The Medicare Evidence Development & Coverage Advisory Committee (MEDCAC) met on September 22 to consider the available evidence of clinical benefits and harms of on-label and off -label uses of BMPs (bone morphogenetic proteins).
This meeting had all the makings of a big Fall Classic. The big BMP companies, Medtronic (Infuse) and Stryker (OP-1) were invited to make the case to Medicare that adequate evidence exists to determine the clinical benefits of their products for patients.
Also lined up were the big societies (NASS, AAOS and AANS/CNS) and the Blue Cross Blue Shield Association Technology Evaluation Center to advise the committee on the state of the evidence. The BCBS tech assessment had the names of Richard A. Deyo, M.D., M.P.H. and Sohail K. Mirza, M.D., M.P.H. attached as peer reviewers, both chosen for their “expertise and diverse perspectives.”
MEDCAC
Not since 2006, when the committee considered the clinical evidence for lumbar fusion, had MEDCAC been convened to talk about spinal procedures. Here was a chance to check the barometer for the use of biologics in spine and whether or not Medicare would consider providing national coverage for these products.
It was also the first time costs were considered in the technical assessment. More on that later….
The 16-member committee, actively chaired by Clifford Goodman, Ph.D., included NASS President Ray Baker, M.D., and NASS Advocacy Chair Raj Rao, M.D. Both physicians were there in their private roles as clinical professors. The panel also included John Kirkpatrick, M.D., FACS, a member of the FDA orthopedic panel that originally voted to recommend approval for Infuse and Kevin Bozic, M.D., MBA, a well known public policy expert.
The Centers for Medicare and Medicaid Services (CMS) wanted to know how confident the committee was that adequate evidence exists to make a decision on whether or not the use of BMPs in various indications improved “meaningful health outcomes” of patients. Those indications include the off- and on-label use of the BMPs for the lumbar spine, open tibial fractures, recalcitrant long bone nonunions and cervical spine.
The result?
No fireworks and no disagreements over the clinical evidence summarized by Thomas Ratko, Ph.D., Associate Director of Blue Cross Blue Shield. All the societies complimented the thoroughness of the tech assessment and supported the conclusions reached by Ratko. Medtronic made a modest presentation and Stryker didn’t even show up to advocate for OP-1.
Apparently, everyone was willing to live with the tech assessment.
What were some of the conclusions of the tech assessment regarding adequacy of evidence?
Avoiding Bone Harvest Adverse Events – Moderate
The evidence for improved outcomes with on-label use of Infuse was graded as moderate.
Two RCTs (randomized clinical trials) reported radiographic fusion outcomes to be similar to that of autograft bone. No significant adverse events were attributed to Infuse in any study. However, the size and duration of the RCTs are not sufficient to precisely determine the frequency and severity of adverse events. Thus, the evidence gives moderate support to clinical benefit from the use of Infuse as patients can avoid the additional procedure of autograft bone harvest and its associated adverse events.
OP-1 Lumbar Fusion – Inconclusive
No conclusion could be reached supporting improved outcomes with on-label use of OP-1 for posterolateral lumbar fusion
OP-1 Recalcitrant Long Bone Non-Unions – Low
The evidence for radiographic fusion, pain, and function outcomes is low for on-label use of OP-1 in recalcitrant long bone non-unions.
Infuse in Open Shaft Fractures – Moderate
The evidence is moderate for on-label use of Infuse to enhance bony fusion in acute open shaft fractures.
The main evidence is in one RCT (n=450) (BESTT) that compared two different doses of Infuse versus standard of care. The RCT is supported by a combined subgroup analysis that pooled data from patients with Gustilo-Anderson type III fractures in BESTT with data from a second smaller unpublished RCT (n=60) with identical design.
Infuse Cervical Harm – Insufficient Evidence
The evidence that Infuse improves radiographic fusion success is moderate and no conclusions can be drawn regarding the potential impact of the off-label components on radiographic fusion success. The evidence is insufficient to draw conclusions on the off-label use of OP-1 in fusion of the lumbar-sacral spine.
Regarding the off-label use of Infuse in the cervical spine, the evidence consists of one randomized trial and four nonrandomized comparative studies of off-label use of Infuse for cervical spinal fusion. Two small studies, a randomized trial and a nonrandomized comparative study, reported on radiographic fusion success and changes in mean neck disability scores. The other three nonrandomized studies focused mainly on complications. There is moderate evidence that off-label use of Infuse in anterior cervical spinal fusion increases cervical swelling and related complications. There is insufficient evidence to draw conclusions about radiographic fusion success or associated changes in neck disability scores. There are ten additional off-label uses, each with a single small study, most rated as poor quality. There is insufficient evidence to draw conclusions about any of these off-label uses.
BMP General Harms – Insufficient Evidence
The evidence of BMP-specific harms is insufficient to draw conclusions.
There is moderate evidence that off-label use of Infuse in cervical spinal fusion increases cervical swelling and related complications. The body of evidence suggests that autograft bone harvest is associated with pain at the harvest site, but it is not possible to systematically assess the frequency, duration, and clinical significance. Overall, autograft harms were inconsistently reported.
Infuse Incremental Cost Effectiveness – Price of Pain
The incremental cost effectiveness ratios (ICERs) of the use of Infuse for spinal fusion were based on the cost of the product and the avoidance of bone graft donor site pain.
At a cost of $3, 000, the range of ICERs was between $56, 959 and $162, 714 per QALY (quality-adjusted life year) gained
At a cost of $1, 000, the ICER range is between $17, 763 and $50, 557
At $5, 000, the ICER range is from $96, 155 to $274, 870
At $8, 000, the ICER range is from $154, 948 to $443, 385
This was the first time, according to John Kirkpatrick, that the door had been opened by CMS to consider costs. The panel did not discuss this item, but clearly CMS solicited this information in the technical assessment for the future. Committee members had long discussions about the accounting for the avoidance of donor site pain. It made us think of measuring the price of pain for seniors.
MEDCAC Vote – Confidence in Infuse for Lumbar and Tibial Fractures
After a presentation of the history of the development of BMPs by Julie Glowacki, Ph.D., the Blue Cross tech assessment, and testimony by the orthopedic and spine societies the committee members discussed and voted on their level of confidence in the evidence.
All 16 members were asked to rate their confidence level for 13 questions on the off-label and on-label use of Infuse and OP-1 for various indications.
There were intermediate to high levels of confidence that adequate evidence existed to determine that Infuse improves at least one clinically meaningful health outcome for lumbar spine and open tibial fractures.
The committee strongly and unanimously noted their low level of confidence that the off-label use of Infuse in the cervical spine improves outcomes.
Committee member Rao summed it up for OTW this way:
“It appeared to me that the entire panel voted roughly in line with the consensus positions that were developed and presented by the societies at the meeting—i.e., efficacy with PMA [premarket approval] anterior lumbar use and lack of efficacy for 1-2 level anterior cervical surgery.”
NASS Credibility
Christopher Bono, M.D., who made the NASS presentation told OTW, “There seems to be a general sense that, assuming that harmful effects of BMP have not been underestimated or underreported, that the use of BMP instead of harvesting iliac crest in the Medicare population may have some advantages in Medicare beneficiaries.”
We asked Bono if NASS’ credibility was on the line with its recommendation that CMS should issue a positive NCD (National Coverage Determination) for use of Infuse in the lumbar spine.
“NASS’ credibility is always on the line when making a public statement—particularly to the largest insurer in the country. Our statements were evidence-based when applicable and guided by clinical prudence. NASS’ intent and purpose is to support what is best for patients based on the evidence. I believe we have done that, ” replied Bono.
“In a nutshell, we need better data in the future. There does not seem to be an imminent NCD at this time. However, every spine surgeon should be as familiar with the current literature as they can be in order to make a clinically sound decision for their patients on an individual basis, ” added Bono
The former head of CMS’ Coverage Office, Steven Phurrough, M.D., told OTW a few weeks ago that he did not believe CMS would issue an NCD for BMPs.
However, Larry Biegelsen, a senior analyst at Wells Fargo, wrote on September 23 that the MEDCAC vote increases the odds that CMS will seek to impose some restrictions on off-label uses of BMP.
Whatever CMS decides, the confidence of MEDCAC members and the Blue Cross tech assessment were clear signals of the promise of BMPs—in the right patient for the right indication.
