BurstDR™ micrOdosing stimuLation in De-novo Patients
Phase: NA
Conditions: Pain, Intractable, Pain, Back
Sponsor: Abbott Medical Devices

 
BurstDR™ micrOdosing stimuLation in De-novo patients 
 
 
 
 
NCT03350256 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 1 of 41 
 
 
BOLD 
BurstDR™ micrOdosing stimuLation in De-novo patients 
CRD_924 
Study Document No: < SJM-CIP-No> 
Version [A] 
Date: 05-19-2017 
Clinical Investigation Plan (CIP) 
 
 
Sponsor  
 
 
Abbott 
        
 
 
 
6901 Preston Road 
      
  
 
 
Plano, TX 75024 
        
 
 
 
USA 
 
Coordinating  
 
 
Name/Title 
Investigator                             
Hospital 
       
 
 
 
Department/function 
       
 
 
 
Address 
        
 
 
 
City 
        
 
 
 
Country 
 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 2 of 41 
 
 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation. 
 
 
Principal Investigator 
 
Printed name: 
Signature: 
Date: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 3 of 41 
 
Coordinating Investigator/ National Investigator 
 
SIGNATURE PAGE 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation.  
 
 
Coordinating Investigator/ National Investigator   
 
Printed name: 
Signature: 
Date: 
 
 
 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 4 of 41 
 
Table of Contents 
 
1 
Synopsis ................................................................................................................................................. 8 
 
Objective(s) ................................................................................................................................... 8 
 
Devices Used ................................................................................................................................ 8 
 
Indications for Use ........................................................................ Error! Bookmark not defined. 
 
Design ........................................................................................................................................... 9 
 
Endpoints ..................................................................................................................................... 11 
1.5.1 
Primary Endpoints ................................................................................................................... 11 
1.5.2 
Secondary Endpoints .............................................................................................................. 11 
1.5.3 
Descriptive Endpoint(s), if applicable ...................................................................................... 11 
 
Study Population ......................................................................................................................... 11 
 
Inclusion/Exclusion Criteria ......................................................................................................... 11 
1.7.1 
Inclusion Criteria ...................................................................................................................... 11 
1.7.2 
Exclusion Criteria ..................................................................................................................... 12 
 
Enrollment ................................................................................................................................... 12 
 
Study Assessments ..................................................................................................................... 12 
 
Study Flow Chart, if applicable ..................................................... Error! Bookmark not defined. 
2 
Introduction........................................................................................................................................... 12 
3 
Background and Justification for Clinical Investigation ........................................................................ 13 
4 
Device(s) Under Investigation .............................................................................................................. 14 
 
Identification and Description of the Devices under investigation ............................................... 14 
4.1.1 
Identification ............................................................................................................................ 14 
4.1.2 
Device Description and Intended Purpose .............................................................................. 14 
4.1.3 
Intended Purpose within the Clinical Investigation, if different . Error! Bookmark not defined. 
4.1.4 
Device Handling and Storage .................................................................................................. 15 
 
Description of Comparator Device, if applicable .......................... Error! Bookmark not defined. 
4.2.1 
Identification ............................................................................................................................ 15 
4.2.2 
Comparator Description and Intended Purpose ....................... Error! Bookmark not defined. 
4.2.3 
Justification of Choice of Comparators..................................... Error! Bookmark not defined. 
4.2.4 
Device Handling and Storage ................................................... Error! Bookmark not defined. 
 
Devices Accountability, if applicable ........................................................................................... 15 
5 
Clinical Investigation Design ................................................................................................................ 15 
 
Clinical Investigation Design ....................................................................................................... 15 
 
Objectives .................................................................................................................................... 17 
5.2.1 
Primary Objectives .................................................................................................................. 17 
5.2.2 
Secondary Objectives.............................................................................................................. 17 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 5 of 41 
 
 
Endpoints ..................................................................................................................................... 17 
5.3.1 
Primary Endpoint ..................................................................................................................... 17 
5.3.2 
Secondary Endpoint ................................................................................................................ 17 
5.3.3 
Descriptive Endpoint(s) ........................................................................................................... 18 
 
Study Population ......................................................................................................................... 18 
5.4.1 
Inclusion Criteria ...................................................................................................................... 18 
5.4.2 
Exclusion Criteria ..................................................................................................................... 18 
5.4.3 
Enrollment of Medicare Beneficiaries, if applicable .................. Error! Bookmark not defined. 
5.4.4 
Historically Underrepresented Demographic Subgroups, if applicable ... Error! Bookmark not 
defined. 
6 
Procedures ........................................................................................................................................... 19 
 
Patient Recruitment, if applicable ................................................. Error! Bookmark not defined. 
 
Informed Consent Process .......................................................................................................... 20 
6.2.1 
Special circumstances for informed consent, if applicable ....... Error! Bookmark not defined. 
 
Screening, if applicable ............................................................................................................... 20 
 
Point of Enrollment ...................................................................................................................... 20 
 
Scheduled Procedures ................................................................................................................ 21 
6.5.1 
Baseline ................................................................................................................................... 21 
6.5.2 
Randomization, if applicable ................................................................................................... 21 
6.5.3 
Implant/Procedure .................................................................... Error! Bookmark not defined. 
6.5.4 
Scheduled Follow-ups .............................................................. Error! Bookmark not defined. 
 
Patient Reported Outcome (PRO) Measures, if applicable......................................................... 24 
6.6.1 
PRO measure (Acronym or short name) (Reference) .............. Error! Bookmark not defined. 
 
Unscheduled Visits ...................................................................................................................... 24 
 
Study Flow Chart ......................................................................................................................... 25 
 
Health Care Economic Data Collection, if applicable ................... Error! Bookmark not defined. 
 
Description of Activities Performed by Sponsor Representatives, if applicable .......................... 26 
 
Subject Study Completion ........................................................................................................... 27 
 
Subject Withdrawal ...................................................................................................................... 27 
 
Requirements for Clinical Laboratories, if applicable ................... Error! Bookmark not defined. 
6.13.1 
Central Lab ........................................................................... Error! Bookmark not defined. 
 
Requirements for Clinical Equipment, if applicable ...................... Error! Bookmark not defined. 
 
Study Committees, if applicable ................................................... Error! Bookmark not defined. 
6.15.1 
Steering Committee (SC) ..................................................... Error! Bookmark not defined. 
6.15.2 
Publication Committee (PC) ................................................. Error! Bookmark not defined. 
6.15.3 
Subject Selection Committee (SSC), if applicable ............... Error! Bookmark not defined. 
6.15.4 
Data Safety Monitoring Board (DSMB), if applicable ........... Error! Bookmark not defined. 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 6 of 41 
 
6.15.5 
Clinical Events Committee (CEC) ........................................ Error! Bookmark not defined. 
7 
Statistical Considerations ..................................................................................................................... 28 
 
Hypotheses .................................................................................................................................. 28 
7.1.1 
Primary [Safety/Effectiveness] Endpoint Hypothesis(es) ........................................................ 28 
7.1.2 
Secondary [Safety/Effectiveness] Endpoint Hypothesis(es) .... Error! Bookmark not defined. 
 
Justification of Clinical Investigation Design ............................................................................... 28 
 
Multiplicity .................................................................................................................................... 28 
 
Overall Sample Size .................................................................................................................... 28 
 
Timing of Analysis ....................................................................................................................... 28 
 
Success Criteria .......................................................................................................................... 29 
 
Interim Analysis ........................................................................................................................... 29 
 
Statistical Criteria for Termination ............................................................................................... 29 
 
Deviations from Statistical Plan ................................................................................................... 29 
8 
Risks and Benefits ............................................................................................................................... 29 
 
Risks Associated with the Device Under Investigation ............................................................... 29 
8.1.1 
Anticipated Adverse Device Effects ........................................................................................ 29 
8.1.2 
Risks Associated with Clinical Investigation Assessments ..................................................... 30 
 
Risk Control Measures ................................................................................................................ 30 
 
Possible interactions with concomitant treatments ..................................................................... 30 
 
Anticipated Benefits ..................................................................................................................... 30 
 
Risk-to-Benefit Rationale ............................................................................................................. 30 
 
History of Device Modifications or Recall, if applicable ................ Error! Bookmark not defined. 
9 
Requirements for Investigator Records and Reports ........................................................................... 30 
 
Deviations from CIP..................................................................................................................... 30 
 
Safety Reporting .......................................................................................................................... 31 
9.2.1 
Subject Death .......................................................................................................................... 31 
9.2.2 
Unanticipated Adverse Device Effect, if applicable .................. Error! Bookmark not defined. 
9.2.3 
Device Deficiency (DD), if applicable ....................................... Error! Bookmark not defined. 
9.2.4 
Complaints, if applicable.......................................................................................................... 31 
 
Source records ............................................................................................................................ 32 
 
Records Retention ....................................................................................................................... 32 
10 
Clinical Data Handling ..................................................................................................................... 32 
 
Protection of Personally Identifiable Information ......................................................................... 33 
 
Data Management Plan ............................................................................................................... 33 
 
Document and Data Control ........................................................................................................ 33 
10.3.1 
Traceability of Documents and Data ................................................................................... 33 
10.3.2 
Recording Data .................................................................................................................... 33 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 7 of 41 
 
11 
Monitoring ........................................................................................................................................ 33 
12 
Compliance Statement .................................................................................................................... 33 
 
Statement of Compliance ............................................................................................................ 33 
 
Quality Assurance Audits and Regulatory Inspections ............................................................... 34 
 
Repeated and Serious Non-Compliance ..................................................................................... 34 
13 
Suspension or Premature Termination of the Clinical Investigation ............................................... 34 
14 
Clinical Investigation Conclusion ..................................................................................................... 35 
15 
Publication Policy ............................................................................................................................ 35 
16 
Reporting Results on ClincalTrials.gov Website, if applicable ......... Error! Bookmark not defined. 
Appendix A: CIP Revisions ......................................................................................................................... 36 
Appendix B: Definitions ............................................................................................................................... 37 
Appendix C: Labels ...................................................................................... Error! Bookmark not defined. 
Appendix D: Bibliography ............................................................................................................................ 39 
Appendix E: Case Report Form .................................................................................................................. 40 
Appendix F: Informed Consent Form .......................................................................................................... 41 
 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 8 of 41 
 
1 
Synopsis 
The purpose of this study is to evaluate the therapeutic efficacy of microdosing BurstDRTM stimulation in 
spinal cord stimulation (SCS) patients with chronic intractable back and/or leg pain. Microdosing 
BurstDRTM consists of periods during which stimulation is delivered with standard BurstDRTM stimulation 
parameters alternated with periods during which no stimulation is being delivered. Previous results show 
that patients using standard BurstDRTM can be programmed with microdosing with no changes to 
therapeutic efficacy (Vesper et. al, 2017). In this study we propose to evaluate therapeutic efficacy of 
BurstDRTM microdosing, and determine optimal microdosing programming parameters in chronic pain 
patients, who are eligible for SCS therapy. 
 
Objective(s) 
• 
The primary objective is to evaluate the efficacy of BurstDRTM microdosing stimulation in patients 
with chronic intractable back and/or leg pain with no prior history of SCS therapy.  
• 
The secondary objectives are to evaluate the optimal microdosing program, evaluate the long 
term efficacy of BurstDRTM stimulation on patient’s pain intensity, and evaluate the improvements 
in quality of life, disability, anxiety, depression, catastrophizing and overall satisfaction. 
 
Devices Used 
The following devices will be used in this clinical investigation: 
 
Table 1: Identification of Devices under Investigation 
Device name 
Model/Type 
Manufacturer 
Region/ Country 
Investigational or Market 
Released 
Abbott Invisible trial external pulse 
generator (EPG) 
3599 (Base), 3032 
(Header) 
Abbott 
US/OUS 
Released 
Abbott Invisible trial Clinician 
Programmer 
3870, 3872 
Abbott 
US/OUS 
Released 
Abbott Invisible trial Patient Controller 
3871, 3873 
Abbott 
US/OUS 
Released 
Abbot Percutaneous trial lead 
31XX 
Abbott 
US/OUS 
Released 
Abbott Lead extension 
33XX 
Abbott 
US/OUS 
Released 
Abbott Prodigy internal pulse generator 
(IPG) 
3799 
Abbott 
US/OUS 
Released 
Abbott Prodigy MRI IPG 
3772 
Abbott 
US/OUS 
Released 
Abbott Prodigy Charger 
3730 
Abbott 
US/OUS 
Released 
Abbott Prodigy Patient Programmer 
3856 
Abbott 
US/OUS 
Released 
Abbott Rapid Programmer 
programming device 
3835 
Abbott 
US/OUS 
Released 
Abbott Proclaim IPG 
3660, 3662 
Abbott 
US/OUS 
Released 
Abbott Clinician Programmer App 
3874 
Abbott 
US/OUS 
Released 
Abbott Patient Controller App 
3875 
Abbott 
US/OUS 
Released 
Abbott commercially available 
percutaneous leads 
31X6, 318X, 314X, 
315X, 316X 
Abbott 
US/OUS 
Released 
Abbott  commercially available paddle 
leads 
322X, 321X, 328X, 
324X, 326X, 3240 
Abbott 
US/OUS 
Released 
Abbott Cinch™ Lead Anchor 
1194 
Abbott 
US/OUS 
Released 
Abbott Swift-Lock™ Anchor 
1192 
Abbott 
US/OUS 
Released 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 9 of 41 
 
 
Design 
This is a prospective, open label, multicenter feasibility trial to evaluate the therapeutic efficacy of different 
BurstDRTM microdosing patterns in patients with chronic intractable pain.  
 
Subjects, eligible for SCS therapy, who are diagnosed with chronic intractable back and/or leg pain, will 
be considered for inclusion in this study. After baseline evaluation, subjects will undergo a SCS trial using 
the Abbott Invisible Trial system.  During the trial implant phase, SCS leads will be implanted in the dorsal 
column based on physician discretion. According to standard clinical practices performed in the United 
States (US), the trial phase will last around 3-7 days. At the start of the trial phase, patients will be 
programmed with the first ON/OFF stimulation pattern (30 second STIM ON, 90 seconds STIM OFF).  
Patients who do not achieve adequate pain relief (at least 50% reduction in back and/or leg VAS from 
baseline) within the first 3-4 days will be reprogrammed to a new ON/OFF stimulation pattern (5 seconds 
ON/ 15 seconds OFF). Patients, who still do not achieve adequate pain relief within 2 to 3 days from 
reprogramming, will be reprogrammed to a continuous mode of BurstDRTM stimulation and their trial 
evaluation will continue. These patients will be evaluated for an additional 2 days. At the end of the SCS 
trial, all subjects that experience at least 50% pain relief (according to average back and/or leg VAS) 
using one of the two microdosing burst stimulation paradigms will be considered further participation in 
the study. See Figure 1. 
 
 
Fig 1: Representation of the decision making algorithm for the SCS trial phase of the study 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 10 of 41 
 
Patients who have passed the trial phase and have received permanent implantation will be programmed 
based on the stimulation mode used for their trial success. Pain intensity, quality of life, disability, anxiety, 
depression, pain catastrophizing, satisfaction, and medication usage will be assessed at baseline, after 
SCS trial and at the 1, 3 and 6 month follow up. Adverse events will be collected throughout the study 
period. 
 
During the month leading to the 1 month follow up visit, patients’ pain relief will be evaluated on a weekly 
basis according to Figure 2. Briefly, patients who do not achieve adequate pain relief (greater or equal to 
pain relief achieved during the trial phase) will try lower stimulation ON/OFF ratios to determine the lowest 
possible stimulation ratio whilst maintaining adequate pain relief. This stimulation ON/OFF ratios will start 
from a ratio of 1:12 (Program 1) and increase to a potential ON/OFF ratio of 1:3 (Program 5) – Once the 
most optimal microdosing program is determined (as per algorithm in Figure 2), the patient will continue 
the rest of the study with that program.  If inadequate pain relief is experienced anytime during the study, 
the BurstDRTM microdosing parameters will be altered as per the algorithm in Figure 2. 
 
Option 1: Patients who underwent a successful 
trial using 30s ON:90s OFF BurstDRTM 
microdosing 
Option 2: Patients who underwent a successful 
trial using 5s ON:15s OFF BurstDRTM 
microdosing 
 
 
Figure 2: Representation of the decision making algorithm for the SCS 1 month post permanent implant 
phase of the study 
 
The total duration of the study is expected to be 2 years. 
 
The clinical study will be conducted in up to 6 centers in the United States 
 
Up to 60 subjects will be enrolled in this study. 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 11 of 41 
 
 
Endpoints 
There is 1 primary endpoint and 3 secondary endpoints in this clinical investigation. 
1.4.1 
Primary Endpoints 
• 
Evaluate the change in pain intensity between baseline, trial and long-term follow up evaluations 
using the Visual Analog Scale (VAS) assessments. 
1.4.2 
Secondary Endpoints 
• 
Evaluate the optimal microdosing program required  to maintain optimal pain relief on a patient 
specific basis 
• 
Evaluate the change in European Quality of life – 5 Dimensions (EQ-5D) scores between 
baseline, SCS trial and follow up visits 
• 
Evaluate the change in Oswestry Disability Index (ODI) scores between baseline, SCS trial and 
follow up visits 
• 
Evaluate the change in Hospital Anxiety and Depression scale (HADS) scores between baseline, 
SCS trial and follow up visits 
• 
Evaluate the change in Pain Catastrophizing Scale  (PCS) scores between baseline, SCS trial 
and follow up visits 
• 
Evaluate the change in Patient Global Impression of Change (PGIC) between SCS trial and 
follow up visits 
• 
Evaluate the change in medication usage between baseline, SCS trial and follow up visits 
1.4.3 
Descriptive Endpoint(s) 
Descriptive endpoints are reported using only summary statistics and no hypothesis tests will be 
performed. 
 
• 
Optimal microdosing program 
• 
Medication Usage 
 
Study Population 
The intended population of this clinical investigation consists of patients diagnosed with chronic 
intractable back and/or leg pain with no prior history of neuromodulation therapies. 
 
Inclusion/Exclusion Criteria 
1.6.1 
Inclusion Criteria 
• 
Subject is able to provide informed consent to participate in the study; 
• 
Subject diagnosed with chronic intractable pain associated with back and/or limbs; 
• 
Subject is 18 years of age or older; 
• 
Subject has failed to respond to at least 6 months of conventional treatment which may include 
pharmacological treatment, physical therapy, epidural injections; 
• 
Subject has a back and/or leg pain intensity of at least 6.0 cm out of 10.0 cm on the average back 
and/or leg pain VAS at baseline; 
• 
Subject’s medical record has been evaluated by the Investigator to ensure that the subject is a 
good candidate for a neurostimulation system;  
• 
Subject is on  stable pain medications with a total opioid for at least 28 days prior to enrolling in 
this study, and  is willing to stay on those medications with no dose increase until the 3 month 
visit; 
• 
Subject is willing to cooperate with the study requirements including compliance with the regimen 
and completion of all office visits; 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 12 of 41 
 
• 
Female candidates of child-bearing potential agree to commit to the use of an effective method of 
contraception (including but not limited to sterilization, barrier devices, oral contraceptives, 
intrauterine devices (IUDs), condoms, rhythm method, or abstinence) for the duration of the study 
1.6.2 
Exclusion Criteria 
• 
Subject has a current diagnosis of a coagulation disorder, bleeding diathesis, progressive 
peripheral vascular disease, post-herpetic neuralgia or uncontrolled diabetes mellitus; 
• 
Subject is currently participating in a clinical investigation that includes an active treatment arm; 
• 
Subject has been implanted with or participated in a trial period for a neurostimulation system; 
• 
Subject has an infusion pump; 
• 
Subject has evidence of an active disruptive psychological or psychiatric disorder as determined 
as per standard of care; 
• 
Subject has a current diagnosis of a progressive neurological disease as determined by the 
Investigator; 
• 
Subject is immunocompromised; 
• 
Subject has an existing medical condition that is likely to require repetitive MRI evaluation in the 
future (i.e. epilepsy, stroke, multiple sclerosis, acoustic neuroma, tumor); 
• 
Subject has history of cancer requiring active treatment in the last 12 months; 
• 
Subject has an existing medical condition that is likely to require the use of diathermy in the 
future; 
• 
Subject has documented history of allergic response to titanium or silicone; 
• 
Subject has a documented history of substance abuse (narcotics, alcohol, etc.) or substance 
dependency in the 6 months prior to baseline data collection; 
• 
Subject is a female candidates of child bearing potential that are pregnant (confirmed by positive 
urine/blood pregnancy test); 
• 
Subject has life expectancy of less than 6 months; 
• 
Subject is involved in an injury claim under current litigation 
 
Enrollment 
A patient becomes a subject once he/she has been fully informed about the study, has agreed to 
participate, signed & dated the consent. 
 
Study Assessments 
Subjects will undergo a baseline assessment to collect primary and secondary outcome measures prior to 
the SCS trial. Specifically, baseline assessments will include: pain rating as assessed by the VAS, quality 
of life as assessed by EQ-5D, disability as assessed by ODI, anxiety and depression as assessed by the 
HADS, and pain catastrophizing as assessed by the PCS. Medication usage will also be collected during 
the baseline visit. 
 
Subjects will be implanted with trial SCS system according to clinical practice and practitioner’s discretion. 
At the end of the SCS trial period, subjects who experienced a reduction of 50% or more in average pain 
back and/or leg VAS scores with one of the two microdosing stimulation paradigms will be offered 
permanent implant and further participation in the study. The same primary and secondary outcomes 
measures will be collected at the end of the SCS trial period as well as at the 1, 3 and 6 months follow up 
visit, with the inclusion of patient satisfaction as assessed by the PGIC. Programming parameters will 
also be assessed during these visits. 
2 
Introduction 
This document is a clinical investigation plan (CIP) for the BOLD clinical investigation. This clinical 
investigation is intended to evaluate the therapeutic efficacy of microdosing BurstDRTM stimulation in 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 13 of 41 
 
spinal cord stimulation (SCS) patients with chronic intractable back and/or leg pain. This clinical 
investigation is sponsored by Abbott. 
 
This clinical investigation will be conducted in accordance with this CIP. All parties involved in the conduct 
of the clinical investigation will be qualified by education, training, or experience to perform their tasks and 
this training will be documented appropriately. 
3 
Background and Justification for Clinical Investigation 
Spinal cord stimulation (SCS) is increasingly being used as an alternative for the treatment of chronic, 
intractable pain. In a systematic meta-analysis of the literature, Taylor et al. (2006) reported that SCS 
reduces pain, improves quality of life, reduces analgesic use, allows some patients to return to work and 
may also result in significant cost savings over time, while having minimally significant adverse events in 
patients with neuropathic back and/or leg pain. 
 
Patients receiving conventional tonic SCS (electrical pulses delivered in the 40-60Hz stimulation 
frequency range) experience paresthesia or a tingling sensation. Burst SCS is a newer paradigm that is 
currently approved worldwide. Burst stimulation eliminates or greatly reduces the incidence of paresthesia 
(Courtney et al. 2014), and it entails delivering groups of pulses called burst trains (A) repeated at a burst 
rate (B); within each burst train, several pulses are issued at an intra-burst rate (C) (See Figure 3). 
Individual pulses are characterized by a pulse amplitude (D) and pulse width. 
 
Figure 3: 
 
 
 
While the efficacy of standard burst stimulation parameters is known (Courtney et al. 2014, DeRidder et 
al., 2010, 2013), its comparison to more energy efficient settings is unknown.  
 
Burst microdosing consists of delivery of intermittent doses of burst stimulation. Preliminary evidence 
supports that the therapeutic efficacy of burst microdosing results in a similar clinical outcome compared 
to standard burst stimulation (Vesper et al. 2017). Use of these new energy efficient stimulation 
parameters has the potential to prolong the battery life of a non-rechargeable, primary cell Implantable 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 14 of 41 
 
Pulse Generator (IPG). It also has the potential to improve patient convenience by decreasing the 
frequency with which the patient has to recharge a non-primary cell IPG. 
In this study, we aim to evaluate the therapeutic efficacy of different BurstDRTM microdosing patterns in 
patients with chronic intractable pain 
4 
Device(s) Under Investigation 
 
Identification and Description of the Devices under investigation 
4.1.1 
Identification 
 
Table 2: Identification of Devices under Investigation 
Device name 
Model/Type 
Manufacturer 
Region/ Country 
Investigational or 
Market Released 
Abbott Invisible trial external 
pulse generator (EPG) 
3599 (Base), 
3032 (Header) 
Abbott 
US/OUS 
Released 
Abbott Invisible trial Clinician 
Programmer 
3870, 3872 
Abbott 
US/OUS 
Released 
Abbott Invisible trial Patient 
Controller 
3871, 3873 
Abbott 
US/OUS 
Released 
Abbot Percutaneous trial lead 
31XX 
Abbott 
US/OUS 
Released 
Abbott Lead extension 
33XX 
Abbott 
US/OUS 
Released 
Abbott Prodigy internal pulse 
generator (IPG) 
3799 
Abbott 
US/OUS 
Released 
Abbott Prodigy MRI IPG 
3772 
Abbott 
US/OUS 
Released 
Abbott Prodigy Charger 
3730 
Abbott 
US/OUS 
Released 
Abbott Prodigy Patient 
Programmer 
3856 
Abbott 
US/OUS 
Released 
Abbott Rapid Programmer 
programming device 
3835 
Abbott 
US/OUS 
Released 
Abbott Proclaim IPG 
3660, 3662 
Abbott 
US/OUS 
Released 
Abbott Clinician Programmer 
App 
3874 
Abbott 
US/OUS 
Released 
Abbott Patient Controller App 
3875 
Abbott 
US/OUS 
Released 
Abbott commercially available 
percutaneous leads 
31X6, 318X, 
314X, 315X, 
316X 
Abbott 
US/OUS 
Released 
Abbott  commercially available 
paddle leads 
322X, 321X, 
328X, 324X, 
326X, 3240 
Abbott 
US/OUS 
Released 
Abbott Cinch™ Lead Anchor 
1194 
Abbott 
US/OUS 
Released 
Abbott Swift-Lock™ Anchor 
1192 
Abbott 
US/OUS 
Released 
 
4.1.2 
Device Description and Intended Purpose 
Abbott Invisible trial external pulse generator (EPG): a 16 channels, software controlled, battery 
powered, and external stimulator that generates the electrical pulses to be used during the trial phase of 
the study  

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 15 of 41 
 
Abbott Invisible trial Clinician Programmer: software compatible with iOS™ App 8.1 or later to be 
used on iPad mini™; enables the clinician to program the Abbott Invisible trial EPG 
Abbott Invisible trial Patient Controller: software compatible with iOS™ App 8.1 or later to be used on 
iPad touch™; enables patient-controlled therapy adjustment of the Abbott Invisible trial EPG 
Abbott Percutaneous trial lead: sterile stimulating electrode placed in the epidural space of the spinal 
cord and connected to the EPG 
Abbott Lead extension: sterile extension that connects the pulse generator to the stimulating electrode 
Abbott Prodigy: a 16 channels, software controlled, rechargeable battery powered, internal stimulator to 
be used during the follow up phase of the study that generates the electrical pulses. 
Abbott Prodigy MRI: a 16 channels, software controlled, rechargeable battery powered, internal 
stimulator to be used during the follow up phase of the study that generates the electrical pulses. 
Abbott Prodigy Charger: The IPG Charging System provides the capability to recharge the IPG battery 
while stimulation is either on or off.  The charging system has several main parts: AC line cord, AC power 
supply, power cable, and charger antenna.  The charger transmits RF energy through the antenna to the 
IPG battery to recharge it. 
Abbott Patient Programmer: the patient programmer allows subjects to adjust stimulation intensity and 
to select a different stimulation programs in the Prodigy MRI IPG. 
Abbott Rapid Programmer: the rapid programmer enables the clinician to program the Prodigy IPG.   
Abbott Proclaim internal pulse generator (IPG): a 16 channels, software controlled, battery powered, 
internal stimulator to be used during the follow up phase of the study that generates the electrical pulses 
Abbott Clinician Programmer App: software compatible with iOS™ App 8.3 or later to be used on iPad 
mini™; enables the clinician to program the Proclaim IPG 
Abbott Patient Controller App: software compatible with iOS™ App 8.1 or later to be used on iPad 
touch™; enables patient-controlled therapy adjustment of the Proclaim IPG 
Abbott percutaneous leads lead: sterile stimulating electrode that are placed in the epidural space of 
the spinal cord and connected to the Proclaim or Protégé IPG 
Abbott paddle leads: sterile stimulating electrodes that are placed in the epidural space of the spinal 
cord and connected to the Proclaim or Protégé IPG 
Abbott Cinch™ Lead Anchor: securing device designed to reduce lead migration and breakage 
Abbott Swift-Lock™ Anchor: securing device designed to reduce lead migration and breakage 
4.1.3 
Device Handling and Storage 
Sponsor requires all investigational products be stored, according to the labeling and Instructions for Use, 
in a secure area to prevent unauthorized access or use. 
4.1.4 
Identification 
 
Devices Accountability 
Device accountability not required in post market studies 
5 
Clinical Investigation Design 
 
Clinical Investigation Design 
This is a prospective, open label, multicenter feasibility trial to evaluate the therapeutic efficacy of different 
BurstDRTM microdosing patterns in patients with chronic intractable pain.  
 
Subjects diagnosed with chronic intractable back and/or leg pain, with no prior history of SCS therapy, will 
be considered for inclusion in this study. After baseline evaluation, subjects will undergo a SCS trial using 
the Abbott Invisible Trial system.  During the trial implant phase, SCS leads will be implanted in the dorsal 
column based on physician discretion. According to standard clinical practices performed in the United 
States (US), the trial phase will last around 3-7 days. At the start of the trial phase, patients will be 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 16 of 41 
 
programmed with the first ON/OFF stimulation pattern (30 second STIM ON, 90 seconds STIM OFF).  
Patients who do not achieve adequate pain relief (at least 50% reduction in back and/or leg VAS from 
baseline) within the first 3-4 days will be reprogrammed to a new ON/OFF stimulation pattern (5 seconds 
ON/ 15 seconds OFF). Patients, who still do not achieve adequate pain relief within 2 to 3 days from 
reprogramming, will be reprogrammed to a continuous mode of BurstDRTM stimulation and their trial 
evaluation will continue. These patients will be evaluated for an additional 2 days. At the end of the SCS 
trial, all subjects that experience at least 50% pain relief (according to average back and/or leg VAS) 
using one of the two microdosing burst stimulation paradigms will be considered further participation in 
the study. See Figure 1. 
 
Patients who have passed the trial phase and have received permanent implantation will be programmed 
based on the stimulation mode used for their trial success. Pain intensity, quality of life, disability, anxiety, 
depression, pain catastrophizing, satisfaction, and medication usage will be assessed at baseline, after 
SCS trial and at the 1, 3 and 6 month follow up. Adverse events will be collected throughout the study 
period. 
 
During the month leading to the 1 month follow up visit, patients’ pain relief will be evaluated on a weekly 
basis according to Figure 2. Briefly, patients who do not achieve adequate pain relief (greater or equal to 
pain relief achieved during the trial phase) will try lower stimulation ON/OFF ratios to determine the lowest 
possible stimulation ratio whilst maintaining adequate pain relief. This stimulation ON/OFF ratios will start 
from a ratio of 1:12 (Program 1) and increase to a potential ON/OFF ratio of 1:3 (Program 5) – Once the 
most optimal microdosing program is determined (as per algorithm in Figure 2), the patient will continue 
the rest of the study with that program.  If inadequate pain relief is experienced anytime during the study, 
the BurstDRTM microdosing parameters will be altered as per the algorithm in Figure 2. 
 
Option 1: Patients who underwent a successful 
trial using 30s ON:90s OFF BurstDRTM 
microdosing 
Option 2: Patients who underwent a successful 
trial using 5s ON:15s OFF BurstDRTM 
microdosing 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 17 of 41 
 
Figure 2: Representation of the decision making algorithm for the SCS 1 month post permanent implant 
phase of the study 
 
The total duration of the study is expected to be 2 years. 
 
The clinical study will be conducted in up to 6 centers in the United States. 
 
Approximately 60 subjects will be enrolled in this study. 
 
Objectives 
The objective of this clinical investigation is to evaluate the therapeutic efficacy of microdosing BurstDRTM 
stimulation in spinal cord stimulation (SCS) patients with chronic intractable back and/or leg pain. 
5.2.1 
Primary Objectives 
• 
To evaluate efficacy of microdosing BurstDRTM stimulation in patients with chronic intractable 
back and/or leg pain that have never received neuromodulation treatments before. 
 
5.2.2 
Secondary Objectives 
• 
Evaluate the optimal microdosing program required  to maintain optimal pain relief on a patient 
specific basis 
• 
Evaluate the long term efficacy of BurstDRTM stimulation on patients’ pain intensity 
• 
Evaluate the improvements in quality of life, disability, anxiety, depression, catastrophizing, 
medication and overall satisfaction of patients using microdosing BurstDRTM stimulation 
 
Endpoints 
There is 1 primary endpoints and 7 secondary endpoints in this clinical investigation. 
5.3.1 
Primary Endpoint 
• 
Evaluate the change in pain intensity between baseline, trial and long-term follow up evaluations 
using the Visual Analog Scale (VAS) assessments. 
5.3.2 
Secondary Endpoint 
• 
Evaluate the optimal microdosing program required  to maintain optimal pain relief on a patient 
specific basis 
• 
Evaluate the change in European Quality of life – 5 Dimensions (EQ-5D) scores between 
baseline, SCS trial and follow up visits 
• 
Evaluate the change in Oswestry Disability Index (ODI) scores between baseline, SCS trial and 
follow up visits 
• 
Evaluate the change in Hospital Anxiety and Depression Scale (HADS) scores between baseline, 
SCS trial and follow up visits 
• 
Evaluate the change in Pain Catastrophizing Scale  (PCS) scores between baseline, SCS trial 
and follow up visits 
• 
Evaluate the change in Patient Global Impression of Change (PGIC) between SCS trial and 
follow up visits 
• 
Evaluate the change in medication usage between baseline, SCS trial and follow up visits 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 18 of 41 
 
5.3.3 
Descriptive Endpoint(s) 
Descriptive endpoints are reported using only summary statistics and no hypothesis tests will be 
performed. 
 
• 
Optimal microdosing program 
• 
Medication Usage 
 
Study Population 
The intended population of this clinical investigation consists of patients diagnosed with chronic 
intractable back and/or leg pain with no prior history of neuromodulation therapies. 
5.4.1 
Inclusion Criteria 
• 
Subject is able to provide informed consent to participate in the study; 
• 
Subject diagnosed with chronic intractable pain associated with back and/or limbs; 
• 
Subject is 18 years of age or older; 
• 
Subject has failed to respond to at least 6 months of conventional treatment which may include 
pharmacological treatment, physical therapy, epidural injections; 
• 
Subject has a back and/or leg pain intensity of at least 6.0 cm out of 10.0 cm on the average back 
and/or leg pain VAS at baseline; 
• 
Subject’s medical record has been evaluated by the Investigator to ensure that the subject is a 
good candidate for a neurostimulation system;  
• 
Subject is on  stable pain medications with a total opioid for at least 28 days prior to enrolling in 
this study, and  is willing to stay on those medications with no dose increase until the 3 month 
visit; 
• 
Subject is willing to cooperate with the study requirements including compliance with the regimen 
and completion of all office visits; 
• 
Female candidates of child-bearing potential agree to commit to the use of an effective method of 
contraception (including but not limited to sterilization, barrier devices, oral contraceptives, 
intrauterine devices (IUDs), condoms, rhythm method, or abstinence) for the duration of the study 
5.4.2 
Exclusion Criteria 
• 
 Subject has a current diagnosis of a coagulation disorder, bleeding diathesis, progressive 
peripheral vascular disease, post-herpetic neuralgia or uncontrolled diabetes mellitus; 
• 
Subject is currently participating in a clinical investigation that includes an active treatment arm; 
• 
Subject has been implanted with or participated in a trial period for a neurostimulation system; 
• 
Subject has an infusion pump; 
• 
Subject has evidence of an active disruptive psychological or psychiatric disorder as determined 
as per standard of care; 
• 
Subject has a current diagnosis of a progressive neurological disease as determined by the 
Investigator; 
• 
Subject is immunocompromised; 
• 
Subject has an existing medical condition that is likely to require repetitive MRI evaluation in the 
future (i.e. epilepsy, stroke, multiple sclerosis, acoustic neuroma, tumor); 
• 
Subject has history of cancer requiring active treatment in the last 12 months; 
• 
Subject has an existing medical condition that is likely to require the use of diathermy in the 
future; 
• 
Subject has documented history of allergic response to titanium or silicone; 
• 
Subject has a documented history of substance abuse (narcotics, alcohol, etc.) or substance 
dependency in the 6 months prior to baseline data collection; 
• 
Subject is a female candidates of child bearing potential that are pregnant (confirmed by positive 
urine/blood pregnancy test); 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 19 of 41 
 
• 
Subject has life expectancy of less than 6 months; 
• 
Subject is involved in an injury claim under current litigation 
6 
Procedures 
The clinical study will be conducted in accordance with the CIP.  All parties participating in the conduct of 
the clinical study will be qualified by education, training, or experience to perform their tasks and this 
training will be documented appropriately. Approval from the Sponsor must be received prior to initiating 
study procedures. 
 
Patients will be informed about the study to determine if he/she is interested in participating. Eligible 
patients will read, sign and date the informed consent and will continue to participate in the study as 
subjects. Subjects diagnosed with chronic intractable back and/or leg pain, with no prior history of SCS 
therapy, will be considered for inclusion in this study and will be assessed at baseline and all follow up 
visits. 
 
The assessments will include: 
• 
Pain intensity as assessed by the Visual Analog Scale (VAS) 
• 
Quality of life as assessed by the European Quality of Life – 5 Dimensions (EQ-5D) 
• 
Disability as assessed by the Oswestry Disability Index (ODI) 
• 
Anxiety and Depression as assessed by the Hospital Anxiety and Depression Scale (HADS) 
• 
Pain Catastrophizing as assessed by the Pain Catastrophizing Scale (PCS) 
• 
Satisfaction as assessed by the Patient Global Impression of Change (PGIC) 
• 
Medication Usage 
• 
Adverse Events 
 
After baseline evaluation, subjects will undergo a SCS trial using the Abbott Invisible Trial system. During 
the trial implant phase, SCS leads will be implanted in the dorsal column based on physician discretion. 
According to standard clinical practices performed in the United States (US), the trial phase will last 
around 3-7 days. At the start of the trial phase, patients will be programmed with the first ON/OFF 
stimulation pattern (30 second STIM ON, 90 seconds STIM OFF).  Patients who do not achieve adequate 
pain relief (at least 50% reduction in back and/or leg VAS from baseline) within the first 3-4 days will be 
reprogrammed to a new ON/OFF stimulation pattern (5 seconds ON/ 15 seconds OFF). Patients, who still 
do not achieve adequate pain relief within 2 to 3 days from reprogramming, will be reprogrammed to a 
continuous mode of BurstDRTM stimulation and their trial evaluation will continue. These patients will be 
evaluated for an additional 2 days. At the end of the SCS trial, all subjects that experience at least 50% 
pain relief (according to average back and/or leg VAS) using one of the two microdosing burst stimulation 
paradigms will be considered further participation in the study. See Figure 1. 
 
Patients who have passed the trial phase and have received permanent implantation will be programmed 
based on the stimulation mode used for their trial success. Pain intensity, quality of life, disability, anxiety, 
depression, pain catastrophizing, satisfaction, and medication usage will be assessed at baseline, after 
SCS trial and at the 1, 3 and 6 month follow up. Adverse events will be collected throughout the study 
period. 
 
During the month leading to the 1 month follow up visit, patients’ pain relief will be evaluated on a weekly 
basis according to Figure 2. Briefly, patients who do not achieve adequate pain relief (greater or equal to 
pain relief achieved during the trial phase) will try lower stimulation ON/OFF ratios to determine the lowest 
possible stimulation ratio whilst maintaining adequate pain relief. This stimulation ON/OFF ratios will start 
from a ratio of 1:12 (Program 1) and increase to a potential ON/OFF ratio of 1:3 (Program 5) – Once the 
most optimal microdosing program is determined (as per algorithm in Figure 2), the patient will continue 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 20 of 41 
 
the rest of the study with that program.  If inadequate pain relief is experienced anytime during the study, 
the BurstDRTM microdosing parameters will be altered as per the algorithm in Figure 2. 
 
The following sections provide a detailed description of procedures required by this CIP. 
 
Informed Consent Process 
The Principal Investigator or his/her authorized designee will conduct the Informed Consent Process, as 
required by applicable regulations and the center’s IRB/EC. This process will include a verbal discussion 
with the subject on all aspects of the clinical investigation that are relevant to the subject’s decision to 
participate, such as details of clinical investigation procedures, anticipated benefits, and potential risks of 
clinical investigation participation. During the discussion, the Principal Investigator or his/her authorized 
designee will avoid any improper influence on the subject and will respect subject’s legal rights. The 
subject shall be provided with the informed consent form written in a language that is understandable to 
the subject and has been approved by the center’s IRB/EC. The subject shall have adequate time to 
review, ask questions and consider participation. 
 
If the subject agrees to participate, the Informed Consent form must be signed and dated by the subject 
and by the person obtaining the consent. The signed original will be filed in the subject’s hospital or 
research charts, and a copy will be provided to the subject. 
 
The Principal Investigator or his/her authorized designee will document the informed consent process in 
the subject’s hospital and/or research charts. The date of signature will be entered on an applicable Case 
Report Form (CRF). 
 
Failure to obtain informed consent from a subject prior to clinical investigation enrollment should be 
reported to Sponsor within 5 working days and to the reviewing center’s IRB/EC according to the IRB’s/ 
EC’s reporting requirements. 
 
If, during the clinical investigation, new information becomes available that can significantly affect a 
subject's future health and medical care, the Principal Investigator or his/her authorized designee will 
provide this information to the subject. If relevant, the subject will be asked to confirm their continuing 
informed consent in writing. 
 
Screening 
Potential patients presenting at the investigational sites will be fully informed about the clinical 
investigation, following the established Informed Consent process (described in section 6.1). Once a duly 
dated and signed Informed Consent Form is obtained, the screening procedures may begin.  
 
Records of patients who are screened must be maintained. 
 
In case the subject does not meet all inclusion criteria or meets any of the exclusion criteria, the subject is 
considered a screening failure. The Principal Investigator or the delegated study personnel will record the 
screening failure in the hospital records and on a screening log as required. 
 
Point of Enrollment 
Subject is considered enrolled in the clinical investigation from the moment the subject has provided a 
written Informed Consent and has been confirmed to meet all inclusion criteria and none of the exclusion 
criteria. 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 21 of 41 
 
The Principal Investigator or delegated study personnel will record enrollment information (name of the 
clinical investigation, date of consent and Inclusion/exclusion information) in the hospital records and 
complete and submit an applicable CRF in a timely manner. 
 
Notification of enrollment to the Sponsor is considered to have occurred when the Sponsor has received 
the applicable CRF. 
 
Scheduled Procedures 
The Principal Investigator is responsible for ensuring all clinical investigation data is collected as required 
per CIP scheduled procedures. 
6.4.1 
Baseline 
Baseline visit activities can occur at the same visit of enrollment after the informed consent has been 
obtained.   
 
The following assessments and information will be collected at the baseline visit 
• 
Demographics- include subject’s Age and Gender 
• 
Physical examination- include subject’s height and weight 
• 
Indication for device/ procedure 
• 
Previous therapies tried for indications 
• 
Clinical investigation specific examinations 
 
Pain intensity as assessed by the VAS 
 
Quality of life as assessed by the EQ5D 
 
Disability as assessed by the ODI 
 
Anxiety and Depression as assessed by the HADS 
 
Pain Catastrophizing as assessed by the PCS 
 
Medication Usage 
 
 
Timing of visit 
Activities at visit 
Case Report Form 
Screening/Baseline 
• 
Subject assesses pre-trial pain levels, quality of 
life, disability, anxiety, depression, pain 
catastrophizing, and medication usage.  
 
• 
VAS Form 
• 
EQ-5D Form 
• 
ODI Form 
• 
HADS Form 
• 
PCS Form 
• 
Medication Usage Form 
 
6.4.2 
SCS Trial 
During the trial implant phase, SCS leads will be implanted in the dorsal column based on physician 
discretion. According to standard clinical practices performed in the United States (US), the trial phase 
will last around 3-7 days. At the start of the trial phase, patients will be programmed with the first ON/OFF 
stimulation pattern (30 second STIM ON, 90 seconds STIM OFF).  Patients who do not achieve adequate 
pain relief (at least 50% reduction in back and/or leg VAS from baseline) within the first 3-4 days will be 
reprogrammed to a new ON/OFF stimulation pattern (5 seconds ON/ 15 seconds OFF). Patients, who still 
do not achieve adequate pain relief within 2 to 3 days from reprogramming, will be reprogrammed to a 
continuous mode of BurstDRTM stimulation and their trial evaluation will continue. These patients will be 
evaluated for an additional 2 days. At the end of the SCS trial, all subjects that experience at least 50% 
pain relief (according to average back and/or leg VAS) using one of the two microdosing burst stimulation 
paradigms will be considered further participation in the study. Patients who still do not achieve adequate 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 22 of 41 
 
pain relief will be reprogrammed to a continuous mode of BurstDRTM stimulation and their trial evaluation 
will continue. These patients will be evaluated for an additional 2 days. 
 
The following assessments and information will be collected at the SCS Trial visit 
• 
Surgery Form  
• 
Clinical investigation specific examinations 
 
Programming Form 
 
The following activities will be performed at the SCS Trial visit: 
• 
SCS Trial Lead(s) Implant 
• 
EPG Device programming 
 
Timing of visit 
Activities at visit 
Case Report Form 
SCS Trial 
• 
SCS trial lead implant 
• 
EPG programming 
 
• 
Surgery Form 
• 
Programming Form 
 
 
6.4.3 
End of Trial 
During the End of Trial visit, subjects will complete the same questionnaires completed during the 
baseline visit.  If the VAS score is < 50% of the VAS collected during the screening visit and is not using 
the two microdosing burst stimulation paradigms, the subject will exit the study. Subjects whose VAS 
score at the end of the trial is >50% of the VAS collected during the screening visit and is using one of the 
two microdosing burst stimulation paradigms, will be considered for permanent lead and IPG 
implantation. 
 
The following assessments and information will be collected at the End of Trial visit: 
• 
Clinical investigation specific examinations 
 
Pain level as assessed by the VAS 
 
Quality of life as assessed by the EQ-5D 
 
Disability as assessed by the ODI   
 
Anxiety and Depression as assessed by the HADS 
 
Pain Catastrophizing as assessed by the PCS 
 
Satisfaction as assessed by the PGIC  
 
Medication usage; 
 
Programming Form 
 
Timing of visit 
Activities at visit 
Case Report Form 
End of Trial 
• 
Subject assess pain levels, quality of life, disability, 
anxiety, depression, pain catastrophizing, 
satisfaction, medication usage, and programming   
 
 
• 
VAS Form 
• 
EQ-5D Form 
• 
ODI Form 
• 
HADS Form 
• 
PCS Form 
• 
PGIC Form 
• 
Medication Usage Form 
• 
Programming Form 
 
 
6.4.4 
Permanent Implant 
Permanent implant will be performed according to standard clinical practice. 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 23 of 41 
 
 
The following assessments and information will be collected at the Permanent Implant visit 
• 
Surgery Form  
 
The following activities will be performed at the Permanent Implant visit: 
• 
SCS Permanent Lead(s) Implant 
• 
IPG Implant 
 
Timing of visit 
Activities at visit 
Case Report Form 
SCS Permanent 
Implant 
• 
SCS permanent lead implant 
• 
IPG implant 
• 
Surgery Form 
 
6.4.5 
Activation 
IPG will be programmed using burst stimulation according to standard programming techniques. 
 
The following assessments and information will be collected at the Activation visit 
• 
Clinical investigation specific examinations 
 
Programming Form 
 
Timing of visit 
Activities at visit 
Case Report Form 
Activation 
• 
IPG programming 
 
• 
Programming Form 
 
6.4.6 
Scheduled Follow-ups 
 
Subjects will be followed up for 6 months post-activation visit with follow-up assessments at 1, 3 and 6 
months. During each visit, subjects will complete the same questionnaires completed during the end of 
trial visit. 
The following assessments and information will be collected at the End of Trial visit: 
• 
Clinical investigation specific examinations 
 
Pain level as assessed by the VAS 
 
Quality of life as assessed by the EQ-5D 
 
Disability as assessed by the ODI   
 
Anxiety and Depression as assessed by the HADS 
 
Pain Catastrophizing as assessed by the PCS 
 
Satisfaction as assessed by the PGIC  
 
Medication usage; 
 
Programming Form 
 
Timing of visit 
Activities at visit 
Case Report Form 
End of Trial 
• 
Subject assess pain levels, quality of life, disability, 
anxiety, depression, pain catastrophizing, 
satisfaction, medication usage, and programming   
 
 
• 
VAS Form 
• 
EQ-5D Form 
• 
ODI Form 
• 
HADS Form 
• 
PCS Form 
• 
PGIC Form 
• 
Medication Usage Form 
• 
Programming Form 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 24 of 41 
 
 
 
Patient Reported Outcome (PRO) Measures 
The Study Coordinator or designee will administer patient-reported outcome questionnaires. It is 
important the subject understands the meaning of all words and instructions in the questionnaires. The 
subject should be instructed to ask any questions about the questionnaires if further explanation is 
needed. Once the questionnaires are completed, the Study Coordinator or designee will review for 
completeness to verify that all questions have been answered according to the directions provided. 
 
The following PRO measures will be collected according to the study requirements. 
 
• 
Pain level as assessed by the VAS 
• 
Quality of life as assessed by the EQ-5D 
• 
Disability as assessed by the ODI  
• 
Pain Catastrophizing as assessed by the PCS 
• 
Anxiety and Depression as assessed by the HADS 
 
Unscheduled Visits 
An Unscheduled Visit is defined as any visit where an active study subject returns to the participating 
study site for medical care outside of a specified study visit.  Unscheduled visits may include subjects 
returning to the office for an adverse event. The visit should be documented by completing the 
Unscheduled Visit Form and any other applicable forms (Adverse Event, Deviation, Death and/or 
Withdrawal Form. 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 25 of 41 
 
 
Study Flow Chart 
 
The Study Flow Chart and the Table 2 below summarize subject flow and requirements of this clinical 
investigation. 
 
Figure 1: Study Flow Chart 
 
 
 
 
 
 
 
 
 
 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 26 of 41 
 
 
 
Table 2: List of all clinical investigation specific tests and procedures 
 
                Visit 
 
 
Study Activity 
Enrollment  
 
Baseline 
 
SCS Trial 
 
End of 
Trial 
 
SCS 
Implant  
 
Activation 
 
Follow-up 
Visits* 
 
Informed Consent 
Process 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria Screening 
X 
 
 
 
 
 
 
VAS Assessment 
 
X 
 
X 
 
 
X 
Enrollment Form 
X 
 
 
 
 
 
 
EQ-5D Assessment 
 
X 
 
X 
 
 
X 
ODI Assessment 
 
X 
 
X 
 
 
X 
HADS Assessment 
 
X 
 
X 
 
 
X 
PCS Assessment 
 
X 
 
X 
 
 
X 
PGIC Assessment 
 
 
 
X 
 
 
X 
Trial System 
Implant 
 
 
X 
 
 
 
 
Permanent System 
Implant 
 
 
 
 
X 
X 
 
Adverse Event 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Deviation 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Termination 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Death 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) If applicable 
* Follow up visit assessments will be performed at months 1(30 ± 21 days), 3(90 ± 21 days) and (180 ± 
21 days) 
 
Description of Activities Performed by Sponsor Representatives 
Trained sponsor personnel may perform certain activities to ensure compliance to the clinical 
investigational plan and may provide technical expertise. 
 
Sponsor personnel may:  
• 
Provide technical support to the Investigators during trial 
 
Sponsor personnel will not:  
• 
Perform the informed consent process  
• 
Provide medical diagnosis or treatment to subjects  
• 
Discuss a subject’s condition or treatment with a subject without the approval and presence of a 
health care practitioner  
• 
Independently collect clinical investigational data 
 
While Sponsor representatives may perform these activities, the Principal Investigator remains 
responsible for ensuring all clinical investigation data is collected as required per CIP. 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 27 of 41 
 
 
Subject Study Completion 
Subject participation in the clinical investigation will conclude upon completion of the 6-month visit. Upon 
completion of subject participation in the clinical investigation, the subject will return to standard of care. 
 Subject Withdrawal 
Subjects must be informed about their right to withdraw from the clinical investigation at any time and for 
any reason without sanction, penalty or loss of benefits to which the subject is otherwise entitled. 
Withdrawal from the clinical investigation will not jeopardize their future medical care or relationship with 
the investigator. Subjects will be requested to specify the reason for the request to withdraw. The 
investigator must make all reasonable efforts to retain the subject in the clinical investigation until 
completion of the clinical investigation. 
 
The investigator may decide to withdraw a subject from the study at any time with reasonable rationale. 
The subject’s future care will not be influenced by a decision, voluntary or otherwise, to withdraw from the 
study. All reasonable efforts should be made to retain the subject in the clinical study until completion of 
the study. 
 
Reasons for subject’s withdrawal include, but are not limited to: 
 
• 
Subject refuses to continue participating in the study 
• 
Subject does not meet the inclusion/exclusion criteria and does not require additional follow-up 
for safety reasons. 
• 
Subject is deceased (cause must be documented) 
• 
Subject’s non-compliance 
• 
Subject’s participation is terminated by the PI or investigator, although the subject consented, 
since participation is no longer medically appropriate 
• 
Subject is ‘lost to follow up’: Subject does not adhere to the scheduled follow up visits but has 
not explicitly requested to be withdrawn from the clinical study. (This does not apply to missed 
visits). Site personnel should at all times make all reasonable efforts to locate and 
communicate with the subject in order to achieve subject compliance to the scheduled follow 
up visits: 
 
A subject will be considered ‘Lost to Follow Up’ after a minimum of 2 phone calls 
of a physician or delegate at the investigational site to the subject or contact. 
These 2 phone calls need to be documented in the subject’s hospital records. 
 
If these attempts are unsuccessful, a letter should be sent to the subject’s last 
known address or general practitioner (GP) and a copy of this letter should be 
maintained in the subject’s hospital records. 
 
Note: If a subject misses one or more of the scheduled follow up visits (inclusive of the assigned visit 
windows), this will be considered as a missed visit. The subject may therefore still return for subsequent 
visits and will not be excluded from the study. 
 
If a subject withdraws from the clinical study, the site will record the subject’s reasons for withdrawal, on a 
Withdrawal CRF. 
 
When subject withdrawal from the clinical study is due to an adverse event the subject will be followed 
until resolution of that adverse event or determination that the subject’s condition is stable. The status of 
the subject’s condition should be documented at the time of withdrawal.   
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 28 of 41 
 
The third follow up visit will be the final study visit. The subject will complete the questionnaires as in the 
previous follow up visit and will exit the study. 
7 
Statistical Considerations 
The following section describes the statistical methods for the clinical investigation and justification of the 
design. Additional details on statistical analyses, including sensitivity analyses, poolability analyses, 
subgroup analyses and analysis of descriptive endpoint(s) may be maintained in a separate Statistical 
Analysis Plan (SAP).  
 
Hypotheses 
This study is an open label, multi-center, feasibility study. Thus, there is no requirement for a formal 
hypothesis testing. We do anticipate improvements in primary and secondary outcomes. The results 
obtained in this study will potentially be used to generate a level-1 evidence based study with formal 
statistical hypotheses testing. 
7.1.1 
Primary [Safety/Effectiveness] Endpoint Hypothesis(es) 
7.1.1.1 
Analysis Methodology  
The primary analysis to assess improvement in pain intensity, using VAS, will be conducted using 
repeated measures ANOVA (RMANOVA). Post-hoc Tukey’s pairwise comparisons will follow to 
determine specific differences between follow-up visits. Secondary analyses to assess improvements in 
quality of life, disability, anxiety, depression catastrophizing and satisfaction will be conducted using 
repeated measures ANOVA (RMANOVA) or the most appropriate statistical methods. 
7.1.1.2 
Sample Size Determination 
We will enroll approximately 60 subjects in up to 4 study centers in the US. This study is a feasibility trial 
and no sample size calculations are required.  
 
7.1.1.3 
Missing Data 
Missing data will be reported at each visit for each outcome. No imputations will be performed for missing 
data. 
 
Justification of Clinical Investigation Design 
This is a prospective, open label, multicenter feasibility trial to evaluate the therapeutic efficacy of different 
BurstDRTM microdosing patterns in patients with chronic intractable pain. Use of these new energy 
efficient stimulation parameters has the potential to prolong the battery life of a non-rechargeable, primary 
cell Implantable Pulse Generator (IPG). It also has the potential to improve patient convenience by 
decreasing the frequency with which the patient has to recharge a non-primary cell IPG. Thus, it is crucial 
to evaluate these potential energy efficient stimulation parameters in SCS eligible patients. 
 
Multiplicity 
All statistical tests will be performed with a type-1 error rate 0.05, unless otherwise stated. Family-wise 
error for RMANOVA will be addressed using Tukey’s pairwise post-hoc comparisons. 
 
Overall Sample Size 
We will enroll up to 60 subjects.  

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 29 of 41 
 
 
Timing of Analysis 
Interim analyses may be conducted after the end of trial visit. 
 
Success Criteria 
There are no formal success criteria. This is an observational study. 
 
Interim Analysis 
No formal interim analysis is planned for this study. 
 
Statistical Criteria for Termination 
There are no statistical criteria for termination of this clinical investigation. 
 
Deviations from Statistical Plan 
If any deviations from the original statistical plan occur, such deviations will be documented in the clinical 
study report or statistical report containing the analysis results. 
8 
Risks and Benefits 
The risks associated with SCS can be found in the Instructions for Use. The study does not require any 
additional procedures over the standard of care. There are no additional risks introduced to study 
subjects. 
 
Risks Associated with the Device Under Investigation 
We do not foresee any additional risk, beyond those normally associated with SCS therapy, described 
below. 
8.1.1 
Anticipated Adverse Device Effects 
In addition to those risks commonly associated with surgery, the following risks are associated with 
implanting or using this neurostimulation system for SCS: 
 
• 
Undesirable changes in stimulation, which may be related to cellular changes in tissue around 
the electrodes, changes in electrode position, loose electrical connections, or lead failure 
• 
Lead migration, causing changes in stimulation and/or reduced pain relief 
• 
Epidural hemorrhage, hematoma, infection, spinal cord compression, or paralysis from 
placement of a lead in the epidural space 
• 
Cerebrospinal fluid (CSF) leakage 
• 
Paralysis, weakness, clumsiness, numbness, or pain below the level of the implant 
• 
Persistent pain at the electrode or IPG site 
• 
Seroma (mass or swelling) at the IPG site 
• 
Infection of the lead extension at the exit zone during trial or infection of the IPG site 
• 
Allergic or rejection response to implant materials 
• 
Implant migration or skin erosion around the implant 
• 
Anticipated adverse device effects 
• 
Battery failure 
 
These adverse events and adverse device effects are not specific to the study, but related to the 
approved SCS implant procedure. 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 30 of 41 
 
8.1.2 
Risks Associated with Clinical Investigation Assessments 
There are no additional risks associated with the clinical investigation assessments beyond standard of 
care. 
 
Risk Control Measures 
Every possible effort will be taken to minimize the risks, including: 
• 
Careful selection of experienced Investigators for the clinical investigation  
• 
Adequate monitoring for each clinical investigation site 
• 
Conducting the clinical investigation in accordance with the CIP, all applicable laws and 
regulations and any conditions of approval imposed by the appropriate IRB/EC or applicable 
regulatory authorities where the clinical investigation is performed 
• 
Preparation of the SCS device and performance SCS implant procedure in accordance with the 
device IFUs 
• 
Training of Investigators on the CIP  
 
Possible interactions with concomitant treatments 
There are no possible interactions with concomitant medical treatment and/or concurrent medical 
intervention beyond those associated with standard medical care using SCS. 
 
Anticipated Benefits 
There are no additional clinical benefits associated with the participation in this study beyond those 
anticipated with standard clinical SCS 
 
Risk-to-Benefit Rationale 
There are no additional risk-to-benefits associated with the participation in this study beyond those 
anticipated with standard clinical SCS. 
9 
Requirements for Investigator Records and Reports 
 
Deviations from CIP 
A deviation is defined as an instance(s) of failure to follow, intentionally or unintentionally, the 
requirements of the CIP. The investigator should not deviate from the CIP. 
 
In some cases, failure to comply with the CIP may be considered failure to protect the rights, safety and 
well-being of subjects; such non-compliance exposes subjects to unreasonable risks. Examples: failure to 
adhere to the inclusion/exclusion criteria, failure to perform safety assessments intended to detect 
adverse events. Investigators should seek to minimize such risks by adhering to the CIP. 
 
The PI must maintain accurate, complete, and current records, including documents showing the date of 
and reason for each deviation from the CIP. Relevant information for each deviation will be documented 
as soon as possible on the applicable CRF. The site will submit the CRF to the Sponsor. 
 
The PI is required to adhere to local regulatory requirements for reporting deviations to IRB/EC. 
 
Under emergency circumstances, deviations from the CIP to protect the rights, safety and well-being of 
subjects may proceed without prior approval of the Sponsor and the IRB/EC. Such deviations shall be 
documented and reported to the Sponsor and the IRB/EC as soon as possible. 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 31 of 41 
 
 
Safety Reporting 
Safety surveillance within this study and the safety reporting performed both by the investigator and 
Sponsor starts as soon as the procedure begins. This is defined as from the time the [dilator/device 
delivery system has been introduced into the body. 
 
The safety surveillance and the safety reporting will continue until the last investigational visit has been 
performed, the subject is deceased, the subject/investigator concludes his participation into the clinical 
investigation or the subject withdrawal from the clinical investigation. 
 
All adverse event data including deaths and device deficiency data (if applicable) will be collected 
throughout the clinical investigation and will be reported to the Sponsor on a CRF. 
 
Adverse events will be monitored until they are adequately resolved or the subject has ended his/her 
participation in the trial, whichever comes first. The status of the subject’s condition should be 
documented at each visit. 
 
The investigator will report the event to the IRB/EC per their reporting requirements.  
 
Reportable events to sponsor are considered:  
 
• 
All Adverse Device Effects 
• 
All Serious Adverse Events (whether or not the event is considered device or procedure related 
and regardless the randomization group) 
• 
(if applicable) device deficiencies, that could have led to a serious adverse device effect 
 
if either suitable action had not been taken;  
 
if intervention had not been made or 
 
if circumstances had been less fortunate 
 
All events mentioned above will be reported to the Sponsor, as soon as possible, but no later than 72 
hours of first learning of the event. 
 
Reportable events shall be submitted to the Sponsor. The Sponsor will ensure that all applicable events 
and device deficiencies are reported to the relevant authorities as per regulations. The sites should notify 
the Sponsor of reportable adverse events.. Additional information may be requested by the Sponsor in 
order to support the reporting of AEs to regulatory authorities. The investigator must notify the IRB/EC, if 
appropriate, in accordance with national and local laws and regulations, of the AEs reported to the 
Sponsor. All adverse events will be reported as per applicable regulatory requirements. 
9.2.1 
Subject Death 
All subject deaths are to be documented and reported to the sponsor within 72 hours after becoming 
aware of the event. 
All subjects’ deaths should be documented using the “Death Form” and a “Withdrawal Form”. 
9.2.2 
Complaints 
During the study, the investigator will be responsible for reporting all complaints. A complaint is defined as 
any written, electronic or oral communication that alleges deficiencies related to the identity, quality, 
durability, reliability, safety, effectiveness or performance of a device after it is released for distribution. 
 
If the complaint involves an AE, the investigator must complete an AE CRF, including the information on 
the complaint and submit to Abbott as soon as possible.  
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 32 of 41 
 
Should a subject death be caused by the Abbott device or the device contributed to the death, the 
investigator should complete a Form 3500A (MedWatch) and submit to Abbott and the FDA within 10 
days after becoming aware of the event. 
 
Source records 
Source documents will be created and maintained by the investigational site team throughout the clinical 
investigation. The data reported on the CRFs will be derived from, and be consistent with, these source 
documents, and any discrepancies will be explained in writing. 
 
The following data can be recorded directly in the CRFs: 
• 
Pain VAS scores 
• 
EQ-5D scores 
• 
ODI scores 
• 
HADS scores 
• 
PCS scores 
• 
PGIC scores 
• 
Medication usage form 
• 
Programming form 
• 
Adverse events form 
 
Records Retention 
The Sponsor and the Principal Investigators will maintain the clinical investigation documents as required. 
Measures will be taken to prevent accidental or premature destruction of these documents. The Principal 
Investigator or the Sponsor may transfer custody of records to another person/party and document the 
transfer at the investigational site or the Sponsor’s facility, as appropriate. 
 
These documents must be retained by the investigational site for a period of 2 years after the conclusion 
of the clinical investigation and made available for monitoring or auditing by the Sponsor’s representative 
or representatives of the applicable regulatory agencies. 
 
All original source documents must be stored for the maximum time required by the regulations at the 
hospital, research institute, or practice in question. If original source documents can no longer be 
maintained at the site, the investigator will notify the Sponsor.  
10 Clinical Data Handling 
The Sponsor will be responsible for the data handling. The Sponsor and/or its affiliates will be responsible 
for compiling and submitting all required reports to governmental agencies. Data will be analyzed by the 
Sponsor and may be transferred to the Sponsor’s locations worldwide and/or any other worldwide 
regulatory authority in support of a market-approval application. 
 
During this study the following documents will be produced: 
• 
Patient’s ICF 
• 
Enrollment case report form 
• 
Inclusion/Exclusion case report form 
• 
VAS case report form 
• 
EQ-5D case report form 
• 
ODI case report form 
• 
HADS case report form 
• 
PCS case report form 
• 
PGIC case report form 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 33 of 41 
 
• 
Medication usage form 
• 
Programming form 
• 
Adverse events form 
 Protection of Personally Identifiable Information 
Abbott respects and protects personally identifiable information collected or maintained for this clinical 
investigation. The privacy of each subject and confidentiality of his/her information will be preserved in 
reports and when publishing any data. Confidentiality of data will be observed by all parties involved at all 
times throughout the clinical investigation. All data will be secured against unauthorized access. 
 Data Management Plan 
A Data Management Plan (DMP) will describe procedures used for data review, database cleaning, and 
issuing and resolving data queries. If appropriate, the DMP may be updated throughout the clinical 
investigation duration. All revisions will be tracked and document controlled. 
 
Subject data will be captured in a validated electronic data capture (EDC) system hosted by the Sponsor. 
CRF received data for the clinical investigation will be entered by trained Abbott personnel. An electronic 
audit trail will be used to track any subsequent changes of the entered data. 
 Document and Data Control 
10.3.1 Traceability of Documents and Data 
The investigator will ensure accuracy, completeness legibility and timeliness of the data reported to the 
Sponsor on the CRFs and in all required reports. 
10.3.2 Recording Data 
The CRFs will be signed and dated by the authorized site personnel. Any change or correction to data 
reported on a paper CRF will be dated, initialed and explained if necessary, and will not obscure the 
original entry. 
11 Monitoring 
It is the responsibility of the Sponsor to ensure the clinical investigation is conducted, recorded and 
reported according to the approved CIP, subsequent amendment(s), applicable regulations and guidance 
documents. 
 
Centralized monitoring will occur through routine internal data review. This monitoring is designed to 
identify missing and inconsistent data, data outliers, and potential CIP deviations that may be indicative of 
site non-compliance. On-site monitoring may occur at the discretion of the Sponsor. 
12 Compliance Statement 
 Statement of Compliance 
This clinical investigation will be conducted in compliance with the most current regional and local laws 
and regulations. Principles of Good Clinical Practice will be followed as based on the most current version 
of the World Medical Association (WMA) Declaration of Helsinki. 
 
The investigator will sign a Clinical Trial Agreement and agrees to be compliant with it. The investigator 
will not start enrolling subjects or requesting informed consent from any subject prior to obtaining IRB/EC 
approval and relevant Regulatory Authority approval, if applicable, and authorization from the Sponsor in 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 34 of 41 
 
writing for the clinical investigation. If additional requirements are imposed by the IRB/EC or relevant 
Regulatory Authority, those requirements will be followed. If any action is taken by an IRB/EC or a 
relevant Regulatory Authority with respect to the clinical investigation, that information will be forwarded to 
the Sponsor. 
 
As the Sponsor, Abbott has taken up general liability insurance in accordance with the requirements of 
the applicable local laws. An appropriate Abbott country representative will be utilized to understand the 
requirements for the type of insurance that will be provided for subjects, and such information will be 
incorporated into the site informed consent, as applicable. If required, additional subject coverage or a 
clinical investigation specific insurance will be provided by the Sponsor. 
 Quality Assurance Audits and Regulatory Inspections 
The investigator and/or delegate should contact the Sponsor immediately upon notification of a regulatory 
authority inspection at the site. A monitor or designee will assist the investigator and/or delegate in 
preparing for the audit. The Sponsor may perform quality assurance audits, as required. 
 
The Principal Investigator or institution will provide direct access to source data during and after the 
clinical investigation for monitoring, audits, IRB/EC review and regulatory authority inspections, as 
required. The Principal Investigator or institution will obtain permission for direct access to source 
documents from the subject, hospital administration and national regulatory authorities before starting the 
clinical investigation. 
 Repeated and Serious Non-Compliance 
In the event of repeated non-compliance or a one-time serious non-compliance, as determined by the 
Sponsor, a monitor or designee will attempt to secure compliance by one or more of the following actions: 
• 
Visiting the investigator, 
• 
Contacting the investigator by telephone, 
• 
Contacting the investigator in writing, 
• 
Retraining of the investigator. 
 
If an investigator is found to be repeatedly non-compliant with the signed agreement, the CIP or any other 
conditions of the clinical investigation, the Sponsor will either secure compliance or, at its sole discretion, 
terminate the investigator’s participation in the clinical investigation. In case of termination, the Sponsor 
will inform the responsible regulatory authority, as required, and ensure that the IRB/EC is notified, either 
by the Principal Investigator or by the Sponsor. 
13 Suspension or Premature Termination of the Clinical Investigation 
The Sponsor reserves the right to terminate the clinical investigation at any stage, with appropriate written 
notice to the investigators, IRB/ECs and relevant Regulatory authorities, if required.  
 
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in a clinical investigation at the investigational sites for which they are responsible. The 
investigators will follow the requirements specified in the Clinical Trial Agreement.  
 
If suspicion of an unacceptable risk to subjects arises during the clinical investigation or when so 
instructed by the IRB/EC or regulatory authority, the Sponsor may suspend the clinical investigation while 
the risk is assessed. The Sponsor will terminate the clinical investigation if an unacceptable risk is 
confirmed. If the Sponsor completes an analysis of the reasons for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, the Sponsor will inform the 
Principal Investigators, IRB/EC, or regulatory authority, where appropriate, of the rationale, providing 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 35 of 41 
 
them with the relevant data supporting this decision. Approval from the IRB/EC or regulatory authority, 
where appropriate, will be obtained before the clinical investigation resumes. If subjects have been 
informed of the suspension, the Principal Investigator or authorized designee will inform them of the 
reasons for resumption. 
 
If the Sponsor suspends or prematurely terminates the clinical investigation at an individual 
investigational site in the interest of safety, the Sponsor will inform all other Principal Investigators. 
 
If suspension or premature termination occurs, the Sponsor will remain responsible for providing 
resources to fulfill the obligations from the CIP and existing agreements for following up the subjects 
enrolled in the clinical investigation, and the Principal Investigator or authorized designee will promptly 
inform the enrolled subjects at his/her investigational site, if appropriate. 
14 Clinical Investigation Conclusion 
The clinical investigation will be concluded when: 
• 
All sites are closed AND 
• 
The final report has been provided to investigators or the Sponsor has provided formal 
documentation of clinical investigation closure. 
15 Publication Policy 
Publications or presentations of clinical investigation methods or results will adhere to Abbott’s publication 
policy, which is based on Good Publication Practices and International Committee of Medical Journal 
Editors (ICMJE) guidelines. A copy of the policy will be provided upon request of the investigator. 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 36 of 41 
 
Appendix A: CIP Revisions 
 
Procedure for CIP Amendments 
 
This CIP may be amended as appropriate by the Sponsor. Rationale will be included with each amended 
version in the revision history table below. The version number and date of amendments will be 
documented. 
 
The acknowledgement of the amended CIP by the Coordinating Investigator (if applicable) and the 
Principal Investigators will be collected on the signature pages. 
 
IRB/EC and relevant Regulatory Authorities, if applicable, will be notified of amendments to the CIP. 
 
Revision History 
Amendment 
Number 
Version 
Date 
Rationale 
Details 
Not 
Applicable 
VA 
ddMMMyyyy 
First release of CIP 
NA 
 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 37 of 41 
 
Appendix B: Definitions 
 
Non-study Specific Definitions 
 
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 under clinical investigation. 
 
This definition includes events related to the investigational medical device or the comparator. 
This definition includes events related to the procedures involved. 
 
Serious Adverse Event (SAE) 
An adverse event that led to: 
• 
Death 
• 
A serious deterioration in the health of the subject, that either resulted in: 
o 
A life-threatening illness or injury OR 
o 
A permanent impairment to a body structure or a body function OR 
o 
An in-patient or prolonged hospitalization OR 
o 
A medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function OR 
• 
Fetal distress, fetal death or a congenital abnormality or birth defect 
 
A planned hospitalization for a pre-existing condition, or a procedure required by the CIP is not 
considered a serious adverse event. 
 
Adverse Device Effect (ADE) 
An adverse event related to the use of an investigational medical device. 
 
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. 
 
This definition includes any event resulting from the use error or from intentional misuse of the 
investigational medical device. 
 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious adverse 
event. 
 
Unanticipated Adverse Device Effect (UADE) 
As defined in 21 CFR §812.3, unanticipated adverse device effects (UADE) are defined as any serious 
adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, 
a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the CIP or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects.   
 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 38 of 41 
 
Anticipated Serious Adverse Device Effect (ASADE) 
A serious adverse device effect which by its nature, incidence, severity or outcome has been previously 
identified in the risk analysis report. 
 
Unanticipated Serious Adverse Device Effect (USADE) 
A serious adverse device effect which by its nature, incidence, severity or outcome has not been 
identified in the current version of the risk analysis report. 
 
Device Deficiency (DD) 
A Device Deficiency is defined as an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance. Device deficiencies include malfunctions, use errors and 
inadequate labeling. 
 
Vulnerable Subject 
Vulnerable subject is defined as individual whose willingness to volunteer in a clinical investigation could 
be unduly influenced by the expectation, whether justified or not, of benefits associated with participation 
or of retaliatory response from senior members of a hierarchy in case of refusal to participate. 
EXAMPLE Individuals with lack of or loss of autonomy due to immaturity or through mental disability, 
persons in nursing homes, children, impoverished persons, subjects in emergency situations, ethnic 
minority groups, homeless persons, nomads, refugees, and those incapable of giving informed consent. 
Other vulnerable subjects include, for example, members of a group with a hierarchical structure such as 
university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members 
of the armed forces, and persons kept in detention. 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 39 of 41 
 
Appendix C: Bibliography 
 
Courtney P, Espinet A, Mitchell B, Russo M, Muir A, Verrills P, Davis K. (2015) Improved Pain Relief With 
Burst Spinal Cord Stimulation for Two Weeks in Patients Using Tonic Stimulation: Results From a Small 
Clinical Study. Neuromodulation. Jul;18(5):361-6.  
Crosby ND, Goodman Keiser MD, Smith JR, Zeeman ME, Winkelstein BA. Stimulation parameters define 
the effectiveness of burst spinal cord stimulation in a rat model of neuropathic pain. Neuromodulation. 
2015 Jan;18(1):1-8  
DeRidder D., Vanneste S., Plazier M., van der Loo E., & Menovsky T. (2010). Burst Spinal Cord 
Stimulation: Toward Paresthesia-Free Pain Suppression. Neurosurgery, 66(5): 986-990.  
DeRidder D, Plazier M, Kamerling N, Menovsky T, Vanneste S. (2013). Burst Spinal Cord Stimulation for 
Limb and Back Pain. World Neurosurg. 2013 Jan 12. pii: S1878-8750.  
de Vos CC, Bom MJ, Vanneste S, Lenders MW, de Ridder D.(2014). Burst spinal cord stimulation 
evaluated in patients with failed back surgery syndrome and painful diabetic neuropathy. 
Neuromodulation.17(2):152-9.  
Taylor RS. (2006). 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. Apr;31(4 Suppl):S13-9. Review  
Vesper J, Slotty P, Poeggel-Kraemer K, Littges H, Agnesi F, Venkatesan L. Therapeutic Efficacy of 
BurstDRTM Microdosing in Treatment of Chronic Pain. Presented at the North American Neuromodulation 
Society Conference 2017. Las Vegas, NV, USA.  
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 40 of 41 
 
Appendix D: Case Report Form 
Case report forms will be kept under a separate cover and are available upon request. 
 
 

 
Study Document No: < SJM-CIP-XXXXX> Ver. [A] 
Study Name: BOLD 
 
Clinical Investigation Plan 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express 
written consent of Abbott. 
 
Page 41 of 41 
 
Appendix F: Informed Consent Form 
Study specific informed consent will be kept under a separate cover and is available upon request.