TEC Assessment Index

Artificial Intervertebral Disc Arthroplasty for Treatment of Degenerative Disc 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 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 January 2009, 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 and ProDisc-C artificial discs (approved via premarketing application [PMA] approval by the U.S. Food and Drug Administration [FDA] in July and December 2007, respectively). Studies using any non-FDA-approved or precursor devices were excluded.

Main Results

Randomized, controlled trials of Prestige ST and ProDisc-C were reviewed. The designs of the two 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%).

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 ≥15. 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 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 disc was noninferior to ACDF as assessed by the NDI with improvements of ≥15 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, χ2 1 df).

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 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 and none undergoing AIDA. Other perioperative and surgical outcomes were similar between groups.

Author's Comments and Conclusions

After 2 years' follow-up, trials of the Prestige ST and ProDisc-C discs found noninferiority as measured by the NDI and overall success composite outcome. Although informative, the evidence is not sufficient to allow concluding whether AIDA with either device is as beneficial as ACDF because of uncertainty regarding longer-term outcomes. Experience with ACDF and its high success rate requires a convincing rationale and supporting evidence to utilize a different procedure—noninferiority alone is insufficient. Neither trial provides adequate direct evidence over a relevant follow-up period (suggested to be 5 to 7 years) on subsequent adjacent-level DDD in control and investigational group patients.

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 and ProDisc-C Cervical discs received U.S. Food and Drug Administration (FDA) marketing approval in July and December 2007, 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.

A third product (Bryan Cervical Disc) received an approvable decision by an FDA advisory panel July 17, 2007, but had not received final marketing approval at the time this Assessment was originally prepared. As this Assessment was in press, the Bryan disc received PMA approval from the FDA (May 12, 2009). The Bryan disc is intended for use in patients similar to those for whom the Prestige device is indicated. As this Assessment excluded studies using any non-FDA-approved or precursor devices, evidence on the Bryan disc was not included in the original body of the Assessment; data on this device are included in Appendix C of this Assessment. The addition of these data does not change the conclusions of this Assessment.

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

Evidence derives from two randomized controlled trials designed to test noninferiority—one of the Prestige ST and the other of the ProDisc-C. The Prestige ST trial compared AIDA (n=276) with anterior plated ACDF using allograft bone (n=265); the ProDisc-C trial compared AIDA (n=103) with ACDF (n=106). The evidence is insufficient to support conclusions concerning the comparative effect of AIDA on health outcomes.

First, the evidence does not permit conclusions on the long-term performance of AIDA and adverse events. Device performance, durability, and revisability are key considerations for the relatively young population enrolled in these trials. The available evidence also is insufficient to permit conclusions as to whether or not AIDA affects the postsurgical development of adjacent-level DDD. In contrast, conclusions on the relative safety of cervical disc arthroplasty appear sufficiently supported in the short term.

Second, trial results demonstrated noninferiority for AIDA versus ACDF for the primary and overall success composite outcome. In the Prestige ST trial, while superiority with respect to the neurological status was found, and thus for the composite including it, quantitative data on neurological status are not available and it is not known whether it was obtained by blinded examiners, precluding interpreting its clinical meaning and relevance. Further, the Prestige ST trial did not find better outcomes of AIDA in terms of the NDI, a clinically validated, multidimensional outcome measure of neck pain and disability caused by cervical DDD. Taken together, these uncertainties preclude determining 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 does not permit conclusions as to whether AIDA for the cervical spine improves net health outcomes or is as beneficial as established alternatives.

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

Whether artificial disc arthroplasty for the cervical spine 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.

TEC Assessment Index

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;