A Post Market Observational Cohort Study to Assess the Performance of the Spinal Modulation Dorsal Root Ganglion Stimulator System for the Management of Chronic Post Surgical Pain
Conditions: Chronic Post Surgical Pain
Sponsor: Abbott Medical Devices

 
 
 
Clinical Investigation Plan Cover Page 
 
 
 
 
 
 
 
 
 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott. 
87173 CIP Posting Cover Page Ver B 
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Page 1 of 1
 
NCT Number: NCT02335229 
NL Post Surgical 
A Post Market Study to Assess the Spinal Modulation Dorsal Root Ganglion  
Stimulator System in Chronic Post Surgical Pain 
Study Document No: 20-SMI-2013 
Version 2.0 
Date: 24-May-2013 
 
 
Sponsor  
 
 
Abbott 
        
 
 
SJM Coordination Center BVBA 
The Corporate Village 
Da Vincilaan 11 Box F1 
1935 Zaventem, Belgium 
 

20-SMI-2013 
 
 
DRG Stimulation 
Proprietary Information: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Spinal Modulation, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A Post Market Observational Cohort Study  to 
Assess the Performance of the Spinal 
Modulation Dorsal Root Ganglion 
Neurostimulator System for the Management of 
Chronic Post Surgical Pain 
 
 
 
Protocol 20-SMI-2013 
 
 
 
Spinal Modulation 
1135 O’Brien Dr. 
Menlo Park, CA 94025 
USA

20-SMI-2013 
 
 
DRG Stimulation 
Proprietary Information: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Spinal Modulation, Inc. 
 
 
 
A Post Market Observational Cohort Study to Assess the Performance of the Spinal 
Modulation Dorsal Root Ganglion Neurostimulator System for the Management of 
Chronic Post Surgical Pain  
 
Protocol ID 
20-SMI-2013 
Short title 
Performance of the Spinal Modulation DRG 
Neurostimulator System 
Version 
Version 2.0 
Date 
24 May 2013 
 
Principal investigator 
 
Prof. Dr. Dr. M. W. Hollmann, MD, DEAA 
Department of Anesthesiology,  
Academic Medical Centre,  
University of Amsterdam,  
Meibergdreef 9,  
Postbus 22660  
H1Z-120,  
 
1100 DD Amsterdam,  
The Netherlands 
Phone:  +31 20 566 3630 
              +31 20 566 2533 (Secr.) 
Fax:       +31 20 697 9441 
e-mail:   m.w.hollmann@amc.uva.nl 
 
 
Coordinating investigator / 
project leader 
 
 
Dr. F. Wille, MD, FIPP,  
Department of Anesthesiology,  
Academic Medical Centre,  
University of Amsterdam,  
Meibergdreef 9,  
Postbus 22660  
1100 DD , Amsterdam 
Phone:   +31 20 566 9111  
Fax:        +31 20 697 9441 
e-mail:    f.wille@amc.uva.nl 
 

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Proprietary Information: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Spinal Modulation, Inc. 
 
 
 
Study Investigator 
Jennifer Breel RN, MPA 
Diakonessenhuis Zeist 
Internal postbox 53 
Postbox 1002 
3700 BA, Zeist 
The Netherlands 
Phone:  +31 88 250 5037 
Fax:       +31 88 250 9236 
e-mail:    jbreel@diakhuis.nl 
 
 
Sponsor 
 
Spinal Modulation 
1135 O’Brien Dr. 
Menlo Park, CA 94025 
USA 
 

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Proprietary Information: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Spinal Modulation, Inc. 
 
 
 
PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Sponsor Clinical Representative: 
 
Jeffery Kramer, PhD 
Chief Scientific Officer 
Vice President, Clinical Field Operations 
 
 
 
 
Principal Investigator: 
 
Professor M.W. Hollmann 
 
 
 
 
 
 
 

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Proprietary Information: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Spinal Modulation, Inc. 
 
 
 
TABLE OF CONTENTS 
 
1. 
INTRODUCTION AND RATIONALE ............................................................................... 10 
2. 
OBJECTIVES .................................................................................................................. 12 
3. 
STUDY DESIGN ............................................................................................................. 12 
4. 
STUDY POPULATION .................................................................................................... 14 
4.1 
Population  .............................................................................................................. 14 
4.2 
Inclusion criteria ...................................................................................................... 14 
4.3 
Exclusion criteria..................................................................................................... 14 
4.4 
Sample size calculation .......................................................................................... 15 
5. 
TREATMENT OF SUBJECTS ........................................................................................ 15 
5.1 
Treatment ............................................................................................................... 15 
5.2 
Use of co-intervention ............................................................................................. 15 
6. 
DESCRIP!ION OF THE DEVICE................................................................................ 14 
6.1 
Name and descrip!ion of neurostimulator system ................................................... 14 
6.2 
Summary of known and potential risks and benefits .............................................. 14 
6.3 
Device utilization ..................................................................................................... 16 
6.4 
Devices ................................................................................................................... 16 
7. 
METHODS ...................................................................................................................... 16 
7.1 
Assessments .......................................................................................................... 16 
7.2 
Randomisation, blinding and treatment allocation .................................................. 16 
7.3 
Study procedures ................................................................................................... 16 
7.4 
Withdrawal of individual subjects ............................................................................ 20 
7.5 
Replacement of individual subjects after withdrawal .............................................. 20 
7.6 
Follow-up of subjects withdrawn from treatment .................................................... 21 
7.7 
Premature termination of the study......................................................................... 19 
8. 
SAFETY REPORTING .................................................................................................... 19 
8.1 
Applicable local laws and regulations ..................................................................... 19 
8.2 
Adverse and serious adverse events...................................................................... 21 
8.3 
Follow-up of adverse events ................................................................................... 22 
8.4 
Data Safety Monitoring Board (DSMB) ................................................................... 24 
9. 
STATISTICAL ANALYSIS ............................................................................................... 24 
9.1 
Descrip!ive statistics ............................................................................................... 24 
9.2 
Analysis .................................................................................................................. 23 
10. 
ETHICAL CONSIDERATIONS ................................................................................... 25 
10.1 
Regulation statement .............................................................................................. 25 
10.2 
Recruitment and consent ........................................................................................ 23 
10.3 
Benefits and risks assessment ............................................................................... 26 
10.4 
Compensation for injury .......................................................................................... 24 
10.5 
Compensation ........................................................................................................ 24  
11. 
ADMINISTRATIVE ASPECTS AND PUBLICATION .............................................. 25 
11.1 
Handling and storage of data and documents ........................................................ 25 

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Proprietary Information: This document and the information contained herein may not be reproduced, used or 
disclosed without written permission from Spinal Modulation, Inc. 
 
 
 
11.2 
Amendments .......................................................................................................... 25 
11.3 
Annual progress report ........................................................................................... 25 
11.4 
End of study report ................................................................................................. 26 
11.5 
Public disclosure and publication policy ................................................................. 26 
12. 
REFERENCES ........................................................................................................... 28 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS 
 
 
AE 
Adverse Event 
AIMDD 
Active Implantable Medical Devices Directive 
BPI 
Brief Pain Inventory 
BSI 
British Standard Institution 
CE mark 
Conformité Européenne (In accordance to European Regulations) 
CIBG 
executive agency of the Dutch Ministry of Health, Welfare and Sport 
CRF 
Case Report Form 
CRPS 
Complex Regional Pain Syndrome 
CV 
Curriculum Vitae 
DSMB 
Data Safety Monitoring Board 
DRG 
Dorsal Root Ganglion 
EQ-5D 
© 1987 EuroQol Group. EQ-5D™ is a trade mark of the EuroQol Group   
EU 
European Union 
FBSS 
Failed Back Surgery Syndrome 
FU 
Follow Up 
GCP 
Good Clinical Practice 
INS 
Implantable Neuro Stimulator 
ISO 
International Organisation for standardisation 
REC 
Research Ethical Committee 
SAE 
Serious Adverse Event 
SAS 
Statistical Analysis System 
SCS 
Spinal Cord Stimulation 
Sponsor 
The party that commissions the organisation or performance of the research 
SPSS 
Statistical computer program 
TNS 
Trial Neuro Stimulator 
VAS            Visual Analogue Scale 
 
 

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SUMMARY 
 
Rationale: Initial clinical studies have shown that stimulation of the Dorsal Root Ganglion 
(DRG) can significantly reduce chronic intractable pain. These results have supported the CE 
marking of the Spinal Modulation Neurostimulator system in the management of chronic 
pain. Following the requirements of the AIMDD, Spinal Modulation will also collect clinical 
data on the commercially available Neurostimulator System.  
 
Objective: The purpose of this Post Market Observational Cohort Study is to evaluate the 
commercially available Spinal Modulation DRG Neurostimulator system, in the management 
of chronic post-surgical pain, in patients whom are routinely scheduled to receive a Spinal 
Modulation Neurostimulator system.  
 
Study design: This is a prospective, single-arm, multi -centre, post market observational 
cohort study to collect data on pain relief, quality of life, physical functioning, subject safety, 
and subject satisfaction.  
 
Device: Commercially available Spinal Modulation DRG Neurostimulator System for the 
management of chronic intractable pain (CE 567069).  
 
Study population: Males and females of at least 18 years of age, suffering from chronic 
post surgical pain for at least 6 months, whom are routinely scheduled to receive a 
commercially available Spinal Modulation DRG Neurostimulator System. 
 
Intervention: For the post market observational cohort study, the subjects will be asked to 
complete the standard evaluation questionnaires at baseline. Under monitored anaesthesia 
care, subjects will undergo minimally invasive placement of leads in the lateral epidural 
space of the neural foramen, following standard procedures. Subjects who have a successful 
trial will be implanted with the internal neurostimulator (INS) and will be followed for 24 
months. They will be asked to complete questionnaires at the follow-up visits as per standard 
follow-up neuromodulation care in the Netherlands. 
 
Follow-up visits: The patients will visit the hospital for the following standard follow-up (FU) 
visits: Baseline, Trial NeuroStimulator procedure, End of Trial, INS implant, 1 week, 1, 3, 6, 
12 and 24 months post-operatively. If necessary, the site may contact the patients 
telephonically at 8 weeks, 9 months and 18 months FU. 
 
Risks: There are no additional risks or burdens to the patients participating in this post 
market observational cohort study. The implantation of the system and collection of follow up 
data is a standard procedure in dedicated neuromodulation Pain Clinics in The Netherlands. 
The data collected consists of standard questionnaires on pain relief, quality of life, physical 
functioning, subject safety and subject satisfaction.  
 

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1 
INTRODUCTION AND RATIONALE 
History 
Neuromodulation for the treatment of chronic pain has been used for over a century1. The 
first use of electricity in the spine for neuromodulation of pain was conducted by Norm 
Shealy in 19672. The development of spinal cord stimulation (SCS) technology has grown 
rapidly in the past 40 years and is now used in over 40,000 new patients each year.  
 
Spinal Neuromodulation 
Several recent systematic reviews have provided evidence that stimulation technology is a 
safe and effective treatment option for patients suffering from chronic, intractable pain3-5. The 
rate of serious complications is relatively low3-5. The treatment has been found to be 
successful in approximately 50% of patients that have a positive stimulation trial period6,7. In 
the largest prospective trial published to date, Kumar and colleagues found a significant 
reduction in leg pain when compared to a conventional medical management control 
group6,8. In a similar manner, Kemler and colleagues found that SCS can be effective in the 
treatment of complex regional pain syndrome (CRPS)9-11. Despite varying levels of success 
in the literature, approximately 50% of patients will not receive adequate pain relief from 
traditional spinal cord stimulation. This suggests that alternative neuromodulation techniques 
are needed to improve pain relief in these patients.  
 
Therapy Description 
The Spinal Modulation Dorsal Root Ganglion Neuromodulation System consists of a two-
phase treatment process: 1) a temporary trial phase and 2) a permanent implant phase.  
The first phase involves implanting stimulation electrodes (or “leads”) into the epidural space, 
which are connected to an external Trial NeuroStimulator (TNS) to electrically stimulate the 
Dorsal Root Ganglion (DRG). If patients experience sufficient pain relief during this trial 
stimulation,  they will receive an Implantable NeuroStimulatior (INS) system (phase 2). 
 
Rationale 
The use of electrical neuromodulation techniques in the successful treatment of various pain 
conditions is a proven therapy. Research into the role of the DRG in the development and 
maintenance of chronic pain has led to the development of an electrical neurostimulator 
system which specifically targets the DRG. This protocol describes a post market 
observational cohort study to collect the outcome data of the new commercially available 
Spinal Modulation DRG Neurostimulator System. 

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This post market observational cohort study is set up to collect prospective data on the 
performance of the commercially available Spinal Modulation DRG Neurostimulator system 
in subjects routinely scheduled to receive this system for the management of chronic post-
surgical pain. 
 
 
 
  

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2 
OBJECTIVES 
 
The objective for this multi-centre post market observational cohort study is to assess the 
performance of the commercially available Spinal Modulation DRG Neurostimulator System 
in the management of chronic post-surgical pain. The performance will be measured using 
the following assessments: 
 
Primary Objective: 
 
Pain relief measured using a Visual Analogue Scale (VAS).  
 
Secondary Objectives: 
 
Quality of life (EQ-5D) 
 
Physical functioning (BPI) 
 
Pain distribution 
 
Paraesthesia distribution 
 
Sleep quality 
 
Subject satisfaction 
 
Device safety by monitoring  
 
Device settings and procedural data 
 
3 
STUDY DESIGN 
This study is a prospective, single-arm, multi-centre post market observational cohort study, 
designed to assess the clinical effects of the commercially available Spinal Modulation DRG 
Neurostimulator System, in the management of chronic post-surgical pain. Subjects that are 
routinely scheduled to receive DRG stimulation will be asked to participate in this 
observational cohort study. They will be screened based upon the standard inclusion and 
exclusion criteria for neuromodulation in The Netherlands. Informed Consent will be obtained 
and they will then be enrolled into the cohort. Baseline parameters will then be measured in 
subjects using standard questionnaires and according to standard neuromodulation practice. 
 
The study consists of two distinct phases in which the patients are asked to complete 
questionnaires, corresponding to the two-phase treatment process: 1) Temporary Trial 
Stimulation, and, 2) Implantable Stimulation (Figure 1).  
Subjects will “trial” an external neurostimulator system for a period of time in line with 
standard hospital practices but no longer than 30 days (phase 1). If subjects experience 
sufficient pain relief in their primary area of pain, according to current neuromodulation 
guidelines, they will be eligible to proceed with the second phase of the treatment. If the 

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eligible subjects agree to move forward into Phase 2, they will undergo another surgical 
procedure in which the Spinal Modulation implantable Neurostimulator will be implanted. 
Subjects will be seen for follow-up at 1 week, 4 weeks, 3 months, 6 months, 12 months and 
24 months following implantation (Figure 1). The site can contact the subjects telephonically 
for a follow-up at 8 weeks, 9 months and 18 months if desired (optional). 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Phase 1 – Temporary Trial Neurostimulation 
Following consent and entry into the post market observational cohort study, baseline 
parameters will be measured by means of the standard evaluation questionnaires used in 
The Netherlands 
 
Protocol Phase 2 – Implantable Stimulation and Follow Up 
If subjects experience sufficient pain relief in their primary area of pain during the TNS 
procedure or during the course of the trial phase, they will be eligible for INS implantation.  
Subjects will be followed for 24 months following implant, returning to the clinic at regular 
follow-up intervals (1 week, 4 weeks, 3 months, 6 months, 12 months and 24 months). 
Subjects have the option to return to the clinic at unscheduled times to have the device 
reprogrammed as needed or for other reasons. This can be captured as an interim visit. The 
site may contact the patients by phone at 8 weeks, 9 months and 18 months for follow-up 
(optional). 
 
Figure 1. Basic design and follow-up schedule for subjects enrolled into the post-market 
observational cohort study. Subjects who have consented and been enrolled will undergo a two-
phase process for advancement through the cohort. A detailed follow-up scheduled can be found in 
the Methods section. 

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4 
STUDY POPULATION 
4.1 Population  
30 male and female subjects, (minimum age 18 years old) suffering from chronic post- 
surgical pain, for a minimum of 6 months, whom are routinely scheduled for a DRG 
stimulation will be recruited by the study site and Investigators for inclusion in the cohort. 
 
Subjects must meet all of the inclusion and none of the exclusion criteria to be enrolled in 
the post market observational cohort study. Subjects will read and sign an informed 
consent prior to the treatment. Subjects will be recruited from the site’s existing patient 
population and through new patient contacts as normally progresses in standard clinical 
practice.  
 
4.2 Inclusion criteria  
1) Subject is at least 18 years old 
2) Subject is able and willing to comply with the follow-up schedule and protocol 
3) Chronic post surgical pain for at least 6 months  
4) Failed conservative treatments for chronic pain including but not limited to 
pharmacological therapy, physical therapy and interventional pain procedures for 
chronic pain 
5) Minimum baseline pain rating of 60 mm on the VAS in the primary region of pain 
6) Subject is able to provide written informed consent 
7) Pain medication dosage has been stable for at least 30 days 
8) Patient has been included for implantation according to standard criteria from the 
Dutch Neuromodulation Society 
 
4.3 Exclusion criteria 
1) Female subject of childbearing potential is pregnant/nursing, plans to become 
pregnant or is unwilling to use approved birth control  
2) Escalating or changing pain condition within the past month as evidenced by 
investigator examination 
3) Subject has had corticosteroid therapy at an intended site of stimulation within the past 
30 days 
4) Subject has had radiofrequency treatment of an intended target DRG within the past 3 
months 
5) Subject currently has an active implantable device including ICD, pacemaker, spinal 
cord stimulator or intrathecal drug pump 
6) Subject is unable to operate the device 
7) Subjects with indwelling devices that may pose an increased risk of infection 

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8) Subjects currently has an active infection 
9) Subject has participated in another clinical investigation within 30 days 
10) Subject has a coagulation disorder or uses anticoagulants that, in the opinion of the 
investigator, precludes participation 
11) Subject has been diagnosed with cancer in the past 2 years. 
12) Patient has no other exclusion criteria according to standard criteria from the Dutch 
Neuromodulation Society 
 
4.4 Sample size calculation 
As this is a post market observational cohort study, no sample size calculations are 
necessary. We aim to enrol 30 subjects in this cohort. 
 
 
5 
TREATMENT OF SUBJECTS 
5.1 
Treatment 
The Physician Implant Manual provides a detailed description of the implant and surgical 
technique. Following informed consent and baseline measurements, subjects will begin 
phase one of a two-phase treatment process. Phase 1 is the Trial Phase and consists of 
percutaneously implanting neurostimulator leads into the epidural space and connecting 
them to an external neurostimulator. This system is then “trialed” for a period of time not 
to exceed 30 days. If the subject achieves sufficient pain relief in their primary area of 
pain according to Dutch Neuromodulation criteria during the trial phase, they will progress 
to Phase 2, the implantation phase. In this phase, the implanted leads will be connected 
to an implantable neurostimulator. The entire system is implanted under the skin for the 
duration of device use. The therapy is fully reversible and the leads and device can be 
removed through a similar procedure. 
 
 5.2 Use of co-intervention  
Subjects may continue using medication for the treatment of their pain condition. The 
prescription of medication for pain will be dictated by the Pain Specialist according to 
standard care. 

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6 
Description of the Device 
6.1 Name and description of Neurostimulator System 
 
The Spinal Modulation Neurostimulator System consists of the following components: 
- 
Trial Neurostimulator 
- 
Implantable Neurostimulator 
- 
Trial Lead Kit 
- 
Implant Lead Kit 
- 
Connector Cable Kit 
- 
Tunneling Tool Kit 
- 
Clinical Programmer 
- 
Patient Programmer 
- 
Auxillary Magnet Kit 
- 
Programmer Charger Kit 
- 
Programmer Carrying case 
- 
Lead Accessories Kit 
- 
22 cm Small Curve Delivery Sheath Kit 
- 
22 cm Big Curve Delivery Sheath Kit 
- 
Lead Extension Kit 
 
 
A detailed description of the components can be found in the physician implant manual. 
 
On 16 November 2011, BSI granted Spinal Modulation, Inc. a CE mark for the Spinal 
Modulation DRG Neurostimulator System for the Management of Chronic Intractable 
Pain (CE 567069). The system has been notified to the CIBG in the Netherlands on 24 
November 2011.  
 

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6.2 
Summary of known and potential risks and benefits 
A summary of the known and potential risks and benefits can be found in the 
accompanying manuals that are included in the packaging of the components. The 
general risks associated with the Spinal Modulation DRG Neurostimulator System are 
similar to those associated with other currently approved Spinal Cord Stimulator systems. 
Possible risks to the subjects include both device and procedural based risks. The most 
common side effects and risks are: 
 
Pain (where the needle is to be inserted) 
 
Pain caused by understimulation due to lead migration 
 
Pain over the implantable neurostimulator site (only applicable in Phase 2) 
 
Escalating pain 
 
Bleeding (where the needle has been inserted) 
 
Headache 
 
Infection 
 
Localized collection of serous (clear) fluid at injection site 
 
Discomfort during the treatment 
 
Allergic or rejection response to implant materials 
 
Constant pain at the lead site 
 
Stimulation of the chest wall 
 
Lead migration (movement) and/or local skin breakage 
 
Weakness 
 
Clumsiness 
 
Numbness 
 
Temporary muscle activation 
 
Very rare risks and side effects include: 
 
 
Cerebral Spinal Fluid (CSF) leakage 
 
Tissue damage 
 
Nerve damage 
 
Spinal cord compression  
 
Swelling 
 
Paralysis  
 
Hematoma  
 
Seroma  
 
Sensory loss  
 
Skin erosion around the INS or leads 
 
Battery failure and/or battery leakage 
 
Lead breakage requiring replacement of the lead 
 
Hardware malfunction requiring replacement of the neurostimulator  
 
Pain from a non-injurious stimulus to the skin (allodynia) 
 
An exaggerated sense of pain (hyperesthesia) 
 
 
 

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6.3 
Device utilization 
 
A detailed description of device utilization can be found in the Physican Implant Manual. 
All investigators involved in the study have been trained on the use of the Spinal 
Modulation DRG Neurostimulator System and already have experience in the use of the 
commercially available products. 
 
6.4 
Devices  
The devices that will be used in the post market observational cohort study are 
commercially available products and will be bought and paid for according to the 
standard hospital system. Serial and lot numbers of the products used will be added to 
the patient files to document and identify the devices.  
 
 
7 
Methods 
7.1 
Assessments 
During the scheduled follow-ups the following measurements will be performed. Table 1 
in appendix A gives a detailed description of the measurements per follow-up. 
 
Pain relief (VAS) 
 
Quality of life (EQ-5D) 
 
Physical functioning (BPI) 
 
Pain distribution 
 
Paresthesia Distribution  
 
Sleep quality 
 
Subject satisfaction  
 
Device safety 
 
Device settings and procedural information 
 
7.2 Randomisation, blinding and treatment allocation 
As this is an observational study, no randomisation or blinding will occur. All subjects will 
be receiving the Spinal Modulation DRG Neurostimulator System and data will be 
collected at each follow-up time point. 
 
7.3 Study procedures 
During the post market observational cohort study, data will be collected on Case Report 
Forms (CRFs). A copy of the CRFs will be provided for review.  
 

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Subject Screening and baseline 
Subjects presenting with chronic post-surgical pain for at least 6 months will be screened 
for possible entry into the post market observational cohort study. Subjects will be 
screened according to the Inclusion/Exclusion criteria and only subjects meeting all 
Inclusion criteria and none of the Exclusion criteria will be enrolled. The post market 
observational cohort study will be explained to all subjects and subjects will provide 
informed consent prior to any data collection for the study. Subjects will be allowed to 
discuss their participation in the cohort with the study physician, clinical staff, family, 
friends and personal or external physician.  
 
Following subject screening and acquisition of Informed Consent, subjects will undergo a 
baseline assessment to collect clinical data prior to lead implantation and stimulation.  
 
Trial Stimulation Lead Implant Procedure 
Following collection of baseline measurements, subjects will begin Phase 1 of the two-
step treatment process.  
 
End of TNS Trial Phase  
At the end of the Trial Phase, pain relief will be assessed to determine whether a subject 
should receive an INS implant. The duration of the trial will be at the investigators 
discretion and in line with current clinical practice.  This may be done in the theatre during 
the TNS procedure or after an extended trial period but should be no longer than 30 
days. 
  
INS Implant Procedure 
Eligible subjects willing to continue with the implant will undergo surgery to implant the 
internal neurostimulator (INS). If the subdural leads are removed during the trial period, 
new leads will also be implanted at this time (see Physician Implant Manual for detailed 
information regarding the procedure). Each subject will receive a hand-held Patient 
Programmer that can be used to adjust stimulation amplitude as needed. 
 
 

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Regular Follow-ups 
Subjects will be followed according to the standard follow-up schedule for 24-months 
following implant at regular intervals: 1-week (±5 days), 4 weeks (±1 week), 3 month (±2 
weeks), 6 month (±2 weeks), 12 months (±2 weeks) and 24 months (±2 weeks). The 
given time-windows are advisable and therefore visits outside the time windows will not 
be seen as a protocol deviation. If desired, the Investigators may contact the subjects 
telephonically for evaluations at 8-weeks, 9-months and 18 months post-implant.  
 
Prior to completing the required measurements, the subject will have his/her stimulator 
reprogrammed if needed or applicable. 
 
 
 
24-month follow-up (Study Exit) 
The study will end 24 months following INS implantation. At this visit, the regular follow-
up assessments as outlined in appendix A will be acquired and a trial exit form will be 
completed.  
Following completion of the study, subjects will continue to use the Spinal Modulation 
DRG Neurostimulator System. They will be monitored by their physician in accordance 
with standard medical procedures.  
 
Interim Programming/Revision/Replacement/Explant (if necessary) 
During the course of the cohort, subjects will have the option to return to the study site at 
any time to have their neurostimulator re-programmed to achieve maximal benefit. If any 
part of the Spinal Modulation Neurostimulator System becomes dysfunctional or requires 
adjustment following implantation, the patient will come to the site for analysis of the 
problem (interim visit). In appendix A, the assessments are listed for an interim visit and a 
revision (if applicable). 
 
7.4 Withdrawal of individual subjects 
Subjects can leave the study at any time for any reason without any consequences. The 
investigator can decide to withdraw a subject from the study for urgent medical reasons. 
 
7.5 Replacement of individual subjects after withdrawal 
Subjects that are withdrawn during the study will not be replaced. 
 

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7.6 Follow-up of subjects withdrawn from treatment 
Any patient leaving the study will receive standard follow-up care in accordance with the 
criteria of the Dutch Neuromodulation Society. 
 
7.7 Premature termination of the study 
The Post Market Observational Cohort Study will be terminated prematurely if the 
Investigators feel there is a risk to the subjects enrolled. Subject safety will continue to be 
monitored by the Investigators for the duration of the device.  
 
 
8 
SAFETY REPORTING 
8.1 
Applicable local laws and regulations 
All AEs and SAEs will be reported according to the applicable local laws and regulations 
for CE marked products 
8.2 
Adverse and serious adverse events 
Adverse events are defined as any undesirable experience occurring in a subject during 
the study, whether or not considered to be related to the Spinal Modulation DRG  
Neurostimulator System. All adverse events reported spontaneously by the subject or 
observed by the investigator or his staff will be recorded. 
 
Adverse events related to the commercially available Spinal Modulation DRG 
Neuromodulation System will be reported to Spinal Modulation representatives and 
handled according to the Spinal Modulation internal vigilance regulations for CE marked 
products. 
 
Clinical study staff will start assessing subjects for adverse events (AEs) once the 
Informed Consent form has been signed and at each visit thereafter. They will be 
instructed to request AE information in a nonspecific, non-suggestive manner. 
Investigators will report all AEs regardless of causality. 
 

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Serious Adverse Events (SAE): 
A serious adverse event is any untoward medical occurrence or effect that:  
- 
results in death; 
- 
is life threatening (at the time of the event); 
- 
requires hospitalization or prolongation of existing inpatients’ hospitalization; 
- 
results in persistent or significant disability or incapacity; 
- 
is a congenital anomaly or birth defect; 
- 
is a new event in the cohort likely to affect the safety of the other study subjects, such 
as an unexpected outcome of an adverse reaction, major safety finding from a newly 
completed animal study, etc. 
 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.   
 
For the purposes of this study the following events will not be reported as serious 
adverse events due to the nature of the treatment. 
 
Prolonged hospitalization as a result of a revision procedure, which is allowed in the 
protocol. 
 
Hospitalization as a result of or in conjunction with treatment that is part of the 
subject’s conventional medical management. 
 
All SAEs must be reported within 24 hours of the investigational site’s knowledge of the 
occurrence by entering the required information into the appropriate CRF. 
 
The following SAE information will be provided as available: 
 
Patient ID; 
 
SAE term, onset date, severity, and causal relationship; 
 
Basic demographic information (e.g., age, gender, etc.); 
 
The outcome(s) attributable to the event (death, life-threatening, inpatient 
hospitalization or prolongation of existing hospitalization, persistent or significant 
disability/incapacity, congenital anomaly/birth defect or other important medical 
event(s)); 
 
A summary of relevant test results, pertinent laboratory data, and any other relevant 
medical history; 

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 
Date study device was implanted; 
 
Supplemental information may include, but may not be limited to, the following 
records: laboratory results, progress notes, admission and emergency room notes, 
discharge summaries, autopsy reports, death certificates, etc. 
 
The Investigator will report all SAEs in accordance with the regulatory reporting 
requirements. Documentation will be provided to the sponsor. 
 
 
For each AE or SAE the following information will be recorded on the appropriate CRF: 
 
Name of event: The Investigator should use standard medical terminology that 
clearly describes the pathophysiology of the event and identifies the body system 
affected. 
 
Onset date: Date that the AE was first experienced at the reported severity and 
frequency. 
 
Resolution date: Date that the AE was last experienced or was completely 
resolved. In the case of an AE that changes in severity or frequency, the resolution 
of the AE is the date it was last experienced at the previously reported severity. 
 
Severity: All AEs will be graded according to the following: 
o Mild, easily tolerated by the subject, causing minimal discomfort and not 
interfering with every day activities; 
o Moderate, sufficiently discomforting to interfere with normal every day 
activities; 
o Severe, prevents normal, everyday activities; Life threatening, places the 
subject in immediate risk of death 
 
Relationship to study device: All AEs will have a study device causality 
assessment performed at the time of reporting the event to document the 
Investigator’s perception of causality. As stated in the ISO standards, adverse 
events classified as device-related should involve one of the following: 
o Insufficient or inadequate instructions for use 
o Deployment of the device 
o Implantation of the device 
o Operation of the device 
o Malfunction of the device 
o Misuse of the device 
 

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If the Investigator feels the AE is related to the implant procedure and related or 
possibly related to the device, he/she should assign causality to either “Related to 
the Device” or “Possibly related to the Device.” 
 
Unexpected Adverse Device Event (UADE) 
Unexpected adverse reactions are adverse events, of which the nature, or severity, is not 
consistent with the applicable product information (e.g. IFU).  
UADEs will be reported to regulatory authorities as is outlined and required by law. 
Expedited reporting will occur in the timeframes that regulatory authority deems 
appropriate. 
 
8.3 
Follow-up of adverse events 
All adverse events determined to be device related will be followed until they have 
abated, or until a stable situation has been reached. All AEs determined to not be device 
related with be followed through the end of the study. All SAEs, regardless of the 
relationship to the device will be followed until resolution or stabilization unless the 
subject is lost to follow-up. Depending on the event, follow up may require additional tests 
or medical procedures as indicated, and/or referral to the general physician or a medical 
specialist. 
 
8.4 
Data Safety Monitoring Board (DSMB) 
We will not have a DSMB for this study. 
 
 
9 
STATISTICAL ANALYSIS 
9.1 
Descriptive statistics 
Descriptive statistics will be used to evaluate the means and standard deviations of data 
collected as well as to compute the changes in the outcomes compared to baseline.  
 
9.2 
Analysis 
Univariate, multivariate and covariate statistical analyses will be conducted as appropriate 
to statistically tests for both primary and secondary outcomes. Statistical analyses will be 
conducted utilizing SAS and/or SPSS statistical software. Post-hoc power analyses will 
also accompany the omnibus testing and post-hoc analyses determining differences 

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between baseline and treatment means. All levels of significance will be deemed to occur 
at p<0.05. 
 
10 
ETHICAL CONSIDERATIONS 
10.1 
Regulation statement 
The current Post Market Cohort will adhere to the ethical principles of the Declaration of 
Helsinki (2008) and will use the Medical Research Involving Human Subjects Act (WMO), 
the ISO 14155:2011, the MEDDEV 2.12/2 rev 2, as well as standards set forth in 
GCP/ICH guidelines according to US 21 CFR, Part 50 as guidelines. 
 
10.2 
Recruitment and consent 
All proposed subjects will be recruited for this study once the ethics committee has 
confirmed that the Medical Research involving Human Subjects Act (WMO) does not 
apply to this  Post Market Observational Cohort Study and that an official approval of this 
study is not required. Potential subjects will be identified from the investigator’s patient 
population and will be informed about the purpose, nature, and duration of the cohort. 
Interested volunteer subjects will then have the protocol, the treatment, the follow-up 
regimen, and the risks and benefits fully explained to them by the investigator. The 
potential subject will be given as much time as needed to read the consent form and 
have the study procedures and alternative therapies discussed prior to signing the 
Informed Consent form.. An example of the Informed Consent form and patient 
information letter is provided. The consent form must be read by the subject, the subject’s 
questions answered, and the form signed by the subject before treatment can be 
performed. All subjects will receive copies of their signed informed consent documents.  

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10.3 
Benefits and risks assessment 
The benefits of this cohort could enable improved treatment of chronic, intractable pain, 
while the potential risks are similar to currently-used spinal cord stimulation systems 
which are generally minor. Feedback from this study will be part of future device designs 
that may benefit subjects who suffer from chronic intractable pain. 
 
There are no additional risks to participation in this post market observational cohort 
study. The implantation of the system is a standard procedure in the hospital and the 
data that is collected consists of standard questionnaires regarding pain relief, quality of 
life and subject satisfaction that are normally measured according to the criteria of the 
Dutch Neuromodulation Society. 
 
Careful monitoring of subjects will ensure that any potential side-effects or adverse 
events are noticed and treated as quickly as possible. Reporting of adverse events will 
adhere to applicable regulatory requirements  
 
 
10.4 
Compensation for injury 
The sponsor/investigator has a liability insurance that provides cover for damage to 
subjects through injury or death caused by the use of the device. As this cohort 
represents no risk to the subject (see section 10.3), no additional cohort insurance is 
deemed needed. 
  
10.5 
Compensation 
Subjects that participate in the cohort will be compensated for additional travel expenses 
which would not have been incurred had they not been part of this study. Subjects will not 
be provided compensation above and beyond reasonable travel expenses. 

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11 
ADMINISTRATIVE ASPECTS AND PUBLICATION 
11.1 
Handling and storage of data and documents 
The Sponsor and their designated representatives will make every reasonable effort to 
protect the confidentiality of the subjects participating in the cohort. Except as required by 
law, subjects will not be identified by name, social security number, address, telephone 
number, or any other direct personal identifier. A unique identification code will be 
assigned to each subject participating in this cohort. Information regarding the code will 
be kept in a secure location. All subject data will be stored in locked offices. All electronic 
data will be password-protected on computers stored in locked offices. Access to subject 
information will be limited to study personnel only. Any data, including photographs, 
videos, and interviews with the subject that may be published in abstracts, scientific 
journals, marketing material or presented at medical meetings will reference a unique 
subject code and will not reveal the subject’s identity without the express approval of the 
subject. Subjects will be asked for approval at the start of the cohort as part of the patient 
informed consent. It is possible that subject personal health records may be disclosed to 
other agencies such as regulatory bodies as per country regulations. 
 
Data storage will reside at both the clinical research site, any contract agent acting on 
behalf of the sponsor, and at the Sponsor Company, Spinal Modulation. Sites will retain 
data collected during the post market observational cohort study for a minimum of 5 
years. The sponsor will retain the data per Company Standard Operating Procedures. 
 
11.2 
Amendments  
Amendments are changes made to the post market observational cohort study after 
confirmation by the METC that the Medical Research Involving Human Subjects Act 
(WMO) does not apply to this study.  The METC will be notified of all substantial 
amendments to the protocol that will influence the WMO applicability. The METC will not 
be notified of non-substantial amendments.  
 
11.3 
Annual progress report 
The sponsor/investigator will not submit a summary of the progress of the cohort to the 
METC as this is not a regulatory requirement.  
 

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11.4 
End of study report 
The Investigator will not provide a final report to the METC and other regulatory bodies, 
as this is not a regulatory requirement . 
 
11.5 
Public disclosure and publication policy 
Per national guidelines (where applicable) and medical journal editorial board guidelines, 
the post market observational cohort study will be registered with a public clinical trial 
registry. The results will be published. Publication of the data collected during this cohort 
will be in accordance with clinical trial agreements. The Institution and the Principal 
Investigators involved in the cohort have the right to publish the methods, results of, and 
conclusions from, the cohort, subject to this clause and in accordance with copyright law. 
Each Discloser must ensure that it gives notice of any proposed publication drafted by it 
and/or other personnel involved in the conduct of the cohort to the Sponsor at least 30 
days before any forwarding to a party that is not bound by the confidentiality obligations. 
The Sponsor may, within that 30-day period do any one or more of the following; Provide 
comments on the proposed publication to the relevant Discloser, in which case the 
Discloser must consider such comments but will not be bound to follow them; Request 
delay of publication for no more than 90 days to allow the Sponsor to file patent 
applications or take other measures to preserve its proprietary rights, in which case the 
Institution must abide by that request; In case there are differences in interpretation of the 
research results, both the vision of the Discloser and the sponsor need to be mentioned. 
Request that the Discloser remove specified Confidential Information (other than the 
results of the Study) from the publication, in which case the Institution must remove such 
specified Confidential Information as is reasonably required to protect the Intellectual 
Property of the Sponsor.  
 
If the Discloser has not received any comments from the Sponsor on the proposed 
publication within 30 days of giving notice to the Sponsor, the Discloser may proceed to 
make the publication.  
 

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Where the Sponsor intends to publish the method, results, or conclusions from the 
cohort, any person named as an author on that publication or otherwise noted as the 
Principal Investigator or an investigator of the cohort; in the publication, will be given a 
reasonable opportunity to review the publication and request the removal of his or her 
name from the publication and the Sponsor shall comply with any such request. 
In all publications the Sponsor’s support of the cohort shall be acknowledged. 
The Sponsor may publish a summary of the cohort results and conclusions on the 
Sponsor’s on-line Clinical Trial Register before or after publication by another method. 
The Sponsor may freely use, copy, and disseminate any manuscript following its 
publication in a journal without further obligation to the Disclosers. 
 

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12 
REFERENCES 
 
1. 
Gildenberg, P.L., History of Electrical Neuromodulation for Chronic Pain. Pain Medicine, 
2006. 7(S1): p. S7-S13. 
2. 
Shealy, C.N., J.T. Mortimer, and J.B. Reswick, Electrical inhibition of pain by stimulation 
of the dorsal columns: preliminary clinical report. Anesth Analg, 1967. 46(4): p. 489-
91. 
3. 
Cameron, T., Safety and efficacy of spinal cord stimulation for the treatment of chronic 
pain: a 20-year literature review. J Neurosurg, 2004. 100(3 Suppl Spine): p. 254-67. 
4. 
Taylor, R.S., J.P. Van Buyten, and E. Buchser, Spinal cord stimulation for chronic back 
and leg pain and failed back surgery syndrome: a systematic review and analysis of 
prognostic factors. Spine (Phila Pa 1976), 2005. 30(1): p. 152-60. 
5. 
Taylor, R.S., J.P. Van Buyten, and E. Buchser, Spinal cord stimulation for complex 
regional pain syndrome: a systematic review of the clinical and cost-effectiveness 
literature and assessment of prognostic factors. Eur J Pain, 2006. 10(2): p. 91-101. 
6. 
Kumar, K., et al., Spinal cord stimulation versus conventional medical management for 
neuropathic pain: a multicentre randomised controlled trial in patients with failed back 
surgery syndrome. Pain, 2007. 132(1-2): p. 179-88. 
7. 
North, R.B., et al., Spinal cord stimulation versus repeated lumbosacral spine surgery for 
chronic pain: a randomized, controlled trial. Neurosurgery, 2005. 56(1): p. 98-106; 
discussion 106-7. 
8. 
Kumar, K., et al., The effects of spinal cord stimulation in neuropathic pain are 
sustained: a 24-month follow-up of the prospective randomized controlled multicenter 
trial of the effectiveness of spinal cord stimulation. Neurosurgery, 2008. 63(4): p. 762-
70; discussion 770. 
9. 
Kemler, M.A., et al., Spinal cord stimulation in patients with chronic reflex sympathetic 
dystrophy. N Engl J Med, 2000. 343(9): p. 618-24. 
10. Kemler, M.A., et al., The effect of spinal cord stimulation in patients with chronic reflex 
sympathetic dystrophy: two years' follow-up of the randomized controlled trial. Ann 
Neurol, 2004. 55(1): p. 13-8. 
11. Kemler, M.A., et al., Effect of spinal cord stimulation for chronic complex regional pain 
syndrome Type I: five-year final follow-up of patients in a randomized controlled trial. 
J Neurosurg, 2008. 108(2): p. 292-8. 
 

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Appendix A: Table 1 
 
 
 
Follow-up Schedule Post Market Cohort 20-SMI-2013
CRF #
Assessment
Baseline
TNS Procedure/Programming
End of TNS 
Trial
INS Implant/Programming
1-week
F/U
4-week 
F/U
2-month 
F/U
3-month 
F/U
6-month 
F/U
9-month 
F/U
12-month 
F/U
18-month 
F/U
24-month 
F/U
Interim Visit
Revision
Informed Consent Form
X
 
CRF - 1
Inclusion / Exclusion Criteria
X
CRF - 2
Medical History
X
CRF - 5
Medication Utilization
X
X
X
CRF - 6
Pain Distribution 
X
X
X
X
X
X
X
X
X
CRF - 7
Pain Measurement 
X
X
X
X
X
X
X
X
X
CRF - 8
HRQoL
X
X
X
X
X
X
X
CRF - 9
Functional  Assessment
X
X
X
X
X
X
X
CRF - 10
Psychological Disposition 
X
X
X
X
X
X
X
CRF - 11
Procedural Evaluation 
X
X
X
CRF - 15
Paresthesia Mapping
X
X
X
X
X
X
X
CRF - 16
Programming
X
X
X
X
X
X
X
X
CRF - 33
Sleep Quality
X
X
X
X
X
CRF - 19
Subject Satisfaction 
X
X
X
X
X
X
X
X
X
X
CRF - 17
AE Reporting 
+
+
+
+
+
+
+
+
+
+
+
+
CRF - 18
SAE Reporting 
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
CRF - 25
Protocol Deviation
+
+
+
+
+
+
+
+
+
+
+
+
CRF - 14
Revision 
X
CRF - 21
Trial Exit
+
X
+
+
Required = X
Only if needed = +