Medtronic 6470318 Instructions for Use

BRYAN® CERVICAL DISC 0381326E Rev. C

2020-05-11

IMPORTANT INFORMATION ON THE BRYAN® CERVICAL DISC

DESCRIPTION

The BRYAN® Cervical Disc is a cervical disc replacement device comprised of two titanium shells, two titanium retaining wires,
a polycarbonate polyurethane nucleus, a polyether polyurethane sheath, and two titanium seal plugs. The articulating surfaces
of the device are polyurethane and titanium.

The nucleus is designed to fit between the two shells. The bone-contacting side of each shell includes a sintered titanium
porous coating to provide bony ingrowth. The nucleus-contacting side of each shell has a center pin which interacts with a
central hole in the nucleus to control the range of motion and help prevent nucleus expulsion. A stop or wing on the anterior
aspect of the device, which extends superiorly on the cephalad shell and inferiorly on the caudal shell, is intended to prevent
migration of the device into the spinal canal. A polyurethane sheath surrounds the nucleus and is attached to each shell with
titanium retaining wires, forming a closed compartment. The device is supplied pre-assembled with the exception of saline and

two seal plugs. Prior to implantation, the surgeon fills the BRYAN
function as an initial lubricant for the prosthesis. The surgeon screws titanium alloy seal plugs into one hole in each shell to
initially retain the saline.

The prosthesis is held in the intervertebral disc space by the fit of each shell’s outside diameter and convex outer surfaces into a
custom-milled cavity created in each vertebral endplate by the surgeon prior to device implantation. The prosthesis was
designed to allow for the following motions from the neutral position ex vivo: approximately ±11° flexion/extension, ±11° lateral
bending, ±7° rotation, and ±1 mm translation for all cervical disc sizes. The available components are shown in Table 1.

Table 1: BRYAN

Catalog Number Diameter (mm)

6470314 14
6470315 15
6470316 16
6470317 17
6470318 18

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Cervical Disc Device Sizes

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Cervical Disc with sterile saline. The saline is intended to

After implantation of the device, the resultant interbody height is approximately 6mm.
Implied warranties of merchantability and fitness for a particular purpose or use are specifically excluded.

INDICATIONS

The BRYAN® Cervical Disc is indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following single­level discectomy for intractable radiculopathy and/or myelopathy. The BRYAN

approach. Intractable radiculopathy and/or myelopathy is defined as any combination of the following: disc herniation with
radiculopathy, spondylotic radiculopathy, disc herniation with myelopathy, or spondylotic myelopathy resulting in impaired
function and at least one clinical neurological sign associated with the cervical level to be treated, and necessitating surgery as
demonstrated using computed tomography (CT), myelography and CT, and/or magnetic resonance imaging (MRI). Patients

receiving the BRYAN
BRYAN

®

Cervical Disc.

®

Cervical Disc should have failed at least six weeks of non-operative treatment prior to implantation of the

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device is implanted via an open anterior

CONTRAINDICATIONS

The BRYAN® Cervical Disc should not be implanted in patients with the following conditions:

▪ Active systemic infection or infection at the operating site.
▪ Allergy to titanium, polyurethane, or ethylene oxide residues.
▪ Osteoporosis defined as a DEXA bone mineral density T-score equal to or worse than -2.5.
▪ Moderate to advanced spondylosis characterized by bridging osteophytes, marked reduction or absence of motion, or

collapse of the intervertebral disc space of greater than 50% of its normal height.

▪ Marked cervical instability on radiographs (e.g., radiographic signs of subluxation greater than 3.5mm or angulation of the

disc space more than 11° greater than adjacent segments).

▪ Significant cervical anatomical deformity or compromised vertebral bodies at the index level (e.g., ankylosing spondylitis,

rheumatoid arthritis, or compromise due to current or past trauma).

▪ Significant kyphotic deformity or significant reversal of lordosis.
▪ Symptoms necessitating surgical treatment at more than one cervical level.

WARNINGS

Correct sizing and placement of the device is essential to optimal performance. The BRYAN® Cervical Disc should only be used
by surgeons experienced in the surgical procedure and have undergone adequate hands-on training with this specific device.
Medtronic will offer hand-on training to physicians prior to the first surgical treatment. A lack of adequate experience and/or
training may lead to a higher incidence of adverse events, such as neurological complications.

Due to the proximity of vascular and neurological structures to the implantation site, there are risks of serious or fatal
hemorrhage and risks of neurological damage with the use of this device. Serious or fatal hemorrhage may also occur if the
major cervical blood vessels are eroded or punctured during implantation and are subsequently damaged due to breakage of
implants, migration of implants, or if pulsatile erosion of the vessels occurs because of close apposition of the implants.

PRECAUTIONS

The safety and effectiveness of this device has not been established in patients with the following conditions:

▪ Axial neck pain as solitary symptom.
▪ Not skeletally mature.
▪ Prior cervical spine surgery, including prior surgery at the index level.
▪ Facet joint pathology of involved vertebral bodies.
▪ Active malignancy.
▪ Paget’s disease, osteomalacia, or other metabolic bone disease.
▪ Chronic or acute renal failure or history of renal disease.
▪ Taking medications known to potentially interfere with bone/soft tissue healing (e.g., steroids).
▪ Pregnant.
▪ Unstable cardiac disease.
▪ Diabetes mellitus requiring daily insulin management.
▪ Extreme obesity as defined by the NIH Clinical Guidelines Body Mass Index (i.e., BMI ≥40).

There were no patients in the pivotal study who were less than 21 years of age. The safety and effectiveness of this device has
not been studied in the pediatric or adolescent age group (<21 years old).

The safety and effectiveness of this device has not been established in patients who were not refractory to at least six weeks of
unsuccessful conservative treatment or had signs of progression or spinal cord/nerve root compression with continued non­operative care.

Implanted metal alloys release metallic ions into the body. The long term effect of these ions on the body is not known.
In order to minimize the risk of periprosthetic vertebral fractures, surgeons must consider all comorbidities, past and present,

medications, previous treatments, etc. Surgeons should screen patients to determine if a DEXA bone mineral density
measurement is necessary. If DEXA is performed, the patient should not receive the BRYAN® Cervical Disc (per the
Contraindications) if the DEXA bone mineral density T-score is ≤ -2.5, as the patient may be osteoporotic. It may also be
advisable to exclude patients with a T score ≤ -1.0, as those patients may be osteopenic.

Patients in the clinical study were instructed to use non-steroidal anti-inflammatory drugs (NSAIDs) for two weeks
postoperatively. Dosing and frequency were left to the discretion of the physician. It has been reported in the literature that
short-term postoperative use of NSAIDs may reduce the instance of heterotopic ossification.

Correct selection of the appropriate implant size is extremely important to ensure the placement and function of the disc.
Patient selection is extremely important. In selecting patients for a total disc replacement, the following factors can be of

extreme importance to the success of the procedure: the patient’s occupation or activity level; a condition of senility, mental
illness, alcoholism or drug abuse; certain degenerative diseases (e.g., degenerative scoliosis or ankylosing spondylitis) that may
be so advanced at the time of implantation that the expected useful life of the device is substantially decreased, and medical
conditions that may affect postoperative management, such as Alzheimer’s disease and emphysema.

Surgical implants must never be re-used or re-implanted. Even though the device appears undamaged, it may have small
defects and internal stress patterns that may lead to early breakage.

This system was designed for single patient use only. Do not reuse, reprocess, or resterilize this product. Reuse, reprocessing,
or resterilization may compromise the structural integrity of the device and/or create a risk of contamination of the device, which
could result in patient injury, illness, or death.

Use aseptic technique when removing the BRYAN
Use care when handling a BRYAN

implant. Damaged implants are no longer functionally reliable.
BRYAN

manufacturers.
Patients should be instructed in postoperative care procedures and should be advised of the importance of adhering to these

procedures for successful treatment with the device. Patients should be advised to avoid any activities that require repeated

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Cervical Disc components should not be used with components or instruments of spinal systems from other

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disc component to ensure it does not come in contact with objects that could damage the

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Cervical Disc device from the innermost packaging.

bending, lifting, and twisting, such as athletic activities. Gradual increase in physical activity will depend on individual patient
progress.

PHYSICIAN NOTE: Although the physician is the learned intermediary between the company and the patient, the important
medical information given in this document should be conveyed to the patient.

FOR US AUDIENCES ONLY

CAUTION: FEDERAL LAW (USA) RESTRICTS THESE DEVICES TO SALE BY OR ON THE ORDER OF A PHYSICIAN.

MRI Information for the BRYAN® Cervical Disc Implant

MR Conditional

Non-clinical testing demonstrated that the BRYAN
following conditions:

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Cervical Disc is MR Conditional. It can be scanned safely under the

▪ Static magnetic field of 1.5 Tesla and 3.0 Tesla
▪ Highest spatial gradient magnetic field of 720 Gauss/cm
▪ Maximum whole body average specific absorption rate (SAR) of 2.0 W/kg or less under Normal Operating Mode only, for 15

minutes of scanning (per pulse sequence).

In non-clinical testing, the BRYAN
averaged SAR of 2.1 W/kg, as assessed by calorimetry for 15 minutes of MR scanning (per pulse sequence) in a 1.5 Tesla MR
system (1.5 Tesla/64 MHz, Magnetom, Siemens Medical Solutions, Malvern, PA. Software Numaris/4,Version Syngo MR 2002B

DHHS). Additionally, the BRYAN
body averaged SAR of 2.7 W/kg, as assessed by calorimetry for 15 minutes of MR scanning (per pulse sequence) in a 3 Tesla
MR system (3 Tesla/128 MHz, Excite, G3.0-052B, General Electric Healthcare, Milwaukee, WI).

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Cervical Disc produced a maximum temperature rise of 1.7º C at a maximum whole body

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Cervical Disc System produced a maximum temperature rise of 2.0ºC at a maximum whole

Artifact Information

MR image quality may be compromised if the area of interest is in the same area or relatively close to the position of the
BRYAN

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Cervical Disc. The artifact size information is as follows:

Pulse Sequence T1-SE T1-SE GRE GRE
Signal Void Size

Imaging Plane Parallel Perpendicular Parallel Perpendicular

The image artifact extends approximately 25 mm from the device when scanned in non-clinical testing using a gradient echo
sequence in a 3 Tesla MR system (Excite, HDx, Software 14X.M5, General Electric Healthcare, Milwaukee, WI) using a
transmit/receive RF body coil.

582 mm

2

557 mm

2

1,350 mm

2

1,287 mm

2

MRI Patient Counseling Information

Physicians should communicate with the patient the following information about MR with respect to the BRYAN® Cervical Disc:

▪ BRYAN

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Cervical Disc performance has been established for MRI systems at field strengths of 1.5 and 3.0 Tesla.

▪ During an MRI, the patient may notice a warming sensation around the implant or feel a tingling sensation. If the warming or

tingling sensation is uncomfortable, the patient should communicate this to the MR technologist, the MRI should be
stopped, and the settings adjusted to reduce or eliminate the sensation. The highest temperature change observed in non­clinical testing was +2.0ºC (associated with specific conditions listed).

▪ Additionally, the metal in the implant may cause the MRI image to be distorted in the area around the implant. The MRI can

be adjusted to minimize the image distortion.

Physicians should instruct patients to:

▪ Inform any healthcare personnel (e.g., doctor or MR technologist) that they have an implanted cervical disc prior to

receiving an MRI.

▪ The patient’s doctor will recommend whether or not an MRI is appropriate.

POTENTIAL ADVERSE EVENTS

Risks associated with the use of the BRYAN® Cervical Disc include those commonly associated with any surgery, those
specifically associated with cervical spinal surgery using an anterior approach, and those associated with a spinal implant, as

well as those pertaining to the BRYAN
categories. There is also the risk that this surgical procedure will not be effective, and may not relieve or may cause worsening
of preoperative symptoms. Some of these effects were observed in the clinical study and therefore have been previously
reported in the adverse events tables.

1. Risks associated with any surgical procedure are those such as abscess; cellulitis; wound dehiscence; wound necrosis;

edema; hematoma; heart and vascular complications; hypertension; thrombosis; ischemia; embolism; thromboembolism;
hemorrhage; thrombophlebitis; adverse reactions to anesthesia; pulmonary complications; gastrointestinal complications;
organ, nerve or muscular damage; seizure, convulsion, or changes to mental status; and complications of pregnancy
including miscarriage and fetal birth defects.

2. Risks associated with anterior interbody surgery of the cervical spine include dysphagia; dysphasia; dysphonia; hoarseness;

vocal cord paralysis; laryngeal palsy; sore throat; recurring aspirations; nerve deficits or damage; tracheal, esophageal, and

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Cervical Disc. However, the causality of these adverse events is not exclusive to these

pharyngeal perforation; airway obstruction; external chylorrhea; warmth or tingling in the extremities; deficit or damage to
the spinal cord, nerve roots, or nerves possibly resulting in paralysis or pain; dural tears or leaking; cerebrospinal fistula;
discitis, arachnoiditis, and/or other types of inflammation; loss of disc height; loss of proper curvature, correction, height or
reduction of the spine; vertebral slipping; scarring, herniation or degeneration of adjacent discs; surrounding soft tissue
damage, spinal stenosis; spondylolysis; otitis media; fistula; vascular damage and/or rupture; and headache.

3.

Risks associated with implants in the spine, including the BRYAN

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device, are early or late loosening of the components;
disassembly; bending or breakage of any or all of the components; implant migration; malpositioning of implant; loss of
purchase; sizing issues with components; anatomical or technical difficulties; implant fracture; bone fracture; skin
penetration, irritation, pain, bursitis resulting from pressure on the skin from component parts in patients with inadequate
tissue coverage over the implant; foreign body reaction to the implants including possible tumor formation, autoimmune
disease, metallosis, and/or scarring; possible tissue reaction; bone resorption; bone formation that may reduce spinal
motion or result in a fusion, either at the treated level or at adjacent levels; development of new radiculopathy; myelopathy
or pain; tissue or nerve damage caused by improper positioning and placement of implants or instruments; loss of
neurological function; decreased strength of extremities; decreased reflexes; appearance of cord or nerve root injury; loss of
bowel and/or bladder control; and interference with radiographic imaging because of the presence of the implant.

4. Wound, local, and/or systemic infections.

5. Surgical instrument bending or breakage, as well as the possibility of a fragment of a broken instrument remaining in the

patient.

6. Inability to resume activities of normal daily living, including loss of consortium.

7. Death.

NOTE: Additional surgery may be necessary to correct some of the adverse effects.

CLINICAL STUDIES

A multi-center, prospective, randomized, non-inferiority clinical trial of the BRYAN® Cervical Disc was conducted in the US
comparing the anterior spinal use of the BRYAN

plating stabilization, the control, for reconstruction of the disc from C3-C7 following single-level discectomy for intractable
radiculopathy and/or myelopathy.

The IDE study was approved for a total of 470 patients. Medtronic performed a pre-specified interim statistical analysis when
approximately 300 implanted subjects had completed their 24-month follow-up visit. As predetermined at the time of the IDE

study initiation, if the results of this interim analysis demonstrated non-inferiority of the subjects receiving the BRYAN
compared to controls, the sponsor would submit a marketing application.

A total of 463 patients were treated at 30 investigational centers in the clinical trial: 242 patients in the investigational BRYAN
device treatment group and 221 patients in the control group. A post-approval study required as a condition of PMA approval
was conducted to follow the original IDE subject cohort through 120 months postoperatively. Additionally, an enhanced
surveillance study was also conducted collect adverse event and complaint information for five (5) years after device approval.

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device to anterior cervical discectomy and fusion (ACDF) using allograft and

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device

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SUMMARY OF THE IDE AND POST-APPROVAL STUDY (PAS) METHODS

Study Objectives

IDE Study

The primary objective of the IDE study was to demonstrate that the overall success rate for the investigational BRYAN® Cervical
Disc treatment is statistically non-inferior to the overall success rate of the control treatment at 24 months following surgery. If
statistical non-inferiority was established, the investigational treatment is considered to be safe and effective, and the study was
considered a success.

Other secondary objectives were to compare the success rates of individual effectiveness endpoints and neurological status at
24 months following surgery.

Post-approval Study

The primary objective of the post-approval study was to demonstrate that the overall success rate for the investigational
BRYAN

following surgery. If statistical non-inferiority was established, the investigational treatment is considered to be safe and
effective, and the study was considered a success.

Other secondary objectives were to compare the success rates of individual effectiveness endpoints and neurological status at
120 months following surgery.

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Cervical Disc treatment is statistically non-inferior to the overall success rate of the control treatment at 120 months

Enhanced Surveillance Study

The study objective was to collect the information for any adverse event and complaint, including those not associated with any
adverse clinical effect, received by the company for the BRYAN

®

Cervical Disc device following 5 years after device approval.

Study Designs

IDE Study

The IDE study was a multi-center, prospective, randomized, controlled clinical trial comparing the BRYAN® Cervical Disc
treatment to the control treatment. Data were collected at pre-operative, discharge, 6 weeks, 3 months, 6 months, 12 months (1
year), and at 24 months (2 years). Additionally, 36 month data (3 years) was also collected prior to the start of the post-approval
study.

Post-approval Study

The post-approval study was a prospective study to continue follow-up on the subjects who participated in the IDE study. Data
were collected at 48 months (4 years), 60 months (5 years), 84 months (7 years), and at 120 months (10 years).

Enhanced Surveillance Study

Enhanced Surveillance data was collected annually on the post-market device for five (5) years after PMA approval.

Inclusion and Exclusion Criteria

To qualify for enrollment in the IDE study, subjects met all of the following inclusion criteria and none of the following exclusion
criteria.

Inclusion Criteria

▪ Requires surgical treatment at any one level (C3-4, C4-5, C5-6, or C6-7) that failed conservative treatment (by the

investigator or referring physician) lasting at least six weeks; for any combination of the following: disc herniation with
radiculopathy, spondylotic radiculopathy, disc herniation with myelopathy, or spondylotic myelopathy. The six-week
conservative treatment period may be waived in cases of myelopathy requiring immediate treatment (e.g., acute onset of
clinically significant signs).

▪ The requirement for surgical treatment must be demonstrated using computed tomography (CT), or myelography and CT,

and/or magnetic resonance imaging (MRI).

▪ Patient must score 30 or more points on the NDI questionnaire and exhibit at least one clinical sign associated with the

cervical level to be treated (i.e., abnormal reflex, decreased motor strength, or abnormal dermatome sensitivity).

▪ Skeletally mature (at least 21 years old).
▪ Willing and likely to follow the requirements of the protocol.
▪ Voluntarily signs the Patient Informed Consent.

Exclusion Criteria

A patient meeting any of the following criteria was to be excluded from the study:

▪ Active systemic infection or infection at the operating site.
▪ Metabolic bone disease, such as osteoporosis, which is defined as a bone mineral density T-score equal to or worse than –

2.5.

Note: If the investigator detects the presence of significant radiolucence, bone mineral density (BMD) scan in the spine,
wrist, and femoral neck must be obtained to verify the absence of osteoporosis.

▪ Known allergy to titanium, polyurethane, or ethylene oxide residuals.
▪ Concomitant conditions requiring steroid treatment.
▪ Diabetes mellitus requiring daily insulin management.
▪ Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index.
▪ Pregnancy.
▪ Axial neck pain as the solitary symptom.
▪ Previous cervical spine surgery.
▪ A medical condition that may interfere with the postoperative management program, such as advanced emphysema, or

Alzheimer’s disease.

▪ A medical condition that may result in patient death prior to study completion.

▪ Unstable cardiac disease.

▪ Active malignancy.
▪ Current or recent history of substance abuse (alcoholism and/or narcotic addiction) requiring intervention.
▪ Signs of being geographically unstable, such as recent or pending divorce, or high level of job dissatisfaction.

Patients with the following radiographic features at the symptomatic level were excluded from the study. These features at
adjacent levels did not disqualify the patient from the study.

▪ Significant cervical anatomical deformity (e.g., ankylosing spondylitis, rheumatoid arthritis, etc.).
▪ Moderate to advanced spondylosis. Patients who demonstrate advanced degenerative changes. Such advanced changes

are characterized by any one or combination of the following:

▪ Bridging osteophytes.

▪ Marked reduction or absence of motion.

▪ Collapse of the intervertebral disc space of greater than 50% of its normal height.
▪ Radiographic signs of subluxation greater than 3.5mm.
▪ Angulation of the disc space more than 11° greater than adjacent segments.

▪ Significant kyphotic deformity or significant reversal of lordosis.

Study Population

IDE and Post-Approval Studies

The studies included 463 enrolled subjects who were at least 21 years old at the time of the surgery and met the study inclusion
and exclusion criteria.

Enhanced Surveillance Study

The study population was as per device indication. This device is indicated in skeletally mature patients for reconstruction of the
disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy.

Post-Operative Care

The recommended post-operative care included avoidance of heavy physical activity and limitations on extended automobile
rides, working, lifting, bending and twisting. The recommended post-operative regimen also included avoidance of physically
demanding sports or recreational activities for 3 months post-operatively. The decision whether to use a post-operative orthosis
was left to the discretion of the investigator. Investigational patients were instructed to use NSAIDs for the first two weeks
postoperatively.

IDE and PAS Follow-up Schedules

For the IDE study, patients were evaluated preoperatively (within 2 months of surgery), intraoperatively, and post-operatively at
6 weeks, 3 months, 6 months, 12 months (1 year), and at 24 months (2 years). Additionally, patients were also evaluated at 36
months (3 years) prior to the beginning of the post-approval study. For the post-approval study, patients were evaluated at 48
months, 60 months, 84 months, and 120 months. Complications and adverse events, device-related or not, were evaluated over
the course of the clinical trial. At each evaluation timepoint, the primary and secondary clinical and radiographic outcome
parameters were evaluated. For the IDE, success was determined from data collected during the initial 24 months of follow-up.
For the post-approval study, success was determined from the data collected up to 120 months.

Data Source

New data collection

Study Endpoints

IDE and PAS Study Endpoints

The primary endpoint was determined at 24 months (for the IDE) and 120 months (for the PAS) as a composite variable termed
overall success which included key safety and efficacy considerations. The efficacy variable was Neck Disability Index (NDI)
success, which was defined as at least 15-points improvement in the postoperative NDI score compared to the pre-operative
score. Safety variables included:

▪ Maintenance or improvement in neurological status from preoperative
▪ No serious adverse events classified as implant associated or implant/surgical procedure associated, and
▪ No additional surgical procedure classified as a “failure.”

Secondary endpoints for both the IDE and post-approval studies included neck pain, arm pain, general heatlh status, patient
satisfaction, patient global perceived effect, and gait assessments.

Enhanced Surveillance Study Endpoint

Complaints and adverse events for up to five (5) years after BRYAN® Cervical Disc device approval.

Strengths and Limitations of the Clinical Study Design

The following are important study design strengths of the IDE, post-approval, and enhanced surveillance studies:

▪ The PAS provided extended term profile of safety and effectiveness as well as functional data established on a multicenter,

randomized, controlled clincal trial.

▪ The consistency of data gathering approaches and endpoints was maintained through both the IDE and post-approval

studies.

▪ The strength and reliability of the final IDE and PAS conclusions were confirmed by several sensitivity analyses.
▪ The study design minimized potential biases by integrating a wide variety of assessments including subjective data,

physician-judged and core laboratory-assessed evaluations.

▪ The duration of the enhanced surveillance study was five (5) years after PMA approval which allowed time to monitor longer

term adverse events and complaints received by the sponsor for the device in the post-marketing setting.

The following potential study design limitations should also be considered when interpreting the results of the IDE, post­approval, and enhanced surveillance studies:

▪ Though there were no significant differences in Adverse Event (AE) rates between the groups, categorization of AE is

suboptimal in that all systemic AEs were considered non-device or non-procedure related, which may or may not be the
case. AE rates should be interpreted accordingly.

▪ Data on neurologic outcomes is incomplete in that relatedness to the device and procedure could not be determined and

should be interpreted accordingly.