FDA Panel Supports BRYAN Cervical Disc, but not Superiority Claim
BY JOHN MCCORMICK, JULY 17, 2007
Today was a long day in Gaithersburg, Maryland exploring the ins and outs of wear debris and Bayesian statistics. Luckily the dirty work was left to an 11-member panel of sober experts appointed by the FDA to make recommendations on the data for potential approval of the Medtronic BRYAN cervical disc. The panel's voting members decided 7-1 in favor of recommending FDA approval but dismissed the notion that the BRYAN disc was a superior treatment to cervical fusion.
Duly noting that the BRYAN clearly demonstrated non-inferiority to fusion, the panel indicating that cervical disc was not a superior treatment to cervical fusion may not bode well for cervical discs' reimbursement. Lest you disagree, we note how CMS recently proposed non-coverage of lumbar discs for medicare patients. Time will tell on this point since CMS will review the data with a fresh eye, but we should all salute Medtronic for going for the gold.
Note aside, this was a highly focused discussion that all but ignored Monday's announcement that the FDA had separately approved Medtronic's Prestige cervical disc which is the first cervical disc approval in the USA.
As expected, Medtronic did a stand-up job of presenting its data. Front and center was Dr. Rick Sasso, principal investigator, who set forth the IDE clinical results in a cogent framework. We summarize the study findings below.
Summary Trial Design
- Prospective, randomized controlled
- Investigational treatment: BRYAN cervical disc (241 patients)
- Control: ACDF (cervical fusion plate) with allograft spacer (221 patients)
- Single level
- 30 centers
- Evaluation: 6wks, 3mos, 6mos, 12mos, 24 mos
- Objectives: Non-inferiority in overall success (primary); superiority in overall success (secondary)
Findings
- All available data at 24 mos: >380 patients
- Overall success rate: claimed statistical superiority (P = 96.9%)
- Neurological success rate: claimed statistical superiority (P ~ 100%)
- Adverse events non-controversial
- Neck disability: claimed statistical superiority (P = 98.0%)
- Mean neck and arm pain: statistical non-inferiority (P ~ 100%)
- SF-36 physical (PCS): statistical non-inferiority (P = 94.3%)
- SF-36 mental (MCS): statistical non-inferiority (P = 87.2%)
- Safe and effective
So how did the panel react? They understandably did a deep dive on wear debris concerning the BRYAN polyurethane nucleus, but surprisingly couldn't get off the point. The discussion dwelled and continued to dwell on rabbit kidneys, oxidization of excised implants, porosity of the BRYAN's polyurethane sheath and the like. A panel member even cast a negative vote over the issue. Medtronic did a good - actually a great - job of indicating low wear debris for the 2 year time period, but the panel just kept on drilling and, in our opinion, missed the oil. What the panel should have spent more time on is the BRYAN happening to be a first generation device that involves a highly engineered surgical technique. The procedure is so exacting that it should remain accessible to an elite group of surgeons who have the skill to set up a mitre-box over the surgical site, literally mill perfectly aligned spherical indentations into the vertebral endplates that exactly fit the implant. These and other steps involved with implanting the BRYAN take virtuosic talent. The BRYAN is not for every spine surgeon. Training issues and how the surgical complexity influences outcomes only received lip service by the panel. In Medtronic's defense, training patients were included in the data (in contrast to J&J's Charite study) so that may have ameliorated the issue statistically, but not every community doc is a principal investigator in an FDA clinical trial either!
A quick takeaway before we get to the panel findings: folks developing artificial nucleus technologies should take heed that the FDA (again, understandably) is going to bore into the wear debris issues. So nucleus start-ups, be warned. If a hard polyurethane core surrounded by titanium for cervical is going to nearly get keel-hauled (no pun intended, Pro-Disc lovers), then you can bet some of those soft poly cores rubbing up against lumbar vertebral endplates may end up walking the plank.
The FDA then put some solid formal questions to the panel which, in turn, interpreted Medtronic's data to answer. We summarize here:
FDA: Wear debris truly an issue?
Panel: Ultimately no in the short run, but there is long run concern
FDA: Motion preserved and does this help adjacent level?
Panel: Motion preserved, but adjacent level requires years if not decades of study
FDA: Labeling?
Panel: Training more important than labeling. No need for OR time or discussing use of NSAIDS in labeling.
FDA: Safety?
Panel: IDE demonstrated safety for the time period covered.
FDA: Efficacy?
Panel: IDE demonstrated efficacy for the time period covered.
FDA: Statistical superiority to fusion?
Panel: Not successfully demonstrated.
FDA: Post approval study with long term follow up required?
Panel: Yes.
The FDA questions helped frame the conditions that the panel attached to the vote. Again the vote was 7-1 in favor of the BRYAN with the following conditions attached
- No discussion of adjacent level in labeling/literature
- Re-run a study of how wear debris potentially effects kidneys in rabbits
- No claims allowed of superiority to fusion in product literature
- Extensive surgeon training
- Patient education
- Remove DDD indication in labeling and replace with alternative for single level decompression for C3-C7
- Post approval study on adjacent level disease with 10yr follow up
All in all, an interesting day and cervical disc arthroplasty is here with Prestige and all the more so with BRYAN. The vote and panel findings should therefore be considered a success for Medtronic, cervical discs and ultimately patients. Soon enough we'll see ProDisc-C hit the market and by 2010/2011 an additional six discs are expected to enter the fray. The Prestige approval and the likely eventual BRYAN approval are certain to give Medtronic a running start in what is going to be a highly competitive market populated with entrants fighting for every sporadic reimbursement dollar.
