Safety and Feasibility of a Vertebral Body Tethering Technique for Pediatric Idiopathic Scoliosis
Phase: NA
Conditions: Idiopathic Scoliosis
Sponsor: Patrick Cahill, MD

 
 
 
 
 Title:  
Safety and Feasibility of a Vertebral Body 
Tethering Technique for Pediatric 
Idiopathic Scoliosis  
NCT#: 
NCT03194568 
Short Title:  
Vertebral Body Tethering Outcomes  
Drug or Device Name(s):  
Anterior Vertebral Tether Device  
From the Creo® Stabilization System, 
Transition™ Stabilization System, and SILC™ 
Fixation System of Globus Medical, Inc.  
FDA IDE:  
G170023  
Regulatory Sponsor:  
Patrick J. Cahill, MD  
eIRB Number:  
17-013694  
Protocol Date:  
02/27/2020  
  
Amendment 1 Date: 07/18/2017  
Amendment 2 Date: 07/28/2017  
Amendment 3 Date: 11/05/2017  
Amendment 4 Date: 06/29/2018 
Amendment 5 Date: 06/07/2019  
Amendment 6 Date: 07/12/2019  
Amendment 7 Date: 09/23/2019  
Amendment 8 Date: 02/27/2020  
 
 

 
 
 
 
 
 
 
 
ii
 
Title: 
Safety and Feasibility of a Vertebral Body Tethering 
Technique for Pediatric Idiopathic Scoliosis 
Short Title: 
Vertebral Body Tethering Outcomes 
Drug or Device Name(s): 
Anterior Vertebral Tether Device 
From the Creo® Stabilization System, Transition™ Stabilization 
System, and SILC™ Fixation System of Globus Medical, Inc. 
FDA IDE: 
G170023 
Regulatory Sponsor: 
Patrick J. Cahill, MD 
 
eIRB Number: 
17-013694 
Protocol Date: 
06/29/2018 
Amendment 1 Date: 07/18/2017 
Amendment 2 Date: 07/28/2017 
Amendment 3 Date: 11/05/2017 
Amendment 4 Date: 06/29/2018 
 
Amendment 5 Date: 06/07/2019 
Amendment 6 Date: 07/12/2019 
Amendment 7 Date: 09/23/2019 
Amendment 8 Date: 02/27/2020 
Sponsor and Study Principal Investigator: 
Patrick J. Cahill, MD 
The Children’s Hospital of Philadelphia 
3401 Civic Center Blvd 
Philadelphia, PA 19104 
Phone: (215) 590-1527 
Email: cahillp1@email.chop.edu 
 
Study Sub-Investigator: 
John M. Flynn, MD 
The Children’s Hospital of Philadelphia 
3401 Civic Center Blvd 
Philadelphia, PA 19104 

 
 
 
 
 
 
 
 
iii
Phone: (215) 590-5751 
Email: flynnj@email.chop.edu 
 
 

  
 
 
 
 
 
 
 
iv 
TABLE OF CONTENTS 
Table of Contents .................................................................................................................. iv 
Abstract ................................................................................................................................. ix 
Protocol Synopsis .................................................................................................................. xi 
1 
BACKGROUND INFORMATION AND RATIONALE ....................................................................... 1 
1.1 
INTRODUCTION ..................................................................................................................................... 1 
1.1.1 
The Principle of Growth Modulation .............................................................................................. 1 
1.1.2 
Current standard of care ................................................................................................................. 2 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL PRODUCT OR INTERVENTION..................................... 4 
1.2.1 
Vertebral Body Tethering ................................................................................................................ 4 
1.2.2 
Implant ............................................................................................................................................. 4 
1.2.3 
Surgical Technique .......................................................................................................................... 4 
1.3 
FINDINGS FROM NON-CLINICAL AND CLINICAL STUDIES ..................................................................... 6 
1.3.1 
Clinical studies ................................................................................................................................ 6 
1.3.2 
Non clinical studies ......................................................................................................................... 9 
1.4 
RELEVANT LITERATURE AND DATA ..................................................................................................... 9 
1.4.1 
Curves Below 50 Degrees With A High Liklihood of Progression to 50 Degrees .......................... 9 
1.5 
COMPLIANCE STATEMENT .................................................................................................................. 11 
2 
STUDY OBJECTIVES ............................................................................................................................ 11 
2.1 
PRIMARY OBJECTIVE (OR AIM)........................................................................................................... 11 
2.2 
SECONDARY OBJECTIVES (OR AIM) .................................................................................................... 11 
3 
INVESTIGATIONAL PLAN .................................................................................................................. 11 
3.1 
GENERAL SCHEMA OF STUDY DESIGN................................................................................................ 11 
3.1.1 
Screening Phase ............................................................................................................................ 11 
3.1.2 
Study Intervention (Surgery) ......................................................................................................... 11 
3.1.3 
Post-operative Follow-up .............................................................................................................. 12 
3.2 
ALLOCATION TO TREATMENT GROUPS AND BLINDING ...................................................................... 12 
3.3 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES ................................................................. 12 
3.3.1 
Duration of Study Participation .................................................................................................... 12 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected ................................................ 12 
3.4 
STUDY POPULATION ........................................................................................................................... 13 
3.4.1 
Inclusion Criteria .......................................................................................................................... 13 
3.4.2 
Exclusion Criteria ......................................................................................................................... 13 
4 
STUDY PROCEDURES .......................................................................................................................... 14 
4.1 
SCREENING PHASE .............................................................................................................................. 14 
4.1.1 
Visit 1 (Screening & Pre-operative Visit) ..................................................................................... 14 
4.2 
STUDY TREATMENT PHASE (SURGERY).............................................................................................. 14 
4.2.1 
Visit 2 (Surgical Intervention) ....................................................................................................... 14 
4.3 
POST-SURGICAL FOLLOW-UP PHASE................................................................................................... 15 
4.3.1 
Visit 3 (POD 21) ............................................................................................................................ 15 
4.3.2 
Visit 4 (POD 45) ............................................................................................................................ 15 
4.3.3 
Visit 5 (POD 90) ............................................................................................................................ 15 
4.4 
EXTENDED FOLLOW-UP PHASE ........................................................................................................... 16 
4.4.1 
Visit 6 (POD 180) .......................................................................................................................... 16 
4.4.2 
Visit 7 (POD 365) .......................................................................................................................... 16 
4.4.3 
Visit 8 (POD 730) .......................................................................................................................... 17 
4.5 
LONG-TERM FOLLOW-UP PHASE ........................................................................................................ 17 
4.6 
UNSCHEDULED VISITS ........................................................................................................................ 17 
4.7 
SUBJECT COMPLETION/WITHDRAWAL ............................................................................................... 17 
4.7.1 
Early Termination Study Visit ....................................................................................................... 18 

  
 
 
 
 
 
 
 
v
4.8 
LIVE CASE PRESENTATION ................................................................................................................. 18 
5 
STUDY EVALUATIONS AND MEASUREMENTS............................................................................ 19 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS ................................................ 19 
5.1.1 
Pre-operative Visit ......................................................................................................................... 19 
5.1.2 
Surgical Intervention and Post-operative Course ......................................................................... 20 
5.1.3 
POD 21 Follow up......................................................................................................................... 21 
5.1.4 
POD-45 and POD-90 Follow-up .................................................................................................. 21 
5.1.5 
POD-180, POD-365, POD-730 Follow-up ................................................................................... 22 
5.1.6 
Laboratory Evaluations ................................................................................................................. 22 
5.1.7 
Other Evaluations, Measures ........................................................................................................ 23 
5.2 
SAFETY EVALUATION ......................................................................................................................... 23 
5.3 
EFFICACY EVALUATION...................................................................................................................... 23 
5.4 
CHART REVIEW FOR WITHDRAWN SUBJECTS ..................................................................................... 24 
6 
STATISTICAL CONSIDERATIONS .................................................................................................... 25 
6.1 
PRIMARY ENDPOINT ........................................................................................................................... 25 
6.2 
SECONDARY ENDPOINTS .................................................................................................................... 25 
6.3 
STATISTICAL METHODS ...................................................................................................................... 25 
6.3.1 
Baseline Data ................................................................................................................................ 25 
6.3.2 
Safety Analysis ............................................................................................................................... 25 
6.3.3 
Efficacy Analysis ........................................................................................................................... 26 
6.3.4 
Live Case Demonstration Analysis ................................................................................................ 26 
6.4 
SAMPLE SIZE AND POWER .................................................................................................................. 26 
6.5 
INTERIM ANALYSIS ............................................................................................................................. 27 
6.6 
STOPPING RULES ................................................................................................................................ 27 
6.6.1 
Stopping rules for any SAE related to the study procedure (surgery)........................................... 27 
6.6.2 
Stopping rules for SAEs that are device-related ........................................................................... 27 
7 
STUDY DEVICE ...................................................................................................................................... 28 
7.1 
DESCRIPTION ...................................................................................................................................... 28 
7.2 
PACKAGING ........................................................................................................................................ 28 
7.3 
LABELING AND TRACKING.................................................................................................................. 28 
7.4 
INDICATIONS FOR USE ........................................................................................................................ 29 
7.4.1 
Intent of the Device: ...................................................................................................................... 29 
7.4.2 
Patient population: ........................................................................................................................ 29 
7.4.3 
Curve types: ................................................................................................................................... 29 
7.4.4 
Levels that will be treated: ............................................................................................................ 29 
7.4.5 
Growth and skeletal maturity assessment: .................................................................................... 29 
7.4.6 
Range of curve magnitudes that will be treated: ........................................................................... 29 
8 
SAFETY MANAGEMENT ..................................................................................................................... 30 
8.1 
CLINICAL ADVERSE EVENTS .............................................................................................................. 30 
8.2 
ADVERSE EVENT REPORTING ............................................................................................................. 30 
8.3 
DEFINITION OF AN ADVERSE EVENT ................................................................................................... 30 
8.4 
DEFINITION OF A SERIOUS ADVERSE EVENT (SAE) ........................................................................... 30 
8.4.1 
Relationship of AE/SAE to study intervention or device ............................................................... 31 
8.5 
RECORDING PLAN FOR AES/SAES ...................................................................................................... 31 
8.6 
IRB/IEC NOTIFICATION OF SAES AND OTHER UNANTICIPATED PROBLEMS ..................................... 32 
8.6.1 
Follow-up report ........................................................................................................................... 33 
8.7 
INVESTIGATOR REPORTING REQUIREMENTS TO IRB AND FDA ......................................................... 33 
8.8 
SPONSOR REPORTING REQUIREMENTS TO FDA AND IRB .................................................................. 34 
8.9 
MEDICAL EMERGENCIES..................................................................................................................... 35 
9 
STUDY ADMINISTRATION ................................................................................................................. 36 
9.1 
DATA COLLECTION AND MANAGEMENT ............................................................................................ 36 

  
 
 
 
 
 
 
 
vi 
9.2 
CONFIDENTIALITY .............................................................................................................................. 37 
9.3 
REGULATORY AND ETHICAL CONSIDERATIONS.................................................................................. 37 
9.3.1 
Data and Safety Monitoring Plan.................................................................................................. 37 
9.3.2 
Risk Assessment ............................................................................................................................. 38 
9.3.3 
Potential Benefits of Trial Participation ....................................................................................... 40 
9.3.4 
Risk-Benefit Assessment ................................................................................................................ 41 
9.4 
RECRUITMENT STRATEGY .................................................................................................................. 41 
9.5 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ............................................................ 41 
9.6 
PAYMENT TO SUBJECTS/FAMILIES ...................................................................................................... 41 
10 
PUBLICATION ........................................................................................................................................ 42 
11 
REFERENCES ......................................................................................................................................... 43 
12 
APPENDIX ................................................................................................................................................ 47 
12.1 
APPENDIX 1: CLAVIEN-DINDO COMPLICATIONS CLASSIFICATION SYSTEM (FROM DINDO, ET AL.) ..... 47 

 
 
 
 
 
 
 
 
 
 
vii
ABBREVIATIONS AND DEFINITIONS OF TERMS 
Adams’s 
Forward 
Bending Test 
Subject stands with their back to the examiner, and bends 
forward at the waist, with knees in extension. The 
examiner looks at the horizontal plane of the spine, and 
measures the angle created between a rib hump and the 
horizontal plane. This is measured with an inclinometer. 
Adding on 
Phenomenon where there is a worsening of the scoliotic 
curve after spinal fusion. This usually occurs at levels 
distal to the distal end of the spinal fusion. 
AE 
Adverse Event 
AIS 
Adolescent Idiopathic Scoliosis 
AT 
Anterior Tethering 
Bending/Bolst
er x-ray 
Coronal radiograph of the entire spine, with the patient 
positioned in lateral flexion. The lateral flexion is done 
towards the convex side of the curve, to ‘lessen’ the 
appearance of the curve’s magnitude. This is done either 
standing, with the patient bending under their own power; 
or in the lateral decubitus position, with a pillow or 
‘bolster’ placed at the apex of the convexity of the curve. 
Coronal spine 
x-ray 
Radiograph of the coronal plane of the entire spine, 
usually also extending distally to include the femoral 
head/neck. 
HRQOL 
Health-Related Quality of Life 
JIS 
Juvenile Idiopathic Scoliosis 
Lenke 
Classification 
Standardized classification system for idiopathic 
scoliosis. The system has three components: 1) main 
curve type (1-6), 2) lumbar spine modifier (A, B, C), and 
3) sagittal thoracic modifier (-, N, +). 
ORC 
Office of Research Compliance 
PET 
Polyethylene Terephthalate 
PFT 
Pulmonary Function Test 
PSF 
Posterior Spinal Fusion 
Risser Scale 
Indirect measure of skeletal maturity, based on the 
ossification of the iliac crest. Graded on a scale of 0-5; 1 
being ¼ ossified, and 4 being completely ossified. 0 
shows no ossification, and 5 is completely ossified with 
fusion of the iliac apophysis to the iliac crest. 
SAE 
Serious Adverse Event – any undesirable experience 
associated with use of the medical device that results in 

 
 
 
 
 
 
 
 
 
 
viii
death, is life-threatening, requires inpatient 
hospitalization, or prolongs existing hospitalization. 
Sagittal spine 
x-ray 
Radiograph of the entire spine taken in the sagittal plane. 
Sanders Bone 
Age 
Standardized method of measuring skeletal maturity that 
is predictive of scoliotic curve progression. This method 
involves analysis of the ossification centers of the hand, 
using an AP radiograph of the entire hand. 
SOC 
Standard of Care 
Thoracic/Lum
bar flexion test 
Subject stands with trunk erect while measuring tape is 
placed proximally on the spinous process of C7 and 
distally to S1. The subject then bends forward at the 
waist, with knees in extension. Following flexion of the 
vertebrae, using the same bony landmarks, the examiner 
calculates the difference in distance between the starting 
and ending positions. 
Thoracic/Lum
bar lateral 
flexion test 
Subject stands erect with the feet flat on the floor. Place 
one end of a measuring tape on the tip of the middle 
finger and the other on the floor on a point directly 
beneath the middle finger. The patient then laterally 
flexes their trunk. The difference following the lateral 
flexion motion is measured. 
TLSO 
Thoraco-lumbo-sacral Orthosis 
UDI 
Unique Device Identification 
VBT 
Vertebral Body Tethering 

  
 
 
 
 
 
 
 
ix 
ABSTRACT 
Context: 
Scoliosis is a condition in which the spine is deformed by a curvature in the coronal plane. It 
is generally associated with a twisting (axial plane) deformity as well. It can have a variety 
of underlying etiologies and the etiology is used to classify the types of scoliosis. Idiopathic 
scoliosis is sub-classified in two ways: by age of onset and by magnitude of deformity. 
Curves between 10 and 25 degrees are considered mild. Curves between 25 and 50 degrees 
are classified as moderate. Curves greater than 50 degrees are termed severe. The current 
standard of care for moderate scoliosis in patients with remaining growth is to utilize a 
thoracolumbosacral orthosis (TLSO brace) to prevent progression of deformity. The 
scientific evidence has supported the efficacy of this intervention in avoiding progression of 
the Cobb angle to 50 degrees or more. 
If treated with a TLSO brace, many idiopathic scoliosis patients would conceivably be 
subjected to years of brace wear and the cost and psychological factors inherent therein. 
Additional downsides of brace treatment include the potentially negative psychosocial 
impact of wearing an external sign of deformity during adolescence, a key period of 
emotional development. Prior research has identified negative psychosocial effects related to 
wearing a brace in children. 
Recent evidence has suggested that certain curve patterns will likely progress to 50 degrees 
or more, despite treatment with a TLSO brace. Sanders, et al. demonstrated a correlation of 
Cobb angle (greater than 35 degrees) and skeletal maturity (bone age 4 or less) to the risk of 
progression to 50 degrees or more, despite TLSO bracing. The evidence supports that the 
current practice of TLSO bracing is not an effective treatment to avoid progression to 50 
degrees in these patients. It is on this population (thoracic Cobb angle greater than 35 
degrees, bone age of 4 or less) that we intend to test the safety and efficacy of anterior 
vertebral body tethering to avoid curve progression to 50 degrees. 
Objectives: 
The objectives of this study are to assess the safety and feasibility of anterior vertebral body 
tethering surgery to treat idiopathic scoliosis. 
Study Design: 
This is a pilot study, non-randomized, open label study of the anterior insertion of an 
Anterior Vertebral Tether Device in pediatric scoliosis. The study will be conducted at a 
single site - The Children’s Hospital of Philadelphia. 
Setting/Participants: 
This is a single-site, Sponsor-Investigator led pilot study of vertebral body tethering for 
pediatric idiopathic scoliosis in children aged 8-16 years. 
 

  
 
 
 
 
 
 
 
x
Study Interventions and Measures:  
The study intervention is surgical orthopedic implantation of the Anterior Vertebral Tether 
Device, by way of thoracoscopic surgery under general anesthesia. The primary outcome 
measures include assessments of safety of the insertion procedure and of the device, as well 
as the secondary measure of feasibility by determining the ability to successfully implant the 
investigational device. Monitoring will be conducted by a Safety Officer, who has extensive 
training and experience in surgical procedures. 

  
 
 
 
 
 
 
 
xi 
PROTOCOL SYNOPSIS 
Study Title 
Safety and Feasibility of a Vertebral Body Tethering Technique 
for Pediatric Idiopathic Scoliosis 
Funder 
Departmental Funds 
Clinical Phase 
Pilot Study 
Study Rationale 
Anterior surgical approach and instrumentation is an accepted 
standard treatment for idiopathic scoliosis (IS). This study will 
assess whether the intervention (anterior vertebral tethering) is a 
safe and feasible method of anterior approach surgery for spinal 
deformity in pediatric scoliosis. 
Study Objectives 
Primary 
• 
To determine the safety of anterior vertebral tethering surgery in 
patients who have been recommended to have surgical 
intervention. 
Secondary 
• 
To determine the feasibility of anterior vertebral tethering surgery in 
patients who have been recommended to have surgical 
intervention. 
Test Articles 
Anterior Vertebral Tether Device 
Globus Medical, Inc. 
Transition™ Stabilization System 
SILC™ Fixation System 
CREO® Thoracolumbar Stabilization System 
Study Design 
 
This is a single center prospective, open-label pediatric clinical 
device trial with a single surgical intervention. 
Subject Population 
Key criteria for 
Inclusion and Exclusion: 
 
 
 
 
 
 
 
 
 
Inclusion Criteria 
1. Males or females age 8 to 16 years old at time of enrollment 
(inclusive) 
2. Diagnosis of idiopathic scoliosis 
3. Sanders bone age of less than or equal to 4 
4. Thoracic curve of greater than or equal to 35 degrees and 
less than or equal to 60 degrees 
5. Lumbar curve less than 35 degrees 
6. Patient has already been identified for and recommended to 
have surgical intervention 
7. Spina bifida occulta is permitted 

 
 
 
 
 
 
 
 
 
 
xii
 
 
Subject Population 
Key criteria for 
Inclusion and Exclusion: 
 
 
8. Spondylolysis or Spondylolisthesis is permitted, as long as it 
is non-operative, the patient has not had any previous 
surgery for this, and no surgery is planned in the future 
9. Completed standard-of-care procedures as outlined in 
Section 5 
Exclusion Criteria 
1. Pregnancy (current) 
2. Prior spinal or chest surgery 
3. MRI abnormalities (including syrinx greater than 4mm, 
Chiari malformation, or tethered cord) 
4. Neuromuscular, thoracogenic, cardiogenic scoliosis, or any 
other non-idiopathic scoliosis 
5. Associated syndrome, including Marfan Disease or 
Neurofibromatosis 
6. Sanders bone age greater than 4 
7. Thoracic curve less than 35 degrees or greater than 60 
degrees 
8. Lumbar curve greater than or equal to 35 degrees 
9. Unable or unwilling to firmly commit to returning for 
required follow-up visits 
10. Investigator judgement that the subject/family may not be a 
candidate for the intervention 
 
Number Of Subjects  
 
The study will be conducted at The Children’s Hospital of 
Philadelphia, Division of Orthopedics in up to 40 subjects. Subject 
inclusion will be based on interest of patients who present to the 
orthopedic clinic and satisfy the inclusion/exclusion criteria. 
Study Duration 
Each subject’s active participation will last post-operatively and 
until approximately two years after skeletal maturity. The entire 
study is expected to last at least 10 years. 
Study Phases: 
Screening 
 
 
Study Treatment 
 
 
 
 
1. Screening phase: Subjects will be screened by study staff 
during a clinical visit in the orthopedics department. Eligible 
subjects will be approached and if interested, enrolled during 
a routine clinical exam. 
2. Study treatment: The subject will undergo surgical 
intervention using an accepted standard-of-care anterior 
approach using components from Globus Medical Inc. 
products, the Creo® Stabilization System, Transition™ 
Stabilization System, and SILC™ Fixation System. The 
investigational device is identified as the Anterior Vertebral 
Tether Device, comprising the staples, screws and locking 

 
 
 
 
 
 
 
 
 
 
xiii
 
 
Post-op Follow-Up 
 
 
 
caps from Creo® and the PET cord from the Transition™ 
Stabilization System and SILC™ Fixation System. 
3. Post-operative follow-up: Subjects will be followed at 
regular time points at 21, 45, and 90 days post-op during the 
post-operative phase. Patients will also be seen at visits 180, 
365, and 730 days post-op during the extended follow-up 
phase. Long-term follow-up, beyond two years post-
operatively, will occur through chart review of subjects, 
through two years beyond attaining skeletal maturity, which 
will be conducted under a separate study. 
Efficacy Evaluations 
The exploratory therapeutic efficacy evaluation measurement is 
thoracic Cobb angle (to nearest degree) at the pre-operative visit to 
Cobb angle during follow-up, especially at two years post-op (POD 
730). 
Safety and Feasibility 
Evaluations 
We will use phase-specific endpoints to measure safety and 
feasibility: 
1) Study treatment phase: Any individual-level intraoperative 
events including neuromonitoring events (loss or change in 
neurological signaling or function), unanticipated events 
during surgery, and SAEs. 
2) Post-operative active phase: Incidence of infection (within 
90 days post-op), pneumothorax, bronchopulmonary plug, or 
any reportable SAE. 
3) Extended follow-up phase: Incidence of over-correction, 
implant failure (measured on serial x-ray), incidence of 
curve progression to more than 50 degrees at two year 
follow-up, or incidence of secondary surgery or re-operation 
to correct further spine deformity (not related to trauma or 
other issues not related to the initial surgery/disease). 
Additional follow-up, through two years beyond skeletal 
maturation, will be conducted by periodic chart review. 
4) Feasibility will be assessed by the capacity to successfully 
implant all components of the anterior vertebral tether device 
in subjects. 
Statistical And Analytic 
Plan 
The enrollment target of 40 subjects for this initial study of the 
device is based primarily on feasibility rather than statistical 
concerns. As such, analyses will be primarily descriptive for safety 
and feasibility. The Cobb angle, the exploratory therapeutic 
endpoint, will be evaluated as a continuous variable. 
Data And Safety 
Monitoring Plan 
The PI and Safety Officer will meet regularly to discuss any safety 
events. Safety Officer reports will be forwarded to the IRB during 
continuing review per CHOP Office of Research Compliance 
monitoring guidance. Safety reporting will be according to IRB 

 
 
 
 
 
 
 
 
 
 
xiv 
SOP 408 and governing FDA guidelines. The PI and study team 
will also comply with all CHOP Office of Research Compliance 
monitoring standards. The PI will meet with the study team 
regularly to discuss study progress and ensure data fidelity. 

 
xv  
 
 
 
 
 
 
 
TABLE OF STUDY PROCEDURES 
Study Phase 
Pre-op / 
Screening 
Surgery 
Post-Operative Phase 
Extended Follow-up Phase 
Visit Number 
1 
2 
N/A 
3 
4 
5 
6 
7 
8 
Study Days 
Pre-op 
 
0 
1-44 (or until 
discharge) 
21 (+/- 
21 days) 
45 (+/- 
21 days) 
90 (+/- 
21 days) 
180 (+/- 
90 days) 
365 (+/- 
90 days) 
730 (+/- 
90 days) 
Clinical Care (SOC) Evaluations: 
All 
procedures 
included 
here are 
standard-of 
care for a 
surgical 
orthopedic 
spine 
patient 
X-ray: Hand Bone Age 
* 
 
 
 
 
 
 
 
 
X-ray: AP/PA and Lateral 
Spine 
X 
 
 
* 
X 
X 
X 
X 
X 
X-ray: Bending bolster films 
X 
 
 
 
* 
* 
* 
* 
* 
MRI: MRI Spine (can be 
obtained at any time prior to 
pre-op) 
X 
 
 
 
 
 
 
 
 
Pulmonary Function Test 
* 
 
 
 
 
 
 
* 
* 
History and physical exam with 
height and weight 
X 
 
 
X 
X 
X 
X 
X 
X 
Anaesthesia Evaluation 
X 
 
 
 
 
 
 
 
 
Pregnancy Test (as applicable) 
X 
 
 
 
 
 
 
 
 
Bloodwork 
X 
X 
X 
 
 
 
 
 
 
Post-operative inpatient 
management by treating 
physician and inpatient staff 
 
X 
X 
 
 
 
 
 
 
X-ray: AP/PA and Lateral 
Spine (performed at discharge) 
 
 
X 
 
 
 
 
 
 
Research Evaluations: 
Medical Record Review 
X 
X 
 
X 
X 
X 
X 
X 
X 

 
xvi  
 
 
 
 
 
 
 
 
Review Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
 
 
Informed Consent/Assent 
X 
 
 
 
 
 
 
 
 
Study Specific Physical Exam 
X 
 
 
 
X 
X 
X 
X 
X 
SRS 30 Questionnaire (completed by subject) 
X 
 
 
 
 
 
X 
X 
X 
Clinical Photographs 
X 
 
 
 
 
 
X 
X 
X 
Anterior tethering surgery under general 
anaesthesia with spinal cord monitoring 
 
X 
 
 
 
 
 
 
 
Intraoperative fluoroscopy (< 1hr) 
 
X 
 
 
 
 
 
 
 
Complications Evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
KEY: 
X = Procedure is performed at that visit 
* = Optional standard-of-care procedure, performed at discretion of treating physician 
Italics = Procedures which are performed as standard-of-care 
Bold = Procedures with greater than minimal risk 
NOTE: Long-term follow-up through two years after skeletal maturity will take place under a separate observational research protocol 

1 
 
 
 
 
1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 
Introduction 
Scoliosis is a condition in which the spine is deformed by a curvature in the coronal plane. It 
is generally associated with a twisting (axial plane) deformity as well. It can have a variety 
of underlying etiologies, and the etiology is used to classify the types of scoliosis. Scoliosis 
related to conditions affecting the nervous system or muscle function are termed 
neuromuscular scoliosis. Neuromuscular scoliosis is often related to conditions such as 
cerebral palsy, muscular dystrophies, spina bifida, or paralysis [1]. Another type of scoliosis 
is congenital scoliosis; scoliosis related to malformation of the bony structures of the spine. 
Some syndromes are associated with a high incidence of scoliosis including Marfan 
syndrome and neurofibromatosis. These forms of scoliosis are termed syndromic scoliosis 
[2]. Idiopathic scoliosis is scoliosis not due to any of the above mentioned causes. It is a 
diagnosis of exclusion. 
Idiopathic scoliosis is sub-classified in two ways: by age of onset and by magnitude of 
deformity. Curves between 10 and 25 degrees are considered mild. Curves between 25 and 
50 degrees are classified as moderate. Curves greater than 50 degrees are termed severe. 
Idiopathic scoliosis occurs in 2-3% of the population with decreasing frequency at higher 
magnitudes of deformity. Idiopathic scoliosis diagnosed before age 3 is classified as 
infantile idiopathic scoliosis; between 3 and 10, juvenile idiopathic scoliosis; 10 to 18 
adolescent idiopathic scoliosis; greater than 18 is adult idiopathic scoliosis. The diagnosis is 
retained throughout life; a juvenile idiopathic scoliosis patient does not become an 
adolescent idiopathic scoliosis patient at age 10. 
Further classification of surgically treated adolescent idiopathic scoliosis has been derived 
by Lenke et al. [3], in an attempt to guide treatment. The classification system takes into 
account factors such as the location of the deformity (thoracic vs. lumbar vs. both), number 
of curves, the flexibility of the deformity, and the sagittal plane. This classification system 
has been widely adopted in medical literature on the condition. 
1.1.1 The Principle of Growth Modulation 
Although the etiology of idiopathic scoliosis is largely unknown, some genetic factors have 
been implicated [4]. Biomechanical imbalance leading to asymmetrical spinal growth has 
also been postulated as the mechanism for progression, though there is limited evidence to 
link idiopathic scoliosis progression to a biomechanical cause [5]. Many treatments have 
been proposed to manage the progression of idiopathic scoliosis. Among the various 
treatment methods used, bracing and surgical fusion remain the most common treatments to 
alter the natural history of the disease [6]. Although spinal fusion and instrumentation for 
scoliosis correction has high intermediate success rates with few complications, it is among 
the most invasive procedures. Loss of motion following fusion and potential for adjacent 
segment degeneration is a long-term concern. 
In the field of limb deformities, the concept of growth modulation by a staple in a growing 
child (introduced by Blount) is utilized as part of the accepted common practice and as the 
standard of care for management of limb deformity [7]. It is presumed that compressive 
implants such as staples inhibit growth according to the Hueter-Volkmann principle [8]. 

2 
 
 
 
 
More recently, similar concepts have been applied successfully for spine growth modulation. 
These devices provide compressive forces on the convex side of the curve utilizing the 
Hueter-Volkman principle; slowing the growth on the convex side of the curve and 
enhancing the growth on the concave side. This effect has been demonstrated in animal 
models [9]. Furthermore, they have shown to preserve motion at the instrumented levels. 
Radiographic and chemical analysis performed in the animals have shown that disc function 
is maintained after the application of such a device [9]. 
1.1.2 Current standard of care 
1.1.2.1 Moderate Scoliosis (Curves 25-50 Degrees) 
The care for moderate scoliosis in patients with remaining growth is in a state of clinical 
equipoise. Almost all practitioners utilize one of three strategies: immediate spinal fusion, 
observation with delayed fusion once a curve reaches fifty degrees, and bracing. Based on 
evaluation of the current body of literature and his clinical experience, he selects immediate 
fusion for those in whom bracing will be ineffectual in preventing progression to 50 degrees 
or more. The sponsor-investigator does utilize observation with delayed fusion in those 
patients in whom progression to 50 degrees is a high probability. Evidence from Charles et 
al. and Sanders et al. have provided evidence to predict which patients will have inevitable 
progression to 50 degrees and beyond by stratifying skeletal maturity and Cobb angle. The 
practice of fusion of curves less than 50 degrees is supported by a query of the Harms’ Study 
Group database on fusion for AIS. This consortium is the largest registry for AIS fusions 
and is made up of the most prominent thought leaders in the field. The registry demonstrates 
that the thoracic Cobb angle of patients who have under gone fusion averages 56 degrees 
(std. dev. 13 degrees). Furthermore, a delay in spinal fusion can lead to the need for a longer 
spinal fusion that may be inclusive of the lumbar curvature [10-11]. 
The sponsor investigator utilizes bracing in his practice in those patients in whom bracing 
has a probability of altering the natural history. Support of bracing as a general invention 
derives from recently published studies. In 2010, Katz and colleagues [12] examined the 
efficacy of bracing and published a study that utilized heat sensors within braces to quantify 
brace wear compliance. In that study, Katz and colleagues [12] determined the brace success 
rate to be 82% in patients who wore their brace for more than 12 hours per day. In 2013, 
Weinstein and colleagues [13] demonstrated an improvement over the natural history with 
brace treatment and a correlation between hours of brace wear and efficacy of bracing in 
adolescent idiopathic scoliosis (AIS). 
The prospective studies of bracing have led to analysis of various subpopulations treated 
with bracing and published literature suggests that bracing in ineffectual for those patients 
who are early in the skeletal maturation process. The most important difference in the results 
presented by Weinstein and colleagues [13] and Katz and colleagues [12] and the proposed 
study is the level of maturity (and therefore natural history) of the treatment population. The 
average age of initiation of bracing in both the Weinstein et al. and Katz et al. studies was 
12.7 years. In a subsequent study of AIS patients treated with bracing from the Katz et al. 
study, Karol and colleagues demonstrated a more than five-fold increased risk of bracing 
failure in Risser 0 patients compared to Risser 1 patients [14]. The study results of Karol et 
al. and others suggest that there may be a level of skeletal immaturity below which bracing 

3 
 
 
 
 
cannot alter the natural history of moderate idiopathic scoliosis [15]. The study reported that 
63% of patients with Risser 0 and open triradiate cartilage progressed to the point of 
requiring a fusion. The efficacy of bracing in this cohort was significantly less than those 
with closed triradiate cartilages (P<0.001). Furthermore, those patients with Risser 0, open 
triradiate cartilage, and a Cobb angle of 30 degrees or greater had a 74% incidence of 
progression to fusion. Jarvis and colleagues [16] reported that fusion was avoided in only 
49% of those patients with juvenile idiopathic scoliosis (JIS) treated with bracing, which 
raises the question of whether bracing has any impact on the natural history in JIS. Charles 
et al. further stratified JIS by Cobb angle [17]. The study showed that curves more than 30 
degrees prior to the puberty growth spurt progressed to a magnitude requiring surgery in 
100% of cases despite bracing. 
For these reasons, the practice of the Sponsor-Investigator is to perform a spinal fusion in 
those patients with a curve less than 50 degrees who would have a high likelihood of 
progression to a Cobb angle beyond 50 degrees and in whom bracing would likely fail. The 
decision making by the PI exactly mirrors the inclusion criteria: a) those patients who meet 
the parameters for inclusion would otherwise be offered a spinal fusion, and b) those who do 
not meet the inclusion criteria would be recommended bracing or observation. 
Additional negative aspects of brace management in inappropriate populations are coming to 
light. If treated with a brace, many idiopathic scoliosis patients would conceivably be 
subjected to years of brace wear and the cost and psychological factors inherent therein. 
Brace treatment includes the potentially negative psychosocial impact of wearing an external 
sign of deformity during adolescence, a key period of emotional development. Prior research 
has identified negative psychosocial effects related to wearing a brace in children [18]. Such 
ramifications were further explored in a recent study by Misterska and colleagues [19], who 
found that the patients experienced a moderate level of stress specifically related to brace 
wear despite only low stress levels related to perceived spinal deformity. From a patient 
reported outcome point of view, the treatment is worse than the disease. 
 
1.1.2.2 Severe Scoliosis (Curves 50 Degrees and Greater) 
Spinal fusion is the current standard of care for curves at or near 50 degrees in AIS and JIS. 
Posterior spinal fusion (PSF) involves a midline approach to the back, placement of spinal 
anchors (usually pedicle screws), and fusion with bone graft across the posterior laminae. 
The course of treatment is predictable and safe. Newton et al. reported on the treatment of 
the most common subtype of AIS – Lenke 1 curves – which comprise about half of all AIS 
cases. He reported that a posterior spinal fusion will require a four hour surgery with a five 
day hospital stay with a blood loss of approximately 800cc [20]. Anterior spinal fusion is 
often utilized as well and this may involve a thoracotomy (open procedure) or thoracoscopy. 
Thoracoscopic anterior spinal fusion also has consistent outcomes in terms of radiographic 
results and expected course of treatment [21]. 

4 
 
 
 
 
1.2 
Name and Description of Investigational Product or Intervention 
1.2.1 Vertebral Body Tethering  
Vertebral body tethering (VBT) will be performed via an anterior thoracoscopic approach 
(see “Surgical Technique” below). This approach is safe and effective at achieving access to 
the spine for the purposes of instrumentation, and has predictable perioperative course and 
little to no long-term impacts on health and function. This surgical approach is utilized as a 
common approach for the current standard of care anterior-type spinal fusion [21, 22]. 
Thoracoscopic anterior approaches do not seem to carry any increased risk over other 
approaches for spinal fusion, namely posterior spinal fusion and open anterior spinal fusion. 
The reason it is not uniformly utilized is that the fusion is less reliable in this approach with 
the pseudo-arthrosis rate in thoracoscopic surgery reported at 11% vs. 3% in posterior spinal 
fusion [20]. This concern is irrelevant in VBT as fusion is not the goal. 
1.2.2 Implant 
The implants utilized are comprised of components from Globus Medical, Inc., the Creo® 
Stabilization System, Transition™ Stabilization System, and SILC™ Fixation System 
systems. The Creo® system is designed and indicated to be used in anterior thoracoscopic 
spinal fusion for spinal deformity. We anticipate placing centering staples, screws and 
locking caps from the Creo® system in a manner identical to how they are approved for use. 
However, rather than performing a discectomy, placing bone graft, and placing a rigid rod, 
we will place a flexible Polyethylene Terephthalate (PET) cord (from the Globus Medical, 
Inc. Transition™ Stabilization System or SILC™ Fixation System). The cords are approved 
as part of posterior spinal stabilization systems. The implanted investigational device will be 
composed of the staples, screws and locking caps from the Creo® system and the PET cord 
from the Transition™ Stabilization System or SILC™ Fixation System, and will be referred 
to in this IDE application as the Anterior Vertebral Tether Device (AVTD). Zimmer Spine, 
Inc. has a posterior PET cord as part of their Dynesis® system but they do not have an 
anterior thoracoscopic implant system that it can be used with. Some surgeons have 
suggested modifying posterior screws from the Dynesis® system for anterior use for 
vertebral tethering but these screws do not have sizing for pediatric indications, as the 
Creo® system does. Furthermore, the Dynesis® system does not have a centering/stabilizing 
staple, which is a common component of anterior spinal instrumentation systems. In August 
2019, the FDA approved The Tether™ – Vertebral Body Tethering System, developed by 
Zimmer Biomet Spine. 
1.2.3 Surgical Technique 
The surgical technique has been described by Samdani, et al. [23, 24]: 
The patient is intubated with a double lumen endotracheal tube with fiber optic 
assistance. A Foley catheter is placed. The patient is positioned in a lateral decubitus 
position with the operative (convex curve) side facing up. The operative flank is 
prepped and draped from midline anteriorly to midline posteriorly. Fluoroscopic 
assistance is utilized to mark out the location of the various vertebra and three 5mm 
incisions are made to insert the ports in triangular fashion. The apex incision is made 

5 
 
 
 
 
at the anterior axillary line at the 5th intercostal space. The other two incisions are made 
at the midaxillary line at the 3rd intercostal space and the 8th intercostal space. Through 
the first port a camera is introduced, harmonic scalpel through the second, and 
endoscopic “peanut” is placed through the third incision. The pleura is dissected off 
the vertebral bodies laterally along the length of the curve, and anteriorly to the rib 
heads. Care is taken to identify and coagulate the segmental vessels. A 15mm port is 
then inserted over the most cephalad vertebral body ready to be tethered. Over the 
anterior aspect of the most cephalad vertebral body, a 3 prong staple (Creo® 
Stabilization System, Globus Medical, Inc.) is introduced while maintaining caution 
that the staple is not introduced in the foramen. Using fluoroscopy the position of the 
staple is confirmed, and then a 5.2mm tap is used to create a screw hole under 
fluoroscopic guidance. The tap is begun on the convex side of the curve towards the 
concave side, across the anterolateral portion of the vertebral body. Next, an 
appropriately sized screw (Creo® Stabilization System, Globus Medical, Inc.) is 
placed, with position of the screw confirmed by fluoroscopy. Utilizing the same skin 
incision, the 15mm port is moved to the next intercostal space. The vessel ligation, 
staple placement, tap, and screw placement are then repeated at the next vertebral 
body- moving cephalad to caudad. Generally, up to 3 intercostal spaces can be 
accessed through the same skin incision. Patients who are instrumented to L3 require 
a mini-open retroperitoneal approach. 
After all of the screws are placed, the caudal 15mm port is used to pass the PET cord 
(Transition™ Stabilization System or SILC™ Fixation System, Globus Medical, Inc.) 
through the tulips of all of the screws. The set screw (Creo® Stabilization System, 
Globus Medical, Inc.) is then placed on the most caudal screw tulip using a T-handle 
pusher. The set screw is locked in place using a locking cap (Creo® Stabilization 
System, Globus Medical, Inc.), thereby securing the PET cord on the most caudal 
screw. Correction is achieved by tensioning the PET cord and through translation of 
the spine. Once the correction achieved is satisfactory to the surgeon, the set screws 
are tightened on each screw tulip- moving caudad to cephalad. Fluoroscopic images 
should be obtained after each screw is tightened, to confirm curve correction. These 
fluoroscopic images also confirm that there is no pulling out, plowing, or other 
untoward changes in the screw placements in the vertebral bodies. 
Once all screws have been tightened, global AP and Lateral x-rays of the spine should 
be performed to confirm correction of the curvature. Once satisfactory correction is 
confirmed in this manner, the PET cord should be trimmed, to leave about 2cm at 
either end to accommodate any future adjustment if necessary. At this juncture, the 
implantation of the investigational device, the Anterior Vertebral Tether Device, 
composed of staples, screws and set screws from the Creo® Stabilization System, and 
the PET cord from the Transition™ Stabilization System or SILC™ Fixation System, 
is complete. An attempt should be made to re-approximate the pleura, though this is 
difficult with the implant. A chest tube should be placed in one of the 5mm port sites. 
The hemithorax is then irrigated, the lung is re-inflated under direct vision, and the 
incisions are closed in layers. 

6 
 
 
 
 
1.3 
Findings from Non-Clinical and Clinical Studies  
1.3.1 Clinical studies 
When anterior spinal fusion is selected it is more often performed in cases where only one 
curve, the thoracic or the lumbar curve, requires a fusion [25]. We are proposing similar 
indications and applications for vertebral body tethering – a single thoracic curve requiring 
treatment. Anterior spinal fusion provides good clinical and radiographic results. The 
approach for anterior spinal fusion for AIS is most often performed with thoracoscopic 
guidance. The thoracoscopic approach is less invasive than its alternative, an open 
thoracotomy. Newton et al. reported on five year results of thoracoscopic anterior fusion 
showing that Cobb angle correction averaged 56% [22, 26], and total lung capacity at 91% 
of expected. These results were not different than the two year outcomes in the same 
patients, suggesting that any slight negative impact of anterior thoracoscopy did not lead to a 
progressive decline in pulmonary function. Furthermore, although open anterior spinal 
fusion is associated with a significant decline in objective measurements in pulmonary 
function, thoracoscopic anterior surgery was not different in its impact on pulmonary 
function than posterior spinal fusion [27, 28]. Faro et al. demonstrated that pulmonary 
function declines three months after both open and thoracoscopic anterior scoliosis surgery 
but recovers by one year post-op in thoracoscopic surgery but not in open anterior surgery 
[29]. 
In a comparison of the three approaches for fusion of the thoracic spine for AIS (open 
anterior, thoracoscopic anterior, and posterior), Newton et al. in another study reported that 
Cobb angle correction (57%) was similar in all groups, blood loss and incidence of 
transfusion was greater but surgical time was less in the posterior group, and SRS-22 scores 
were equivalent [20]. Furthermore, they reported decreased pulmonary function in the open 
anterior groups but similar pulmonary function tests (PFTs) in posterior and thoracoscopic 
patients. Lonner et al. also addressed the impact of surgical approach on pulmonary function 
[25]. The authors reported a decrease in forced expiratory volume in 1 second (FEV1) and 
functional vital capacity (FVC) as a percent of expected by 4-5% but an increase in total 
lung capacity (TLC) of 3% (Tables 1 and 2). These changes are of minimal clinical 
significance. 
Table 1: Demographics (adapted from Lonner et al, 2015) 
Approach Type 
N 
Sex Distribution 
Mean Age at 
Surgery 
(Range)* 
Mean 
Numbers 
Levels Fused 
Lenke Curve 
Type 
Thoracotomy 
68 
61 female, 7 male 
14.3 (10-21) 
6.6 
1 
Thoracoscopic 
44 
39 female, 5 male 
13.9 (10-18) 
6.1 
1 
Thoracoabdominal 
19 
18 female, 1 male 
14.8 (13-18) 
4.1 
5 
*Not significantly different. 
 
 

7 
 
 
 
 
Table 2: Mean Percent-predicted Values Preoperatively to Follow-up (adapted from Lonner et al, 
2015) 
 
Percent predicted 
FEV1 
Percent predicted 
FVC 
Percent predicted 
TLC 
Thoracotomy 
Mean pre-operative 
83.3 
88.1 
85.6 
Mean follow-up 
72.3 
75.1 
77.6 
 (Pre-post) 
-11.0 
-13.0 
-8.0 
P 
<0.001 
 
<0.001  
≤ 0.001  
Thoracoscopic 
Mean pre-operative 
82.5 
87.2 
85.0 
Mean follow-up 
78.1 
82.5 
88.2 
 
-4.4 
-4.7 
3.2 
P 
<0.004 
NS 
NS 
Thoracoabdominal 
Mean pre-operative 
90.3 
93.7 
94.7 
Mean follow-up 
83.5 
87.7 
95.1 
 
-6.8 
-6.0 
0.4 
P 
NS 
NS 
NS 
FEV1 indicates forced expiratory volume in 1 second; FVC, forced vital capacity; NS, non-
significant; TLC, total lung capacity 
There is room for improvement over the outcomes of posterior spinal fusion. In particular, 
the durability of the procedure is coming into question. Posterior pedicle screw constructs 
came into popularity in the early 2000’s and new 10 year post-op data is demonstrating a 
concerning trend. The Harms Study Group, a multicenter consortium of scoliosis 
practitioners and researchers, has recently shown that almost 10% of AIS fusions require 
revision surgery by 10 years post-op and that this trend is progressive [30] (Figure 1). 
 

8 
 
 
 
 
Figure 1: Re-operation rates (“Survival Curve”) of posterior spinal fusion over time. 
(Personal Communication from Peter Newton) 
 
Other authors have also reported on high long term re-operation rates following AIS fusion 
surgery ranging from 4.6% to 19% [31-33]. One theory is that a fusion imparts increased 
stress on unfused segments below a fusion. Marks et al. have shown that patients will retain 
total lumbar motion after a posterior spinal fusion by increasing motion in the unfused areas 
[34]. The authors postulate that increased motion may lead to degeneration of discs and facet 
joints. These findings of supraphysiologic motion below a posterior spinal fusion may 
explain some of the decreasing durability of posterior spine fusion. Green et al. have studied 
the health of intervertebral discs below a spinal fusion at an average of 11.8 years following 
posterior spinal fusion [35]. The authors found that disc degeneration was occurring in 85% 
of patients when graded by the Firman scale, an objective validated measure of disc 
degeneration [35]. Vertebral tether surgery will allow for continued motion of the 
instrumented levels and thus avoid the long lever-arm effect of a long fusion that may be 
contributing to early degeneration. Additional reports have questioned the durability of 
posterior spinal fusion. Upasani et al. reported on increased pain in patients at five years 
post-spinal fusion compared to at two years [36]. Lastly, posterior spinal fusion in patients 
who have not had their pubertal growth spurt, the population in whom we are proposing 
vertebral tethering, are at increased risk of complications and re-operation. Sponseller et al. 
reported that patients with open triradiate cartilages undergoing spinal fusion surgery have 
an increased rate of “adding on” (development of deformity below a fusion) and the 
response of the un-instrumented lumbar curve is less predictable [37]. 
Ideally, longitudinal outcomes of current standards of care including anterior thoracoscopic 
and posterior pedicle screw instrumented fusion would be used as a standard against which 
new technology can be compared. However, such data is a half century away. Furthermore, 
the pace of change and improvement in spinal deformity instrumentation and surgery tells us 
that change is inevitable [38]. 

9 
 
 
 
 
1.3.2 Non clinical studies 
There have been several animal studies of vertebral tethering. Peter Newton and colleagues 
at The University of California at San Diego and Rady Children’s Hospital have performed 
spinal tethering studies in bovine and porcine models [39-41]. The first study the authors 
published was in an immature bovine model [40]. They utilized a stainless steel tether. They 
demonstrated those animals who had a sham surgery without placement of the tether did not 
develop a curvature while those with placement of two rods did develop a curve. This was 
offered as a proof of concept that tension of a tether could alter growth and change 
alignment. In the porcine model, the investigators demonstrated the ability of a spinal tether 
to induce deformity in immature animals proportionally to the duration it was left in place, 
offering further evidence of the effect of growth in contributing to the deformity rather than 
tension of the implant alone [42]. Further evidence of the effect of growth driving the 
change in alignment was offered in a subsequent study of the bovine model [39]. They 
demonstrated equivalent deformity magnitude after 12 months between groups in which the 
tether was tensioned and those in which it was placed without tension. 
1.4 
Relevant Literature and Data 
The natural history of scoliosis after maturity has been described in several populations 
treated non-operatively and followed longitudinally. One cohort is from Scandinavia and 
was reported by Danielsson and Nachemson [43]. The other is from Iowa and was reported  
by Weinstein and colleagues [44, 45]. Nachemson reported a cohort of 117 scoliosis patients 
with a variety of types of scoliosis including those classified as congenital scoliosis, 
neuromuscular scoliosis, post-infectious scoliosis, and idiopathic scoliosis [46]. Decreased 
life expectancy was reported in this group. A subsequent sub-analysis of only the idiopathic 
scoliosis patients in this group revealed that there was no increase in mortality compared to 
the general population. Weinstein et al. reported a group of idiopathic scoliosis patients 
treated with observation [45]. They showed that, despite an increase in back pain symptoms, 
there was no increase in mortality rates compared to the aged matched general population. 
Furthermore, they identified Cobb angle greater than 50 degrees as a predictor of continued 
progression in adulthood. Greater than 85% of these patients progressed at a rate of ~1.1 
degrees per year. Weinstein demonstrated a cobb angle greater than 50 degrees as a factor 
predictive of further progression in adolescents in a subsequent study [44]. This forms the 
basis for current indications of surgical fusion for curves greater than 50 degrees. 
Conversely, curves less than 30 degrees at the end of growth did not progress nor did they 
exhibit any pain or pulmonary dysfunction. The desire to keep curves below thirty degrees 
forms the recommendation for initiation of brace management in curves that are 25 - 30 
degrees. 
1.4.1 Curves Below 50 Degrees With A High Liklihood of Progression to 50 Degrees 
 Further studies have elucidated which curves in immature patients will progress to 50 
degrees before reaching skeletal maturity. Rather than taking a reactive approach to these 
curves, we propose early treatment of this population with vertebral tethering. Dimeglio et 
al. demonstrated that immature patients with idiopathic scoliosis with a Cobb angle of 30 
degrees or greater prior to their pubertal growth spurt will universally progress to 50 degrees 
by the end of growth [47]. Dimeglio suggests several measures for identifying the onset of 

10 
 
 
 
 
pubertal growth spurt including the changes of various bone growth centers remote from the 
spine. These include the appearance (radiographically) of the sesamoid bone in the thumb, 
the presence of two distinct ossification centers in the olecranon (elbow), and an open tri-
radiate cartilage (hip socket). Sanders et al. have also demonstrated a correlation of risk of 
progression to a Cobb angle of 50 degrees between markers of skeletal maturity and Cobb 
angle [48]. They developed an easily applied scoring system of 1-7 to a hand x-ray. The 
advantage of a hand x-ray is that it encompasses a large number of growth centers, does not 
require additional training of radiology personnel, and is remote from more radiosensitive 
organs. The maturity based progression assessment derived by Sanders assigns a risk of 
progression to a Cobb angle of 50 degrees or more. It is this risk of progression to 50 
degrees on which we base our treatment decision for vertebral body tethering. Table 3 
illustrates that there is significant risk for progression if a patient’s curve is above 35 
degrees, and is a Sanders stage of 4 or less. Therefore our inclusion criteria for this study are 
set to include patients with curves above 35 degrees and a Sanders stage of 4 or less. 
We have selected an upper limit of 60 degrees due to the theoretical concern of achieving 
higher amounts of correction during periods of limited growth. In retrospective series by 
Samdani et al., the average Cobb angle of treated curves was 44 degrees [23, 24]. 
Table 3: Projected risk of progression of scoliosis to above 50 degrees, based on curve 
magnitude and bone age. (From Sanders, et al. 2008) 
 

11 
 
 
 
 
1.5 
Compliance Statement 
This study will be conducted in full accordance with all applicable Children’s Hospital of 
Philadelphia Research Policies and Procedures and all applicable Federal and state laws and 
regulations including 45 CFR 46, 21 CFR Parts 50, 54, 56, 312, 314 and 812. All episodes 
of noncompliance will be documented. 
The investigators will perform the study in accordance with this protocol, will obtain 
consent and assent, and will report unanticipated problems involving risks to subjects or 
others in accordance with The Children’s Hospital of Philadelphia IRB Policies and 
Procedures and all federal requirements. Collection, recording, and reporting of data will be 
accurate and will ensure the privacy, health, and welfare of research subjects during and 
after the study. 
2 
STUDY OBJECTIVES 
The purpose of the study is to determine the safety and feasibility of Anterior Vertebral 
Body Tethering surgery on patients with idiopathic scoliosis. 
2.1 
Primary Objective (or Aim) 
The primary objective is to assess the safety of Anterior Vertebral Body Tethering surgery 
in patients recommended for surgery in the immediate post-operative period. 
2.2 
Secondary Objectives (or Aim) 
The secondary objective is to assess feasibility by determining the ability to successfully 
implant the investigational device in study subjects who have been recommended for 
surgical intervention. 
3 
INVESTIGATIONAL PLAN 
3.1 
General Schema of Study Design 
3.1.1 Screening Phase 
Subjects will be screened from patients presenting to the orthopedic clinic for routine 
clinical care who have been indicated for scoliosis surgery by the treating physician. Patients 
who satisfy the inclusion and exclusion criteria will be approached and presented 
information about the clinical study. Those subjects and families who are interested in 
pursuing the clinical study will be enrolled by providing informed consent/assent. This 
phase will last one day. 
3.1.2 Study Intervention (Surgery) 
Enrolled patients who have completed the pre-operative course for anterior spine surgery 
(pre-operative SOC and pre-operative study procedures) will undergo the study intervention 
comprising implantation of staples, anterior vertebral body screws, locking caps and PET 
cord (the Anterior Vertebral Tether Device) under general anesthesia. This phase will last 1 
day (day of surgery). This surgical intervention is estimated to last about 5.5 hours; 2.5 

12 
 
 
 
 
hours of anesthesia induction and preparation, 2.5 hours of surgery, and 30 minutes of 
emergence from anesthesia. 
3.1.3 Post-operative Follow-up 
The post-operative follow-up phase of the study will last approximately 90 days, beginning 
with the day after the surgical intervention. This period has three set time points for follow-
up, which will occur during standard-of-care clinical follow-up visits for spine patients 
receiving surgical intervention. The three time-points are a POD 21 wound check, POD-45 
clinical visit, and a POD-90 clinical visit. During these three clinical visits physical exams, 
radiographs, and AE/SAE data will be collected depending on the visit. POD 2-44 will be 
monitored for known complications and AE/SAEs only, as there will be no clinical 
outcomes data to collect during this time. This data will be abstracted from the medical 
records. In addition, the patient will be under SOC post-operative care for patients who have 
undergone anterior spinal surgery. Data from any SOC interventions will also be abstracted 
from the medical record. 
In unique circumstances, the Investigator may determine it is necessary for the Subject to be 
seen for a follow-up visit(s) at an outside institution due to geographic, travel, other 
restrictions. In such a case the Investigator will communicate with the physician evaluating 
the Subject at the outside institution and Subject to ensure all necessary data points and 
AE/SAE information are captured. If possible copies of the Subject’s medical record for this 
visit will be obtained by the study team. 
3.2 
Allocation to Treatment Groups and Blinding 
The study will not be blinded, as the patient must make an informed decision to undergo the 
intervention, and the surgeon must perform the intervention. Introduction of a sham or 
placebo group would be impractical and unethical in this context. The study will only enroll 
one cohort - the anterior tethering (intervention) cohort. 
3.3 
Study Duration, Enrollment and Number of Sites 
3.3.1 Duration of Study Participation 
The subject will be followed for at least eight visits over a two year (730 day) period: one 
day for recruitment/consent, one day for the study intervention (surgery), one day for each 
visit: POD21, POD45, POD90, POD180, POD365, and POD730. These visits follow the 
schedule for a patient’s standard-of-care follow-up for anterior spinal surgery. Any off-study 
visits within the study window will not be captured, unless they are related to an AE/SAE. 
There is a three-week grace period for post-operative study visits, and a 90 day grace period 
for extended follow-up visits, making the initial study participation period 730 + 90 days 
after the day of surgery. Long-term follow-up through at least two years following skeletal 
maturity will take place through a separate observational study.  
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
The study will be conducted at The Children’s Hospital of Philadelphia. 

13 
 
 
 
 
This study is a clinical investigation of the anterior vertebral tethering procedure in up to 40 
subjects using the investigational device elements as described within this protocol. Based 
on a broad review of patient visits over the past year, we may expect to enroll about 5-10 
patients per year. 
3.4 
Study Population 
3.4.1 Inclusion Criteria 
1) Males or females age 8 to 16 years old at time of enrollment (inclusive) 
2) Diagnosis of idiopathic scoliosis 
3) Sanders bone age of less than or equal to 4 
4) Thoracic curve of greater than or equal to 35 degrees and less than or equal to 60 degrees 
5) Lumbar curve less than 35 degrees 
6) Patient has already been identified for and recommended to have surgical intervention 
7) Spina bifida occulta is permitted 
8) Spondylolysis or Spondylolisthesis is permitted, as long as it is non-operative, the 
patient has not had any previous surgery for this, and no surgery is planned in the future 
9) Completed standard-of-care procedures, as outlined in the Table of Study Procedures 
10) Subject consent and (if applicable) assent 
3.4.2 Exclusion Criteria 
1) Pregnancy (current) 
2) Prior spinal or chest surgery 
3) MRI abnormalities (could include syrinx greater than 4mm, Chiari malformation, or 
tethered cord) 
4) Neuromuscular, thoracogenic, cardiogenic scoliosis, or any other non-idiopathic 
scoliosis 
5) Associated syndrome, including Marfan syndrome or neurofibromatosis 
6) Sanders bone age greater than 4 
7) Thoracic curve less than 35 degrees or greater than 60 degrees 
8) Lumbar curve greater than or equal to 35 degrees 
9) Unable or unwilling to firmly commit to returning for required follow-up visits 

14 
 
 
 
 
10) Investigator judgement that the subject/family may not be a candidate for the 
intervention 
Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations 
of these criteria must be reported in accordance with IRB Policies and Procedures. 
4 
STUDY PROCEDURES 
4.1 
Screening Phase 
4.1.1 Visit 1 (Screening & Pre-operative Visit) 
• Informed consent/assent 
• Medical record and x-ray review for eligibility screening (research) 
• History and physical exam with height and weight 
• Research specific physical exam (research) 
• Anesthesia evaluation 
• Pulmonary function test (completed at treating physician’s discretion) 
• Bloodwork (outlined in Section 5.1.6) 
• Pregnancy test, as applicable 
• X-ray: bending bolster, AP/PA, lateral spine, and hand bone age 
• SRS 30 Questionnaire (research) 
• Clinical photographs (research) 
• Medical record and x-ray information abstraction (research) 
4.2 
Study Treatment Phase (Surgery) 
4.2.1 Visit 2 (Surgical Intervention) 
This phase includes the surgical intervention - vertebral body tethering through anterior 
thoracoscopic approach under general anesthesia and fluoroscopic guidance. This process is 
described in Section 2. 
Data from the surgery will be abstracted by medical record review for adverse events or 
complications. Intra-operative data (including radiographs) will also be abstracted from the 
medical record/surgical logs. Results from the surgery and inpatient stay will be abstracted 
at the time of discharge, except for those events which fall under the reporting guidelines of 
AE/SAEs. All AE/SAEs will be reported according to reporting guidelines listed in Section 
8. 

15 
 
 
 
 
4.3 
Post-surgical Follow-up Phase 
This phase will include monitoring for post-operative complications/SAE, as well as three 
SOC clinical visits in this phase, where the subject will also undergo a research visit. This 
phase also includes all inpatient recovery in the post-operative period, which includes post-
operative bloodwork and radiographs. Information from SOC procedures will also be 
abstracted from the medical records and radiology databases. 
4.3.1 Visit 3 (POD 21) 
• X-ray: AP/PA and lateral spine (completed at treating physician’s discretion) 
• History and physical exam with height and weight 
• Medical record review and abstraction (research) 
• Complications review (research) 
4.3.2 Visit 4 (POD 45) 
• X-ray: AP/PA and lateral spine 
• X-ray: Bending bolster films (completed at treating physician’s discretion) 
• History and physical exam with height and weight 
• Research specific physical exam (research) 
• Medical record review and abstraction (research) 
• X-ray review and abstraction (research) 
• Complications review (research) 
4.3.3 Visit 5 (POD 90) 
• X-ray: AP/PA and lateral spine 
• X-ray: Bending bolster films (completed at treating physician’s discretion) 
• History and physical exam with height and weight 
• Research specific physical exam (research) 
• Medical record review and abstraction (research) 
• X-ray review and abstraction (research) 
• Complications review (research) 

16 
 
 
 
 
4.4 
 Extended Follow-up Phase 
This phase will include monitoring for post-operative complications/SAEs, as well as three 
SOC clinical visits in this two year phase, where the subject will also undergo a research 
visit. Information from SOC procedures will also be abstracted from the medical records and 
radiology databases.  
4.4.1 Visit 6 (POD 180) 
• X-ray: AP/PA and lateral spine 
• X-ray: Bending bolster films (completed at treating physician’s discretion) 
• History and physical exam with height and weight 
• Research specific physical exam (research) 
• Medical record review and abstraction (research) 
• X-ray review and abstraction (research) 
• Complications review (research) 
• Clinical photographs (research) 
• SRS 30 Questionnaire (research) 
4.4.2 Visit 7 (POD 365) 
• X-ray: AP/PA and lateral spine 
• X-ray: Bending bolster films (completed at treating physician’s discretion) 
• Pulmonary function test (completed at treating physician’s discretion) 
• History and physical exam with height and weight 
• Research specific physical exam (research) 
• Medical record review and abstraction (research) 
• X-ray review and abstraction (research) 
• Complications review (research) 
• Clinical photographs (research) 
• SRS 30 Questionnaire (research) 

17 
 
 
 
 
4.4.3 Visit 8 (POD 730) 
• X-ray: AP/PA and lateral spine 
• X-ray: Bending bolster films (completed at treating physician’s discretion) 
• Pulmonary function test (completed at treating physician’s discretion) 
• History and physical exam with height and weight 
• Research specific physical exam (research) 
• Medical record review and abstraction (research) 
• X-ray review and abstraction (research) 
• Complications review (research) 
• Clinical photographs (research) 
• SRS 30 Questionnaire (research) 
• Study completion CRF (research) 
4.5 
Long-Term Follow-up Phase 
We are planning a long-term follow-up phase (LTFU) through approximately two years 
after each subject reaches skeletal maturity. Following the extended follow-up phase 
(approximately two years post-operative), the LTFU will be an observational study 
involving chart review. This will be performed under a separate research study. Device-
related SAEs and relevant data to assess safety and feasibility endpoints up to two years 
after skeletal maturity will be reported in accordance with FDA requirements.  
4.6 
Unscheduled Visits 
Unscheduled clinic visits will be made through the department’s/hospital’s clinical 
schedulers. As part of clinical care, physical evaluations and tests may be conducted. At 
these visits, the only research procedures performed will be medical record/radiographic 
record abstraction and complications review. 
4.7 
Subject Completion/Withdrawal 
Subjects may withdraw from the study at any time without prejudice to their care. They may 
also be discontinued from the study at the discretion of the Investigator for lack of adherence 
to study treatment or visit schedules, AEs, or due to non-compliance. However, in order to 
collect important study-related data for this investigational device, as much as is feasible, the 
Investigator and study team will make efforts to follow-up subjects who do not strictly 
adhere to timely visit schedules. The Investigator and study team may do this via emails, 
phone calls, or letters. The Investigator may also withdraw subjects who violate the study 

18 
 
 
 
 
plan, or to protect the subject for reasons of safety or for administrative reasons. It will be 
documented whether or not each subject completes the clinical study. If the Investigator 
becomes aware of any serious, related adverse events after the subject completes or 
withdraws from the study, they will be recorded in the source documents and on the CRF. 
Subjects who are withdrawn from the study during the post-operative follow-up phases due 
to AEs/SAEs, such as tether failure or implant re-operation, will no longer be followed at 
study-specific visits. These subjects have the option to consent and allow for continued 
monitoring by medical and radiographic record review through the end of the two-year 
Extended Follow-up Phase. Subjects who are withdrawn from the study also have the option 
to enroll in a separate LTFU observational study.  
4.7.1 Early Termination Study Visit 
Subjects that withdraw from the study prior to study completion will have all data collected 
to date kept on file. Subjects who wish to be withdrawn from the study may do so, 
preferably by submitting a written request addressed to the site’s PI. A ‘Study Completion 
CRF’ will be filed for each subject. 
4.8 
Live Case Presentation 
A live case demonstration may be performed for one subject’s surgery. Selection of an 
eligible subject, consent process, conduct of the surgical procedure, and subsequent follow-
up visits and monitoring will be performed as defined in the protocol and similarly to 
subjects who are not participating in the live case demonstration. 
 

19 
 
 
 
 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 
Screening and Monitoring Evaluations and Measurements 
5.1.1 Pre-operative Visit 
5.1.1.1 Screening 
• Potential subject is identified by the treating surgeon (match inclusion/exclusion 
criteria, surgical candidate) 
• Complete informed consent/assent 
• Review inclusion/exclusion criteria, complete inclusion/exclusion checklist 
• Complete subject screening CRF 
5.1.1.2 Pre-operative Medical Record/Radiograph Review 
• Name 
• Age 
• Sex 
• Race 
• Ethnicity 
• Date of birth 
• MRN 
• Diagnosis 
• Clinical and surgical history (including history of pregnancy) 
• Radiographic information and reports (including pre-operative coronal/sagittal; spine 
MRI) 
• PFT data (if available) 
5.1.1.3 Pre-operative Anesthesia Evaluation and Bloodwork (abstracted from medical 
record) 
• Result of anesthesia evaluation: fitness for surgery, special notes 
• Bloodwork results/levels 
5.1.1.4 Pre-operative Physical Examination 
• Standing height 
• Weight 

20 
 
 
 
 
• BMI – (reported as %) as calculated by the medical record 
• Trunk flexibility measurements (standardized): Adam’s Forward bending 
test/inclinometer (degrees), thoracic and lumbar flexion (cm), thoracic and lumbar 
lateral flexion (cm) 
• Data abstracted from clinical care exam (medical records, radiology reports, 
pulmonology tests) 
• SRS 30 Questionnaire 
• Clinical photographs 
5.1.1.5 Pre-operative Radiographs (abstracted from medical record) 
• AP/PA and lateral spine films 
• Bone age hand radiograph (performed at physician discretion) 
• Bending bolster films 
5.1.2 Surgical Intervention and Post-operative Course 
5.1.2.1 Intra- and Post-operative Procedures 
• Anterior tethering surgery under general anesthesia with spinal cord monitoring 
• Intraoperative fluoroscopy (<1 hour) 
• AP/PA and lateral standing radiographs of the spine 
5.1.2.2 Intraoperative Data (abstracted from medical record) 
• Operative efficiency times (i.e. surgical start time, surgical end time) 
• Intra-operative estimated blood loss 
• Blood products utilized: cell saver (cc) given, other transfused blood products (cc) 
• Number of portals 
• Implant tracking Information:  
o Brand and model information of each implanted device 
o Part number, lot number, and UDI of staples, screws, locking caps, and PET 
cord 
o Type and size of screws used 
• The extent of annulectomy (complete or partial) and the presence of pleural closure 
• Whether a thoracoplasty was performed will be noted along with number of ribs and 
whether the pleura was cut or not (internal vs. external thoracoplasty – if used) 
• Posterior based discectomy 
• Antibiotic use 
• Type and dose of antifibrinolytic 
• Time-exposure of fluoroscopic x-ray during procedure 

21 
 
 
 
 
5.1.2.3 Post-surgical Data (abstracted from medical record) 
• Chest tube drainage on day #1 - #5, and total collected 
• Post-operative day of extubation as well as chest tube removal will be noted 
• Post-operative day the patient was converted entirely to oral pain medication 
• Visual Analogue Scores (measures the intensity of a child’s pain experience) at 
discharge will be recorded. This is used to record the amount of back pain a patient is 
experiencing. 
• Day of discharge will be recorded 
• The use of a post-operative brace and the number of months utilized will be recorded 
• Bloodwork levels and results from the hospital stay will be recorded 
• Complications will be recorded: Complications will be recorded and status will be 
updated until resolved. This data collection methodology will be standardized via the 
complication form in the patient’s study binder. 
• Post-operative drain: type and drainage amounts daily until d/c of drain 
• Data abstracted from medical records, radiology reports, and surgical logs 
• Post-operative bloodwork 
5.1.3 POD 21 Follow up 
• Medical and radiographic record review: data abstracted from clinical care exam 
(medical records, radiology reports, pulmonology tests) 
• Standing height 
• Weight 
• BMI 
5.1.4 POD-45 and POD-90 Follow-up 
5.1.4.1 Post-Operative Visit 
• Medical and radiographic record review: data abstracted from clinical care exam 
(medical records, radiology reports, pulmonology tests) 
• Standing height 
• Weight 
• BMI 
• Trunk flexibility measurements (standardized): Adam’s Forward bending test 
(degrees) only 

22 
 
 
 
 
5.1.5 POD-180, POD-365, POD-730 Follow-up 
5.1.5.1 Extended Follow-up Visit 
• Medical and radiographic record review: data abstracted from clinical care exam 
(medical records, radiology reports, pulmonology tests) 
• Standing height 
• Weight 
• BMI 
• Trunk flexibility measurements (standardized): Adam’s Forward bending test 
(degrees), thoracic and lumbar flexion (cm), thoracic and lumbar lateral flexion (cm) 
• SRS 30 Questionnaire 
• Clinical photographs 
5.1.6 Laboratory Evaluations 
5.1.6.1 Bloodwork 
Pre-operative bloodwork to be performed: 
• CBC (Complete Blood Count) with(out) Differential 
• CMP (Comprehensive Metabolic Panel) with(out) Albumin 
• PT/INR (Prothrombin Time) 
• PTT Profile (Partial Thromboplastin Profile) 
• Type & Screen 
These tests are performed pre- and post-operatively for all patients undergoing surgery, at 
clinical discretion. This is done as part of the anesthesia team’s routine evaluation of the 
subject, and for tracking safe recovery. Results of these blood tests will be monitored for any 
abnormal or incidental findings. Abnormal or incidental findings will be documented and 
communicated to the treating physician(s). The treating physician(s) will determine if these 
findings would alter the subject’s treatment course in any way. 
5.1.6.2 Pregnancy Testing: Performed at pre-operative visit only 
A blood or urine pregnancy test will be performed for female subjects 11 years of age and 
older, or any female who has begun menses will be required to complete a blood or urine 
sample pregnancy test. Results of such testing will be provided to the study participant, 
unless it is determined that she is unable to understand the significance or implications of a 
positive test result. In this case, the parent(s) will be informed of the positive result. In the 
event of pregnancy, the participant will not receive the study intervention. Participants who 
are found to be pregnant will be advised to contact family planning counseling services. 

23 
 
 
 
 
5.1.7 Other Evaluations, Measures 
Clinical Evaluations/Measurements: 
• Adam’s Forward Bending Test: Subject stands with their back to the examiner, and 
bends forward at the waist, with knees in extension. The examiner looks at the 
horizontal plane of the spine, and measures the angle created between a rib hump and 
the horizontal plane. This is measured with an inclinometer. 
• Thoracic/Lumbar Flexion Test: Subject stands with trunk erect while measuring tape 
is placed proximally on the spinous process of C7 and distally to S1. The subject 
then bends forward at the waist, with knees in extension. Following flexion of the 
vertebrae, using the same bony landmarks, the examiner calculates the difference in 
distance between the starting and ending positions. 
• Thoracic/Lumbar Lateral Flexion Test: Subject stands erect with the feet flat on the 
floor. Place one end of a measuring tape on the tip of the middle finger and the other 
on the floor on a point directly beneath the middle finger. The patient then laterally 
flexes their trunk. The difference following the lateral flexion motion is measured. 
• Clinical Photographs: Photographs will be taken of the subject at specified time 
points. The photographs will not include facial features, and include the torso from 
the top of the shoulders to the iliac crests. The patient should stand in a natural 
standing position for AP, PA, lateral right, and lateral left photos. The subject will 
perform the Adam’s Forward Bending Test, and a photograph will be taken from the 
view of the examiner (PA). Photos will be taken without shirt or hospital gown. It is 
permissible for female subjects to wear a top covering that allows for a clear view of 
the spine and trunk (bra, sports bra, bathing suit top, or similar). 
Other Measurements: 
• Sanders Bone Age: Attached as Supplement 1 
• SRS 30: Attached as Supplement 2  
5.2 
Safety Evaluation 
Subject safety will be monitored by recording all AEs and SAEs, and will be recorded on the 
complication form in the patient’s study binder. The evaluation of safety is a primary 
objective of this research study. There will be a clear classification of “device-related” 
adverse events. Device-related adverse events are those events directly related to the 
integrity, safety, or biomechanics of the Anterior Vertebral Tether Device, as described in 
this IDE application, comprised of the staples, screws, locking caps, and PET cord. This can 
include variables like device breakage or device migration. Other adverse events which are 
considered not device-related are those that are related to the act of surgery and medical 
recovery. The type of events will be documented on the CRF. 
5.3 
Efficacy Evaluation 
This is a safety and feasibility clinical trial. A therapeutic exploratory endpoint for this VBT 
procedure will be measurement of the Cobb angle. The Cobb angle is a coronal plane 
radiographic measurement of curvature of the spine. This angle will be recorded for the pre-
operative coronal spine radiograph, as well as all subsequent serial radiographs. The change 

24 
 
 
 
 
in Cobb angle (reduction) will be the primary exploratory therapeutic evaluator of efficacy. 
‘Success’ of the intervention will be defined by a final Cobb angle of less than or maintained 
at less than 50 degrees, for curves which were less than 50 degrees pre-operatively. For 
curves which were greater than 50 degrees pre-operatively, a Cobb angle which is less than 
or maintained at less than 50 degrees is considered a ‘success’. 
5.4 
Chart Review for Withdrawn Subjects 
Subjects who are withdrawn from the study during the follow-up phase due to AEs/SAEs 
will no longer follow the study visit schedule nor participate in study-specific procedures. 
These subjects have the option to consent and allow for continued monitoring by medical 
and radiographic record review through the end of the two-year Extended Follow-up Phase. 
Subjects who are withdrawn from the study also have the option to enroll in a separate 
LTFU observational study.  

25 
 
 
 
 
6 
STATISTICAL CONSIDERATIONS 
6.1 
Primary Endpoint 
The primary endpoint is safety, and will consist of the rate of AEs/SAEs in anterior VBT 
surgery. 
6.2 
Secondary Endpoints 
The secondary endpoint is feasibility, as determined by the ability to successfully implant 
the investigational device in study subjects. 
6.3 
Statistical Methods 
6.3.1 Baseline Data 
Baseline and demographic characteristics will be summarized by standard descriptive 
summaries (e.g. means and standard deviations for continuous variables such as age and 
percentages for categorical variables such as sex). Categorical data analysis methods such as 
chi-square will be used for dichotomous variables and t-test for continuous data (such as 
differences in Cobb angle). Logistic regression analysis will be conducted to analyze various 
factors associated with adverse events in the anterior tethering surgical procedure. 
6.3.2 Safety Analysis 
The safety endpoint will be factors associated with the adverse events in patients that have 
undergone anterior VBT surgery. Variable reporting for adverse event will be dichotomous. 
Descriptive statistics will be used to report number and type of adverse events. Further, chi-
square or Fisher’s-exact test analysis will be used to identify variables that correlate with 
adverse events following anterior tethering surgery. Further, logistic regression will be 
conducted to clarify which variables are associated with adverse outcomes. Odds ratio along 
with confidence intervals will be reported. 
 
All subjects will begin the safety analysis at Study Day 0 (day of surgery). Intraoperative 
and post-intervention medical events or signs and symptoms of the complications arising 
after the start of study intervention will be captured using list of common events associated 
with anterior VBT surgery. Adverse signs, symptoms, and/or laboratory abnormalities 
already existing prior to the baseline visit will be captured in the medical history assessment. 
The date of onset, severity, and end date (if relevant) will be documented. 
Medical events resulting from any procedure performed in the study will be collected as 
adverse events (AEs). The event description, date of onset, end date, severity, and outcome 
will be documented for the study-related AEs. The frequencies of AEs by type, body system, 
severity and relationship to study intervention will be summarized. SAEs (if any) will be 
described in detail. A distinction will be made between those AEs/SAEs which are “device-
related”, those which are “not device-related”, and those which are “uncertain to be related”. 
“Device-related” complications will include any events directly related to the integrity, 
safety, or biomechanics of the Anterior Vertebral Tether Device composed of the 
investigational staples, screws, locking caps, and PET cord. Device-related AE incidence 
will be summarized along with the corresponding exact binomial 95% two-sided confidence 
intervals. 

26 
 
 
 
 
6.3.3 Efficacy Analysis 
This initial clinical study using the Anterior Vertebral Tether Device for pediatric idiopathic 
scoliosis is focused on safety and feasibility, not efficacy, as primary endpoints. There will 
be an exploratory therapeutic endpoint, Cobb angle change, based on an intention to treat 
approach and will include all subjects who have undergone the intervention. 
The exploratory therapeutic endpoint used for efficacy will be change in post-operative 
Cobb angle compared to pre-operative Cobb angle, measured on coronal radiograph of the 
spine. Considering change in Cobb angle is a continuous variable, a t-test will be used to 
detect any change in Cobb angle post-operatively. Linear regression will be utilized to 
assess which variables are associated with change in post-operative Cobb angle. 
6.3.4 Live Case Demonstration Analysis 
Data collected from the subject participating in the live case demonstration will be stratified 
from the rest of the subjects during analysis. A comparative analysis will be performed to 
determine whether there are significant differences in risks and outcomes between the live 
case subject and subjects who were not involved in a live case presentation. If such 
differences exist, the data from the live case presentation will be excluded from efficacy 
analyses and independently analyzed. Exclusion of the live case subject from analyses will 
not impact the power calculations described in Section 6.4. 
 
6.4 
Sample Size and Power 
The purpose of this study is to longitudinally follow a cohort of patients treated with a novel 
use of an implanted device, referred to as the Anterior Vertebral Tether Device, to explore 
safety and feasibility of the implant. Based on device implantation in up to 40 subjects, the 
study will not be sufficiently powered to gain statistical significance. However, this 
preliminary study will allow some insight into the safety of implantation, as measured by the 
acceptability of adverse events, as well as feasibility of implantation, as estimated by the 
proportion of successful implants of the Anterior Vertebral Tether Device. The regulatory 
status of such an implant requires that the Sponsor obtains an IDE. There is no active 
comparative group in this limited study. Notably, there is a useful comparator group from 
review of published data (historical controls) and from the data of the Harms Study Group 
(CHOP IRB# 06-005052), for which the Sponsor has access. A comparative analysis will be 
performed combining data from this clinical trial with IRB# 06-005052 to evaluate patient 
factors and clinical outcomes depending on the intervention received. Data from this clinical 
trial will not be shared with IRB# 06-005052. 
Using data observing pre and post thoracic and lumbar measurements for a small sample of 
subjects; for the thoracic measurements, a sample size of 40 will have >80% power to detect 
a difference in means of 17.9, assuming a standard deviation of differences of 6.6, using a 
paired t-test with a 5% two-sided significance level. For the lumbar measurements, a sample 
size of 40 will have >80% power to detect a difference in means of 6.5, assuming a standard 
deviation of differences of 5.38, using a paired t-test with a 5% two-sided significance level. 
Sample size calculations were performed using NQuery software. 

27 
 
 
 
 
6.5 
Interim Analysis 
The study team will perform interim analyses based on the stopping rules listed in section 
6.6 (below). If any of these rules are met, the study will halt enrollment until appropriate 
measures can be put in place to reduce patient risk. All reporting of AEs/SAEs during the 
study will adhere to the guidelines in Section 8 (Safety Management). 
6.6 
Stopping Rules 
The stopping rules for this study will be based on the prevalence of SAEs. There is special 
consideration given to SAEs that are found to be “device-related”, as outlined below. 
6.6.1 Stopping rules for any SAE related to the study procedure (surgery) 
• 
SAE in all of the first 5 patients or  
• 
SAE in 7 of first 10 patients or  
• 
SAE in greater than 50% of patients after 15 cases 
 
6.6.2 Stopping rules for SAEs that are device-related  
Definition of Terms: 
• 
Screw failure – screw, locking caps, and/or centering staple have loosened from the 
vertebra AND require re-operation. 
• 
Tether failure – the tether has broken or lost tension. Diagnosed at any time point after 3 
months by increased angulation at a disc space on standing PA radiograph or increase in 
disc wedging on side bending x-ray to the side away from the implant. Also, it is only an 
SAE if noted before maturity, overall Cobb angle worsens compared to the first erect 
measurement, AND requires re-operation. 
• 
Implant re-operation - any problem with the implant that requires re-operation including 
re-operation for overcorrection with any of the following: a removal of all or part of the 
implant, loosening of the tension on the implant, or spinal fusion. 
Stopping Rules 
• Screw/locking cap/staple failure stopping point: 3 of first 5 cases, 5 of first 10, or in 
greater than 50% of cases 15 and beyond. 
• Tether failure stopping point: 3 of first 5 cases, 5 of first 10, or greater than 50% of 
cases 15 and beyond. 
• Implant failure re-operation stopping point: occurs in 3 of first 5, 5 of first 10, or 
greater than 50% of cases 15 and beyond. 
 
 

28 
 
 
 
 
7 
STUDY DEVICE 
7.1 
Description 
The device under investigation is the “Anterior Vertebral Tether Device”, comprised of 
components from Globus Medical, Incorporated systems: The Creo® System and the 
Transition™ Stabilization System or SILC™ Fixation System.  From the Creo® System 
come the staples, screws, and locking caps of the investigational device. From the 
Transition™ Stabilization System or SILC™ Fixation System comes the Polyethylene 
Terephthalate (PET) cord. These four components are part of a 510K-cleared implant system 
distributed by Globus Medical, Inc. The Creo® and Transition™ Globus systems are 
classified as Class II under 21 CFR 888.3070, and SILC™ Fixation System Globus system is 
classified as Class II under 21 CFR 888.3010. The devices are manufactured and distributed 
according to manufacturer guidelines and in compliance with 21 CRF 820. 
The entire systems are supplied to CHOP as part of routine surgical treatment. The systems 
supplied also includes hydroxyapatite-coated titanium alloy Ti6Al4V (ASTM F136) or alloy 
Ti6Al4Nb (ASTM F1295) pedicle screws, polycarbonate urethane spacers and bumpers, 
titanium alloy spools, end spools, and set screw ends. The rest of the system will be 
discarded according to the appropriate CHOP OR policies and procedures. 
7.2 
Packaging 
The device is part of commercially marketed systems from Globus Medical, Inc. As such, 
the device is packaged according to manufacturer guidelines and in compliance with 21 CFR 
820.130. 
7.3 
Labeling and Tracking 
The device is part of a commercially marketed system from Globus Medical, Inc. As such 
the device will be labeled according to manufacturer guidelines and in compliance with 21 
CFR 801. 
Specific device label parameters of the staples, screws, locking caps, and PET cord will be 
tracked by the study team to comply with FDA standards for investigational device tracking. 
Those parameters include: 
• Manufacturer of device 
• Model name of device 
• Device Part Number 
• Device Lot Number 
The device will be received and processed in the usual standard process per hospital 
standard operating procedures. The medical record and device form, which will contain the 
parameters stated above, will be the source documents for tracking implanted devices. The 
process for device handling and tracking will be conducted in accordance with our study 
device tracking SOP. 

29 
 
 
 
 
7.4 
Indications for Use 
7.4.1 Intent of the Device:  
• The device is intended to normalize the vertebral column of those with pediatric 
idiopathic scoliosis, by applying tensional force. 
7.4.2 Patient population:  
• Males and females diagnosed with idiopathic scoliosis (all types - infantile, juvenile, 
adolescent). 
• Spina bifida occulta is permitted. 
• Spondylolysis or Spondylolisthesis is permitted, as long as it is non-operative, the 
patient has not had any previous surgery for this, and no surgery is planned in the 
future. 
7.4.3 Curve types: 
• We will use the Lenke classification system for curve type. The Lenke Classification 
system is a classification for AIS. For those subjects with AIS, the Lenke types 
eligible for inclusion are Lenke types 1, 2, and 3. For those subjects with JIS and IIS 
(idiopathic scoliosis diagnosed before age 10), subjects with curves patterns that 
match all other criteria to be classified as Lenke types 1, 2, and 3 will be included. 
7.4.4 Levels that will be treated: 
• Thoracic levels T4-L1 (i.e., most cephalad and caudad levels that may be treated). 
7.4.5 Growth and skeletal maturity assessment: 
• Chronological age 8-16 years (inclusive) 
• Sanders bone age less than or equal to 4. 
7.4.6 Range of curve magnitudes that will be treated:  
• Thoracic curve greater than or equal to 35 degrees and less than or equal to 60 
degrees 
• Lumbar curve less than 35 degrees 
 
 

30 
 
 
 
 
8 
SAFETY MANAGEMENT 
8.1 
Clinical Adverse Events 
Clinical adverse events (AEs) will be monitored throughout the study. 
8.2 
Adverse Event Reporting 
Unanticipated problems related to the research involving risks to subjects or others that 
occur during the course of this study (including SAEs) will be reported to the IRB in 
accordance with CHOP IRB SOP 408: Unanticipated Problems Involving Risks to Subjects. 
AEs that are not serious but that are notable and could involve risks to subjects will be 
summarized in narrative or other format and submitted to the IRB at the time of continuing 
review.  
8.3 
Definition of an Adverse Event 
An adverse event is any untoward medical occurrence in a subject who has received an 
intervention (drug, biologic, or other intervention). The occurrence does not necessarily 
have to have a causal relationship with the treatment. An AE can therefore be any 
unfavorable or unintended sign (including an abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of a medicinal product, whether or 
not considered related to the medicinal product.  
We will use the Clavien-Dindo Classification system [47], as well as the Comprehensive 
Complication Index (based off of the Clavien-Dindo system) [48] to classify and analyze 
patient adverse events. Grade I and Grade II events will be considered AEs. (See 
Appendix 1 for classification table) 
8.4 
Definition of a Serious Adverse Event (SAE) 
An SAE is any adverse event that results in any of the following outcomes: 
• death, 
• a life-threatening event (at risk of death at the time of the event), 
• requires inpatient hospitalization or prolongation of existing hospitalization, 
• a persistent or significant disability/incapacity, or 
• a congenital anomaly/birth defect in the offspring of a subject. 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered a serious adverse event when, based upon appropriate 
medical judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
A distinction should be drawn between serious and severe AEs. A severe AE is a major 
event of its type. A severe AE does not necessarily need to be considered serious. For 
example, nausea which persists for several hours may be considered severe nausea, but 

31 
 
 
 
 
would not be considered serious. On the other hand, a stroke that results in only a limited 
degree of disability may be considered a mild stroke, but would be considered serious. 
We will use the Clavien-Dindo Classification system [47], as well as the Comprehensive 
Complication Index (based off of the Clavien-Dindo system) [48] to classify and analyze 
patient adverse events. Grade III (a/b), Grade IV (a/b), and Grade V events will be 
considered SAEs. (See Appendix 1 for classification table) 
8.4.1 Relationship of AE/SAE to study intervention or device 
The relationship of each Event to the study intervention should be characterized using one of 
the following terms in accordance with CHOP IRB Guidelines: definitely, probably, 
possibly, unlikely, or unrelated. In this case, the “study intervention” in considered to be 
the surgical intervention and implantation of the medical device (Anterior vertebral body 
tethering surgery under general anesthesia with spinal cord monitoring). This includes (but 
is not limited to) induction of anesthesia, incision and surgical approach, device 
implantation, and recovery. For each SAE, the PI and Safety Officer will make a case-
by-case determination on the relationship of the SAE to the study procedure, which 
will be documented in the study documents. 
There will be further classification of the Event as either “device-related”, “not device-
related”, or “uncertain to be device-related”. Device-related adverse events are those events 
directly related to the integrity, safety, or biomechanics of the implanted device. This can 
include variables like device breakage or device migration. Other adverse events which are 
considered not device-related are those that are related to the act of the surgery and medical 
recovery (anesthesia, incision and surgical approach, post-operative recovery, etc.). This 
distinction will be indicated in the study documents. For each Event, the PI and Safety 
Officer will make a case-by-case determination on whether the Event is “device 
related”, “not device related”, or “uncertain”. An event which is classified as “device 
related” will be considered an Adverse Device Effect. Adverse device effects have 
special reporting guidelines, as outlined below. 
8.5 
Recording plan for AEs/SAEs 
Surgery and Post-operative Phase (Day 0 – POD 90): 
For these phases, all AEs (including SAEs) will be noted in the study records and reported 
per IRB and FDA requirements outlined below. The subjects will be encouraged to contact 
the office with any concerns, and the medical record will be monitored by study staff for 
indications of AEs. 
Extended Follow-up Phase (POD 91-POD 730): 
For this phase, all SAEs will be recorded (regardless of cause). Only AEs which are deemed 
“device related” will be recorded on study documents and reported per IRB and FDA 
requirements outlined below. The subjects will still be encouraged to contact the office with 
any concerns, and the medical record will be monitored by study staff for indications of 
SAEs or device-related AEs. 
Long-term Follow-Up (POD 730 through approximately two years after skeletal maturity): 

32 
 
 
 
 
An observational study involving chart review of medical charts from CHOP and external 
sources as needed will be undertaken for long-term follow-up. All SAEs identified from the 
medical records that are considered device related, up to two years after skeletal maturity, 
will be reported in accordance with FDA requirements. This will be performed under a 
separate research protocol. 
Only the AEs/SAEs indicated above will be recorded in a patient-specific study binder, kept 
in the secure orthopedics research office. The binder will contain a full description of the 
event, including the nature, date and time of onset, determination of non-serious versus 
serious, intensity (mild, moderate, severe), duration, causality, and outcome of the event. 
Hard copies of the primary documents (medical record notes) describing the event and any 
associated treatment will be printed and kept in the patient-specific study binder. A 
redundant copy of adverse events will be kept in the study REDCap database and will be 
maintained by the study team separately from the patient-specific study binder. The study 
binder will serve as the official record of all Events. 
8.6 
IRB/IEC Notification of SAEs and Other Unanticipated Problems 
The Investigator will promptly notify the IRB of all on-site unanticipated, serious adverse 
events that are related to the research activity. Other unanticipated problems related to the 
research involving risk to subjects or others will also be reported promptly. Written reports 
will be filed using the eIRB system and in accordance with the timeline below. External 
SAEs that are both unexpected and related to the study intervention will be reported 
promptly after the investigator receives the report. External events that do not change the 
risk to subjects or result in a change to the research protocol will be reported to the IRB 
following IRB recommendations. 
REPORTING REQUIREMENTS TO THE IRB 
Type of Unanticipated 
Problem 
Initial Notification  
(Phone, Email, Fax) 
Written Report 
Internal (on-site) SAEs 
Death or Life 
Threatening  
24 hours 
Within 2 calendar days 
Internal (on-site) SAEs 
All other SAEs 
7 days 
Within 7 business days 
Unanticipated Problems 
Related to Research 
7 days  
Within 7 business days 
All other AEs 
N/A 
Brief Summary of 
important AEs may be 
reported at time of 
continuing review 

33 
 
 
 
 
8.6.1 Follow-up report 
If an SAE has not resolved at the time of the initial report and new information arises that 
changes the investigator’s assessment of the event, a follow-up report including all relevant 
new or reassessed information (e.g., concomitant medication, medical history) should be 
submitted to the IRB. The investigator is responsible for ensuring that all SAE are followed 
until either resolved or stable. 
8.7 
Investigator Reporting Requirements to IRB and FDA 
INVESTIGATOR REPORTING TO THE FDA/DEVICE MANUFACTURER 
Type of Report 
Description of Report 
Submit to: 
Timeline 
Unanticipated Adverse 
Device Effects 
Report of any 
unanticipated adverse 
device effect 
IRB and FDA 
Within 10 working days after 
investigator first leans of 
effect. 
Withdrawal of IRB 
approval 
If IRB withdrawn from 
study site 
Sponsor 
Within 5 working days 
Progress Report 
FDA Form 3419 
IRB, FDA, 
Sponsor  
Regular intervals, no less 
than every 6 months for the 
first 24 months of the study. 
Then regular intervals, no 
less than yearly, after the first 
24 months of the study. 
 
Deviations from the 
investigational plan 
If deviation of 
investigational plan 
occurred in order to 
protect subject’s life or 
physical well-being (i.e. 
during an emergency) 
IRB, Sponsor 
Within 5 working days 
Informed Consent 
If investigator used 
device without obtaining 
informed consent 
IRB, Sponsor 
Within 5 working days 
Final Report 
Complete and final 
investigative report 
IRB, Sponsor 
Within 3 months of study 
completion or study 
termination 
Other Reports 
Any access or reports on 
request 
IRB, FDA 
Per request 

34 
 
 
 
 
Voluntary Reports 
At discretion of 
investigator. Voluntary 
adverse event reporting 
is done through Form 
3500A. 
IRB, FDA 
As deemed by investigator 
8.8 
Sponsor Reporting Requirements to FDA and IRB 
SPONSOR REPORTING TO THE IRB/FDA  
Type of Report 
Description of 
Report 
Submit to: 
Timeline 
Unanticipated Adverse 
Device Effects 
Report of any 
unanticipated 
adverse device 
effect 
FDA and 
reviewing IRB(s) 
Within 10 working days 
after sponsor first receives 
notice. May submit further 
reports at FDA requests 
Withdrawal of IRB 
approval 
If IRB withdraws 
approval of 
investigation or 
part of the 
investigation 
FDA and 
reviewing IRB(s) 
and participating 
investigators 
Within 5 working days of 
receipt of notice 
Withdrawal of FDA 
approval 
If FDA withdraws 
approval 
Reviewing IRB(s) 
and participating 
investigators 
Within 5 working days of 
receipt of notice 
Current Investigator List 
Current list of 
names and 
addresses of all 
participating 
investigators 
FDA 
12 month intervals 
Progress Report 
FDA Form 3419 
FDA and 
reviewing IRB(s) 
Regular intervals, no less 
than every 6 months for the 
first 24 months of the study. 
Then regular intervals, no 
less than yearly, after the 
first 24 months of the study. 
Recall and Device 
Disposition 
If Sponsor 
requests return, 
repair, or disposal 
of device, and 
why 
FDA and 
reviewing IRB(s) 
Within 30 working days 
after request is made 

35 
 
 
 
 
Final Report 
Complete and 
final investigative 
report 
FDA and 
reviewing IRB(s) 
1. Notify FDA within 30 
working days 
2. Submit final report to 
FDA and IRBs within 6 
months 
Informed Consent 
If investigator 
used device 
without obtaining 
informed consent 
FDA 
Within 5 working days of 
receipt of notice 
Significant risk device 
determination 
IRB determination 
of significant risk 
of the medical 
device 
FDA 
Within 5 working days of 
receipt of notice of the 
determination 
Other 
Any access or 
reports on request 
FDA and 
reviewing IRB(s) 
Per request 
8.9 
Medical Emergencies 
If a medical emergency occurs in the hospital system, it will be reported following the above 
guidelines and timelines. If no emergencies are identified through chart review, subjects will 
be asked at designated follow-up if they have sought medical care for any reason between 
research visits. Any events will be reported through the above policies and procedures. 
Subjects who contact the study team or clinical offices regarding a medical emergency will 
be referred to the appropriate health care professional to manage their emergency, and 
contact will be documented in the medical record. 

36 
 
 
 
 
9 
STUDY ADMINISTRATION 
9.1 
Data Collection and Management 
1. Confidentiality: 
A master list will be maintained separately from the coded data collection sheet and 
will contain the subject ID number, name, MRN, date of birth, dates of service, 
approximate date at which the subject will need to reconsent upon turning 18, and 
whether or not the subject has consented for the use of their data for future research 
studies. The list will be password-protected so that only the study staff will have 
access. Data will be collected on each subject using the subject’s Study ID number. 
Data, including PHI, will be managed and stored using the research-focused 
electronic data capture system REDCap, under an agreement with the software’s 
development consortium, led by Vanderbilt University. REDCap supports two 
secure, web-based applications designed exclusively to support data capture for 
research studies. REDCap is a PHP web application served by Apache Tomcat over 
a 128-bit SSL connection using a signed certificate. The application relies on a 
study-specific data dictionary defined in an iterative self-documenting process that 
will be conducted by all members of the research team. The data dictionary is the 
foundation for custom case report form design and validated coding of variables. 
Authentication of research staff will be performed via LDAP using CHOP’s 
enterprise Active Directory service. The application generates a complete audit trail 
of user activity, provides reporting, and has an automated export mechanism to 
common statistical packages (SAS, SPSS, Stata, R/S-Plus).  
A patient-specific study binder will be kept for each enrolled patient. The study 
binder will contain adverse event information, signed consent forms, paper forms 
collected during testing, as well as all other relevant documentation. These will be 
stored in a locked research office. 
2. Data Sharing: 
Coded data will be transferred from CHOP to Dr. Sriram Balasubramanian at Drexel 
University for research collaboration and data analysis via CD/DVD, secure 
electronic file transfer, and/or on protected Excel spreadsheets sent by secured 
hospital email. All data transferred will be labeled with the subject’s study ID and 
will not include PHI. Dr. Balasubramanian at Drexel University will not have access 
to the master list, therefore this data will not be identifiable to them. 
A Limited Data Set, including images, will be transferred from CHOP to Globus 
Medical, Inc. as part of a license agreement executed between the two parties for use 
in the manufacturer’s humanitarian device exemption (HDE) submission. Images 
will be limited to images of subjects’ torsos and will not include video recordings, 
subject faces, or identifiable features. Data will be sent by secure electronic file 
transfer and with hardcopy source documents. Hardcopy documents will be redacted 
to remove identifiers and be transferred via courier or in-person from study team 
member to an authorized representative of Globus Medical, Inc. Data transferred will 

37 
 
 
 
 
not include PHI, except dates of service, and Globus Medical, Inc. will not have 
access to the master list to link data back to subjects.  
3. Security: 
The master sheet will be a password protected Excel file kept in the secure 
orthopedic research drive at CHOP. The REDCap MySQL database is replicated in 
real time to a completely redundant instance of MySQL. The redundant instance is 
available for restoration of the primary database or for manual failover in the case of 
primary database failure. Time-stamped backup files are made from the replicated 
database daily by CHOP Research Information Systems using automated backup 
routines. Backup files are encrypted and transferred to a secure file server accessible 
only to designated personnel. A rolling seven-day window of backup files is 
maintained in an immediately available online state, with a larger window 
maintained in a compressed file archive available at a reduced speed of access. Daily 
destructive database backup files are stored on the database server and are deleted 
only after successful backup of the entire database to file. In the event of data error, 
loss or corruption, research personnel will work with CHOP Research Information 
Systems to determine the most appropriate recovery strategy. Data and backups are 
stored in the CHOP Research Information Systems Storage Area Network (SAN). 
Access to the SAN directories where data are stored will be limited to Research 
Information Systems personnel, with authentication performed using CHOP’s 
enterprise Active Directory service. The data from the application will be compiled 
on a secured survey web platform that is encrypted using AES 256 bit encryption. 
The data collected on paper forms during testing will be secured in the patient-
specific study binders in a locked research office. 
 
4. Anonymization, de-identification or destruction: 
Data will be collected on each subject using the subject’s study ID number. Study 
personnel will store a list connecting the subject’s PHI to study ID. All PHI collected 
from this study will be destroyed two years after the last marketing application has 
been approved or two years after all research of the study has been completed, and as 
approved by the Sponsor. 
9.2 
Confidentiality 
All data and records generated during this study will be kept confidential in accordance with 
Institutional policies and HIPAA on subject privacy and that the Investigator and other site 
personnel will not use such data and records for any purpose other than conducting the 
study. 
No identifiable data will be used for a future study without first obtaining IRB approval. 
9.3 
Regulatory and Ethical Considerations 
9.3.1 Data and Safety Monitoring Plan 
The PI will monitor data and safety throughout the duration of the study and will report any 
adverse events in accordance with IRB policies. The PI, Safety Monitor, and study team will 

38 
 
 
 
 
perform interim safety analyses as outlined in Section 6.6. Safety monitoring will be handled 
internally by the study Safety Monitor and CHOP Office of Research Compliance (ORC). 
We will also submit reports to the FDA, device manufacturer, or both as per medical device 
reporting requirements specified in 21CFR803. 
9.3.2 Risk Assessment 
This section outlines risks associated with the study procedures. 
9.3.2.1 Surgical Procedure: Anterior-approach thoracoscopic vertebral body tethering 
(greater than minimal risk) 
• Radiation Exposure (Fluoroscopy and X-ray): This study involves exposure to 
radiation from intraoperative fluoroscopy and x-rays. The patient will receive a 
radiation dose, which is necessary for completion of the operation. Radiation can 
increase the risk of cancer after many years but at a dose much higher than the 
patient will receive. Because of the low dose of radiation, it is very likely that the 
patient will see no ill effects.  
Radiation exposure will be tracked during the surgery. This will be recorded as 
fluoroscopic exposure time recorded in minutes. The widely-accepted ALARA (as 
low as reasonably acceptable) principle will be used to ensure surgeons are imparting 
the lowest radiographic dose possible onto the patient [49]. 
• Neurological Injury: There is risk for neurological injury in all surgeries involving 
spinal correction and device implantation. Intra-operative neuromonitoring (IONM) 
will be used by the surgical team to monitor for this risk. There are no known 
adverse neuromonitoring events occurring with this surgery in the literature [21]. 
• Bleeding: Bleeding is a risk for any surgical procedure. Every reasonable effort will 
be made by the surgical staff to reduce blood loss. Estimated blood loss during 
surgery (EBL) will be recorded on CRFs. 
• Infection: Infection is a risk for any surgical procedure or hospital stay. All CHOP 
SOPs regarding sterile procedures and institutional policies on infection prevention 
will be followed to prevent infection. The patient will be placed on CHOP 
Orthopedics SOP for pre- and post-operative antibiotic regimen for spine surgery 
patients. 
• Pain: Pain is a risk for a patient during post-operative recovery. CHOP orthopedics 
pain team will be consulted for pain management in the time following the surgery, 
to best manage post-operative pain. 
• Pneumothorax: After surgery, the patient will be monitored for pneumothorax by 
inpatient hospital staff. If a pneumothorax is found, it may cause elongation of the 
patient’s hospital stay, or require medical/surgical intervention. 
• Bronchopulmonary plug: After surgery, the patient will be monitored for presence of 
a bronchopulmonary plug by inpatient hospital staff. If a bronchopulmonary plug is 
found, it may cause elongation of the patient’s hospital stay, or require a 
medical/surgical intervention. 
• Implant Failure: We will diligently monitor the patient both during and after surgery 
for signs of implant failure. Some types of implant failure could be: 

39 
 
 
 
 
o Screw failure – screw and/or centering staple have loosened from the vertebra 
AND require re-operation. 
o Tether failure – the tether has broken or lost tension. Diagnosed at any time 
point after 3 months by increased angulation at a disc space on standing PA 
or increase in disc wedging on side bending x-ray to the side away from the 
implant. Also, it is only an SAE if noted before maturity, overall Cobb 
worsens compared to the first erect measurement, AND requires re-operation. 
o Implant re-operation - any problem with the implant that requires re-
operation including re-operation for overcorrection with any of the following: 
a removal of all or part of the implant, loosening of the tension on the 
implant, or spinal fusion. 
• Overcorrection: It is possible for the device to impart more than the intended 
correction to the spine curvature. This event will be monitored by consistent follow-
up throughout the study, and may require medical or surgical intervention. 
It should be noted that the above risks are the same risks that are present for standard-of-
care surgery for spinal surgery. All appropriate clinical care procedures and pathways 
followed for standard-of-care spine surgeries will take place for these subjects. 
9.3.2.2 No greater than minimal risk study procedures: 
• Review of medical records: There is a risk of breach of confidentiality and privacy as 
a result of medical record review. This risk is minimized as detailed in Section 9. 
• Administration of questionnaires: The questionnaires have the potential to make 
subjects feel uncomfortable. Subjects will be allowed to skip questions which they 
are not comfortable answering without compromising their participation in the study. 
• Study-specific physical exam: The study physical exam uses non-invasive 
measurement techniques commonly employed in clinical practice. 
• Clinical photographs: There is a risk of breach of confidentiality in subject 
photographs. This risk is minimized by not including the face of the subjects, and by 
the data protection plan in Section 9. 
9.3.2.3 Risks associated with live case demonstration: 
• Extended anesthesia exposure: Time under anesthesia may be extended minimally, at 
most a few minutes, due for example to additional setup procedures, however, this 
preparation will be done by specialized staff in tandem with the standard surgical 
preparation to not add extra time under anesthesia.  
• Infection risk: There may be added risk of infection with more personnel and 
additional equipment in the room. However, any additional staff that may be in the 
operating room will be educated on safe clinical practices when entering and will 
remain outside of the sterile field during observation. Only the surgeon and other 
relevant clinicians will be allowed in the sterile field. Any additional equipment used 
will be covered with sterile cloth and utilized only as necessary during the procedure. 
• Surgeon distraction: This risk will be addressed by having a separate surgeon 
handling commentary of the procedure, allowing the performing investigator and 
surgical team to continue the surgery as would normally be conducted without 
distraction. 

40 
 
 
 
 
• Breach of confidentiality: There is a risk of loss of privacy if identifying information 
is inadvertently disclosed during the surgery. Staff will be aware to not disclose 
identifying information during the surgical case, unless necessary. If identifying 
information is disclosed, the videotaped record will be edited to remove those 
frames. No recording system can completely guard against risks such as a breach 
caused by an intentional intrusion, inadvertent disclosure of information, or the 
failures or limitations of equipment used to transmit live or recorded data. 
The investigators believe these additional risks associated with the live case demonstration 
are minimal. 
 
9.3.3 Potential Benefits of Trial Participation 
There may be some direct benefits to trial participation. First, studies have shown that there 
is a lower surgical risk in anterior-approach spine surgery compared to the posterior 
approach [19]. 
Vertebral body tethering has the theoretical potential for improvement over the outcomes of 
posterior spinal fusion. In particular, the durability of the posterior spinal fusion is coming 
into question. Posterior pedicle screw constructs came into popularity in the early 2000’s 
and new 10 year post-op data is demonstrating a concerning trend. The Harms Study Group, 
a multicenter consortium of scoliosis practitioners and researchers have recently shown that 
almost 10% of AIS fusions require revision surgery by 10 year post-op and that this trend is 
progressive [28]. Other authors have also reported on high long term re-operation rates 
following AIS fusion surgery ranging from 4.6% to 19% [29-31]. One theory is that a fusion 
imparts increased stress on unfused segments below a fusion. Marks et al. have shown that 
patients will retain total lumbar motion after a posterior spinal fusion by increasing motion 
in the unfused areas [32]. The authors postulate that increased motion may lead to 
degeneration of discs and facet joints. These findings of supraphysiologic motion below a 
posterior spinal fusion may explain some of the decreasing durability of posterior spine 
fusion. Green et al. have studied the health of intervertebral discs below a spinal fusion at an 
average of 11.8 years following posterior spinal fusion [33]. The authors found that disc 
degeneration was occurring in 85% of patients and the discs when graded by the Firman 
scale, an objective validated measure of disc degeneration, demonstrated an average 
decrease from 1.1 pre-op to 1.8. Vertebral tether surgery will allow for continued motion of 
the instrumented levels and thus avoid the long lever-arm effect of a long fusion that may be 
contributing to early degeneration. Additional reports have questioned the durability of 
posterior spinal fusion. Upasani et al. reported on increased pain in patients at five years 
post-spinal fusion compared to at two years [34]. Lastly, posterior spinal fusion in patients 
who have not had their pubertal growth spurt, the population in whom we are proposing 
vertebral tethering, are at increased risk of complications and re-operation. Sponseller et al. 
reported that patients with open triradiate cartilages undergoing spinal fusion surgery have 
an increased rate of adding on (development of deformity below a fusion) and the response 
of the un-instrumented lumbar curve is less predictable [35]. 

41 
 
 
 
 
The basic science literature suggests that this study intervention has the potential benefit to 
preserve motion of the spine in long-term follow-up, compared to traditional PSF [37-39]. 
Indirectly, participation in this trial will benefit the scientific community as a whole. Results 
from this trial will guide standard practice in a novel approach to spinal surgery in the 
pediatric population. 
9.3.4 Risk-Benefit Assessment 
The known risks and direct (and indirect) benefits will be presented to the patients by the 
Investigators without bias. The Investigators believe that benefits outweigh the risks based 
on all current knowledge and literature on the subject. 
9.4 
Recruitment Strategy 
Subjects will be recruited by the Investigator and study team in the orthopedic clinic. 
Potential subjects who may satisfy the inclusion/exclusion criteria will be identified by the 
clinical staff, and will contact a study team member. The study team member will use the 
“Screening CRF” to assess preliminarily whether a potential subject may meet 
inclusion/exclusion criteria. Then, the study team member will confer with the PI and/or 
Investigators to determine whether the patient should be approached to offer the clinical trial 
to the subject and family. Potentially eligible patients will then be approached for informed 
consent/assent. Before being presented with the clinical trial, patients that qualify in 
accordance with the FDA-approved labeling of the HUD, The Tether – Vertebral Body 
Tethering System, will be offered the approved device first. 
In addition, the study recruitment material will be posted on CHOP Orthopaedics 
department website as an additional source for recruiting potential subjects. A printed packet 
hand-out will also be available to interested families. These recruitment materials will 
include information regarding the surgical procedures, risks and follow-up care. 
9.5 
Informed Consent/Assent and HIPAA Authorization 
After the subject has made the decision to have surgery and discussed this decision with 
their doctor, potential subjects who may satisfy the inclusion/exclusion criteria will be 
identified by the clinical staff, who will contact a study team member. Eligible patients will 
then undergo consent/assent during their orthopedic visit. This will take place in a private 
exam room in the clinic. The study will be explained to the patients/families and they can 
decide whether to participate in the study. Subjects and their families will be given the 
opportunity to ask questions and may take as long as they need to make a decision. 
For subjects that are withdrawn from the study due to AEs/SAEs, as determined by the 
investigator, they will undergo consent/assent during their orthopedic visit to decide whether 
they agree to review of medical and radiographic records following the occurrence of the 
AE/SAE up to two years post-operatively.  
9.6 
Payment to Subjects/Families 
No payment will be given to subjects or families. 

42 
 
 
 
 
10 PUBLICATION 
Following the completion of subject enrollment, data collection, and analysis, a manuscript 
will be prepared and submitted to an appropriate journal in order to contribute to the 
literature on this topic. 
 

43 
 
 
 
 
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12 APPENDIX 
12.1 Appendix 1: Clavien-Dindo complications classification system (from Dindo, 
et al.)