TEC Assessment Index
Artificial Intervertebral Disc Arthroplasty for Treatment of Degenerative Disc Disease of the Cervical Spine
Assessment Program
Volume 22, No. 12
November 2007
Executive Summary
Background
An estimated 60% of individuals older than 40 years have radiographic evidence of cervical degenerative disc disease (DDD) secondary to spondylosis. Symptoms of DDD include neck and arm pain associated with radiculopathy or myelopathy, respectively. Untreated, the signs and symptoms of cervical DDD may decrease or stabilize, but may worsen. Initial conservative, noninvasive therapies aim to relieve pain and prevent permanent injury to the spinal cord and nerve roots. Typically, if at least 2 to 6 months of conservative treatment is ineffective, or the patient becomes unable to perform activities of daily living, surgical intervention is 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. More recently, artificial intervertebral disc arthroplasty (AIDA) has been proposed as an alternative procedure in patients for whom ACDF is indicated. 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 hypothesized that properly performed AIDA maintains anatomical disk space height, normal segmental lordosis, and physiological motion patterns at the index and adjacent cervical levels. Furthermore, maintenance of physiological spinal motion patterns has been proposed to reduce risk for subsequent development of adjacent-level DDD secondary to altered kinematics at segments above or below the fusion site. These hypotheses have been used as 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 2007, limited to English-language articles on human subjects.
Selection Criteria
The central focus of the Assessment is the randomized, investigational device exemption (IDE) clinical trial of the Prestige ST artificial disc, which was approved (via premarketing application [PMA] approval) by the U.S. Food and Drug Administration (FDA) in July 2007. Other studies were not included as they used a precursor device to the Prestige disc and presented preliminary data. Clinical results for the Bryan disc are available from the FDA, and are summarized in the Appendix of this Assessment, even though the device has not received final approval.
Main Results
The available evidence for the Prestige ST disc consists of one unblinded, randomized, controlled trial (RCT) in which disc arthroplasty (n=276) was compared to anterior-plated ACDF using allograft bone (n=265). The trial was a noninferiority design (delta=0.1), that used Bayesian analysis of 12- and 24-month data with noninformative or uniform priors to calculate the posterior probabilities of noninferiority. A secondary analysis to assess statistical superiority was performed for all investigational group outcomes that were shown noninferior to corresponding control group outcomes.
Patients (mean age 43–44 years, 46% males) 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 for a period of less than 6 weeks (4–6% of cases), from 6 weeks to 6 months (29–34%), and for more than 6 months (60–63%).
In this study, AIDA with the Prestige disc was shown to be statistically noninferior to ACDF in all three primary outcome variables (Neck Disability Index [NDI], neurological status, and functional spinal unit [FSU] height). The neurological status outcome reached the prespecified level for statistical superiority, but neither the NDI nor the FSU did so. The primary composite endpoint of the trial (“overall success”) was defined as attainment of all of the following: success as defined for the three primary outcome variables, plus a requirement for no serious implant- or procedure-associated adverse event and no additional surgical procedure classified as a failure. Because of difficulty in evaluating FSU height, due to anatomical interference with the radiographic image, an alternate overall success determination was also made based on the criteria without the FSU height. Both overall success composite endpoints for AIDA were found to be statistically noninferior, as well as superior to ACDF. However, it appears that the neurological status outcome was the main driver of superiority in overall success for AIDA in this trial, given the lack of statistical superiority for the NDI and FSU outcomes.
Perioperative and surgical outcomes were similar between groups. Radiographic fusion was shown for 97.5% of ACDF patients at 24-month follow-up. Cervical neck angular motion was maintained at preoperative levels at the surgical level in arthroplasty patients and restricted, as expected, in ACDF patients. Radiographic evidence of adjacent-segment degeneration was not assessed, nor is information available from the clinical study on wear debris in the disc space. Secondary surgical procedures, classified as revisions, hardware removals, and supplemental fixations were reported, but their clinical relevance is not clear.
Author's Conclusions and Comments
Analysis of the results of the Prestige ST disc IDE pivotal trial data raises a number of concerns. In particular, the 24-month follow-up period does not permit conclusions about long-term device performance, durability, and potential need for revision. These are key considerations for the young (mid-40s) patients who underwent arthroplasty in the Prestige study and for those likely to undergo AIDA in clinical practice. This concern is underscored by the FDA approval conditions that the Prestige device manufacturer continue the IDE study for 7 years to evaluate the safety and function of the device, and perform a 5-year, enhanced surveillance study to more fully characterize adverse events associated with AIDA in a broader patient population.
A second concern with the Prestige trial is that the noninferiority study design makes it difficult to discern whether or not AIDA produces a net health benefit compared to ACDF. Thus, the statistical superiority (benefit) of the overall success outcome for AIDA compared to ACDF appears to have been driven solely by the reported statistical superiority of the neurological status variable, which was only one of three components of that composite endpoint. However, the investigators provided no details on how the neurological status itself was measured and evaluated, thus precluding analysis of its three subcomponents, their clinical relevance, and their relative contribution to the overall success rate. Thirdly, failure to blind physician outcome assessors and patients to study treatments could have biased results toward favoring disc arthroplasty (“new” treatment) over ACDF (“old” treatment). Finally, the Prestige disc trial provides no direct evidence on subsequent adjacent-level DDD in control or 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.
One cervical disc arthroplasty product (Prestige ST Cervical Disc) received FDA marketing approval July 16, 2007. The Prestige ST Cervical Disc is indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy. The device is 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 which 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 second 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 prepared. The Bryan disc is indicated for use in patients similar to those for whom the Prestige device is indicated.*
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.
One noninferiority design RCT is available that compares AIDA (n=276) with anterior plated ACDF using allograft bone (n=265). For several reasons, this evidence is insufficient to support conclusions concerning the effect of AIDA on health outcomes.
First, the evidence from the IDE trial 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 the pivotal trial. The available evidence also is insufficient to permit conclusions as to whether or not AIDA affects the postsurgical development of adjacent-level DDD. By contrast, conclusions on the relative safety of cervical disc arthroplasty appear sufficiently supported in the short term.
Second, although the study results consistently demonstrated statistical noninferiority for AIDA versus ACDF in all three primary outcome variables, and for the overall success composite outcome, the neurological status was the only primary outcome variable for which statistical superiority was shown. It thus appears to be the primary determinant of statistical superiority for the overall success of the disc versus ACDF. However, quantitative data on the neurological status are not available, which precludes analysis of its clinical meaning and relevance. Further, the study failed to demonstrate statistical superiority for AIDA in terms of the NDI, which is a clinically validated, multidimensional outcome measure of neck pain and disability caused by cervical DDD. Taken together, these uncertainties make it difficult to determine the effect of AIDA on health outcomes in more specific, validated terms than the ill-defined neurological status variable and by extension the overall success rate. Finally, failure to blind patients and physician outcomes assessors to the study treatment allocation could have biased study results, favoring disc arthroplasty over ACDF.
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 artificial intervertebral disc arthroplasty for the cervical spine improves the net health outcome 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.
*As this Assessment was in press, the ProDisc™-C Total Disc Replacement received premarketing application (PMA) approval on December 17, 2007 (http://www.fda.gov/cdrh/pdf7/p070001.html).
TEC Assessment Index
NOTICE OF PURPOSE:TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated.
KEYWORDS: 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;
