FDA Faulted for Lax Standards on Medical-Device Approval

The Food and Drug Administration's process for approving medical devices is inadequate and has led to the approval of products—including brain stimulation devices for psychiatric disorders—that have not been proven effective.

So said the consumer watchdog group Public Citizen in a report published on the online biomedical journal Plos Medicine last month. The report specifically highlighted the approval of vagus nerve stimulation (VNS) devices for long-term treatment of treatment-resistant depression as evidence of the agency's lax approval process.

Public Citizen is a nonprofit advocacy group based in Washington, D.C., founded in 1971 by Ralph Nader.

The report states that in the only randomized, controlled trial of VNS, the device did not demonstrate a statistically significant benefit on the primary measure of depression at 10 weeks. Yet it was approved anyway in 2005 by the director of the FDA's Center for Devices and Radiological Health (CDRH) over the objections of FDA scientists, according to Public Citizen.

But VNS is only one example of a device that made it through an approval process that Public Citizen says is broken. The watchdog group's report, “Left to Their Own Devices: Breakdowns in United States Medical Device Premarket Review,” charges that the FDA allows a lower approval standard for devices than their drug counterparts and relies excessively on a fast-track process for medical devices.

“We think there is a lower standard for approval of devices than for drugs, both in the legislation and in how the FDA interprets the legislation,” Jonas Hines, M.D., lead author of the report, told Psychiatric News. “We don't see a justifiable reason for that distinction. Many of these devices are being used to treat disease, so it is hard to fathom why one wouldn't require the same level of rigor in approving them as is required for drugs.”

Hines is a research associate at Public Citizen and an internal medicine resident at the University of California, San Francisco.

VNS Evidence Said Lacking

Regarding the approval of VNS, Hines said the device, despite FDA approval, is viewed with skepticism by many because of the lack of credible evidence of efficacy, a situation that damages the reputation of both the agency and of psychiatry. “There is a product on the market that is viewed as snake oil—what does that do for other viable treatment options?” he asked.

The Public Citizen report is especially critical of a commonly used alternate route to market approval for devices known as the 510(k), which is for medical devices that do not need to undergo a full premarket approval review. With a 510(k) application, device manufacturers can secure market approval on a fast track simply by showing that the device is “substantially equivalent” to an existing device (known as a “predicate” device); once a device is cleared as a 510(k), it may serve as a predicate device for subsequent 510(k) submissions.

Public Citizen states that compared with the standard premarket approval process, the 510(k) review is less stringent, less expensive, and faster. Moreover, unlike the prior-to-market-approval applications, direct evidence of effectiveness is usually not required.

Manufacturers denied clearance under 510(k) can seek approval through a “de novo” process. This process is for devices that are not substantially equivalent to an already marketed device because they are different in design or intended use from any device previously approved or cleared. The report notes that transcranial magnetic stimulation was approved for depression under a “de novo” application after being denied 510(k) clearance using electroconvulsive therapy as the predicate device.

Dick Thompson, an FDA spokesperson responding to the report, told Psychiatric News that the agency was reviewing its approval process for devices and would take the report's criticisms under consideration. “We are in the process of conducting an internal review of our 510(k) clearance program to improve our decision making and better support our mission to protect and promote public health,” Thompson said.

He added that the effort is “part of a broader set of initiatives published as CDRH's 2010 Strategic Priorities, which outlines the areas we think present significant opportunities to improve our effectiveness. These priorities are accompanied by time frames so that CDRH can operate with transparency and the public can monitor our progress.”

At press time CDRH released two reports addressing concerns about its process for approval of devices. One report focuses on ways to strengthen and clarify the 510(k) program. The other evaluates CDRH's use of science in decision making, with an eye toward adapting to new scientific information while maintaining regulatory predictability necessary for innovation.

Among the recommendations contained in the report is one that would revise regulations to explicitly require 510(k) submitters to provide a summary of all scientific information known or that the submitter should reasonably know regarding the safety and effectiveness of the device under review. This is not required now for 510(k) submissions and, as a result, relevant information may not be included in an initial submission.

Mark Leahey, president and CEO of the Medical Device Manufacturers Association, was more dismissive of the criticism. “The FDA's review process for medical devices is known throughout the world as the gold standard of patient safety and efficacy,” he told Psychiatric News. “Public Citizen's report clearly shows their unwillingness to recognize the diversity and complexity of the medical device market.”

New Business Model Needed

One psychiatrist who has been involved in research on brain stimulation devices for mental disorders, including VNS, said he agrees with much of Public Citizen's report—including its comments on the approval of VNS.

“The reality is that VNS for treatment-resistant depression has not been shown in a prospective, randomized, controlled trial to have efficacy,” said Mark George, M.D., who implanted the first experimental VNS in a patient. “The FDA allowed approval of the device without it, and I think it has hurt the field.

“Clinicians don't really know if it works, and insurance won't pay for it,” George told Psychiatric News. “So now we have a big question mark around an approved device, desperate patients, and a technology that is languishing. In retrospect, I wonder if the FDA had been more strict whether we would be in a better place.”

He is a distinguished professor of psychiatry, radiology, and neurosciences at the Medical University of South Carolina.

George noted that transcranial magnetic stimulation (TMS), which was cited in the Public Citizen report as an example of a “de novo” device approved without evidence of efficacy, did in fact later prove effective in a large randomized, controlled trial—but only after it was already approved by the FDA as a de novo device. The results of the Optimization of TMS for Depression Trial (OPT-TMS) were reported in the May Archives of General Psychiatry (Psychiatric News, June 4).

“We now have unambiguous Class I prospective randomized, controlled evidence that TMS works to treat acute depression, but not because the FDA required it for prior-to-market approval,” George said.

George added that a more rigorous process for approval of devices is clearly needed. But a central problem is that medical devices are typically manufactured by small start-up companies that do not have the capital to sponsor large randomized, controlled trials such as are possible for pharmaceutical companies.

He suggested something like an Orphan Drug Act—which helps pharmaceutical companies bring drugs to market for rare conditions—may be necessary in the device market.

“There is a revolution ongoing in brain stimulation technology, but the business model is not the same as for pharmaceutical companies. If we are going to produce medical devices and demand a higher level of proof, as we should, we have to acknowledge the need for a new business model and not overly restrict research and development. These devices have enormous potential, but we cannot use the pharmaceutical business model, where the companies had to bet tens of millions of dollars for a clinical approval trial before market approval. The FDA, industry, and NIH need to find a new cooperative model to do the needed science and promote, rather than stifle, device-based innovations that will help patients.”

“Left to Their Own Devices: Breakdowns in United States Medical Device Premarket Review” is posted at <www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000280>. The two FDA reports on its approval process are posted at <www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHReports/default.htm> and <http://globalmessaging1.prnewswire.com/clickthrough/servlet/clickthrough?msg_id=6655302&adr_order=15&url=aHR0cDovL3d3dy5mZGEuZ292L0Fib3V0RkRBL0NlbnRlcnNPZmZpY2VzL0NEUkgvQ0RSSFJlcG9y%0AdHMvZGVmYXVsdC5odG0%3D>.