rights, safety or welfare of the patient or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., Ethics 
Committee (EC)/ Competent Authority (CA)) of the revised protocol must be obtained prior 
to implementation. 
15. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a patient in an emergency. An investigator shall notify the 
sponsor and the reviewing EC of any deviation from the investigational plan to protect the 
life or physical well-being of a patient 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 paper CRF. Sites may 

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also be required to report deviations to the 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, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
16. Device/Equipment Accountability 
The study will use only the commercially available Boston Scientific Vercise™ PC System 
with the DBS Directional Lead. No investigational equipment will be used as test equipment. 
No device tracking/accountability is required.  
17. Compliance 
17.1. Statement of Compliance 
This study will be conducted in accordance with ISO 14155: Clinical Investigation of 
Medical Devices for Human Subjects – Good Clinical Practice, ethical principles that have 
their origins in the Declaration of Helsinki, and pertinent individual country laws and 
regulations. The study shall 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. 
17.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation 
plan/, ISO 14155, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing EC, and prevailing local and/or country 
laws and/or regulations, whichever affords the greater protection to the patient. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Prior to beginning the study, sign the Investigator Brochure Signature Page 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 site 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. 

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• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a patient 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 as applicable per the protocol and observed device deficiency. 
• Report to sponsor, per the protocol requirements, all Serious Adverse Events (SAEs) and 
device deficiencies that could have led to a Serious Adverse Device Event (SADE) and 
potential/Unexpected Serious Adverse Device Event (USADE) or Unexpected Adverse 
Device Event (UADE). 
• Report to the EC and regulatory authorities any SAEs and device deficiencies that could 
have led to a SADE and potential/USADE or UADE, if required by the national 
regulations or this protocol or by the 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 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
• Allow and support regulatory authorities and the EC when performing auditing activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local EC requirements. 
• Provide adequate medical care to a patient during and after a patient’s participation in a 
clinical study in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
• Inform the patient of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the patient with necessary instructions on proper use, handling, 
storage, and return of the investigational device when it is used/operated by the patient. 
• Inform the patient of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the patient with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 

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treatment, including decoding procedures for blinded/masked clinical investigations, as 
needed. 
• Ensure that clinical medical records are clearly marked to indicate that the patient is 
enrolled in this clinical study. 
• Ensure that, if appropriate, patients 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). 
• Inform, with the patient’s approval or when required by national regulations, the patient’s 
personal physician about the patient’s participation in the clinical investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a patient’s premature withdrawal 
from clinical investigation while fully respecting the patient’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. 
17.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal 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.  
17.3. Ethics Committee 
Prior to gaining Approval-to-Enroll status, the investigational site will provide to the sponsor 
documentation verifying that their 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 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 patients into the study and shipment of investigational product/equipment. 
Prior approval must also be obtained for other materials related to patient recruitment or 
which will be provided to the patient. 
Annual EC approval and renewals will be obtained throughout the duration of the study as 
required by local/country or EC requirements. Copies of the Investigator’s reports and the EC 
continuance of approval must be provided to the sponsor.  

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17.4. Sponsor Responsibilities 
All information and data sent to BSC concerning patients or their participation in this study 
will be considered confidential by BSC. Only authorized BSC personnel or a BSC 
representative including, but not limited to Contract Research Organization (CRO) 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 patient name. 
Boston Scientific will keep patients’ identifiable health information confidential in 
accordance with all applicable laws and regulations.  Boston Scientific may use patients’ 
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 patients; patient names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
17.4.1. Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during implant, testing required by the protocol, 
and follow-ups. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of BSC equipment/devices (including 
programmers, analyzers, and other support equipment). 
At the request of the investigator and while under investigator supervision, BSC personnel 
may operate equipment during implant or follow-up, assist with the conduct of testing 
specified in the protocol, and interact with the patient to accomplish requested activities. 
Typical tasks may include the following. 
• Interrogating the device or programming device parameters to investigator-requested 
settings as well as operating investigational equipment 
• Performing lead diagnostic and impedance measurements 
• Clarifying device behavior, operation or diagnostic output as requested by the 
investigator or other health care personnel 
• Assisting with the collection of study data from programmers and other equipment 
• Entering technical data on technical source form as long as the responsible investigator 
verifies and signs the completed worksheet  
• Print out programming reports directly from the clinician programmer and provide 
original to clinical site as source documentation 

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• Provide technical expertise/support to patients during office visits and/or during 
teleconference calls/electronic communications with the principal investigator or their 
delegated site staff and the patient.  
• Enter data on paper case report forms, with clinician verification  
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to patients 
• Discuss a patient’s condition or treatment with a patient without the approval and 
presence of the investigator 
• Independently collect critical study data (defined as primary or secondary endpoint data) 
17.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for patients in the study will be obtained. 
18. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research 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 Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The study may also be patient to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
19. Potential Risks and Benefits 
Based on clinical experience with the commercially available DBS therapy for PD, there are 
anticipated risks that may be associated with the use of the Vercise™ PC System. These 
include risks in the surgical implant procedure, from the presence of the device within the 

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body, related to stimulation (e.g. neuropsychiatric, neurocognitive, motor, etc.), and 
symptoms that are difficult to distinguish from PD progression and/or medication side 
effects.  
19.1. Anticipated Adverse Events  
All potential Anticipated Adverse Events as specified in the Vercise™ PC system's 
Directions for Use (DFU) are applicable to study subjects. 
19.2. Anticipated Adverse Device Effects  
All potential Anticipated Adverse Device Effects as specified in the Vercise™ PC system's 
Directions for Use (DFU) are applicable to study subjects. 
19.3. Risks Associated with the Study Device(s)  
All potential risks associated with the Study Devices as specified in the Vercise™ PC 
system's Directions for Use (DFU) are applicable to study subjects. 
19.4. Risks associated with Participation in the Clinical Study 
The following risks maybe associated with patients’ participation in the clinical study: 
• Subjects may find it difficult, uncomfortable, or tiresome to complete study visits, 
study-diaries and questionnaires. 
• Subjects may experience various symptoms related to the temporary withdrawal of 
Parkinson medications and withdrawal of neurostimulation, which is a condition 
required of specific study visits. Symptoms may include, but are not limited to, 
worsening of Parkinson’s disease signs, apathy, anxiety, disturbance in cognition, or 
changes in sleep. In addition, the discontinuation of Parkinson medications is 
associated with a remote risk of developing a life-threatening condition known as 
neuroleptic malignant syndrome.  
• As various deep brain stimulation settings are tested, subjects may experience side 
effects including, but not limited to, a sensation of tingling, muscle spasm, change in 
speech, mood, vision, cognition, disturbance of balance, coordination, tremor, 
dizziness. 
• Subjects with postural instability or gait disturbances either due to their Parkinson’s 
disease or as a side effect of DBS may be at a risk of falling while completing motor 
tasks as required for certain study assessments.   
 
 

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19.5. Possible Interactions with Concomitant Medical Treatments 
While concomitant use of Parkinson medications is being adjusted to fit a subject’s changed 
requirements with use of DBS, subjects may experience symptoms of excess or inadequate 
dopaminergic states. As a result, subjects may experience symptoms including, but not 
limited to dyskinesias, rigidity, tremor, apathy or other known symptoms associated with 
changes in Parkinson medication dosage.  
19.6. 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 patient 
selection criteria, close monitoring of the patient's physiologic status during research 
procedures and/or follow-ups, and by promptly supplying BSC with all pertinent information 
required by this protocol.  
All efforts will be made to minimize the aforementioned potential risks using the following 
approaches: 
• Selection of Investigators who are experienced and skilled in the treatment of patients 
with Parkinson’s Disease as per BSC’s site selection and qualification procedures; 
• Physician judgment may be used to eliminate, halt, reduce, or avoid testing that may pose 
a greater risk to a patient. 
• Clearly defined inclusion and exclusion criteria that ensure only appropriate patients are 
enrolled; 
• Ensuring that follow-up of patients is consistent with current medical practice; 
• Safety review processes; 
• Frequent monitoring visits to investigational sites. 
19.7. Anticipated Benefits 
While it is uncertain if a patient will experience significant benefit from study participation, 
it is possible that a more effective DBS programming setting than with conventional 
programming approaches or cylindrical electrodes can be identified. 
19.8. Risk to Benefit Rationale 
The purpose of this study is to compile characteristics of real-world outcomes for Boston 
Scientific Corporation’s commercially approved Vercise™ PC System for DBS, when used 
according to the applicable Directions for Use. The mechanism of action of the Vercise™ PC 
System is the same as other commercially available DBS systems.  Based on the clinical data 
for BSC’s approved Vercise™ DBS system, Medtronic’s approved Activa DBS System, and 
St Jude’s approved Infinity DBS system, the risk-to-benefit ratio for BSC Vercise™ DBS 
System is within reason for foreseeable risks.  However, studies do not always predict all 

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side effects that may be experienced. Observation and follow-up of all patients is required as 
outlined in the protocol. 
20. Safety Reporting 
20.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories: 
• All Serious Adverse Events 
• All  Device Related Adverse Events 
• All Study Procedure Related Adverse Events 
• Unanticipated Serious Adverse Device Effects 
• New findings/updates in relation to already reported events 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any AE required by the protocol, experienced by the study patient after informed consent 
and once considered enrolled in the study (as defined in study patient classification section), 
whether during or subsequent to the procedure, must be recorded in the CRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity of 
frequency during the course of the investigation. Death should not be recorded as an AE, but 
should only be reflected as an outcome of ONE (1) specific SAE (see Error! Reference 
source not found. for AE definitions). 
Refer to Section 19 for the known risks associated with the study device(s). 
20.2. Definitions and Classification 
Adverse event definitions are provided in Error! Reference source not found.. 
Administrative edits were made to combine definitions from ISO 14155-2011 and MEDDEV 
2.7/3 (2015). 
 
Table 20.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155-2011 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
patients, users or other persons, whether or not related to the 
investigational medical device.  

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Table 20.2-1: Safety Definitions 
Term 
Definition 
Ref: MEDDEV 2.7/3 (2015) 
 
 
NOTE 1: This includes events related to the investigational medical 
device or comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
Adverse event related to the use of an investigational medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies 
or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
Adverse event that: 
• Led to death, 
• Led to  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 prolongation of existing hospitalization 
, or 
o in medical or surgical intervention to prevent life-threatening illness 
o 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 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
 
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
 
 
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 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in 
the risk analysis report. 
Device Deficiency 
An inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 

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Table 20.2-1: Safety Definitions 
Term 
Definition 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3 (2015) 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
 
 
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 Error! Reference source not 
found.Error! Reference source not found. for AE definitions).  
Refer to Section 19 for the known risks associated with the study device(s). 
NOTES: 
• 
For the purposes of this study, hospitalization is defined as any in-patient admission. 
• 
Hospitalizations occurring for the purpose of performing a planned procedure as per 
routine/standard of care such as programming sessions or standard evaluation, staged 
implant procedures or rehabilitation are NOT to be reported as a SAE. 
• 
Any complications or adverse events that occur during an elective/planned 
hospitalization, should be reported if they meet the protocol specified definitions. 
However, the original elective/planned hospitalization(s) should not be reported as an 
SAE. 
• 
Sensations or side effects that occur during programming should not be reported as AEs. 
However, persistent unpleasant sensations or side effects caused that occur after the 
completion of programming will be reported. 
• 
Ineffective therapy (e.g. lack of efficacy, lack or decrease of therapeutic response) will 
not be collected as an adverse event, since failure to achieve therapeutic response is an 
issue of efficacy, not safety.  No AE of “Ineffective Therapy” should be reported when 
using the expanded parameter range for purposes of improving ineffective therapy. 
However, AEs due to sudden loss of efficacy (e.g. loss of stimulation leading to a fall or 
injury) will be collected. 
• 
The subject’s Parkinson Disease symptoms will not be collected as AEs, unless they 
have worsened beyond baseline and beyond the expected disease progression over time. 
This worsening event could occur in the context of a device malfunction or with a 
properly-functioning device as determined by investigator. 
• 
Device migration will not be collected as an adverse event. However, an AE that results 
from the device/lead migration should be reported as an AE. Device migration should be 
reported as a device deficiency.  

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20.3. Relationship to Study Device(s) 
The Investigator must assess the relationship of the AE to the study device (hardware and 
stimulation) or procedure. See criteria in Table 20.3-1:  

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Table 20.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
 
Relationship to the device or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
- the event has no temporal relationship with the use of the investigational device or 
the procedures; 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the 
device or procedure; the serious event can be attributed to another cause (e.g. an 
underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the investigational device 
used for diagnosis, when applicable; harms to the patient are not clearly due to use 
error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Unlikely Related 
The relationship with the use of the device seems not relevant and/or the event can 
be reasonably explained by another cause, but additional information may be 
obtained. 
Possibly Related 
The relationship with the use of the investigational device is weak but cannot be 
ruled out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/ clinical condition or/and an effect of another device, drug or 
treatment). Cases were relatedness cannot be assessed or no information has been 
obtained should also be classified as possible. 
Probably Related 
The relationship with the use of the investigational device seems relevant and/or 
the event cannot reasonably explained by another cause, but additional information 
may be obtained. 

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Table 20.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Causal Relationship 
The serious event is associated with the investigational device or with procedures 
beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with investigational device use/application 
or procedures; 
- the event involves a body-site or organ that 
o the investigational device or procedures are applied to; 
o the investigational device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the patient is due to error in use; 
- the event depends on a false result given by the investigational device used for 
diagnosis, when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious event. 
 
Adverse events must be assessed according to their relationship to one of the following 
categories: 
• Device Hardware-Related AEs: AEs that can reasonably be attributed to the mere 
physical presence of the device or to deficiency of the device (i.e., an allergic 
response to device materials).  
• Stimulation-Related AEs: AEs that can reasonably be attributed to the effects of 
stimulation. A relationship to stimulation may be determined by demonstrating a 
predictable response to the alternating between stimulation-on and stimulation-off 
settings.  However, a relationship to stimulation may also be reported without 
demonstrating a predictable response to the alternating between the stimulation-on 
and stimulation-off settings if in the opinion of the Investigator the AE is potentially 
related to stimulation. 
• Study Surgical Procedure Related AEs: AEs that can reasonably be attributed to a 
study protocol required surgical procedure. 

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20.4. Investigator Reporting Requirements  
The communication requirements for reporting to BSC are as shown in Table 20.4-1. All 
protocol required safety reporting may be reported to Boston Scientific via phone, fax or 
email. 
 
The investigator must report Adverse Device Effects, Serious Adverse Events (regardless of 
relationship to device hardware, stimulation and/or study procedure), Unanticipated Serious 
Adverse Device Effects, and Device Deficiencies for each subject from the time of Informed 
Consent through the end of study participation.  
 
 
 
Table 20.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline post-market studies*  
(MEDDEV 2.12/2 rev.2 (2012):  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Unanticipated Serious 
Adverse Device Effect  
 
Complete AE CRF page 
with all available new and 
updated information.  
 
• Within 1 business day of first becoming aware of 
the event. 
• Terminating at the end of the study 
Serious Adverse Event  
Complete AE CRF page 
with all available new and 
updated information.  
• Within 10 business days after becoming aware of 
the event or as per local/regional regulations. .  
• Reporting required through the end of the study 
Provide all relevant source 
documentation 
(unidentified) for reported 
event upon request of the 
sponsor 
• When documentation is available 
Serious Adverse Device 
Effects 
Complete AE CRF page 
with all available new and 
updated information. 
• Within 2 business days of first becoming aware of 
the event or as per local/regional regulations. 
• Reporting required through the end of the study 
Provide all relevant source 
documentation 
(unidentified) for reported 
event 
• When documentation is available 
Device Deficiencies 
(including but not limited 
to failures, malfunctions, 
and product 
nonconformities) 
Note:  Any 
Investigational Device 
Deficiency that might 
have led to a serious 
Complete device deficiency 
form with all available new 
and updated information.  
• Within 2 business days of first becoming aware of 
the event. Reporting required through the end of 
the study 

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Event Classification 
Communication Method  
Communication Timeline post-market studies*  
(MEDDEV 2.12/2 rev.2 (2012):  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
adverse event if a) 
suitable action had not 
been taken or b) 
intervention had not been 
made or c) if 
circumstances had been 
less fortunate is 
considered a reportable 
event. 
Adverse Device Effects 
Complete AE CRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness 
and relationship to the 
device.  
• In a timely manner  (e.g. recommend within 30 
business days) after becoming aware of the 
information 
• Reporting required through the end of the study 
• Reporting required for procedure, hardware and 
stimulation related adverse events. 
Abbreviations: AE=adverse event; CRF=case report form;  
*Please note that post-market studies are clinical studies where the  medical devices used in the study bear the 
regulatory approval and are used for the same approved indications 
20.5. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, 
product nonconformities, and inadequacy in the information supplied by the manufacturer) 
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 failures and malfunctions should 
also be documented in the patient’s medical record. 
Device deficiencies (including but not limited to failures, malfunctions, and product 
nonconformities) are not adverse events. However, an adverse event that results from a 
device failure or malfunction would be recorded as an adverse event on the appropriate CRF. 
Any Device Deficiency that might have led to a serious adverse event if a) suitable action 
had not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate is considered a reportable event. 
20.6. Reporting to Regulatory Authorities / ECs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the EC, and regulatory authorities of 
USADE and SAE as required by local/regional regulations. 

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20.7. Subject Death Reporting 
A subject death during the study should be reported to Boston Scientific as soon as possible 
and, in any event, within three (3) calendar days of site notification. The site’s EC must be 
notified of any deaths in accordance with that site’s EC policies and procedures.  
Notification of death must include a detailed narrative (death letter) that provides detailed 
information describing the circumstances surrounding the death. A death narrative in the 
local language is acceptable, if accompanied by a translation in English. The details listed 
below should be addressed in the death narrative, in order for BSC to understand the 
circumstance surrounding the death:  
• Date and time of death  
• Place death occurred  
• Immediate cause of death  
• Whether the death was related to the pulse generator, lead/catheter, clinical investigation, 
procedure, or patient condition  
• Whether or not the death was witnessed  
• Device status and/or activity at the time of death  
• Any other circumstances surrounding the death  
• Approximate time interval from the initiating event to death (temporal course)items to 
consider include, but are not limited to: information regarding last time subject was seen by 
investigator, last office visit, etc. 
• Investigator or sub-investigator signature and date  
 
Also submit the following documentation:  
If the patient expired in the hospital:  
• A copy of the medical records for that admission (e.g., H & P, consults, test results, 
operative reports, and/or progress notes from the hospital chart)  
• Death certificate (if available)  
• Autopsy report (if applicable)  
 
If the patient expired outside of the hospital (e.g., home):  
• A copy of the most recent clinic visit (if not already submitted to Boston Scientific)  
• Death certificate (if available)   
Whenever possible, the IPG should be interrogated. Investigational leads and related Boston 
Scientific system components (e.g., IPGs) should be removed intact and returned promptly to 
Boston Scientific for analysis.  
21. Informed Consent 
Patient participation in this clinical study is voluntary.  Informed Consent is required from 
each patient or his/her 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.  

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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 
accepted by BSC or its delegate (e.g. CRO), and approved by the site’s 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 site’s EC.  Any modification requires acceptance from BSC prior to use of the 
form.  The ICF must be in a language understandable to the patient and if needed, BSC will 
assist the site in obtaining a written consent translation. Translated consent forms must also 
have EC 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 at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• 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 patient’s 
decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of patients to participate, 
• not waive or appear to waive patient’s legal rights, 
• use native language that is non-technical and understandable to the patient or his/her legal 
representative, 
• provide ample time for the patient to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing patients throughout the 
clinical study.  
The ICF shall always be signed and personally dated by the patient or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the patient 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 site 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 patient 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. EC), as appropriate. 
If new information becomes available that can significantly affect a patient's future health 
and medical care, that information shall be provided to the affected patient(s) in written form 
via a revised ICF or, in some situations, enrolled patients may be requested to sign and date 

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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 applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the EC. The new version of the ICF must be approved by the EC. 
Acceptance by Boston Scientific is required if changes to the revised ICF are requested by 
the site’s EC. The EC will determine the patient population to be re-consented. 
22. Committees 
22.1. Safety Monitoring Process 
To promote early detection of safety issues, the Medical Director will provide evaluations of 
safety events. Success of this program requires dynamic collection of unmonitored data as 
soon as the event is reported. During regularly scheduled monitoring activities, clinical 
research monitors will support the dynamic reporting process through their review of source 
document and other data information.  
23. Suspension or Termination 
23.1. 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 patients.  Investigators, associated ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of study termination. 
23.1.1. 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 patients enrolled in the study. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
23.2. Termination of Study Participation by the Investigator or Withdrawal of EC 
Approval 
Any investigator or EC in the DIRECT-DBS Study may discontinue participation in the 
study or withdrawal approval of the study, respectively, with suitable written notice to 
Boston Scientific. Investigators, associated ECs, and regulatory authorities, as applicable, 
will be notified in writing in the event of these occurrences. 

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23.3. Requirements for Documentation and Patient 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 sites by Boston Scientific. The 
EC and regulatory authorities, as applicable, will be notified. Detailed information on how 
enrolled patients will be managed thereafter will be provided.  
In the event an EC terminates participation in the study, participating investigators, 
associated ECs, and regulatory authorities, as applicable, will be notified in writing. Detailed 
information on how enrolled patients will be managed thereafter will be provided by Boston 
Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility; detailed information on how enrolled patients 
will be managed thereafter will be provided by Boston Scientific. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the patients. 
23.4. Criteria for Suspending/Terminating a Study Site 
Boston Scientific Corporation reserves the right to stop the inclusion of patients at a study 
site at any time after the study initiation visit if no patients have been enrolled for a period 
beyond 3 months after site initiation, or if the site has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of site 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 patients. The EC and regulatory authorities, as applicable, will be notified. 
All patients enrolled in the study at the site will continue to be followed per standard of care. 
The Principal Investigator at the site must make provision for these follow-up visits unless 
BSC notifies the investigational site otherwise. 
24. Publication Policy 
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. 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. 

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• 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.  
25. Reimbursement and Compensation for Patients 
25.1. Patient Reimbursement 
Travel and other expenses incurred by patients as a result of participation in the study will be 
reimbursed in accordance with pertinent country laws and regulations and per the study site’s 
regulations.   
25.2. Compensation for Patient’s Health Injury 
Boston Scientific Corporation will purchase an insurance policy to cover the cost of potential 
health injury for study patients, and if required by applicable law.  
26. Bibliography 
1. 
World Health Organization. The Global Burden of Disease: 2004 Update. Available 
from: http://www.who.int. 
2. 
de Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006 
Jun;5(6):525-35. 
3. 
DeLong M, Juncos JL. "Chapter 366. Parkinson's Disease and Other Extrapyramidal 
Movement Disorders" (Chapter). In: Fauci A, Braunwald E, Kasper D, Hauster S, 
Longo D, Jameson J, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 
17th ed: McGraw-Hill Companies, Inc.; 2008. 
4. 
Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, Larsen 
JP, Lees A, Oertel W, Poewe W, Rascol O, Sampaio C. Review of the therapeutic 
management of Parkinson's disease. Report of a joint task force of the European 
Federation of Neurological Societies and the Movement Disorder Society-European 
Section. Part I: early (uncomplicated) Parkinson's disease. Eur J Neurol. 2006 
Nov;13(11):1170-85. 
5. 
Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, Hallett 
M, Miyasaki J, Stevens J, Weiner WJ. Practice Parameter: treatment of Parkinson 
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Wojtecki L, Wolf E, Poewe W, Voges J. A randomized trial of deep-brain stimulation 
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Blond S, Burbaud P, Bioulac B, Destee A, Cornu P, Pollak P. Clinical and economic 
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27. Abbreviations and Definitions  
27.1. Abbreviations 
Abbreviations are shown in Error! Reference source not found..   
Table 27.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
AE 
Adverse Event 
BSC 
Boston Scientific Corporation 
BSN 
Boston Scientific Neuromodulation 
CA 
Competent Authority 
CDRS 
Clinical Dyskinesia Rating Scale 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DBS 
Deep Brain Stimulation 
DFU 
Directions for Use 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
ETS 
External Trial Stimulator 
FDA 
Food and Drug Administration 
GLNT 
Great Lakes NeuroTechnologies 
HCP 
Health Care Personnel 
ICF 
Informed Consent Form 
ICH 
International Committee on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
IEC 
Independent Ethics Committee 
IPG 
Implantable Pulse Generator 
IRB 
Institutional Review Board 
ISO 
International Standards Organization 
ITT 
Intent-To-Treat 
mA 
milliamps 
MEDDEV 
Medical Device Directives 
PC 
Primary Cell 
PD 
Parkinson’s disease 
PDQ 
Parkinson’s disease Questionnaire 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
STN 
Subthalamic nucleus 
UADE 
Unanticipated Adverse Device Effect 
UPDRS III 
Unified Parkinson Disease Rating Scale version 3.0, subsection III 

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27.2. Definitions 
Terms are defined in Error! Reference source not found..  
Table 27.2-1: Definitions 
 
Term 
 
Definition 
Activation 
The process of turning on the implantable pulse generator (IPG) 
for the first time after implant and the programming of 
stimulation parameters. 
CE Mark 
The CE mark, or formerly EC mark, is a mandatory conformity 
marking for certain products sold within the European Economic 
Area (EEA) since 1985. 
Enrollment 
A patient is considered to be enrolled as a research subject in the 
study after informed consent is obtained. 
Monopolar review 
A process where the therapeutic window for each contact is 
determined, i.e., measurement of efficacy and side effect 
thresholds. 
Ring Mode 
A restriction to device programming where any stimulation 
delivered is omnidirectional (i.e. all contacts in each directional 
row have the same amplitude of current being delivered). 
Source Data 
All information in original records of clinical findings, 
observations, or other activities in a clinical investigation, 
necessary for the reconstruction and evaluation of the clinical 
investigation. 
Source Document 
Printed, optical or electronic document containing source data. 
Examples: Hospital records, laboratory notes, device 
accountability records, photographic negatives, radiographs, 
records kept at the investigation site, at the laboratories and at the 
medico-technical departments involved in the clinical 
investigation. 
Unrestricted Mode 
A programming mode without restrictions, used opposite of Ring 
Mode in the Crossover Phase of the study. 
Vercise™ PC 
The Vercise™ PC DBS system manufactured by Boston 
Scientific Neuromodulation 

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Table 27.2-1: Definitions 
 
Term 
 
Definition 
Abbreviations are defined in Error! Reference source not found.