Medtronic 6982246 Instructions for Use

Page 1

PRESTIGE™ CERVICAL DISC

Implant package contents (superior and inferior disc components, bone screws, lock screws) provided sterile. Instrument set contents provided non-sterile.

2017-02-15

0381252E Rev. C

IMPORTANT INFORMATION ON THE PRESTIGE™ CERVICAL DISC

DESCRIPTION

The PRESTIGE™ Cervical Disc is a two-piece articulating metal-on-metal device that is inserted into the intervertebral disc space at a single cervical level using an anterior approach. The device is manufactured from wrought type 316 stainless steel (ASTM F-138) and consists of two metal plates which function via a ball and trough mechanism. The superior component of the implant contains the ball portion of the mechanism, and the inferior component incorporates the trough portion. The flat portion of each component, which contacts the vertebral endplate, is roughened through a grit blasting process.

Each component is affixed to the vertebral body by two bone screws through an anterior flange. The bone screws are held in place by a lock screw mechanism. In the implanted disc, the bone screws are divergent in the cephalic/caudal direction and convergent in the medial/lateral direction.

The device assembly was designed to allow the following motions ex-vivo: a minimum of 10° motion off the neutral position in flexion/extension and lateral bending, unconstrained axial rotation, and 2 mm of anterior/posterior translation.

The available components are shown in the table below.

Table 1: PRESTIGE™ Cervical Disc Device Configurations

Catalog Number Component Description

6961260 6 mm x 12 mm Disc Assembly 6961460 6 mm x 14 mm Disc Assembly 6961660 6 mm x 16 mm Disc Assembly 6961270 7 mm x 12 mm Disc Assembly 6961470 7 mm x 14 mm Disc Assembly 6961670 7 mm x 16 mm Disc Assembly 6961870 7 mm x 18 mm Disc Assembly 6961480 8 mm x 14 mm Disc Assembly 6961680 8 mm x 16 mm Disc Assembly 6961880 8 mm x 18 mm Disc Assembly 6960013/6961340* Self-Tap Bone Screw 4.0 mm x 13 mm 6960015/6961540* Self-Tap Bone Screw 4.0 mm x 15 mm 6960113/6961345* Self-Tap Bone Screw 4.5 mm x 13 mm 6960115/6961545* Self-Tap Bone Screw 4.5 mm x 15 mm 6960120/6961120* Lock Screw

* Catalog number for screws in implant box / catalog number for separately packaged extra screws, if needed. Implied warranties of merchantability and fitness for a particular purpose or use are specifically excluded. See the MDT Catalog

or price list for further information about warranties and limitations of liability.

Page 2

INDICATIONS

The PRESTIGE™ Cervical Disc is indicated in skeletally mature patients for reconstruction of the disc at one level from C3-C7 following single-level discectomy for intractable radiculopathy (arm pain and/or a neurological deficit) with or without neck pain, or myelopathy due to a single-level abnormality localized to the disc space and at least one of the following conditions confirmed by radiographic imaging (CT, MRI, X- rays): herniated nucleus pulposus and/or osteophyte formation. The PRESTIGE™ device is implanted via an open anterior approach. Patients should have failed at least 6 weeks of conservative treatment prior to implantation of the PRESTIGE™ Cervical Disc.

CONTRAINDICATIONS

The PRESTIGE™ Cervical Disc should not be implanted in patients with an active infection or with an allergy to stainless steel.

WARNINGS

The PRESTIGE™ Cervical Disc should only be used by surgeons who are experienced in the surgical procedure and have undergone adequate training with this device. 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 great 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:

▪ More than one cervical level with DDD; ▪ Not skeletally mature; ▪ Clinically significant cervical instability; ▪ Prior fusion at adjacent cervical level; ▪ Severe facet joint pathology of involved vertebral bodies; ▪ Prior surgery at treated level; ▪ Osteopenia, osteomalacia, or osteoporosis as defined by bone mineral density T-score of -3.5, or -2.5 with vertebral crush

fracture;

▪ Spinal metastases; ▪ 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; and ▪ Severe insulin dependent diabetes.

In addition, safety and effectiveness of the device has not been established in patients who have not undergone at least six weeks of 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 (especially those devices with metal-on-metal articulating surfaces). The long term effect of these ions on the body is not known.

Wear rates higher than those predicted based on bench testing have been observed during in vivo wear analyses of several explanted PRESTIGE™ Cervical Disc devices. In addition, there has been evidence of metallosis accompanied by a chronic macrophage-dominated inflammatory response in subjects who have had the device removed. While there has been no direct causal association between the wear-related findings and implant loosening/osteolysis, device failure or overall clinical outcomes, high wear and associated metallosis and chronic inflammation are potential precursors of longer-term failure.

PRE-OPERATIVE

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; and 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.

Correct selection of the appropriate implant size is extremely important to assure the placement and function of the disc. See the surgical technique manual for step-by-step instructions.

INTRA-OPERATIVE

Use aseptic technique when removing the PRESTIGE™ Cervical Disc Replacement components from the innermost packaging. Use care when handling a PRESTIGE™ component to ensure that it does not come in contact with objects that could damage

the implant. Exercise care to ensure that implantation instruments do not contact the highly polished articulating surfaces of the endplates. Damaged implants are no longer functionally reliable.

To prevent unnecessary damage to the bearing surfaces, ensure that tissue debris is not trapped within the assembly. PRESTIGE™ Cervical Disc Replacement components should not be used with components or instruments of spinal systems

from other manufacturers. See the surgical technique manual for step-by-step instructions. 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.

Page 3

POST-OPERATIVE

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

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, including the avoidance of heavy lifting, repetitive bending, and high-impact exercise or athletic activity for 60 days postoperative.

POTENTIAL ADVERSE EVENTS

Risks associated with the use of the PRESTIGE™ Cervical Disc include: 1) those commonly associated with any surgery; 2) those specifically associated with cervical spinal surgery using an anterior approach; and 3) those associated with a spinal implant, as well as those pertaining to the PRESTIGE™ Cervical Disc. However, the causality of these adverse events is not exclusive to these 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 may have been previously reported in the adverse events table.

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; 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 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 PRESTIGE™ 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; cessation of bone growth of the operated portion of the spine; 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 or other types of urological system compromise; gastrointestinal and/or reproductive system compromise; 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: For the specific adverse events that occurred in the clinical study of the PRESTIGE™ Cervical Disc, please see

Safety Results in the CLINICAL STUDIES section below. 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 PRESTIGE™ Cervical Disc was conducted in the United States comparing the anterior spinal use of the PRESTIGE™ device to fusion using allograft and plating stabilization, the control, in the treatment of patients with symptomatic degenerative disc disease for an Investigational Device Exemption (IDE) (G010188). A total of 541 patients were enrolled in the clinical trial: 276 patients in the investigational PRESTIGE™ device treatment group and 265 patients in the control arm. Fifty-nine additional continued access patients also received the investigational treatment. Twenty-five of the continued access patients were simultaneously enrolled into a Metal Ion cohort, and had blood collected for metal ion analysis at each follow-up time point.

A Post-Approval Study required as a condition of PMA approval was also conducted to follow the original IDE subject cohort through 84 months postoperatively.

Page 4

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 PRESTIGE™ Cervical Disc treatment is statistically non-inferior to, the overall success rate of the control treatment at 24 months following surgery as determined by a prespecified non-inferiority margin of 0.10. 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.

PAS Study

The primary objective of the post-approval study was to demonstrate that the overall success rate for the investigational PRESTIGE™ Cervical Disc treatment is statistically non-inferior to the overall success rate of the control treatment at 84 months following surgery, as determined by a pre-specified non-inferiority margin of 0.10. 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 84 months following surgery.

Study Designs

IDE Study

The IDE study was a multi-center, prospective, randomized, controlled clinical trial comparing the investigational PRESTIGE™ 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).

PAS 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 36 months (3 years), 60 months (5 years), and 84 months (7 years) postoperative to determine the long-term safety and effectiveness of the device.

Inclusion and Exclusion Criteria

Patient eligibility criteria were defined in the original IDE clinical study protocol. No exclusion of any patient was planned for the post-approval study. As defined in the IDE study protocol, prospective patients were diagnosed with symptomatic cervical degenerative disc disease according to the following inclusion/exclusion criteria. Patients were geographically stable and were able to attend follow-up examinations at the investigational site. In addition, all patients agreed to undergo the necessary preoperative and postoperative evaluations specified in the Clinical Investigational Plan (CIP).

Inclusion Criteria:

All patients participating in this study were required to meet all of the following inclusion criteria:

1. Cervical degenerative disc disease defined as: intractable radiculopathy and/or myelopathy with at least one of the following characteristics and producing symptomatic nerve root and/or spinal cord compression as documented by patient history {e.g., pain [neck and/or arm pain], functional deficit and/or neurological deficit, and radiographic studies (e.g., CT, MRI, xrays, etc.)}:

a) herniated disc

b) osteophyte formation

2. One cervical level requiring surgical treatment;

3. C3-C4 disc to C6-C7 disc level of involvement;

4. Unresponsive to non-operative treatment for approximately six weeks or has the presence of progressive symptoms or

signs of nerve root/spinal cord compression in the face of continued non-operative management;

5. No previous surgical intervention at the involved level or any subsequent, planned/staged surgical procedure at the involved or adjacent level(s);

6. At least 18 years of age at the time of surgery;

7. Preoperative Neck Disability Index score ≥ 30;

8. Preoperative neck pain score of > 20 (based on the Preoperative Neck and Arm Pain Questionnaire);

9. Not pregnant at the time of surgery;

10. Willing to comply with the study plan and sign the Patient Informed Consent Form.

Exclusion Criteria:

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

1. Cervical spinal condition other than symptomatic cervical disc disease requiring surgical treatment at the involved level;

2. Documented or diagnosed cervical instability defined by dynamic (flexion/extension) radiographs showing:

a) Sagittal plane translation > 3.5 mm or;

b) Sagittal plane angulation > 20°;

Page 5

3. More than one cervical level requiring surgical treatment;

4. Fused level adjacent to the level to be treated;

5. Severe pathology of the facet joints of the involved vertebral bodies;

6. Previous surgical intervention at the involved level;

7. Previously diagnosed with osteopenia or osteomalacia;

8. Any of the following that may be associated with a diagnosis of osteoporosis (if any of the below risk factors were present, a

DEXA Scan was required to determine eligibility, with a measured BMD of -3.5, or 2.5 with vertebral crush fracture, considered a criteria for exclusion):

a) Postmenopausal non-black female over 60 years of age who weighs less than 140 pounds.

b) Postmenopausal female that has sustained a non-traumatic hip, spine, or wrist fracture.

c) Male over the age of 70.

d) Male over the age of 60 that has sustained a non-traumatic hip or spine fracture.

9. Presence of spinal metastases;

10. Overt or active bacterial infection, either local or systemic;

11. Severe insulin dependent diabetes;

12. Chronic or acute renal failure or prior history of renal disease;

13. Fever (temperature > 101° F oral) at the time of surgery;

14. Documented allergy or intolerance to stainless steel, titanium, or a titanium alloy;

15. Mental incompetence. (If questionable, psychiatric consult was obtained);

16. Incarceration;

17. Pregnancy;

18. Alcohol and/or drug abuse, as defined by currently undergoing treatment for alcohol and/or drug abuse;

19. Use of drugs (e.g., steroids or methotrexate) which may interfere with bone metabolism within two weeks prior to the

planned date of spinal surgery (excluding routine perioperative anti-inflammatory drugs;

20. History of an endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget’s Disease, renal osteodystrophy, Ehlers-Danlos Syndrome, or osteogenesis imperfecta);

21. Condition that requires postoperative medications that interfere with the stability of the implant or fusion, such as steroids. (Excluding low dose aspirin for prophylactic anticoagulation and routine perioperative anti-inflammatory drugs);

22. Treatment with an Investigational therapy within 28 days prior to implantation surgery, or plans for such treatment earlier than 16 weeks following the study treatment.

Study Population

The studies included 541 enrolled IDE, continued access and metal ion study subjects who were at least 18 years old at the time of the surgery and met the study inclusion and exclusion criteria.

Post-Operative Care

The recommended post-operative care included avoidance of heavy lifting, repetitive bending, and high-impact exercise or athletic activity for 60 days postoperatively. Avoidance of prolonged NSAID use (beyond 2 weeks postop) was also specified in the postoperative regimen, although the use of NSAIDs was recommended for the first two weeks postoperatively. The use of electrical bone growth stimulators was prohibited during the 24-month follow-up period. Patients who smoked were also encouraged to discontinue smoking.

IDE and PAS Follow-up Schedules

For the IDE study, patients were evaluated preoperatively (within 6 months of surgery), intraoperatively, and postoperatively at 6 weeks, 3, 6, 12, and 24 months. For the PAS study, patients were evaluated at 36, 60, and 84 months. At each evaluation time point, the primary and secondary clinical and radiographic outcome parameters were evaluated as shown in Table 2. 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 84 months.

Page 6

Table 2: Schedule of Study Assessments

Evaluation Pre-op Surgery/ Hospital Discharge 6 wks

Preoperative Information

Obtain Screening Form X

Confirm Patient Eligibility X

Obtain Informed Consent X

Open Randomization Envelope X

Case Report Forms

Patient Enrollment X

Patient Qualification X

Preoperative Data X

Prior History Questionnaire X

Neurological Status X X X X X X X X X

Preoperative Gait Assessment and Foraminal Compression Test X

Preoperative Patient Survey X

Preoperative Neck Disability Index X

Preoperative Neck and Arm Pain Questionnaire X

Health Status Questionnaire (SF-36) X X X X X

Radiologic Data X X X X X X X X X X

Surgery Data X

Hospital Discharge X

Postoperative Data X X XXX

Postoperative Patient Survey X X XXXXXX

Neck Disability Index X X XXXXXX

Postoperative Neck and Arm Pain Questionnaire X X X X X X X X

Postoperative Gait Assessment and Foraminal Compression Test X X X X X X X X

Adverse Event Form (if any) X X X X X X X X X

Patient Accountability (if needed) X X X X X X X X

Outstanding (Unresolved) Adverse Event (if any) X X X X X X X X X

Imaging

Radiographs and Scans

Anterior/Posterior X-ray X X X X X X X X X X

Lateral X-ray X X X XXXXXXX

Right/Left Lateral Bend X-rays X X X X X X X X X

Flexion/Extension X-rays X X X X X X X X X

CT and/or MRI X

DEXA Scan X

IDE Study Post-approval Study

(± 2wks)

3 Mo

(± 2wks)

6 Mo

(± 1 Mo)

12 Mo

(± 2 Mo)

24 Mo

(± 2 Mo)

36 Mo

(± 3 Mo)

60 Mo

(± 3 Mo)

84 Mo

(± 3 Mo)

Data Source

New data collection

IDE and PAS Study Endpoints

The primary endpoint for both the IDE and post-approval studies was a composite variable termed “overall success” which included key safety and effectiveness considerations. The effectiveness component of the overall success variable was comprised of both Neck Disability Index (NDI) and disc height success as measured by Functional Spinal Unit (FSU) height. The safety components of the overall success variable were neurological status success, absence of a serious implant- or implant/surgical procedure-associated adverse event or a second surgery that is classified as a “failure”. The combined effectiveness and safety component determined whether a patient was an overall success. An alternate overall success determination was also evaluated without disc height success. Overall success was determined at the 24-month time point for the IDE and the 84-month time point for the post-approval study.

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

Strengths and Limitations of the Clinical Study Design

The following are important study design strengths of the IDE study as well as the post-approval study:

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

randomized, controlled clinical trial.

▪ The consistency of data gathering approaches and endpoints was maintained through both the IDE and the PAS 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 following potential study design limitations should also be considered when interpreting the results of the IDE study as well as the post-approval study:

▪ Although overall success (without FSU) data was available for 89% of all subjects at 24 months, due to the long-term nature

of the IDE and the post-approval studies, progressive lower follow-up rates at each subsequent follow-up visit through 84 months were anticipated, which may affect interpretation of long-term study results.

▪ Several of the primary and secondary study endpoints are subjective (e.g., NDI, pain scores, SF-36), and this subjectivity

may present biases.

Page 7

▪ Both the investigator and the patient were blinded to the randomized treatment throughout the screening and informed

consent process; however, the patient and surgeon were not blinded following the assignment of treatment group by the sponsor. Like other clinical studies appraising artificial cervical disc devices, it was unfeasible to mask subjects to their treatment assignment. This was well-adjusted by integrating result measures judged by both the surgeon and core laboratories.

▪ The capability to evaluate device performance for individual segments of the subject population is limited. This limitation is

mainly because the study was not designed to assess performance among subgroups. Any subgroup analyses should be evaluated with caution.

SUMMARY OF THE IDE AND POST-APPROVAL STUDY RESULTS

Subject Accountability

The subject accountability data for the patients enrolled IDE and post-approval studies covering 34 sites are summarized in

Table 3.

Table 3: Subject Accountability

IDE Study Post Approval Study

6 Mo

(± 1 Mo)

(86.2%)

(66.2%)

224

172

(± 2 Mo)

263

(95.6%)

204

(74.2%)

12 Mo

223

(87.1%)

172

(67.2%)

(± 2 Mo)

251

(91.3%)

189

(68.7%)

24 Mo

220

(86.6%)

169

(66.5%)

(± 3 Mo)

198

(72.0%)

150

(54.5%)

36 Mo

160

(63.2%)

124

(49.0%)

(± 3 Mo)

220

(81.8%)

167

(62.1%)

60 Mo

188

(76.1%)

138

(55.9%)

(± 3 Mo)

212

(78.8%)

168

(62.5%)

84 Mo

Variable Inv Ctrl Inv Ctrl Inv Ctrl Inv Ctrl Inv Ctrl Inv Ctrl Inv Ctrl

Total Enrolled Patients 276 265 276 265 276 265 276 265 276 265 276 265 276 265

Cumulative Withdrawn(s) After Surgery 0214171919513514

Cumulative Deaths 01010202032525

Theoretical Follow-up

Patients Evaluated Early

Patients Not Yet Over due

Expected

Evaluable for Overall Success without FSU (% of Total Expected) 254

Evaluable for Overall Success with FSU (% of Total Expected) 197

276 262 275 260 275 256 275 254 275 253 269 247 269 246

(92.0%)

(71.4%)

3 Mo

(± 2wks)

00000000000000

239

181

256

(93.1%)

196

(71.3%)

(91.2%)

(69.1%)

182

(74.0%)

135

(54.9%)

______________________________________________________________

Theoretical=Enrolled- Cumulative Deaths - Cumulative Withdrawn After Surgery

Patients that completed follow-up visits early in the visit window.

Number of patients who did not have evaluation on or before 08 Oct 2012 but were within the window.

Expected = Theoretical + Patients Evaluated Early for visit - Not Yet Overdue

Subject Demographics and Baseline Parameters

Table 4 summarizes the study patient demographics and baseline characteristics for the PRESTIGE™ Investigational and

control groups. The demographics of the study population are consistent with the demographics reported for prior cervical artificial disc studies conducted in the U.S. The investigational and control treatment groups were very similar with regards to the demographics and baseline parameters, and there were no statistical differences (p<0.05) for any of the variables in Table 4 with the exception of alcohol use

Table 4: Study Patient Demographics and Baseline Characteristics

Variables Inv

(N=276)

Age (years) 43.3 ± 7.6 43.9 ± 8.8 0.435

Height (inches) 67.4 ± 3.9 67.5 ± 4.2 0.767

Weight (lbs.) 181.7 ± 39.7 184.7 ± 41.5 0.389

Sex (% male) 128/276 (46.4%) 122/265 (46.0%) 1.000

Race

Caucasian

Black

Asian

Hispanic

Other

260/276 (94.2%)

6/276 (2.2%) 1/276 (0.4%) 7/276 (2.5%) 2/276 (0.7%)

Marital Status

Single

Married

Divorced

Separated

Widowed

44/276 (15.9%)

188/276 (68.1%)

36/276 (13.0%)

5/276 (1.8%) 3/276 (1.1%)

Ctrl

(N=265)

243/265 (91.7%)

13/265 (4.9%)

2/265 (0.8%) 6/265 (2.3%) 1/265 (0.4%)

32/265 (12.0%)

204/265 (77.0%)

24/265 (9.1%)

3/265 (1.1%) 2/265 (0.8%)

p-value

0.448

0.240

Page 8

Table 4: Study Patient Demographics and Baseline Characteristics (continued)

Variables Inv

(N=276)

Education Level

< High School

High School

h School

> Hig

10/276 (3.6%)

73/276 (26.4%)

193/276 (69.9%)

Worker’s Compensation 32/276 (11.6%) 35/265 (13.2%) 0.603

Unresolved Spinal Litigation 30/276 (10.9%) 32/265 (12.1%) 0.687

Tobacco Used 95/276 (34.4%) 92/265 (34.7%) 1.000

Alcohol Used 120/276 (43.5%) 141/265 (53.2%) 0.025

Preoperative Work Status 182/276 (65.9%) 166/265 (62.6%) 0.473

Duration of Symptom

< 6 Weeks

6 Weeks to 6 Months

> 6

Months

21/276 (7.6%)

81/276 (29.3%)

174/276 (63.0%)

Previous Neck Surgery 1/276 (0.4%) 2/265 (0.8%) 0.617

Preoperative Medication use

Non-Narcotics

Weak Narcotics

Strong Narcotics

Muscle Relaxants

197/274 (71.9%) 130/275 (47.3%)

57/273 (20.9%)

119/274 (43.4%)

Preoperative Pain Status

Neither Arm or Neck Pain

Arm Pain Only

Neck Pain Only

Arm and Neck Pain

1/276 (0.4%) 1/276 (0.4%)

33/276 (12.0%)

241/276 (87.3%)

Baseline ROM Angulation 7.55 ± 4.25

Range: 0.43 - 24.85

Baseline ROM Translation 0.26 ± 0.26:

Range: 0.00 - 1.96

NDI 55.7 ± 14.8

Range: 6.0 – 94.0

SF-36 PCS 31.9 ± 7.0

Range: 15.3 – 51.7

SF-36 MCS 42.4 ± 12.1

Range: 16.3 – 65.3

Neck Pain Score 68.2 ± 22.7

Range: 2.0 – 100.0

Arm Pain Score 59.1 ± 29.4

Range: 0.0 – 100.0

Ctrl

(N=265)

14/265 (5.3%)

77/265 (29.2%)

173/265 (65.5%)

15/265 (5.7%)

89/265 (33.6%)

161/265 (60.8)

187/263 (71.1%) 127/263 (48.3%)

58/264 (22.0%)

114/264 (43.2%)

0/265 (0.0%) 0/265 (0.0%)

26/265 (9.8%)

238/265 (90.2%)

7.87 ± 4.32

Range: 0.74 – 21.34

0.26 ± 0.25

Range:0.00 – 1.64

56.4 ± 15.9

Range: 26.0 – 100.0

32.0 ± 7.5

Range: 7.9 – 56.0

42.7 ± 12.4

12.4

Range: 14.1 – 70.8

69.3 ± 21.5

Range: 20.0 – 100.0

62.4 ± 28.5

Rang

e: 0.0 – 100.0

p-value

0.458

0.435

0.849

0.863

0.833

1.000

0.491

0.446

0.989

0.632

0.760

0.795

0.553

0.191

Surgical and Hospitalization Information

Table 5 summarizes the information related to the surgical procedures and postoperative hospitalizations of subjects. The most

common treated surgical levels were C5-C6 and C6-C7. Table 6 summarizes device implanted by size and level. The mean operative time; mean estimated blood loss volume; and the hospitalization times were similar in both groups.

Table 5: Surgical Results

Inv Ctrl p

erative Time (hrs)

Mean ± SD 1.6 ± 0.6 1.4 ± 0.5 <0.001

EBL (ml)

Mean ± SD 60.1 ± 63.0 57.5 ± 68.1 0.635

Hospitalization (days)

Mean ± SD 1.1 ± 0.6 1.0 ± 0.5 0.041

Spinal level treated

(%) 7 (2.5) 10 (3.8)

3-4

(%) 14 (5.1) 15 (5.7)

4-5

- Value

0.041

Page 9

Table 5: Surgical Results (continued)

Inv Ctrl p

(%) 142 (51.4) 149 (56.2)

5-6

(%) 113 (40.9) 91 (34.3)

6-7

- Value

Table 6: All PRESTIGE™ Devices Implanted by Size and Level

Treated Level

C3-C4 C4-C5 C5-C6 C6-C7 Total by Implant Size

Implant Size combinations (Upper/Lower)

Upper: 6mm x 12mm Lower: 6mm x 12mm

Upper: 7mm x 12mm Lower: 7mm x 12mm

Upper: 7mm x 12mm Lower: 7mm x 14mm

Upper: 7mm x 14mm Lower: 7mm x 14mm

Upper: 8mm x 12mm Lower: 8mm x 12mm

Upper: 8mm x 14mm Lower: 8mm x 14mm

4 8 89 52 153/276 (55.4%)

0 3 23 16 42/276 (15.2%)

0 0 0 1 1/276 (0.4%)

2 2 20 30 54/276 (19.6%)

0 1 6 4 11/276 (4.0%)

1 0 4 10 15/276 (5.4%)

Total by Treated Level 7/276 (2.5%) 14/276 (5.1%) 142/276 (51.4%) 113/276 (40.9%) 276/276 (100.0%)

Safety Results

The safety of the PRESTIGE™ was assessed by monitoring intraoperative and postoperative complications. Radiographs were examined for evidence of device migration or breakage. Observations of subsidence were reported by investigators as adverse events. All radiographic endpoints were evaluated independently by a core laboratory.

Adverse Events

The adverse effects, as shown in Table 7 below, were reported from the 276 PRESTIGE™ device patients and 265 control patients enrolled in the multi-center clinical study. Adverse event rates presented are based on the number of patients having at least one occurrence for a particular adverse event divided by the total number of patients in that treatment group. Statistical comparison of the adverse events was conducted using time to event analysis respectively for the cumulative event rate for any adverse events up to 24-months visit and up to 84-months visit as shown in Table 8. The overall cumulative AE rate for events up to 24-months visit (89.2% in the investigational group versus 90.2% in the control group, p-value form log-rank test = 0.692) and up to 84-months visit (97.7% in the investigational group versus 94.5% in the control group, p-value form log-rank test =

0.958) are comparable between the two treatment groups. Additionally, Table 9 and 10, respectively summarize the adverse

events that are classified as device or device/surgical procedure related and the adverse events that are serious.

Page 10

Table 7: Adverse Events for US IDE5 and Post-Approval Studies

IDE PAS

6 Mo (≥5

Control

Mo-<9

Mo)

Invest

12 Mo (≥9

Control

Mo-<19

Mo)

Invest

Control

24 Mo

(≥19 Mo-

<30 Mo)

Invest

# of Patients Reporting &

Total adverse events

Inv #

Patients

(% of

276) Total # Events

Control

Complication

Surgery Post-

Invest

Control

operative

(1 day-<4

Wks)

Invest

Control

6 Wks

(≥4

Wks-<9

Wks)

Invest

Control

3 Mo (≥9

Wks-<5

Mo)

Invest

(≤ 24 Mo)

Patients

265) Total # Events

Ctrl #

(% of

36 Mo

(≥30 Mo-

<42 Mo)

Invest

Control

48 Mo

(≥42 Mo-

<54 Mo)

Invest

Control

60 Mo

(≥54 Mo-

<66 Mo)

Invest

Control

72 Mo

(≥66 Mo-

<78 Mo)

Invest

Control

84 Mo

(≥78

Mo-<90

Mo)

Invest

Control

# of Patients

Reporting &

Total adverse events

(≤ 84 Mo)

Inv #

Patients

(% of

276) Total # Events

Ctrl #

Patients

(% of

265) Total # Events

Anatomical/Tec hnical Difficulty

Cancer 00 0 100000030215 (1.8)52 (0.8)2211001610012 (4.3)145 (1.9)

Cardiovascular 00 2 2003 2 12112106 18 (6.5)2713 (4.9)14833556945439 (14.1)5731 (11.7)

Carpal Tunnel Syndrome

Death 00 0 0000 1 000 1 0 1 0 (0.0)03 (1.1)300220000002 (0.7)25 (1.9)

Dysphagia/ Dysphonia

Gastrointestinal 0 3 4 4 0 1 4 2 5 2 15 12 7 9 30 (10.9)3530 (11.3)339566166937556 (20.3)8251 (19.2)

Implant Displacement/ Loosening

Infection 2 0 7 3 1 5 6 1 4 2 11 8 6 9 32 (11.6)3724 (9.1)281171061121075762 (22.5)8441 (15.5)

Neck and/or Arm Pain

Neurological 4 1 9 10 10 5 13 11 15 5 23 19 10 21 68 (24.6)8460 (2

Non-Union 00 0 0020 2 030 2 0 0 0 (0.0)09 (3.4)900000000000 (0.0)09 (3.4)

Non-Union Pending

Other

Other Pain

Respiratory 1 0 1 2001 0 122 2 4 3 10 (3.6)108 (3.0)9136222441222 (8.0)2419 (7.2)

Spinal Event 0 1 3 416614366 9 81423 (8.3)2750 (18.9)54311518612956645 (16.3)5682 (30.9)

Subsidence 00 0 00000100000 1 (0.4)10 (0.0)000000000203 (1.1)30 (0.0)

Trauma 0 0 6 3 6 6 14 14 15 10 22 11 26 18 72 (26.1)8950 (18.9)6220 17 14 22 19 16 19 18 11 9 107 (38.8)

Urogenital 0 0 0 0013 2 237 2101 20 (7.2)228 (3.0)98 5 16 2 4 7 3 5 5 2 44 (15.9)5823 (8.7)

Vascular Intra-Op21 211000000010 5 (1.8)62 (0.8)210010000006 (2.2)73 (1.1)

Any Adverse Events

10 000000000000 1 (0.4)10 (0.0)000000000001 (0.4)10 (0.0)

00 10113100937418 (6.5)217 (2.6)9020131102124 (8.7)2712 (4.5)

561511131210110024 (8.7)2422 (8.3)23201224101029 (10.5)3126 (9.8)

00 010110000211 2 (0.7)25 (1.9)511002100106 (2.2)67 (2.6)

5 1 26 17 30 12 28 39 49 29 34 42 33 28 145 (52.5)

00 000001060707 0 (0.0)021 (7.9)2100000000010 (0.0)022 (8.3)

3 6 19 17 10 8 13 13 19 6 35 27 33 48 81 (29.3)

2 3 5 4 9 4 13 16 20 14 31 19 37 24 82 (29.7)

25 22 100 80 70 55 109 121 136 90 210 169 195 195 235 (85.1)

121 (45.7)

205

85 (32.1)

132

64 (24.2)8436 22 47 25 26 22 28 11 19 11 137 (49.6)

117

219 (82.6)

845

16 21 23 14 27 15 7 4 6 11 178 (64.5)

168

2.6)7212 8 5 12 14 13 6 4 11 11 99 (35.9)

34 21 34 19 43 38 13 31 17 10 137 (49.6)

125

164 127 173 137 180 146 125 97 99 80 259 (93.8)

732

284

132

273

172

1586

148 (55.8)

233

87 (32.8)

120

127 (47.9)

244

107 (40.4)

175

106

93 (35.1)

144

232 (87.5)

1319

______________________________________________________________

Based on 24-month cohort at time of interim analysis as pre-specified in IDE protocol.

Control=Single level anterior interbody fusion procedure with allograft and plate stabilization.

Other consists of various events that do not fit into another category, such as allergic reaction, depression, or insomnia.

Other Pain consists of non-neck and/or arm pain events such as headache, lower back pain, or leg pain.

Page 11

Table 8: Statistical Comparison of Adverse Events Rates using Time to Event Analysis

Treatments Number of Patients Cumulative Rate (%) P-Values

Inv

Anatomical/Technical Difficulty 1 0 0.4 0.0 0.327 0.327 1 0 0.4 0.0 0.327 0.327

Cancer 5 2 2.6 1.2 0.325 0.353 12 5 5.2 2.4 0.148 0.174

Cardiovascular 18 13 7.5 7.8 0.521 0.491 39 31 17.8 15.5 0.601 0.609

Carpal Tunnel Syndrome 18 7 8.9 3.7 0.049 0.050 24 12 10.6 6.0 0.076 0.072

Death 0 3 0.0 1.7 0.068 0.068 2 5 0.9 2.2 0.197 0.165

Dysphagia/ Dysphonia

Gastrointestinal 30 30 12.6 15.9 0.707 0.769 56 51 24.7 24.9 0.915 0.976

Implant Displacement/ Loosening

Infection 32 24 13.7 12.7 0.419 0.363 62 41 27.0 20.5 0.091 0.093

Neck and/or Arm Pain 145 121 58.3 53.6 0.156 0.094 178 148 70.2 64.8 0.094 0.070

Neurological 68 60 27.9 29.9 0.731 0.615 99 87 42.5 41.5 0.790 0.631

Non-Union 0 9 0.0 3.6 0.002 0.002 0 9 0.0 3.6 0.002 0.002

Non-Union - Pending 0 21 0.0 11.6 <0.001 <0.001 0 22 0.0 10.0 <0.001 <0.001

Other

Other Pain

Respiratory 10 8 5.2 4.5 0.788 0.795 22 19 9.7 10.1 0.897 0.841

Spinal Event 23 50 10.4 24.7 <0.001 <0.001 45 82 20.9 38.9 <0.001 <0.001

Subsidence 1 0 0.4 0.0 0.341 0.341 3 0 2.3 0.0 0.087 0.145

Trauma 72 50 32.4 25.0 0.102 0.118 107 93 44.9 44.9 0.688 0.445

Urogenital 20 8 10.4 3.7 0.045 0.053 44 23 20.1 12.2 0.024 0.018

Vascular Intra-Op 5 2 1.8 0.8 0.280 0.281 6 3 2.2 1.3 0.360 0.330

Any Adverse Events 235 219 89.2 90.2 0.692 0.708 259 232 97.7 94.5 0.958 0.722

(N=276)

24 22 8.7 8.4 0.916 0.929 29 26 11.5 10.5 0.868 0.935

2 5 1.1 2.5 0.200 0.190 6 7 3.1 3.1 0.623 0.449

81 85 34.3 42.9 0.359 0.475 137 127 57.2 57.1 0.637 0.639

82 64 37.4 31.0 0.305 0.373 137 107 58.7 50.1 0.081 0.134

Ctrl

(N=265)

Up to 24 Months Visit Up to 84 Months Visit

Inv

(N=276)

Ctrl

(N=265)

(Inv Vs Ctrl)

Log- Rank Wilcoxon Inv

Number of Patients Cumulative Rate (%) P-Values

(N=276)

Ctrl

(N=265)

Inv

(N=276)

Ctrl

(N=265)

(Inv Vs Ctrl)

Log- Rank Wilcoxon

Table 9: Adverse Events Classified as Device-Related or Device/Surgical Procedure-Related in US IDE5 and PostApproval Studies

Surgery Post-

Complication

Invest

Dysphagia/ Dysphonia

Implant Displacement/ Loosening

Neck and/or Arm Pain

Neurological 0 0 0 0 1010002000 4 (1.4)40 (0.0)00000000000 4 (1.4)40 (0.0)

Non-Union 0 0 0 0 0102030100 0 (0.0)07 (2.6)70000000000 0 (0.0)07 (2.6)

Non-UnionPending

Spinal Event 0 0 0 0 1000000000 1 (0.4)10 (0.0)00011201220 7 (2.5)73 (1.1)

Subsidence 0 0 0 0 0000100000 1 (0.4)10 (0.0)00000000000 1 (0.4)10 (0.0)

Trauma 0 0 0 0 00000010 00 1 (0.4)10 (0.0)00000000000 1 (0.4)10 (0.0)

Any Adverse Events

0 0 1 0 00000000 00 1 (0.4)10 (0.0)00000000000 1 (0.4)10 (0.0)

0 0 0 1 01100002 11 2 (0.7)25 (1.9)51100210010 6 (2.2)67 (2.6)

0 0 0 0 10001000 00 2 (0.7)20 (0.0)00000000000 2 (0.7)20 (0.0)

0 0 0 0 00010605 04 0 (0.0)016 (6.0)160000000001 0 (0.0)017 (6.4)

0 0 1 1 32232938 15 11 (4.0)1227 (10.2)281111411231 20 (7.2)2232 (12.1)

Control

operative (1 day-<4 Wks)

Invest

Control

6 Wks

(≥4 Wks-

<9 Wks)

Invest

Control

IDE PAS

3 Mo (≥9

Wks-<5

Invest

Mo)

(≥5 Mo-

<9 Mo)

Control

6 Mo

Invest

12 Mo

(≥9 Mo-

<19 Mo)

Control

Invest

24 Mo

Mo-<30

Control

# of Patients Reporting

(≥19

Total adverse events

Mo)

Patients

(% of 276)

Total # Events

Invest

Control

Inv #

(≤ 24 Mo)

(% of 265)

Ctrl #

Patients

Total # Events

36 Mo

(≥30

Mo-<42

Mo)

Invest

48 Mo

Mo-<54

Control

(≥42

Mo)

Invest

60 Mo

Mo-<66

Control

(≥54

Mo)

Invest

72 Mo

Mo-<78

Control

(≥66

Mo)

Invest

84 Mo

Mo-<90

Control

# of Patients Reporting

(≥78

Total adverse events

Mo)

Patients

(% of 276)

Total # Events

Invest

Control

Inv #

(≤ 84 Mo)

(% of 265)

Ctrl #

Patients

Total # Events

Page 12

Table 10: Adverse Events Classified as Serious Adverse Events in US IDE5 and Post-Approval Studies

IDE PAS

6 Mo (≥5

Mo-<9

Mo)

12 Mo (≥9

Mo-<19

Mo)

24 Mo

(≥19 Mo-

<30 Mo)

# of Patients Reporting &

Total adverse events

(≤ 24 Mo)

Ctrl #

(% of

276) Total # Events

192

Patients

(% of

Total # Events

102 (38.5)

Patients

Wks)

6 Wks (≥4

Wks-<9

Surgery Post-

Complication Inv

Cancer 00 0 10000002021 4 (1.4)42 (0.8)2211001610012 (4.3)135 (1.9)

Cardiovascular001 0 002001805113 (4.7)162 (0.8)2512332503024 (8.7)348 (3.0)

Carpal Tunnel Syndrome

Death 00 0 00001000101 0 (0.0)03 (1.1)30022000000 2 (0.7)25 (1.9)

Dysphagia/ Dysphonia

Gastrointestinal001 2 011111855514 (5.1)1614 (5.3)153252102531331 (11.2)4025 (9.4)

Implant Displacement/ Loosening

Infection 100 1 0101101315 4 (1.4)410 (3.8)11323241332216 (5.8)1918 (16.8)

Neck and/or Arm Pain

Neurological 10 1 2 1012006100 9 (3.3)105 (1.9)5010510102213 (4.7)1413 (4.9)

Non-Union 00 0 0 0202030100 0 (0.0)08 (3.0)80000000000 0 (0.0)08 (3.0)

Non-Union Pending

Other

Other Pain

Respiratory 10 0 00000001110 3 (1.1)31 (0.4)11031002100 9 (3.3)93 (1.1)

Spinal Event 000 2 133624452510 (3.6)1224 (9.1)25051600130010 (3.6)1435 (13.2)

Trauma 002 1 104622638320 (7.2)2313 (4.9)158566107896245 (16.3)6135 (13.2)

Urogenital 000 0 0010101151 8 (2.9)82 (0.8)26510004212124 (8.7)2812 (4.5)

Vascular Intra-Op20 0 100000000002 (0.07)21 (0.4)11000000000 3 (1.1)31 (0.4)

Any Adverse Events

00 1 0111000505110 (3.6)132 (0.8)2010130001114 (5.1)175 (1.9)

10 0 00000001000 2 (0.7)20 (0.0)00001100000 3 (1.1)31 (0.4)

00 0 00000000000 0 (0.0)00 (0.0)00000000010 1 (0.4)10 (0.0)

00 5 0733632463222 (8.0)2516 (6.0)19432110001028 (10.1)3320 (

00 0 00000000100 0 (0.0)01 (0.4)10000000000 0 (0.0)01 (0.4)

00 1 40144531047623 (8.3)2721 (7.9)2287781093104346 (16.7)5944 (16.6)

00 1 31022431059524 (8.7)2718 (6.8)2713 5 10 10 7 7 13 3 2 0 54 (19.6)7240 (15.1)

6 0 13 17 12 12 22 31 19 19 67 37 53 36 106 (38.4)

operative (1 day-<4

Inv Ctrl Inv Ctrl Inv Ctrl Inv Ctrl Inv Ctrl Inv Ctrl Inv #

Ctrl

Wks)

3 Mo (≥9

Wks-<5

Mo)

36 Mo (≥30 Mo<42 Mo)

InvCtrlInvCtrlInvCtrlInvCtrlInvCtrl Inv #

265)

54 38 52 48 50 33 49 34 25 14 160 (58.0)

152

48 Mo

(≥42 Mo-

<54 Mo)

60 Mo

(≥54 Mo-

<66 Mo)

72 Mo

(≥66 Mo-

<78 Mo)

84 Mo (≥78 Mo<90 Mo)

# of Patients Reporting &

Total adverse events

(≤ 84 Mo)

Ctrl #

(% of

276)

Total #

422

Patients

(% of

265)

Total #

Events

149 (56.2)

319

Patients

Events

7.5)

Table 11 provides summary data on the number of adverse events in each treatment group by treatment level, including posthoc statistical analysis and comparison between the PRESTIGE™ investigational group and control group through the 24month visit and 84-month visit for each level. The 95% confidence interval (CI) was derived using the normal approximation to the binomial distributions with standard error derived using Farrington and Manning Method.

Table 11: Summary of Total Adverse Events by Level Treated through 24 and 84 Months

Adverse Events Up to 24 Months Adverse Events# Up to 84 Months

Observed Event Rate Point Estimate and

Inv

(N=276)

Ctrl

(N=265)

95% Confidence

Limit*

(P(I) - P(C))

Any Adverse

Event

Observed Event Rate Point Estimate and

Inv

(N=276)

Ctrl

(N=265)

95% Confidence

Limit*

(P(I) - P(C))

C3-C4 7/7 (100.0%) 9/10 (90.0%) 0.100 [-0.127, 0.327] 7/7 (100.0%) 9/10 (90.0%) 0.100 [-0.127, 0.327] C4-C5 13/14 (92.9%) 12/15 (80.0%) 0.129 [-0.123, 0.380] 14/14 (100.0%) 12/15 (80.0%) 0.200 [-0.022, 0.422] C5-C6 127/142

(89.4%)

124/149 (83.2%)

0.062 [-0.017, 0.141] 139/142 (97.9%)

131/149

(87.9%)

0.100 [ 0.040, 0.159]

C6-C7 88/113 (77.9%) 74/91 (81.3%) -0.034 [-0.146, 0.077] 99/113 (87.6%) 80/91 (87.9%) -0.003 [-0.094, 0.088]

#Including all adverse events that happened during the IDE study and the PAS study. *Confidence Limits for the proportion difference are derived by using the Farrington-Manning method.

Table 12 lists the brief definition of each category of adverse events.

Page 13

Table 12: Adverse Event Categories

Adverse Event Category Definition

Anatomical/Technical Difficulty Intraoperative (or perioperative) difficulty due to the patient’s physical structure

or due to a technical problem during the study surgery. Cancer A malignancy or malignant tumor/neoplasm Cardiovascular (i.e. MI, Stroke) Any condition of the heart and heart related vessels with exception of injury

sustained during study surgery. Carpal Tunnel Syndrome Condition in which there is soreness, tenderness, and weakness of the muscles

of the thumb caused by pressure on the medial nerve at the point at which it

goes through the carpal tunnel of the wrist. Death Termination of life due to any cause. Dysphagia/Dysphonia Difficulty in swallowing or speaking; including hoarseness or voice disorders. Gastrointestinal Condition pertaining to the entire alimentary system including the mouth,

esophagus, stomach, small intestine, large intestine, rectum, and anus.

Conditions involving the liver, gall bladder, bile duct, and pancreas are also

included in this category. Implant Displacement/Loosening Incomplete or partial dislocation of the implant, wear around the implant,

loosening of the implant surface, or breakage of any implant or implant

component. Spinal Event Event involving diagnoses at one or more spine levels; usually confirmed via

radiologic findings. Infection An infection regardless of pathogen, which may or may not be confirmed by

culture or laboratory test. Neck and/or Arm Pain Pain involving the neck, arm, or neck and arm, such events may include

discomfort and spams in these regions, but does not include neurological

symptoms. Neurological Event that involves a feeling or awareness of condition within the body resulting

from stimulation of sensory receptors or involves stimulation of the motor

neurons that induce movements, as nerves or muscles. Non-Union Failure of the vertebral bodies to fuse at the treated level and more than likely

required surgical intervention. This applies to the control group only. Non-Union Outcome Pending Delay in the vertebral bodies to fuse at the treated level or fusion outcome

unknown. More than likely did not require surgical intervention. This applies to

the control group only. Other Event not associated with any other categories (e.g., weight loss, tinnitus,

substance abuse, insomnia). Other Pain Pain (including stiffness, strain, tightness) in an area that is not of the cervical

spine region. Respiratory Ailments or symptoms associated with respiration or the respiratory system. Subsidence Sinking or settling of the artificial disc into the vertebral body. Trauma Physical injury caused by a physical force or traumatic event (or damage

inflicted on the body as the direct result or indirect result of an external force

(e.g. motor vehicle accident, fall, etc.). Urogenital Event related to or affecting the organs or functions of excretion and

reproduction. Note: Urinary tract infections are captured under Infection. Vascular Injury Intra-OP Injury to a vascular structure that is sustained during the course of the operative

procedure; initial study surgery only.

Subsequent Surgical Interventions

Table 13 summarizes the secondary surgical interventions in the PRESTIGE™ and control treatment groups that occurred up to

the 24-month visit and up to 84-month visit. Revisions, removals, and supplemental fixations were considered second surgery failures in the clinical study. Table 13 also presents the statistical comparison of secondary surgeries between the PRESTIGE™ and control treatment groups. The rate of patients who had any secondary surgery at the target level were significantly less in the investigational group up to 24-month visit and up to 84-month visit. Similar trend was observed in the following categories: revisions and elective removal.

Page 14

Table 13: Secondary Surgical Procedures

Secondary Surgeries Up to 24 Months Secondary Surgeries Up to 84 Months

Treatment

Revisions 0 4 0.038 0.038 0 5 0.019 0.020

Removal 6 8 0.446 0.407 8 8 0.808 0.604

Removal - Elective 0 4 0.032 0.032 0 13 <0.001 <0.001

Supplemental Fixations 0 3 0.065 0.065 0 5 0.017 0.017

Re-operations 4 2 0.483 0.485 4 4 0.894 0.843

Total Patients Who Had Any Second Surgery at the Treated Level 9 19 0.025 0.022 11 29 <0.001 <0.001

Number of patients

Inv

(N=276)

Ctrl

(N=265)

P-Value

(Inv vs Ctrl)

Log-Rank Wilcoxon

Number of patients

Inv

(N=276)

(N=265)

Ctrl

P-Value

(Inv vs Ctrl)

Log-Rank Wilcoxon

Table 14: Secondary Surgical Interventions at the Index Level – Procedure Details

Days To

Index Level

Surgery

Time To

Index Level

Surgery

Group Cause/Adverse Event Action

Investigational Right shoulder pain / C5

radiculopathy

C4-C5 decompressive foraminotomy

Investigational Neck pain with headaches C6-C7 explant of PRESTIGE™

Secondary

Surgical

Intervention

Category

Re-Operation 57 6 Weeks

Removal 261 6 Months

Cervical Disc followed by ACDF

Investigational Left arm pain and

Cervical foraminotomy Re-Operation 289 12 Months paresthesia into forearm and hand; left cervical radiculopathy

Investigational Neck / shoulder arm pain /

decreased sensation in little finger

Investigational Radiating arm pain C5-C6 posterior foraminotomy,

C6-C7 explant of PRESTIGE™

Cervical Disc followed by C5-C7

ACDF

Removal 303 12 Months

Re-Operation 336 12 Months discectomy, and nerve root exploration

Investigational C8 radiculopathy C6-C7 explant of PRESTIGE™

Removal 438 12 Months

Cervical Disc followed by ACDF

Investigational Motor Vehicle Accident C5-C6 posterior cervical

Re-Operation 455 12 Months laminectomy

Investigational Radiating arm pain C5-C6 explant of PRESTIGE™

Removal 508 12 Months Cervical Disc followed by removal of osteophytes and C5-C6 segmental fixation

Investigational C6 nerve root blunting and

facet disease secondary to baseball injury

Investigational Left side radiculopathy C5-C6 explant of PRESTIGE™

C5-C6 explant of PRESTIGE™ Cervical Disc Followed by C5-C7 ACDF

Removal 786 24 Months

Removal 833 24 Months Cervical Disc

Investigational Numbness and tingling, left

arm; C4-C5, C6-C7 annular tears

Investigational Broken screws inferior to the

artificial disc in the C6 vertebral body

C5-C6 explant of PRESTIGE™ Cervical Disc followed by C4-C7 ACDF

C5-C6 explant of PRESTIGE™ Cervical Disc followed by anterior and posterior fusion

Removal 1095 36 Months

Removal 2564 84 Months

Control Residual foraminal stenosis Left foraminotomy Revision 2 1 day - <4

weeks Control Deltoid weakness, left C5 posterior foraminotomy Re-Operation 43 6 Weeks Control Esophageal abscess C5-C6 removal of cervical plate

Removal 63 3 Months and allograft, debridement of esophageal abscess, and esophageal fistula repair

Control HNP At C5-C6 C6-C7 removal of cervical plate

Revision 88 3 Months followed by C5-C7 ACDF with two level plate

Page 15

Table 14: Secondary Surgical Interventions at the Index Level – Procedure Details (continued)

Days To

Index Level

Surgery

Time To

Index Level

Surgery

Group Cause/Adverse Event Action

Control C7 pain and numbness C5-C7 fusion with allograft and

Secondary

Surgical

Intervention

Category

Revision 98 3 Months anterior plate

Control Adjacent level disc herniation C5-C7 discectomy and fusion Revision 140 3 Months Control Fusion has not yet fused Bone Growth Stimulator Supplemental

183 6 Months

Fixation - External

Bone Growth

Stimulator

Control Patient with continued neck

and arm pain

Bone Growth Stimulator Supplemental

Fixation - External

185 6 Months

Bone Growth

Stimulator

Control Pseudoarthrosis Bone Growth Stimulator Supplemental

207 6 Months

Fixation - External

Bone Growth

Stimulator

Control Neck pain, headaches and

dizziness

C5-C6 removal of cervical plate and allograft followed by graft,

Removal 241 6 Months

BMP, and plate

Control Posterior cervical region/

trapezius pain/spasm; bilateral arm pain

Control C7 pain and numbness Bone Growth Stimulator Supplemental

C5-C6 removal of cervical plate and allograft; ACDF with iliac crest and stem cells

Removal 272 6 Months

278 12 Months

Fixation - External

Bone Growth

Stimulator

Control Patient with continued neck

and arm pain

C5-C6 removal of cervical plate and allograft followed by C5-C6

Removal 284 12 Months

cervical fusion with graft, BMP and plate

Control Pseudoarthrosis C5-C6 removal of cervical plate

Removal 293 12 Months and allograft followed by cervical fusion with autograft and plate

Control C7 pain and numbness C5-C6 removal of cervical plate

Removal 326 12 Months followed by C5-C7 revision arthrodesis with graft and plate

Control Pseudoarthrosis External Bone Growth Stimulator Supplemental

352 12 Months

Fixation - External

Bone Growth

Stimulator

Control Neck and shoulder pain Bone Growth Stimulator Supplemental

372 12 Months

Fixation - External

Bone Growth

Stimulator

Control Neck pain with right posterior

scapular pain

Control Neck and shoulder pain C6-C7 removal of cervical plate

C6-C7 removal of cervical plate to facilitate a C5-C6 ACDF

Removal -

385 12 Months

Elective

Removal 399 12 Months and allograft followed by C4-C7 anterior cervical fusion with graft, BMP, and plate

Control Degenerative changes C6-

C7; C5-C6 lucency; remodeling at C5-C6

C5-C6 removal of cervical plate (elective) followed by C6-C7 cervical discectomy and fusion

Removal -

Elective

407 12 Months

anteriorly; facet inflammatory changes C5-C6; foraminal bony encroachments at C6C7 and C5-C6

Page 16

Table 14: Secondary Surgical Interventions at the Index Level – Procedure Details (continued)

Secondary

Group Cause/Adverse Event Action

Surgical

Intervention

Category

Control Chronic C6-C7

radiculopathy, C4-C5 mild

C5-C6 posterior cervical fusion with screws and rods

Supplemental

Fixation spondylosis, foraminal narrowing and left arm pain

Control Involuntary thumb/torso

movements

Control Neck pain, glenohumeral

joint, cervical spondylosis

C4, C5, C6, C7, and T1 cervical laminectomy

C5-C6 removal of anterior cervical plate; exploration of C5-C6 fusion;

Re-Operation 506 12 Months

Removal -

Elective

C6-C7 ACDF with C5-C7 instrumentation

Control C7 pain and numbness C5-C7 posterior fusion with plating Supplemental

Fixation

Control Pseudoarthrosis C5-C6 posterior lateral cervical

fusion

Control C6-C7 incomplete fusion;

neck pain with headaches

C6-C7 removal of cervical plate followed by C5-C6 ACDF

Control Lucency C5-C6 removal of cervical plate

Supplemental

Fixation

Removal -

Elective

Removal 840 24 Months followed by C5-C6 anterior cervical discectomy with allograft and plate

Control C6-C7 incomplete fusion;

neck pain with headaches

C5-C6, C6-C7 right foraminotomies with C6-C7 nerve root

Revision 1050 36 Months

decompression

Control Neck and shoulder pain C6-C7 posterior fusion with BMP

and posterior instrumentation

Control Neck pain radiating to right

shoulder/arm due to motor

C5-C6 removal of cervical plate followed by C6-C7 ACDF with plate

Supplemental

Fixation

Removal -

Elective vehicle accident, small right posterior osteophytes with cord edema at C6-C7, right HNP with moderate spinal stenosis

Control C6-C7 pseudoarthrosis;

resorption of graft

Control C6-C7 pseudoarthrosis;

resorption of graft

C6-C7 posterior fusion with BMP Supplemental

Fixation

Bone Growth Stimulator Supplemental

Fixation - External

Bone Growth

Stimulator

Control C6-C7 herniation, foramen

impingement, osteophyte compression

C5-C6 removal of cervical plate, C6-C7 anterior discectomy and osteophytectomy with anterior

Removal -

Elective

interbody fusion and plating

Control Neck and left arm pain C5-C6 removal of cervical plate,

C6-C7 foraminotomy with

Removal -

Elective

arthrodesis instrumentation

Control C3-C4 severe spondylitic

changes with bilateral

C5-C6 removal of cervical plate; C3-C4 and C4-C5 ACDF

Removal -

Elective spurring, left paracentral disc osteophytes complex, bilateral foraminal encroachment, and C4-C5 severe spondylitic changes

Control C4, C5, and C6 foraminal

stenosis; C5-C6 herniation

C6-C7 removal of cervical plate followed by C5-C6 discectomy with

Removal -

Elective

anterior plating

Control Degenerative changes at C5-

C6 with possible small disc

C5-C7 removal of cervical plate followed by C5-C6 ACDF with

Removal -

Elective

cervical plate

Days To

Index Level

Surgery

Time To

Index Level

Surgery

474 12 Months

513 12 Months

525 12 Months

613 24 Months

756 24 Months

1094 36 Months

1211 36 Months

1259 36 Months

1391 48 Months

1512 48 Months

1560 48 Months

1665 60 Months

1679 60 Months

1729 60 Months

Page 17

Table 14: Secondary Surgical Interventions at the Index Level – Procedure Details (continued)

Days To

Index Level

Surgery

1806 60 Months

2242 72 Months

2425 84 Months

Time To

Index Level

Surgery

Group Cause/Adverse Event Action

protrusion, osteophytes at C5-C6

Control Shallow protrusion and

hypertrophy at C3-C4, mild stenosis and protrusion at C5-C6, adjacent segment degeneration at C5-C6

Control C6-C7 spondylosis; C6-C7

disc bulge; C4 spondylosis

Control Osteophytosis and

arthropathy C5

Control Right C6 radiculopathy and

foraminal narrowing at C6-C7

Control Epidural abscess C5-C6 laminectomy with

Revision of cervical fusion Removal -

C5-C6 removal of cervical plate with placement of artificial cervical disc

C6-C7 removal of cervical plate and local bone followed by C5-C6 ACDF

C5-C6 anterolateral foraminotomy, right

evacuation of epidural abscess

Secondary

Surgical

Intervention

Category

Elective

Removal -

Elective

Removal -

Elective

Re-Operation 2486 84 Months

Re-Operation 2514 84 Months

Explant Analysis Findings

The histology analysis of the peri-prosthetic tissue demonstrated metallosis, metallic debris, and corrosion products with an attendant mild to moderate chronic inflammatory host response. However, none of the tissue samples from any of the accessions showed histologic evidence of muscle attachment destruction, nerve damage, bone resorption, osteolysis, eryptosis, pseudo-tumors, or lymphocytic masses.

Metal Ion Analysis

Implanted metal alloys release metallic ions into the body (especially those devices with metal-on-metal articulating surfaces). In a prospective, longitudinal study of 25 subjects examining serum chromium (Cr) and nickel (Ni) concentrations in subjects implanted with PRESTIGE™ Cervical Disc, the median Cr and Ni concentrations observed at pre-op were 0.07 ng/mL Cr and

0.09 ng/mL Ni and at 84 months were 0.20 ng/mL and 0.19 ng/mL, respectively. The maximum concentrations observed in these patients was <2.0 ng/ml for chromium and <1.1 ng/ml for nickel. A review of adverse events for subjects implanted with the PRESTIGE™ Cervical Disc did not reveal any signs or symptoms suggestive of systemic metal toxicity.

Neurological Status

Table 15 below shows the distributions of patients in the two treatment groups whose postoperative neurological condition was

either maintained or improved for the three functions assessed (i.e., motor function, sensory function, and reflexes). The overall neurological success rates were high for both groups. The overall neurological success rates at all postoperative time periods are greater than or equal to 88.2% for investigational group and greater than or equal to 79.7% in the control group, which are the neurological success rates that were observed at 84 months postoperatively. Similar results were observed at all postoperative time points. Non-inferiority of the investigational group was achieved for overall neurological success at all time-points including 24-month visit and 84-month. Superiority of the investigation group was achieved for overall neurological success in six of the eight established time points (3, 12, 24, 36, 60 and 84 months, with the exception of six weeks and six months).

Table 15: Summary of Success Rates of Neurological Status

value

ime Point Variable Inv

(N= 276)

6 weeks Motor 264 (96.7%) 242 (95.3%) <0.001 0.201

Sensory 257 (94.1%) 239 (94.1%) <0.001 0.491

Reflexes 265 (97.4%) 240 (94.5%) <0.001 0.043

Overall 245 (90.1%) 222 (87.4%) <0.001 0.166

3 Months Motor 249 (97.3%) 232 (96.3%) <0.001 0.264

Sensory 240 (93.8%) 223 (92.5%) <0.001 0.295

Reflexes 250 (98.0%) 229 (95.0%) <0.001 0.032

Overall 235 (91.8%) 210 (87.1%) <0.001 0.045

6 Months Motor 251 (97.7%) 222 (97.4%) <0.001 0.417

Sensory 245 (95.3%) 215 (94.3%) <0.001 0.304

Reflexes 250 (97.3%) 221 (96.9%) <0.001 0.410

Ctrl

(N= 265)

Non-inferiority

(d=0.1)

Superiority

Page 18

Table 15: Summary of Success Rates of Neurological Status (continued)

value

ime Point Variable Inv

(N= 276)

Overall 238 (92.6%) 205 (89.9%) <0.001 0.146

12 Months Motor 262 (99.2%) 216 (95.6%) <0.001 0.004

Sensory 249 (94.3%) 203 (89.8%) <0.001 0.032

Reflexes 259 (98.1%) 215 (95.1%) <0.001 0.032

Overall 245 (92.8%) 194 (85.8%) <0.001 0.006

24 Months Motor 244 (97.2%) 209 (95.0%) <0.001 0.106

Sensory 237 (94.4%) 195 (88.6%) <0.001 0.012

Reflexes 246 (98.0%) 209 (95.0%) <0.001 0.036

Overall 230 (91.6%) 184 (83.6%) <0.001 0.004

36 Months Motor 194 (98.5%) 151 (93.8%) <0.001 0.009

Sensory 189 (95.9%) 139 (86.3%) <0.001 <0.001

Reflexes 190 (96.4%) 153 (95.0%) <0.001 0.253

Overall 182 (92.4%) 134 (83.2%) <0.001 0.004

60 Months Motor 217 (99.1%) 185 (97.9%) <0.001 0.157

Sensory 210 (95.9%) 171 (90.5%) <0.001 0.014

Reflexes 210 (95.9%) 175 (92.6%) <0.001 0.075

Overall 202 (92.2%) 162 (85.7%) <0.001 0.017

84 Months Motor 205 (97.2%) 174 (95.6%) <0.001 0.204

Sensory 195 (92.4%) 158 (86.8%) <0.001 0.033

Reflexes 201 (95.3%) 163 (89.6%) <0.001 0.016

Overall 186 (88.2%) 145 (79.7%) <0.001 0.011

Ctrl

(N= 265)

Non-inferiority

(d=0.1)

Superiority

Effectiveness Results

Primary Effectiveness Analysis

The primary endpoint was determined at 24 months (for the IDE) and 84 months (for the PAS) as a composite of the following parameters: pain and functional disability, neurological status, adverse events, secondary surgical interventions, and a radiographic spinal unit height determination. This was termed overall success.

Individual subject success (i.e. overall success) was defined as attainment of all of the following:

1. An improvement of at least 15 points from the baseline Neck Disability Index (NDI) score;

2. Maintenance or improvement in neurological status;

3. No serious adverse event classified as implant-associated or implant/surgical procedure-associated;

4. No additional surgical procedure classified as “Failure”; and

5. Functional spinal unit (FSU) height maintenance. FSU height was considered maintained if it did not decrease more than 2

mm after 6 weeks following surgery.

Because of difficulty in evaluating FSU, due to anatomical interference with the radiographic image, an alternative overall success determination was made based on the above criteria without the addition of functional spinal unit (FSU) height maintenance.

Overall Success Summary

Table 16 below presents the observed success rates for each group and the p-values of the non-inferiority and superiority of the

investigational group over the control group for individual outcome parameters and overall success at 24-month visit and 84month visit. The p-value values were calculated using the z-test of the normal approximation to the binomial distributions with the standard error derived using Farrington and Manning Method. Non-inferiority of the PRESTIGE™ group to the control group was demonstrated for all endpoints listed in Table 16 at both 24 and 84 months. Statistical superiority of the PRESTIGE™ group to the control group was also demonstrated for overall success (both with and without the FSU height component) and the neurological variable at both 24 and 84 months. The NDI and FSU components were not found to be statistically superior in the PRESTIGE™ group at the 24 month or 84 month time points.

Page 19

Table 16: Statistical Comparison of Overall Success and Its Components

24 Months 84 Months

Inv Ctrl P-Value Inv Ctrl P-Value

Primary

Outcome

Variable

Observed

Rate (95%

Confidence

Interval)

NDI Success 82.2%

(76.9%,

86.7%)

Neurological Success

91.6%

(87.5%,

94.8%)

FSU Height Success

97.4%

(94.0%,

99.1%)

Overall Success (without FSU)

Overall Success (with FSU)

77.7%

(72.0%,

82.7%)

77.8%

(71.2%,

83.5%)

Observed

Rate

(95%

Confidence

Interval)

80.8%

(75.0%,

85.8%)

83.6%

(78.1%,

88.3%)

95.1%

(90.6%,

97.9%)

67.7%

(61.1%,

73.9%)

63.9%

(56.2%,

71.1%)

Observed

Non-

Inferiority

Superiority

Rate

(95%

Confidence

Interval)

< 0.001 0.349 84.8%

(79.3%,

89.4%)

< 0.001 0.004 88.2%

(83.0%,

92.2%)

< 0.001 0.131 95.8%

(91.5%,

98.3%)

< 0.001 0.008 75.0%

(68.6%,

80.7%)

< 0.001 0.002 72.6%

(65.2%,

.2%)

Observed

Rate (95%

Confidence

Interval)

80.1%

(73.5%,

85.7%)

79.7%

(73.1%,

85.3%)

96.9%

(92.1%,

99.1%)

63.7%

(56.3%,

70.7%)

60.0%

(51.2%,

68.3%)

The number of patients with primary outcome variable data at 24 and 84 months are listed in Table 17.

Non-

Inferiority

Superiority

< 0.001 0.109

< 0.001 0.011

< 0.001 0.683

< 0.001 0.008

< 0.001 0.010

Table 17: Patient Data Available for Overall Success and Its Components

24 Months 84 Months

Primary Outcome Variable

Inv Ctrl Inv Ctrl

NDI 253 219 211 181 Neurological 251 220 211 162 FSU Height 190 164 166 127 Overall Success (without FSU)* 251 220 212 182 Overall Success (with FSU)* 189 169 168 135

*If a patient failed based on either a second surgery or serious, possibly implant- or implant/surgical procedure-associated adverse event, the patient was counted as an Overall Success failure and included in the analysis, regardless of whether or not they had the FSU measurement, NDI score, or neurological

outcome.

A time course of overall success for both treatment groups is shown in Table 18.

Table 18: Time Course of Observed Success Rates

Variables Cohort 3 Mo 6 Mo 12 Mo 24 Mo 36 Mo 60 Mo 84 Mo

NDI Inv (N=276) 219/253

Ctrl (N=265) 174/235

Neurological Inv (N=276) 235/256

Ctrl (N=265) 210/241

FSU Height Inv (N=276) 200/200

Ctrl (N=265) 182/182

Overall Success (without FSU)*

Overall Success (with FSU)*

Inv (N=276) 207/254

Ctrl (N=265) 154/239

Inv (N=276) 163/197

Ctrl (N=265) 113/181

(86.6%)

(74.0%)

(91.8%)

(87.1%)

(100.0%)

(81.5%)

(64.4%)

(82.7%)

(62.4%)

IDE PAS

210/257 (81.7%)

173/224 (77.2%)

238/257 (92.6%)

205/228 (89.9%)

199/200 (99.5%)

174/175 (99.4%)

197/256 (77.0%)

159/224 (71.0%)

150/196 (76.5%)

119/172 (69.2%)

217/263 (82.5%)

176/222 (79.3%)

245/264 (92.8%)

194/226 (85.8%)

202/205 (98.5%)

164/172 (95.3%)

204/263 (77.6%)

151/223 (67.7%)

157/204 (77.0%)

110/172 (64.0%)

208/253 (82.2%)

177/219 (80.8%)

230/251 (91.6%)

184/220 (83.6%)

185/190 (97.4%)

156/164 (95.1%)

195/251 (77.7%)

149/220 (67.7%)

147/189 (77.8%)

108/169 (63.9%)

163/197

(82.7%)

127/159

(79.9%)

182/197

(92.4%)

134/161

(83.2%)

143/148

(96.6%)

118/120

(98.3%)

154/198

(77.8%)

105/160

(65.6%)

114/150

(76.0%)

81/124

(65.3%)

187/219 (85.4%)

156/187 (83.4%)

202/219 (92.2%)

162/189 (85.7%)

153/165 (92.7%)

128/134 (95.5%)

172/220 (78.2%)

135/188 (71.8%)

119/167 (71.3%)

90/138

(65.2%)

179/211 (84.8%)

145/181 (80.1%)

186/211 (88.2%)

145/182 (79.7%)

159/166 (95.8%)

123/127 (96.9%)

159/212 (75.0%)

116/182 (63.7%)

122/168 (72.6%)

81/135

(60.0%)

Table 19 provides overall success for both treatment groups stratified by the treated level including post-hoc statistical analysis and comparisons between the groups for each level.

Page 20

Table 19: Overall Success by Treated Level

24 Months 84 Months

Observed Rate

(95% Confidence

Interval)

50.0%

(15.7%, 84.3%)

80.0%

(28.4%, 99.5%)

54.5%

(23.4%, 83.3%)

50.0%

(18.7%, 81.3%)

68.8%

(59.9%, 76.8%)

63.7%

(54.1%, 72.6%)

69.7%

(58.1%, 79.8%)

65.9%

(49.4%, 79.9%)

Non-Inferiority Superiority Observed Rate

0.355 0.500 75.0%

0.636 0.755 33.3%

0.003 0.013 75.0%

0.007 0.029 75.0%

0.008 0.250 69.7%

<0.001 0.046 69.7%

<0.001 0.014 81.6%

<0.001 0.015 79.6%

(95% Confidence

Interval)

(19.4%, 99.4%)

(0.8%, 90.6%)

(42.8%, 94.5%)

(60.2%, 78.2%)

(59.6%, 78.5%)

(71.9%, 89.1%)

(66.5%, 89.4%)

Observed Rate

(95% Confidence

(8.5%, 75.5%)

(11.8%, 88.2%)

(26.2%, 87.8%)

(9.9%, 81.6%)

(50.0%, 69.4%)

(44.7%, 66.3%)

(61.6%, 85.0%)

(58.8%, 89.3%)

Interval)

37.5%

50.0%

60.0%

42.9%

60.0%

55.7%

74.6%

76.5%

Non-Inferiority Superiority

0.059 0.110

0.576 0.682

0.104 0.226

0.031 0.081

0.001 0.068

<0.001 0.024

0.006 0.154

0.067 0.363

Levels Treated Primary Outcome

C3-C4 Overall Success

C4-C5 Overall Success

C5-C6 Overall Success

C6-C7 Overall Success

Variable

(without FSU)

Overall Success

(with FSU)

(without FSU)

Overall Success

(with FSU)

(without FSU)

Overall Success

(with FSU)

(without FSU)

Overall Success

(with FSU)

Inv Ctrl P-Value Inv Ctrl P-Value

Observed Rate

(95% Confidence

Interval)

50.0%

(11.8%, 88.2%)

60.0%

(14.7%, 94.7%)

92.9%

(66.1%, 99.8%)

85.7%

(57.2%, 98.2%)

72.7%

(64.1%, 80.2%)

74.1%

(65.0%, 81.9%)

83.5%

(74.9%, 90.1%)

84.5%

(72.6%, 92.7%)

Sensitivity Analyses

To assess the impact of lost to follow-up at 84-month visits, which includes the slightly unbalanced distribution of some baseline variables and the overall success status at 24 months among the subjects with 84-month follow-up versus those without, several sensitivity analyses were conducted. To assess the impact of slightly unbalanced distribution of some baseline variables, propensity score analyses were conducted to adjust for any confounding effect of the demographic and prognostic variables, regardless whether they were significantly different between the subjects who completed PAS versus those who did not. Overall 32 variables, including the gender, worker’s comp and unresolved spinal litigation which show some imbalance among the subjects with 84-month follow-up versus those without, were used to construct the propensity score for the two treatment groups. The result shows that by the adjusting propensity score, most conclusions are consistent with the initial results without adjustment. Table 20 shows the result of the overall success without FSU at 24 months and 84 months with the propensity score adjustment and without adjustment, the conclusion of non-inferiority and superiority for overall success without FSU are consistent using these two different methods. The same conclusion holds for the overall success with FSU and the component of the primary endpoint as well.

Table 20: Overall Success without FSU at 24 Months and 84 Months with/without Propensity Score Adjustment

Observed Rate P-Value

Investigational Control Non-Inferiority Superiority

Overall success at 24 Months (without FSU)

Overall success at 84 Months (without FSU)

Without Propensity Score Adjustment 77.7% 67.7% <0.001 0.008 With Propensity Score Adjustment 77.7% 67.7% <0.001 0.004 Without Propensity Score Adjustment 75.0% 63.7% <0.001 0.008 With Propensity Score Adjustment 75.0% 63.7% <0.001 0.017

In addition, to assess the slightly unbalanced distribution of the overall success status at 24 months among the subjects with 84month follow-up versus those without, several sensitivity analyses, including “Missing = Failure”, “Missing = Success”, “Last Observation Carried Forward (LOCF)” were performed to evaluate the impact of the missing data in the analysis of primary endpoints. Table 21, using the overall success without FSU at 84 months as an example, shows that the conclusion remains robust regardless of type of sensitivity analysis.

Table 21: Overall Success without FSU at 84 Months under Various Scenarios

Observed Overall Success

(without FSU)

Missing = Failure

Missing = Success

Overall Success (without FSU)

LOCF Overall Success

(without FSU)

Investigational Group

(N=276)

159/212 (75.0%)

159/276 (57.6%)

223/276 (80.8%)

201/284 (73.4%)

Control Group

(N=265)

116/182

(63.7%)

116/265

(43.8%)

164/265

(61.9%)

168/254

(66.1%)

P-value

(Non-inferiority)

< 0.001 0.008

< 0.001 < 0.001

< 0.001 0.055

< 0.001 0.035

P-value

(Superiority)

In addition, the tipping point analyses were conducted to further support the above conclusion. Again, using overall success without FSU at 84-month as an example, the analyses shows that in order to reach the tipping point for the non-inferiority conclusion, there must be at least 45 more control successes than investigational successes, which is dramatically biased in favor of the control group. Additionally, in order to reach the superiority conclusion, there must be at least 18 more control

Page 21

successes than investigational success group, which is also biased in favor of the control group. Similar conclusion holds for overall success with FSU at 84 months as well.

These analyses confirm that the overall study conclusion remains robust despite the slight unbalanced distribution of some baseline variables and the overall success status at 24 months among the subjects with 84-month follow-up versus those without.

Secondary Effectiveness Analysis

The secondary endpoints assessed were Neck Pain, Arm Pain, SF-36 Health Survey and, Gait Assessment while other measurement include Foraminal Compression, Work Status, Patient Satisfaction, Radiographic, Global Perceived Effect, and Doctor’s Perception. Table 22 describes the results of the secondary effectiveness endpoints and other measurements at 24 and 84 months.

Table 22: Secondary Endpoints and Other Measurements

IDE PAS

24-Month Observed Success Rate 84 -Month Observed Success Rate

Variable

Neck pain

Success

Failure

Arm pain

Success

Failure

SF-36 PCS

Success

Failure

SF-36 MCS

Success

Failure

Patient Perceived Effect

Success

Failure

Patient Satisfaction

Success

Failure

Doctor Perception

Success

Failure

Gait

Success

Failure

Work Status

Median days until return to work

Inv

(N=276)

241/253 (95.3%)

12/253 (4.7%)

231/253 (91.3%)

22/253 (8.7%)

210/248 (84.7%)

38/248 (15.3%)

169/248 (68.1%)

79/248 (31.9%)

236/252 (93.7%)

16/252 (6.3%)

222/252 (88.1%)

30/252 (11.9%)

233/251 (92.8%)

18/251 (7.2%)

247/251 (98.4%)

4/251 (1.6%)

45 Days 61 Days n/a

Ctrl

(N=265)

213/219 (97.3%)

6/219 (2.7%)

208/219 (95.0%)

11/219 (5.0%)

186/216 (86.1%)

30/216 (13.9%)

150/216 (69.4%)

66/216 (30.6%)

199/219 (90.9%)

20/219 (9.1%)

192/219 (87.7%)

27/219 (12.3%)

194/220 (88.2%)

26/220 (11.8%)

219/220 (99.5%)

1/220 (0.5%)

Inv

(N=276)

201/210 (95.7%)

9/210 (4.3%)

192/210 (91.4%)

18/210 (8.6%)

173/208 (83.2%)

35/208 (16.8%)

151/208 (72.6%)

57/208 (27.4%)

197/210 (93.8%)

13/210 (6.2%)

195/211 (92.4%)

16/211 (7.6%)

193/211 (91.5%)

18/211 (8.5%)

206/211 (97.6%)

5/211 (2.4%)

Ctrl

(N=265)

172/180 (95.6%)

8/180 (4.4%)

167/180 (92.8%)

13/180 (7.2%)

141/178 (79.2%)

37/178 (20.8%)

125/178 (70.2%)

53/178 (29.8%)

164/181 (90.6%)

17/181 (9.4%)

155/181 (85.6%)

26/181 (14.4%)

151/182 (83.0%)

31/182 (17.0%)

179/182 (98.4%)

3/181 (1.6%)

Radiographic Assessments

For patients receiving the PRESTIGE™ device, the mean angular motion values at 24 and 84 months postoperative, respectively, were 7.73° (n=238) and 6.75° (n=206) as compared to a preoperative value of 7.55° (n=216). The range of motion values measured from flexion/extension radiographs at 24 months and at 84 months for the PRESTIGE™ device patients are presented in the histogram below.

Range of Motion

Overall, 206 subjects had range of motion data collected at 84 months, with 58 (28.2%) having a range of motion (ROM) ≤ 4° and 148 (71.8%) have range of motion > 4°. The NDI, neck pain, arm pain, neurological, secondary surgery, serious associated adverse events success status, ROM summary tables compared clinical endpoints between the investigational subjects with a range of motion > 4° to those with a range of motion ≤ 4°. All of the data show that there is no significant difference between these two subgroups at any time-point.

Additionally, Medtronic conducted a correlation analysis for the range of motion with NDI, neck pain and arm pain as continuous variables. This analysis did not appear to show any correlation between range of motion and any of these variables at any time point.

The following two figures show the ROM at 24-month and 84-month visits.

Page 22

Figure 1: Histogram of PRESTIGE™ Cervical Disc Angular Range of Motion at 24 Months

Number of Patients by ROM at 24 Months in Investigational Group

Number of Patients

Note: Parenthesis '(' or ')' indicates exclusive, and square bracket '[' or ']' indicates inclusive. For example, (1° -2°] means >1° and <=2°. 0=0°, 1=(0°-1°], 2=(1°-2°], 3=(2°-3°], 4=(3°-4°], 5=(4°-5°], 6=(5°-6°], 7=(6°-7°], 8=(7°-8°], 9= (8°-9°], 10=(9°-10°], 11=(10°-11°], 12=(11°-12°], 13=(12°-13°], 14=(13°-14°], 15=(14°-15°], 16=(15°-16°], 17=(16°-17°], 18=(17°-18°], 19=(18°-19°], 20=(19°-20°], 21=(20°-21°], 22=(21°-22°].

ROM

Figure 2: Histogram of PRESTIGE™ Cervical Disc Angular Range of Motion at 84 Months

Number of Patients by ROM at 84 Months in Investigational Group

Number of Patients

ROM

Bridging Bone

Heterotopic ossification (HO) was not collected as a part of the IDE and post-approval study protocols. However, bridging bone (an extreme scenario of HO) was assessed for the investigational subjects during the IDE and post-approval studies. Bridging bone was defined as evidence of a continuous bony connection from the superior vertebral body to the inferior vertebral body laterally, anteriorly, and/or posteriorly. The radiographic results are shown in Table 23. Two investigational patients were found to have bridging bone at the 24-month time point while twenty investigational patients were found to have bridging bone at the 84-month time point.

Additional subgroup analyses at 84 months (20 investigational Patients with bridging bone versus 181 investigational patients without bridging bone) were also conducted in order to determine whether bridging bone was correlated with clinical outcomes. The analysis assessed the following clinical outcomes: NDI, Neck/Arm pain, and overall success. Data demonstrated that patients with bridging bone had similar clinical outcomes when compared to patients without bridging bone at all time-points. In conclusion, the study data suggests that bridging bone was not correlated with unwanted safety or effectiveness consequences and was not linked to specific patient or surgical variables.

Table 23: Time Course of Bridging Bone

6 Weeks

3 Months

6 Months

12 Months

24 Months

Bridging Bone PRESTIGE Subjects

(N=276)

No 267 (100.0%)

Yes 0 (0.0%)

No 253 (100.0%)

Yes 0 (0.0%)

No 254 (99.6%)

Yes 1 (0.4%)

No 255 (98.5%)

Yes 4 (1.5%)

No 248 (99.2%)

Page 23

Table 23: Time Course of Bridging Bone (continued)

Bridging Bone PRESTIGE Subjects

(N=276)

Yes 2 (0.8%)

36 Months

60 Months

84 Months

No 183 (96.3%)

Yes 7 (3.7%)

No 196 (93.8%)

Yes 13 (6.2%)

No 181 (90.0%)

Yes 20 (10.0%)

Radiolucency

A post-hoc analysis of radiographic observations was conducted to assess for radiolucency. A total of 17 unique investigational patients were found to have an observation of radiolucency and/or device loosening.

At 84 months post-operative, nine of the 17 identified radiolucency cases were considered mild, five moderate and only three patients were scored as having severe radiolucency. Fourteen of these 17 patients were considered an overall success. Only one case with observed radiolucency (and one of three severe radiolucency cases) was associated with a device removal. However, this removal was associated with a traumatic event and inferior bone screw fracture. Histology findings for this patient were similar to other explanted subjects (without observed radiolucency) with no acute inflammation, osteolysis, pseudotumor or lymphatic masses observed. Therefore, trauma and device breakage (screw fracture) may be associated with this device loosening, severe radiolucency adjacent to the device, and device removal.

Adjacent Segment Disease

Several biomechanical studies have shown increased pressure in the disc spaces adjacent to an anterior cervical fusion and increased range of motion (ROM) in the adjacent discs. Disc disease and degeneration in general, however, are difficult to measure and characterize. Therefore, the examination and comparison of additional surgeries at adjacent levels were of primary interest for this post-approval study as mentioned in the protocol, because of their clinical significance.

Cumulatively up to the end of the post-approval study at the 84-month follow-up, 11 investigational patients (4.6%, life-table estimate) underwent additional surgeries as shown in Table 24 and Table 25. During the same time frame, 24 control patients (11.9%, life-table estimate) underwent additional surgeries at any level other than the index procedure. The difference was statistically significant (p = 0.008; log-rank test). Figure 3 illustrates the time-to-event comparison between Investigational and Control Groups for additional surgeries involved with other cervical levels over the study period.

Table 24: Subjects with Adjacent Level Surgical Treatment

Treatment

Any Adjacent Surgery Occurred in Cervical Region

Number of Patients

Inv Ctrl Inv Ctrl Log-Rank Wilcoxon

Up to 24 Months 4 11 1.5 4.6

Up to 84 Months 11 24 4.6 11.9

Cumulative Rate

(%)

P-value

(Inv vs Ctrl)

0.008 0.008

Additional non-surgical interventions or procedures were also compared between the treatment groups. The rate of any intervention appeared to be lower in the Investigational Group (1.4% versus 5.3%) as compared to the Control Group and the frequencies of facet injection, ESI, steroid injection, trigger point injection were all numerically lower in the investigational group. Collectively, these data reflect long-term therapeutic advantage in favor of the investigational group.

Figure 3: Comparison of Time to Additional Surgery Involved with Adjacent Levels between Investigational and Control Groups

Treatment

Group

% Patients Who Had Secondary Surgeries Involved with Adjacent Levels

PRESTIGE® ST Control

Logrank=0.008

Months from Index Surgery to Second ary Surgery

Page 24

Table 25: Secondary Surgical Interventions at the Adjacent Level – Procedure Details

Group Patient ID

Investigational 1916 C6-C7

Investigational 1002 C6-C7 Herniated disc C5-C6 C5-C7 ACDF Other 368 12 Months

Investigational 1209 C5-C6 Motor Vehicle Accident C6-C7 microdiscectomy and fusion Other 510 12 Months

Investigational 3141 C5-C6

Investigational 307 C5-C6 Facet pain, cervical C4-C5 ACDF with PEEK and BMP Other 917 36 Months

Investigational 2802 C5-C6 Left side radiculopathy C3-C4 anterior, C6-C7 posterior instrumentation Other 1077 36 Months

Investigational 2858 C5-C6

Investigational 2802 C5-C6 Left side radiculopathy Removal of wires from surgery in May 2006 Other 1116 36 Months

Investigational 3144 C5-C6 C6-C7 disc disease and migraine headaches C6-C7 anterior cervical discectomy Other 1371 48 Months

Investigational 2855 C5-C6

Investigational 2802 C5-C6 Left side radiculopathy C3-C7 posterior fusion Other 1575 48 Months

Investigational 2807 C6-C7

Investigational 615 C4-C5

Investigational 3144 C5-C6 Suspected failed fusion at C6-C7 C6-C7 exploration and re-fusion Other 2150 72 Months

Investigational 2807 C6-C7 Numbness in fingers with neck and shoulder C5-C6 posterior cervical fusion Other 2215 72 Months

Investigational 615 C4-C5

Control 3310 C6-C7 HNP at C5-C6 C5-C7 ACDF with two level cervical plate Revision 88 3 Months

Control 2507 C5-C6 C7 pain and numbness C5-C7 fusion with allograft and anterior plate Revision 98 3 Months

Control 1713 C5-C6 Adjacent level disc herniation C5-C7 discectomy and fusion Revision 140 3 Months

Control 2507 C5-C6 C7 pain and numbness

Control 215 C6-C7 Neck pain with right posterior scapular pain C5-C6 ACDF Removal - Elective 385 12 Months

Control 2716 C6-C7 Neck and shoulder pain

Control 3117 C5-C6

Control 2915 C6-C7 C3-4 foraminal stenosis, C5-6 herniated disc Posterior cervical foraminotomy Other 482 12 Months

Control 608 C6-C7 Involuntary thumb/ torso movements C4, C5, C6, C7, and T1 cervical laminectomy Re-Operation 506 12 Months

Control 1112 C5-C6

Control 2507 C5-C6 C7 pain and numbness C5-C7 posterior fusion with plating

Control 226 C5-C6 Adjacent segment disease at C6-7 C6-C7 ACDF Other 550 12 Months

Control 235 C6-C7

Control 2507 C5-C6

Control 908 C5-C6 HNP C6-C7 C6-C7 ACDF Other 959 36 Months

Control 235 C6-C7

Control 1820 C6-C7 Headaches C3-C4 ACDF Other 1183 36 Months

Control 1914 C5-C6

Control 231 C5-C6

Control 1208 C5-C6 Neck and left arm pain

Control 528 C5-C6

Control 2918 C6-C7

Control 803 C6-C7

Control 219 C5-C6 Right-sided neck pain and shoulder pain

Control 539 C4-C5

Control 219 C5-C6 Right-sided neck pain and shoulder pain C3, C4, C5 right medial branch radiofrequency Other 1901 60 Months

Control 2507 C5-C6

Index Surgery

Level

Cause/Adverse Event Action

Neck / shoulder arm pain / decreased sensation

C6 nerve root blunting and facet disease

Numbness and tingling, left arm; C4-C5 / C6-C7

Cervical strain, C6-C7 subluxation, C4-C5/C6-C7

Pain in right arm, numbness in fingers with neck

Disc bulging and end plate spurring at C4-C5

Degenerative changes C6-C7; C5-C6 lucency;

remodeling at C5-C6 anteriorly; facet

inflammatory changes C5-C6; foraminal bony

encroachments at C6-C7 and C5-C6

Neck pain, glenohumeral joint, cervical

Incomplete fusion at C6-7; neck pain with

C3-C4 disc degeneration, C3-C4 bulging, C3-C4

Incomplete fusion at C6-7; neck pain with

Neck pain radiating to right shoulder/arm due to

motor vehicle accident, small right posterior

osteophytes with cord edema at C6-C7, right

HNP with moderate spinal stenosis

C6-C7 herniation, foramen impi ngement,

Severe spondylitic changes C3-C4 with bilateral

spurring, left paracentral disc osteophytes

complex, bilateral foraminal encroachment, and

severe spondylitic changes at C4-C5

Foraminal stenosis C4, C5 and C6; herniation at

Degenerative changes at C5-C6 with possible

small disc protrusion, osteophytes at C5-C6

Shallow protrusion and hypertrophy at C3-C4,

mild stenosis and protrusion at C5-C6, adjacent

C3-C4 disc degeneration, C3-C4 bulging, C3-C4

in little finger

secondary to baseball injury

annular tears

hypermobility

and shoulder

and C6-C7

spondylosis

headaches

pseudoarthrosis

headaches

osteophyte compression

C5-C6

segment degeneration at C5-C6

pseudoarthrosis

C5-C7 ACDF Removal 303 12 Months

C5-C7 ACDF Removal 786 24 Months

C5-C6 explant of PRESTIGE™ cervical disc followed

C4-C5, C6-7 anterior cervical microdiscectomy and

C3-C6 radiofrequency of the median branch of the

C3-C5 radiofrequency of the median branch of the

C5-C7 radiofrequency of the median branch of the

C5-C7 radiofrequency of the medial branch of the

C5-C6 removal plate followed by C5-C7 revision

arthrodesis with autograft and cervical plate

C6-C7 removal of cervical plate and allograft followed

by C4-C7 anterior cervical fusion with BMP and plate

C5-C6 removal of cervical plate (elective) followed by

C5-C6 removal of anterior cervical plate; exploration

of C5-C6 fusion; C6-C7 ACDF using PEEK and BMP

C6-C7 removal of cervical plate followed by C5-C6

C5-C7 removal of plating, C4-C5 ACDF Other 846 24 Months

C5-C6, C6-C7 right foraminotomies with C6-C7 nerve

C5-C6 removal of cervical plate followed by C6-C7

C5-C6 removal of cervical plate, C6-C7 anterior

discectomy and osteophytectomy with anterior

C5-C6 removal of cervical plate, C6-C7 foraminotomy

C5-C6 removal of cervical plate; C3-C4 and C4-C5

C6-C7 removal of cervical plate followed by C5-C6

C5-C7 removal of cervical plate followed by C5-C6

C3, C4, C5 radiofrequency ablation of right sided

C4-C6 removal of anterior cervical plate followed by

by C4-C7 ACDF

placement of an artifical disc

C5-C6 discectomy and fusion Other 1694 60 Months

dorsal rami/cervical-right

dorsal rami/cervical-left

dorsal rami/cervical-right

dorsal rami/cervical-left

C6-C7 cervical discectomy and fusion

with instrumentation from C5 TO C7

ACDF

root decompression

ACDF with plate

interbody fusion and plating

with arthrodesis instrumentation

ACDF

discectomy with anterior plating

ACDF with Cervical plate

medial branch nerves

Revision of cervical fusion Removal - Elective 1806 60 Months

C3-C4 ACDF

Secondary

Surgical

Intervention

Category

Removal 1095 36 Months

Other 1546 48 Months

Other 1944 60 Months

Other 2260 72 Months

Other 2406 84 Months

Other 2446 84 Months

Removal 326 12 Months

Removal 399 12 Months

Removal - Elective 407 12 Months

Removal - Elective 513 12 Months

Supplemental

Fixation

Removal - Elective 756 24 Months

Revision 1050 36 Months

Removal - Elective 1211 36 Months

Removal - Elective 1512 48 Months

Removal - Elective 1560 48 Months

Removal - Elective 1665 60 Months

Removal - Elective 1679 60 Months

Removal - Elective 1729 60 Months

Other 1768 60 Months

Other 1959 60 Months

Days to

Adjacent

Level

Surgery

Time to Adjacent

Level Surgery

525 12 Months

Page 25

Table 25: Secondary Surgical Interventions at the Adjacent Level – Procedure Details (continued)

Group Patient ID

Control 1720 C5-C6

Control 219 C5-C6 Right-sided neck pain and shoulder pain C3, C4, C5 right medial branch radiofrequency Other 2062 72 Months

Control 2507 C5-C6

Control 2809 C5-C6

Control 219 C5-C6

Control 215 C6-C7

Control 2918 C6-C7

Control 1612 C6-C7 Osteophytosis and Arthropathy C5

Control 2918 C6-C7 Pre-vertebral abscess

Index Surgery

Level

Cause/Adverse Event Action

Chronic C6-C7 radiculopathy, C4-C5 mild

spondylosis and foraminal narrowing, neck and

C3-C4 disc degeneration, C3-C4 bulging, C3-C4

C6-C7 spondylosis; C6-C7 disc bulge; C4

Right-sided neck pain and shoulder painRight-

sided neck pain and shoulder pain

Foraminal narrowing C3-C4 and canal narrowing

Foraminal stenosis C4, C5 and C6; herniation at

chest pain

pseudoarthrosis

spondylosis

C4-C5

C5-C6

C5-C6 hardware removal and C6-C7 ACDF Other 1988 60 Months

C3-C4 anterior cervical discectomy, redo with internal

C5-C6 removal of cervical plate with placement of

C4 right hemilaminectomy; C4-C5 medial facetectomy

C6-C7 removal of cervical plate followed by C5-C6

C4-C5 drainage of possible abscess and removal of

fixation and iliac bone graft

artificial cervical disc

C3, C4, C5 right medial branch radiofrequency Other 2293 72 Months

and foraminotomy

C4-C5 anterior cervical discectomy with fusion Other 2423 84 Months

ACDF with interbody cage, plate, and local bone

plating

Secondary

Surgical

Intervention

Category

Other 2183 72 Months

Removal - Elective 2242 72 Months

Other 2401 84 Months

Removal - Elective 2425 84 Months

Other 2436 84 Months

Days to

Adjacent

Level

Surgery

Time to Adjacent

Level Surgery

Fusion Outcome Data

Ten patients were found to have had a device removal followed by fusion surgery at the target level. Of these patients, postfusion imaging data was available for only six of the patients. In those six patients, various degrees of bridging bone were observed. The radiographic observations suggested that only one out of the six patients was judged as likely not fused, two out of the six patients was judged as likely undetermined and three out of the six patients were judged as likely fused.

Conclusions Drawn from the Study Data

In summary, the overall success rate for the Investigational Group at 24 and 84 months was found to be not only statistically non-inferior to the Control Group rate, but also superior, regardless of which definition of overall success was used. Therefore, the primary clinical study objective was met, thus indicating that the PRESTIGE™ Cervical Disc System is as safe and effective in the long term as the current standard of care for treating symptomatic cervical degenerative disc disease.

PACKAGING

Packages for each of the components should be intact upon receipt. If a loaner or consignment system is used, all sets should be carefully checked for completeness and all components including instruments should be carefully checked to ensure that there is no damage prior to use. Damaged packages or products should not be used, and should be returned to MEDTRONIC.

CLEANING AND DECONTAMINATION

Unless just removed from an unopened MEDTRONIC package, all instruments and implants must be disassembled (if applicable) and cleaned using neutral cleaners before sterilization and introduction into a sterile surgical field or (if applicable) return of the product to MEDTRONIC. Cleaning and disinfecting of instruments can be performed with aldehyde-free solvents at higher temperatures. Cleaning and decontamination must include the use of neutral cleaners followed by a deionized water rinse.

Note: certain cleaning solutions such as those containing formalin, glutaraldehyde, bleach and/or other alkaline cleaners may damage some devices, particularly instruments; these solutions should

not be used. Also, many instruments require

disassembly before cleaning.

All products should be treated with care. Improper use or handling may lead to damage and/or possible improper functioning of the device.

STERILIZATION

The contents of the implant package for the PRESTIGE™ Cervical Disc, including the superior and inferior disc components, bone screws, and lock screws, are provided sterile via gamma irradiation. The contents of instrument sets are provided nonsterile.

Unless marked sterile and clearly labeled as such in an unopened sterile package provided by the company, all implants and instruments used in surgery Only sterile products should be placed in the operative field. Unless specified elsewhere, these products are recommended to be steam sterilized by the hospital using one of the sets of process parameters below:

mustbe sterilized by the hospital prior to use. Remove all packaging materials prior to sterilization.

Table 26: Sterilization Parameters

METHOD CYCLE TEMPERATURE EXPOSURE TIME

Steam Pre-Vacuum 270°F (132°C) 4 Minutes Steam Gravity 250°F (121°C) 60 Minutes Steam* Pre-Vacuum* 273°F (134°C)* 20 Minutes* Steam* Gravity* 273°F (134°C)* 20 Minutes*

Page 26

NOTE: Because of the many variables involved in sterilization, each medical facility should calibrate and verify the sterilization process (e.g. temperatures, times) used for their equipment.

*For outside the United States, some non-U.S. Health Care Authorities recommend sterilization according to these parameters so as to minimize the potential risk of transmission of Creutzfeldt-Jakob disease, especially of surgical instruments that could come into contact with the central nervous system.

Remove all packaging material prior to sterilization. Only sterile implants and instruments should be used in surgery. No implant should be re-used once it comes into contact with human tissue or body fluid. Always immediately clean and re-sterilize instruments that have been used in surgery. This process must be performed before handling or (if applicable) returning to MEDTRONIC.

CONFORMANCE TO STANDARDS

The PRESTIGE™ Cervical Disc is manufactured from type 316 stainless steel per ASTM F138.

PRODUCT COMPLAINTS

Any Health Care Professional (e.g., customer or user of this system of products), who has any complaints or who has experienced any dissatisfaction in the product quality, identity, durability, reliability, safety, effectiveness and/or performance, should notify the distributor or MEDTRONIC. Further, if any of the implanted spinal system component(s) ever “malfunctions,” (i.e., does not meet any of its performance specifications or otherwise does not perform as intended), or is suspected of doing so, the distributor should be notified immediately. If any MEDTRONIC product ever “malfunctions” and may have caused or contributed to the death or serious injury of a patient, the distributor should be notified immediately by telephone, fax or written correspondence. When filing a complaint, please provide the component(s) name and number, lot number(s), your name and address, the nature of the complaint and notification of whether a written report from the distributor is requested. Complaints may also be reported directly to Medwatch at http://

www.fda.gov/medwatch.

FURTHER INFORMATION

Recommended directions for use of this system (surgical operative techniques) are available at no charge upon request. If further information is needed or required, please contact MEDTRONIC.

DEVICE RETRIEVALS

Should it be necessary to remove a PRESTIGE™ Cervical Disc device, please call MEDTRONIC prior to the scheduled surgery for product/tissue retrieval information.

FOR US AUDIENCES ONLY

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

Page 27

Medtronic Sofamor Danek USA, Inc.

1800 Pyramid Place Memphis, TN 38132 Telephone: 800 933 2635 (USA)

901 396 3133 (Outside USA)

Fax: 901 396 0356

DESCRIPTION OF DEVICE MARKINGS

Batch code

Catalogue number

CAUTION: Federal law (USA) restricts these devices to sale by or on the order of a physician.

Consult instructions for use

Do not re-use

For US audiences only

The device complies with European Directive MDD 93/42/EEC

Medtronic B.V.

Earl Bakkenstraat 10 6422 PJ Heerlen The Netherlands Tel: + 31 45 566 80 00

Authorized representative in the European Community

Do not use if package is damaged

Manufacturer

Sterilized using irradiation

Use-by date