TEC Assessment Index

Artificial Lumbar Disc Replacement

Assessment Program
Volume 22, No. 2
June 2007 

Executive Summary

Background

Low back pain is an extremely common condition that affects up to 20% of the U.S. population. Degenerative disc disease (DDD) is a major common cause of low back pain. Replacing the disc with an artificial disc is one proposed method to alleviate the pain associated with DDD. There are two U.S Food and Drug Administration- (FDA-) approved products, the Charité disc and the ProDisc.

Objective

This Assessment will review the available evidence to determine if artificial lumbar disc replacement is an effective treatment for chronic degenerative disc disease.

Search Strategy

MEDLINE search (via PubMed) through May 2007, using the search terms "Charité" or "ProDisc" or "intervertebral disk/[MeSH] OR spinal OR spine OR lumbar."

Selection Criteria

Central focus of the report is the randomized clinical trials of the Charité and ProDisc artificial discs. Case series reports were abstracted, but are relatively uninformative regarding effectiveness because of lack of control groups.

Main Results

Each disc type has been evaluated with one randomized, clinical trial. The trials were designed as noninferiority trials, with the comparator being fusion. The validity of a noninferiority trial rests on several assumptions:

• The comparator treatment should have well-known and precise knowledge of effectiveness compared to no treatment. This knowledge and the noninferiority margin designated for the trial should assure that the new treatment is superior to no treatment.
  
• The trial should also achieve historical levels of effectiveness in the known comparator.
  
• Finally, an acceptable margin of inferiority is reasonable for a new treatment if there are obvious advantages of the new treatment, such as patient acceptability, convenience, invasiveness, or cost.

The effectiveness of fusion for chronic degenerative disc disease is not well established. There are few clinical trials and results are inconsistent. Neither of the studies discussed the effectiveness of fusion or justified the size of the noninferiority margin. The possible advantages of the artificial disc in terms of physical functioning should be measurable as a principal outcome.

The clinical trial of the Charité disc randomized 205 patients to the Charité disc and 99 patients to receive fusion using the BAK cage. Patients receiving the Charité disc had a composite success rate of 57.1%, and patients receiving the BAK cage had a success rate of 46.5%. This met the specified noninferiority criteria with a p-value of 0.0001. This would not have met statistical significance for a traditional superiority trial with conventional levels of significance. The overall success rate was lower than specified in pretrial sample size calculations. In other outcomes, the Charité disc was not statistically significantly superior to BAK fusion, with the exception of patient satisfaction.

The clinical trial of the ProDisc randomized 162 patients to the ProDisc and 80 patients to circumferential fusion. The overall success rate was 63.5% for the ProDisc, and 45.1% for fusion. This met statistical significance using traditional p-value calculation for a superiority trial. The success rates were lower than specified in pretrial sample size calculations. However, success rates were based on patients completing the trial rather than the full, randomized sample. The lack of documentation of missing data and subjects makes it difficult to know which patients were ultimately included in the analysis, particularly those with early device failures, of which there were 6 ProDisc device failures and 2 fusion device failures. Some outcomes showed the ProDisc to be superior, others showed no difference from fusion.

Author's Conclusions and Comments

Given what is known about fusion as a comparator treatment, both noninferiority trials may not provide evidence of efficacy. The specific noninferiority margins are not justified. The lower-than-expected success rates also raise additional questions regarding the validity of a noninferiority trial and the noninferiority margin selected. Viewed from the perspective of superiority trials, both trials are also suspect. The Charité trial showed little evidence of superiority, and the ProDisc analysis is problematic because of missing values and uncertain outcomes for all patients.

Based on the available evidence, the Blue Cross and Blue Shield Medical Advisory Panel made the following judgments about whether the artificial lumbar disc for treatment of degenerative disc disease 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.

In October 2004, the U.S. Food and Drug Administration (FDA) granted premarket application (PMA) approval for the Charité Artificial Disc, stating that the device is indicated for spinal arthroplasty in skeletally mature patients with DDD at one level from L4-S1. DDD is defined as discogenic back pain with degeneration of the disc confirmed by patient history and radiographic studies. As a condition of approval, the manufacturer has agreed to conduct a postapproval study, using a maximum of 366 patients (201 randomized investigational subjects, 67 training investigational subjects, and 98 control subjects). Postapproval study patients will be evaluated for a period of 5 years post-implantation.

The FDA granted approval to the ProDisc in August 2006 and is indicated for spinal arthroplasty in skeletally mature patients with DDD at one level from L3-S1. Patients should have no more than Grade 1 spondylolisthesis at the involved level. Patients receiving the ProDisc should have failed at least 6 months of conservative treatment prior to implantation. The manufacturer agreed to conduct a postapproval study to obtain 5-year follow-up data from all subjects in the clinical study. The study will utilize the same endpoints as the Investigational Device Exemption clinical study, and also evaluate adjacent segment degeneration and correlation of range-of-motion with Oswestry Disability Index and visual analog scale scores.

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

Current evidence supporting the effectiveness of artificial lumbar disc is insufficient. Case series evidence is inadequate to establish efficacy. The randomized trials of the Charité disc and ProDisc are suspect as valid noninferiority trials and do not prove superiority.

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

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

The evidence is insufficient to determine whether the use of artificial lumbar discs improves the net health outcome or whether they are as beneficial as any established alternatives.

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

Whether the use of artificial lumbar discs improves health outcomes has not been established in the investigational settings.

Therefore, the use of artificial lumbar discs for degenerative disc disease does not meet the TEC criteria.

TEC Assessment Index

KEYWORDS: Orthopedics/PainManagement(category); Surgery/Surgical Alternatives/Interventional Radiology(category); annulus; arthroplasty; artificial disc; artificial disk; back; BAK; cage; Charite; composite; DDD; degenerative disk disease; degenerative disk disease; disability; disc; discogenic; discography; disk; fusion; index; intent; intention; intent-to-treat; intervertebral; ITT; lumbar; Morris; noninferior; non-inferior; noninferiority; non-inferiority; nucleus; ODI; Oswestry; pain; pedicle screw; ProDisc; prostheses; prosthesis; prosthetic; Rowland; Rowland-Morris; scale; sciatica; score; sensitivity analysis; spinal; spine; spondylolisthesis; spondylosis; stenosis; surgery; surgical; total disc replacement; treat; VAS; vertebra; vertebrae; vertebral; visual analog; visual analogue