Holy “Sham-WOW” Rocky, talk about comparative effectiveness.
Vertebroplasty with PMMA isn’t any more effective in treating vertebral compression fractures than “control intervention” treatments. That’s the conclusion of two studies released on August 6 in the New England Journal of Medicine (NEJM).
Various media outlets characterized the control treatments as a “sham” treatment. A “sham” treatment refers to any pharmaceutical product or device/procedure that mimics the treatment under study and can be used as a placebo in a clinical trial. In this case, the “sham” treatments were primarily performed at the Mayo Clinic in Minnesota and Monash University’s Cabrini Hospital in Malvern, Australia.
David Kallmes, M.D.The Australian study (N Engl J Med. 2009 Aug 6;361(6):557-568), led by Rachelle Buchbinder, Ph.D., concluded that there was “no beneficial effect” of vertebroplasty as compared to the control intervention treatment. The control intervention treatment in this study consisted of a little lidocaine, a massage and some aromatherapy.
The Mayo study (N Engl J Med. 2009 Aug 6;361(6):569-579), led by David Kallmes, M.D., found that “improvements…were similar” for the two groups of patients.
“It is absolutely shocking, ” said Kallmes, an interventional neuroradiologist, in an August 5 story on Forbes.com.
To be clear, the studies showed that vertebroplasty was effective in reducing pain in patients. It’s just that the actual insertion of polymethylmethacrylate (PMMA) cement didn’t appear to make a difference to the outcome. If that is the case, the answer to the improvement of patients’ pain appears to be found in examining the control intervention treatment.
Control Intervention Treatment
When we contacted Dr. Kallmes, he noted that his research team did not refer to a “sham” procedure. They called it a “control intervention.”
He told OTW on August 8:,
While many are referring to our study as a “sham” trial, we prefer the term “control intervention.” Remember that we did perform an intervention with sedation and local anesthesia. Also, I would caution against concluding that, since patients in our trial responded to local anesthesia alone, that they might respond in the same way outside of a trial. They did not respond to simple local anesthesia—they responded to local anesthesia that they thought was a vertebroplasty.
Both groups of patients were hooked to an IV and given sedation and pain-killing shots in their back. The vertebroplasty group got shots of cement into their vertebrae. For the control intervention treatment, doctors simulated the cement injection by pressing the back, tapping instruments and having the strong-smelling cement on hand.
Patients are usually awake during such surgery, so surgeons and staff tried to make sure that patients in the control group thought they got the full treatment. Kallmes said that surgeons gave the same verbal commentary to patients receiving and not receiving the cement.
Not only were the patients kept in the dark about which procedure they were undergoing, but also the medical staff didn’t know if a given patient would be assigned to the control group until the last minute. “I wanted everyone in the procedure room to really be thinking like it was going to be the real thing, ” said Kallmes in a St. Paul Pioneer Press story on August 5.
The researchers do not know why patients receiving the control intervention procedure felt better, but they suggest it could be due to the anesthesia, the placebo effect, or that the fractures healed on their own over time.
So, a little lidocaine, a massage, some aromatherapy, and good operating room theater fooled patients into thinking they got the cement injections. Maybe next time, surgeons can swab the patient’s back with a ShamWow® towel and add some drumming.
“Too Early to Kill Vertebroplasty”
Kallmes did the study, according to the August 5 Forbes story, because he always thought the results reported for vertebroplasty seemed too good to be true―everyone got good results no matter how much cement was injected or what technique was used. He also said that the mechanism for vertebroplasty was a bit of a mystery. If the procedure was that good, he figured, it would be easy to prove it.
Kallmes also told CBS Evening News on August 5, “Everybody says they want evidence-based medicine.” But, he continued, “Sometimes the evidence isn’t what you asked for.”
“We aren’t saying the vertebroplasty doesn’t work, because somehow it does, ” says Kallmes.
He said it is too early to kill the procedure, but he thinks doctors need to stop doing it routinely outside of research trials. Buchbinder went further. She doesn’t think vertebroplasty should be done any more outside of research studies. She said there were some risks, and researchers did not demonstrate benefits.
Complications
Wells Fargo Senior Analyst Mike Matson wrote on August 6 that if there is no clinical advantage to vertebroplasty, then patients are being subjected to anesthesia and PMMA cement. Leakage of bone cements can result in soft tissue damage, nerve root pain and compression, pulmonary embolism, respiratory and cardiac failure, and death. Each of these complications has been reported in both vertebroplasty and kyphoplasty procedures.
No such adverse events were reported in these studies.
“While there is only a 1% adverse event rate reported in the literature, it has been well documented that the adverse event rate may be underrepresented. Even if this is not the case, the severity of these events could potentially no longer be outweighed by positive clinical results, ” wrote Matson.
Comparative Effectiveness
This study might pump in some oxygen to proposed healthcare reform legislation currently being debated in town hall meetings across the country and the $1.1 billion approved for comparative effectiveness research in the stimulus package last February.
Jim Weinstein, M.D.The goal of comparative effectiveness is to get better data on which medical procedures and devices provide value for the money. “The results [of the vertebroplasty studies] are a very big deal for all of health care, ” said Dartmouth’s Jim Weinstein, M.D, in the Forbes article. “This is what the president is asking us to do―find the answer and pay for value. If things work let’s pay for it, if it doesn’t, let’s not.”
Each year Medicare pays for roughly 40, 000 vertebroplasty procedures at a cost of $3, 000 or more each, said Weinstein. If the new studies’ findings are correct, much of that money has been wasted. He estimates that at least that many (more expensive) kyphoplasty procedures are done.
With five spine societies telling CMS last fall that kyphoplasty adds no value to vertebroplasty, and now these studies saying vertebroplasty has no beneficial effect over the use of anesthesia, a push on the back and a good show in the operating room, one has to wonder where a possible CMS coverage decision about vertebral compression fracture (VCF) treatments ends up.
Vertebroplasty
In 1999, the Food and Drug Administration reclassified bone cement to a low-risk regulatory category. At that time, the cement was sold to attach prosthetic joints to the bone, such as in the knee or hip.
Five years later, the FDA allowed makers of cement, including Stryker, Johnson & Johnson, and Cook, to market their products for use in a vertebroplasty―without a prosthetic, and without needing a controlled trial that vertebroplasties work.
An August 5 Wall Street Journal article reported that an FDA official said the agency’s decision was based on previous use of bone cements to fill in fractured bones. “We determine it’s not so extremely different that it’s outside the box, ” said Heather Rosecrans, who directs the agency’s review of such devices.
Markets
Since the FDA reclassification, the U.S. market for vertebroplasty has reached an annual sales level of about $245 million in 2008 and is projected to grow annually at a rate of 13.5%. Kyphoplasty’s annual sales volumes are higher at around $500 million, according to PearlDiver estimates.
PearlDiver Senior Analyst Matt Menze forecasts that VCF treatments in the U.S. will rise to almost 300, 000 procedures by 2012. Kyphoplasty is expected to capture the majority of those procedures.
Number of Procedures
Source: PearlDiver
Wells Fargo’s Matson wrote on August 7 that these studies have refocused investors on the risks within the VCF market. He notes that this is not a risk to the level of reimbursement per se, but it is a risk to whether insurers (particularly Medicare) choose to continue to cover VCF treatments.
Matson doesn’t believe that these studies will deter surgeons and interventionalists from performing vertebroplasties, but he believes they could impact the primary care referral channel and stifle growth. He says the studies don’t bode well for future referrals and could be a substantial risk for Medtronic’s Kyphon acquisition and Orthovita’s Cortoss product.
Kyphoplasty Impact
We asked Medtronic spokesperson Marybeth Thorsgaard about the studies.
In a prepared statement for OTW, the company said the studies about vertebroplasty “do not imply anything about balloon kyphoplasty. Vertebroplasty and balloon kyphoplasty are different types of spinal procedures providing different outcomes for patients.”
Thorsgaard pointed to the FREE trial reported in the February 24 online edition of The Lancet. (2009 Mar 21;373(9668):1016–1024. Epub 2009 Feb 24).
According to Thorsgaard, that study of 300 patients at 21 centers in eight countries provides clinical evidence of improved outcomes with balloon kyphoplasty compared to non-surgical care when treating patients with acute vertebral compression fractures.
In addition, she noted that Medtronic is running its KAVIAR trial of kyphoplasty versus vertebroplasty.
Kallmes hopes doctors will wait for more data from that study. “We need to do more research with a larger number of patients to identify which subgroups of patients might benefit, ” Kallmes said in the Pioneer Press story. “I would not want to comment on kyphoplasty, except to say that we are doing trials currently comparing the two procedures.”
“There is no plausible reason why it [kyphoplasty] would work where vertebroplasty doesn’t work, ” said Australia’s Buchbinder in the Forbes story. She calls for blinded trials looking at the benefits of kyphoplasty.
University of Washington neuroradiologist Jeffrey Jarvik, who worked on the vertebroplasty study added, “It absolutely calls into question the benefit of kyphoplasty as well.”
NASS Comment
Finally, we went to the largest spine society in the U.S., the North American Spine Society, for comment about the impact of the studies.
In a written response, Charles Branch, M.D., NASS President and neurosurgeon at Wake Forest University said,
NASS acknowledges these studies and their contribution to our evidence base. Studies like these aid the medical community in our drive to develop meaningful guidelines to provide the best care for our patients. NASS looks forward to the opportunity to review these studies fully and to determine their significance as they relate to patient care.
These studies are significant, according to a number of surgeon thought leaders who have a lot of influence with their societies and payers. It’s hard to imagine that these studies are not being considered by Dr. Phurrough and the coverage team at CMS.
So this is what comparative effectiveness might look like in the near future.
Holy Sham-WOW, Rocky.
