Gather the evidence!

131

After a searing debate between David F Kallmes and Allan Brook on the place for vertebroplasty, 60% of SIR delegates voted for more randomised trials on the procedure. Vertebroplasty has been in the eye of a storm following the publication of two papers in August 2009 which found no benefit for the treatment, over a sham injection

David F Kallmes, professor of Radiology, Mayo Clinic, Rochester, USA, and Allan Brook, director of interventional neuroradiology, Montefiore Medical Center, and associate professor of Radiology and neurosurgery at the Albert Einstein College of Medicine, New York, USA, debated the topic “Vertebroplasty has been demonstrated to be no better than placebo, and hence has no place in the interventionalists’ armamentarium”.


Kallmes, speaking for the motion, won the majority of audience votes polled at the session which took place at the Society of Interventional Radiology’s 35th Annual Meeting in March 2010, Tampa, USA. “We know that spine augmentation works. Substantial improvement may be seen even without polymethylmethacrylate (PMMA) and most of the short- and long-term complications with the procedure are related to PMMA,” said Kallmes. He won 60% of the votes polled at the session.


Kallmes’ presentation was titled “Augmentation should be done in trials and registries”, and he said, “What we would like to know is whether PMMA matters, are there important subgroups of patients that benefit most from the procedure and is one type of augmentation better than another?

“How do we find out the answers we are seeking? Not by simply continuing current practice, not by discussing past trials over and over and not through debates. It is only by doing new trials and registries,” he said. “If we refocus our energies away from debating and towards designing, funding and carrying out new trials, we can optimise care for millions of future patients,” Kallmes said.

Brook, Kallmes’ opponent in the debate, argued that vertebroplasty has been demonstrated to be better than a placebo, and so had a place in the interventionalists’ armamentarium.


He said vertebral augmentation is a valid, efficacious and safe procedure in properly selected patients. “Medical judgment, physician expertise, and patient education on practice standards is both prudent and necessary,” he said.


Brook told Spinal News International that since the 1980s vertebroplasty had developed into the standard of care after conservative management has failed.


“In the August of 2009, two papers were published by the New England Journal of Medicine which created quite a stir. These two randomised, controlled trials were the first to be published of this scientific calibre. But INVEST (Investigational vertebroplasty efficacy and safety trial. Kallmes et al) which randomised an injection of anaesthetic around the facet/pedicle (called the sham) vs. cement injection into the vertebrae demonstrated significant decrease in pain in both arms of the study. There was a slight trend that vertebroplasty was better but not to a scientifically significant amount,” he said. Brook said that there were many factors that needed to be integrated into an informed doctor-patient decision process. “Many experienced interventional physicians feel strongly that there were significant biases in these two studies. The first of these is a bias regarding the type of patients who were selected. The majority of patients in these two small series were treated for sub-acute and chronic fractures by standard criteria.This clearly obviates much of the benefit that would be demonstrated in acute fractures.The other serious flaw was the lack of direct physical exam before and after documenting the exact pain of the fracture site vs. any back pain in the geriatric population.


“Questionnaires do not substitute for an experienced pain physician or surgeon. Immediate high-level imaging was also lacking for many of the patients. This may account for some residual pain, as we know adjacent fractures occur in 20% of this population. The NEJM studies excluded many patients who we typically treat, including all inpatients who are incapacitated and forced to be hospitalised.”


Brook concluded, “We are all dedicated to finding subgroups of patients who will benefit from augmenting the weak osteoporotic bone and those who will heal without intervention.”


The cost factor


The results from the Kallmes et al and Buchbinder et al studies have led to heated debate about vertebroplasty, its effectiveness and the cost. While some interventionalists have continued to slam the two studies, others maintain that the randomised controlled trials published in the NEJM offer the best evidence to date. There have been articles in the media suggesting that many interventional radiologists are defending vertebroplasty on a financial basis. J Kevin McGraw, Riverside Radiology and Interventional Associates, Columbus,USA, said: “Some in the media have opined that interventional radiologists are trying to continue performing vertebral augmentation purely for financial gain. My group probably has one of the largest vertebral augmentation practices in the country. If we stopped performing these procedures today the financial impact on my group would result in less than 1% loss in revenue. This assumes that we do nothing with the time spent treating compression fractures. In reality, we would perform other procedures or interpret imaging studies. So the financial impact would be much less. The reason the SIR feels we should continue performing vertebral augmentation is for patient care. Obviously, we need continued research in this area. I do not want our senior citizens denied coverage for a procedure that works to alleviate pain from compression fractures.”


Subgroup analysis


Waleed Brinjikji of the Mayo Clinic, presented the results of a subgroup analysis of the INVEST study, comparing pain improvement over time between vertebroplasty and a sham procedure in patients with severe pain. Of the 131 patients enrolled in the study, 30 patients in the vertebroplasty group and 31 in the control group reported severe pain at baseline. Both groups achieved significant improvements in pain and disability after 30 days. However, the improvements were similar between groups.


“Our results demonstrate that both vertebroplasty and control patients with severe pain had similar improvements in pain and pain-related disability at days three, 14 and 30, following the procedure. It is important to note that in both of these groups, there was a significant improvement in pain that was immediate and sustained. In other words, vertebroplasty provided excellent pain relief for patients with severe pain, however, this pain relief was statistically similar to that seen in the control group,” said Brinjikji.


In a separate session at the SIR Annual meeting, Kallmes said that multiple prospective randomised trials were the only way of moving the field forward. He told delegates results of the INVEST trial showed that, “Without doubt, vertebroplasty, the procedure, works. However, this trial is at least provocative that the obvious clinical benefit may not derive from the infused cement. And, very importantly, it shows that we can blind patients, even in an interventional trial.


“I have no doubt that continued implementation of vertebroplasty will provide ongoing substantial patient benefit. Informed patients, however, might be interested to know that almost equal benefit might be gained without the cement. We owe it to those future patients to understand what we are doing,” he said.


Kallmes stated that he really did not want to do a lot of subgroup analysis on INVEST, and referred to Jean Raymond who quoted Schulz and Grimes (Lancet 2005): “At best, unplanned, uncontrolled subgroup findings can only be used as the hypothesis for another trial. Until such a trial is performed, the answer to a randomised controlled trial that does not confirm one’s beliefs is not the conduct of several subanalyses until one can see what one believes. Rather, the answer is to re-examine one’s beliefs carefully.”

(Visited 26 times, 1 visits today)