Radiological devices panel meeting

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Thursday, December 16, 1999

8:30 a.m.

Double Tree Hotel

1750 Rockville Pike

Rockville, Maryland

Brian S. Garra, M.D., Chairperson

Robert J. Doyle, Executive Secretary

Judy M. Destouet, M.D.

Steven E. Harms, M.D.

Arnold W. Malcolm, M.D.

A. Patricia Romilly-Harper, M.D.

Alicia Y. Toledano, Sc.D.

James B. Smathers, Ph.D.

Wendie Berg, M.D., Ph.D.
Marilyn Peters, M.N. M.P.H.
Raymond P. Silkaitis, Ph.D.

Dan Schultz, M.D.


Call to Order: Brian Garra, M.D. 4

FDA Introductory Remarks: Robert J. Doyle 6

Open Public Hearing 10

Morgan Nields

Dr. Daniel Kopans
Open Committee Discussion 20
Special Presentation: David Feigal, M.D. 21
Introductory Remarks: David Feigal, M.D. 23
Charge to the Panel: Brian Garra, M.D. --
PMA Background: Dan Schultz, M.D. 27
G.E. Medical Systems Presentation of P990066
Introduction, Device Description, and

Non-Clinical Studies: Scott Donnelly 35

Clinical Studies: R. Edward Hendrick, Ph.D. 46
FDA Presentations
PMA Overview: John Monahan 71
Physics Review: Robert Gagne, Ph.D. 74
Statistical Review of Clinical Data:

Harry Bushar, Ph.D. 88

ROC Analysis: Robert F. Wagner, Ph.D. 92
Labeling Review and Proposed Market Study:

William Sacks, M.D., Ph.D. 106

Panel Discussion: Judy M. Destouet, M.D. 125
Open Public Hearing

Dr. Earl Steinberg 175

Dr. Daniel Kopans 177
Panel Recommendations and Vote 181

Call to Order

DR. GARRA: I would like to call this meeting of the Radiological Devices Panel to order. I would like to request everyone in attendance at this meeting to sign in on the attendance sheet at the door. Actually, I haven't done that myself.

I note for the record that the voting members present constitute a quorum as required by 21 CFR Part 14. At this time, I would like each panel member at the table to introduce him or herself and state his or her specialty, position title, institution and status on the panel.

I will begin with myself. I am Brian Garra. My position is Vice Chairman of Radiology at the University of Vermont, College of Medicine. I am the Chairman of this panel and a voting member.

DR. MALCOLM: My name is Arnold Malcolm, Director of Radiation Oncology at Provident St. Joseph Medical Center, Burbank, California. I am a radiation oncologist and a voting member on the panel.

MS. PETERS: My name is Marilyn Peters. I am the patient health education coordinator for the Department of Veterans Affairs, West Los Angeles Health Care Center. I am the consumer rep, a non-voting member.

DR. SILKAITIS: My name is Raymond Silkaitis. I am a temporary industry representative for this panel. I am Vice President of Regulatory Affairs for Gliatech. I have been in the medical-device industry for about twenty years.

DR. SCHULTZ: My name is Dan Schultz. I am the Acting Division Director for the Division of Reproductive, Abdominal and Radiological Devices, Office of Device Evaluation, Center for Devices, FDA.

DR. SMATHERS: Jim Smathers, Professor of Radiation Oncology at UCLA. I am a voting member of the panel.

DR. ROMILLY-HARPER: Pat Romilly, Medical Director, Indianapolis Breast Center. I am a voting member of the panel.

DR. BERG: Dr. Wendie Berg, Director of Breast Imaging at the University of Maryland. I am a temporary voting member.

DR. DESTOUET: Judy Destouet. I am Chief of Mammography for Advanced Radiology in Baltimore, Maryland, and I am a voting member of the panel.

MR. DOYLE: I am Bob Doyle with the FDA. I am the Executive Secretary of this panel.

DR. HARMS: I am Steve Harms. I am Professor of Radiology at the University of Arkansas. I am a voting member of the panel.

DR. GARRA: At this point, Mr. Doyle would like to make a few introductory comments.

FDA Introductory Remarks

MR. DOYLE: The following announcement addresses conflict of interest issues associated with this meeting and is made part of the record to preclude even the appearance of any impropriety.

To determine if any conflict existed, the agency reviewed the submitted agenda for this meeting and all financial interests reported by the committee participants. The conflict of interest statutes prohibit special government employees from participating in matters that could affect their, or their employer's, financial interests.

However, the agency has determined that participation of certain members and consultants, the need for whose service outweighs the potential conflict of interest involved, is in the best interest of the government. Therefore, a waiver has been granted to Dr. James Smathers for his interests in a firm that could potentially be affected by the panel's recommendations.

Copies of this waiver may be obtained from the Agency's Freedom of Information Office, Room 12A-15, of the Parklawn Building.

We would like to note for the record that the agency took into consideration other matters regarding Dr. Brian Garra who reported interests in a firm at issue but in matters that are not related to today's agenda. The agency has determined, therefore, that he may participate fully in all discussions.

In the event that the discussions involve any other products or firms not already on the agenda for which an FDA participant has financial interests, the participant should excuse him or herself from such involvement and the exclusion will be noted for the record.

With respect to all other participants, we ask, in the interest of fairness, that all persons making statements or presentations disclose any current or previous financial involvement with any firm whose products they may wish to comment upon.

If anyone has anything to discuss concerning these matters, please advise me now and we can leave the room to discuss them. I don't see any.

The FDA seeks communications with industry and the clinical community in a number of different ways. First, FDA welcomes and encourages premeetings with sponsors prior to all IDE and PMA submissions. This affords the sponsor an opportunity to discuss issues that could impact the review process.

Second, the FDA communicates through the use of guidance documents. Towards this end, FDA develops two types of guidance documents for manufacturers to follow when submitting a premarket application. One type is simply a summary of the information that has historically been requested on devices that are well understood in order to determine substantial equivalence.

The second type of guidance document is one that develops as we learn about new technology. FDA welcomes and encourages the panel and industry to provide comments concerning our guidance documents.

I would also like to remind you that the meetings of the Radiological Devices Panel tentatively scheduled for the first half of next year are February 7 and May 15. You may wish to pencil in these dates on your calendar but, please, recognize that these dates are tentative at this time.

DR. GARRA: Thank you.

We are ready to proceed with the first of the two half-hour open public hearing sessions for this meeting. The second session will occur this afternoon after the panel discussion. At these times, public attendees are given an opportunity to address the panel to present data or views relevant to the panel's activities.

Some individuals have already indicated they would like to address the meeting. If there are any others who would like to address the panel, if you could please identify yourselves to Mr. Doyle at this time.

I don't see any others.

I would like to remind public observers at this meeting, while this portion of the meeting is open to public observation, public attendees may not participate except at the request of the Chairman.

I would ask, at this time, that the persons addressing the panel come forward to the microphone and speak clearly as the transcriptionist is dependent upon this means for providing an accurate transcript of the proceedings of the meeting. If you have hard copy of your talk available, please provide it to the Executive Secretary for use by the transcriptionist to help in the accurate recording of the proceedings.

We are also requesting that all persons making statements either during the open public hearings or during the open committee discussion portions of the meeting to disclose if they have any financial interest in any medical-device company before making your presentation to the panel.

In addition to stating your name and affiliation, please state the nature of your financial interest and the organization you represent. Of course, no statement is necessary from employees of that organization. A definition of financial interests in the sponsor company include compensation for time and services of clinical investigators, assistants and staff in conducting the study and appearing at the panel meeting on behalf of the applicant.

The second is a direct stake in the product under review such as being the inventor of the product, patent holder, owner of shares of stock, et cetera and, finally, but not only, owner or part owner of the company, of course.

We can now begin the first open public portion of this meeting. Each speaker will be allowed a maximum of five minutes. We will start with Mr. Morgan Nields, President of Fischer Imaging Corporation.

Open Public Hearing

MR. NIELDS: Thank you and good morning. My name is Morgan Nields. I am Chairman and CEO of Fischer Imaging Corporation from Denver, Colorado. I would point out that Fischer Imaging is a public company. I am a significant shareholder in the company. Our company is engaged in clinical testing of digital mammography devices with the intent of providing an application to the FDA for approval shortly.

Secondly, I am also a direct shareholder in the publicly traded company, General Electric, who is presenting a PMA submission today in front of this panel.

My comments today on the PMA submission before the panel seek to improve upon the FDA approval process. No matter what action is taken on the PMA, it may not facilitate our ability to bring appropriate technology to the public service unless we address elements of the process which are, clearly, defective.

The marginal gain from a PMA approach may be lost in the sea of related process problems. To clarify this point, I will offer a brief case study of what has actually been happening with the key advancement in diagnostic imaging technology digital mammography systems.


I would like to show a couple of slides of what we are talking about. Just to orient some of the members of the panel, the image on the left, this is the same contrast detail phantom imaging with digital mammography on the left allowing one to see clearly small objects at very low contrast with approximately the same dose as a film-screen ACR-accredited system on the right.


Just a couple of images of what digital mammograms look like printed on laser film, for those of you who are mammographers.


In November, 1994, over five years ago, we first visited FDA to present information supporting a 510(k) clearance pathway citing both zero mammography and Fuji computed radiography as predicate systems, particularly since they already cleared Fuji CR 510(k) cited breast imaging as one of its intended uses.

From then until now, this process has been nightmarish for our company as well as for the other companies and, in my opinion, contrary to the intent of the 1997 Food and Drug Administration Modernization Act.


Section 205 of FDAMA directed the agency to consider the least burdensome means of approval for new devices, in this section right here. The PMA process selected by FDA in September of this year essentially makes digital-mammography systems class III devices. Class III devices are the highest-risk devices regulated by FDA and include, for example, implantable devices where a failure or malfunction could cause death.

Sixteen months ago, this same advisory panel concluded that clinical trials were not necessary to clear the technology. The panel and the agency recognized that studies to measure the accuracy of mammography are very difficult to perform due to the high intra-observer variability of the readers.

The panel, including several invited mammography experts, concluded that a simple features analysis would suffice to establish equivalency to film mammography. The panel's conclusions were ignored by FDA and, as importantly, sixteen months later, FDA has been unable to provide draft guidance to the public regarding the requirement for determining substantial equivalence.


FDA has mandated that the 510(k) review should be limited to the minimum necessary to show substantial equivalence but industry and the agency have not reached agreement on this with respect to digital mammography. The FDA has, however, issued two policy letters to only four manufacturers. Because I believe these policy letters should be made available as a matter of public record, I have included these letters in the record of these meeting.

These letters are dated February 9 and SeptemberÊ13, 1999 and were sent to four manufacturers attempting to bring digital-mammography systems to the market. I am aware of at least five additional companies interested in this field who have no idea what types of requirements may be necessary for premarket clearance. Perhaps these policy statements will be of help to them.

I also have included two letters our company sent to FDA, a proposed clinical-trial design of May 20, 1999 and a follow-up letter of September 20 pleading for a response to the May 20 letter. The last letter includes a December 7 letter from FDA, a belated response to our letter of May 20.

Both the February and September policy letters from FDA make it clear that any submitted studies must include ground truth, sensitivity, specificity or ROC, receiver operator characteristics analysis. The September letter further indicates a PMA pathway would essentially required in that a postmarket approval screening study would been to be conducted.


FDAMA directed FDA to consider the benefits and risks of new life-saving technology and to utilize postmarket approval studies as a means of gathering crucial patient data for high-risk devices. FDA refers to this section of FDAMA in the September 13 letter regarding the imposition of a new requirement for postmarket approval studies.

I submit Congress never intended these types of expensive postmarket approval studies were to be used for class-II 510(k)-type devices. This regulatory quagmire could be avoided if the agency were to follow the mandate of FDAMA which directs FDA to consider outside scientific expertise and to develop a workable scientific dispute-resolution procedure for matters of scientific controversy.


These sections here cover some of those thoughts. Given that there is unanimity among manufacturers, expert radiologists and patient-advocacy groups the large-scale clinical trials are not necessary, I suggest digital-mammography clearance is an issue of "scientific controversy."

Requesting help, for example, from the National Cancer Institute or the RSNA to determine an appropriate premarket clearance pathway would meet the Congressional intent of FDAMA. We all know it is easy to be a critic but harder to solve the actual problem. There are several reasonable approaches to solve this regulatory conundrum.

In the December 7 letter, FDA stated that diagnostic and screening mammography are essentially the same procedure but, in fact, screening mammography is coded under CPT code 76092 and is reimbursed at a lower level than diagnostic mammography which has its own set of CPT codes.

HCFA reimburses based on FDA clearance and labeled indications for use and, therefore, is unlikely to reimburse a screening mammogram performed on a system that is cleared only for diagnostic mammogram. In addition, the American College of Radiology standards differentiate clearly between a screening mammogram and a diagnostic mammogram.

It would appear reasonable for manufacturers to label only for diagnostic mammography and even, at their choice, contraindicate screening in the labeling. Another approach to solve this problem is to use existing MQSA regulations to measure the performance of digital-mammography systems.


MQSA regulations require that mammography centers submit image quality and dose measurements to an accrediting body by means of specially designed breast phantoms and dosimeters. In addition, two sets of clinical films are submitted for scoring by a review panel of radiologists. If digital-mammography systems meet these criteria, and I am quite certain they do, it would be self-evident they are substantially equivalent to existing film-screen systems.

MQSA regulations already contain training requirements of at least eight hours each for radiologists, radiologic technologists and physicists for new modalities like digital mammography. This training goes beyond the applications training manufacturers would provide.

In addition, MQSA audit regulations require physicians to keep detailed outcome records for all mammographic procedures. A simple comparison of data will establish whether digital mammography finds more or less cancers per thousand women screened.

Call-back and false-positive rates and a host of other variables currently measured under MQSA will allow a continuous benchmark of digital mammography's performance. MQSA regulations provide an already designed framework for the agency to monitor the relative performance of digital-mammography systems.

Requesting that radiologists and manufacturers provide access to FDA for this data would provide oversight to the agency. While large NCI-funded trials are expected to provide good outcomes data on the accuracy of both film-screen and digital mammography, at least four years will be required before results are known. I don't believe that these trials should be made part of a PMA postmarket approval study requirement.

CDRH is responsible for assuring that exposure to manmade sources of radiation is minimized as a matter of public health. Mandating the double exposure of thousands of healthy women is simply not justified given the many other alternatives available to clear this technology.

Regarding the application before the panel today, if the data presented comply with the February and September policy letters from FDA which detail requirements for statistically significant studies including ground truth, sensitivity and specificity or ROC analysis, then the application for clearance should be approved not as a PMA but as a 510(k).

Thank you for your attention.

DR. GARRA: Thank you very much. Some interesting points were brought up there.

Mr. Doyle has an announcement.

MR. DOYLE: I have been advised that Dr. Kopans would like to make a statement.

DR. GARRA: Please come forward, Dr. Kopans.

DR. KOPANS: Good morning.

DR. GARRA: Would you please state your affiliation and any financial interests.

DR. KOPANS: I am Dr. Daniel Kopans. I am the Director of the Breast Imaging Division at the Massachusetts General Hospital in Boston and a Professor of Radiology at the Harvard Medical School.

I would like to read this and then I will be happy to submit it in writing. As an expert in breast-cancer detection and diagnosis, I am very concerned about the FDA's decision to require a postmarket approval for digital mammography. I believe that this will not only delay access to this important development in mammography but it will make it very difficult and expensive to improve our ability to detect and diagnose breast cancer.

This will be detrimental to American women. New film-screen technologies only require a 510(k) process for approval and digital detectors are merely electronic film-screen combinations.

FDA employees have suggested that digital mammography will provide radiologists with such new information that they will not know what they are seeing and this will lead to unnecessary biopsies. There are absolutely no data to support this belief. I am unaware of any expert in breast imaging who would support this concern.

Digital mammography is nothing more than an X-ray image of the breast. All radiologists who are involved in the interpretation of conventional film-screen mammograms can interpret digital mammographies. The adoption of digital chest radiography only required the submission of a few cases to demonstrate comparability.

The requirement of the FDA for a large screening trial for digital mammography is not warranted and would be a great waste of money. The efficacy of mammography has already been established. The only thing that large trials will do is to demonstrate well-established variation between observers.

This does not detect the detector systems but, rather, the individual radiologists. Direct image comparisons and physics evaluation should suffice to demonstrate that digital detectors are comparable to film-screen combinations.

Other observer studies will be misleading and an unnecessary expense. The postmarket approval process is unnecessarily onerous. Perhaps, of even greater concern, is that its use will mean that any future alteration in the equipment will require a detailed resubmission. This will drastically slow and may curtail the future development of digital mammography to the detriment of women's health.

All of the experts in breast imaging that I know that have experience with digital mammography have supported a 510(k) process. It is unclear who, therefore, is advising the FDA. Dr. Henney and the FDA should explain why they have failed to respond to legitimate queries submitted by myself and Dr. Carl Dorsey from the University of Massachusetts and other queries submitted by the International Digital Mammography Development Group.

The failure of the FDA to respond to legitimate questions raised by international experts suggests that the FDA's motivation may be driven by politics. This is inappropriate and not acceptable when the health of American women is at stake.

Given the significance of this approval process, FDA should disclose all who have been involved in the agency's decision including any political pressures that have been employed to cause this major impediment to improving the healthcare of women. Approval for digital mammography should be accomplished through a 510(k) process.

DR. GARRA: Thank you.

Open Committee Discussion

DR. GARRA: Mr. Doyle has a quick announcement to make.

MR. DOYLE: For the record, I would like to read an appointment to temporary voting status that has been signed by Dr. David W. Feigal, the Director of the Center of Devices and Radiological Health.

Pursuant to the authority granted under the Medical Devices Advisory Committee Charter dated OctoberÊ27, 1990 and as amended August 18, 1999, I appoint Wendie A. Berg, M.D., Ph.D., as a voting member of the Radiological Devices Panel for the meeting on December 16, 1999.

For the record, she is a special government employee and a consultant to this panel under the Medical Devices Advisory Committee. She has undergone the customary conflict of interest review and has reviewed the material to be considered at this meeting.

DR. GARRA: Thank you.

We are going to go back and proceed to the open committee discussion on PMA 990066 for a mammography system that uses as its detector a solid-state X-ray imaging device. However, before we get to the particulars of the PMA, I would like to ask Dr. David Feigal, Director of the Center for Devices and Radiological Health, to come forward to make a pair of special presentations.

Dr. Feigal.

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