Medtronic Inc.’s (NYSE:MDT) Infuse bone growth product created a stir this summer after an entire edition of the Spine Journal was devoted to problems with a slew of peer-reviewed articles by company-backed doctors.
The journal’s investigation found that 13 Medtronic-backed studies downplayed or omitted entirely evidence of safety risks from Infuse.
A Senate probe and a raft of lawsuits soon followed. MDT shares stalled on the news, plus allegations that Medtronic’s paid consultants may have concealed Infuse’s infertility risk in men. Medtronic weathered the storm and share prices rebounded.
Medtronic spokesman Steve Cragle told MassDevice in July that the company hadn’t “heard any feedback from our customers that they are reducing their expected use.” Infuse, Cragle told us, is a “physician-pull product,” meaning that Medtronic reps don’t actively promote it and aren’t compensated for any Infuse sales.
“So it’s up to the physician to determine when to use our product,” Cragle wrote in an email.
Medtronic pulls down between $700 million and $750 million from Infuse alone, analysts estimate.
Now comes Becker’s Orthopedic, Spine & Pain Management Review and its poll of 10 spine surgeons. The review asked the docs whether the revelations about Infuse have changed their use of the product:
- Dr. Neel Anand, Director of Orthopedic Spine Surgery, Cedars-Sinai Spine Center, Los Angeles:
"The articles that came out in The Spine Journal have not changed my practice regarding BMP. The reason is simple: while it is true that BMP is being used off-label and in some indications where it wasn’t appropriate, there are other situations where we can achieve great results. There have been some complications with cervical spine use and instances of extra bony formation, which are extremely rare compared to the number of patients who receive BMP. In studies we have published, we have noted very clearly that the dosage of BMP needs to be restricted to the minimum possible to achieve fusion. In deformity correction and minimally invasive surgery, we have published the average dose per level of how much BMP is needed. It is possible complications can arise when higher doses are administered. Given all of this, with appropriate understanding of the product and proper usage my use of BMP has not changed.
"I do think that BMP (Infuse) is one of the biggest scientific advances in orthopedics and spine surgery in this century. It is the only biologic protein on the market that has been extensively studied prior to introduction on the market. It clearly has been one of the most effective bone forming proteins to enhance fusion and has had a big impact on the market because it has made minimally invasive surgery truly effective. Now, we are able to avoid a separate surgery of harvesting local bone from the iliac crest, which used to be routine when we did fusions prior to the use of BMP. This procedure in itself has 25 percent to 30 percent morbidity in terms of chronic pain. The introduction of BMP has enhanced our fusion rates significantly and has avoided the morbidity of the above bone harvesting.
"When counseling patients on their option of surgery using BMP, we need to go over the risk and benefits, and if appropriately used the benefits far outweigh the risks. There has been a recent study that showed patients who received BMP were at increased risk of retrograde ejaculation, but that was one study in one individual practice. We need to see if the same holds true among other surgeons. Unfortunately there are going to be some complications with any procedure we do, but to blame it on a product that has been extensively researched isn’t right. Its more important we understand the issues and address them appropriately and most important share the knowledge with our patients and let them be part of the decision making process. In the end, it’s about assessing the risks and benefits for each individual patient."
- Dr. Joshua Auerbach, Chief of Spine Surgery, Bronx-Lebanon Hospital Center, Bronx, New York:
"I currently use BMP very sparingly. The first reason is that my particular practice consists mostly of primary cervical and lumbar degenerative conditions, and pediatric deformity, which typically have good environments in which to achieve fusion. Given the types of cases I am most commonly performing, I have been able to achieve the desired results in fusion cases without using BMP.
"Another factor in deciding whether or not to use BMP is cost. In my hospital-based practice in the South Bronx, as in all hospitals, containing costs while still achieving excellent outcomes is of paramount importance, so we choose our implants carefully and use bone graft extenders when needed. With increasingly limited resources, a careful and evidence-based approach to resource allocation is critical for the continued success of our hospital. While the literature demonstrates success with BMP in many clinical scenarios, it is still not clear whether or not the addition of BMP in the common degenerative cervical and lumbar conditions I primarily treat leads to clinically improved outcomes when compared with local autograft, with or without bone graft extenders."
- Dr. Hyun Bae, Spine Surgeon, St. John’s Health Center, Santa Monica, Calif.:
"I think BMP is an incredibly potent and incredibly efficacious molecule. Nothing that we have as far as bone graft substitutes — whether that is DBM, allograft, bone marrow aspirate or PRP — has ever come close to the effectiveness of BMP in producing bone. However, when we are dealing with a potent molecule, we are going to have complications and side effects. If you think about antibiotics, they are potent molecules that help with infection, but even they are associated with complications because they are so potent. To think that we have a molecule that can drive osteogenesis single handedly, create bone de novo and not have any other mechanistic side effects would be naïve.
"Since the recent controversy over BMPs, I think use has decreased, but not substantially. In the future, we will start using it in situations that are more appropriate and stick to on-label applications. What’s really going to be fleshed out from all this is the understanding of the different demands of various fusion environments. I think most of us can agree that BMP is an incredibly useful product and it will be used more for cases where the demand for fusion is the greatest.
The FDA indications for on-label use of BMP are currently very restrictive. I would say around 95 percent of BMP use is currently off-label because the on-label use is limited to one level surgery with a specific spinal cage that is no longer commonly used."
- Dr. Robert Bray Jr., Founder, DISC Sports & Spine Center, Marina del Rey, Calif.:
"Over the years, I have limited my use of BMP quite a bit. I only use it in interbody fusions. I have stopped using it during transforaminal lumbar interbody fusions because of bony overgrowth, and I don’t use it with posterior surgeries or scoliosis. I use BMP with PEEK and anterior fusions, but I use a very small dosage (usually half of the small kit). Using it in low doses with cages to contain the BMP can produce very good results.
"I’ve sat on the Congress of Neurological Surgeons panel for osteobiologics for about four years and I’ve spoken specifically on the complications with BMP. There has been massive use of BMP in off-label characteristics, and there are varying estimates saying that BMP is used in about 75 percent of spinal fusions cases. There has also been a massive cost increase for hospitals because BMP alone can cost $3,000-$7,000 per case, and more when surgeons use it with scoliosis cases. This is a direct increase in the cost of healthcare and you can’t increase the cost of healthcare that much without someone to off-set it, especially without the literature showing it does something dramatically better than the current standard of care.
"What we’ve seen across the board is a significant pull-back in BMP use. BMP is an incredibly powerful tool to make fusion happen, but now we are asking whether it is worth the expense or whether it will break the piggy bank.”
- Dr. Gino Chiappetta, Spine Surgeon, University Orthopaedic Associates, New Brunswick, N.J.:
"I use Infuse solely for lumbar cases, not cervical cases. For me, the big issue is cost; does the cost-benefit outweigh the risks associated with using BMPs? In the lumbar cases, I use BMP for either revision surgery, long-fusion constructs spanning several levels and adult scoliosis patients. I don’t use it for single- or two-level fusions because I think using an autograft produces a comparable result but doesn’t cost as much money. For me, the fusion rate has been excellent with the use of BMP, but I don’t use it routinely because I think I can get equally good results using a cheaper product.
"Hospitals are pretty aggressive about analyzing the cost for cases and in many situations BMP does end up hurting the hospital because there isn’t any profit or the hospital actually loses money on the case. Hospitals are certainly concerned with cost post-healthcare reform and it’s something we keep in mind with every case we do. I think the companies will see a decrease in BMP use, which will force them to decrease the cost. Hospitals will tell surgeons they can’t use BMP unless they are pre-approved cases, and only certain cases will be pre-approved. The product will become less used and less profitable for the companies, so the cost will have to come down.
"Future research and longer-term studies will certainly guide us in BMP use, especially with proper patient selection. I think the studies will show who really needs BMP versus who can achieve a good clinical outcome without it. We will also look at the cost-effectiveness for BMP use. In the short term, BMP might be more expensive, but if the revision surgery rate is lower in BMP patients, there could be a decreased cost of healthcare in the long term."
- Dr. Robert Eastlack, Spine Surgeon, Scripps Clinic, San Diego:
"BMP is a very important scientifically proven tool for us. It’s been around for many years and we are continuing to find out more about it. Initially, BMP was used in a way that we thought was appropriate based on animal studies and early clinical trials. Over time we’ve begun to understand that BMP can adversely affect nerve and other tissues, and in hindsight most practitioners have appropriately changed their pattern of usage.
"BMP is an important tool for spine surgeons, and we will continue to find use for it in the future. My hope is that we can harness its capacities in a wiser fashion, perhaps within a cocktail of other important adjuvants that facilitate bone growth. These most recent controversies have brought out the need for potentially higher scrutiny of new technology, particularly on the editorial side of things. Equally importantly, the backlash against it needs to be measured and judicious. It’s been hyped up and we don’t want to throw the baby out with the bathwater.
"There’s also a financial side of the equation. Hospitals are having a challenging time managing the cost of BMP. In addition many practitioners utilize BMP in a manner termed ‘off-label,’ which simply means the FDA did not make any decisions about its use in those scenarios. This isn’t uncommon because technology in medicine is evolving much faster than bureaucrats and regulators can keep pace with at the FDA. At the end of the day, I think it’s going to be a useful tool and we’ll have a better understanding of how to harness the dosage to achieve a fusion without the side effects for our patients. The combined use of BMP and other products in a more effective manner will foster new product development, and therefore result in a downward pressure on prices for these biologics."
- Dr. Andrew Hecht, Co-Director of Spine Surgery, Mount Sinai Department of Orthopaedics, New York City:
"I know everyone is very much concerned about the article that came out in The Spine Journal this past summer, but it hasn’t swayed me one way or another. I use Infuse on select cases because it can be a very powerful tool for select patients. I think most surgeons are using it in various places in the spine and finding upsides and downsides to its use.
"I think when we locate the appropriate dosage signs, we will see increased efficacy. Some spine surgeons have used Infuse in the cervical spine and experienced complications. When we use Infuse for patients in the neck, we use a very small dosage and combine it with steroids to achieve a good fusion. I don’t think Infuse is going to disappear; as we figure out the dosage, I think it will become a more potent tool for surgeons to use.
"For now, I only use Infuse on the most challenging cases, such as three- or four-level fusions, and it has worked well for me. I don’t use it on one or two level fusions, and I think surgeons for the most part are using it judiciously.”
- Dr. Thomas Schuler, Founder, Virginia Spine Institute, Reston:
"I worked on the original study for using BMP for the anterior approach to lumbar fusion with the LT cage. Now, we use BMP for lumbar fusion where it is FDA approved, as well as some off-label applications. Since the FDA sent out the warning letter about using BMP in the cervical spine, we initiated a study looking at our patients who are at a high risk for non-union in the cervical spine. We agree that BMP has an inflammatory effect to initiate fusion and most of the complications in the cervical spine were from using an incorrect dose. We’ve been doing the study for the past three years in the cervical spine for revision surgeries or other complex fusion cases and have had good results.
"We are also using BMP in multi-level fusions because we can gain a significant improvement for patients who are at risk of non-union. BMP has been a game changer in terms of the way spine surgeons practice, and more importantly the results they can give their patients. Minimally invasive fusion surgery isn’t possible without it. Looking at the studies, we went from a high non fusion rate of 17-18 percent down to 1 percent with the use of BMP. This has greatly improved the lives of Americans because they undergo less surgery with a higher fusion rate. The use of BMP is critical and beneficial for people who need it. People are always going to throw stones, but the question is whether we want to go back to the Stone Age without BMP."
- Dr. Brian Subach, Director of Research, Virginia Spine Institute, Reston:
"The biggest thing we face is dealing with well informed patients who demand the use of biologics like BMP. Leah Carreon, MD, and her colleagues recently published a study showing that patients who do not receive BMP had a higher rate of complications and an increased rate of revision surgery compared to patients receiving BMP, so using BMP can actually be more cost-effective in the long run. Hospital administrators want us to justify why we are using BMP for certain cases. We want to do the best we can for our patients through good surgical technique and careful research validating results for both the on- and off-label use of BMP.
"We feel strongly that the use of BMP has changed people’s lives. Using iliac crest bone graft is a brutal procedure that quite simply does not need to be done. We have found BMP to be a safe and effective alternative to harvesting bone from the pelvis. With judicious use of the product as an adjunct to fusion, our results and outcomes using BMP have been outstanding."
- Dr. Greg Yoshida, Medical Director of Spine Deformity/Scoliosis, Tri-City Regional Medical Center, Hawaiian Gardens, Calif.:
"I have been using BMP less and less over the years, one reason being that there’s a cost factor. I stopped using posterolateral gutters because I’ve found the dosing is too low in the sponge. In the rat and dog model, the dosage was much higher for that indication as well. I know some people who use BMP for everything.
If a substance promises to give you 100 percent or close to it without harvesting the patient’s own bone, most surgeons are all for it. I’ve become very strict with my application because of some complications patients can experience. I’ve used BMP with different cages, but never by itself because I think it’s important to keep it contained.
"I used to use it sometimes in the neck instead of a resorbable cage or allograft and it worked wonderful there. I never had any patients with adverse reactions, but I know there have been adverse reactions to that application. When complications occur, surgeons were using a ton of BMP in the neck and laying it against the front of the spine, which is right next to the esophagus. Even though I’ve avoided these things and had a good result with BMP in the cervical spine, I wanted to avoid controversy so I don’t use it there anymore. When something becomes controversial, I become stricter with it."