FDA’s latest strategy for digital mammography sparks criticism from technology’s proponents

PMAs will require post-approval screening trial

With its latest communication on the regulatory process for full-field digital mammography to some vendors last month, the Food and Drug Administration’s Center for Devices and Radiological Health has sparked another controversy. Although its new strategy has not yet taken on the force of guidance, news of the agency’s latest thinking about digital mammography systems has led some industry watchers to express serious concern about the timely clearance of this technology.

On Sept. 13, in faxed letters to vendors with which it has already been in communication, the agency recommended a new path to clearance for digital mammography (SCAN 9/29/99), a premarket approval application (PMA). In a copy of the letter obtained by SCAN, the agency outlines its new strategy, explaining that, based on its experience to date, the limited clinical trials initially proposed for the 510(k) process have proven flawed, making it difficult for vendors to produce data necessary to “accurately characterize the clinical performance” of digital mammography devices.

The agency suggests that those manufacturers that have not conducted full-screening trials for their 510(k) applications submit a PMA, including data from preclinical testing, feature analysis, and limited enriched clinical trials (that include patients with known cancers). The letter also states that part of this PMA package is a required, non-enriched, post-approval screening trial.

This combination of PMA and post-market screening study satisfies the FDA Modernization Act mandate for a balance of pre- and post-market data, according to the agency, which will accept proposals from manufacturers for joint studies, perhaps overseen by a third party such as the National Electrical Manufacturers Association or the National Cancer Institute. The FDA plans to publish a more formal guidance outlining the new strategy in the near future, according to Dr. Susan Alpert, director of the Office of Device Evaluation.

Although the letter reflects the agency’s belief that its new regulatory strategy for digital mammography will bring the technology to market within “a reasonably short time from now,” digital mammography advocates are concerned that in fact the new proposal will further delay the technology’s launch, perhaps fatally.

“The FDA says they want to get the technology to market and make the process as painless as possible, but what they’re proposing is not painless,” said Bill Cioffi, national marketing manager for conventional imaging systems at Fuji Medical Systems, which sells CR systems for digital mammography use outside the U.S. “They’ll accept an enriched study prior to marketing approval, but then insist on an unrealistically large post-market screening study. This is not less burdensome (than the 510[k]).”

In addition to concerns about the financial and time resources required to prepare a PMA application and to conduct a screening trial—which the FDA estimates would require at least 20,000 to 30,000 patients—digital mammography experts question whether vendors and the FDA will communicate effectively about study parameters.

“With each slight change (in the technology), companies will have to make a PMA amendment,” said Dr. Etta Pisano, director of breast imaging at the University of North Carolina. “A screening trial could cost up to $20 million, and even if (companies conducted) a screening trial, the FDA hasn’t defined what a successful trial would be.”

Although the FDA recognizes that it is expensive to do clinical trials, it stands by its conclusion that a large-scale trial is necessary to establish digital mammography’s substantial equivalency to screen-film.

“We’ve tried to find a way to move this technology forward with less expensive trials,” Alpert said. “But if you need the data, you need the data. It’s not OK to say it’s just too expensive to get the data we need. The fact is, the FDA is data-driven, and the (existing) data shows us that digital and conventional mammography are not obviously equivalent.”

But clinical experts continue to believe that it is possible to conduct trials under the 510(k) paradigm that prove digital mammography’s substantial equivalence to screen-film. In letters to FDA commissioner Dr. Jane Henney, researchers who have used digital mammography devices have stressed the technology’s equivalence to screen-film systems and what they believe to be its benefits, including higher contrast resolution than screen-film, and have urged the agency to, at the most, require comparability in a 510(k) study.

The International Digital Mammography Development Group, an organization that has been lobbying the FDA for prompt clearance of digital mammography devices, has emphasized that the process of establishing viable digital mammography guidelines has been unnecessarily delayed, and has asked the agency to publish revised reader study guidelines to allow manufacturers to proceed with 510(k) approval of devices under development.

Alpert agrees the process has taken too long, but links its length to the learning curve about the technology of both the agency and manufacturers, as well as mammography’s screening nature.

“We’ve been developing policy while (manufacturers) have been developing the technology,” she said. “It has taken too long, but the length of the process is linked to the screening characteristic of digital mammography.”

As for concern that the FDA’s study parameters for a screening trial will remain unclear, the FDA will incorporate study protocol in the guidance it plans to publish, according to Alpert, who will be leaving her position for another FDA post later this month (see story, page 5.)

“There are different ways to do a full-screening study,” Alpert said. “(Study parameters) will be part of the guidance, and we’ll be happy to talk with companies individually about this.”

Despite the agency’s reassurances, some believe that the time has come to enlist outside help in bringing digital mammography technology to market.

“With FDAMA, Congress told the FDA that for matters of scientific controversy, it wanted the agency to use an outside regulatory panel. Digital mammo is (a perfect example) of why the FDA needs outside scientific review. A third party should take this task on,” said an industry source who requested anonymity.