Good Intentions, but Not-So-Good Consequences in Using Unapproved Medical Devices for Rare Diseases

The humanitarian device exemption is a little-known regulation that permits certain medical devices to be used on patients without having undergone the research trials generally required for FDA approval. A recent story in the New York Times showed the potential benefits and pitfalls of giving treatment that hasn’t passed rigorous testing.

The exemption program is based on good intentions. It’s used for small numbers of patients who have no other treatment options. It doesn’t make financial sense for companies to invest in the development and testing of devices for a market of only a few patients, so the exemption requires a manufacturer to show only that a device is safe and has a “probable” benefit. It doesn’t need to prove its effectiveness, which is the usual standard.

The program is similar to one governing drugs for extremely rare diseases, sometimes called “orphan drugs” for “orphan diseases.”

Critics of the practice charge that ineffective products approved for exemption can be sold for years while potentially lifesaving ones might not be able to prove their worth. And an exempted device may be used by doctors in other applications, a practice known as “off-label” use. It’s illegal for manufacturers to promote and market drugs and products for uses other than the ones for which they have been FDA-approved, but it’s not illegal for doctors to expand their application.

The Times illustrated the device exemption with the $500,000 BSD-2000, a device that uses intense heat (hyperthermia) to combat cancer. It is FDA-approved for women too desperately ill with cervical cancer to withstand chemotherapy. That is a tiny population; as one oncologist told The Times, “I see, like, one patient like this a year.”

The BSD-2000 got its exemption in 2011. A few hospitals bought the pricey machine, but failed to participate in a study of patients that the manufacturer agreed to perform as a part of the machine’s approval. Cancer experts were surprised that the FDA had approved the machine in the first place, given its tiny market of suitable patients.

A couple months ago, Dr. William Maisel, chief scientist at the FDA’s device unit, defended the BSD study ordered by the agency. But last month, the agency and the machine’s producer agreed to kill it in favor of a study intended to capture more patients, including some cancer patients on whom the device is expected to be used off-label.

The new study is intended to generate only safety information, not data about the treatment’s effectiveness.

BSD Medical makes another hyperthermia machine, the BSD-500, that the FDA approved in 1983 for the treatment of breast cancer and tumors that lie just below the skin. Although studies have indicated potential effectiveness of the BSD-2000 (devised to treat deep-seated tumors), it has failed since the 1980s, according to The Times, to achieve medical acceptance amid changing cancer treatment strategies and unsuccessful clinical trials.

One hyperthermia expert told The Times that if the FDA approved the BSD-2000 without better data collection, it could retard rather than advance the technology.

Since 1997, when the device exemption program started, about 50 products – heart pumps, orthopedic implants, optical aids – have been approved through it. And patients have benefited – one recently exempted device enhances vision in the nearly blind.

To qualify for the program, products must be intended for conditions that affect fewer than 4,000 patients annually. But the exemption, according to The Times, also has offered a loophole to market devices to far larger groups.

In 2006, the FDA tried to withdraw exemptions for two companies that sold implanted devices to close a tiny opening in the heart based on data suggesting it might reduce the risk of stroke.

The exemption covered patients with a patent foramen ovale (PFO) who had had two strokes despite taking drugs intended to prevent them. But PFO patients who had a single stroke or never had one soon demanded the device, under the presumption that it worked.

The manufacturers voluntarily withdrew them from the exemption program and ran clinical trials in the hope of gaining full approval. But by then, other devices were being used off-label to close PFO. Three studies subsequently failed to show that the devices were better than drugs in preventing strokes.

In 2007, the FDA denied full approval of the BSD-2000 to treat deeper-seated tumors. The agency determined that the results of a company-sponsored clinical trial performed at two hospitals in Holland were inadequate to show that it was safe and effective.

But one group in that study – women with advanced cervical cancer unable to tolerate chemotherapy – survived longer if treated with radiation and hyperthermia than with radiation alone. So FDA officials urged BSD Medical to seek an exemption for that patient group, and the company so.

Some advocates of hyperthermia say they believe that the exemption will lead to other trials that can shed light on the treatment’s value. Or not: The Times’ hyperthermia expert was concerned that justifying the machine’s cost could lead facilities to use the BSD-2000 for different kinds of cancers. Those results, she said, probably will be of little value to anyone.

Patrick Malone & Associates, P.C. listed in Best Lawyers Rated by Super Lawyers Patrick A. Malone
Washingtonian Top Lawyer 2011
Avvo Rating 10.0 Superb Top Attorney Best Lawyers Firm
Contact Information