Study to Demonstrate the Value of Fast-Acting Subperception (FAST) Using the Spectra WaveWriter™ Spinal Cord Stimulator System in the Treatment of Chronic Pain (COMBO Study)
Phase: NA
Conditions: Chronic Pain
Sponsor: Boston Scientific Corporation

COVER PAGE 
 
FAST STUDY (NCT04231409) 
Study to Demonstrate the Value of Fast-Acting Subperception (FAST) using the Spectra WaveWriter™ 
Spinal Cord Stimulator System in the Treatment of Chronic Pain (A4070) 
 
 
 
 
 
 
This serves as a cover page for the FAST Study – A Sub-study of COMBO Study (NCT03689920) 
 
 
 
Version E (Current Version): 31 Jan 2020 
 
 
Sponsored By 
Boston Scientific Neuromodulation Corporation 
25155 Rye Canyon Loop 
Valencia, CA 91355 
United States of America 

Form/Template 92120219_Rev/Ver C 
         Confidential               FAST Study Appendix to COMBO Study, 92285183, Rev/Ver E 
 
Page 1 of 38 
 
 
 
Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain 
 
FAST Study 
COMBO Sub-Study 
 
A4070  
CLINICAL INVESTIGATION PLAN 
 
NCT03689920 
 
Sponsored By 
Boston Scientific Neuromodulation Corporation  
25155 Rye Canyon Loop 
Valencia, CA 91355 
United States of America 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
 
 
 
 
 
 

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Contact Information 
Role 
Contact  
Clinical Contact 
Natalie Bloom Lyons 
Director, U.S. Clinical Operations 
Boston Scientific Neuromodulation Corporation 
25155 Rye Canyon Loop 
Valencia, CA 91355  
Telephone: (763) 228-9040  
Fax: (661) 949-4592   
Email: natalie.bloomlyons@bsci.com 
 
Roshini Jain  
Director, Clinical Sciences and Scientific Communications 
Clinical Research Department 
Boston Scientific Neuromodulation 
25155 Rye Canyon Loop 
Valencia, CA 91355 USA 
Telephone: (661) 949-4350 
Fax: (661) 949-4592 
Email: Roshini.jain@bsci.com 
Coordinating Principal 
Investigator 
Mark S. Wallace, M.D. 
University of California San Diego Medical Center 
9300 Campus Point Dr  
La Jolla, CA  92037 United States 
 
 
 

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2. Protocol Synopsis 
FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
Primary 
Objective 
To evaluate the effectiveness of Spinal Cord Stimulation (SCS) with 
fast-acting subperception (FAST) as compared to subperception SCS 
in patients with chronic pain when using the Boston Scientific Spectra 
WaveWriter SCS System. 
Secondary 
Objectives  
To determine the impact of Spectra WaveWriter SCS System on global 
patient outcomes including quality of life, patient preference, etc.   
Indication(s) for 
Use  
The Spectra WaveWriter Spinal Cord Stimulator (SCS) System is 
indicated as an aid in the management of chronic intractable pain of the 
trunk and/or limbs, including unilateral or bilateral pain associated with 
the following: failed back surgery syndrome, Complex Regional Pain 
Syndrome (CRPS) Types I and II, intractable low back pain and leg 
pain. 
Commercial 
Device/System  
BSC Spectra WaveWriter™ SCS System 
Study Design 
Prospective, multi-center, parallel-group randomized controlled trial 
with an adaptive design  
Planned 
Number of 
Subjects 
Up to 148 randomized subjects 
Planned 
Number of Sites 
/ Countries 
Up to 25 sites in the United States. 
 

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FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
Safety 
Parameters 
Rates of occurrence of all device hardware, device stimulation and 
procedure related non-serious adverse events, all serious adverse events, 
and unanticipated adverse events through the end of the study. 
Primary 
Effectiveness 
Endpoint 
Proportion of subjects with 50% or greater reduction from Baseline Visit 
in average overall pain intensity at 3 months post-randomization, with 
no increase in baseline average daily opioid medications used to treat 
pain. 
Secondary 
Effectiveness 
Endpoint 
The following secondary endpoints will be analyzed as a comparison 
between the two groups. Assessments required for deriving each 
endpoint are denoted in parentheses. 
 Percentage of subjects who report clinically significant 
improvement in overall pain post-activation  (Activation 
Questionnaire)  
 Change in average overall pain intensity from pre-activation to 
post-activation (Activation Questionnaire) 
 Change in overall pain intensity from Baseline Visit to 3 mo. 
post-randomization Visit (VRS)  
 Percent Pain Relief in overall pain at 3 mo. post-randomization 
Visit (PPR) 
 Patient global impression of change at 3 mo. post-randomization 
Visit (PGI-C) 
 Clinician global impression of change at 3 mos. post-
randomization Visit (CGI-C) 
 Treatment Satisfaction at 3 months post-randomization Visit 
(TSQM-9m) 
 Change in disability from Baseline Visit to 3 mos. post-
randomization Visit (ODIv2.1a) 
 
Change in sleep from Baseline Visit to 3 mos. post-randomization 
Visit (PSQI)
Exploratory 
Endpoints 
The following exploratory endpoints will be evaluated. Assessments 
required for deriving each endpoint are denoted in parentheses 

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FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
 Change in average low back pain intensity from pre-activation to 
post-activation (Activation Questionnaire) 
 Change in average leg pain intensity from pre-activation to post-
activation (Activation Questionnaire) 
 Change in average overall pain intensity from Baseline Visit to 
6, 9 12 and 24 months post-randomization Visits (VRS) 
 Change in average low back pain intensity from Baseline Visit to 
6, 9 12 and 24 months post-randomization Visits (VRS) 
 Change in average leg pain intensity from Baseline Visit to 6, 9 
12 and 24 months post-randomization Visits (VRS) 
 Change in average overall pain intensity from Baseline Visit to 
6, 9 12 and 24 months post-randomization Visits (NRS) 
 Change in average low back pain intensity from Baseline Visit to 
6, 9 12 and 24 months post-randomization Visits (NRS) 
 Change in average leg pain intensity from Baseline Visit to 6, 9 
12 and 24 months post-randomization Visits (NRS) 
 Percent pain relief of overall pain at 6, 9 12 and 24 months post-
randomization Visits (PPR) 
 Percent pain relief of low back pain at 6, 9 12 and 24 months 
post-randomization Visits (PPR) 
 Percent pain relief of leg pain at 6, 9 12 and 24 months post-
randomization Visits (PPR) 
 Clinician global impression of change at 6, 9 12 and 24 months 
post-randomization Visits (CGI-C) 
 Patient global impression of change at 6, 9 12 and 24 months 
post-randomization Visits (PGI-C) 
 Treatment satisfaction at 6, 9 12 and 24 months post-
randomization Visits (TSQM-9m) 
 Change in quality of life from Baseline Visit to 6, 9 12 and 24 
months post-randomization Visits (SF-36v2) 

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FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
 Change in disability from Baseline Visit to 6, 9 12 and 24 
months post-randomization Visits (ODIv2.1a) 
 
Change in sleep from Baseline Visit to 6, 9 12 and 24 months post-
randomization Visit (PSQI) 
Follow-up 
Schedule 
Study events occur at the following time points: 
 Screening  
 Opioid Medication Lock Visit (Up to 35 days following 
Informed Consent) 
 Baseline Period (14 days) 
 Baseline Visit (0 - 7 days post Baseline Period) 
 Implant Procedures (up to 90 days post Baseline Visit)  
 Healing Period (0 - 28 days) 
 Randomization Visit (Day 0) 
 Programming Lock Visit (70 - 14 days post-randomization Visit)
 3 Month Visit (90 + 14 days post-randomization Visit) 
 6-Month Visit (180 ± 30 days post-randomization Visit) 
 9-Month Visit (270 ± 30 days post-randomization Visit) 
 Year 1 Visit (365 ± 30 days post-randomization Visit) 
 Year 2 Visit (730 ± 30 days post-randomization Visit) 
Study Duration Enrollment is expected to be completed in approximately 14 months; 
therefore, the total study duration is estimated to be approximately 41 
months. 
Participant 
Duration 
The study duration for each subject is expected to be approximately 27 
months. 
Inclusion 
Criteria 
IC1. 
Chronic pain of the trunk and/or limbs for at least 6 months with 
back pain greater or equal to leg pain.    

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FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
IC2. 
Chronic, intractable pain of the trunk and/or limbs which has 
been refractory to conservative therapy (E.g. pain medications, 
physical therapy, facet joint/medial branch nerve blocks.) 
IC3. 
No back surgery within 6 months prior to Screening 
IC4. 
Average overall pain intensity (leg and/or low back pain) of 6 or 
greater on a 0-10 numerical rating scale at Baseline Visit based 
on 7-day recall 
IC5. 
If taking prescription opioids for primary chronic pain complaint 
(low back and/or leg pain), must have been on a stable 
prescription (same drug(s) and dose(s)) 30 days prior to 
Screening 
IC6. 
Consumed an average total daily morphine equivalent of ≤200 
mg during the 30 days prior to Screening 
IC7. 
Willing and able to comply with all protocol-required procedures 
and assessments/evaluations  
IC8. 
Baseline Oswestry Disability Index score ≥40 and ≤80 
IC9. 
22 years of age or older when written informed consent is 
obtained  
IC10. Eligible candidate for SCS from a psychological and psychiatric 
standpoint as determined within 180 days prior to Baseline Visit, 
per site’s routine screening process  
IC11. Able to independently read and complete all questionnaires and 
assessments provided in English 
IC12. If female of childbearing potential: not pregnant, as evidenced 
by a negative pregnancy test at Screening 
IC13. Subject signed a valid, IRB-approved informed consent form 
(ICF) provided in English
Exclusion 
Criteria 
EC1. Average leg pain intensity is greater than average low back pain 
intensity as reported during Baseline Period 
EC2. Patient exhibits catastrophization based on physician evaluation 
(e.g., average overall daily pain intensity of 10 on a 0-10 
numerical rating scale, every day during the 7 days prior to 
Screening, based on patient recall)

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FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
EC3. Radiographic evidence of spinal instability requiring fusion 
EC4. Primary pain complaint of vascular origin (e.g. peripheral 
vascular disease) 
EC5. Spinal pain secondary to neoplasm, infection, autoimmune 
disorder with spinal involvement, or a spinal metabolic disorder  
EC6. Visceral pain referred to the low back and/or legs 
EC7. Any pain-related diagnosis or medical/psychological condition 
that, in the clinician’s best judgment, might confound reporting 
of study outcomes (e.g. pelvic pain, anginal pain, chronic 
migraine, brain or spinal cord tumor) 
EC8. Require implantation of lead(s) in the cervical epidural space 
EC9. Current systemic infection, or local infection in close proximity 
to anticipated surgical field, at Screening 
EC10. High surgical risk 
EC11. Body mass index ≥ 45 at Screening 
EC12. Terminal illness with anticipated survival < 12 months 
EC13. Current condition associated with risk of immunocompromise 
that might increase risk of infection during study duration  
EC14. Currently on any anticoagulant medications that cannot be 
discontinued during perioperative period 
EC15. Significant cognitive impairment at Screening that, in the 
opinion of the Investigator, would reasonably be expected to 
impair the study candidate’s ability to participate in the study 
EC16. Participating (or intends to participate) in another drug or device 
clinical trial that may influence the data that will be collected for 
this study 
EC17. Previous spinal cord stimulation trial or is already implanted 
with an active implantable device(s) (e.g. pacemaker, drug 
pump, implantable pulse generator) 
EC18. A female who is breastfeeding

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FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
EC19. A female of childbearing potential planning to get pregnant 
during the course of the study or not using adequate 
contraception  
EC20. Plan to receive any massage or manipulation directly over the 
leads or by the anticipated location of the IPG or treatments that 
involve sudden jerking motions of the torso at any time during 
the course of the study 
EC21. A condition currently requiring or likely to require the use of 
MRI or diathermy 
EC22. Any injury or medical/psychological condition that might be 
significantly exacerbated by the implant surgery or the presence 
of an implantable stimulator or otherwise compromise subject 
safety 
EC23. Unable to operate the study device   
Statistical Methods  
Primary 
Statistical 
Hypothesis 
The primary statistical hypothesis in this study is that the proportion of 
subjects with 50% or greater reduction from Baseline Visit in average 
daily overall pain intensity at 3 months post randomization in the FAST 
group is non-inferior compared to the Control (i.e.  subperception) group 
 H0:  πt -  πc  ≤ -0.20 
 
H1:  πt -  πc  > -0.20 
 
Where πt and πc are the proportion of subjects with 50% or greater 
reduction from Baseline in average daily overall pain intensity at 3 
months post randomization with no increase in baseline average daily 
opioid pain medications using FAST and  subperception settings, 
respectively. The study’s non-inferiority margin is 0.20.  
Statistical Test 
Method 
The 95% confidence interval of πt -  πc will be computed. The study will 
be considered a success if, using the Intent-To-Treat (ITT) analysis, the 
lower bound of the two-sided 95% confidence interval for the difference 
is great than -0.20. 

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FAST Study  
A Study to Demonstrate the Value of Fast-Acting Subperception (FAST) 
using the Spectra WaveWriter™ Spinal Cord Stimulator System in the 
Treatment of Chronic Pain  
Sample Size 
Parameters 
Test significance level (α) 
           0.025 
1 or 2 sided test                            
1 
Difference in Response (πt - πc) 
0.05 
Non-inferiority margin (δ) 
           0.20 
Proportion of Responder in Control group (πc)    0.60 
Power (1- β)                                     0.80 
N  
 
 
 
 
140 with three interim looks  
Attrition (%)                                     5% 
N 
                                                148 
Interim 
Analysis 
The study will have a total of four looks, with three interim analyses at: 
 
 20 randomized subjects at 3-Month Visit: futility stopping 
 60 randomized subjects at 3-Month Visit: futility and effectiveness 
stopping 
 100 randomized subjects at 3-Month Visit: effectiveness stopping 
The adaptive design will use the Lan-DeMets group sequential method 
(Lan and DeMets 1983) with the O’Brien-Flemming α-spending 
function (O'Brien and Fleming 1979) and Pocock β-spending function 
(Pocock 1977). 
 
 

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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................3 
3. 
TABLE OF CONTENTS .......................................................................................................12 
3.1. Table of Figures .....................................................................................................14 
3.2. Table of Tables ......................................................................................................14 
4. 
INTRODUCTION.................................................................................................................15 
5. 
COMMERCIAL DEVICE DESCRIPTION (PART OF STANDARD OF CARE) ..........................15 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................15 
6.1. Primary Objective .................................................................................................15 
6.2. Secondary Objective .............................................................................................15 
6.3. Primary Endpoint .................................................................................................15 
6.4. Secondary Endpoints ............................................................................................15 
6.5. Exploratory Endpoints .........................................................................................16 
6.6. Safety Parameters .................................................................................................17 
7. 
STUDY DESIGN .................................................................................................................17 
7.1. Scale and Duration ................................................................................................17 
7.2. Treatment Assignment ..........................................................................................18 
7.3. Justification for the Study Design ........................................................................18 
8. 
SUBJECT SELECTION ........................................................................................................19 
8.1. Study Population and Eligibility ..........................................................................19 
8.2. Inclusion Criteria ..................................................................................................19 
8.3. Exclusion Criteria .................................................................................................20 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................22 
9.1. Point of Enrollment ...............................................................................................22 
9.2. Withdrawal ............................................................................................................22 
9.3. Subject Status and Classification .........................................................................22 
9.4. Enrollment Controls .............................................................................................22 
9.5. End-of-Study Action Plan.....................................................................................23 

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10. STUDY METHODS .............................................................................................................23 
10.1. Data Collection ......................................................................................................23 
10.2. Study Candidate Screening ..................................................................................25 
10.3. Informed Consent..................................................................................................25 
10.3.1. Screening Period .......................................................................................25 
10.4. Opioid Medication Lock Visit (Up to 35 days following informed consent) ....25 
10.5. Baseline Period (14 days) ......................................................................................25 
10.6. Baseline Visit (0 – 7 days post Baseline Period) .................................................25 
10.7. Implant Procedures (Up to 90 days following the Baseline Visit) ....................26 
10.8. Healing Period (0 - 28 days following Implant Procedures) .............................26 
10.9. Randomization Visit (Day 0) ................................................................................26 
10.10. 
Programming Lock Visit (Day 70 - 14 days post randomization Visit)
 
27 
10.11. 
3-Month Visit (90 + 14 days post randomization Visit) ......................27 
10.12. 
6-Month Visit (180 ± 30 days post randomization Visit) .....................28 
10.13. 
9-Month Visit (270 ± 30 days post randomization Visit) .....................29 
10.14. 
Year 1 and Year 2 Visit (365 ± 30 days post randomization Visit and 
730 ± 30 days post-randomization Visit)) ............................................................30 
10.15. 
Unscheduled Visit ...................................................................................31 
10.15.1. Revision or Replacement of Leads, Extensions and/or IPGs ...................31 
10.15.2. Interventional Pain Procedures .................................................................31 
10.16. 
Medication Requirements ......................................................................31 
10.17. 
Study Completion ...................................................................................32 
10.18. 
Source Documents ..................................................................................32 
11. STATISTICAL CONSIDERATIONS ......................................................................................32 
11.1. Endpoints ...............................................................................................................32 
11.1.1. Primary Endpoint ......................................................................................32 
11.1.1.1. Hypotheses ...............................................................................32 
11.1.1.2. Sample Size ..............................................................................33 
11.1.1.3. Statistical Methods ...................................................................33 
11.1.2. Efficacy Endpoints ....................................................................................33 
11.1.3. Exploratory Endpoints ..............................................................................34 
11.2. General Statistical Methods .................................................................................35 
12. DATA MANAGEMENT .......................................................................................................35 

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12.1. Data Collection, Processing, and Review ............................................................35 
12.2. Study Assessments .................................................................................................35 
12.2.1. Activation Questionnaire ..........................................................................35 
12.3. Data Retention .......................................................................................................35 
13. DEVIATIONS......................................................................................................................36 
14. COMPLIANCE ....................................................................................................................36 
15. MONITORING ....................................................................................................................36 
16. POTENTIAL RISKS AND BENEFITS ...................................................................................36 
17. SAFETY REPORTING .........................................................................................................36 
18. INFORMED CONSENT ........................................................................................................37 
19. COMMITTEES ...................................................................................................................37 
19.1. Safety Monitoring Process ....................................................................................37 
20. SUSPENSION OR TERMINATION........................................................................................37 
21. PUBLICATION POLICY ......................................................................................................37 
22. BIBLIOGRAPHY .................................................................................................................37 
23. ABBREVIATIONS AND DEFINITIONS .................................................................................38 
23.1. Abbreviations.........................................................................................................38 
23.2. Definitions ..............................................................................................................38 
 
 
3.1. Table of Figures 
Figure 7.1-1: FAST Study Design .......................................................................................... 17 
 
3.2. Table of Tables 
Table 8.2-1: Inclusion Criteria ................................................................................................ 20 
Table 10.1-1: Data Collection Schedule .............................................................................. 24 
Table 23.1-1: Abbreviations ................................................................................................... 38 
 

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4. Introduction 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
5. Commercial Device Description (part of Standard of Care) 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document. 
6. Study Objectives and Endpoints 
6.1. Primary Objective 
The primary objective of this study is to evaluate the effectiveness of Spinal Cord 
Stimulation (SCS) with fast-acting subperception (FAST) as compared to subperception SCS 
in patients with chronic pain when using the Boston Scientific Spectra WaveWriter SCS 
System. 
6.2. Secondary Objective 
The secondary objective of this study is to determine the impact of Spectra WaveWriter SCS 
System on global patient outcomes including quality of life, patient preference, etc.   
6.3. Primary Endpoint 
The primary endpoint is the proportion of subjects with 50% or greater reduction from the 
Baseline Visit in average overall pain intensity at 3 months post randomization, with no 
increase in baseline average daily opioid medications used to treat pain. 
6.4. Secondary Endpoints 
The following secondary endpoints will be analyzed as a comparison between the two 
groups. Assessments required for deriving each endpoint are denoted in parentheses. 
 Percentage of subjects who report clinically significant improvement in overall pain 
post-activation (Activation Questionnaire)  
 Change in average overall pain intensity from pre-activation to post-activation 
(Activation Questionnaire) 

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 Change in overall pain intensity from Baseline Visit to 3 mo. post-randomization 
Visit (VRS)  
 Percent Pain Relief in overall pain at 3 mo. post-randomization Visit (PPR) 
 Patient global impression of change at 3 mo. post-randomization Visit (PGI-C) 
 Clinician global impression of change at 3 mos. post-randomization Visit (CGI-C) 
 Treatment Satisfaction at 3 months post-randomization Visit (TSQM-9m) 
 Change in disability from Baseline Visit to 3 mos. post-randomization Visit 
(ODIv2.1a) 
 
Change in sleep from Baseline Visit to 3 mos. post-randomization Visit (PSQI) 
6.5. Exploratory Endpoints 
The following exploratory endpoints will be evaluated. Assessments required for deriving 
each endpoint are denoted in parentheses 
 Change in average low back pain intensity from pre-activation to post-activation 
(Activation Questionnaire ) 
 Change in average leg pain intensity from pre-activation to post-activation (Activation 
Questionnaire ) 
 Change in average overall pain intensity from Baseline Visit to 6, 9 12 and 24 months  
post-randomization Visits (VRS) 
 Change in average low back pain intensity from Baseline Visit to 6, 9 12 and 24 
months post-randomization Visits (VRS) 
 Change in average leg pain intensity from Baseline Visit to 6, 9 12 and 24 months 
post-randomization Visits (VRS) 
 Change in average overall pain intensity from Baseline Visit to 6, 9 12 and 24 months 
post-randomization Visits (NRS) 
 Change in average low back pain intensity from Baseline Visit to 6, 9 12 and 24 
months post-randomization Visits (NRS) 
 Change in average leg pain intensity from Baseline Visit to 6, 9 12 and 24 months  
post-randomization Visits (NRS) 
 Percent pain relief of overall pain at 6, 9 12 and 24 months post-randomization Visits 
(PPR) 
 Percent pain relief of low back pain at 6, 9 12 and 24 months post-randomization 
Visits (PPR) 
 Percent pain relief of leg pain at 6, 9 12 and 24 months post-randomization Visits 
(PPR) 

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 Clinician global impression of change at 6, 9 12 and 24 months post-randomization 
Visits (CGI-C) 
 Patient global impression of change at 6, 9 12 and 24 months post-randomization 
Visits (PGI-C) 
 Treatment satisfaction at 6, 9 12 and 24 months post-randomization Visits (TSQM-
9m) 
 Change in quality of life from Baseline Visit to 6, 9 12 and 24 months post-
randomization Visits (SF-36v2) 
 Change in disability from Baseline Visit to 6, 9 12 and 24 months post-randomization 
Visits (ODIv2.1a) 
 
Change in sleep from Baseline Visit to 6, 9 12 and 24 months post-randomization Visit 
(PSQI) 
 
6.6. Safety Parameters 
Safety parameters include the rates of occurrence of all device hardware, device stimulation   
and procedure related non-serious adverse events, all serious adverse events, and 
unanticipated adverse events through the end of the study. 
 
7. Study Design 
The study is a prospective, multi-center, parallel group randomized controlled trial with an 
adaptive design. All participants will receive the Spectra WaveWriter Spinal Cord Stimulator 
(SCS) system and followed per the study schedule as shown in study schematic Figure 7.1-1. 
7.1. Scale and Duration 
The study will randomize up to 148 subjects at up to 25 investigational sites in the United 
States. Enrollment is expected to take approximately 14 months and a subject’s participation 
in the study, from the point of enrollment until study completion, should last approximately 
27 months.   
The study is expected to last approximately 41 months from the first patient enrolled until the 
end of study close-out activities. 
 
Figure 7.1-1: FAST Study Design 
 

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7.2. Treatment Assignment 
All enrolled subjects who pass eligibility criteria will receive a trial. Subjects with a positive 
trial will proceed to receive permanent implant. Following permanent implant, all subjects’ 
device will be randomized in a 1:1 ratio to either receive:  
 WaveWriter Settings: Fast-acting subperception (FAST) 
 Conventional Settings: Subperception   
 
7.3. Justification for the Study Design 
The study is a prospective, multi-center, parallel group randomized controlled trial with an 
adaptive design. The study is designed to demonstrate the value of fast-acting subperception 
for sustained clinically significant pain relief in patients with chronic pain when using the 
Boston Scientific Spectra WaveWriter SCS System. Additionally, the impact of the Spectra 
WaveWriter SCS System on global patient outcomes, quality of life and patient preference 
will also be evaluated.  
A prospective study design will eliminate the bias associated with case selection in a 
retrospective review and will ensure that identical procedures are followed for data capture 
and review.  

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A multi-center design will minimize the impact on treatment outcome that may potentially 
result from differences in patient selection, regional differences in the patient demographic, 
and differences in investigator technique and patient management.   
The study design includes two groups (arms) – WaveWriter group and Conventional group. 
The WaveWriter group will receive fast-acting subperception (FAST) as available in the 
WaveWriter SCS System while the conventional group will receive subperception 
programming.  The Conventional group will serve as a control in this study. Randomization 
(1:1) will minimize selection bias and impact of demographic variables.  
The primary endpoint is the proportion of subjects with 50% or greater reduction (responder 
rate) from the Baseline Visit in average overall pain intensity at 3 months post-
randomization, with no increase in baseline average daily opioid medications used to treat 
pain. A 3-month endpoint was chosen as 3 months provides adequate time for a subject to 
have their programming parameters optimized.  
8. Subject Selection  
8.1. Study Population and Eligibility  
Study candidates will be drawn from the population of patient’s resident in pain management 
or surgical medical practices.  The study eligibility criteria are listed below.  
8.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8.2-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion (see Section 8.3-1) 
is met.  
 

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Table 8.2-1: Inclusion Criteria 
Clinical 
Inclusion 
Criteria 
IC1. Chronic pain of the trunk and/or limbs for at least 6 months with 
back pain greater or equal to leg pain.    
IC2. Chronic, intractable pain of the trunk and/or limbs which has been 
refractory to conservative therapy (E.g. pain medications, physical 
therapy, facet joint/medial branch nerve blocks.) 
IC3. No back surgery within 6 months prior to Screening 
IC4. Average overall pain intensity (leg and/or low back pain) of 6 or 
greater on a 0-10 numerical rating scale at Baseline Visit based on 7-
day recall 
IC5. If taking prescription opioids for primary chronic pain complaint 
(low back and/or leg pain), must have been on a stable prescription 
(same drug(s) and dose(s)) 30 days prior to Screening 
IC6. Consumed an average total daily morphine equivalent of ≤200 mg 
during the 30 days prior to Screening 
IC7. Willing and able to comply with all protocol-required procedures 
and assessments/evaluations  
IC8. Baseline Oswestry Disability Index (ODI) score ≥40 and ≤80 
IC9. 22 years of age or older when written informed consent is obtained  
IC10. Eligible candidate for SCS from a psychological and psychiatric 
standpoint as determined within 180 days prior to Baseline Visit, per 
site’s routine screening process  
IC11. Able to independently read and complete all questionnaires and 
assessments provided in English 
IC12. If female of childbearing potential: not pregnant, as evidenced by a 
negative pregnancy test at Screening 
IC13. Subject signed a valid, IRB-approved informed consent form (ICF) 
provided in English
 
8.3. Exclusion Criteria 
Subjects who meet any one of the following criteria cannot be included in this study or will 
be excluded from this clinical study. 
 
Table 8.3- 1 Exclusion Criteria  

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Clinical 
Exclusion 
Criteria 
EC1. Average leg pain intensity is greater than average low back pain 
intensity as reported during Baseline Period 
EC2. Patient exhibits catastrophization based on physician evaluation 
(e.g., average overall daily pain intensity of 10 on a 0-10 numerical 
rating scale, every day during the 7 days prior to Screening, based 
on patient recall) 
EC3. Radiographic evidence of spinal instability requiring fusion 
EC4. Primary pain complaint of vascular origin (e.g. peripheral vascular 
disease) 
EC5. Spinal pain secondary to neoplasm, infection, autoimmune disorder 
with spinal involvement, or a spinal metabolic disorder  
EC6. Visceral pain referred to the low back and/or legs 
EC7. Any pain-related diagnosis or medical/psychological condition that, 
in the clinician’s best judgment, might confound reporting of study 
outcomes (e.g. pelvic pain, anginal pain, chronic migraine, brain or 
spinal cord tumor) 
EC8. Require implantation of lead(s) in the cervical epidural space 
EC9. Current systemic infection, or local infection in close proximity to 
anticipated surgical field, at Screening 
EC10. High surgical risk 
EC11. Body mass index ≥ 45 at Screening 
EC12. Terminal illness with anticipated survival < 12 months 
EC13. Current condition associated with risk of immunocompromise that 
might increase risk of infection during study duration  
EC14. Currently on any anticoagulant medications that cannot be 
discontinued during perioperative period 
EC15. Significant cognitive impairment at Screening that, in the opinion of 
the Investigator, would reasonably be expected to impair the study 
candidate’s ability to participate in the study 
EC16. Participating (or intends to participate) in another drug or device 
clinical trial that may influence the data that will be collected for 
this study 
EC17. Previous spinal cord stimulation trial or is already implanted with an 
active implantable device(s) (e.g. pacemaker, drug pump, 
implantable pulse generator) 
EC18. A female who is breastfeeding 
EC19. A female of childbearing potential planning to get pregnant during 
the course of the study or not using adequate contraception 

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EC20. Plan to receive any massage or manipulation directly over the leads 
or by the anticipated location of the IPG or treatments that involve 
sudden jerking motions of the torso at any time during the course of 
the study 
EC21. A condition currently requiring or likely to require the use of MRI 
or diathermy 
EC22. Any injury or medical/psychological condition that might be 
significantly exacerbated by the implant surgery or the presence of 
an implantable stimulator or otherwise compromise subject safety 
EC23. Unable to operate the study device
 
9. Subject Accountability 
9.1. Point of Enrollment 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
 
9.2. Withdrawal 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
9.3. Subject Status and Classification 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
9.4. Enrollment Controls 
The overall enrollment in the study will be capped at 148 randomized subjects. Per site 
enrollment will be capped initially at 12 randomized FAST subjects. The initial cap of 12 
randomized FAST subjects at any one site can be increased based upon written 
communication of sponsor approval. 

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The study will implement a formal Enrollment Communication Plan. The plan will outline 
the specific activities, as well as the nature and timing of communications to investigators in 
order to minimize the risk of enrollment beyond the protocol-specified enrollment caps 
determined by the statistical analysis plan. 
9.5. End-of-Study Action Plan  
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
10. Study Methods 
10.1. Data Collection 
The data collection schedule is shown in table below. 

 
 
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Table 10.1-1: Data Collection Schedule 
 
 
Screening
Opioid 
Medication 
Lock Visit
Baseline 
Period 
Baseline 
Visit 
Implant 
Procedures 
(Trial and 
Permanent)
Randomization/ 
Activation Visit 
Programming 
Lock Visit
3-
Month Visit 
6-Month Visit
9-Month Visit
1-Year Visit
2-Year Visit
End of Study
Unscheduled 
Visit
Up to 35 days 
following 
informed 
consent
14 days post-
Medication 
Lock
(0 - 7 days 
post 
Baseline 
Period)
Up to 90 days 
post-Baseline 
Visit
Day 0
70  - 14 days
90 + 14 days 
post 
randomization
180 ± 30 days 
post 
randomization
270 ± 30 days 
post 
randomization
365 ± 30 days 
post 
randomization
730 ± 30 days 
post 
randomization
Informed Consent (ICF)
X
Inclusion/Exclusion Criteria Evaluation
Demography
X
Medical History
X
Beck Depression Inventory (BDI-II)
X
 X
X
X
Oswestry Disability Index (ODI v2.1a)
X
X
X
X
X
X
Short Form Health Survey 36 item (SF-36v2)
X
X
X
X
X
X
EQ-5D-5L
X
X
X
X
X
X
Pain Intensity (NRS)
X
X
X
X
X
X
Pain Intensity (VRS)
X
X
X
X
X
X
Pittsburgh Sleep Quality Index (PSQI)
X
X
X
X
X
X
Procedure Information
X
₸
X**
End of Trial Assessment
X
Programming Parameters***
X
X
X
X
X
X
X
X
X
Activation Questionnaire
X
Clinician Global Impression of Change (CGI-C)
X
X
X
X
X
Patient Global Impression of Change (PGI-C)
X
X
X
X
X
Percent Pain Relief (PPR)
X
X
X
X
X
Preference Questionnaire
X
X
X
X
Treatment Satisfaction Questionnaire (TSQM-9m)
X
X
X
X
X
Concomitant Medications (opioid pain medications)
X
X
X
X
X
X
X
X
X
X
X
Adverse Events (AE)
X
X
X
X
X
X
X
X
X
X
X
X
X
Opioid Medications Locked 
Healing Period (0-28 days)
**For unscheduled visits where procedures are performed.
***Only when device programming is performed.
₸ The device will remain off after permanent implant until the Activation Visit

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10.2. Study Candidate Screening 
Subjects’ eligibility for the study will be assessed based on study Inclusion and Exclusion 
criteria listed in Sections 9.2 and 9.3, respectively. Subjects who have provided informed 
consent and who have been determined to not meet all eligibility requirements will be 
withdrawn. 
10.3. Informed Consent 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
10.3.1. Screening Period  
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.    
10.4. Opioid Medication Lock Visit (Up to 35 days following informed consent) 
The Opioid Medication Lock Visit will occur within 35 days following informed consent. 
However, this visit may occur on the same day as that of the Informed consent as well 
following completion of consent.  
At this visit, the subject’s opioid pain medications will be locked, with no increase in 
type/dose/route/frequency, until the 3-Month post-randomization Visit.  
At this visit (or during the screening period), the investigator will convert the subject’s opioid 
medication prescriptions from PRN to a fixed dose, as needed.  
10.5. Baseline Period (14 days) 
The Baseline Period will last for 14 consecutive days following the Opioid Medication Lock 
Visit. At the end of the Baseline Period, subjects will return to the clinic for their Baseline 
Visit.  
Subjects are to not make any increases to their opioid pain medications during this period.  
10.6. Baseline Visit (0 – 7 days post Baseline Period)  
At the Baseline Visit, subjects will return to the clinic to complete remaining screening 
requirements. Any adverse since the last study visit will be collected.  
The following assessments, as outlined in Table 11.1-1, will be conducted: 
 Demographics 

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 Medical history  
 Beck Depression Inventory (BDI-II) 
 Oswestry Disability Index (ODIv2.1a) 
 Short Form Health Survey 36 (SF-36v2) 
 EQ-5D 5-Level 
 Pain Intensity: VRS 
 Pain Intensity: NRS 
 Pittsburg Sleep Quality Index (PSQI)  
 
Subjects that meet all study criteria will be scheduled for the device implant procedures (trial 
and permanent implant of the SCS system). If a subject fails to meet all the eligibility criteria, 
they will be withdrawn from the study. 
End of Visit Information: 
 Subjects should be reminded not to make any increases to their opioid medications. 
10.7. Implant Procedures (Up to 90 days following the Baseline Visit) 
Subjects will have up to 90 days following the Baseline Visit to receive their Spectra 
WaveWriter System. Subjects will undergo a trial procedure per standard of care. Following 
a successful trial, i.e. at least 50% pain reduction in their overall pain as compared with 
Baseline, the subject will proceed to permanent implantation. Subjects with an unsuccessful 
implant procedure will be followed for 2 weeks for procedure related adverse events then 
withdrawn from the study. Acute opioid pain medications may be taken. 
10.8. Healing Period (0 - 28 days following Implant Procedures) 
The subject’s device will remain inactivated (device OFF) for up to 28 days following the 
permanent implantation procedure to allow for healing. Acute opioid pain medications may 
be taken during this period. No additional scheduled assessments will be completed during 
this period.  
For those subjects receiving the surgical (paddle) lead, it is recommended that their device 
remain inactivated (device OFF) as part of healing for 21-28 days.  
10.9. Randomization Visit (Day 0) 
At the Randomization Visit, subjects will be randomized in a 1:1 ratio to either receive  
 WaveWriter Settings: Fast-acting subperception  
 Conventional Settings: Subperception  
Subjects will receive their assigned treatment settings up to 3 Mo. Visit. Any protocol 
required adverse events since the last study visit will be collected.  

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The Activation Questionnaire must be completed prior to and post-activation to document 
pain scores, time taken, etc.  
Subjects must stop taking acute opioid pain medications, as applicable, and are not to 
increase their opioid pain medications up to the 3-Month Visit.  
Information regarding programming parameters will be collected. To aid in programming it 
is recommended that thoracic and/or lumbar imaging is obtained at this visit or up to 7 days 
prior to the visit to show the position(s) of the study device lead(s). In the event of suspected 
lead migration, imaging may be performed to document lead positions. 
End of Visit Information:  
 Subjects will receive instructions on the use of the device including the Remote 
Control and charging system. 
 Subjects are to contact the site in an event that any additional intervention is 
warranted, to report a complaint and/or a suspected adverse event, 
reprogramming, etc. 
 Subjects should be reminded not to make any increase in their opioid pain 
medications.  
10.10. 
Programming Lock Visit (Day 70 - 14 days post randomization Visit) 
At the Programming Lock Visit, subjects will return to the clinic to have their programs 
locked. Any protocol required adverse events since the last study visit will be collected.  
No further changes to the subject’s programs (for e.g. electrode configuration) will be 
allowed except to resolve a device and/or stimulation-related AE.  
Information regarding programming parameters and device information may be collected. 
End of Visit Information:  
 Subjects will receive instructions on the use of the device including the Remote 
Control and charging system, as needed.  
 Subjects are to contact the site in an event that any additional intervention is 
warranted, to report a complaint and/or a suspected adverse event, 
reprogramming, etc. 
 Subjects should be reminded not to make any increase in their opioid medications. 
10.11. 
3-Month Visit (90 + 14 days post randomization Visit)  
During the 3-Month Visit, subjects will return to the clinic for study evaluations and 
programming. Any protocol required adverse events since their last study visit will be 
collected.  
The following assessments will be completed as summarized in Table 11.1-1: 
 Beck Depression Inventory (BDI-II) 
 Oswestry Disability Index version 2.1a (ODI v2.1a) 
 Short Form Health Survey 36 items (SF-36 v2) 

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 EQ-5D 5-Level 
 Pain Intensity: VRS 
 Pain Intensity: NRS 
 Clinical Global Impression of Change (CGI-C) 
 Patient Global Impression of Change (PGI-C)  
 Percent Pain Relief (PPR) 
 Pittsburg Sleep Quality Index (PSQI)  
 Treatment Satisfaction Questionnaire for Medication - modified (TSQM-9m) 
Following completion of assessments, subjects’ device will be programmed as needed and 
programming information may be collected. At this visit, all subjects may receive 
programming as available on the device with no restrictions. .  
 In the event of suspected lead migration or to aid programming the subject’s device, 
imaging may be performed to document lead position. 
 Any additional instructions related to charging of the device and/or use of Remote 
Control may be provided. 
End of Visit Information:  
 Subjects will receive instructions on the use of the device including the Remote 
Control and charging system, as needed.  
 Subjects are to contact the site in an event that any additional intervention is 
warranted, to report a complaint and/or a suspected adverse event, 
reprogramming, etc. 
  Subjects’ opioid medications are no longer locked and can be changed, if needed 
for the remainder of the study 
10.12. 
6-Month Visit (180 ± 30 days post randomization Visit)  
During the 6-Month Visit, subjects will return to the clinic for study evaluations and 
programming. Any protocol required adverse events since their last study visit will be 
collected.  
The following assessments will be completed as summarized in Table 11.1-1: 
 Oswestry Disability Index version 2.1a (ODI v2.1a) 
 Short Form Health Survey 36 items (SF-36 v2) 
 EQ-5D 5-Level 
 Pain Intensity: NRS 
 Pain Intensity: VRS 
 Clinical Global Impression of Change (CGI-C) 
 Patient Global Impression of Change (PGI-C)  

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 Percent Pain Relief (PPR) 
 Pittsburg Sleep Quality Index (PSQI)  
 Preference Questionnaire 
 Treatment Satisfaction Questionnaire for Medication - modified (TSQM-9m) 
Following completion of assessments, subjects’ device will be programmed as needed and 
programming information may be collected. 
 In the event of suspected lead migration or to aid programming the subject’s device, 
imaging may be performed to document lead position. 
 Any additional instructions related to charging of the device and/or use of Remote 
Control may be provided. 
End of Visit Information:  
 Subjects will receive instructions on the use of the device including the Remote 
Control and charging system, as needed.  
 Subjects are to contact the site in an event that any additional intervention is 
warranted, to report a complaint and/or a suspected adverse event, 
reprogramming, etc. 
 Changes to opioid pain medications are allowed up to End of Study Visit. 
10.13. 
9-Month Visit (270 ± 30 days post randomization Visit)  
During the 9-Month Visit, subjects will return to the clinic for study evaluations and 
programming. Any protocol required adverse events since their last study visit will be 
collected.  
The following assessments will be completed as summarized in Table 11.1-1: 
 Oswestry Disability Index version 2.1a (ODI v2.1a) 
 Short Form Health Survey 36 items (SF-36 v2) 
 EQ-5D 5-Level 
 Pain Intensity: NRS 
 Pain Intensity: VRS 
 Clinical Global Impression of Change (CGI-C) 
 Patient Global Impression of Change (PGI-C)  
 Percent Pain Relief (PPR) 
 Pittsburg Sleep Quality Index (PSQI)  
 Preference Questionnaire 
 Treatment Satisfaction Questionnaire for Medication - modified (TSQM-9m) 
Following completion of assessments, subjects’ device will be programmed as needed and 
programming information may be collected.  

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 In the event of suspected lead migration or to aid programming the subject’s device, 
imaging may be performed to document lead position. 
 Any additional instructions related to charging of the device and/or use of Remote 
Control may be provided. 
 
End of Visit Information:  
 Subjects will receive instructions on the use of the device including the Remote 
Control and charging system, as needed.  
 Subjects are to contact the site in an event that any additional intervention is 
warranted, to report a complaint and/or a suspected adverse event, 
reprogramming, etc. 
10.14. 
Year 1 and Year 2 Visit (365 ± 30 days post randomization Visit and 730 ± 
30 days post-randomization Visit))  
During the 1 and 2 Year Visits, subjects will return to the clinic for study evaluations and 
programming. Any protocol required adverse events since their last study visit will be 
collected.  
The following assessments will be completed as summarized in Table 11.1-1: 
 Beck Depression Inventory (BDI-II) 
 Oswestry Disability Index version 2.1a (ODI v2.1a) 
 Short Form Health Survey 36 items (SF-36 v2) 
 EQ-5D 5-Level 
 Pain Intensity: NRS 
 Pain Intensity: VRS 
 Clinical Global Impression of Change (CGI-C) 
 Patient Global Impression of Change (PGI-C)  
 Percent Pain Relief (PPR) 
 Pittsburg Sleep Quality Index (PSQI)  
 Preference Questionnaire 
 Treatment Satisfaction Questionnaire for Medication - modified (TSQM-9m) 
Following completion of assessments, subjects’ device will be programmed as needed and 
programming information may be collected. 
 In the event of suspected lead migration or to aid programming the subject’s device, 
imaging may be performed to document lead position. 
 Any additional instructions related to charging of the device and/or use of Remote 
Control may be provided. 
End of Visit Information:  

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 Subjects will receive instructions on the use of the device including the Remote 
Control and charging system, as needed.  
 Subjects are to contact the site in an event that any additional intervention is 
warranted, to report a complaint and/or a suspected adverse event, 
reprogramming, etc. 
 
The 2 Year Visit is the End of Study Visit and End of Study Action Plan (ESAP) will be 
followed as described in Section 10.5.  
10.15. 
Unscheduled Visit 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
10.15.1. Revision or Replacement of Leads, Extensions and/or IPGs 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
10.15.2. Interventional Pain Procedures 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
10.16. 
Medication Requirements 
Opioid Medication Lock Period (Medication Lock visit to 3-Month Visit):  
Investigators/Subjects will not be allowed to increase opioid pain medications from the 
Medication Lock visit until completion of the 3-Month Visit. 
The use of acute opioid pain medication for procedural discomfort is allowed during the 
Procedures and Healing Period and in the event of the revision or replacement of leads, 
extensions and/or IPG, per site’s routine care. 
Opioid Medication Open Period (3-Month Visit to End of Study visit) 
Investigators/Subjects may change opioid pain medications during the pain medication open 
period, from the 3-Month Visit to the End of Study Visit as needed.  

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10.17. 
Study Completion 
All randomized subjects permanently implanted will be followed through completion of the 
2-Year Visit or study withdrawal. The End of Study Action Plan defines the actions to be 
taken when the subject reaches the end of their study participation.  
10.18. 
Source Documents 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
11. Statistical Considerations 
11.1. Endpoints 
11.1.1. Primary Endpoint 
The primary endpoint for this study is the proportion of subjects with 50% or greater 
reduction from Baseline Visit in average overall pain intensity at 3 months post 
randomization with no increase in baseline average opioid medications used to treat pain. 
The percentage of overall pain will be assessed on a scale of 0-100% based on the Percent 
Pain Relief (PPR) questionnaire. Opioids will be calculated for each subject based on 
Concomitant Medications.   
Opioid prescription dose will be calculated as milligram morphine-equivalent (MME) based 
on the method described by McPherson (Mcpherson 2009).  
11.1.1.1. Hypotheses 
The primary statistical hypothesis in this study is that the proportion of subjects with 50% or 
greater reduction from Baseline Visit in average daily overall pain intensity at 3 months post 
randomization in the FAST group is non-inferior compared to the Control (i.e.  subperception) 
group  
 H0: πt - πc ≤ -0.20 
 
H1: πt - πc > -0.20 
 
Where πt and πc are the proportion of subjects with 50% or greater reduction from Baseline in 
average daily overall pain intensity at 3 months post randomization with no increase in 
baseline average daily opioid pain medications using FAST and subperception settings, 
respectively. The study’s non-inferiority margin is 0.20. 

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11.1.1.2. Sample Size  
The required sample size for this study was calculated based on the following assumptions in 
East 6.5: 
Test significance level (α) 
 
 
 
0.025 
1 or 2 sided test 
 
 
 
 
1 
Difference in Response (πt - πc) 
 
 
0.05 
Non-inferiority margin (δ) 
 
 
 
0.20 
Proportion of Responder in Control group (πc) 
0.60 
Power (1- β)  
 
 
 
 
0.80 
N 
 
 
 
 
 
 
140 with three interim looks  
Attrition (%)  
 
 
 
 
5% 
N 
 
 
 
 
 
 
148 
Therefore, a total of 148 randomized subjects are required.  
11.1.1.3. Statistical Methods 
The 95% confidence interval of πt -  πc will be computed. The study will be considered a 
success if, using the Intent-To-Treat (ITT) analysis, the lower bound of the two-sided 95% 
confidence interval for the difference is great than -0.20.  
11.1.2. Efficacy Endpoints 
The following secondary endpoints will be analyzed as a comparison between the two 
groups. Assessments required for deriving each endpoint are denoted in parentheses. 
 Percentage of subjects who report clinically significant improvement in overall pain 
post-activation  (Activation Questionnaire)  
 Change in average overall pain intensity from pre-activation to post-activation 
(Activation Questionnaire) 
 Change in overall pain intensity from Baseline Visit to 3 mo. post-randomization 
Visit (VRS)  
 Percent Pain Relief in overall pain at 3 mo. post-randomization Visit (PPR) 
 Patient global impression of change at 3 mo. post-randomization Visit (PGI-C) 
 Clinician global impression of change at 3 mos. post-randomization Visit (CGI-C) 
 Treatment Satisfaction at 3 months post-randomization Visit (TSQM-9m) 
 Change in disability from Baseline Visit to 3 mos. post-randomization Visit 
(ODIv2.1a) 
 Change in sleep from Baseline Visit to 3 mos. post-randomization Visit (PSQI) 

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11.1.3. Exploratory Endpoints 
The following exploratory endpoints will be evaluated. Assessments required for deriving 
each endpoint are denoted in parentheses 
 Change in average low back pain intensity from pre-activation to post-activation 
(Activation Questionnaire) 
 Change in average leg pain intensity from pre-activation to post-activation (Activation 
Questionnaire) 
 Change in average overall pain intensity from Baseline Visit to 6, 9 12 and 24 months 
post-randomization Visits (VRS) 
 Change in average low back pain intensity from Baseline Visit to 6, 9 12 and 24 
months post-randomization Visits (VRS) 
 Change in average leg pain intensity from Baseline Visit to 6, 9 12 and 24 months 
post-randomization Visits (VRS) 
 Change in average overall pain intensity from Baseline Visit to 6, 9 12 and 24 months 
post-randomization Visits (NRS) 
 Change in average low back pain intensity from Baseline Visit to 6, 9 12 and 24 
months post-randomization Visits (NRS) 
 Change in average leg pain intensity from Baseline Visit to 6, 9 12 and 24 months 
post-randomization Visits (NRS) 
 Percent pain relief of overall pain at 6, 9 12 and 24 months post-randomization Visits 
(PPR) 
 Percent pain relief of low back pain at 6, 9 12 and 24 months post-randomization 
Visits (PPR) 
 Percent pain relief of leg pain at 6, 9 12 and 24 months post-randomization Visits 
(PPR) 
 Clinician global impression of change at 6, 9 12 and 24 months post-randomization 
Visits (CGI-C) 
 Patient global impression of change at 6, 9 12 and 24 months post-randomization 
Visits (PGI-C) 
 Treatment satisfaction at 6, 9 12 and 24 months post-randomization Visits (TSQM-
9m) 
 Change in quality of life from Baseline Visit to 6, 9 12 and 24 months post-
randomization Visits (SF-36v2) 
 Change in disability from Baseline Visit to 6, 9 12 and 24 months post-randomization 
Visits (ODIv2.1a) 

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 Change in sleep from Baseline Visit to 6, 9 12 and 24 months post-randomization 
Visit (PSQI) 
 
The exploratory endpoints are intended to generate hypotheses for future studies. 
Consequently, no correction for multiple testing will be performed for the exploratory 
endpoints. All exploratory endpoints will be clearly identified as such in study reports. 
11.2. General Statistical Methods 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
12. Data Management 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
12.1. Data Collection, Processing, and Review 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document 
12.2. Study Assessments 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.  
 
12.2.1. Activation Questionnaire 
The Activation Questionnaire is administered by site personnel at the 
activation/randomization visit and will collect information related to subject’s overall 
improvement in pain scores, time taken to achieve pain relief, etc.   
12.3.  Data Retention 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 

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Information that is common to both is not repeated in this document 
13. Deviations 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
14.  Compliance 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
15. Monitoring 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
. 
16. Potential Risks and Benefits 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
17. Safety Reporting 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   

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18. Informed Consent 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
19. Committees 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
19.1. Safety Monitoring Process 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
20. Suspension or Termination 
20.1 This is an appendix to the COMBO Study and only contains information that is unique 
to this sub-study. 
 
Information that is common to both is not repeated in this document.   
21. Publication Policy 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
22. Bibliography 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   

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23. Abbreviations and Definitions  
23.1. Abbreviations 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.   
 
New abbreviations shown below.  
Table 23.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
FAST 
Fast Acting Subperception  
23.2. Definitions 
This is an appendix to the COMBO Study and only contains information that is unique to this 
sub-study. 
 
Information that is common to both is not repeated in this document.