A diaphragm pacing system recently approved for patients with amyotrophic lateral sclerosis (ALS) could provide some benefits, but neurologists say the implantable device is not a proven panacea and that more research is needed to better define its role in treatment.
The system, intended for ALS patients who have respiratory problems and intact phrenic nerves, aims to help preserve patients' breathing by stimulating the diaphragm muscles to keep them conditioned.
It consists of four electrodes implanted in the diaphragm; a fifth electrode implanted under the skin; an electrode connector, which groups the five electrodes exiting the skin into a socket; an external pulse generator; and a removable cable to connect the electrode socket to the generator.
The US FDA granted a “humanitarian device exemption” on Sept. 28 to the device manufacturer Synapse Biomedical Inc., of Oberlin, OH, based on data from a company-sponsored clinical trial involving 86 patients at nine medical centers with chronic hypoventilation.
According to a company spokesperson, the patients who used the NeuRx DPS [diaphragm pacing system] plus non-invasive ventilation (NIV) — such as BiPAP — survived 16 months longer (on average) — from the time of diagnosis — than patients who just used NIV; the patients who only used NIV were in a different study. Survival time was measured unatil death or the need for a full time ventilator and tracheostomy. The company also reported a nine-month survival benefit when measured from the start of NIV.
The system was approved in 2008 for use in patients with spinal cord injuries. Its most famous patient was actor Christopher Reeve, who was paralyzed in a riding accident.
The FDA, in granting the humanitarian device exemption, asked Synapse Biomedical, to do a post-approval study, which is being conducted at several U.S. sites. In addition, the company is conducting a 108-person randomized clinical trial in the United Kingdom, a company spokesperson said. Researchers also are planning to publish the results of the device's effect on sleep patterns.
The device is being sold to hospitals at the cost of $21,250, which does not cover the cost of surgery and other related treatment. The company anticipates that private insurers and Medicare will provide coverage. The system is already being used for ALS in some European countries.
The data submitted to the FDA was not obtained in a randomized, controlled trial, ALS specialists not involved with the data collection told Neurology Today. One analysis compared the results of the study involving 86 patients to those involving standard therapy at an ALS Clinic at Johns Hopkins University, said neurologist Robert G. Miller, MD, director of the Forbes Norris MDA/ALS Research Center at California Pacific Medical Center in San Francisco. The other analysis, he noted, compared pretreatment and post-treatment values of breathing tests for each patient.
Seven of Dr. Miller's patients received the device. “I have to say that no patient looked me in the eye and said, ‘Holy mackerel! What a benefit,’” Dr. Miller told Neurology Today in an interview. He, his co-neurologists and nurses also did not observe “any dramatic impact,” he said.
Still, Dr. Miller said the overall data collected during the clinical trial suggests that the diaphragm pacing system could be a useful therapy for ALS patients, though he said more research is needed to define which patients would likely benefit the most. For now, he characterizes the device as an “an adjunct therapy”— another tool, along with feeding tubes, BiPAP, and riluzole — that could possibly benefit many ALS patients.
Dr. Miller said he can understand the skepticism he has heard from some neurologists, who feel there has been too much hype about the device before all the facts are in. “Some people think there is nothing there and others feel the company might be right. I would say I'm somewhere in the middle,” Dr. Miller said.
He noted that the manufacturer claims the implantation can be done using minimally invasive laparoscopic surgery, but the surgery is not without risk. Two of his center's patients experienced complications from the surgery — one developed pneumonia and the other had capnothorax.
Hiroshi Mitsumoto, MD, Wesley J. Howe Professor of Neurology at Columbia University, told Neurology Today, his office had received calls from ALS patients wanting the device. He is not yet convinced, however, of its worth.
“I have to say that the more we have in the armamentarium to manage ALS the better, but we have to be cautious until we see a published paper,” he said. “Patients are grasping at straws,” he said, and they need as much information as possible to make informed decisions about how best to manage an incurable disease. He said that a carefully designed randomized clinical trial comparing the device to traditional treatment would help better define its usefulness.
“I welcome having more options,” he said. “But before we can recommend this to patients we have to know more.
THE PITFALLS OF THE HUMANITARIAN EXEMPTION
Several papers and recent articles have questioned the concept of FDA approval of therapies and devices on the basis of the humanitarian exemption.
In the Oct. 11 issue of Health Affairs, Joseph J. Fins, MD, and colleagues argue that the FDA's granting of a humanitarian device exemption to allow patients to access deep brain stimulation for obsessive-compulsive disorder, for example, removes the requirement for a clinical trial of the appropriate size and statistical power. “Bypassing the rigors of such trials puts patients at risk, limits opportunities for scientific discovery, and gives device manufacturers unique marketing opportunities,” the authors wrote. “We argue that Congress and federal regulators should revisit the humanitarian device exemption to ensure that it is not used to sidestep careful research that can offer valuable data with appropriate patient safeguards.”
For more discussion on concerns about the humanitarian exemption, see:
- Fins JJ, Mayberg J, Schlaepfer TE, et al. Misuse of the FDA's humanitarian device exemption in deep brain stimulation for obsessive-compulsive disorder. Health Aff 2011; 30:302-311.
- Hurley D. Should the FDA rescind the humanitarian exemption for DBS? Neurology Today 2011; March 3, 2011: neurotodayonline.com.