There came a point in the design of the five-year, 286 patient Pro-Disc-L clinical study where the FDA decided that patients with greater than Level 1 spondylolisthesis should not receive the implant. Here is the specific FDA guidance to physicians.
ProDisc-L is for “spinal arthroplasty in skeletally mature patients with degenerative disc disease (DDD) at one 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 1 spondylolisthesis at the involved level.” (Emphasis added.)
That was in 2006.
That particular guidance is part of the FDA’s Summary of Safety and Effectiveness Data guidance for physicians.
Apparently, Anthem Blue Cross has a different point of view.
On May 13, 2013 Anthem Blue Cross issued a clinical guidance document (# CG-SURG-33) which is at best confused and at worst contradicts FDA guidance. Here’s a direct quote:
“Lumbar artificial intervertebral disc (LAID) implantation is considered medically necessary when ALL (emphasis theirs) of the following criteria are met:
Spondylolisthesis with 1 or moreof the following:
Progressive or severe neurologic deficits (for example, bowel or bladder dysfunction); or
Adults (age greater than 18) with persistent and significant symptoms, despite an adequate trial of at least 6 months of conservative care with low-grade spondylolisthesis demonstrated on x-ray;
Degenerative disc disease is limited to the single spinal level at which the LAID is planned; AND
An FDA approved LAID device is used in accordance with FDA labeling (including any label requirement regarding the degree of spondylolisthesis); AND
A single level in the lumbar spine will be treated with an LAID device; AND
The individual is skeletally mature; AND
There are no contraindications to lumbar AID device implantation, (including those listed in the FDA labeling) including, but not limited to, the following:
Active systemic infection or infection localized to the site of implantation; or
Osteopenia or osteoporosis (defined as DEXA bone density measured T-score less than -1.0); or
Bony lumbar spinal stenosis; or
Isolated radicular compression syndromes, especially due to disc herniation; or
Pars defect; or
Clinically compromised vertebral bodies at affected level due to current or past trauma; or
Lytic spondylolisthesis or degenerative spondylolisthesis of grade greater than 1”
Evidence-Based Medicine
The FDA required ProDisc L to undergo a five-year, 17 center, 286 patient, 35 surgeon clinical study. Furthermore, the study had to meet with FDA approved design characteristics including being preoperatively blinded, randomized and to incorporate an independent data analysis in order to assure that the information provided would be both clinically relevant and accurate. The effort required to meet the FDA criteria was enormous and required literally hundreds of people and tens of millions of dollars.
Anthem Blue Cross’ May 13 guidance to physicians was so contrary to the ProDisc clinical study that one of the principal investigators in that study, Dr. Jack Zigler, penned the following open letter.
An Open Letter to the FDA:
Anthem Blue Cross Defies the FDA on ProDisc-L Indications
The Medical Device Amendments to the Food, Drug, and Cosmetic Act were enacted in 1976 to “provide for the safety and effectiveness of medical devices intended for human use.”1 With this direct mandate from the US Congress, the FDA’s responsibility ultimately evolved into an active oversight role in the scientific testing of Class III devices, which, since 1996, have largely consisted of multicenter prospective randomized control trials comparing outcomes of an investigational device compared to an FDA-approved control device or procedure.
ProDisc-L underwent such a clinical study beginning in 2001 (PMA# P050010), ultimately resulting in FDA approval for commercialization of the product in 2006.
Concomitant with their approval of the ProDisc-L, FDA published a Summary of Safety and Effectiveness Data that is available on their website2. This document lists indications for use as extrapolated from the inclusion and exclusion criteria used in the multicenter prospective study. The SS&E data are used in formulating labeling which guides use of the device by medical professionals, and, until recently, by the insurance industry.
Despite FDA approval of the ProDisc-L for single level on-label usage in 2006, several major insurance companies have non-scientifically and arbitrarily continued to internally define its use as “experimental and investigational”, frustrating surgeons who have watched two-year and five-year long-term outcomes data reported publicly at international meetings and then ultimately published in the peer-reviewed scientific literature3,4. With no clear oversight to the insurance industry, and very poor political support from their national organizations, surgeons have fought an individual and frustrating effort against these indefensible insurance industry practices which have denied access to care for their patients.
[Insurance companies have employed other means to deny access to this FDA-approved technology to patients. Besides designing internal and self-serving definitions of “experimental and investigational,” they have relied on “guidelines” which appeared, without benefit of scientific validation or review by spine surgeons or their societies. The Milliman Guidelines and the ACOEM [American College of Occupational and Environmental Medicine] Guidelines are but two examples which selectively “review” the scientific literature and then make “recommendations” for treatment algorithms that are adopted as dictum by insurance companies. These guidelines frequently rely heavily on older literature, while ignoring the more scientifically valid Level 1 data generated by FDA IDE [investigational device exemption] studies demonstrating the efficacy of both fusion and arthroplasty in appropriately-selected patients who have failed conservative care.
Another mechanism has been the insurance industry’s shift to internal peer review. Previously, second opinions were rendered by community surgeons who would interview and examine patients, review their imaging studies, and offer an independent opinion. Because this removed any control the insurance company may have had over the direction of the case, a quiet movement began in the late ‘90’s and early 2000’s, uniform across the insurance industry, which brought second opinions “in-house” with insurance company-contracted physicians.
A cadre of physicians and surgeons of uncertain qualification were retained by the insurance company to make telephone contact with the treating surgeon within a narrow window of time. In a typical phone call contact, the review physician briefly allows the surgeon to present the case, but then parrots the insurance company’s policy while denying the request for surgical authorization. These often poorly-informed review physicians (not really a peer, because they are very frequently not same-specialty physicians) then offer a further appeal process so the request can be reviewed by an “in-specialty” physician, with an additional built-in time delay. When that physician again repeats the company policy and denies the procedure as “experimental and investigational,” a third level of appeal can be invoked, again with a more onerous time delay to the patient. By this time, many patients have become frustrated and give up, accepting medical pain management or a lumbar fusion.]
Most recently, an even more egregious ruse has placed the insurance company above the FDA in determining indications for devices which have successfully navigated the PMA process. Anthem Blue Cross, after settling a class-action lawsuit brought by its California members for failing to authorize use of the ProDisc-L, has resorted to this new tactic. Usurping the mandate of the FDA, the insurance industry has now explored new territory with Anthem’s May 2013 decision to change the inclusion criteria listed in the SS&E document for ProDisc-L, in effect changing the labeling of the ProDisc-L device5,6.
In the SS&E document for the ProDisc-L single level study, indications are for “spinal arthroplasty in skeletally mature patients with degenerative disc disease (DDD) at one level from L3-S1.” The SS&E goes on to state “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 1 spondylolisthesis at the involved level.” (The emphasis is mine).
Every spine surgeon understands that patients should have either no spondylolisthesis, or at worst, no more than Grade 1. Many surgeons don’t realize the rationale for this inclusion, since degenerative anterior spondylolisthesis is typically a primary disease of the facet joints, causing instability and stenosis, both contraindications to ProDisc-L. This aspect of the inclusion criteria was actually placed to capture patients with less than one grade of posterior retrolisthesis, which is not infrequently seen with disc space collapse, especially at L5-S1. Degenerative retrolisthesis is the result of height loss and capsulo-ligamentous laxity, which can both be improved by mobilization and disc height restoration during ProDisc-L implantation. There was certainly no requirement in the IDE study for a patient to have spondylolisthesis as a condition of enrollment!
Anthem’s Clinical Guideline for medical necessity of the ProDisc-L (referred to internally by Anthem as a lumbar artificial intervertebral disc (LAID) device) now require spondylolisthesis to even consider approval of the procedure (emphasis mine). This new requirement bypasses the scientific scrutiny used by the FDA in its approval process, over-riding it by a business decision made by insurance company executives and their internal medical directors. All the time, money, and work effort that went into a 17 center, 286 patient, 35 surgeon effort with clinical and administrative support by hundreds of other personnel now over more than 10 years of clinical follow-up has been superseded by a business decision.
Anthem Blue Cross now REQUIRES SPONDYLOLISTHESIS AS A CONDITION FOR ARTHROPLASTY. This is absolutely NOT part of the IDE study design, or its data analysis for success, nor it’s labeling, nor is it contained in the FDA’s SS&E statement. Anthem Blue Cross MADE THIS UP! They are, in essence, ignoring the FDA’s labeling and are essentially creating their own. Should an insurance company have the right to twist the results of an IDE study and the FDA’s labeling, and change the indications?
Is this a precedent we want to go unchallenged? Should an insurance company have the right to alter the labeling of any device? Is the FDA willing to allow this to happen, despite its mandate from Congress that it should be the body with responsibility to “provide for the safety and effectiveness of medical devices”?
This is a first effort by the insurance industry to blatantly overstep the boundaries of FDA labeling. I would hope the FDA will not allow this to go on without investigation. As a surgeon who has participated in FDA trials, worked with FDA on site audits, and written several scientific papers reporting on these hard-fought databases, I ask the FDA to act in the interests of our patients to protect their access to care that has been vetted through a rigorous scientific process with layers of oversight, producing some of the best scientific evidence ever generated. The scientifically proven benefits of this technology, in the appropriately-selected patient, should not be denied to patients based on non-scientific fiat by the insurance industry.
Jack E. Zigler, M.D., FACS, FAAOS
Medical Director, Texas Back Institute
Former Clinical Professor of Orthopaedic Surgery
USC School of Medicine
Zigler JD, Walsh J, Zigler JE: Medical Device Reporting: Issues with Class III Medical Devices. Food and Drug Law Journal 62: No. 3, 573-58, 2007
www.fda.gov
Zigler J et al: Results of the Prospective, Randomized, Multicenter Food and Drug Administration Investigational Device Exemption Study of the ProDisc-L Total Disc Replacement Versus Circumferential; Fusion for the Treatment of 1-Level Degenerative Disc Disease. Spine 32: No. 11, 1155-1162, 2007
Zigler JE, Delamarter RB: Five-year Results of the prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential arthrodesis for the treatment of single-level degenerative disc disease. J Neurosurg Spine17: 493-501, 2012
ProDisc-L SS&E Indications pages 1-2
Anthem Guidelines for LAID pages 1-2