The Centers for Medicare and Medicaid Services are planning a September meeting to examine the on- and off-label uses of bone-morphogenetic proteins used in several prominent spinal implants and procedures.
The Sept. 22 meeting of the agency’s Medicare Evidence Development & Coverage Advisory Committee will look to answer a number of questions about the products, including "the clinical benefits and harms of on-label and off -label use of BMPs," according to its website.
"The on-label and off -label use of BMPs has rapidly grown since becoming clinically available in 2001," according to the website. "There are reports stating that up to 85 percent of BMP use is for off-label indications, mostly in the spine. There have also been a number of reports of adverse events associated with the use of BMPs."
The committee will consider seven questions on BMPs, answering each on a scale of one to five (with one indicating low confidence and five indicating high confidence):
- How confident are you that there is adequate evidence to determine whether or not the use of BMPs in each of the following indications improves at least one of the clinically meaningful health outcomes?
- On-label use in
- Lumbar spine ( FDA Ref. LS and LS HDE)
- Open tibial fracture ( FDA Ref. T)
- Recalcitrant long bone nonunions (FDA Ref. LB)
- Off-label use in
- Cervical spine
- Lumbar spine
- All other
Note: Questions 2-6 should be addressed only for those indications where the panel is confident that there is adequate evidence (mean vote of 2.5) to consider the question.
- On-label use in
- How confident are you that there is adequate evidence to determine that the use of BMPs in the lumbar spine for each of the indications identified below improves at least one of the clinically meaningful health outcomes?
- FDA PMA on-label use (FDA Ref. LS)
- FDA HDE on-label use (FDA Ref. LS HDE)
- Off-label use
- How confident are you that the evidence is adequate to conclude that the use of BMPs for FDA HDE on-label use in recalcitrant long bone non-unions improves at least one of the clinically meaningful health outcomes? (FDA Ref. LB)
- How confident are you that the evidence is adequate to conclude that the use of BMPs for FDA PMA approved on-label use for the treatment of acute, open tibial fractures improves at least one of the clinically meaningful health outcomes? (FDA Ref. T )
- How confident are you that the evidence is adequate to conclude the off-label use of BMPs in the cervical spine improves at least one of the clinically meaningful health outcomes?
- How confident are you that these conclusions are generalizable to:
- the Medicare patient population?
- community based settings?
Discussion Questions
- In the absence of evidence based guidelines, what types of research are needed to address evidence gaps so that physicians can appropriately counsel patients on the risks and benefits of the use of BMPs?
Here’s a handy reference to the history of Food & Drug Administration actions regarding BMPs:
| Question Reference | Date | Infuse (rhBMP -2) | OP-1 (rhBMP -7) | Indications | |
|---|---|---|---|---|---|
| LS | Lumbar Spine Anterior | July 2, 2002 | Approved PMA for Infuse Bone Graft/LT Cage (P000058) – Medtronic Sofamor Danek | Spinal fusion procedures in skeletally mature patients with degenerative disc disease at one level from L4-S1 via anterior open or anterior laparoscopic approach. DDD confirmed by patient history, function deficit and/or neurological deficit and radiographic studies. May have up to Grade I. Spondylolisthesis at involved level. Should have had at least six months of nonoperative treatment prior to surgery with Infuse Bone Graft/LT Cage device. | |
| December 1, 2003 | Approval for the inclusion of additional fusion cage component designs for use with the InFuse Bone Graft Component. The device as modified will include the previous device, along with InFuse Bone Graft/Inter Fix Threaded Fusion Device and Inter Fix RP Threaded Fusion Device. (P000058/S004) – Medtronic Sofamor Danek | All indications are the same as the approval for the Infuse Bone Graft/LT Cage, except that these devices are only approved to be implanted via an anterior open approach. | |||
| July 29, 2004 | Approval for 1) the extension of the levels of use, 2) modification of the indications, 3) change in storage temperature limit and 4) revisions to instruction for use. Infuse Bone Graft –LT Cage Lumbar tapered fusion device (P000058/S002) – Medtronic Sofamor Danek | Extended levels of use from L4-S1 to L2-S1. Modified indications to allow the device to be used in subjects who may have retrolisthesis in conjunction with DDD. |
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| Note: There are additional supplemental approvals to P000058 not listed here that deal with things other than indications for use, such as packaging, minor design modifications, storage temperature, etc. | |||||
|
LS HDE |
Lumbar Spine Posterolateral | April 7, 2004 | Approved HDE (H020008) Stryker Biotech | Indicated for use as an alternative to autograft in compromised patients requiring revision posterolateral (intertransverse) lumbar spinal fusion, for whom autologous bone and bone marrow harvest are not feasible or are not expected to promote fusion. Examples of compromising factors include osteoporosis, smoking and diabetes. | |
| October 10, 2008 | Approved HDE for Infuse/mastergraft posterolateral revision device. (H040004) – Medtronic Sofamor Danek | This device is indicated for repair of symptomatic, posterolateral spine pseudarthrosis. This device is intended to address a small subset of patients for whom autologous bone and/or bone marrow harvest are not feasible or are not expected to promote fusion. These patients are diabetics and smokers. This device is indicated to treat two or more levels of the lumbar spine where previous fusion has failed. | |||
| LB | Long Bone | October 17, 2001 | Approved HDE (H010002) – Stryker Biotech | As alternative to autograft in recalcitrant long bone nonunions where use of autograft is unfeasible and alternative treatments have failed. | |
| T | Tibia | April 30, 2004 | INFUSE PMA (P000054) – Wyeth Pharmaceuticals, Inc. | Approved for treating acute, open tibial shaft fractures that have been stabilized with IM nail fixation after appropriate wound management. INFUSE Bone Graft must be applied within 14 days after the initial fracture. Prospective patients should be skeletally mature. | |
| Sinus | March 9, 2007 | INFUSE Bone Graft PMA (P050053) – Medtronic Sofamor Danek | Indicated as an alternative to autogenous bone graft for sinus augmentations, and for localized alveolar ridge augmentations for defects associated with extraction sockets. | ||
| July 1, 2008 | FDA issued a public health notification regarding BMP in cervical spine fusion. The FDA warned of life-threatening complications associated with BMP when used in the cervical spine. BMP is not approved for use in the cervical spine. | ||||
| March 31, 2009 | *FDA- Orthopedic and Rehab Devices Panel advised not to approve Stryker OP-1 (P060021) for posterolateral lumbar spinal fusion in adult patients with degenerative spondylolisthesis. | ||||
*Stryker submitted an application with the FDA for OP-1 Putty spinal product and hoped for approval by late 2007. FDA requested additional data which significantly delayed the company’s expectation for approval. FDA convened an advisory committee to review this issue and did not recommend approval (2009). No further action by FDA.
