In its press release accompanying the Approval Letter, the FDA noted, “The approval of the human device exemption was based on a review of data from 26 patients with severe treatment-resistant OCD who were treated with the device at 4 sites.” Those results were published in the May 2008 issue of Molecular Psychiatry.2 The researchers concluded that DBS produced “clinically significant symptom reductions and functional improvement in about two-thirds of patients” and that any adverse effects “were overwhelmingly transient.”
An article published in the February 2011 issue of Health Affairs called into question the FDA’s grant of the HDE.3 Citing the dearth of evidence that supports the safe and effective use of DBS for OCD, the authors argue that the FDA should rescind the HDE for Reclaim and urge 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.”
A short history of DBS
The seeds of DBS were sown as long ago as 1870, when German researchers Gustav Fritsch and Eduard Hitzig4 published an article on their experiments in stimulating a dog’s cerebrum with electrical current. Within a few years, researchers had replicated these findings in humans.5 Inspired by this discovery, researchers and clinicians applied electrical stimulation to map the cortex in the 1930s, probe deeper into the brain in the 1950s, aid in placement of surgical lesions in the 1960s, and treat chronic pain and movement disorders in the 1970s.6
DBS as we know it today is the product of these early developments and the advent of implantable cardiac pacemaker technology. Some of the earliest, successful clinical uses of the new DBS technology were for the treatment of Parkinson disease and chronic pain.7,8
Reports of the use of DBS to treat OCD began to appear in the early 2000s.6 These short-term studies on samples of 1 to 4 patients reported moderate to dramatic reductions in OCD symptoms. The turning points in both clinical application and FDA policy, however, can be tied to the article published in Molecular Biology in 2008.2 Four “small-scale” studies conducted in medical centers in Leuven/Antwerp, Belgium; Butler Hospital/Brown University, Providence, RI; the Cleveland Clinic; and the University of Florida collaborated on a study with a total of 26 subjects. Greenberg and colleagues note that DBS “has emerged as a well-accepted alternative to ablative procedures for movement disorders” and that “[i]t is currently be-ing investigated for highly resistant OCD.” The researchers placed the DBS apparatus in the most common location chosen by earlier researchers: the junction of the ventral capsule/ventral striatum. They used the Yale-Brown Obsessive Compulsive Scale to measure results.
Patients who had failed “to obtain meaningful OCD improvement after adequate conventional treatment” were selected for the study. Patients who had had psychotic or manic episodes in the past 3 years were excluded, as were those who exhibited medical conditions that contradicted surgery. The researchers tabulated results on all patients for at least 12 months and for as long as 36 months. The outcomes were positive: “clinically significant symptom reductions and functional improvements were seen in over 60%” and “the vast majority of adverse effects were transient.” Moreover, because of an apparent “learning curve,” the more recent patients tended to exhibit better outcomes than earlier patients, which implied even better results in the future.
The lead investigator on the project, Benjamin D. Greenberg, MD, PhD, put the results succinctly in Medtronic’s press release that would accompany the FDA’s announcement of HDE approval for Reclaim: “Our work, plus that of colleagues in Europe, shows that DBS is a promising treatment for a subset of patients with OCD who have re-mained very ill and debilitated despite aggressive use of medications and cognitive-behavioral therapy.”9
FDA’s HDE for Reclaim
Congress created the HDE with its enactment of the Safe Medical Devices Act of 1990 (SMDA). Congress had recognized that research and development costs might surpass anticipated market returns for devices designed to treat rare diseases and conditions. The SMDA established the Humanitarian Use Device (HUD) which, by way of an HDE grant, is exempt from the FDA’s requirement of costly and time-consuming clinical trials to demonstrate the effectiveness of a medical device. The FDA may grant an HDE if:
• The device is to be used to treat or diagnose a disease or condition that affects fewer than 4000 individuals in the United States per year
• The device would not be available to a person with such a disease or condition unless the exemption is granted
• No comparable device . . . is available to treat or diagnose the disease or condition
• The device will not expose patients to an unreasonable or significant risk of illness or injury, and the probable benefit to health from using the device outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment10
Unlike conventional medical device applications, an HDE application need not contain clinical data that demonstrate effectiveness. Rather, the HDE application need only provide “reasonable assurance . . . based upon valid scientific evidence, that in a significant portion of the target population, the use of the device for its intended uses and conditions of use . . . will provide clinically significant results.”
