**Definitions and Scope**

This is a non-coverage Local Coverage Determination (LCD) for lumbar
artificial disc replacement in beneficiaries 60 years of age and younger.
National Coverage Determination (NCD) 150.10 makes lumbar artificial disc
replacement a non-covered service for beneficiaries over 60 years of age. For
beneficiaries age 60 years and younger, the NCD leaves the determination to
local Medicare Administrative Contractors (MACs). Palmetto GBA has determined
that lumbar artificial disc replacement is not reasonable and necessary in
beneficiaries 60 years of age and younger. Revision of a previously placed
artificial disc is, therefore, also not covered. Artificial disc removal
without prosthetic disc revision is not discussed by this LCD.

**Background**

Lower back pain is a common condition that can be caused by a number of
structures in the spine, 1 of which is the intervertebral disc. For patients
who have degenerative disc disease (DDD) at a single level to which their back
pain is attributed and which has not responded to conservative treatment, disc
replacement (also referred to as total disc arthroplasty) has been proposed as
a potential treatment. The goal is to replace the degenerated disc with an
artificial disc, which will not cause pain while hopefully maintaining range
of motion as much as possible. A number of artificial discs have been
developed for the lumbar spine, some of which have been introduced into the
United States as Food and Drug Administration (FDA) approved devices.

For the purposes of coverage policy, a meaningful benefit in human subjects
must be demonstrated. This MAC considers a clinically meaningful benefit to be
a change in symptoms evident to the patient as he or she goes about daily
life. As such, while lumbar artificial discs may preserve range of motion,
range of motion preservation does not itself make a treatment reasonable and
necessary. Only studies designed to assess clinical outcomes or composite
outcomes that included at least 1 clinical measure were considered relevant to
this coverage determination. Studies that strictly assessed biomechanics,
radiographic changes, or other strictly physiologic effects were not evaluated
and are not considered relevant to coverage determination.

A number of artificial discs are available in the United States with different
indications, and much of the literature is device-specific, so this summary
will categorize the evidence by device. As will be reviewed below, lumbar disc
replacement appears to be regarded as an alternative treatment approach to
fusion, which in itself is not considered in this LCD.

**CHARITE  and INMOTION ******

The first artificial disc to be FDA approved for use in the lumbar spine was
the CHARITE **** artificial disc. CHARITE **** was subsequently replaced by
the INMOTION **** artificial disc, which was approved under the CHARITE ****
Artificial Disc Registration. CHARITE **** received a FDA premarket approval
decision on 10/26/2004, but has subsequently been officially withdrawn on
1/5/2012 (FDA CHARITE **** 1). While CHARITE **** and INMOTION ****
artificial disc systems are unavailable for routine clinical use in the United
States currently, the clinical research done on this device family is reviewed
for its relevance to artificial disc replacement in general.

The premarket approval clinical study for CHARITE **** artificial disc in the
Unites States was a non-inferiority randomized study comparing CHARITE ****
to anterior lumbar interbody fusion with a BAK cage in patients with single-
level DDD, the results of which are available on the FDAs website (FDA
CHARITE **** 2). Specifically, the study enrolled subjects between the ages
of 18 and 60 years with single-level DDD between L4 and S1 who had no prior
spine surgery except prior discectomy, laminotomy, laminectomy, or nucleolysis
at the same level and had not improved with 6 months of conservative
management. Subjects were required to have a diagnosis of DDD with back and/or
leg pain with radiographic findings consistent with disc degeneration but
without evidence of nerve root compromise or significant central or lateral
recess stenosis. Subjects were also required to have an Oswestry Disability
Index (ODI) score of at least 30/50 and Visual Analog Score (VAS) of at least
40 mm. Patients were excluded from enrollment if they had DDD at more than 1
level, greater than 3 mm spondylolisthesis, morbid obesity, compression or
burst trauma to L4-S1, pregnancy, active infection, psychosocial disorders,
autoimmune disease, recent investigational drug or device use, spinal tumor,
isthmic spondylolisthesis, or significant lumbar scoliosis. Clinical
effectiveness was established at 24 months post-operatively with a primary
composite endpoint consisting of ODI improvement, device failures, major
complications, and neurological deterioration. The device sponsor recommended
a 25% ODI improvement to meet the threshold of success, and the FDA requested
a 15 point improvement in ODI (a more stringent standard).

A total of 304 patients were studied with 99 assigned to receive fusion, and
205 assigned to receive CHARITE **** implantation. Follow-up data at 24
months was collected on 81 of the patients randomized to fusion and 184 of the
patients randomized to CHARITE **** implantation. On the FDA-requested
primary endpoints, the overall success was 54% for the fusion group and 58%
for the CHARITE **** group. The group treated with CHARITE **** had results
that met both the manufacturers proposed and the FDAs requested overall
outcome requirements for non-inferiority of CHARITE **** as compared with
fusion using a 90% confidence interval. This study was a non-inferiority study
and as such was not planned to show a difference in overall success. However,
based on numbers provided in the FDA report, there appears to be no
statistically significant difference in overall composite success on either
the manufacturers proposed or the FDAs requested outcomes (p=0.334 and p =
0.592 respectively). In looking at the individual elements of the composite
endpoint, there were very few differences between the 2 treatment groups in
device failure success, major complications success, and neurologic status.
With regards to success as measured by ODI improvement, 71% of the CHARITE
**** group and 62% of the fusion group met the manufacturers proposed
definition of success. For the FDAs requested definition of success in ODI
reduction, 64% of the CHARITE **** group and 58% of the fusion group achieved
successful reductions in ODI score. Though statistical significance testing is
not reported for ODI change specifically in the FDA report, a Fisher exact
test on this data shows that the difference is not significant for either
outcome (p = 0.156 and p = 0.412 respectively).

Results from this study have been separately reported in the peer-reviewed
literature as well as in a manuscript that reported only the manufacturer-
proposed definition of success and did not report results for the FDA-defined
endpoint of ODI success (Blumenthal, 2005). This manuscript reports the data
for all of the patients enrolled in the study and appears to assign patients
lost to follow-up to the non-response group. This manuscript reports a
statistically significant difference in outcomes on the composite measure of
success (p < 0.0001), but our own analysis of their data using Fishers exact
test (the reported analytic method of choice for categorical outcomes) shows a
non-significant finding (p = 0.087). The difference in mean ODI and VAS score
was reported in the study at 2 years as not being statistically significantly
different.

Longer term follow-up data was reported from the initial FDA trial for some
patients at 5 years in a later paper (Guyer, 2009). This later report
presented follow-up data from 58% of the originally studied cohort of patients
coming from 8 of the 14 initial study sites. Results are reported regarding
the number of subjects who achieved the FDA requested composite outcome as
well as each individual component of the composite outcome. In the fusion
group 51.2% of subjects met the criteria of overall success at 5 years post-
operatively compared with 57.8% of those who received CHARITE ****
implantation, which met the threshold for non-inferiority. Significance
testing for the difference between groups is not reported, but using a 2-sided
Fishers exact test and ignoring patients who were not followed up, the
difference between groups is not significant (p = 0.576). For ODI improvement
in particular, 65% of subjects met the FDA requested threshold in the control
group compared with 68% in the CHARITE **** , a nonsignificant difference (p
= 0.8443). The editors of the journal also placed a comment in the manuscript
indicating that BAK cage used in the fusion control group was a largely
abandoned fusion device at the time of study publication.

**ProDisc **

ProDisc-L received a FDA premarket approval decision on 8/14/2006 with
indications as follows:

This device is indicated for spinal arthroplasty in skeletally mature
patients with DDD at 1 level from L3-S1. DDD is defined as discogenic back
pain with degeneration of the disc confirmed by patient history and
radiographic studies. These DDD patients should have no more than Grade I
spondylolisthesis at the involved level. Patients receiving the ProDisc-L
Total Disc Replacement should have failed at least 6 months of conservative
treatment prior to implantation of the ProDisc Total Disc Replacement (FDA
ProDisc 1).

The premarket approval clinical study for ProDisc-L was a non-inferiority
study comparing ProDisc-L to circumferential fusion in patients with single-
level DDD, the results of which are available on the FDAs website (FDA
ProDisc 2). Specifically, the study enrolled subjects between the ages of 18
and 60 years with single-level DDD between L3 and S1 who had no prior spinal
fusions and had not improved with 6 months of conservative management. The
diagnosis of DDD was established based on the presence of back and/or leg pain
with radiographic findings consistent with disc degeneration. Subjects were
also required to have an ODI score of at least 20/50 and to be
psychosocially, mentally and physically able to fully comply. Patients were
excluded from enrollment if they had DDD at more than 1 level, too small
vertebral endplates, allergies to 1 of the prosthetic disc materials,
compromised vertebral bodies, facet joint disease, lytic spondylolisthesis,
greater than grade I spondylolisthesis, spinal stenosis, disease of bone
quality, morbid obesity, pregnancy, active infection, use of medications that
interfere with bone healing, autoimmune disease, systemic viral illness, or
active malignancy. Clinical effectiveness was established with a primary
composite endpoint consisting of ODI improvement, no need for reoperation,
Short Form (SF)-36 improvement, neurological status, and radiographic success
24 months following surgery.

A total of 242 patients were randomized with 80 assigned to receive fusion,
and 162 assigned to receive ProDisc-L implantation. Data was also reported
for an additional 50 subjects who received ProDisc-L outside of
randomization, but this non-randomized group was not considered in the
effectiveness comparisons. Follow-up data at 24 months was collected on 71 of
the patients randomized to fusion and 149 of the patients randomized to
ProDisc-L implantation. On the FDA-requested primary endpoints, the overall
success was 40.8% for the fusion group and 53.4% for the  ProDisc-L group.
The group treated with ProDisc-L had results that met the FDAs requirements
for non-inferiority of ProDisc-L as compared with fusion. This study was not
planned to show a statistically significant difference in overall success,
though the FDA summary report indicates that using a 1-sided Fishers exact
test, a difference was found between the ProDisc-L and control groups with p
= 0.0438 on the FDA requested definition of success (while a 2-sided test
value is not reported, this would not have been significant with a 2-sided
test). The difference between the 2 groups was statistically significant
(p=0.0053) with the applicant-proposed success criteria and would have been
significant even with the use of 2-sided testing.

Results of the initial FDA approval study have also been published in separate
manuscript in the peer-reviewed literature (Zigler, 2007).

Some of the subjects included in the initial FDA approval study were followed
for 3 more years (a total of 5 years of post-operative follow-up) as part of a
post-approval study. Results were published on the FDA website (FDA ProDisc
3) and in the peer-reviewed literature (Zigler, 2012). There was an 85.1%
follow-up in the ProDisc-L group and a 74.7% follow-up in the fusion group.
Composite statistical success was not significantly different between the 2
groups at 5 years (p=0.7438). Secondary outcomes including ODI, SF-36, and VAS
Pain were not statistically significantly different between the 2 groups at 5
years.

In addition to the FDA premarket approval study comparing ProDisc-L to
fusion, a study was published comparing surgical outcomes in patients treated
with the Pro-Disc II to conservative management in patients with lower back
pain by authors with no reported competing interests (Hellum, 2011). Patients
were considered for inclusion with DDD only at the lower spinal levels and
were excluded if they had symptoms of nerve root impingement. The primary
outcome was mean change in ODI at 1 and 2 years post-operatively with a pre-
specified difference of 10 points being considered the minimum clinically
meaningful difference. A total of 86 patients were randomized to each group.
One and 2 years post-operatively, both groups had improvement with a reduction
from 42.8% to 33.0% at 1 year and 30.0% at 2 years in the rehabilitation
group. The group treated with disc arthroplasty had a reduction from a mean
ODI of 41.8% at baseline to 22.3% at year 1 and 21.2% at year 2. The between
group difference in outcomes was considered statistically significant (p <
0.001 and p = 0.001 at 1 and 2 years respectively) favoring disc arthroplasty.
However, the between group difference at 2 years was reported as 8.4 points on
the ODI, which was below the pre-specified threshold for a clinically
important difference of 10 points.

**activL  Artificial Disc**

activL received a premarket approval decision on 6/11/2015.

Per FDA website: This device is indicated for reconstruction of the disc at 1
level (L4-L5 or L5-S1) following single-level discectomy in skeletally mature
patients with symptomatic DDD with no more than grade I spondylolisthesis at
the involved level. DDD is defined as discogenic back pain with degeneration
of the disc confirmed by patient history, physical examination, and
radiographic studies. The activL artificial disc is implanted using an
anterior retroperitoneal approach. Patients receiving the activL artificial
disc should have failed at least 6 months of nonoperative treatment prior to
implantation of the device" (FDA activL 1).

The premarket approval clinical study for activL was a non-inferiority study
comparing activL to a control group who received disc arthroplasty with 1 of
the other 2 disc replacement devices available in the United States, CHARITE
**** or ProDisc-L, in patients with single-level DDD, the results of which
are available on the FDAs website (FDA activL 2). Specifically, the study
enrolled subjects between the ages of 18 and 60 years with single-level DDD
between L4 and S1 who had no prior spine surgery except prior microdiscectomy,
laminotomy, hemilaminectomy, nucleoplasty, or intradiscal electro-thermal
annuloplasty and had not improved with 6 months of conservative management.
Subjects were required to have a diagnosis of DDD with back pain with
radiographic findings consistent with disc degeneration but without leg pain
suggestive of radiculopathy, myelopathy, or significant sagittal stenosis < 8
mm. Subjects were also required to have an ODI score of at least 40/50. An
abbreviated list of additional exclusionary criteria is as follows: morbid
obesity, active infection, psychosocial disorders, autoimmune disease, recent
investigational drug or device use, spinal tumor, isthmic spondylolisthesis,
significant lumbar scoliosis, viral infection precluding surgery, insulin-
dependent diabetes, prior intra-abdominal inflammation, prior nephrectomy, or
history of thromboembolic disease. Clinical effectiveness was established at
24 months post-operatively with a primary composite endpoint consisting of ODI
improvement (number who achieved a 15 point improvement), neurological status,
radiographic range of motion status, device status, and no serious device
related adverse events. A second composite clinical endpoint was also
requested by the FDA, which did not include range of motion. It appears that
this was not a pre-specified analytic decision. Data were also reported at 12
months, 3 years, and 4 years, in addition to numerous secondary endpoints.
This study was designed to demonstrate non-inferiority, but if non-inferiority
was demonstrated there was a pre-specified plan to test for superiority of
activL over the control groups treatment.

A total of 376 patients were enrolled and proceeded to surgery, 52 of whom
were not randomized, leaving a total of 324 randomized subjects, 218 to
activL and 106 to the control group. Complete follow-up data at 24 months was
available for 223 subjects, but in reporting results, subjects for whom
follow-up data was unavailable were considered failures. Data was also
reported for patients who were not randomized, but this data is not considered
in the primary efficacy analysis. On the originally specified composite
measure, including range of motion, 42.2% of subjects in the activL group and
28.3% of subjects in the control group were found to achieve success. activL
was both non-inferior to (p < 0.0001) and superior to (p = 0.02) control. Much
of the difference between the 2 groups on the composite outcome appeared to be
due to range of motion differences, leading to the FDAs request for analysis
with a composite endpoint not including this component. On the composite
measure of overall success excluding range of motion, 61.9% of subjects in the
activL group and 52.8% of subjects in the control group were found to achieve
success. The activL group had non-inferior (p = 0.0004) but not superior (p =
0.1485) outcomes compared with the control group. In each of the individual
components of the composite endpoint, only range of motion was significantly
different (p = 0.0065). Success on ODI (specified as a 15 point improvement)
was achieved in 75.2% of the activL group and 66.0% of the control group, a
non-significant difference (p = 0.0874). While it was not part of the pre-
specified primary outcome, and completeness of follow-up data was limited,
results are reported for 3 and 4 years of post-operative follow-up for the 2
composite outcome measures (with and without range of motion) treating losses
to follow-up as treatment failures. Using a 2-sided Fisher exact test,
differences between the 2 treatment groups were not significant at either time
point for either composite outcome.

The results of the FDA approval study for activL have also published in the
peer-reviewed literature (Garcia, 2015). We are unaware of additional longer
term follow-up data in other subsequently published studies.

**Other Studies**

A study comparing lumbar total disc replacement using multiple disc
replacement systems compared with fusion has also been published with follow-
up at 2 years (Berg, 2009) and at 5 years (Skold, 2013). In this study 80
patients were randomized to receive 1 of 3 prosthetic discs, and 72 patients
were randomized to receive fusion. The 3 prosthetic discs used included the
CHARITE **** , ProDisc, and Maverick artificial discs. The fusion methods
used were posterior lumbar interbody fusion or posterolateral fusion. Results
were not further stratified by disc or fusion method. The primary outcome
measured was global assessment of symptoms rated on a 5 point scale from
worse to totally pain free. However, a specific threshold does not appear
to have been selected for defining treatment success in this study. Prior
research has used any level of improvement on the global assessment as a
threshold for defining a clinically important difference (Hagg, 2003).

At 2 years the pain free fraction of each treatment arm was 30% for disc
replacement and 15% for the fusion group, a statistically significant
difference (p = 0.031). However, the differences between the proportion of
patients who achieved other levels of improvement were not statistically
significantly different at 2 years. It appears that 70 of the 80 subjects in
the disc replacement group had some improvement, and 62 of the 72 subjects in
the fusion group had some improvement. Therefore, if the threshold of any
level of improvement is used to define treatment success, then from the data
reported, the difference in success was statistically insignificant at 2 years
post-operatively (p = 0.815). Data from 5 year outcomes shows a statistically
significant difference in the proportion of patients who were totally pain
free 38% versus 15% for the disc replacement and fusion groups respectively (p
= 0.002). However, if a threshold of any level of improvement is used as a
marker of treatment success, then 71 of the 80 disc replacement subjects had
success, and 62 of 72 fusion patients had success, an insignificant difference
(p = 0.634).

A number of meta-analyses of lumbar total disc replacement have also been
performed with varying results.

A meta-analysis compared lumbar total disc replacement to fusion for the
treatment of lower back pain with 2 and 5 year post-operative results (Yajun,
2010). This meta-analysis included a total of 5 randomized controlled trials.
The meta-analysis included only 1 and 2-level disease and included CHARITE
**** , ProDisc, Maverick, and FlexiCore devices. Anterior and posterior
fusion approaches were included. This analysis found a statistically
significant difference favoring disc replacement over fusion at 2 years. There
was a mean difference of 5 points on the VAS and a mean difference of 4 points
on the ODI 2 years post-operatively. The study authors described this
difference as clinically insignificant. There was no statistically significant
difference 5 years post-operatively.

A Cochrane review and meta-analysis examined lumbar total disc replacement for
the treatment of lower back pain (Jacobs, 2013). A total of 7 randomized
controlled trials had results pooled. The trials included CHARITE **** ,
ProDisc, Maverick, and FlexiCore devices in subjects with both single and
2-level disease. Treatments used in the control group included fusion and
rehabilitation. Included studies reported results for up to 2 years post-
operatively. There was a mean difference of roughly 5 points on the VAS and a
mean difference of roughly 4 points on the ODI between disc replacement and
control treatment. The authors specified clinically important differences of
15 on the VAS and 10 on the ODI. Using these criteria for clinical importance,
the statistically significant findings favoring disc replacement were
concluded by the authors to be clinically insignificant.

Another, meta-analysis combining results of 6 randomized-controlled trials
(Wei, 2013) compared total disc replacement to fusion surgery in the treatment
of lower back pain using 2 year post-operative outcomes. The meta-analysis
contained studies concerning both single level and 2-level disease and
included CHARITE **** , ProDisc, and Maverick devices. Fusion techniques
included both anterior and posterior approaches. The meta-analysis used random
effects models and found results favoring disc replacement on the VAS of pain
as well as the ODI. The authors concluded that wider spread adoption of the
use of artificial disc replacement would be appropriate.

An important concern in a number of the studies above is determining a
clinically important change. While the premise of the artificial disc is that
it offers an advantage to fusion from its ability to preserve range of motion,
radiographically measured range of motion is not an outcome that addresses a
patients symptoms or ability to engage in life activities. Notably, the FDA
approval studies of artificial discs were all based on composite outcome
measures each of which included a radiographic outcome, which did not itself
necessarily; translate to clinically meaningful improvement in the patients
life. However, these composite endpoints also included measures of clinical
symptom experience, with the ODI being incorporated in all 3 composite
measures. Presently, the ODI is 1 of the most important and commonly used
clinical outcomes in studies of the human spine. In 2 of the 3 devices studied
(CHARITE **** / INMOTION **** and ProDisc-L), the sponsor-proposed and the
FDA requested definitions of ODI success differed.

Treatment with the CHARITE **** / INMOTION **** disc arthroplasty system has
been specifically studied in patients with DDD who have back and/or leg pain
and was compared with fusion in a high quality study. The FDA approval study
showed that treatment with CHARITE **** / INMOTION **** was at least as good
as surgical fusion, but this effect was demonstrated in a population of
patients with DDD without spondylolytic spondylolisthesis, high grade
spondylolisthesis, or spinal stenosis. Regardless, a benefit of using CHARITE
**** / INMOTION **** as compared with fusion was not shown in the
manufacturer proposed or FDA-requested definitions of primary composite
outcome success at 2 years or in the FDA-requested definition of composite
outcome success at 5 years of post-operative follow-up. There was also not a
significant difference in success as measured by ODI score alone using the
manufacturers (25% improvement) or the FDAs definition of ODI success (15
point improvement). In summary high quality research provides evidence that
the CHARITE **** / INMOTION **** is at least as good as surgical fusion for
lower back pain due to DDD but not superior to this treatment.

The ProDisc-L has been specifically studied in patients with DDD who have
back and/or leg pain and was compared with fusion in a high quality study. The
FDA approval study showed that ProDisc-L was at least as good as surgical
fusion in a population of patients with DDD without spondylolytic
spondylolisthesis, high grade spondylolisthesis, or spinal stenosis.
Regardless, a benefit of using ProDisc-L as compared with fusion was not
shown in the FDA-requested primary composite outcome at 2 years or in the
manufacturer proposed or FDA-requested outcomes at 5 years of post-operative
follow-up. A later study compared the ProDisc-II to rehabilitation in
patients with lower back pain and DDD. While treatment with the ProDisc was
found to result in greater improvement as measured by ODI than rehabilitation,
this difference did not meet the investigators pre-specified threshold of a
clinically meaningful difference which agrees with research by Hagg (2003). In
summary high quality research provides evidence that the ProDisc-L is at
least as good as surgical fusion for the treatment of lower back pain due to
DDD but not superior to this treatment. There is also evidence that treatment
with ProDisc-L is superior to conservative management, but the benefit is
below the threshold of a clinically meaningful difference.

The activL device has been specifically studied in patients with DDD who have
back and/or leg pain and was compared with the other 2 artificial discs
approved for the United States market in a high quality study as part of the
FDA premarket approval process. The FDA approval study showed that activL was
at least as good as the other artificial discs in a population of patients
with DDD without spondylolytic spondylolisthesis, high grade
spondylolisthesis, or spinal stenosis. However, there was not a clear
advantage of treatment with activL as compared with these other products, and
as reviewed above, the other 2 lumbar disc replacement systems do not clearly
demonstrate a meaningful benefit in comparison with either fusion or
conservative management.

The study involving multiple artificial discs with 2 and 5 year post-operative
results published by Berg (2009) and Skold (2013), respectively, provided
evidence that patients treated with total disc replacement were more likely to
be pain free at 2 years and 5 years post-operatively than those treated with
posterior interbody fusion or posterolateral fusion. However, this particular
outcome is the best outcome and does not capture other subjects who might be
considered to have a successful response to treatment. If one considers those
patients who had some degree of improvement a treatment success, then the
proportion of patients with treatment success in either treatment group is
very similar. Additionally, the fusion techniques used in this study as a
comparison are worth noting. The original study for CHARITE **** used an
anterior lumbar interbody fusion rather than a posterior interbody or
posterolateral fusion as were used in this study. Moreover, there are concerns
that posterolateral fusion, 1 of the techniques used in this study, produces
fewer favorable outcomes than interbody fusion techniques (Mummaneni, 2014).

Other lumbar artificial discs that have been studied include the Maverick,
FlexiCore, KineFlex-L, and AcroFlex, none of which have been available in
the United States or have been used as a control in a pivotal trial for a
device that currently is available, and as such, studies of these discs are
not reviewed for coverage determination. Additionally, studies reviewing
mechanical properties of artificial discs and mechanical properties of the
spines of patients who have had artificial discs placed have been done, but
since these studies do not inform regarding clinical outcomes, they are not
considered here for the purposes of coverage determination.

Three meta-analyses combining data from multiple trials using multiple disc
replacement devices and control treatment approaches were reviewed. There was
significant overlap between the literature incorporated in each meta-analysis,
and they had similar findings of a small statistically detectable difference
in outcomes favoring disc replacement 2 years post-operatively. However, this
small difference is not clinically meaningful, and is a small difference
measured typically in comparison to a treatment that is itself controversial
for the treatment of lower back pain.

Treatment with all 3 disc arthroplasty systems that have been available in the
United States for lumbar spine disc replacement have demonstrated non-
inferiority to either fusion or to other disc replacement systems that have
previously been established as non-inferior to fusion in high quality
research. However, all of these disc replacement systems have been studied
specifically in patients with primarily lower back pain for whom there are not
concerns of instability or nerve root involvement. This population is 1 in
which spinal fusion is a controversial treatment, and which appears to be of a
limited benefit. Additionally, superiority to fusion or other disc replacement
systems has not been clearly established for any of the available disc
replacement devices. Of the 3 lumbar disc replacement devices on the market,
only ProDisc has been studied in comparison to conservative treatment in a
high quality study, and while a statistically detectable benefit was found,
this benefit did not reach the threshold of being clinically meaningful. In
summary, numerous high quality studies have been performed for the use of
lumbar disc replacement in the treatment of lower back pain, which generally
do not provide evidence of meaningful superiority of disc replacement over
alternative surgical treatments or conservative treatment in patients with
lower back pain.

In populations for whom surgical treatment with fusion is a well-accepted
therapeutic approach, we are unaware of any high quality evidence in which use
of lumbar artificial disc replacement has been studied.