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Technology Evaluation
Center (TEC)


Artificial Vertebral Disc Arthroplasty for Treatment of Degenerative Disease of the Cervical Spine

Executive Summary

Background

Approximately 60% of individuals aged 40 years and older have radiographic evidence of cervical degenerative disc disease (DDD) secondary to spondylosis. Symptoms can include neck and arm pain associated with radiculopathy or myelopathy. Untreated, the signs and symptoms of cervical DDD may diminish, stabilize, or worsen. Initial conservative therapies aim to relieve pain and prevent neurological injury. Typically, if at least 2 to 6 months of conservative treatment is ineffective, or the patient experiences progressive neurological or functional impairments, surgical intervention may be indicated.

Anterior cervical discectomy and fusion (ACDF), using autologous or allogeneic bone, has long been considered the definitive surgical treatment for symptomatic DDD of the cervical spine. Recently, artificial intervertebral disc arthroplasty (AIDA) has been proposed as an alternative. AIDA uses virtually the same surgical approach as ACDF, but differs in that an artificial disc device is secured in the intervertebral space, rather than bone. It has been suggested that properly performed AIDA maintains anatomical disc space height, normal segmental lordosis, and physiological motion patterns at the index and adjacent cervical levels. Maintenance of physiological spinal motion patterns might then reduce risk for developing adjacent-level DDD felt to be secondary to altered mechanics at segments above or below the fusion site. This is the primary rationale for the development and use of artificial disc devices.

Objective

The objective of this Assessment is to determine whether AIDA improves health outcomes when used as an alternative to anterior-plated ACDF for patients with DDD of the cervical spine.

Search Strategy

MEDLINE® was searched (via PubMed) using the terms “cervical disc” and “replacement” or “prosthesis” and also with the term “cervical arthroplasty.” The search was performed through August 2011, limited to English-language articles on human subjects.

Selection Criteria

The Assessment focuses on the randomized, investigational device exemption (IDE) clinical trials of the Prestige ST, ProDisc-C, and Bryan artificial discs (approved via premarketing application [PMA] approval by the U.S. Food and Drug Administration [FDA] in July 2007, December 2007, and May 2009, respectively). Studies using any non-FDA-approved or precursor devices were excluded. Studies examining long-term outcomes of cervical discs were also reviewed.

Main Results

Randomized, controlled trials of Prestige ST, ProDisc-C, and Bryan disc were reviewed. The designs of the 3 trials were nearly identical, employing similar inclusion and exclusion criteria, 24-month duration and follow-up schedule, study endpoints, success criteria, and noninferiority approach and margin (10%). Long-term follow-up studies based on these trials were also reviewed.

Primary outcome measures included the Neck Disability Index (NDI) and neurological status. The NDI is a multidimensional instrument assessing the effects of pain and disability on a patient’s ability to manage everyday life. The tool includes 10 questions addressing neck pain intensity, personal care, lifting, reading, headaches, concentration, work, driving, sleeping, and recreation. A total NDI score is obtained by summing and then expressed as a percentage from 0% to 100%, with a lower percentage indicating less pain and disability. NDI response was reflected by improvement of 15 points or more. The neurological status outcome was a composite measure of motor function, sensory function, and deep tendon reflexes. Neurological success was defined as postoperative maintenance or improvement compared to preoperative status. Details of examiner expertise, blinding, intra- and interobserver variability were not reported in either trial. The primary composite endpoint (“overall success”) was defined as attainment of all of the following: success as defined for the two primary outcome variables, plus a requirement for no serious implant- or procedure-associated adverse event, and no additional surgical procedure classified as a failure.

The Prestige ST disc was evaluated in a randomized, controlled trial in which disc arthroplasty (n=276) was compared to anterior-plated ACDF using allograft bone (n=265; 85% of those randomized to ACDF and 88% to AIDA underwent surgery). Participants were unblinded. Trial quality was rated as poor due to systematic differences between the randomized and treated groups and unclear blinding of neurological assessments.

Patients (mean age 42.1 and 43.5 years in AIDA and ACDF arms, 46% male) had neck and arm pain secondary to DDD at a single level between C3 and C7 with documented presence of a herniated disc or osteophyte formation. Prior to surgery, all had received conservative therapy.

AIDA with the Prestige ST disc was noninferior to ACDF, as assessed by the NDI with improvements of 15 points or more in 84% and 81% of AIDA and ACDF patients, respectively. Neurological status was maintained or improved more often following AIDA (93% versus 84%, p<0.001). For the overall success endpoint, AIDA was judged superior to ACDF (79% versus 68%, p=0.004)—attributable to the neurological status component endpoint.

Perioperative and surgical outcomes were similar between treatment arms. Radiographic fusion was demonstrable for 97.5% of ACDF patients at 24-month follow-up. Cervical neck angular motion was maintained at preoperative levels in arthroplasty patients and restricted, as expected, in ACDF patients. Surgery at adjacent levels was performed in 3 (1.1%) of the AIDA arm and in 9 (3.3%) undergoing ACDF (p=0.07, X2 1 df).

The long-term follow-up study of this trial reports outcomes of approximately half of the participants of the trial at 60 months, some of whom have been lost to follow-up and others who have not yet reached 60 months. Results show outcomes consistent with similar outcomes between the two procedures. Various types of additional surgery were needed less often with the Prestige ST disc.

The ProDisc-C trial differed from the Prestige ST trial by blinding participants to study arm until following surgery. The multicenter trial (13 sites and 13 surgeons) included 209 patients (ProDisc-C, n=103; ACDF, n=106). Mean patient age was 42.1 and 43.5 years in AIDA and ACDF arms, with 46% and 49% male, respectively. At 24 months, follow-up rates were 98% in the ProDisc-C and 95% in the ACDF arms, respectively. Trial quality was rated fair due to inability to determine appropriateness of analyses and apparently unblinded neurological assessments.

AIDA with the ProDisc-C disc was noninferior to ACDF as measured by the NDI—an improvement of 15 points or more in 80% and 78% of AIDA and ACDF patients, respectively. Neurological status was maintained or improved similarly in both groups: AIDA (91%) and ACDF (88%). For the overall success endpoint, AIDA was judged noninferior to ACDF (72% versus 68%), but not superior.

Secondary surgical procedures were more frequent following ACDF (8.5% versus 1.9%, absolute difference 6.6%; 95% CI: 0.6–12.5%). One patient (0.9%) in the ACDF arm underwent adjacent level fusion, while none did in the AIDA group. Other perioperative and surgical outcomes were similar between groups.

Long-term follow-up of this clinical trial was reported at a 48-month outcome point, at which approximately half of the originally enrolled subjects were included in the analysis. Clinical outcomes were similar between the 2 groups, with point estimates in favor of ProDisc-C. There was a cumulative incidence of additional surgeries of 2.9% in the ProDisc-C group and 11.3% in the ACDF group.

The Bryan disc trial enrolled 242 patients to receive AIDA and 221 to receive ACDF. Patient characteristics in terms of mean age and gender were similar to the other clinical trials. At 24 months, follow-up rates were 95% in the Bryan disc and 88% in the ACDF arms, respectively. Trial quality was rated fair.

The trial was also designed as a noninferiority trial. Noninferiority criteria were met for NDI mean improvement, percent NDI success (15-point or more improvement), and overall success. Predefined superiority criteria for the Bryan disc was met for percent NDI success and overall success.

Secondary surgical procedures occurred with similar frequency in both groups, occurring in 2.5% of Bryan disc patients and 3.6% of ACDF patients.

Long-term follow-up of this trial is reported from only a single site of the multicenter clinical trial. The original sample size from this site is small (47 patients), but the follow-up rate is very good at approximately 80%. The clinical outcomes favor the Bryan disc but are not statistically significant. Additional surgery rates were lower for the Bryan disc.

Case series of uncertain quality in terms of outcome assessment and follow-up rates report about 90% good to excellent results of the Bryan disc based on the Odom criteria.

Author’s Comments and Conclusions

After 2 years’ follow-up, trials of the Prestige ST, ProDisc-C, and Bryan discs met noninferiority criteria as measured by the NDI and overall success composite outcome. Although informative, the evidence at 2 years is not sufficient to allow conclusions whether AIDA with either device is as beneficial as ACDF because of uncertainty regarding longer-term outcomes. The reports of long-term outcomes of these devices do not have good follow-up rates. The results of these reports are consistent with continued noninferiority of AIDA for all devices and lower cumulative reoperation rates at 4 to 6 years, but uncertainty remains due to the low follow-up rates. Evidence of these comparative outcomes derives solely from industry-sponsored clinical trials and FDA-mandated follow-up studies. Noninferiority trials are justified when there is some known benefit that offsets a potential increment of inferior primary outcome. This known benefit has never been established for this procedure.

Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether artificial intervertebral disc arthroplasty as a treatment for DDD of the cervical spine meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria.

1. The technology must have final approval from the appropriate governmental regulatory bodies.

The Prestige ST, ProDisc-C, and Bryan discs received U.S. Food and Drug Administration (FDA) marketing approval in July 2007, December 2007, and May 2009, respectively. The discs are indicated in skeletally mature patients for C3-C7 disc reconstruction following single-level discectomy for intractable radiculopathy and/or myelopathy. The devices are implanted via an open anterior approach. Intractable radiculopathy and/or myelopathy should present with at least one of the following items producing symptomatic nerve root and/or spinal cord compression that is documented by patient history (e.g., pain [neck and/or arm pain], functional deficit, and/or neurological deficit), and radiographic studies (e.g., CT, MRI, x-rays, etc.): 1) herniated disc, and/or 2) osteophyte formation.

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.

Evidence derives from 3 randomized controlled trials designed to test noninferiority—one each of the Prestige ST, ProDisc-C, and Bryan discs—and long-term follow-up studies based on these clinical trials. The evidence is insufficient to support conclusions concerning the comparative effect of AIDA on health outcomes.

3. The technology must improve the net health outcome; and

4. The technology must be as beneficial as any established alternatives.

The evidence shows that clinical outcomes are similar at the 2-year outcome point between AIDA and ACDF. The long-term follow-up studies show continued similarity in clinical outcomes at 4 to 6 years and lower cumulative reoperation rates in AIDA patients. The long-term studies have considerable losses to follow-up, and thus the outcomes are uncertain. The rationale for a noninferiority endpoint has never been established, as there is no proven offsetting benefit for AIDA. Thus, there remains uncertainty regarding the health benefit of AIDA.

5. The improvement must be attainable outside the investigational settings.

Whether AIDA improves the net health outcome has not been established in the investigational setting.

Based on the above, artificial intervertebral disc arthroplasty for the treatment of patients with cervical degenerative disc disease does not meet the TEC criteria.


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allograft; anterior; anterior; arthroplasty; artificial; autograft; Bayesian; biomechanics; bone graft; Bryan; cervical; DDD: FSU; degenerative disc disease; disc; discectomy; disk; ; functional spinal unit; fusion; IDE; intervertebral; investigational device exemption; kinematics; lordosis; NDI; neck; Neck Disability Index; noninferiority; plated; plating; Prestige; ProDisc; replacement; spinal; spine; spondylosis; stenosis;