Spinal Cord Stimulation Research Study
Phase: NA
Conditions: Limb Pain, Trunk Pain
Sponsor: MedtronicNeuro

SCS Research Study Clinical Investigation Plan 
MDT18036 
Version 3.0 
Page 1 of 66 
Medtronic Business Restricted 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Clinical Investigation Plan 
Clinical Investigation Plan/Study Title Spinal Cord Stimulation (SCS) Research Study 
Clinical Investigation Plan Identifier MDT18036 / NCT03763708 
Study Product Name Medtronic Implantable Neurostimulation 
Systems 
Sponsor/Local Sponsor Medtronic, Inc 
7000 Central Ave NE 
Minneapolis, Minnesota, 55432 
U.S.A. 
+1-763-514-4000
Document Version and date 3.0, 06 June 2022 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization of 
Medtronic is strictly prohibited. Persons to whom the information is disclosed must know that it is 
confidential and that it may not be further disclosed by them. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 2 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
1. Investigator Statement 
Participating investigators will be provided with a separate investigator agreement to document their 
obligations and commitment with respect to study conduct. 
 
 
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 3 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Table of Contents  
1. 
Investigator Statement ...................................................................................................... 2 
Table of Contents ...................................................................................................................... 3 
Table of Tables .......................................................................................................................... 7 
Table of Figures ......................................................................................................................... 7 
2. 
Glossary .............................................................................................................................. 8 
3. 
Synopsis ............................................................................................................................. 9 
4. 
Introduction ..................................................................................................................... 12 
4.1 Background ........................................................................................................................ 12 
4.2 Purpose .............................................................................................................................. 15 
5. 
Objectives and/or Endpoints ........................................................................................... 15 
5.1 Objectives .......................................................................................................................... 15 
5.1.1 
Primary Objective ................................................................................................................ 15 
5.1.2 
 .......................................................................................................... 15 
6. 
Study Design .................................................................................................................... 15 
6.1 Duration ............................................................................................................................. 16 
6.2 Rationale ............................................................................................................................ 16 
7. 
Product Description.......................................................................................................... 17 
7.1 General .............................................................................................................................. 17 
7.2 Manufacturer ...................................................................................................................... 18 
7.3 
 .......................................................................................................................... 18 
7.4 Product Return .................................................................................................................... 18 
7.5 Product Accountability ......................................................................................................... 18 
8. 
Study Site Requirements ................................................................................................. 19 
8.1 Investigator/Investigation Site Selection ................................................................................ 19 
8.2 Study Site Activation............................................................................................................ 19 
8.3 Role of the Sponsor Representatives ..................................................................................... 20 
9. 
Selection of Subjects ........................................................................................................ 20 
9.1 Study Population ................................................................................................................. 20 
9.2 Subject Enrollment .............................................................................................................. 21 
9.3 Inclusion Criteria ................................................................................................................. 21 
9.4 Exclusion Criteria................................................................................................................. 21 
10. 
Study Procedures .......................................................................................................... 21 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 4 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
10.1 Schedule of Events .............................................................................................................. 21 
10.1.1 
 ......................................................................................................... 22 
10.1.2 
 ......................................................................................................... 23 
10.2 Data Collection .................................................................................................................... 23 
10.3 
 ...................................................................................... 25 
10.4 Subject Screening ............................................................................................................... 25 
10.5 
 ........................................................................ 25 
10.6 Subject Consent .................................................................................................................. 25 
10.7 Enrollment Visit ................................................................................................................... 27 
10.8 
 ......................................................................................... 28 
10.9 
 ................................................................................................... 30 
10.10 
 ........................................................................................ 31 
10.11 
Final Study Visit ........................................................................................................... 32 
10.12 
 ........................................................................................................... 32 
10.13 
Imaging ...................................................................................................................... 32 
10.14 
..................................................................................................... 33 
10.15 
 .................................................................................... 33 
10.16 
System Modification ..................................................................................................... 33 
10.17 
 .............................................................................. 33 
10.17.1 
 ...................................................................................... 33 
10.17.2 
 .............................................................................................................. 33 
10.18 
 ................................................................................................. 34 
10.18.1 
 .................................................................................. 34 
10.18.2 
 .............................................................. 34 
10.18.3 
 ................................................................... 35 
10.18.4 
 ...................................................................................................... 36 
10.18.5 
 ........................................................................... 36 
10.18.6 
Imaging ............................................................................................................................ 36 
10.18.7 
 ................................................................................................... 36 
10.18.8 
 ............................................................................................................ 36 
10.18.9 
 ..................................................................................... 36 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 5 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
10.19 
Assessment of Safety ................................................................................................... 36 
10.20 
Recording Data ............................................................................................................ 36 
10.20.1 
Case Report Form Data ................................................................................................... 37 
10.20.2 
 ............................................................................................................... 37 
10.20.3 
Image Data ...................................................................................................................... 38 
10.20.4 
............................................................................ 38 
10.21 
Deviation Handling ....................................................................................................... 38 
10.22 
Subject Exit, Withdrawal or Discontinuation .................................................................... 39 
11. 
Risks and Benefits ........................................................................................................ 39 
11.1 Potential Risks .................................................................................................................... 39 
11.1.1 
Foreseeable Risks ................................................................................................................ 40 
11.2 Risk Minimization ................................................................................................................ 42 
11.3 Potential Benefits ................................................................................................................ 43 
11.4 Risk-Benefit Rationale .......................................................................................................... 43 
12. 
Adverse Events and Device Deficiencies ...................................................................... 44 
12.1 Adverse Events ................................................................................................................... 44 
12.2 Device Deficiency ................................................................................................................ 45 
12.3 Processing Updates and Resolution ....................................................................................... 45 
12.4 Definitions/Classifications ..................................................................................................... 46 
12.5 Reporting of Adverse Events and Device Deficiencies ............................................................. 51 
12.5.1 
Adverse Event and Device Deficiency Classification ........................................................... 51 
12.5.2 
Adverse Event and Device Deficiency Reporting Requirements ........................................ 52 
12.6 Subject Death ..................................................................................................................... 53 
12.7 Product Complaint Reporting ................................................................................................ 53 
13. 
Data Review Committees ............................................................................................. 54 
14. 
Statistical Design and Methods .................................................................................... 54 
14.1 General Aspects of Analysis .................................................................................................. 54 
14.2 Interim Analysis .................................................................................................................. 55 
14.3 Primary Objective(s) ............................................................................................................ 55 
14.4 Additional Objective(s) ......................................................................................................... 55 
14.5 Safety Assessment .............................................................................................................. 56 
14.6 Sample Size Determination .................................................................................................. 56 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 6 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
14.7 Minimization of Bias ............................................................................................................. 57 
15. 
Ethics ............................................................................................................................ 58 
15.1 Statement(s) of Compliance ................................................................................................. 58 
16. 
Study Administration .................................................................................................... 58 
16.1 Monitoring .......................................................................................................................... 58 
16.1.1 
Monitoring Visits ................................................................................................................. 58 
16.2 Data Management ............................................................................................................... 59 
16.3 Direct Access to Source Data/Documents .............................................................................. 59 
16.4 Confidentiality ..................................................................................................................... 60 
16.5 Liability .............................................................................................................................. 60 
16.6 CIP Amendments ................................................................................................................ 61 
16.7 Record Retention ................................................................................................................ 61 
16.7.1 
Investigator Records ........................................................................................................... 61 
16.7.2 
Sponsor Records ................................................................................................................. 61 
16.8 Reporting Requirements ...................................................................................................... 62 
16.8.1 
Investigator Reports ............................................................................................................ 62 
16.8.2 
Sponsor Reports .................................................................................................................. 62 
16.9 Publication and Use of Information ....................................................................................... 62 
16.10 
Suspension or Early Termination ................................................................................... 62 
17. 
References .................................................................................................................... 63 
18. 
Appendices ................................................................................................................... 66 
19. 
Version History ............................................................................................................. 66 
 
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 7 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Table of Tables 
Table 7-1: Medtronic FDA-Approved Neurostimulators ............................................................................. 18 
Table 10-1: Data collection and study procedure requirements at subject visits ...................................... 23 
Table 10-2: Range of Programmable Neurostimulator Settings ................................................................. 28 
Table 12-1: Adverse Event and Device Deficiency Definitions ................................................................... 46 
Table 12-2: Adverse Event Classification Responsibilities .......................................................................... 52 
Table 12-3: Adverse Event and Device Deficiency Reporting Requirements ............................................. 52 
Table 14-1: Precision by sample size and standard deviation 
 ...................................................... 56 
 
Table of Figures 
Figure 10-1: 
 .......................................................................... 22 
Figure 10-2: 
.......................................................................... 23 
Figure 14-1: Precision by sample size and standard deviation 
 ..................................................... 57 
  
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 8 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
2. Glossary 
 Abbreviation 
Term 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CIP 
Clinical Investigation Plan  
CFR 
Code of Federal Regulations 
CRPS 
Complex Regional Pain Syndrome 
DD 
Device Deficiency 
DDD 
Degenerative Disk Disease 
eCRF 
Electronic Case Report Form 
 
 
FBS 
Failed Back Syndrome 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practices 
HCO 
Health Care Organization 
HCP 
Health Care Professional 
HIPAA 
Health Insurance Portability and Accountability Act 
Hz 
Hertz 
IC/ICF 
Informed Consent/Informed Consent Form 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
µs 
Microseconds 
mA 
Milliamps 
 
 
 
 
 
EDC 
Electronic Data Capture 
RSD 
Reflex Sympathetic Dystrophy 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SCS 
Spinal Cord Stimulation 
 
 
V 
Volts 
Intellis, AdaptiveStim, Restore, RestoreUltra, RestoreAdvanced, RestoreSensor, SureScan, and Vanta are 
trademarks of Medtronic.  
 
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 9 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
3. 
Synopsis 
Title 
Spinal Cord Stimulation (SCS) Research Study  
Clinical Study Type 
Post-market 
Product Name 
Medtronic Implantable Neurostimulation Systems 
Sponsor  
Medtronic, Inc.  
7000 Central Ave NE 
Minneapolis, Minnesota, 55432  
U.S.A. 
+1-763-514-4000 
Indication under 
investigation  
Approved indication of spinal cord stimulation as an aid in the 
management of chronic, intractable pain of the trunk and/or limbs. 
Investigation Purpose 
 
To characterize the effects of stimulation parameters on pain relief 
and other cohort specific outcomes. 
Product Status 
All devices used in this study are commercially available and will be 
used within the intended approved indication. 
Primary Objective 
To characterize the pain scores, specific to the indication associated 
with SCS implant, with different SCS parameters. 
  
 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Design 
This is a prospective, multi-center, post-market study to characterize 
the effects of stimulation parameters on pain relief, 
 
 It is estimated that up to 360 
subjects will be enrolled 
 in the United States.
 
 
  
 
The overall study duration, from first subject enrollment to last 
subject visit, is expected to last approximately 10 years. Multiple on-
label stimulation parameters will be studied throughout the execution 
of this clinical investigational plan. 
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 11 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
1. Implanted with neurostimulation system for an off-label 
indication 
2. Currently enrolled or planning to enroll in an interventional 
clinical study that could potentially confound the study results 
(co-enrollment in an interventional study is only allowed 
when documented pre-approval is obtained from the 
Medtronic study manager, or designee) 
3. If female, pregnant or is of child-bearing potential and 
unwilling to use a medically acceptable form of birth control 
during the study 
4. Has untreated major psychiatric comorbidity, as determined 
by the investigator, or designee 
5. Has a non-rechargeable neurostimulator where the battery 
longevity is not able to be estimated with the battery 
longevity calculator 
 
Study Procedures and 
Assessments 
Upon obtaining informed consent, each subject will complete an 
Enrollment Visit 
 
 
 
 
 
The following measures may be used during the study: 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
Safety Assessments 
Subjects will be assessed from enrollment through the end of the 
study for adverse events related to the following: 
• 
The SCS system and accessories (device-related) 
• 
SCS therapy (therapy-related) 
• 
SCS procedure (procedure-related) 
In addition, all device deficiencies reported during the study will be 
collected.  

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 12 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
 Statistics 
Descriptive statistics will be reported for the primary 
 
objectives.  
 
In addition, the statistical approach may vary based on the research 
question to be addressed in each cohort 
 
 
  
 
Where applicable, hypothesis testing may be performed to 
characterize change from baseline. Hypothesis testing may not be 
performed on all cohorts. Sample sizes in cohorts with hypothesis 
testing will be estimated based on at least 80% power with a 
significance level of 0.05 for two-sided tests or 0.025 for one-sided 
tests.  
 
Sample sizes in cohorts with no hypothesis testing may vary 
depending on the research questions to be addressed.  
 
Device, procedure, and therapy related adverse events and device 
deficiencies will be presented in summary tables. 
 
 
  
4. 
Introduction 
This post-market clinical study will be conducted with up to 40 sites and include subjects treated with 
SCS, consistent with FDA approved indications and instructions for use, using programming parameters 
within the capabilities of approved SCS devices. It is estimated that up to 360 subjects will be enrolled.  
  The study will be 
conducted in accordance with this protocol, the ethical principles that have their origin in the 
Declaration of Helsinki, all applicable regulatory requirements (21 Code of Federal Regulations (CFR) §11 
Electronic records; electronic signatures, 21 CFR §50 Protection of human subjects, 21 CFR§54 Financial 
disclosure by clinical investigators, 21 CFR §56 Institutional review boards, and 21 CFR §803 Medical 
device reporting), and will comply with Good Clinical Practices (GCP) as guidelines for this study. 
4.1 Background 
Spinal cord stimulation (SCS) has been proven to be an effective therapy for pain relief. Three 
parameters are programmed to deliver stimulation in SCS systems: pulse width (µs), frequency (Hz), and 
amplitude (mA or V). Pulse width determines the number of neurons targeted for therapy; while 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 13 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
frequency affects the quality or feeling of the neurostimulation. Amplitude controls the stimulation 
intensity and may be adjusted above or below sensory perception thresholds. Most clinical trials are 
conducted using a range of parameters rather than a specific parameter set; therefore, no conclusions 
can be made about specific parameters. 
Pulse width is the duration of each electric impulse in microseconds. As the duration of the stimulus 
increases, an increase in the recruitment of nerve ﬁbers occurs.  Limited clinical research has been 
conducted on pulse width optimization in SCS. In one single-blinded, prospective study, Yearwood et al. 
(2010) surveyed pulse widths from 50 to 1000 μs in 19 back pain subjects. Approximately 37% of 
subjects selected to increase their pulse width values as compared to their original program and the 
median pulse width of all final programs was 400 μs.1  Abejon et al. (2015) conducted a clinical study 
examining 46 subjects programmed at a fixed frequency of 50 Hz and pulse widths between 50 - 1000 
μs. Subjects achieved the best degree of satisfaction at pulse width 331.27+/- 227 μs and were 
dissatisfied at pulse widths exceeding 700 μs. Subjects preferred pulse widths ranging from 320-500 μs 
which agrees with the Yearwood study for support of longer pulse widths within the conventional 
range.2 
Frequency or rate of stimulation is a parameter that may be modulated to produce different analgesic 
outcomes.3 While the range of frequencies for most rechargeable implantable SCS devices (e.g., 
Medtronic RestoreSensor) is 2 – 1200 Hz, the conventional stimulation frequencies range from 50 to 120 
Hz.4 Since 2010, there has been a focus on using higher frequencies (1000 Hz -10 kHz) for stimulation; 
for which, there are publications reporting significant pain relief.5,6 Several small studies have explored 
the upper limits of conventional SCS frequencies, 1000- 1200 Hz, and have reported that subjects who 
have lost pain relief from conventional SCS at lower frequencies could have pain relief restored at these 
 
1 Yearwood TL1, Hershey B, Bradley K, Lee D. Pulse width programming in spinal cord stimulation: a clinical study. Pain Physician. 2010 Jul-
Aug;13(4):321-35. 
2 Abejón D1, Rueda P, del Saz J, Arango S, Monzón E, Gilsanz F. Is the introduction of another variable to the strength-duration curve necessary 
in neurostimulation? Neuromodulation. 2015 Apr;18(3):182-90; discussion 190. doi: 10.1111/ner.12223. Epub 2014 Aug 29. 
3 Miller JP, Eldabe S, Buchser E, Johanek LM, Guan Y, Linderoth B. Parameters of Spinal Cord Stimulation and Their Role in Electrical Charge 
Delivery: A Review. Neuromodulation. 2016; 19:373-384. 
4 Abejón D1, Cameron T, Feler C, Pérez-Cajaraville J. Electric parameters optimization in spinal cord stimulation. Study in conventional 
nonrechargeable systems. Neuromodulation. 2010 Oct;13(4):281-6; discussion 286-7. doi: 10.1111/j.1525-1403.2010.00290.x. 
5 Al-kaisy A, Palmisani S, Pang D, Sanderson K, Wesley S, Tan Y, McCammon S, Trescott A. Prospective, Randomized, Sham-Control, Double 
Blind, Crossover Trial of Subthreshold Spinal cord Stimulation at Various Kilohertz Frequencies in Subjects Suffering from Failed Back Surgery 
Syndrome (SCS Frequency Study). Neuromodulation. 2018 Jul;21(5):457-465. 
6 Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Brown LL, Yearood TL, Bundschu R, Burton 
AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz High-Frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency 
Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology. 2015 
Oct; 123(4):851-60. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 14 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
higher frequencies.7, 8, 9  In the PROCO study, a published randomized controlled trial, Thompson et al 
(2017) showed equivalent pain relief for 1, 4, 7, and 10 kHz frequencies.10 
Studies have tested sub-perception stimulation amplitudes, but maintained traditional frequency ranges 
(60 – 85 Hz) and pulse widths (210-390 µsec) in small groups of subjects or case reports.11, 12, 13  In one 
small case series of neuropathic pain, parameters set at conventional frequency and pulse width settings 
at sub-perception amplitudes relieved neuropathic pain better than no stimulation but were less 
effective than supra-threshold stimulation.  Recently, new programming algorithms claim to be effective 
at sub-perception amplitudes, but these algorithms include high frequencies14, 15, 16 or long pulse 
widths.17, 18  To date, there are no studies with a focus on surveying the range of amplitudes. 
In addition, the recent studies evaluated various ‘cycling’ or ‘pulsing’ techniques wherein the stimulation 
paradigms are cycled on and off for specific times to improve battery longevity for non-rechargeable 
devices and time between recharges for rechargeable devices. This promising new approach has yet to 
be well characterized or understood as to which cycling parameters are the most efficacious.  In 
conclusion, neurostimulators have the ability to stimulate in a wide range of on-label parameter 
settings; however, more can be understood about the effects of these parameters on patient pain relief 
or physiologic processes that are ultimately related to patient benefits. This study explores the on-label 
parameters to determine these effects.  
 
7 Smith H1, Youn Y, Pilitsis JG. Successful use of high-frequency spinal cord stimulation following traditional treatment failure. Stereotact Funct 
Neurosurg. 2015;93(3):190-3. doi: 10.1159/000380825. Epub 2015 Apr 1. 
8 North JM1, Hong KJ2, Cho PY3. Clinical Outcomes of 1 kHz Subperception Spinal Cord Stimulation in Implanted Patients With Failed 
Paresthesia-Based Stimulation: Results of a Prospective Randomized Controlled Trial. Neuromodulation. 2016 Oct;19(7):731-737. doi: 
10.1111/ner.12441. Epub 2016 May 17. 
9 Youn Y1, Smith H, Morris B, Argoff C, Pilitsis JG. The Effect of High-Frequency Stimulation on Sensory Thresholds in Chronic Pain Patients. 
Stereotact Funct Neurosurg. 2015;93(5):355-9. doi: 10.1159/000438998. Epub 2015 Oct 8. 
10 Thomson SJ1, Tavakkolizadeh M2, Love-Jones S3, Patel NK4, Gu JW5, Bains A6, Doan Q5, Moffitt M5. Effects of Rate on Analgesia in 
Kilohertz Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial. Neuromodulation. 2018 Jan;21(1):67-76. 
doi: 10 1111/ner.12746. Epub 2017 Dec 8. 
11 Benyamin R1, Kramer J, Vallejo R. A case of spinal cord stimulation in Raynaud's Phenomenon: can subthreshold sensory stimulation have an 
effect? Pain Physician. 2007 May;10(3):473-8. 
12 Eddicks S, Maier-Hauff K, Schenk M, Müller A, Baumann G, Theres H. Thoracic spinal cord stimulation improves functional status and 
relieves symptoms in patients with refractory angina pectoris: the first placebo-controlled randomised study. Heart. 2007 May;93(5):585-90. 
Epub 2007 Jan 19. 
13 Wolter T1, Kiemen A, Porzelius C, Kaube H. Effects of sub-perception threshold spinal cord stimulation in neuropathic pain: a randomized 
controlled double-blind crossover study. Eur J Pain. 2012 May;16(5):648-55. doi: 10.1002/j.1532-2149.2011.00060.x. Epub 2011 Dec 19. 
14 Al-Kaisy A1, Palmisani S1, Smith TE1, Pang D1, Lam K2, Burgoyne W3, Houghton R4, Hudson E5, Lucas J2. 10 kHz High-Frequency Spinal 
Cord Stimulation for Chronic Axial Low Back Pain in Patients With No History of Spinal Surgery: A Preliminary, Prospective, Open Label and 
Proof-of-Concept Study. Neuromodulation. 2017 Jan;20(1):63-70. doi: 10.1111/ner.12563. Epub 2016 Dec 26 
15 Van Buyten JP1, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation for the treatment of chronic back pain 
patients: results of a prospective multicenter European clinical study. Neuromodulation. 2013 Jan-Feb;16(1):59-65; discussion 65-6. doi: 
10.1111/ner.12006. Epub 2012 Nov 30. 
16 Kapural L1, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Brown LL, Yearwood TL, Bundschu R, Burton 
AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency 
Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology. 2015 
Oct;123(4):851-60. doi: 10.1097/ALN.0000000000000774. 
17 De Ridder D1, Vanneste S, Plazier M, van der Loo E, Menovsky Burst spinal cord stimulation: toward paresthesia-free pain suppression. 
Neurosurgery. 2010 May;66(5):986-90. doi: 10.1227/01.NEU.0000368153.44883.B3. 
18 De Ridder D1, Plazier M, Kamerling N, Menovsky T, Vanneste S. Burst spinal cord stimulation for limb and back pain. World Neurosurg. 
2013 Nov;80(5):642-649.e1. doi: 10.1016/j.wneu.2013.01.040. Epub 2013 Jan 12. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 16 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
 A study cohort is defined as a group of subjects who share the same recommended 
programming parameters and follow-up visit cadence. These stimulation parameters and visit cadence 
will be provided by Medtronic to each site per study cohort. 
 
 
Cohorts with both rechargeable and non-rechargeable devices may explore on-label 
stimulation parameters 
 
 
 
 
  
The longer enrollment period enables the research of SCS parameters over time as the science and 
technology in SCS develops.  
The 
completion of the study is defined as the approval of the Final Clinical Study Report and closure of all 
sites. 
6.1 Duration 
It is estimated that up to 360 subjects will be 
 
 
 
 
 The overall study duration, from first subject 
enrollment to last subject visit, is expected to last approximately 10 years. The completion of the study 
is defined as the approval of the Final Clinical Study Report and closure of all sites. 
6.2 Rationale 
Patients who receive neurostimulation therapy typically have chronic, intractable pain of the back 
and/or limbs that is not sufficiently managed with medications or other more conservative treatments. 
Oftentimes, this chronic pain is due to or associated with failed back surgery syndrome, complex 
regional pain syndrome or diabetic peripheral neuropathy. 19,20,21,22,23   
 
19 Frey ME, Manchikanti L, Benyamin RM, Schultz DM, Smith HS, Cohen SP. Spinal cord stimulation for patients with failed back surgery 
syndrome: a systematic review. Pain Physician. 2009 Mar-Apr; 12(2):379-97. 
20 Taylor RS. Spinal cord stimulation in complex regional pain syndrome and refractory neuropathic back and leg pain/failed back surgery 
syndrome: results of a systematic review and meta-analysis. J Pain Symptom Manage. 2006 Apr; 31(4 Suppl):S13-9. 
21 Turner JA, Loeser JD, Bell KG. Spinal cord stimulation for chronic low back pain: a systematic literature synthesis. Neurosurgery. 1995 
Dec;37(6):1088-95. 
22 Turner JA, Loeser JD, Deyo RA, Snaders SB. Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain 
syndrome: a systematic review of effectiveness and complications. Pain. 2004 Mar; 108(1-2):137-47. 
23 Duarte RV, Andronis L, Lenders MW, de Vos CC. Quality of life increases in patients with painful diabetic neuropathy following treatment 
with spinal cord stimulation. Qual Life Res. 2016 Jul;25(7):1771-7. doi: 10.1007/s11136-015-1211-4.  

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 17 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Most clinical studies reporting on the pain-relieving effects of SCS are observational case studies with no 
appropriate comparator or systematic reviews of the aforementioned. There are prospective studies 
that demonstrate at least 50% pain relief or improvement in function in 60% of CRPS patients implanted 
with SCS systems24, 25, 26, 27, 28, 50 to 60% of FBSS patients.29,30,31, 28 and 50-63% in Painful Diabetic 
Peripheral Neuropathy patients.23 However, a number of clinical reviews report that the pain-relieving 
effect of SCS can diminish over time.32  While there is a deficiency of multiple evidence-based studies 
demonstrating efficacy of long term SCS, there are even fewer studies that provide sufficient data 
regarding SCS parameter effects (eg, frequencies, pulse widths, cycling duties, etc.) on clinical outcomes 
along with long term effects. Research studies are needed to address the gap in our knowledge of SCS 
parameters and how they differentially, but effectively, modulate central nervous system mechanisms 
that drive chronic intractable pain, the underlying causes, or relief from pain.   
7. 
Product Description 
7.1 General  
This study involves commercially available devices used within their intended approved indication. 
Subjects who have previously been implanted with a Medtronic neurostimulation system (ie, 
neurostimulator, lead(s), extension(s), and accessories) will be enrolled in this study. For non-
rechargeable neurostimulation systems, systems must be able to have the battery longevity be 
calculated with the commercial application on a clinician programming tablet (e.g., Vanta™ with 
AdaptiveStim™). Non-rechargeable neurostimulators where the battery longevity can only be calculated 
manually are excluded from the study. Table 7-1 contains a list including examples of, but not limited to, 
FDA-approved neurostimulators that may be used in the study.  
 
24 Harke H, Gretenkort P, Ladleif HU, Rahman S. Spinal cord stimulation in sympathetically maintained complex regional pain syndrome type I 
with severe disability. A prospective clinical study. Eur J Pain. 2005 Aug;9(4):363-73. 
25 Oakley JC, Weiner RL. Spinal cord stimulation for complex regional pain syndrome: a prospective study of 19 patients at two centers. 
Neuromodulation. 1999 Jan;2(1):47-50. 
26 Kemler MA, Barendse GAM, van Kleef M, de Vet HCW, Rijks CPM, Furnee CA, van den Wildenberg FAJM. Spinal cord stimulation 
inpatients wit chronic reflex sympathetic dystrophy. New Eng J Med. 2000; 343(9):618-624. 
27  Chivukula S, Tempel ZJ, Weiner GM, Gande AV, Chen CJ, Ding D, Moossy JJ. Cervical and cervicomedullary spinal cord stimulation for 
chronic pain: Efficacy and outcomes. Clin Neurol Neursurg. 2014 Dec; 127:33-41. 
28  Deer TR, Skaribas IM, Haider N, Salmon J, Kim C, Nelson C, Tracy J, Espinet A, Lininger TE, Tiso R, Archacki MA, Washburn SN. 
Effectiveness of Cervical Spinal Cord Stimulation for the Management of Chronic Pain. Neuromodulation 2014; 17:265-271. 
29 Burchiel KJ, Anderson VC, Brown FD, Fessler RG, Friedman WA, Pelofsky S, Weiner RL, Oakley J, Shatin D. Prospective, multicenter study 
of spinal cord stimulation for relief of chronic back pain. Spine (Phila Pa 1976). 1996 Dec 1;21(230:2786-94. 
30 Thomson SJ, Tavakkolizadeh M, Love-Jones S, Patek NK, Gu JW, Bains A, Doan Q, Moffitt M. Effects of Rate on Analgesia in Kilohertz 
Frequency Spinal Cord Stimulation: Results of the PROCO Randomized Controlled Trial. Neuromodulation. 2018 Jan;21(1):67-76. Epub 2017 
Dec 8. 
31 Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Brown LL, Yearwood TL, Bundschu R, Burton 
AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency 
Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial. Anesthesiology. 2015 
Oct;123(4):851-60. 
32 Kumar K, Hunter G, Demeria D. Spinal cord stimulation in treatment of chronic benign pain: challenges in treatment planning and present 
status, a 22-year experience. Neurosurgery. 2006 Mar; 58(3):481-96. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 19 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Subjects who participate in the study may be asked to surrender their patient programmer to site 
personnel for follow-up periods (for example, if a subject is implanted with a neurostimulator that can 
be turned off using a recharger and does not require a patient programmer for recharging). 
Site personnel will store each subject’s patient programmer in a secure location. Each subject will be 
given back their patient programmer prior to the end of their participation in the study. 
 
. 
8. 
Study Site Requirements 
8.1 Investigator/Investigation Site Selection 
The role of the principal investigator is to implement and manage the day-to-day conduct of the clinical 
investigation as well as ensure data integrity and the rights, safety and well-being of the subjects 
involved in the clinical investigation. 
The principal investigator shall: 
• 
Be qualified by education, training, and experience to assume responsibility for the proper 
conduct of the clinical investigation 
• 
Be experienced in the field of application and training in the use of spinal cord stimulation 
• 
Be able to demonstrate that the proposed investigational study site: 
 
Has the required number of eligible subjects needed within the recruitment period 
 
Has one or more qualified investigators, a qualified investigational study site team, 
and adequate facilities for the foreseen duration of the clinical investigation 
Study site personnel qualification and training will be completed and documented prior to participation 
in this study. 
8.2 Study Site Activation 
During the site activation process (prior to subject enrollment), Medtronic will train study site personnel 
on the clinical investigation plan (CIP), relevant standards and regulations (as required), informed 
consent (IC), programming, and data collection and reporting tools. If new members join the study site 
team, they will receive training on the applicable study requirements relevant to their role before 
contributing to the study. 
Prior to performing study related activities, all regulatory requirements shall be fulfilled, including, but 
not limited to the following:  
• 
IRB approval (and voting list, as required by local law) of the current version of the CIP and 
IC.  
• 
Fully executed Clinical Trial Agreement (CTA)  

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 20 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
• 
CV/medical license of investigators and key members of the investigation study site team (as 
required).  
• 
Documentation of delegated tasks. 
• 
Documentation of study training.  
In addition, all participating study site staff must be trained on the current version of the CIP as well as 
on the applicable study requirements depending on their role and must be delegated by the principal 
investigator to perform study-related activities.   
Medtronic will provide each study site with documentation of study site/investigator readiness; this 
letter must be received prior to performing study-related activities. 
8.3 Role of the Sponsor Representatives 
In addition to performing monitoring and auditing activities, qualified and trained sponsor 
representatives may provide support at the study site as required for the study under supervision of the 
Principal Investigator, including: 
• 
Provide study training relevant and pertinent to the involvement of personnel conducting 
study activities and investigator responsibilities 
 
 
 
 
 
 
  
 
 
 
 
 
These activities will be performed under the supervision of the investigator, or appropriately delegated 
study personnel, and will not bias the outcome of study, affect the quality of research data, or 
compromise the rights and welfare of human subjects. Any data collection completed by Medtronic 
personnel will be clearly identified as such.  
9. 
Selection of Subjects 
9.1 Study Population 
A Medtronic implantable neurostimulation system is indicated for spinal cord stimulation (SCS) as an aid 
in the management of chronic, intractable pain of the trunk and/or limbs including all conditions 
approved by the FDA at the time of initiation of any individual cohort.  
 
This study will enroll a sub-set of the population indicated for SCS systems. Subjects who meet the 
eligibility criteria listed in Sections 9.3-9.4 are eligible to be enrolled in the study. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 26 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
by the IRB. Any adaptation of the informed consent form must be reviewed by Medtronic and approved 
by the IRB prior to enrolling subjects. The ICF will be provided under separate cover. 
Patient informed consent is defined as legally effective, documented confirmation of a subject’s 
voluntary agreement to participate in a clinical study after information has been given to the subject on 
all aspects of the clinical study that are relevant to the subject’s decision to participate. The informed 
consent process will be performed in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and in accordance with 21 CRF Part 50. 
Prior to entering the study, the principal investigator, or appropriately delegated designee, will explain 
to each subject all aspects of the clinical investigation that are relevant to the subject’s decision to 
participate throughout the clinical investigation including, but not limited to, the following: purpose and 
nature of the study, study procedures, expected study duration, available alternative therapies, and the 
benefits and risks involved with study participation and the potential treatment. 
The investigator shall seek such consent only under circumstances that provide the prospective subject 
sufficient opportunity to consider whether to participate, and that minimize the possibility of coercion 
or undue influence. No informed consent, whether oral or written, may include any exculpatory 
language through which the subject is made to waive or appear to waive any of the subject’s legal rights, 
or releases or appears to release the investigator, the sponsor, the institution, or its agents from liability 
for negligence.  
Subjects are considered enrolled at the time the study specific ICF is signed. If a subject enrolls for 
participation in multiple cohorts, a new consent form will be signed for each subsequent cohort. 
Informed consent must be obtained from the subject prior to initiation of any study-specific procedures. 
Subjects must be able to personally sign and date the consent form to participate in this study. Signing 
and dating of the ICF or HIPAA authorization or other data protection form by a legally authorized 
representative will not be permitted for this study. Subjects will be required to sign and date a HIPAA 
authorization or other data protection form as required by local regulations before participating sites 
can collect, use and submit subject information to the study sponsor. The Consent Form and 
Authorization to Use and Disclose Personal Health Information/ Research Authorization/other legally 
required privacy language must be given to the subject in a language he/she is able to read and 
understand. Only subjects capable of reading and understanding English are eligible to participate in this 
study. 
If the informed consent form is obtained the same day the subject begins participating in study-related 
procedures, it will be documented in the subject’s case history that consent was obtained prior to 
participation in any study-related procedures. 
The original signed ICF must be filed in the hospital/clinical chart and/or with the subject’s study 
documents. A copy of the informed consent form and signed Authorization to Use and Disclose Personal 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 27 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Health Information/Research Authorization/other legally required privacy language must be provided to 
the subject.  
The informed consent form and Authorization to Use and Disclose Personal Health 
Information/Research Authorization/other legally required privacy language must be available for 
monitoring and auditing.  
Any changes to a previously approved informed consent form throughout the course of the study must 
be submitted and approved by Medtronic and the IRB reviewing the application before being used to 
consent a prospective study subject. The document(s) must be controlled (i.e. versioned and dated) to 
ensure it is clear which version(s) were approved by the IRB.  
The investigator must notify the subject of any significant new findings about the study that become 
available during the course of the study which are pertinent to the safety and well-being of the subject, 
as this could impact a subject’s willingness to participate in the study. If relevant, approval may be 
requested from subjects to confirm their continued participation. 
10.7 Enrollment Visit  
A subject is considered enrolled when the consent process has been finalized. The date the subject 
signed the IC and Data Protection Authorization, as required by law, must be documented in the 
subject’s medical records. A log of all subjects enrolled in the study should be maintained. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
The following may be collected during the Enrollment visit, 
 
 
  
 
 
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 29 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
 
Frequency 
Pulse-width 
Amplitude 
Restore, 
RestoreAdvanced 
2 to 130 Hz 
60 to 450 μs 
0 to 10.5 V 
 
 
 
 
 
  
 
 
 
 
  
For subjects with non-rechargeable neurostimulators, estimated battery longevity of the programmed 
active study settings will be calculated on the clinician programmer prior to the end of the visit. The 
estimated battery longevity with the study settings will be reviewed with the investigator and compared 
to that of the settings programmed at the beginning of the visit, if applicable. 
 
 
 
 
 
 
 
 
 
 
 
 
 
During the follow-up period, subjects with rechargeable devices may need to recharge their device more 
or less often; therefore, subjects should be instructed to check their device daily to verify whether 
recharging is needed. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 32 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
10.11 
Final Study Visit 
Upon completion of the last follow-up period, subjects will complete the Final Study Visit. 
 
 
Subjects will be queried for adverse events, device deficiencies, 
 
In addition, information will be collected on the visit case report form for 
any events that, as determined by the investigator, are not reportable as an adverse event but may 
influence accuracy of pain reporting by the subject. 
 
 
 
The following may be collected during the Final Study visit, 
 
 
  
 
 
 
 
 
 
 
 
 
. Subjects will be programmed to a setting per standard of care prior to exiting the study. 
 
 
10.12 
 
Subjects may be called during their participation in the study to reinforce study compliance
 
 
 
 
10.13 
Imaging 
Subjects may be asked to have fluoroscopic or X-ray images taken of their implanted lead(s) as part of 
the study, unless imaging taken prior to the subject’s enrollment or as part of their standard of care are 
available and allow for the anatomical location of the active contacts to be defined. If the subject does 
not have adequate imaging available, imaging may be performed, at no more than 1 visit throughout the 
study, to obtain anterior/posterior and lateral fluoroscopy or X-ray views that allow for the anatomical 
location of the active contacts to be defined. Standard of care images taken during the subject’s 
participation, but not required by the study, may also be collected.  

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 37 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
In general, eCRFs (or paper copies) may not serve as source documents. An exception may be the 
completion of QoL Questionnaires and clinical scales. Source documentation for data elements not 
routinely captured in medical records may vary from study site to study site; the study site may use 
source document worksheets if identified as source documents. 
The investigator must ensure the availability of source documents from which the information on the 
eCRFs was derived. The type and location of source documents should be documented. Where printouts 
of electronic medical records, are provided as source documents, or where copies of source documents 
are retained as source documents, those should be certified. Certification must contain (1) the signature 
of the individual making the copy, (2) the date the copy was made and (3) a statement attesting to the 
accuracy and completeness of the copy.  
The source documents must be made available for monitoring or auditing by Medtronic’s representative 
or representatives of the competent authorities and other applicable regulatory agencies. 
10.20.1 
Case Report Form Data 
This study will use an electronic data capture (EDC) system to collect study required Case Report Form 
(CRF) information.  Electronic CRFs (eCRFs) will be provided by the sponsor; required data will be taken 
from source documents and directly entered into the study database via the eCRFs by the appropriately 
delegated site personnel, in accordance with applicable regulations.  
 
 
  Data from the subject assessments will be entered into the database by delegated site personnel.   
Representatives from the clinical site may not make changes to the diaries except for administrative 
entries.  
The principal investigator, or appropriately delegated personnel, are responsible for entering data on 
the eCRFs.  The principal investigator, or appropriately delegated personnel, is required to approve all 
data on eCRFs via electronic signature. 
10.20.2 
 
 
 
 
 
 
 
 
 
 
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 39 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
10.22 
Subject Exit, Withdrawal or Discontinuation 
A subject has the right to withdraw from the study at any time and for any reason without prejudice to 
their future medical care by the principal investigator or institution.  Subjects will be provided standard 
medical care by their physician after their study participation ends. 
Examples of reasons for study exit include the following: 
• 
Normal study completion 
• 
Subject adverse event 
• 
Subject death 
• 
Subject lost to follow-up 
• 
Investigator decides to terminate the subject’s participation in the study (for example, due to lack of 
compliance, violation of/change in eligibility criteria) 
• 
Subject becomes pregnant 
• 
Medtronic requests subject be discontinued 
• 
Subject voluntarily withdraws from the study 
• 
Any clinical laboratory abnormality, inter-current illness, or other medical condition or situation 
occurs such that continued study participation would not be in the best interest of the subject 
 
A study exit eCRF will be completed for all enrolled subjects; the reason for withdrawal shall be recorded 
on the study exit eCRF. If a subject discontinues from the study prior to normal completion, the eCRFs 
for visits that have occurred up to the point of withdrawal as well as the study exit eCRF should be 
completed.  If a subject exits due to a device, procedure, or therapy-related adverse event or device 
deficiency, the appropriate event eCRFs should also be completed. 
 
In the case that the subject is determined to be lost to follow-up, details of a minimum of two attempts 
and the method of attempt (e.g., one letter and one phone record or two letters) to contact the subject 
must be recorded in the subject’s medical records. In addition, regulations set forth by the governing IRB 
must be followed. 
11. Risks and Benefits 
11.1 Potential Risks 
This is a post-market study and subjects will be treated in accordance with the labeled instructions for 
use and indications for Medtronic’s SCS therapy.  There are foreseeable risks that exist for all SCS 
patients regardless of whether they are in the study.  Furthermore, there are additional risks associated 
with subjects taking part in this study which are stated in Section 11.1.1.5 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 40 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
11.1.1 
Foreseeable Risks 
11.1.1.1 
Risks of Surgery 
Implanting a neurostimulation system has risks similar to other spinal procedures, including spinal fluid 
leak (spinal fluid collection under the skin), headaches, swelling, bruising, bleeding, infection, or 
paralysis.  
Subjects on anticoagulation therapy may be at higher risk for problems after surgery such as hematomas 
that could result in paralysis 
11.1.1.2 
Spinal Cord Stimulation Adverse Events Summary 
The implantation of a spinal cord stimulation system involves risks that are similar to other spinal 
procedures. In addition to those risks associated with surgery, the following adverse events may occur 
with implantation or use of a neurostimulation system. Certain adverse events may necessitate surgical 
intervention. 
• 
Allergic or immune system response to the implanted materials 
• 
Infection 
• 
Lead, extension, or neurostimulator erosion through the skin or migration 
• 
Leakage of cerebrospinal fluid 
• 
Lack of effective therapy or loss of therapeutic effect resulting in return of baseline symptoms 
• 
Patients on anticoagulation therapies may be at greater risk for postoperative complications 
such as hematomas that can result in paralysis 
• 
Persistent pain at the neurostimulator site 
• 
Placement of the epidural lead-extension is a surgical procedure that may expose patients to 
risks of epidural hemorrhage, hematoma, or paralysis 
• 
Radicular chest wall stimulation 
• 
Seroma or hematoma at the neurostimulator site 
• 
Change in stimulation, possibly related to cellular changes around the electrode(s), shifts in 
electrode position, loose electrical connections, lead or extension fractures, which has been 
described by some patients as uncomfortable stimulation (jolting or shocking sensation). 
• 
Formation of reactive tissue around the lead in the epidural space can result in delayed spinal 
cord compression and paralysis, requiring surgical intervention. Time to onset can range from 
weeks to many years after implant. 
• 
Stimulation-dependent gastrointestinal symptoms such as diarrhea, incontinence, or 
constipation 
• 
Stimulation-dependent bladder symptoms such as urinary retention, incontinence, or frequency 
• 
Tissue damage at the implant site 
 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 41 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
11.1.1.2.1 Pregnancy 
The safety and effectiveness of this therapy has not been established for pregnancy, unborn fetus, or 
delivery. The study procedures may involve unknown risks for female subjects, their embryo or fetus 
(unborn child), or delivery if they become pregnant. For this reason, pregnant females have been 
excluded from participating in this study.  Female subjects must agree to not become pregnant during 
the study by using a medically acceptable method of birth control; an identified pregnancy will result in 
immediate study withdrawal. 
11.1.1.3 
System Revision Risk 
The following neurostimulators: RestoreSensor, RestoreUltra, RestoreAdvanced, and Restore will 
require replacement 9 years or earlier from the date a subject received it, regardless of the number of 
times the neurostimulator is recharged. 
The Intellis neurostimulators will provide at least 9 years of operation before replacement is 
recommended.  
The Vanta neurostimulator is non-rechargeable and will require a system revision at the end of service. 
The time for this battery duration depends on the programming parameters for each person and can be 
estimated using the estimated battery longevity feature on the Clinician tablet.  
It is possible that the system will need to be revised (explanted, replaced, or repositioned) earlier than 
the expected duration for each neurostimulator.  Possible reasons for revision/explant may include 
infection, malfunction, and migration of the system components.  The risks associated with system 
revision are equivalent to the commercially available systems. 
11.1.1.4 
Risks Associated with the Recharging System 
The recharger, antenna, and belt are not sterile, and contact with the wound could cause an infection. 
The recharger is not intended to be used on an unhealed wound. 
Use of rechargeable neurostimulation systems may be associated with adverse events including heating 
sensation, discomfort, blistering not caused by heating, skin irritation, or redness near the implanted 
neurostimulator during or after recharging. Subjects should check for skin irritation or redness near the 
neurostimulator during recharging. 
11.1.1.5 
Study-Specific Risks 
As part of the study, subjects may be asked to have fluoroscopic or X-ray images taken.  This may be 
beyond what is standard of care.  A slight increase in cancer risk may exist for people exposed to 
radiation. Following the fluoroscopic procedure, the skin area exposed to the x-rays could react to 
produce an effect similar to a sun burn.  A skin reaction, if it occurs at all, could show up from a few 
hours to a few weeks after the procedure, and usually goes away on its own. 
Parameters used during the study may not be effective, which could result in an increased level of pain. 
Additionally, study parameters may cause an uncomfortable level of stimulation in acute or ambulatory 
settings. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 43 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
 If the subject is determined not to be a candidate, the subject will be programmed per 
standard of care and exited from the study. 
 
 the estimated battery longevity will be 
calculated compared to the current study settings. The programmer will compare the estimated battery 
duration of any new settings to that of the current programming settings and monitor current battery 
level. 
At any point in the course of the study, the patient may exit the study and continue with their standard 
of care for any reason, including concern over battery usage. In addition, the current battery level and 
estimated battery life of the neurostimulator will be reviewed 
 to further 
minimize the likelihood of any unexpected battery usage.  
Further mitigations reside in careful construction of the study. This includes selecting an appropriate 
patient population via inclusion/exclusion screening and closely monitoring subject progress and events 
reported for the study. Additionally, qualified investigators with proper SCS therapy experience will be 
selected, which includes trained personnel to perform any additional imaging taken as a part of the 
study.  
Labeling that contains precautions, warnings, and contraindications, as well as instructions on the use of 
the devices are available to investigators who may provide this information to subjects. 
11.3 Potential Benefits 
There may be no direct medical benefit to subjects participating in the study. During the study subjects 
will have increased interaction with physicians or medical staff compared to routine clinical care, which 
may provide some indirect health benefits.  The SCS settings used during this study may reduce subjects’ 
pain intensity, return subjects to a more fully functional status, improve their quality of life, or limit 
unwanted side effects. The SCS settings used in this study may also prolong the battery longevity of non-
rechargeable neurostimulators or increase time between recharging for rechargeable devices. These 
benefits cannot be guaranteed due to the investigational nature of this study.  
The primary anticipated benefit of this study is to help Medtronic with the understanding of SCS therapy 
and assist with the design of future studies and product improvements.  The information gathered from 
this study could also help clinicians optimize therapy for their patients. 
11.4 Risk-Benefit Rationale 
Subjects participating in this study will be exposed to risks from commercial SCS therapy that have been 
deemed, through existing PMA approval, to be outweighed by the benefits of treating chronic, 
intractable pain within approved indications. Additional risks that exist due to participation in the study, 
including reduced efficacy and uncomfortable stimulation have been minimized by mitigations within 
the study design, and will be properly communicated to potential subjects. The additional risk of earlier 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 44 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
battery depletion resulting in device replacement for patients with non-rechargeable devices has been 
minimized by estimating the battery longevity and will be properly communicated to potential subjects. 
12. Adverse Events and Device Deficiencies 
12.1 Adverse Events 
AE definitions are provided in Table 12-1. Each event is defined according to International Organization 
for Standardization (ISO) 14155.  Where the definition indicates “device”, it refers to any device used in 
the study.  This might be the device under investigation, or any market-released component of the 
system.   
Adverse Event (AE) information will be collected from the time the subject has been enrolled until they 
are discontinued from the study. AE information will be reported to Medtronic on an adverse event 
eCRF, one for each Adverse Event.  
Only those AEs which are related to the following will be collected: 
• 
The SCS system and accessories (device-related) 
• 
SCS therapy (therapy-related) 
• 
SCS procedure (procedure-related) 
 
Each event will be classified according to 5 different levels of causality using the following terms: 
- 
Not Related 
- 
Unlikely 
- 
Possible 
- 
Probable 
- 
Causal 
 
Only events that are classified as possible, probable or causal are considered to be related for data 
analysis. 
 
It is the responsibility of the investigator to identify the occurrence of adverse events and device 
deficiencies and to ensure all required information is accurately documented on the eCRF. See the eCRFs 
for the information to be reported for each adverse event.  
Documented pre-existing conditions are not considered adverse events unless the severity of the 
condition has worsened and is related to the implanted SCS system, procedure, accessories, or therapy. 
Events that are not reportable for this study are:  
- 
Lack of pain relief 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 45 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
o Pain symptoms will be collected as part of the efficacy measures 
- 
Sensation of stimulation (paresthesia) 
o Sensation of stimulation (e.g. tingling, buzzing) will not be reported as this may occur as 
part of this therapy.  Exception: Sensation or stimulation events that are 
uncomfortable to the subject (e.g. shocking, jolting) will be reported. 
- 
Adverse events unrelated to 
o Implanted SCS system, accessories or surgical procedure 
o Spinal cord stimulation therapy 
For adverse events that require immediate reporting, initial reporting may be done by phone, fax, or e-
mail, or on the eCRF by completing as much information as is available. The adverse event eCRF must be 
completed as soon as possible. 
The clinical course of each adverse event must be followed until the adverse event is resolved or the 
subject is in a stable condition. “Ongoing” adverse events must be assessed at each study visit. The 
adverse event eCRF should be updated when there is a change to the information provided on the form 
(e.g. change in intervention, outcome, relatedness, etc.). 
12.2 Device Deficiency 
The DD definition is provided in Table 12-1. DD information will be collected throughout the study and 
reported to Medtronic on a device event eCRF, one for each device deficiency. Note that DD that results 
in an AE to the subject should be captured as an AE only. 
12.3 Processing Updates and Resolution 
For any changes in status of a previously reported adverse event or DD (i.e. change in actions taken, 
change in outcome, change in relatedness), information needs to be updated on, or added to the 
original AE or DD form. All AEs must be followed until the AE has been resolved, is unresolved with no 
further actions planned, the subject dies or exits the study, or until study closure, whichever occurs first.  
In the event that a subject is exited from the study prior to study completion, all efforts should be made 
to continue following the subject until all unresolved system or procedure related AEs, as classified by 
the investigator, are resolved, unresolved with no further actions planned, or 30 days post study exit, 
whichever occurs first. 
At the time of study exit, all collected adverse events that are unresolved must be reviewed and an 
update to the original AE must be reported. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 46 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
12.4 Definitions/Classifications 
Table 12-1: Adverse Event and Device Deficiency Definitions 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 47 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
General 
Adverse Event (AE):  
Any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or 
other persons, whether or not related to the investigational medical device.  
NOTE 1: This definition includes events related to the investigational 
medical device or the 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 investigational medical devices. 
Adverse Device Effect 
(ADE):  
Adverse event related to the use of an investigational medical device. 
NOTE 1: This definition includes adverse events resulting from 
insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
from intentional misuse of the investigational medical device. 
Serious Adverse Event 
(SAE):  
Adverse event that 
a) led to death, 
b) led to serious deterioration in the health of the subject, that either 
resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function,  
c) led to foetal distress, foetal death or a congenital abnormality or birth 
defect. 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not considered 
a serious adverse event. 
Serious Adverse Device 
Effect (SADE):  
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Device Deficiency (DD):  
Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, safety or performance. 
NOTE: Device deficiencies include malfunctions, use errors, and inadequate 
labeling. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 48 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Malfunction: 
Failure of an investigational medical device to perform in accordance with its 
intended purpose when used in accordance with the instructions for use or 
CIP. 
Use Error:  
Act or omission of an act that results in a different medical device response 
than intended by the manufacturer or expected by the user. 
NOTE 1: Use error includes slips, lapses, and mistakes. 
NOTE 2: An unexpected physiological response of the subject does not in itself 
constitute a use error. 
Relatedness 
Device Related 
 
(includes all implantable 
components and features, 
associated introduction 
tools, 
operational and installed 
software and 
programmers as 
defined in the CIP, see 
Section 7.1) 
An AE that results from the presence or performance of any component of the 
system. 
 
Neurostimulator-related: An AE that results from the presence or performance 
(intended or otherwise) of the neurostimulator. 
 
Lead-related: An AE that results from the presence or performance (intended 
or otherwise) of the lead. 
 
Extension-related: An AE that results from the presence or performance 
(intended or otherwise) of the extension. 
 
External Study Device-related: An AE that results from the presence or 
performance (intended or otherwise) of an external study device (e.g. 
programmer, ENS). 
Therapy Related 
Event related to therapy delivery by device. Normally therapy-related events 
resolve when the device is turned off or reprogrammed. This category should 
not include events that resulted from a malfunction of the device (i.e. 
hardware-related events). 
Procedure Related 
An AE that occurs due to any procedure related to the implantation or surgical 
modification of the system. 
Seriousness 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 49 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Serious Adverse Event 
(SAE) 
AE that led to any of the following 
a) death, 
b) serious deterioration in the health of the subject, users or other persons 
as defined by one or more of the following: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
including chronic disease, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body 
function, 
c) fetal distress, fetal death or a congenital abnormality or birth defect 
including physical or mental impairment 
 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the CIP, without serious deterioration in health, is not 
considered an SAE. 
Serious Adverse Device 
Effect (SADE) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Causality 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 50 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Not Related 
Relationship to the device or procedures can be excluded when: 
− 
the event is not a known1 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 diagnosis2, when applicable; 
− 
harms to the subject 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. 
 
1When the event is not a known side effect of the product category the device 
belongs to or of similar devices and procedures, generally is considered “not 
related”. Yet, the unexpected effect shall not be excluded from evaluation and 
reporting. 
2If an investigational device gives an incorrect diagnosis, the patient might, for 
example, receive an unnecessary treatment and incur all the risks that 
accompany that treatment, or might be incorrectly diagnosed with a serious 
disease. In other cases, the patient might not receive an effective treatment 
(thereby missing out on the benefits that treatment would confer) or might 
not be diagnosed with the correct disease or condition.  
Unlikely 
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. 
Possible 
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. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 51 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Probable 
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. 
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 the investigational 
device or procedures are applied to; 
− 
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 subject is due to error in use; 
− 
the event depends on a false result given by the investigational 
device used for diagnosis1, 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. 
 
1If an investigational device gives an incorrect diagnosis, the patient 
might, for example, receive an unnecessary treatment and incur all the risks 
that accompany that treatment, or might be incorrectly diagnosed with a 
serious disease. In other cases, the patient might not receive an effective 
treatment (thereby missing out on the benefits that treatment would confer), 
or might not be diagnosed with the correct disease or condition. 
12.5 Reporting of Adverse Events and Device Deficiencies 
12.5.1 
Adverse Event and Device Deficiency Classification 
All AE and DD will be reviewed by a Medtronic representative. AEs will be classified according to the 
definitions provided.  
Upon receipt of AE at Medtronic, a Medtronic representative will review the AE/DD for completeness 
and accuracy and when necessary will request clarification and/or additional information from the 
Investigator. Medtronic will utilize MedDRA for Regulatory Activities, to assign a MedDRA term for each 
AE based on the information provided by the investigator.  

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 53 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Medtronic 
Submit in a timely manner after the investigator learns of the event or of new 
information in relation to an already reported event. 
IRB 
Submit to IRB per local reporting requirement. 
Sponsor shall submit to: 
IRB 
Submit to IRB per local reporting requirement. 
Investigators 
Submit per local reporting requirement.  
All other reportable AEs 
Investigator shall submit to: 
Medtronic 
Submit in a timely manner after the investigator first learns of the event. 
IRB 
Submit to IRB per local reporting requirement. 
Device Deficiencies 
Investigator shall submit to: 
Medtronic 
Submit in a timely manner after the investigator first learns of the event. 
IRB 
Submit to IRB per local reporting requirement. 
 
12.6 Subject Death 
The investigator must notify Medtronic immediately and the IRB, as required, after learning of a 
subject’s death, regardless of whether or not the death is device, procedure, or therapy-related. The 
investigator should also attempt to determine, as conclusively as possible, whether such deaths are 
related to the device system, procedure, or therapy. Deaths will be captured by a study exit eCRF and an 
adverse event eCRF if related to the device system, procedure, or therapy. 
If an autopsy is conducted, a copy of the report should be provided to Medtronic. Medtronic requests 
that all device system components that were being used at the time of the death be returned to 
Medtronic for analysis. Requested death certificates and/or source documentation should be provided 
to Medtronic.  If the death occurs at a location remote from the study site, it is the study site’s 
responsibility to make every attempt to retrieve all pertinent information related to the subject’s death 
and submit the investigator’s death summary of the known events surrounding the death to Medtronic. 
12.7 Product Complaint Reporting 
It is the responsibility of the investigator to report all product complaint(s) associated with a medical 
device distributed by Medtronic, regardless whether they are related to intended use, misuse or abuse 
of the product. Reporting must be done immediately and via the regular channels for market-released 
products. The reporting of product complaints by the clinical team must be done according to the local 
Standard Operating Procedures. Medtronic will notify the RAs (e.g. CA) as applicable for the following 
incidents immediately upon learning of them and is not limited to AEs and DDs only: 
• 
Any malfunction or deterioration in the characteristics and/or performance of a device, 
as well as any inadequacy in the labeling or instructions for use which led or might have 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 56 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
14.5 Safety Assessment 
Device, procedure, and therapy related adverse events, serious adverse events, and device deficiencies 
will be presented in summary tables within each study cohort report. If applicable, some high-level 
descriptive analyses may be performed by utilizing data across study cohorts. 
14.6 Sample Size Determination 
It is estimated that up to 360 subjects will be enrolled. Considering the research interests of multiple 
stimulation settings and longer enrollment of the study, a sample size of up to 360 subjects is deemed to 
be reasonable to characterize the effects of changes to stimulation settings, as well as to provide data 
for consideration of future studies. 
 
The sample size for each programming parameter group may vary based on the research interests, 
 
Table 14-1 and Figure 14-1. show precision 
estimates (the distance from mean to limits) by sample size and standard deviation of 
A sample 
size of 30 produces a two-sided 95% confidence interval with the precision that is equal to 0.93 when 
the estimated standard deviation is 2.5. 
 
Sample sizes in cohorts with hypothesis testing will be estimated based on at least 80% power with a 
significance level of 0.05 for two-sided tests or 0.025 for one-sided tests. 
 
 
Table 14-1: Precision by sample size and standard deviation 
 
Sample size 
(N) 
Standard deviation (S) 
1.0 
1.5 
2.0 
2.5 
3.0 
10 
0.72 
1.07 
1.43 
1.79 
2.15 
15 
0.55 
0.83 
1.11 
1.38 
1.66 
20 
0.47 
0.70 
0.94 
1.17 
1.40 
30 
0.37 
0.56 
0.75 
0.93 
1.12 
40 
0.32 
0.48 
0.64 
0.80 
0.96 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 57 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Figure 14-1: Precision by sample size and standard deviation 
 
 
 
14.7 Minimization of Bias 
Selection of subjects, treatment of subjects, and evaluation of study data are potential sources of bias. 
Methods that may be incorporated in the study design to minimize potential bias include (but are not 
limited to): 
• 
Limiting subject enrollment in a specific cohort to no more than 25% of total cohort 
sample size. 
• 
 Performing sensitivity analyses beyond the main analysis for the primary objective. 
In summary, potential sources of bias that may be encountered in this study have been considered and 
minimized by careful study design. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 58 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
15. Ethics 
15.1 Statement(s) of Compliance 
The study will be conducted in accordance with this protocol, the ethical principles that have their origin 
in the Declaration of Helsinki, all applicable regulatory requirements (21CFR§50 Protection of Human 
Subjects, 21CFR§56 IRB, and 21CFR§54 Financial Disclosure of Clinical Investigators, and 21CFR§803 
Medical Device Reporting) and will comply with Good Clinical Practices (GCP) as a guideline for this 
study.  The principles of the Declaration of Helsinki have been implemented in this study by means of 
the patient informed consent process, IRB approval, risk benefit assessment, study training, clinical trial 
registration on http://clinicaltrials.gov/, and publication policy.  Study Investigators will be required to 
sign an Investigator Agreement stating their intent to adhere to applicable regulations. 
The study will not begin at any site until an IRB letter approving the protocol, the ICF, and any other 
subject-facing documents is received by Medtronic.   
Details related to stipends provided to study subjects are outlined in the subject ICF.  
16. Study Administration 
16.1 Monitoring 
It is the responsibility of Medtronic to ensure proper monitoring of this study.  Trained Medtronic 
personnel or delegates appointed by Medtronic may perform study monitoring at the study site in order 
to ensure that the study is conducted in accordance with the CIP, the CTA, and the applicable regulatory 
and local requirements. Medtronic, or delegates, must therefore be allowed direct access to the 
subjects’ case histories (clinic and hospital records, and other source data/documentation) upon request 
as per the IC, Research Authorization (where applicable) and CTA.  The principal investigator should also 
be available during monitoring visits.   
16.1.1 
Monitoring Visits 
Frequency of monitoring visits may be based upon subject enrollment, study compliance, number of 
adverse events, number of deviations, observations from previous monitoring visits and any suspected 
inconsistency in data that requires investigation. Regulatory documents will be reviewed at each study 
site. Monitoring for the study, including site initiation visits, interim monitoring visits, and closeout visits, 
will be done in accordance with the study-specific monitoring plan. 
Monitoring visits may be conducted periodically to assess study site progress, the investigator’s 
adherence to the CIP, regulatory compliance including, but not limited to, IRB approval and review of 
the study, maintenance of records and reports, and review of source documents against subject CRFs in 
accordance to the study-specific monitoring plan. Monitors review study site regulatory and study 
compliance by identifying observations of non-compliance and communicating those observations along 
with recommendations for preventative/corrective actions to study site personnel.  Monitors may work 
with study personnel to determine appropriate corrective action recommendations and to identify 
trends within the study or at a particular study site. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 59 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
16.2 Data Management 
This study will use an Electronic Data Capture (EDC) system, which allows the study centers to enter data 
directly to the eCRF in the sponsor’s database over a secure internet connection. This system is fully 
validated and controls user access, ensures data integrity, and maintains audit trails.  
The principal investigator will ensure that only appropriately delegated study personnel are given access 
to the electronic eCRF system; user IDs and passwords may not be shared. 
The principal investigator is responsible for the overall quality (completeness and accuracy) of the data 
entered on the eCRFs and in all other required reports.  Data reported on the eCRFs, must be derived 
from and consistent with source documents, unless otherwise stated in this section or the study 
monitoring plan. If discrepancies in source are identified (eg, during monitoring), these need to be 
corrected or justified in a documented rationale, signed and dated by the principal investigator, or 
authorized delegate, to be maintained as a part of the subject’s records.  The principal investigator will 
review all data entries on a regular basis and ensure any corrections are appropriately made and 
documented.  
The eCRF may be considered source for the following data collection elements: 
• 
Investigator assessment of adverse event relatedness 
• 
Detail pertaining to and reason for protocol deviation 
Even when the eCRF may be considered as source, an alternative method of source documentation is 
always strongly encouraged.  
Required data will be recorded on the appropriate eCRFs at the time of or promptly after each subject’s 
visit. Only authorized persons can complete eCRFs. eCRFs will be approved by the principal investigator, 
or authorized delegate with an electronic signature.  
Medtronic personnel will perform routine edit and consistency checks, in-house and during monitoring 
visits, for items such as missing data or inconsistent data.  Identified data inconsistencies will be 
resolved by use of data queries; investigators and site personnel will review data queries and respond to 
them in a timely manner. The resolved discrepancy will become a part of the eCRF record for the 
subject. At the end of the study, the data will be locked and will be retained indefinitely by Medtronic. 
User access to the EDC system will be granted to each individual based on his or her delegation of 
authority. If a person only authorized to complete eCRFs makes changes to an already signed eCRF, the 
system will require the investigator, or authorized delegate, to re-sign the eCRF. 
16.3 Direct Access to Source Data/Documents 
Source data are defined as all information in original records, certified copies of original records of 
clinical findings, observations, or other activities in a clinical investigation necessary for the 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 60 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
reconstruction and evaluation of the clinical investigation. A source document is a printed, optical, or 
electrical document containing source data. Examples of source documents include the following: 
hospital records, laboratory notes, device accountability records, photographic negatives, radiographs, 
records kept at the investigational site, and at laboratories involved in the clinical investigation. 
The principal investigator is responsible for ensuring source data and documents are complete, legible 
and accurate; and entries are made in a timely manner by appropriately delegated study staff.  
The principal investigator and site personnel will provide the Medtronic monitor(s) with direct access to 
source data that support the data on the CRFs as well as other documentation supporting the conduct of 
the study.   
Medtronic or third-party auditors representing Medtronic may perform Quality Assurance audits to 
verify the performance of the monitoring process and study conduct, and to ensure compliance with 
applicable regulations. Representatives for regulatory bodies, such as the FDA, may also perform site 
inspections related to this clinical study.  The principal investigator, site personnel, and institution will 
provide auditors with direct access to primary source data and all study-related documentation.  
Medtronic will investigate suspected cases of fraud or misconduct as appropriate. 
16.4 Confidentiality 
All records and other information about subjects participating in this clinical study will be treated as 
confidential. Subject confidentiality will be maintained throughout the clinical study to the extent 
permitted by law. That is, every attempt will be made to remove subject identifiers from clinical study 
documents. For this purpose, a unique subject identification code (study - site - subject number) will be 
assigned and used to allow identification of all data reported for each subject. This will also ensure that 
the information can be tracked back to the source data.  
Study data may be made available to third parties, e.g., in the case of an audit or inspection performed 
by regulatory authorities, provided the data are treated confidentially and that the subject’s privacy is 
guaranteed. The identity of a subject will never be disclosed if study data are published. Only 
anonymized data will be analyzed and published. 
16.5 Liability 
Medtronic, Inc. is a wholly owned subsidiary of Medtronic, PLC, which as the parent company of such 
entity maintains appropriate clinical study liability insurance coverage, as applicable and as required 
under applicable laws and regulations and will comply with applicable local law and custom concerning 
specific insurance coverage. If required, a clinical study insurance statement/certificate will be provided 
to the IRB. In addition, subject compensation, indemnification, and insurance may be addressed within a 
separate clinical trial agreement. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 61 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
16.6 CIP Amendments 
Amendments to the CIP may be initiated by Medtronic to address changes to the conduct of the study.   
Amendments to the CIP, and associated documents, must be approved by Medtronic and submitted to 
the IRBs for approval prior to implementation except when necessary to eliminate an immediate or 
apparent immediate hazard to participating subjects. 
16.7 Record Retention 
16.7.1 
Investigator Records 
Documentation for this study will be produced and maintained to ensure that a complete history of the 
study exists.  Documents created for this study, including all versions of original documents, will be 
identifiable and appropriately stored to assure control and traceability of data related to this study. 
The principal investigator is responsible for ensuring all essential study documentation is retained and 
accessible for 2 years (or longer as local law or hospital administration requires) after the investigation is 
terminated or completed.  The retention period may be longer if required by Medtronic or regulatory 
requirements. Medtronic will be responsible for notifying sites of extensions to the 2-year minimum 
record retention requirements.  The principal investigator will ensure that essential study documents 
are not destroyed until written permission has been obtained from Medtronic.  Medtronic will be 
notified in writing of any transfer of study documentation. 
16.7.2 
Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records: 
• 
All correspondence which pertains to the investigation 
• 
Sample of label attached to investigational device 
• 
Signed Investigator Trial Agreements and CV of principal investigator and key members 
of the investigation study site team (as required by local law), delegated task list 
• 
All approved IC templates, and other information provided to the subjects and 
advertisements, including translations 
• 
Copies of all IRB approval letters and relevant IRB correspondence and IRB voting 
list/roster/letter of assurance 
• 
Names of the institutions in which the study will be conducted 
• 
 Monitoring visit reports 
• 
Statistical analyses and underlying supporting data 
• 
Final report of the study 
• 
The CIP, study related reports, and revisions 
• 
Study training records for study site personnel and Medtronic personnel involved in the 
study 
• 
Any other records that local regulatory agencies require to be maintained.  

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 62 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Medtronic records and reports will be maintained in a password-protected document management 
system, and paper documents (where applicable) will be stored in stored in secured file cabinets at 
Medtronic during the course of this study.  
After closure of the study, Medtronic will archive records and reports indefinitely. 
16.8 Reporting Requirements 
16.8.1 
Investigator Reports 
The principal investigator is responsible for the preparation (review and signature) and submission to 
the sponsor of all case report forms, reportable adverse events, device deficiencies, deaths, and any 
deviations from the CIP. If any action is taken by an IRB with respect to this clinical study, copies of all 
pertinent documentation must be forwarded to Medtronic in a timely manner. Reports are subject to 
inspection and to the retention requirements as described in Section 16.7.1 for investigator records.  
16.8.2 
Sponsor Reports 
Medtronic shall prepare and submit complete, accurate, and timely reports as required per geography 
and IRB reporting requirements.  In addition, Medtronic shall, upon request of the reviewing IRB, 
provide accurate, complete and current information about any aspect of the investigation. 
16.9 Publication and Use of Information 
The study will be registered at http://clinicaltrials.gov before first enrollment in the study. Study data 
and results will be made available as required per regulations.   
Medtronic must be notified of any intent to publish data stemming from this clinical study.  
Medtronic has developed a separate publication plan that will provide detailed information about a 
publication committee, if applicable, authorship selection, publication process, and handling requests 
for data. Publications will be governed by the terms of the investigator agreement and publication plan. 
16.10 
Suspension or Early Termination 
Early termination is the closure of a clinical study that occurs prior to meeting defined endpoints. This is 
possible for the whole study or a single center. Suspension is a temporary postponement of study 
activities related to enrollment. This is possible for the whole study or a single center. 
Medtronic reserves the right to suspend or terminate the study or an individual study site at any time. 
Possible reasons for considering study suspension or termination of the study include but are not limited 
to: 
• 
Adverse events associated with the system or product under investigation which might 
endanger the safety or welfare of the subject 
• 
Observed/suspected performance different from the product’s design intent  
• 
Decision by Medtronic 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 63 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
Possible reasons for clinical investigator or center termination or suspension include but are not limited 
to: 
• 
Failure to obtain initial IRB approval or annual renewal of the study 
• 
Persistent non-compliance to the clinical study CIP (e.g. failure to adhere to inclusion/exclusion 
criteria, failure to follow subjects per scheduled follow-ups) 
• 
Lack of enrollment 
• 
Noncompliance to regulations and the terms of the clinical trial agreement (e.g. failure to 
submit data in a timely manner, failure to follow-up on data queries and monitoring findings in a 
timely manner, etc.) 
• 
IRB suspension of the center 
• 
Fraud or fraudulent misconduct is discovered (as defined by local law and regulations) 
• 
Investigator request (e.g. no longer able to support the study) 
17. References 
1. A Yearwood TL1, Hershey B, Bradley K, Lee D. Pulse width programming in spinal cord 
stimulation: a clinical study. Pain Physician. 2010 Jul-Aug;13(4):321-35. 
2. Abejón D1, Rueda P, del Saz J, Arango S, Monzón E, Gilsanz F. Is the introduction of another 
variable to the strength-duration curve necessary in neurostimulation? Neuromodulation. 2015 
Apr;18(3):182-90; discussion 190. doi: 10.1111/ner.12223. Epub 2014 Aug 29. 
3. Miller JP, Eldabe S, Buchser E, Johanek LM, Guan Y, Linderoth B. Parameters of Spinal Cord 
Stimulation and Their Role in Electrical Charge Delivery: A Review. Neuromodulation. 2016; 
19:373-384. 
4. Abejón D1, Cameron T, Feler C, Pérez-Cajaraville J. Electric parameters optimization in spinal 
cord stimulation. Study in conventional nonrechargeable systems. Neuromodulation. 2010 
Oct;13(4):281-6; discussion 286-7. doi: 10.1111/j.1525-1403.2010.00290.x. 
5. Al-kaisy A, Palmisani S, Pang D, Sanderson K, Wesley S, Tan Y, McCammon S, Trescott A. 
Prospective, Randomized, Sham-Control, Double Blind, Crossover Trial of Subthreshold Spinal 
cord Stimulation at Various Kilohertz Frequencies in Subjects Suffering from Failed Back Surgery 
Syndrome (SCS Frequency Study). Neuromodulation. 2018 Jul;21(5):457-465. 
6. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Brown 
LL, Yearood TL, Bundschu R, Burton AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz High-
Frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord 
Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized 
Controlled Trial. Anesthesiology. 2015 Oct; 123(4):851-60. 
7. Smith H1, Youn Y, Pilitsis JG. Successful use of high-frequency spinal cord stimulation following 
traditional treatment failure. Stereotact Funct Neurosurg. 2015;93(3):190-3. doi: 
10.1159/000380825. Epub 2015 Apr 1. 
8. North JM1, Hong KJ2, Cho PY3. Clinical Outcomes of 1 kHz Subperception Spinal Cord 
Stimulation in Implanted Patients With Failed Paresthesia-Based Stimulation: Results of a 
Prospective Randomized Controlled Trial. Neuromodulation. 2016 Oct;19(7):731-737. doi: 
10.1111/ner.12441. Epub 2016 May 17. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 64 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
9. Youn Y1, Smith H, Morris B, Argoff C, Pilitsis JG. The Effect of High-Frequency Stimulation on 
Sensory Thresholds in Chronic Pain Patients. Stereotact Funct Neurosurg. 2015;93(5):355-9. doi: 
10.1159/000438998. Epub 2015 Oct 8. 
10. Thomson SJ1, Tavakkolizadeh M2, Love-Jones S3, Patel NK4, Gu JW5, Bains A6, Doan Q5, Moffitt 
M5. Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the 
PROCO Randomized Controlled Trial. Neuromodulation. 2018 Jan;21(1):67-76. doi: 
10.1111/ner.12746. Epub 2017 Dec 8. 
11. Benyamin R1, Kramer J, Vallejo R. A case of spinal cord stimulation in Raynaud's Phenomenon: 
can subthreshold sensory stimulation have an effect? Pain Physician. 2007 May;10(3):473-8. 
12. Eddicks S, Maier-Hauff K, Schenk M, Müller A, Baumann G, Theres H. Thoracic spinal cord 
stimulation improves functional status and relieves symptoms in patients with refractory angina 
pectoris: the first placebo-controlled randomised study. Heart. 2007 May;93(5):585-90. Epub 
2007 Jan 19. 
13. Wolter T1, Kiemen A, Porzelius C, Kaube H. Effects of sub-perception threshold spinal cord 
stimulation in neuropathic pain: a randomized controlled double-blind crossover study. Eur J 
Pain. 2012 May;16(5):648-55. doi: 10.1002/j.1532-2149.2011.00060.x. Epub 2011 Dec 19. 
14. Al-Kaisy A1, Palmisani S1, Smith TE1, Pang D1, Lam K2, Burgoyne W3, Houghton R4, Hudson E5, 
Lucas J2. 10 kHz High-Frequency Spinal Cord Stimulation for Chronic Axial Low Back Pain in 
Patients With No History of Spinal Surgery: A Preliminary, Prospective, Open Label and Proof-of-
Concept Study. Neuromodulation. 2017 Jan;20(1):63-70. doi: 10.1111/ner.12563. Epub 2016 
Dec 26 
15. Van Buyten JP1, Al-Kaisy A, Smet I, Palmisani S, Smith T. High-frequency spinal cord stimulation 
for the treatment of chronic back pain patients: results of a prospective multicenter European 
clinical study. Neuromodulation. 2013 Jan-Feb;16(1):59-65; discussion 65-6. doi: 
10.1111/ner.12006. Epub 2012 Nov 30. 
16. Kapural L1, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Brown 
LL, Yearwood TL, Bundschu R, Burton AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz High-
frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord 
Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized 
Controlled Trial. Anesthesiology. 2015 Oct;123(4):851-60. doi: 
10.1097/ALN.0000000000000774. 
17. De Ridder D1, Vanneste S, Plazier M, van der Loo E, Menovsky Burst spinal cord stimulation: 
toward paresthesia-free pain suppression. Neurosurgery. 2010 May;66(5):986-90. doi: 
10.1227/01.NEU.0000368153.44883.B3. 
18. De Ridder D1, Plazier M, Kamerling N, Menovsky T, Vanneste S. Burst spinal cord stimulation for 
limb and back pain. World Neurosurg. 2013 Nov;80(5):642-649.e1. doi: 
10.1016/j.wneu.2013.01.040. Epub 2013 Jan 12. 
19. Frey ME, Manchikanti L, Benyamin RM, Schultz DM, Smith HS, Cohen SP. Spinal cord stimulation 
for patients with failed back surgery syndrome: a systematic review. Pain Physician. 2009 Mar-
Apr; 12(2):379-97. 
20. Taylor RS. Spinal cord stimulation in complex regional pain syndrome and refractory neuropathic 
back and leg pain/failed back surgery syndrome: results of a systematic review and meta-
analysis. J Pain Symptom Manage. 2006 Apr; 31(4 Suppl):S13-9. 
21. Turner JA, Loeser JD, Bell KG. Spinal cord stimulation for chronic low back pain: a systematic 
literature synthesis. Neurosurgery. 1995 Dec;37(6):1088-95. 

SCS Research Study Clinical Investigation Plan 
 
 
MDT18036 
Version 3.0 
Page 65 of 66 
 
Medtronic Business Restricted 
 
 
CONFIDENTIAL 
056-F275, Rev D Clinical Investigation Plan Template 
22. Turner JA, Loeser JD, Deyo RA, Snaders SB. Spinal cord stimulation for patients with failed back 
surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and 
complications. Pain. 2004 Mar; 108(1-2):137-47. 
23. Duarte RV, Andronis L, Lenders MW, de Vos CC. Quality of life increases in patients with painful 
diabetic neuropathy following treatment with spinal cord stimulation. Qual Life Res. 2016 
Jul;25(7):1771-7. doi: 10.1007/s11136-015-1211-4.  
24. Harke H, Gretenkort P, Ladleif HU, Rahman S. Spinal cord stimulation in sympathetically 
maintained complex regional pain syndrome type I with severe disability. A prospective clinical 
study. Eur J Pain. 2005 Aug;9(4):363-73. 
25. Oakley JC, Weiner RL. Spinal cord stimulation for complex regional pain syndrome: a prospective 
study of 19 patients at two centers. Neuromodulation. 1999 Jan;2(1):47-50. 
26. Kemler MA, Barendse GAM, van Kleef M, de Vet HCW, Rijks CPM, Furnee CA, van den 
Wildenberg FAJM. Spinal cord stimulation inpatients wit chronic reflex sympathetic dystrophy. 
New Eng J Med. 2000; 343(9):618-624. 
27. Chivukula S, Tempel ZJ, Weiner GM, Gande AV, Chen CJ, Ding D, Moossy JJ. Cervical and 
cervicomedullary spinal cord stimulation for chronic pain: Efficacy and outcomes. Clin Neurol 
Neursurg. 2014 Dec; 127:33-41. 
28. Deer TR, Skaribas IM, Haider N, Salmon J, Kim C, Nelson C, Tracy J, Espinet A, Lininger TE, Tiso R, 
Archacki MA, Washburn SN. Effectiveness of Cervical Spinal Cord Stimulation for the 
Management of Chronic Pain. Neuromodulation 2014; 17:265-271. 
29. Burchiel KJ, Anderson VC, Brown FD, Fessler RG, Friedman WA, Pelofsky S, Weiner RL, Oakley J, 
Shatin D. Prospective, multicenter study of spinal cord stimulation for relief of chronic back pain. 
Spine (Phila Pa 1976). 1996 Dec 1;21(230:2786-94. 
30. Thomson SJ, Tavakkolizadeh M, Love-Jones S, Patek NK, Gu JW, Bains A, Doan Q, Moffitt M. 
Effects of Rate on Analgesia in Kilohertz Frequency Spinal Cord Stimulation: Results of the 
PROCO Randomized Controlled Trial. Neuromodulation. 2018 Jan;21(1):67-76. Epub 2017 Dec 8. 
31. Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Brown 
LL, Yearwood TL, Bundschu R, Burton AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz High-
frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord 
Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized 
Controlled Trial. Anesthesiology. 2015 Oct;123(4):851-60. 
32. Kumar K, Hunter G, Demeria D. Spinal cord stimulation in treatment of chronic benign pain: 
challenges in treatment planning and present status, a 22-year experience. Neurosurgery. 2006 
Mar; 58(3):481-96. 
33. 
 
 
34. 
 
 
35. 
 
 
36.