Nucleus Arthroplasty Volume I

NucleusArthroplasty

Volume I: Fundamentals

Technology

in Spinal Care

1 Introduction

2 About the Editors

C H A P T E R 1 3 How the Disc Degenerates

C H A P T E R 2 10 Nucleus Arthroplasty Motion Preservation Technology

versus Nucleus Replacement

C H A P T E R 3 12 Nucleus Arthroplasty Technology from the U.S. Regulatory Viewpoint

C H A P T E R 4 17 Fundamentals of Reimbursement

C H A P T E R 5 21 Worldwide Orthopedic and Spine Market

C H A P T E R 6 27 Nucleus Arthroplasty Technologies

35 Conclusion

36 Contributing Authors

Table of Contents

This monograph series is a groundbreaking project in therapidly emerging field of non-fusion spinal surgery. Thefull range of nucleus replacement technologies is examined

with discussion on surgical techniques, detailed information

on each cutting-edge device technology, indications, and

patient selection criteria.

Nucleus Arthroplasty Technology in Spinal Care is

published for the medical profession by Raymedica, LLC,

Minneapolis, MN 55431.

The views expressed in this series are those of the authors

and do not necessarily represent those of Raymedica, LLC.

Copyright 2006 Raymedica, LLC. All rights reserved.

Printed in U.S.A.

Introduction

1

The first documented works describing the diagnosis andtreatment of the spine, spinal disorders, and spinal instabilitydate back to 1900-2500 B.C. Interestingly, the documents recom-

mended against the treatment of spinal cord injury. The develop-

ment of therapeutic treatments has a long history starting with

the cane, the first load-sharing device. Today, our efforts to

improve therapies to treat spine disease persist. We continue to

recognize problems, identify issues, and define variables in an

effort to better understand spinal degeneration and to develop

innovative solutions that utilize a wide array of materials and

technologies. Our field has had a rich history of advancements,

accomplishments, and inventiveness. We owe a great debt to the

pioneers who, armed with little more than a detailed knowledge

of anatomy, heralded in the era of spinal surgery. Their trials,

errors, innovations, and teachings have guided our efforts to

ultimately improve clinical outcomes.

Early on, it was recognized that the disc played a vital role in overall

spine health.With great effort and ingenuity, the unique anatomical,

biomechanical, and physiological properties of the disc were eluci-

dated and incorporated into elegant treatment algorithms.We now

have access to an almost overwhelming flow of information about

lumbar disc arthroplasty from countless sources. Central to the evo-

lution of therapies is a better appreciation of the complexities of the

lumbar disc. By combining knowledge gleaned from anatomical dis-

section, biochemical processes, and resultant physiology with a disci-

plined foundation in biomechanics, we have created a fabric of

understanding never before enjoyed. Spine arthroplasty is now an

important and evolving area within the treatment of spinal disor-

ders. This sub-discipline represents the coalescence of many areas of

study focused on the development of new and exciting solutions to

address clinical problems.

These significant advances in our understanding of the spine rep-

resent a culmination of efforts occurring across many fronts. Our

increased understanding of the biological factors at work in disc

disease has been a driving force in the development and emer-

gence of new materials and delivery methods. The critical role

that advanced biocompatible alloys, polymers, and viscoelastic

hydrogels play in the innovation of disc arthroplasty technologies

cannot be over emphasized.

Technological advancements have played a vital role in supporting

and expanding our knowledge of motion preserving disc technolo-

gies. The latest imaging technologies allow a much more detailed

appreciation of pathological processes, such as disc degeneration,

and provide the ability to monitor the results of an intervention.

Computerized finite element analysis offers a risk-free environment

in which to test hypotheses and predict clinical impact. Biochemical

advancements yield an intimate understanding of the chemical envi-

ronment including chemical mediators and potential intervention

portals. This wealth of knowledge can be used to great advantage

when developing disc arthroplasty technologies.

Not to be overlooked, the socioeconomic challenges involved in the

development of new technologies, such as the Nucleus Arthroplasty

motion preservation system, have also become more apparent.

The all important variable of proper patient selection continues to

require constant reassessment and vigilance. Increasingly, third-party

payers control access to care and treatment choice to an alarming

degree. Such considerations can no longer be ignored in the quest

for ideal patient management methods.

This publication has been constructed to provide an overview

of the foundational elements of Nucleus Arthroplasty motion

preservation technology including an understanding of the

degenerative process, current treatment solutions, systematic

treatment approaches, regulatory processes, and reimbursement

concerns. In addition, part one of this series will provide insight

into the potential market and the current players working in the

forefront of Nucleus Arthroplasty development activities. This is

an incredibly exciting field as technologies focused on the repair

and replacement of the diseased disc nucleus will catapult us far

beyond the treatment options we have available today.

In conclusion, we can say that the spine arthroplasty specialist

of today is well prepared to deliver the most advanced solutions

to the clinical puzzle of disc disease with technologies based on

a rich tradition of innovation and compassion coupled with a

tremendous wealth of physiological knowledge and assessment

tools. As spine surgery evolves from mechanical solutions to

therapeutic solutions both surgeons and patients will benefit.

We hope you will find this series on Nucleus Arthroplasty

technology to be a valuable asset.

Reginald J. Davis, MD, FACSCHIEF OF NEUROSURGERY

Baltimore Neurosurgical Associates, PA

Baltimore, MD 21204

Federico P. Girardi, MDASSISTANT PROFESSOR

OF ORTHOPEDIC SURGERY

Hospital for Special Surgery

New York, NY 10021

Federico P. Girardi, MDReginald J. Davis, MD, FACS

2Reginald J. Davis, MD, FACS

Dr. Davis is founder of Baltimore Neurosurgical Associates, chief

of Neurosurgery at the Greater Baltimore Medical Center, and a

faculty member at the Johns Hopkins School of Medicine and

the University of Maryland. He is a Fellow of the American

College of Surgeons and a Diplomate of the American Board

of Surgery. Dr. Davis received his medical degree from Johns

Hopkins University School of Medicine, Baltimore, Maryland.

He has broad experience in advanced procedures such as spinal

stabilization, intradiscal electrothermal therapy, and microendo-

scopic discectomy and has conducted physician training pro-

grams on these procedures. His professional affiliations include

the AANS-CNS Section on Disorders of the Spine, the American

Association of Neurological Surgeons, the Congress of

Neurological Surgeons, and the North American Spine Society.

Federico P. Girardi, MD

Dr. Girardi is assistant attending orthopedic surgeon at the

Hospital for Special Surgery, New York, New York where he spe-

cializes in the treatment of spinal disorders including degenera-

tive disc disease (DDD), spinal deformities, metabolic fractures,

and spinal tumors. Dr. Girardi received his medical degree from

the Universidad Nacional de Rosario, Rosario, Argentina.

He has performed extensive clinical research in the areas of min-

imally invasive surgery, clinical outcomes, and spinal imaging.

He is also interested in basic research on bone, disc, and nerve

tissue regeneration and in the investigation of alternatives to

spinal fusion for the treatment of DDD. His professional affilia-

tions include the North American Spine Society, Scoliosis

Research Society, the European Spine Society, the International

Society for the Study of the Lumbar Spine, and the Spine

Arthroplasty Society.

Raymedica has selected Reginald J. Davis, MD, FACS andFederico P. Girardi, MD, to edit this series of monographson Nucleus Arthroplasty technology, because of their special

interest in this dynamic area of medicine. Both Drs. Davis and

Girardi are noted for their expertise in spine surgery and

advanced training in minimally invasive surgical techniques.

They are well respected for their clinical work and travel

widely to speak and train other physicians.

About the Editors

Reginald J. Davis, MD, FACS Federico P. Girardi, MD

3Chapter 1 How the Disc Degenerates

Jeff S. Silber, MDASSISTANT PROFESSOR

Department of Orthopaedic Surgery

Chief, Division of Spine Surgery

Long Island Jewish Medical Center

New Hyde Park, NY 11040

Kamal Dagly, MDRESIDENT ORTHOPAEDIC SURGERY


Long Island Jewish Medical Center

New Hyde Park, NY 11040

Zoe Brown, MDSPINE RESEARCH FELLOW


The Rothman Institute


Philadelphia, PA 19107

Archit Patel, MDSPINE RESEARCH FELLOW





Ravi PatelMEDICAL STUDENT


Thomas Jefferson University


Alexander R. Vaccaro, MDPROFESSOR

Department of Orthopaedics and Neurosurgery

Co-Chief, Division of Spine Surgery

Co-Spine Fellowship Director

Co-Director Delaware Valley Regional

Spinal Cord Injury Center and




MOLECULAR BIOLOGY OF DISC DEGENERATION

An understanding of the biology of disc degeneration canprovide a better understanding of the diagnosis and treat-ment of low back pain (LBP). The 23 intervertebral discs that lie

between each vertebral segment provide flexibility and increase

physically in size when progressing from the cervical spine to the

sacrum.1 The disc consists of two distinct anatomic regions that

work in unison. They include the fibrous outer annulus fibrosus

and the softer inner cartilaginous nucleus pulposus. The annulus

fibrosus in the lumbar spine has up to 25 layers known as

4lamella containing mostly type I collagen arranged in a parallel

pattern.2 The intricate cross-linked configuration of the fibrils

allows the intervertebral disc to resist tensile forces incurred dur-

ing lumbar spine bending and torsional movements. The inner

nucleus pulposus contains predominantly type II collagen fibers

arranged in a more random fashion. The fibers are surrounded

by a matrix rich in proteins known as proteoglycans. These pro-

teoglycans bind water and have a high water content in a normal

intervertebral disc. This gives the disc its characteristic stiffness

and viscoelasticity allowing compressive resistance to axial loads.3

The concentration of proteoglycans and the water binding capac-

ity of the disc increases when progressing from the outer annulus

fibrosus to the inner nucleus pulposus. In contrast, the concentra-

tion of type II collagen decreases from the inner nucleus to outer

annulus fibrosus. The collagen content of the nucleus is highest

in the cervical spine and decreases in the lumbar spine, while the

proteoglycan content increases in the lumbar spine. The high pro-

teoglycan content in the lumbar spine is ideal due to its water

binding capacity, which allows for an increased resistance to axial

compressive loads where it is most needed.

Over time, proteolytic damage to the fibrillar collagens of the

annulus occurs as a result of collagenase activity. This leads to

a decrease in collagen cross-linking and a weakening in the bio-

mechanical stability of the intervertebral disc and acceleration

of the normal process of disc degeneration or aging. As the disc

ages, the amount of aggregated proteoglycans decreases while

the content of non-aggregated proteoglycans increases leading to

lower osmotic or water binding capacity and a loss of compressive

resistance in the lumbar intervertebral disc.4

The vascularity of the intervertebral disc diminishes as it develops

and grows. The predominant source of intervertebral nutrition

during normal growth is through the vasculature of the vertebral

endplates. However in the adult, calcification of the endplates

occurs, and nutrient uptake and waste elimination occur through

diffusion. This leads to anaerobic metabolism taking a more

prominent role during which lactate production produces an

acidic environment, making proteinases more active and resulting

in further disc degeneration.5

The lumbar intervertebral disc has developed the ability phyloge-

netically to withstand high compressive axial forces. This is accom-

plished by its ability to convert compressive loads into tensile

stresses by utilizing the osmotic pressure of the interstitial fluid

and the proteoglycans located in the nucleus pulposus. As the disc

degenerates further, the annulus fibrosus becomes stiffer and the

osmotic pressure of the nucleus pulposus decreases causing imbal-

ances in load transfer and resulting in increased stresses to the

bony elements of the vertebral endplates. It has been shown that

when heavy loads are applied to the intervertebral disc, the normal

disc biology is disrupted leading to an increase in catabolic

enzymes and an acceleration in intervertebral disc degeneration.6

Certain individuals may be genetically predisposed to the catabolic

events of disc degeneration. Polymorphisms of the vitamin D

receptor, aggrecan gene, type IX collagen, and MMP-3 (matrix

metalloproteinase-3) have all been implicated in accelerated

intervertebral disc degeneration. Furthermore, studies have

shown increased rates of degenerative disc disease in siblings

of affected individuals and a strong correlation in twins.

Chronic discogenic back pain has been linked to many factors

including anatomic structural changes, inflammatory mediators,

and nervous ingrowth into the outer annulus fibrosus. Production

of inflammatory mediators such as interleukin (IL)-1, IL-8,

fibroblast growth factor and intracellular adhesion molecule

(ICAM)-1 by mononuclear cells infiltrating a herniated disc may

also lead to inflammation and pain.7 IL-1 has also been shown to

increase the rate of matrix breakdown as well as decrease the pro-

duction of proteoglycans, thereby, affecting the water content in

the nucleus pulposus. Additionally, herniated discs also produce

nitric oxide synthetase, an enzyme known to lead to the formation

of free radicals which cause direct damage to cell membranes and

matrix proteins.8 These herniated disc fragments can also generate

high levels of phospholipase A2, an enzyme which facilitates the

formation of pro-inflammatory prostaglandins and leukotrienes

both of which are important mediators in the production of pain.

T H E L U M B A R I N T E R V E R T E B R A L D I S CH A S D E V E L O P E D T H E A B I L I T YP H Y L O G E N E T I C A L LY T O W I T H S TA N DH I G H C O M P R E S S I V E A X I A L F O R C E S .

5STAGES OF DISC DEGENERATION

Kirkaldy-Willis described the widely accepted degenerative cas-

cade (pathophysiological model) that occurs in the intervertebral

disc. The cascade is divided into three stages based on the

amount of damage or degeneration to the disc and facet joints at

a given point in time.9 This cascade of individual motion segment

degeneration is thought of as a continuum rather than as three

clearly definable and separate stages.

Stage I (Dysfunctional)

The first stage is known as the dysfunctional stage and occurs

when the initial changes of intervertebral disc degeneration begin.

This occurs between 20-30 years of age and is described by cir-

cumferential fissuring or tearing of the outer annulus fibrosus.

This may result from repetitive vertebral endplate injury leading

to a disruption in the intervertebral vascular supply and impair-

ment of the normal disc metabolism. These pathophysiologic

changes result from years of repetitive microtrauma and usually

present as acute mechanical low back pain episodes or going out

phases. In the initial stages, acute episodes of low back pain are

self limited, and improve with minimal intervention. However,

the pain experienced in this stage may be severely debilitating

because of the large innervation to the outer-third of the annulus

via the sinuvertebral nerves. Over time, the circumferential tears

may combine and form larger radial tears while the inner nucleus

pulposus loses its water-retaining properties due to changes in

aggregating proteoglycans. These changes, mostly a decrease in

amount and organization in proteoglycans, are thought to occur

due to an imbalance in the MMP-3 (matrix metalloproteinase-3)

and TIMP-1 (tissue inhibitor of metalloproteinase-1) proteins

seen in the normal nucleus pulposus. Magnetic resonance imaging

(MRI) studies during this stage may reveal a high intensity zone

(HIZ) lesion in the posterior outer annulus fibrosus and decreased

signal intensity on T2 weighted images (disc desiccation) with or

without disc bulging and without herniation.

Stage II (Instability)

The second stage, known as the instability stage, represents more

severe tissue damage. This stage occurs later in life between 30

and 50 years of age. Intervertebral disc changes occur as the

result of multiple annular tears and delamination of the layers.

Vertebral segment instability occurs, and this results in a decline

in the amount of nuclear proteoglycan composition with a

resulting loss of water content. Increased force transfer to the

annulus occurs with the subsequent loss of intervertebral disc

height. The patient in this stage of degeneration also presents

with periods of low back pain which is usually more intense,

more protracted in duration and requires more aggressive inter-

vention. These episodes occur more frequently, and MRI studies

reveal further loss of intervertebral disc height, a darker disc,

and possibly a herniation.

Figure 1

Stage II: A lateral plain radi-ograph demonstrating partialloss of disc height at the L5-S1interspace. There is radiographicevidence of vertebral bodyendplate deformation and earlyanterior osteophyte formation.

Stage II (Instability)

Figure 2

Stage II: Sagittal MRI demon-strating decreased disc T2 sig-nal intensity at both the L4-L5and L5-S1 levels as a result ofdisc desiccation. There is alsoloss of disc space height atthese levels.

6Stage III (Stabilization)

The third stage, known as the stabilization stage, is the endpoint

in the intervertebral disc degenerative cascade and is exemplified

by endstage tissue damage and attempts at repair. Further nucleus

pulposus resorption occurs with worsening intervertebral disc

space narrowing, fibrosis, endplate irregularities, and the forma-

tion of osteophytes. This stage usually occurs after the age of 60

and may present with symptoms of neurogenic claudication or

radiculopathy from central, lateral recess, and/or foraminal

stenosis. Lower extremity symptoms may prevail over low back

pain in this stage.

DIAGNOSIS

The relationship of lumbar disc degeneration and LBP remains

controversial. This is due to the poor correlation between the

presence of degenerative disc disease (DDD) on imaging studies

and the report of symptoms in the general population. Numerous

studies have documented that a high percentage of asymptomatic

patients have abnormal findings on imaging studies including the

presence of DDD.10-15 However, some authors have reported a

strong correlation between low back pain and the presence of

a HIZ lesion seen in the outer annulus fibrosus. This finding is

thought to represent an annular tear which may lead to sympto-

matic DDD and LBP.16-20 In contrast, Carragee et al20 looked at

the incidence of HIZ annular tears on MRI in a recent prospec-

tive study. He reported the presence of a HIZ lesion in 42 symp-

tomatic patients with LBP but also in 54 asymptomatic patients.

The prevalence of a HIZ lesion was 59% in the symptomatic

group and 24% in the asymptomatic group. The authors con-

cluded that the prevalence of a HIZ lesion in asymptomatic

individuals with DDD was exceedingly high, and the presence

of an HIZ lesion was not meaningful for clinical use.20

Although approximately 80% of adults will experience low back

pain, only 1-2% will undergo an invasive surgical procedure. The

decision to undertake surgical management of DDD is extremely

patient dependent and requires great study due to the ubiqui-

tousness of imaging evidence of spinal degenerative disease. The

pre-surgical work-up should include a thorough history relating

to any spinal complaints and a physical examination followed by

Figure 3

Stage III: Lateral radiograph ofthe lumbar spine with signifi-cant loss of disc height at theL4-L5 interval. Sclerosis is seenat the vertebral endplates andwithin the facet joints.

Stage III (Stabilization)

Figure 4

Stage III: Sagittal MRI demonstrat-ing markedly decreased T2 signal atthe L4-L5 disc space resulting fromendstage disc desiccation.Mildlyincreased T2 signal is seen in theadjacent L4 and L5 vertebral bodiesconsistent with edema.

7a working diagnosis and directed imaging studies. Imaging stud-

ies may include plain radiographs, MRI, computed tomography,

and provocative discography. The relative indications for the

surgical management of lumbar DDD for primarily axial back

pain include the following:

1. Chronic low back pain of discogenic origin for more than

six months that has failed a reasonable comprehensive non-

operative treatment program. This non-operative treatment

program may include physical therapy, chiropractic manip-

ulation, activity modification, a back education program,

oral medications, and/or epidural spinal injections.

2. The absence of neurological signs and symptoms (radicular

findings).

3. Evidence of abnormal disc morphology or DDD on MRI.

4. A concordantly positive provocative discogram which

includes normal control levels above and/or below the

degenerative disc in question.

5. A reasonably normal psychological profile including an

appropriate, educated, and motivated patient that has realis-

tic goals and expectations.21 A pre-surgical psychological

evaluation may also be strongly advised.

6. No litigation/workers compensation claims.

PROCEDURAL CHOICES

If the patient is eligible for surgical intervention, a decision must

be made on the appropriate surgical procedure. The surgical pro-

cedure must address the proposed pain generator which is usu-

ally the intervertebral disc. Many surgical strategies have resulted

in less than satisfactory long-term outcomes. This has led to the

development of newer alternative technologies including nucleus

pulposus replacement, lumbar intervertebral disc replacement,

annular fibrosus augmentation, intradiscal electrothermal annu-

loplasty (IDET), and interbody fusion techniques. Currently, the

favored treatment methods involve removing the pain generator,

the intervertebral disc, through a fusion procedure and using a

variety of bone graft alternatives/extenders or maintaining

motion with an intervertebral disc arthroplasty.

INTERBODY STABILIZATION (FUSION) PROCEDURES

At present, lumbar interbody fusion procedures are the primary

surgical treatment alternative for symptomatic lumbar degenerative

disc disease.22-27 Interbody fusion techniques include stand alone

Anterior Lumbar Interbody Fusion (ALIF), stand alone Posterior

Lumbar Interbody Fusion (PLIF), instrumented (pedicle screw)

Posterior Lumbar Interbody Fusion, Transforaminal Lumbar

Interbody Fusion (TLIF), and anterior/posterior or circumferential

fusions. Which fusion technique results in the highest fusion rate,

the fewest complications, and the best outcomes is continuously

debated among surgeons. Some spine surgeons favor anterior or

posterior-only approaches, while others favor an anterior/posterior

circumferential fusion procedure. Interbody fusion procedures have

been shown to be biomechanically superior to posterolateral inter-

transverse fusions alone in providing support against axial loads.23

Interbody fusion devices or cages come in a variety of shapes and

may be trapezoidal, ramped, lordotic, or cylindrical and are placed

either as a single device or paired. They can be inserted from

either an anterior or posterior approach. Minimally invasive cage

introduction methods designed to decrease surgical morbidity and

improve functional outcomes have been introduced.

The use of stand-alone cages without adjunctive pedicle screw

instrumentation has met with an unacceptable rate of failure

due to continued instability or symptomatic pseudarthrosis, espe-

cially when used over multiple segments or in the setting of cir-

cumferential instability (spondylolisthesis, lateral listhesis).25

The most predictable method of ensuring an interbody fusion is

a 360-degree or combined anterior and posterior spinal fusion.

Interestingly, surgeons continue to debate whether a solid fusion

is necessary to achieve a satisfactory outcome or whether a stable

interspace alone is sufficient.

Anterior surgical procedures may be performed using open or

laproscopic methods. The theoretical advantage of placing an

anterior interbody cage as compared with a posterior interbody

fusion technique is that it optimizes the ability to prepare the

intervertebral endplates through direct visualization.

I N T E R B O D Y F U S I O N P R O C E D U R E S H AV E B E E NS HOWN TO B E B I OM E C H AN I C A L LY S U P E R I O RT O P O S T E R O L A T E R A L I N T E R T R A N S V E R S EF U S I O N S A L O N E I N P R O V I D I N G S U P P O R TA G A I N S T A X I A L L O A D S .

8Additionally, anterior placement provides a biomechanical advan-

tage in restoring lumbar lordosis more efficiently. An anterior

approach often allows for placement of a much larger spacer than a

posterior delivered cage, because there is no need to retract neural

elements. Some surgeons also feel that there is a benefit in avoiding

surgical trauma to the posterior paraspinal musculature. The ante-

rior approach, however, has its own unique complications including

the possibility of retrograde ejaculation, vascular and abdominal

visceral injuries, and post-operative incisional hernias.

The transforaminal lumbar interbody fusion (TLIF) allows place-

ment of an interbody device from the posterior approach but more

laterally than the typical PLIF technique. The proposed advantage

of the TLIF over the PLIF technique is the minimal need for neural

retraction required for cage placement. Originally, the TLIF tech-

nique called for placement of two interbody devices through a

bilateral approach. However, it is quite frequently performed by

placing a single obliquely oriented interbody cage through a unilat-

eral approach. The TLIF approach allows access to the interver-

tebral disc space lateral to the thecal sac. Studies have shown that

anterior placement of a single oblique cage using supplemental

pedicle screw instrumentation approximates the stiffness and

strength of a normal intact spinal segment.28Adjunctive poste-

rior pedicle screw instrumentation is always recommended when

performing a TLIF procedure, as it is with a PLIF.

The standard surgical exposure for posterior interbody fusions

usually involves a posterior midline incision and bilateral

paraspinal soft tissue dissection in order to expose the posterior

elements in a subperiosteal manner. Alternatively, newer tech-

niques involving minimal incisions exploit the use of specially

designed metal tubes or dilators to gradually separate the poste-

rior soft tissues (muscle fibers) creating an appropriately-sized

tunnel. These less invasive techniques may not only reduce

iatrogenic soft tissue injury, but also decrease post-operative

pain, intraoperative blood loss, and allow for faster recovery, as

compared with traditional open techniques. Unfortunately,

working through small tubes reduces the visual field and may

lead to increased surgical times. Interbody devices and pedicle

screws may all be inserted through these less invasive tube

retractor techniques. Complications specific to the posterior

interbody approach include dural lacerations, epidural fibrosus,

and nerve root injuries.29 Rarely, penetration through the ante-

rior annulus resulting in vascular and visceral injuries has also

been reported.

LUMBAR NUCLEUS PULPOSUS/INTERVERTEBRALDISC REPLACEMENT

Lumbar nucleus pulposus and artificial lumbar disc replacement

procedures were introduced to provide pain relief through a sta-

ble motion-sparing reconstruction of the intervertebral segment

via tensioning of the annulus fibrosus or stabilization of the

lumbar motion segment. Unfortunately, the extremely large and

complicated forces that exist in the native lumbar intervertebral

disc present a significant engineering challenge in creating an

ideal implant. Presently, several different types of disc prostheses

designed for use in nucleus pulposus replacement or total disc

arthroplasty procedures are either FDA approved or are being

investigated in clinical studies.

The PDN prosthetic disc nucleus, a nucleus replacement device

for symptomatic degenerative disc disease, has met with good suc-

cess.30 The majority of treated patients reported improved low

back pain and better overall function at two-year follow-up

based on Oswestry and Visual Analog scales. The PDN device

consists of hydrogel core center encased in a high molecular

weight polyethylene sleeve. This device has been shown to shrink

and swell during normal loading and unloading of the lumbar

spine mimicking the healthy human intervertebral disc. It is

hoped that future studies will shed light on the optimum surgical

treatment strategy for symptomatic DDD.

A recent prospective randomized study has demonstrated the

equivalence of an ALIF or total disc arthroplasty in the man-

agement of lumbar DDD. In a controlled, prospective, random-

ized study, 31 60 patients with one-level symptomatic discogenic

lumbar axial back pain were treated with either an ALIF or

an anterior SB Charite artificial disc replacement. The authors

demonstrated comparable improved functional outcome measures

in both treatment groups.

S T U D I E S H A V E S H O W N T H AT A S I N G L EO B L I Q U E C A G E P L A C E D A N T E R I O R LYW I T H S U P P L E M E N TA L P E D I C L E S C R E WI N S T R U M E N TAT I O N A P P R O X I M AT E S T H ES T I F F N E S S A N D S T R E N G T H O F A N O R M A LI N TA C T S P I N A L S E G M E N T .

CONCLUSION

The vast majority of patients with LBP either experience com-

plete resolution of their symptoms or require a short period of

non-operative treatment such as anti-inflammatory medication

or physical therapy. However, the most effective method of sur-

gical intervention is still unclear. It may turn out that nucleus

replacement methods suffice for the majority of patients that

present with recalcitrant low back pain allowing for the use of

technically simpler surgery than afforded by performing a total

disc arthroplasty procedure.

REFERENCES

1. Oegema TR. Biochemistry of the intervertebral disc. Clin Spos Med. 1993;12:419-39.

2. Roberts S. Disc morphology in health and disease. Biochem Soc Trans. 2002;30:864-9.

3. Buckwalter, JA, Mow VC, Boden, SD, Eyre DR,Weidenbaum M. Intervertebraldisc structure, composition, and mechanical function. In: Buckwalter JA,Einhorn TA, Simon SR, editors. Orthopaedic Basic Science-biology and bio-mechanics for the musculoskeletal system. 2nd ed. Rosemont: AmericanAcademy of Orthopaedic Surgeons, 2002:548-55.

4. Buckwalter, JA, Martin J. Intervertebral disc degeneration and back pain. In:Weinstein JN, Gordon SL, editors. Low back pain: a scientific and clinicaloverview. Rosemont, IL: American Academy of Orthopaedic Surgeons, 1996.

5. Ohshima H, Urban JP. The effect of lactate and pH on proteoglycans and pro-tein synthesis rates in the intervertebral disc. Spine 1992; 17:1079-82.

6. MacLean JJ, Lee CR, Grad S, Ito K, Alini M, Iatridis JC. Effects of immobiliza-tion and dynamic compression on the intervertebral disc cell gene expressionin vivo. Spine 2003; 28:973-81

7. Doita M, Kanatani T, Harada T, Mizuno K. Immunohistologic study of theruptured intervertebral disc of the lumbar spine. Spine 1996; 21(2)235-41.

8. Furusawa N, Baba H, Miyoshi N, et al. Herniation of cervical intervertebraldisc: immunohistochemical examination and measurement of nitric oxideproduction. Spine 2001; 26:1110-6.

9. Yong-Hing K, Kirkaldy-Willis WH. The pathophysiology of degenerative dis-ease of the lumbar spine. Orthop Clin North Am. 1983 Jul;14(3):491-504.

10. Erkintalo MO, Salminen JJ, Alanen AM, Paajanen HE, Kormano MJ.Development of degenerative changes in the lumbar intervertebral disc:results of a prospective MR imaging study in adolescents with and withoutlow-back pain. Radiology. 1995 Aug;196(2):529-33.

11. Salminen JJ, Erkintalo M, Laine M, Pentti J. Low back pain in the young.A prospective three-year follow-up study of subjects with and without lowback pain. Spine. 1995 Oct 1;20(19):2101-7; discussion 2108.

12. Savage RA,Whitehouse GH, Roberts N. The relationship between the mag-netic resonance imaging appearance of the lumbar spine and low back pain,age and occupation in males. Eur Spine J. 1997;6(2):106-14.

13. Jensen MC, Brant-Zawadzki MN, Obuchowski N, Modic MT, Malkasian D,Ross JS. Magnetic resonance imaging of the lumbar spine in people withoutback pain. N Engl J Med. 1994 Jul 14;331(2):69-73.

14. Borenstein DG, O'Mara JW Jr, Boden SD, Lauerman WC, Jacobson A,Platenberg C, Schellinger D, Wiesel SW. The value of magnetic resonanceimaging of the lumbar spine to predict low-back pain in asymptomatic sub-jects : a seven-year follow-up study. J Bone Joint Surg Am. 2001 Sep;83-A(9):1306-11.

15. Boden SD, Davis DO, Dina TS, Patronas NJ, Wiesel SW. Abnormal magnetic-resonance scans of the lumbar spine in asymptomatic subjects. A prospectiveinvestigation. J Bone Joint Surg Am. 1990 Mar;72(3):403-8.

16. Lam KS, Carlin D, Mulholland RC. Lumbar disc high-intensity zone: thevalue and significance of provocative discography in the determination ofthe discogenic pain source. Eur Spine J. 2000 Feb;9(1):36-41.

17. Schellhas KP, Pollei SR, Gundry CR, Heithoff KB. Lumbar disc high-intensityzone. Correlation of magnetic resonance imaging and discography. Spine.1996 Jan 1;21(1):79-86.

18. Saifuddin A, Braithwaite I, White J, Taylor BA, Renton P. The value of lumbarspine magnetic resonance imaging in the demonstration of anular tears.Spine. 1998 Feb 15;23(4):453-7.

19. Aprill C, Bogduk N. High-intensity zone: a diagnostic sign of painful lumbardisc on magnetic resonance imaging. Br J Radiol. 1992 May;65(773):361-9.

20. Carragee EJ, Paragioudakis SJ, Khurana S. 2000 Volvo Award winner inclinical studies: Lumbar high-intensity zone and discography in subjectswithout low back problems. Spine. 2000 Dec 1;25(23):2987-92.

21. Kwon BK, Vaccaro AR, Grauer JN, Beiner J. Indications, techniques, and out-comes of posterior surgery for chronic low back pain. Orthop Clin NorthAm. 2003 Apr;34(2):297-308.

22. Tsantrizos A, Baramki HG, Zeidman S, et al. Segmental stability and com-pressive strength of posterior lumbar interbody fusion implants. Spine.2000;25:1899-1907.

23. Enker P, Steffee AD. Interbody fusion and instrumentation. Clin Orthop.1994;300:90-101.

24. Zeidman SM. Intradiscal biomechanics: anterior vs. posterior approach-decisionmaking ALIF vs. PLIF and why? Augmentation vs. stand alone implant.Proceedings of the 16th Annual Meeting of the Federation of SpineAssociations. 2001;10.

25. Shaffrey CI. Indications for threaded interbody devices. Proceedings of the16th Annual Meeting of the Federation of Spine Associations. 2001;9.

26. Zdeblick TA, David SM. A prospective comparison of surgical approach foranterior L4-L5 fusion: laparoscopic versus mini anterior lumbar interbodyfusion. Spine. 2000;25:2682-7.

27. Regan JJ. Laparoscopic lumbar fusion: single surgeon experience in 127 con-secutive cases. Proceedings of the 68th Annual Meeting of the AmericanAcademy of Orthopedic Surgeons. 2001;469.

28. Savas PE, Harris BM, Hilibrand AS, et al. Transforaminal lumbar interbodyfusion: the effect of various instrumentation techniques. Proceedings of the15th Annual Meeting of the North American Spine Society. 2000;216-7.

29. Albert TJ. Complications of cages and dowels. Instructional Course Lecture#209 of the 68th Annual Meeting of the American Academy of OrthopedicSurgeons. 2001.

30. Batterjee KA, Ray CD, Osman MA, et al. One year followup on 17 Saudipatients implanted with a prosthetic disc nucleus. Proceedings of the AnnualMeeting of the International Society for the Study of the Lumbar Spine.2000;114.

31. McAfee PC, Fedder IL, Saiedy S, Shucosky EM, Cunningham BW. SB Charitdisc replacement: report of 60 prospective randomized cases in a US center. JSpinal Disord Tech. 2003 Aug;16(4):424-33.

9

10

Chapter 2 Nucleus Arthroplasty MotionPreservation Technologyversus Nucleus Replacement

The purpose of this chapter is to help clinicians understandthe difference between Nucleus Arthroplasty motion preser-vation technology and nucleus replacement. While the discussion

may seem subjective, the difference between the two terms is vast

and can have a significant impact on a clinical practice.

Nucleus replacement is much like any other joint replacement

within the body. It is meant to replace one biologic component with

another that mimics normal biological function. However, simply

replacing the disc nucleus with a prosthetic device may not address

the problems incurred by patients suffering from degenerative disc

disease (DDD). Unfortunately, DDD is a problem that is not limited

to one portion of the vertebral disc or a single spinal level. Rather,

it is a complex disease that must be

addressed comprehensively.

Nucleus Arthroplasty motion preservation

technology goes beyond nucleus replacement

and involves a comprehensive systematic

approach to DDD. It is not only the implant

that is important in Nucleus Arthroplasty

technology, but the consideration of many factors including proper

patient selection, indications, surgical technique/approach, and

post-operative rehabilitation. Nucleus Arthroplasty technology

involves a complete spectrum of treatment starting with the initial

consultation in the surgeons office and ending with follow-up and

monitoring six months post-surgery. The systematic approach of

Nucleus Arthroplasty technology is better suited to providing pre-

dictable and successful outcomes than the device-only approach

of nucleus replacement.

N U C L E U S A R T H R O P L A S T Y M O T I O NP R E S E R V A T I O N T E C H N O L O G Y G O E SB E Y O N D N U C L E U S R E P L A C E M E N TA N D I N V O LV E S A C O M P R E H E N S I V ES Y S T E M AT I C A P P R O A C H T O D D D .

Reginald J. Davis, MD, FACSCHIEF OF NEUROSURGERY

Baltimore Neurosurgical Associates, PA

Baltimore, MD 21204




New York, NY 10021

11

A discussion of the evolution of hip replacement surgery can set

the stage for the discussion of changes currently occurring

in Nucleus Arthroplasty technology. In the 1970s, a degener-

ated hip joint was treated with a hip replacement device. One

of the biggest problems with early hip replacements was that

the cement used to attach the device to the femur and acetabulum

loosened, resulting in performance problems. The clinical issues

were not simply related to the product but also involved post-

operative patient care. These problems were addressed with a

systematic approach to hip replacement. Uncemented hip

replacement devices with a porous coating that allowed bone in-

growth were developed and replaced devices that were cemented

into place. The new generation implant was designed to function

with the patient and was not merely a device within the body. In

addition to improving the implant-to-patient match, specific

post-operative rehabilitation protocols were developed and opti-

mized. The surgeon provided specific and detailed instructions on

when the patient should put weight on the leg and when he or she

should start walking.

Nucleus replacement therapy is currently in an analogous state

to hip replacement surgery in the 1970s. A systematic approach

involving the whole continuum of care is required to achieve

optimum clinical outcomes with Nucleus Arthroplasty technol-

ogy. Nucleus Arthroplasty system technology is much more

complex than hip replacement given the intricacies of the spine.

It is therefore necessary to address all variables that can affect

the outcome of the treatment. For example, optimal patient

selection and surgical technique without proper rehabilitation

will lead to minimal success. Similarly, thorough post-operative

rehabilitation without appropriate patient selection will also

result in a poor outcome.

While this may seem like common sense, most companies

developing Nucleus Arthroplasty devices have not reached such

a conclusion. Most products are simply nucleus replacement

devices and not arthroplasty systems. Given that each implant

may treat a slightly different indication and require a different

surgical technique means that a unique system involving exten-

sive clinical experience must be developed for each product.

Most disc replacement technologies are not ready for transfor-

mation into Nucleus Arthroplasty systems. While companies

can refine their devices, instruments and surgical techniques

through pre-clinical testing, the indications, patient selection

criteria, and post-operative protocol can only be discerned

through actual clinical experience.

Several issues must be addressed in order to advance the field of

Nucleus Arthroplasty motion preservation system. First, the

process of disc degeneration must be better understood. Not all

DDD is the same, just as not all cases of spondylolisthesis and

herniation are the same. Variations in the process of DDD make

it difficult to treat the condition and to achieve predictable out-

comes. Second, nucleus replacement devices currently being

developed have crossover indications and applications that make

it difficult for the clinician to determine which device is best

suited for a particular patient at a given stage of the disease

process. Additionally, how a patients DDD is classified can

impact patient selection criteria for Nucleus Arthroplasty therapy.

There is a large difference between what is called mild DDD and

what is called early stage DDD. Some clinicians believe severe

disc collapse must be present before a patient is considered to

be in the early stages of DDD. However, in many cases, a patient

may experience pain for an extended period of time, even

though radiographic evidence of DDD is lacking. These patients

may still be good candidates for Nucleus Arthroplasty non-

fusion technology.

Due to the need to develop specific patient selection and indica-

tion criteria for specific devices, the future for the Nucleus

Arthroplasty market will be more individualized as the years

pass. The goal is for a company to have a multitude of device

sizes that can be implanted using a variety of approaches and

implantation techniques. In this way, the implant and surgical

approach can be tailored to address specific patient requirements.

Once again, clinical data is imperative to develop the requisite

patient and product selection criteria. Without valid evidence,

it is more difficult to develop a Nucleus Arthroplasty system that

provides reproducible and successful clinical results. After these

issues are addressed, it is expected that the indications for

Nucleus Arthroplasty systems will be wider than those for total

disc replacements. As more technologies attain long-term clinical

history, the evolution from nucleus replacement to Nucleus

Arthroplasty motion preservation technology will become

clearer to the orthopedic industry, as other arthroplasty

technologies have in the past.

T H E F U T U R E F O R T H E N U C L E U SA R T H R O P L A S T Y M A R K E T W I L L B E M O R EI N D I V I D U A L I Z E D A S T H E Y E A R S G O B Y.

12

REGULATORY OVERVIEW

At the current time, the Food and Drug Administration (FDA)considers the termnucleus arthroplasty as broadly applicableto any device that replaces the nucleus pulposus while preserving the

surrounding annulus. Such devices are intended to reduce pain and

increase function without fusing the spine. The key features of

the FDAs definition include:

Device location (i.e., placement in the nucleus space)

General intent of the device (i.e., not intended to fuse the spine)

Although devices may be varied in their designs, materials, tech-

nological characteristics, and implantation methods, any device

that meets the basic criteria outlined above will be regarded by

the FDA as a Nucleus Arthroplasty system.

The regulatory pathway for marketing approval of Nucleus

Arthroplasty devices involves a Premarket Application (PMA)

submission to the FDA. A PMA should establish reasonable

assurance of safety and effectiveness for a novel therapy or

device, typically using valid scientific evidence that is collected in

a well-controlled clinical trial. FDA approval for an Investigational

Device Exemption (IDE) will allow unapproved devices to be

studied in a clinical trial to gather this data. Such trials are

designed to measure patient pain and function at selected time

points following implantation of the Nucleus Arthroplasty device.

This data is most often compared to a control based on the

current standard of care.

Chapter 3 Nucleus Arthroplasty Technologyfrom the U.S. Regulatory Viewpoint

Glenn A. Stiegman, III, MSVICE PRESIDENT, REGULATORY AFFAIRS

Musculoskeletal Clinical Regulatory Advisers, LLC

New York, NY 10022

13

Currently there are no FDA approved Nucleus Arthroplasty

devices. As of August 2006, four companies are in the process

of conducting five U.S. IDE pilot clinical trials of Nucleus

Arthroplasty technologies.

Although Nucleus Arthroplasty devices may offer many benefits

compared to the current standard of care, device design issues and

clinical concerns must be addressed in order to gather the data

necessary to demonstrate safety and effectiveness. These issues and

concerns should be addressed by means of appropriately-designed

pre-clinical and clinical studies.

CHALLENGES FOR MANUFACTURERS AND THE FDA

Even in the initial stages of development for new and innovative

therapies, the FDA must require that the preliminary safety of the

device be established prior to starting a human clinical trial. This

represents a formidable obstacle for most device manufacturers

because of limitations in testing and characterization methods.

Often when dealing with novel technologies, industry standards

and FDA guidance documents are not available to provide direc-

tion in regard to validation methods. In the case of Nucleus

Arthroplasty devices, the variety of materials, designs, and surgical

implantation techniques have made it virtually impossible to cre-

ate standardized testing that could be applied to the diversity of

devices. Creating tests that are clinically relevant is also challeng-

ing for the device manufacturer. Safety profiles may be very dif-

ferent for each device design; however, testing must be designed

and conducted to demonstrate that devices will not cause unfore-

seen risks. The devices intended use should direct both pre-clini-

cal and clinical evaluations, including material selection, device

design, pre-clinical testing, surgical technique, and clinical study

design. A clear understanding of the devices intended use will

also facilitate regulatory negotiations, and will offer the FDA the

opportunity to provide clear feedback during the pre-clinical and

clinical study design stages.

In the face of all these challenges, it is important for the manufac-

turer to work diligently and consult with the FDA early in the

process to develop appropriate pre-clinical testing. Ideally, this

effort will yield results that are scientifically and clinically relevant,

and that ultimately demonstrate the safety of the device.

REGULATORY REQUIREMENTS

Regulatory requirements for conducting clinical trials and subse-

quent PMA applications include extensive preliminary design

validation and pre-clinical studies. The following are some of the

many challenges involved:

Identifying the appropriate patient population

Selecting appropriate device materials

Designing the optimal device and placement technique

Planning and implementing pre-clinical testing

Implementing the clinical trial

PATIENT POPULATION

Paramount to the development of new treatment alternatives is a

clear understanding of the capabilities and success of available

treatment options in contrast to the unmet patient needs.Within

the confines of degenerative disc disease, the potential playing field

seems to be exceptionally large as there is a significant gap between

the conservative and surgical treatment options that are currently

implemented to cover a wide range of indications and potential

degenerative disease stages.

NUCLEUS ARTHROPLASTY MOTION PRESERVATION TECHNOLOGIESCURRENT U.S. IDE PILOT STUDIES

APPROVAL

COMPANY TECHNOLOGY INDICATION DATE

1 Spine Wave, Inc. NuCore Adjunct To Microdiscectomy Feb-06

2 Raymedica, LLC HydraFlex Not Publicly Available Jun-06

3 Spine Wave, Inc. NuCore Degenerative Disc Disease Jun-06

4 Disc Dynamics, Inc. DASCOR Not Publicly Available Aug-06

5 Pioneer Surgical Technology NUBAC Not Publicly Available Aug-06

prepared by MCRA, LLC

14

In general terms, Nucleus Arthroplasty technologies represent a

host of potential products designed to address degenerative disc

disease. Ideally, the shape, form, and function of each device will

be tailored to meet the individual needs of the patient population

at a specific stage within the degenerative disc cascade.

The success of any Nucleus Arthroplasty device will be directly

tied to the ability of a particular technology to be properly

matched to a defined patient indication. However, trying to

identify the correct patient population and the appropriate time

for surgical intervention are among the biggest clinical chal-

lenges facing those who study Nucleus Arthroplasty devices.

From the regulatory perspective, device manufacturers will be

challenged to both define the intended treatment population

and establish evidence of improvement with the proposed

device in relation to the current standard of care.

DEVICE MATERIAL

Determining the appropriate material is one of the key issues

involved in engineering Nucleus Arthroplasty devices, since inap-

propriate material selection can contribute to potential failure

modes. Each material presents its own regulatory hurdles because

of the lack of validated characterization methods. As material

technologies have advanced, testing standards and characteriza-

tion methods have remained relatively stagnant. Therefore, older

or non-validated testing methods must be used which may pose

risks to the patient if not performed adequately. While the FDA

can provide valuable feedback about the potential risks and con-

cerns associated with each device, appropriate material character-

ization activities (i.e., mechanical, animal, and material tests)

must be determined by the manufacturer.

There are several options that can be used to describe and charac-

terize the device material. General biocompatibility evaluation

and testing as recommended in the ISO Standard 10993 is

required and should be performed at the initial stages of material

development. Animal testing is often required to further study the

material. Ideally, animal testing can be performed in a functional

model in which the device is implanted using similar methods to

those intended for human use. Establishing a functional model

that appropriately evaluates the device in an animal can be difficult

due to the differences in spinal anatomy and biomechanics

between humans and animals. In such instances where an appro-

priate functional evaluation cannot be performed, animal testing

may be conducted in which the primary focus is to evaluate the

effects of material particulate in potential worst-case wear debris

conditions. The particulate test usually consists of implanting an

appropriate and clinically relevant wear debris particle quantity,

shape, and size distribution into the spine of a small animal, such

as a rabbit. The intent of this test is to eliminate potential risks

associated with the material.

DEVICE DESIGN

Obviously, the material and design elements of any Nucleus

Arthroplasty device are intimately linked. The broad spectrum

of available materials has resulted in many different Nucleus

Arthroplasty device designs. The challenge is to determine the

best device design for the intended patient treatment popula-

tion. Each individual design will have specific implications in

regard to indications, patient selection, surgical technique and

post-operative rehabilitation.

Device design performance requirements will also be strongly

influenced by the indications of the selected treatment popula-

tion. As such, it is critical to completely define the design ration-

ale for the device. This can prove to be a daunting task when

working with Nucleus Arthroplasty technologies as the load envi-

ronment could be greatly influenced by many factors such as the

level of the disease, bone quality, placement of the device, and

the degenerative disease stage. This situation is further exacer-

bated by the limited information and clinical experience avail-

able to use in defining appropriate design parameters. All of

these factors can affect the clinical results, welfare of the patient,

and ultimately, the success of a particular device.

N U C L E U S A R T H R O P L A S T Y M O T I O NP R E S E R V A T I O N D E V I C E S M A Y O F F E RA G O O D A L T E R N AT I V E T O T R E A TI N D I C A T I O N S W H E R E T H E R E I S N OR E L I A B L E O R E F F E C T I V E S TA N D A R DO F C A R E .

E A C H I N D I V I D U A L D E V I C E D E S I G N W I L LH AV E S P E C I F I C I M P L I C AT I O N S I N R E G A R DT O I N D I C AT I O N S , PAT I E N T S E L E C T I O N ,S U R G I C A L T E C HN I Q U E AND PO S T- O P E R AT I V ER E H A B I L I TAT I O N .

15

In addition to assessing the potential mechanical challenges

imposed on the design, all potential factors associated with the

surgical approach and device delivery method must also be scru-

tinized. The device may have an ideal design based on biome-

chanical factors, however, the surgical approach, surgical

instruments, and overall surgical procedure may significantly

affect patient outcomes.

PRE-CLINICAL TEST PLANNINGAND IMPLEMENTATION

Preliminary data on Nucleus Arthroplasty devices can be gath-

ered from various studies worldwide. However, most of these

studies have not been long-term, prospectively defined, con-

trolled, randomized, or powered with the sample size required

to make a strong conclusion about the device being studied.

In order to adequately show the device design is safe, potential

failure modes and clinical risks must be described and mitigated.

Mechanical testing is generally used to evaluate device mechanics

under clinically relevant and/or worst-case loads and displace-

ments. The type of test that is required will vary depending on the

particular device design and intent. A complete evaluation of the

device in a biomechanical model such as a cadaver spine is

important to understand the device mechanics and simulated

anatomical performance. Such testing may also provide valuable

information about the device, surgical approach, proposed surgi-

cal instruments, and surgical technique. Loading the spine in var-

ious scenarios may also provide insight into potential clinical

failure modes. While many of these failure modes can be

addressed mechanically, there may still be instances in which the

device performs perfectly in a simulated setting yet shows signifi-

cant failures in subsequent patient evaluations.While mechanical

testing has significant value, comparison of the results to a clinically

successful device or scenario is almost impossible.

CLINICAL TRIAL IMPLEMENTATION

After completing the appropriate pre-clinical testing to charac-

terize device materials, validate the design, and gather prelimi-

nary safety data, a device manufacturer must provide all this

information to the FDA. These results will be reviewed by the

FDA and used to justify approval of the human clinical trial.

The data collected in the trial will be used to demonstrate the

safety and effectiveness of the therapy in the PMA application.

IDE PILOT

Since Nucleus Arthroplasty devices are still considered a novel

therapy that utilize a wide array of designs, materials, and

implantation techniques, the FDA will likely require a pilot study

to ensure that these parameters have been optimized. This is

especially true in cases when bench testing is not adequate to

characterize device safety. The IDE pilot study, also known as a

feasibility study, is a limited human clinical study designed to

answer specific questions associated with the device or implanta-

tion method and to establish the preliminary safety of the device

and surgical technique. The length of a pilot study can vary from

six months to two years and is largely dependent on the ques-

tions or concerns that are being addressed. Specific concerns

about device material, mechanics, or biological effects may

require a study of longer duration while concerns associated

with items such as the surgical technique may be relatively short.

As indicated, a pilot study may assist in addressing concerns that

cannot be tested on the bench. For example, published literature

has reported device expulsions with certain Nucleus Arthroplasty

device designs. However, this particular device failure mode did

not occur during bench, biomechanical, or animal testing.

Clearly, additional bench testing in such situations does not

positively contribute to the existing knowledge base. Thus,

small pilot studies are conducted to provide data that cannot

be obtained strictly through pre-clinical testing.

T H E A B I L I T Y T O U S E T E C H N O L O G I C A L LY A D V A N C E D M AT E R I A L S , D E S I G NP A R A M E T E R S , S U R G I C A L A P P R O A C H E S , A N D I N S T R U M E N TAT I O N A F F O R D E DB Y N U C L E U S A R T H R O P L A S T Y M O T I O N P R E S E R V A T I O N T E C H N O L O G Y C A NM I N I M I Z E T H E R I S K S A S S O C I A T E D W I T H I M P L A N TAT I O N .

16

IDE PIVOTAL

After the pilot study has been completed and all questions or

concerns regarding device safety have been addressed, the manu-

facturer must conduct a clinical study comparing the device to a

valid control. The clinical trial design of the pilot study is often

very similar to the IDE pivotal study. As discussed earlier, select-

ing a control group can prove to be very difficult in the case of

Nucleus Arthroplasty devices. Proper selection of a control group

is extremely important as the treatment results for the control

will serve as a basis for comparison in regard to device safety and

effectiveness. Selection of a control group that does not closely

match the indications and intended patient population will make

it difficult for the FDA and Centers for Medicare and Medicaid

Services (CMS) to determine the clinical meaning behind the

data and how it would translate to the general U.S. population.

As noted above, prior to selecting a control group, it is impera-

tive that the device indications be appropriately defined. The

device indications dictate the process of identifying a proper

control group and directing the design of the pivotal clinical

trial, length of the study, and primary and secondary endpoint

selections. Most Nucleus Arthroplasty devices are indicated for

mild to moderate DDD or instances of acute disc herniation.

Use of Nucleus Arthroplasty devices to address such indications

will require a two-year clinical study. In addition, post-mar-

ket follow-up for a minimum of five years may also be

requested. Appropriately describing the indications for the

intended patient population may well determine the success of

the study and the device itself.

Lastly, establishing the appropriate study endpoints is very

important, as they provide the foundation for the demonstration

of safety and effectiveness as well as supporting evidence for the

device labeling claims. If a manufacturer chooses to exclude rele-

vant endpoints in order to avoid risks or save money, the trial

results may be inadequate to support safety or effectiveness, and

may greatly weaken the manufacturers ability to make label-

ing claims regarding the device performance. Therefore, a

complete and thorough study of all potential study parameters

is recommended, including radiographic, economic, and clinical

assessment measurements.

SUMMARY

Nucleus Arthroplasty motion preservation technology has the

potential to be an excellent treatment alternative for patients in

the mild to moderate stages of DDD. Today, this represents a

relatively large unmet opportunity for advancements in patient

care. However, there are still many unanswered questions that

must be addressed before this device technology can be considered

a viable treatment alternative. As more clinical data becomes

available, manufacturers and the FDA will continue to develop

the expertise required to more appropriately design and evaluate

such devices. Until that time, individual devices must be examined

and studied very carefully on a case-by-case basis.

P R O P E R S E L E C T I O N O F A C O N T R O LG R O U P I S E X T R E M E LY I M P O R TA N T A ST H E T R E A T M E N T R E S U L T S F O R T H EC O N T R O L W I L L S E R V E A S A B A S I S F O RC O M PA R I S O N I N R E G A R D T O D E V I C ES A F E T Y A N D E F F E C T I V E N E S S .

N U C L E U S A R T H R O P L A S T Y M O T I O N P R E S E R V A T I O N T E C H N O L O G Y H A ST H E P O T E N T I A L T O B E A N E X C E L L E N T T R E A T M E N T A L T E R N AT I V E F O RP A T I E N T S I N T H E M I L D T O M O D E R AT E S TA G E S O F D D D . T O D A Y, T H I SR E P R E S E N T S A R E L A T I V E LY L A R G E U N M E T O P P O R T U N I T Y F O RA D V A N C E M E N T S I N P A T I E N T C A R E .

17

THE IMPORTANCE OF REIMBURSEMENT

Obtaining optimal reimbursement is critical to the adoptionof a new device or technology. Even though a particulardevice has received regulatory approval to be marketed, there is

no guarantee that it will be adopted by surgeons if the practice or

hospital cannot obtain reimbursement from third-party payers.

The increasing costs of procedures and devices will make some

surgeons wary of using a product if the prospect of reimburse-

ment is uncertain. However, as the medical device industry con-

tinues to invent and innovate, acquiring reimbursement has

become more difficult. Obtaining proper reimbursement for a

new device is imperative if device manufacturers hope to make

an impact on the market. This is particularly true for orthopedic

devices and technologies because payers are responsible for 90%

of orthopedic procedures. Understanding the reimbursement

process is crucial for medical device companies involved in this

market sector.

Companies can make a multitude of mistakes when seeking reim-

bursement, especially for a groundbreaking treatment such as

Nucleus Arthroplasty technology. Companies may assume that

receiving Food and Drug Administration (FDA) approval will

automatically guarantee reimbursement from payers, but this is

not necessarily the case. A lack of understanding about the clinical

and economic data required to obtain optimal reimbursement can

result in the demise of a Nucleus Arthroplasty company. Therefore,

Nucleus Arthroplasty companies, especially those seeking new or

Chapter 4 Fundamentals of Reimbursement

Kelli HallasVICE PRESIDENT

Field Reimbursement Services

Emerson Consultants, Inc.

Eden Prairie, MN 55344

18

additional codes, must be aware of what government and private

payers require before granting reimbursement for a new device

or technology.

REIMBURSEMENT BASICS

This chapter will review and discuss the basic elements of reim-

bursement in regard to Nucleus Arthroplasty motion preserva-

tion technologies. Most often reimbursement is thought of as a

single entity when in actuality it is composed of the following

three distinct elements:

Coverage

Coding

Payment

Reimbursement is the end result of the interaction of these drivers.

COVERAGE

Coverage refers to a third-party payers decision on whether or

not to pay for a particular procedure, device, therapy, or service

under the health services or benefits that are arranged, provided,

or paid for through a health insurance plan. A coverage determi-

nation is based on whether the procedure, device, therapy, or

service in question is considered a medical necessity. To be con-

sidered medically necessary, the goods or services should meet

the following requirements/conditions:

Appropriate and necessary for the symptoms, diagnosis, or

treatment of a medical condition;

Meet the standards of good medical practice within the med-

ical community in the service area;

Unbiased regarding convenience to the plan member or plan

provider;

Most appropriate level or supply of service that can safely be

provided; and

Provided for the diagnosis or direct care and treatment of the

medical condition.

Note that all of the conditions must be satisfied for the good or

service to be considered a medical necessity.

Coverage can be favorable, unfavorable, or limited in nature. It may

be issued formally within a policy or granted informally on a case-

by-case basis. The coverage of Nucleus Arthroplasty technologies

will vary by payer.Whereas some payers may approve the procedure

for coverage on an individual basis, others will consider the proce-

dure investigational or experimental and deny coverage. This

increased scrutiny is typical for emerging treatments and technolo-

gies.

Obtaining a positive coverage decision is critical to the success of

any technology. The following criteria are considered by payers

when making coverage decisions:

The technology must have final approval from the appropriate

governmental bodiesthe FDA in the U.S.

Scientific evidence must permit conclusions concerning the

effect of the technology on health outcomes.

The technology must improve the net health outcomes.

The technology must be as beneficial as any currently

established alternatives.

Improvement must be attainable outside of the investi-

gational setting.

Peer-reviewed data published in a U.S. journal must be

available, preferably from a multi-centered, double blind,

controlled study conducted in the U.S.

It should also be noted that, although a product may not be

intended for significant use in the Medicare population (patients

age 65 and older), the coverage policies developed by the Centers

for Medicare and Medicaid Services (CMS) heavily influence the

coverage decisions of private payers. Therefore, it is important

that companies consider the impact the technology will have on

the Medicare population during clinical trial design. The final

coverage decision made by CMS on any technology may greatly

impact the companys overall bottom line sales.

CODING

Coding represents the reimbursement language that payers and

providers use to communicate. Codes explain the why and the

what, and are universally accepted among physicians, hospitals,

and payers. Providers report on procedures by using various types

of codes both during clinical trials and after FDA approval. Codes

are dynamic and may change even if the product or procedure

does not. In the long term, it is critical that companies work

closely with CMS, the American Medical Association (AMA),

and relevant professional societies to ensure the development

of appropriate coding recommendations.

M O S T O F T E N R E I M B U R S E M E N T I ST H O U G H T O F A S A S I N G L E E N T I T Y W H E NI N A C T U A L I T Y I T I S C O M P O S E D O F T H EF O L L O W I N G T H R E E D I S T I N C T E L E M E N T S :C O V E R A G E , C O D I N G A N D PA Y M E N T .

During a clinical trial, a code that accurately describes a proce-

dure or service may not exist, so an unlisted procedure code

will be reported. This is most often the case with break-

through and emerging technologies. However, if the appropri-

ate governing body (CMS or AMA) feels that an existing code

can accurately describe the investigational procedure, they may

recommend the use of that code during the clinical trial. In

such instances, it is highly recommended that companies com-

municate with CMS, the AMA, and professional societies, prior

to making any coding recommendations to providers.

Hospitals and physicians use different coding systems (ICD-9-

CM and CPT-4 codes) to report on their work. Each of these

systems will be described separately along with the codes to

report Nucleus Arthroplasty technologies.

Hospitals use ICD-9-CM procedure codes to describe inpatient

surgical, diagnostic, and therapeutic procedures (admitted >24

hours). ICD-9-CM codes are controlled by CMS. During a clini-

cal trial, requests can be submitted to CMS for the creation or

modification of an ICD-9-CM code to allow for accurate classifi-

cation of a new procedure. Formal applications are accepted twice

a year. FDA approval is not required to obtain an ICD-9-CM code

for an inpatient procedure.

CPT-4 codes are used by both physicians and hospital outpatient

departments to describe surgical, non-surgical, and diagnostic

procedures. CPT-4 codes are controlled by the AMA. If the AMA

decides that a procedure is closely related to an existing proce-

dure in consumption of resources, it may recommend use of the

existing code to report the procedure. If the procedure is differ-

ent and distinct from any current coding descriptions, it will rec-

ommend use of an unlisted procedure code during the clinical

trial for tracking and reporting purposes. In the case of Nucleus

Arthroplasty technology, the unlisted procedure code is reported

by the surgeon and will encompass all resource utilization to per-

form the procedure inclusive of the discectomy.

After the clinical trial has been completed, either a professional

society or an external party can file a formal request for either a

new code or modifications to an existing code if the product or

procedure has:

Received FDA approval

Published U.S. peer-reviewed data

Documented widespread use

Support of the professional society

The codes used to report Nucleus Arthroplasty technologies are

listed above in Table 1.

PAYMENT

Payment is determined by contractual terms between healthcare

providers and payers. These arrangements can take different

forms. Examples of hospital payment methodologies include:

Case rate A payment is arranged to cover a specific pro-

cedure, technology, or diagnosis.

Discounted fee for service The payment equals the

amount billed less a pre-negotiated discount.

Fee schedule The facility is paid a flat payment for the

patients admission regardless of resources used or length of

stay (DRG) involved.

Per diem The facility is paid a flat rate per day.

Examples of physician payment methodologies include:

Capitation The physician is paid a certain amount per

member per month to cover the costs of care.

Case rate The surgeon has contracted a fixed fee for a spe-

cific procedure.

Discounted fee for service The payment equals the

amount billed less a pre-negotiated discount.

Fee schedule The physician receives a pre-determined pay-

ment for a particular service.

19

TABLE 1. CODES TO REPORT NUCLEUS ARTHROPLASTY TECHNOLOGIES

Insertion of partial spinal prosthesis, lumbosacral; includes nuclear replacement device lumbar; partialartificial disc prosthesis (flexible) lumbar, and replacement.

Revision or replacement of artificial disc prosthesis, lumbosacral; removal of (partial or total) spinaldisc prosthesis with synchronous insertion of new (partial or total) spinal disc prosthesis lumbosacral;repair of previously inserted spinal disc prosthesis, lumbosacral.

Unlisted procedure of the spine.

CODE TYPE NUMBER DESCRIPTION

84.64

84.68

22899

ICD-9-CM Procedure(hospital)

ICD-9-CM Procedure(hospital)

CPT-4(physician)

20

In the hospital environment, Medicare pays hospitals according

to the DRG (Diagnostic Related Group) methodology. The

DRG system is intended to classify patients into clinically cohe-

sive groups that demonstrate similar patterns of consumption

of hospital resources and length of stay. According to the

Medicare payment system, Nucleus Arthroplasty technology

will be assigned to one of the DRGs listed above in Table 2.

REIMBURSEMENT FOR NEW DEVICES

When a groundbreaking device is substantially more expensive

than devices that are already on the market, companies will

usually seek a new code to receive proper reimbursement.

However, because claims information does not yet exist, many

companies will apply for an add-on payment, which is a tem-

porary provision for new technologies. This additional pay-

ment gives hospitals and surgeons in private practices in the

U.S. an incentive to use products that have recently received

FDA approval. In order to receive an add-on payment, the

product must be:

New,

Substantially improved relative to the existing technology,

diagnosis, or treatment, and

Of sufficient cost.

Add-on payments are difficult to obtain and require sufficient

clinical and economic data in order to prove to payers that such

a payment is justified.

THE CURRENT REIMBURSEMENT STATUS OFNUCLEUS ARTHROPLASTY TECHNOLOGY

It is helpful to consider the status of Nucleus Arthroplasty tech-

nology in order to gain a better appreciation of the current

reimbursement environment for this new technology. Nucleus

Arthroplasty motion preservation technologies are continuously

emerging. Unlike other spine procedures, this breakthrough

technology was not recognized by CMS until October 2004. It

was at this time that CMS created a new subcategory of procedure

codes to classify spine disc replacement technologies including

total and partial replacements.

Although codes were created to enable tracking of Nucleus

Arthroplasty procedures, CMS has collected little claims data

specific to this ICD-9-CM code and technology. This is

because, until recently, no nucleus replacement technologies

have received approval to begin an Investigational Device

Exemption (IDE) clinical trial in the U.S. Due to several recent

approvals, patient outcomes impacting coverage decisions can

now be tracked, and economic data can be collected to ensure

appropriate payment.

Ultimately, it is the responsibility of the industry and health care

providers to assist CMS in making critical coverage and reim-

bursement decisions impacting this technology. Industry must

ensure that economic data is collected and a solid reimburse-

ment strategy is integrated into the early stages of clinical trial

design and product development. Hospitals and physicians must

adhere to coding guidelines set forth to report the procedures.

All activities that take place during the clinical trial phase will

directly impact payer decisions made after FDA approval and will

ultimately affect the economics of this new technology. CMS

requires data to assist payers in making appropriate decisions. To

ensure positive coverage and payment decisions, this data must be

concise, compelling, and show substantial clinical improvement

over the current gold standard. Therefore, design and execution

of a clinical trial can either make or break a technology.

CONCLUSION

The reimbursement landscape for Nucleus Arthroplasty tech-

nologies will continue to evolve. Although a hospital procedure

code exists for the technology; coverage, payment, and physician

CPT-4 codes have yet to be determined. In the end, having a

well-designed reimbursement strategy that engages the efforts

of physicians, professional societies, and industry will have a

positive impact on reimbursement for this technology.

TABLE 2. DRG ASSIGNMENT FOR

NUCLEUS ARTHROPLASTY TECHNOLOGIES

DRG DESCRIPTION

499 Back and neck procedures, except spinal fusion

with complications.

500 Back and neck procedures, except spinal fusion

without complications.

21

OVERVIEW

Over the past 15 years, internal fixation with spinal implantshas been used at an accelerated rate in spinal fusion proce-dures. In the last two years, the advent of non-fusion technologies,

including artificial discs, Nucleus Arthroplasty motion preserva-

tion technology and dynamic stabilization systems, have canni-

balized revenues from traditional fixation and interbody fusion

(IBF) markets. Based on historic data, the orthopedic sector is

trending towards an industry that will be classified by anatomy.

Currently, orthopedics can be divided into four major segments:

Large bone and joint - Hip and knee replacements and

ancillary technologies

Spine - Fusion technologies and now evolving towards

motion preserving technologies

Small bone and joint - From the finger to the shoulder and

from the toe to below the knee joint

Cranio - Maxillo facial

Chapter 5 Worldwide Orthopedicand Spine Market




New York, NY 10021

Viscogliosi Bros., LLCNew York, NY 10022

I N T H E L A S T T W O Y E A R S , T H E A D V E N T O F N O N - F U S I O NT E C H N O L O G I E S , I N C L U D I N G A R T I F I C I A L D I S C S , N U C L E U SA R T H R O P L A S T Y M O T I O N P R E S E R V AT I O N T E C H N O L O G Y A N DD Y N A M I C S TA B I L I Z AT I O N S Y S T E M S , H A V E C A N N I B A L I Z E DR E V E N U E S F R O M T R A D I T I O N A L F I X AT I O N A N D I N T E R B O D YF U S I O N ( I B F ) M A R K E T S .

22

The chart below shows the 2006 estimated market size of the

orthopedic sector by segment. The large bone & joint and spine

sectors are expected to account for the lions share of revenue with

90% of the market. It is anticipated that the orthopedic sector will

have the single largest impact on the global healthcare industry

over the next decade, generating over $100 billion in revenues

worldwide. Future growth is highly dependent on both innovation

and distribution.We can expect to see consolidation in this sector,

which will create efficiencies in distribution and set the stage for

large-scale multinational companies to focus on the entire muscu-

loskeletal system. These companies will work to develop a multi-

faceted arsenal of pharmaceutical, biotech, and nanotech solutions.

Ultimately, the orthopedic sector will grow through life-changing,

surgeon-developed inventions, and the adoption, production, and

global distribution of these devices to patients who demand not

only pain relief, but also the restoration of motion.

The worldwide spine market is estimated to be a $5.8 billion

industry in 2006 and is expected to grow an average 15% to 20%

annually. While historically, this market segment has experienced

a 15% annual growth rate, certain niche markets have been

growing as fast as 40% to 100% per year. The spine market in

2006 is 58 times larger than it was in 1990 when revenues totaled

a mere $100 million. Despite this dramatic increase, this market

is poised for significantly greater growth in the near future due

to a variety of reasons including:

A philosophical revolution toward non-fusion technologies

The availability of new technologies globally to treat

expanding indications

A trend in spine surgery toward less invasive procedures

A demographic increase in the number of patients with

back pain

A continuation of intense scientific interest in the study of

spine and back pain

The increased awareness of successful treatment methods

and technologies among spine surgeons

The interest of surgeons and patients in long-term outcomes

In the last few years, the international spine market has seen the

introduction of non-fusion technologies, including Nucleus

Arthroplasty motion preservation system, artificial discs, and

dynamic stabilization systems. The goal of these motion preserva-

tion technologies is to stabilize the spine yet allow for movement.

Although spinal fusion is a highly documented and proven form

of treatment for many patients, spine surgeons have expressed

significant interest in pain relieving therapies designed to preserve

the natural motion of a given spinal segment while restoring disc

height and stability. Of particular interest are non-fusion therapies

focused on the treatment of patients with mild or moderate disc

conditions. These new motion preserving technologies can be

divided into three broad product categories:

Dynamic stabilization

Nucleus Arthroplasty technology

Total disc replacement (TDR)

It is our belief that these non-fusion technologies are starting to

cannibalize revenues from the traditional fixation and interbody

fusion markets.

U.S. LUMBAR SPINE TREATMENT CONTINUUM

For many years, neurosurgeons and orthopedic spine surgeons

have recognized the limitations of fusion procedures for treating

back pain and have been actively seeking alternatives. While

todays spine market is focused on fusion, we believe this will

change dramatically over the next several years as non-fusion

devices are introduced and proven to be more effective and bene-

ficial for patients. This will significantly affect the industrys

reliance on fusion revenues and will force the current industry

leaders to reevaluate their product portfolios in order to maintain

Documents

Nucleus Arthroplasty Volume I