ATDEPARTMENT OF HEALTH AND HUMAN SERVICES

> FOOD AND DRUG ADMINISTRATION
>
> CENTER FOR DEVICES AND RADIOLOGIC HEALTH
>
> **NATIONAL MAMMOGRAPHY QUALITY ASSURANCE**
>
> **ADVISORY COMMITTEE**
>
> Monday, August 26, 2002
>
> 9:00 a.m.
>
> Holiday Inn Gaithersburg
>
> Two Montgomery Village Avenue
>
> Gaithersburg, Maryland
>
> PARTICIPANTS
>
> Maryanne Harvey, Chair
>
> Charles Finder, M.D., Executive Secretary
>
> MEMBERS
>
> James F. Camburn
>
> Nancy J. Ellingson, R.T. (R)(M)
>
> Alisa M. Gilbert
>
> Miles G. Harrison, Jr., M.D.
>
> Jessica W. Henderson, Ph.D.
>
> Debra M. Ikeda, M.D.
>
> Andrew Karellas, Ph.D.
>
> Amy F. Lee, M.D.
>
> Melissa G. Martin, M.S.
>
> Etta D. Pisano, M.D.
>
> Linda S. Pura, R.N., M.P.
>
> Catalina R. Ramos-Hernandez, M.D.
>
> Amy R. Rigsby, R.T. (M)
>
> Donald C. Young, M.D.
>
> [C O N T E N T S]{.underline}
>
> [Page No.]{.underline}
>
> Opening Remarks:
>
> Maryanne Harvey 4
>
> Conflict of Interest Statement:
>
> Charles Finder, M.D. 4
>
> Introductions 7
>
> Alternative Standards
>
> Charles Finder, M.D. 10
>
> Roger Burkhart, Ph.D. 11
>
> Open Public Hearing
>
> Ken Crocker 23
>
> Pamela Gormley (by Dr. Finder) 33
>
> Overview of MQSA Inspection Findings
>
> and Current Inspection Follow-up Actions:
>
> Michael Divine, M.S. 35
>
> Good Guidance Practices and Directions
>
> for Discussion of the MQSA Guidance under
>
> the Final Regulations:
>
> Charles Finder, M.D. 48
>
> ACRIN Trial of Full Field Digital
>
> Mammography (FFDM):
>
> Etta Pisano, M.D. 121
>
> Potential New Applications of FFDM:
>
> Daniel Kopans, M.D. 169
>
> Inspection Demonstration Project Update:
>
> Charles Gunzburg, M.S. 221
>
> Full Field Digital Mammography
>
> Accreditation and Certification Update:
>
> Kish Chakrabarti, Ph.D. 226
>
> Priscilla Butler, M.S. 236
>
> States as Certification Agencies Update:
>
> Roger Burkhart, Ph.D. 256
>
> Review of Summary Minutes of August
>
> 2001 Meeting 263
>
> Future Meetings 264
>
> [P]{.underline} [R]{.underline} [O]{.underline} [C]{.underline}
> [E]{.underline} [E]{.underline} [D]{.underline} [I]{.underline}
> [N]{.underline} [G]{.underline} [S]{.underline}
>
> **Opening Remarks**
>
> MS. HARVEY: Good morning. The National Mammography Quality Assurance
> Advisory Committee is called to order. We have a very busy schedule
> today so it will be important for us to keep to our schedule as we go.
> My name is Maryanne Harvey, for those of you who haven\'t met me as
> yet.
>
> Dr. Finder will now give us our conflict of interest statement.
>
> **Conflict of Interest Statement**
>
> DR. FINDER: The following announcement addresses conflict-of-interest
> issues associated with this meeting and is made a part of the record
> to preclude even the appearance of any impropriety. To determine if
> any conflict existed, the agency reviewed the submitted agenda and all
> financial interests recorded 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 interest. However, the agency has
> determined that participation of certain members, the need for whose
> services outweighs the potential conflict of interest involved is in
> the best interest of the government.
>
> Therefore, waivers permitting full participation in general matters
> that come before the committee have been granted for certain
> participants because of their financial involvement with facilities
> that will be subject to FDA\'s regulations on mammography quality
> standards with accrediting, certifying or inspecting bodies, with
> manufacturers of mammography equipment or with their professional
> affiliations since these organizations could be affected by the
> committee\'s deliberations.
>
> These individuals are James Camburn, Nancy Ellingson, Alisa Gilbert,
> Maryanne Harvey, Melissa Martin, Linda Pura, Amy Rigsby and Drs. Miles
> Harrison, Jessica Henderson, Catalina Ramos-Hernandez, Debra Ikeda,
> Andrew Karellas, Daniel Kopans, Amy Lee, Etta Pisano and Donald Young.
>
> Copies of the waivers may be obtained from the agency\'s Freedom of
> Information Office, Room 12A-15, of the Parklawn Building.
>
> Several of our members also reported that they received compensation
> for lectures they have given or will give on mammography-related
> issues. However, they have affirmed that these lectures were offered
> because of their expertise in the subject matter and not because of
> their membership on the committee.
>
> We would like to note, for the record, that if any discussion of
> states as certifying bodies was to take place in any meetings of the
> committee, it would be a general discussion only. No vote would be
> taken and no consensus sought.
>
> In the interest of getting as many viewpoints as possible, all SGEs,
> including state employees, would be allowed to participate in the
> general discussion so that all viewpoints could be heard.
>
> In the event that the discussions involve any other matters not
> already on the agenda in which an FDA participant has financial
> interest, the participants 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 accreditation
> bodies, states doing mammography inspections under contract to FDA,
> certifying bodies, mobile units, breast implant imaging, consumer
> complaints and mammography equipment.
>
> MS. HARVEY: Thank you, Dr. Finder.
>
> **Introductions**
>
> Since we have four new members at this meeting\--it is nice to see our
> new members and to see our returning members from last year\--I would
> ask that each one of us give a very short bio so that we can get more
> acquainted with each other\'s experience and background.
>
> Dr. Pisano, could I ask you to begin?
>
> DR. PISANO: I am Dr. Etta Pisano. I am the Chief of Breast Imaging at
> the University of North Carolina in Chapel Hill. I am a radiologist.
>
> DR. YOUNG: I am Don Young. I am a radiologist, a professor of clinical
> radiology at the University of Iowa College of Medicine and practice
> at the hospital and clinics where I direct the breast imaging and
> diagnostic center.
>
> DR. RAMOS-HERNANDEZ: I am Catalina Ramos with the National Breast
> Cancer Organization. We are a not-for-profit advocacy and counseling
> services for patients with breast cancer.
>
> MS. RIGSBY: I am Amy Rigsby. I am the Technical Director of the Rose
> Breast Imaging Center in Houston, Texas. I am a mammographer.
>
> MS. MARTIN: I am Melissa Martin. I am a medical physicist running a
> consulting practice in Southern California.
>
> DR. IKEDA: I am Debra Ikeda. I am Director of Breast Imaging at
> Stanford University Medical Center. I am a radiologist.
>
> DR. KARELLAS: I am Andrew Karellas. I am a medical physicist. I have
> been with the University of Massachusetts as of two weeks ago and now
> I have moved to join the faculty at Emory University in Atlanta.
>
> DR. HARRISON: I am Miles Harrison. I am a surgeon by training. I am
> part of the Sinai Surgical Associates in Baltimore, Maryland and one
> of the designated breast surgeons at the Lapedes Cancer Center which
> is a Hopkins affiliate.
>
> DR. FINDER: Dr. Charles Finder. I am a radiologist working for the
> Food and Drug Administration and I am also the Executive Secretary of
> this committee.
>
> MS. HARVEY: I am Maryanne Harvey. I am with the New York State
> Department of Health. I am a section chief who is responsible for
> mammography and also the Chairman of this committee.
>
> MS. PURA: Good morning. I am Linda Pura. I am one of the clinical
> nurse coordinators for the Los Angeles County Breast Cancer Early
> Detection Program under the Department of Health California, Cancer
> Detection Section. I am also the co-founder and present President of
> the Los Angeles County Susan G. Komer Breast Cancer Foundation.
>
> MR. CAMBURN: I am Jim Camburn. I am Chief of the Radiation Safety
> Section for the State of Michigan.
>
> MS. ELLINGSON: I am Nancy Ellingson. I am a radiologic technologist
> and mammographer. I am with the American Society of Radiologic
> Technologists in Albuquerque, New Mexico. We represent about 100,000
> radiologic technologist members.
>
> MS. GILBERT: I am Alisa Gilbert. I am a seven-year breast cancer
> survivor. I work with Alaska Natives and American Indians. I am the
> Director of the National Native Cancer Survivor Support Network.
>
> MS. HENDERSON: I am Jessica Henderson. I am an eight-year cancer
> survivor and I represent the Oregon Breast and Cervical Cancer
> Coalition.
>
> DR. LEE: Hi. I\'m Amy Lee. I am Assistant Professor of Community
> Medicine at Northeastern Ohio University\'s College of Medicine and
> Administrative Director for the Master of Public Health Program also
> located there. I am also a physician consultant for the local Breast
> and Cervical Cancer Program and, in my former life, before academia, I
> was OB-GYN.
>
> MS. HARVEY: Thank you.
>
> I will now ask Dr. Finder to talk to us about alternative standards.
>
> **Alternative Standards**
>
> DR. FINDER: I just want to give a little bit of background on approval
> for alternative standards. For those not familiar with this section of
> the regulations, FDA may approve an alternative to a quality standard
> that currently exists under Section 900.12 when the agency determines
> that, one, the proposed alternative standard will be at least as
> effective in assuring quality mammography as the standard it proposes
> to replace and, two, the proposed alternative is too limited in its
> applicability to justify an amendment to the standard or it offers an
> unexpected benefit to human health that is so great that the time
> required for amending the standard would represent an unjustifiable
> risk to human health and also that the granting of the alternative is
> in keeping with the purposes of the statute.
>
> Since our last meeting, the division has approved several alternative
> standards and these will be discussed by Dr. Roger Burkhart.
>
> DR. BURKHART: I might begin by referring you to one of the documents
> that you were given in preparation for the meeting, the Modifications
> and Additions to the Policy Help Guidance System, No. 5. You will find
> the new alternative standards included within this document.
>
> The first one, the first new one which we approved last September, is
> found on Page 57 of the document. It is entitled The Manufacturer\'s
> Software Modification of the Automatic Exposure Control, but really
> what it applies to is the testing which has to take place after such
> modifications occur.
>
> Software upgrades or modifications are defined by FDA as being major
> changes in the system which means that, after they are to take place,
> there has to be a mammography equipment evaluation conducted of the
> equipment and any problems that are found have to be corrected before
> the equipment is used on patients.
>
> Also, the regulations require that this evaluation and the testing
> which is involved be done by the physicist on site. But the applicant
> for this particular alternative requirement made a convincing case
> that, in this particular situation, we can assure mammography quality
> if on-site testing is done under conditions of medical physicist
> oversight.
>
> By medical physicist oversight, what we mean is that the physicist has
> to be consulted, but it is his or her decision as to whether they
> actually have to come on site to do the testing or whether somebody
> else can do the testing and send the results to them for evaluation.
>
> As I said, the applicant for this standard made a convincing case that
> medical physicist oversight would assure quality in this particular
> case. So, for this specific software modification has given an
> alternative standard, and when it is applied to the units and the
> models which are listed in the standard, medical physicist oversight
> is an option for the facility.
>
> The second newly approved alternative standard was reapproved last May
> as found on page 58, and it, too, refers to the testing, the testing
> conditions or how the testing is done after the modification takes
> place.
>
> Like the last one I just mentioned, it also started out as a request
> related to a specific software upgrade, but in this case, the
> justification was that the testing which would take place after this
> particular upgrade, was the same type of testing which is done
> routinely by the quality control technologist.
>
> So, it was felt that if the quality control technologist is qualified
> to do this as part of the routine QA program, then, they should be
> able to do it after the software modification, and so it is to be done
> in conditions of medical physicist oversight.
>
> But we got to thinking if it applies to this particular upgrade, it
> could also apply to any with that particular qualification, so we do
> have the authority to expand on requests, and we did that.
>
> We applied this alternative standard to any upgrade or modification of
> the computer software in which the testing afterwards is normally done
> by the quality control technologist.
>
> So, if the manufacturer feels that the modification meets this
> particular standard, they need to consult with us, confirm with us
> that we agree with this, and if we do, then they can go ahead and this
> testing after this modification can be done under conditions of
> medical physicist oversight.
>
> The third new alternative standard, which begins on page 60, is
> different in nature. It deals with the quality assurance program
> including the quality control testing, full field digital mammography
> units, again to be more specific, it deals with the time period for
> which the corrective actions can be taken if the testing reveals that
> there are problems with the system.
>
> Now, in the case of screen-film systems, we were able, at the time of
> the regulations, to define two classes of test failures. There are
> those test failures which are significant enough that the problem
> causing them has to be corrected before the piece of equipment is used
> again on patients.
>
> Then, there are those which for various reasons mostly dealing with
> the fact that there are compensating methods, we can allow more time
> for the correction of the test failures for the problem causing the
> test failures, and the time which was set for that was 30 days.
>
> For screen-film systems, as I say, we can make that distinction, but
> for full field digital mammography systems, which were still in the
> research stage at the time the regulations were being developed, we
> couldn\'t make such a distinction.
>
> So, for full field digital mammography systems, and any other new
> modality that might appear in the coming years, we took a conservative
> public health safety position. We said that any quality control test
> that has failed, the problem causing the failure has to be corrected
> before the equipment can be used on patients.
>
> So, this is what the regulations say, and, of course, the expectation
> is that eventually, if a technology like full field digital
> mammography, once it becomes fully established, eventually, we would
> be able to rewrite the regulations and make a similar distinction as
> we did with screen-film.
>
> But to begin with then, we took this position, but at the same time,
> we tried to make it clear to the manufacturers and also to any
> facility that has a full field digital mammography unit that if they
> feel that there are some of the tests that they can make a case that a
> 30-day correction period could be allowed for test failures of that
> test, they could always apply for an alternative requirement.
>
> About two months ago, General Electric made such an application for
> their Senographe 2000D, full field digital mammography unit, and we
> approved that alternative on July 14th.
>
> Basically, what this alternative does is divide the quality control
> tests of the 2000D into three general groups, and an important one as
> far as terms of the changes which are involved is the third group or
> the group which is labeled with the letter C.
>
> These were tests, quality control tests of the 2000D, which were
> equivalent to quality control tests of screen-film systems for which
> the 30-day correction period was already allowed.
>
> Some of them involved the exact same testing methods using the exact
> same action limits and even testing components which were identical to
> the full field digital mammography system as in some of the
> screen-film systems, so they were than equivalent in that case, they
> were virtually identical.
>
> The other tests were not quite as identical, but basically, for most
> of them, the only difference is that the measurements are done off of
> digital images rather than off of films as it would be in the case in
> screen-film systems.
>
> So, it seemed logical then that if these tests already were allowed a
> 30-day correction period when problems are found, then, it would be
> logical to allow the same 30-day correction period for them with full
> field digital mammography unit, with the 2000D.
>
> During this 30-day correction period\--perhaps I didn\'t make this
> quite clear earlier\--during this 30-day correction period, the
> facility continued to use the part of the system which failed the
> test, they wouldn\'t have to take it out of service.
>
> The other two groups are the remaining tests, and these are still
> tests which, if they are failed, the component which failed the test
> has to be taken out of service until the problem is corrected.
>
> The only reason really for dividing them into two groups is to
> emphasize something which also exists in the screen-film area, and
> that is, it is only the unit or the part of the unit which fails the
> test which has to be taken out of service.
>
> That may mean the whole system in some cases, but it may mean only
> part of others. In the case of the 2000D, the A Group tests are tests
> that the image acquisition part of the system, and so if these tests
> are failed, the facility may have to stop acquiring new images until
> the problem is corrected, but as long as the B Group of tests are
> passed which relate to the interpretation of images, they can continue
> to interpret old images.
>
> The opposite is true, if a test in the B Group is failed, the facility
> may have to stop with the interpretation of images, but as long as the
> A Group of tests are passed, they can continue to acquire and store
> images for each interpretation.
>
> So, then this alternative requirement applies only to the Senographe
> 2000D. As I mentioned, other manufacturers and facilities which own
> full field digital mammography units or the manufacturers, have the
> option of applying for a similar alternative requirement and we will
> consider it and determine whether or not it can be accepted.
>
> These, then, are the three new alternative requirements that we have
> accepted since the last NMQAAC meeting. I would be happy to answer or
> try to answer any questions that you might have on them.
>
> DR. PISANO: What do the other manufacturers have to do, do they have
> to apply for the same thing to get, because obviously, this only
> applied to GE?
>
> DR. BURKHART: It only applies to GE as you would expect as GE was the
> applicant. They would have to go through a similar process, and their
> lists of tests, depending upon their system, will be different. They
> might have different tests, more or less, and are different, that
> could be given a 30-day correction period.
>
> DR. PISANO: Just as a comment, some of the things listed under Item C
> were probably added to the QC manuals of GE at least, and the other
> companies, because of the MQSA requirements for film. So, my
> prediction, I actually have two other units myself, I have GE Fischer
> and a Fuji system at UNC, is that all these tests listed under Item C
> are also required by the other manufacturers.
>
> So, it might expedite things a bit if a more general statement could
> be made about these particular tests rather than every company, I
> don\'t know what the process is, but we would be grateful, those of us
> who are using the equipment, if there could be a more expedited
> process for this.
>
> I hate to shut down a machine just because one of these things that
> wouldn\'t shut down my GE unit, you know, if my Fischer unit had one
> of these problems, you know, before Fischer had the chance to go in
> and apply for it.
>
> So, it would be nice if the FDA could make a more general statement
> about this, just as a user of the device.
>
> MS. HARVEY: One more reminder. Before we speak, let us give our names
> for the record.
>
> DR. PISANO: Oh, sorry. I am Etta Pisano from UNC/Chapel Hill. It is
> just a suggestion of making this more general.
>
> DR. BURKHART: Roger Burkhart again. We thought about that at the time
> we were looking at the GE application. As I mentioned, we did expand
> the second alternative requirement to be broader than the original.
>
> We decided at this stage, though, that since there is still I guess
> not much of a consensus in general on the testing with the different
> models, that it would be best to take each one in turn, but once the
> ground is broken, obviously, you know, it makes it much easier for the
> people coming along behind if the tests are really the same, it would
> only be for any unique things that they might have that we have to
> look at further.
>
> The process I might mention, the process for looking at alternative
> requirements, actually also is described in a general way, and, in
> fact, it is right after the listing of the three alternative
> requirements, the new ones, on page 62, and it basically involves when
> a request comes in, a staff member is assigned to evaluate it.
>
> Sometimes we see right upfront that more information is needed, so the
> staff member will ask for it, but if it looks fairly complete, then,
> we form a committee to look at it and evaluate it.
>
> The committee tries to come up with a consensus, a recommendation
> being either to approve or disapprove or to ask more information, and
> then it goes to the branch chief of the Accreditation and
> Certification Branch, which is the branch responsible for this, to
> agree or disagree, and then it goes to the division director for final
> decision.
>
> So, the process is not really complicated and, as I said, once the
> ground has been broken in that area, it can go fairly fast.
>
> The other point I guess I should mention, too, is that a facility can
> apply, as well as a manufacturer, so you do not have to wait for the
> manufacturer to take action to make the case.
>
> MS. HARVEY: Any comments from our health physicists? Ms. Martin or Dr.
> Karellas.
>
> MS. MARTIN: These standards are fine with me.
>
> DR. KARELLAS: I agree with Melissa. The only thing I am a little
> apprehensive is that physicists just have to watch closer since
> different manufacturers have different requirements, so which is okay,
> that they can do it. Physicists practicing out there are very much
> into that. It just will add a little bit on their time for it. That is
> my only concern, but I am sure they can do it.
>
> MS. HARVEY: Thank you.
>
> DR. BURKHART: Thank you.
>
> **Open Public Hearing**
>
> MS. HARVEY: Now, we are moving into the open public hearing aspect of
> our meeting today.
>
> We have comments on quality control for full field digital mammography
> from Ken Crocker, who is Director of Marketing, Product Planning for
> the Fischer Imaging Corporation. Welcome.
>
> MR. CROCKER: Thank you. My name is Ken Crocker and I very much
> appreciate this opportunity to address the committee on what I think
> is becoming a more important topic as time goes on.
>
> As you all are probably becoming more aware, digital mammography has
> reached a greater degree of acceptance throughout the U.S., and I
> think is becoming more of a standard operating practice with probably
> well over 300 systems already in place throughout the country.
>
> \[Slide.\]
>
> There is I think a few issues developing as this acceptance has
> increased, and I thought it would be important to bring to the
> attention of this committee some of the issues that I think apply to
> not only the manufacturers, but to the accrediting bodies, the FDA,
> and, of course, most importantly, the actual users of the equipment,
> as well.
>
> We are in a situation right now that is rather unique, because when
> the regulations were really originally developed, of course, digital
> mammography was basically only a gleam in the eye of most people, but,
> in fact, we have reached that point that things need to happen now for
> it.
>
> Because of that, the original regulation only stated that the
> Operator\'s Manual from the manufacturer should be followed as the
> appropriate quality control procedure. That is going to result in
> delay in providing oversight to users of the full field digital
> mammography system.
>
> While it may be true that the FDA, as part of the PMA process, does
> review the Operator\'s Manual, and, of course, I think they do a fine
> job of that because they are the same people that are reviewing the
> proposed quality standards that certifying and accrediting bodies
> would propose, so I think we should be confident that they are doing a
> good job in that area, but nonetheless, it provides only a limited
> amount of oversight.
>
> Once the PMA has been approved, the manual is in use, FDA will look at
> quality control charts after six months of use from a facility, but
> that is kind of the end of the process right there, and I think we
> want to get to a point where we have uniformity and standards.
>
> So, basically, I will show you what the proposal is, but the issues
> today, there is a lack of uniformity because you do have each
> manufacturer proposing their quality standard, and there is limited
> oversight because it is primarily that review that happens as part of
> the PMA process.
>
> Dr. Burkhart described the approval of alternate standards process.
> Certainly, you know, I think it has its place, but overall it would
> only be a stopgap measure in this particular instance since we are
> looking at a complete new set of standards for digital mammography,
> and I don\'t think we could rely strictly on that to address all of
> the needs.
>
> \[Slide.\]
>
> So, why does this issue linger? Obviously, hopefully, it hasn\'t
> lingered too long, but right now for us, as manufacturers, there is
> not a tremendous amount of incentive to standardize.
>
> Once we get through that process, which is challenging unto itself, we
> feel pretty confident that we have produced a reasonable quality
> control approach, and unless there is some really undue needs, we
> would prefer to just keep things running, because we want to be able
> to meet all of our customers\' needs.
>
> The MQSA Reauthorization Act of 2002 is not going to substantially
> change the landscape, I don\'t believe, at least in the last versions
> I have seen of it, that it addressed any of the issues that we are
> talking about here related to full field digital mammography.
>
> The approval of alternative standards doesn\'t address the needs of
> accrediting bodies, as well. The accrediting bodies need to be able to
> get more involved with this process of controlling digital
> mammography.
>
> \[Slide.\]
>
> The proposal is to charge the FDA and accrediting bodies with
> development of these uniform standards, and to encourage their
> cooperation. I know we will be hearing from Dr. Chakrabarti this
> afternoon on that, and I know there have been starts into this area,
> but I think there needs to be more urgency applied given how rapidly
> the acceptance is taking place with digital mammography.
>
> We need to charge the FDA and the accrediting bodies to seek guidance
> from industry. Certainly, individual manufacturers are interested and
> willing to participate, and then NEMA, which, of course, is an
> industry group, also has started efforts in that area, as well, and
> would be more than happy to participate in doing that.
>
> Our third point would be that FDA should allow accrediting bodies to
> accept the Manufacturers Manual for accreditation on an interim basis,
> and this would allow the transfer of responsibility over to the
> accrediting bodies, so that they could start becoming involved in this
> process. As of today, you know, they don\'t really have any sort of
> regulatory capabilities in that area.
>
> \[Slide.\]
>
> Charging the accrediting bodies with simplification and uniformity as
> a longer term goal, would also then follow with that, but at least we
> would have that immediate knowledge that the Operators Manual is
> available and accepted by the accrediting bodies and the FDA.
>
> Eliminate the requirement to maintain a film-screen system. As I
> mentioned, the review of the manuals is already carried out by a very
> respected group of individuals at the FDA, that are also responsible
> for the oversight of film-screen certifying and accrediting efforts.
>
> If they are capable of doing that, I would expect they would be
> applying the same degree of rigor to digital mammography, and believe,
> in fact, that they have, so this requirement of maintaining a
> film-screen system, I think imposes an unnecessary burden both on
> users of the systems, as well as the entire community.
>
> Lastly, getting to Dr. Pisano\'s point about why don\'t we just do
> this for all manufacturers, this synchronizing of tests that allow 30
> days for corrective action, certainly, we agree and support that
> position.
>
> Tests that are as common as repeat analysis, I know from our
> standpoint we tried to make things as simple, straightforward, and
> consistent as possible for users of our system so that they wouldn\'t
> have to completely rethink the process of how they do a repeat
> analysis, for example.
>
> I think that the FDA should be charged with developing that uniform
> standard rather than waiting for either a user or a manufacturer to
> come to them. We actually did go to the FDA over a year ago with a
> similar request to what had been made for the GE system, but it is a
> rather challenging process to get through.
>
> I mean I am not blaming anybody for what happened there, but I would
> just say that from my standpoint, I think it would be better for all
> of us if the FDA could take a proactive stance rather than a reactive
> stance to requests for these kinds of changes.
>
> That is all I have prepared. I just want to thank you again for the
> opportunity to address the committee and appreciate your efforts to
> provide the best quality mammography for our community.
>
> MS. HARVEY: Thank you, Mr. Crocker.
>
> Any questions? Yes.
>
> MR. CAMBURN: Jim Camburn from the State of Michigan. I think I have
> one question for you related to one of the things you commented on,
> eliminating the requirement to maintain a film-screen system.
>
> Are you suggesting, then, that the facility would not have any
> film-screen unit at the site where they would have a full field
> digital machine?
>
> MR. CROCKER: Yes. Let me explain a little bit about what the
> requirement is today. The requirement today is that there is at least
> one film-screen system within a particular FDA jurisdiction that is
> under the supervision of a particular radiologist who has
> responsibility.
>
> They don\'t have to be at physically the same location, you could have
> one at a hospital and then you could have a digital at an off-site
> facility, and as long as there was one film-screen present at one of
> those two locations under the jurisdiction of a particular supervising
> radiologist, that would be acceptable.
>
> But we see it all the time now that there are situations where
> different groups of physicians want to become involved with digital
> mammography, they have the experience, they are willing to do the
> quality control that has been approved and recommended by the FDA, but
> they do not want to invest in having a film-screen system, as well.
>
> In fact, they have no intentions of using the film-screen system, but
> because of the way the regulations are today, they will go out, they
> will buy a film-screen system, they will do the absolute minimum to
> maintain the accreditation of that system or certification of that
> system, and therefore, I don\'t think it is really accomplishing much.
>
> I think we are better off letting them focus on the quality control of
> the digital system that they really intend to use.
>
> MR. CAMBURN: We see this from maybe a slightly different perspective
> because we have a number of facilities that have one digital unit and
> one film-screen unit, and they seem to use them differently, at least
> some facilities do. The digital full field mammography machine has a
> relatively small image receptor compared to the larger film size that
> you can get with film-screen imaging.
>
> What they do, they will\--average size patients might fit fine with
> the digital image receptor, but larger patients would require two
> exposures for each projection, and it kind of doubles the patient dose
> in the area that the x-ray beam overlaps.
>
> So, from a radiation dose point of view, isn\'t it better to have the
> ability to do both types of imaging?
>
> MR. CROCKER: I certainly appreciate and agree with what you are
> saying. With the full field digital mammography from Fischer, it has a
> larger field of view, and therefore, in fact, the larger field of view
> is 21 by 29 cm, so the percent of the population that would require a
> multiple stitching together of images is no greater than what would be
> required under a film-screen system.
>
> So, for our particular equipment, we don\'t see that problem, but I
> certainly can understand where you might be concerned about that from
> a radiation dose standpoint with some other systems that are available
> in the marketplace.
>
> MS. HARVEY: Any other questions?
>
> DR. PISANO: I just have a follow-up comment. I actually think from a
> public health viewpoint, in terms of getting digital out to remote
> areas where the images could be beamed back to a central site for
> interpretation, it makes a lot of sense to not require the film
> mammography, because you are probably limiting access to remote areas,
> if they are going to use digital, they also have to have a film
> mammogram unit.
>
> So, I would agree with his comments that he made, that we would like
> to move this process along, I would like to see it moved along, so
> that it is more standard and that the film mammography isn\'t
> required.
>
> MS. HARVEY: Thank you.
>
> Dr. Finder.
>
> DR. FINDER: We have one comment that came in, and the person who
> submitted it would like me to read it into the record. It is a written
> statement from Pamela Gormley, who is a mammography supervisor at Epic
> Imaging in Oregon.
>
> Her statement is as follows:
>
> The following is a mammography item that I believe the FDA needs to
> expedite the changes on. We have had two of the new FFDM GE 2000D
> digital mammography units since October 2000. However, the FDA says we
> still have to have a film-screen unit on the premises, plugged in and
> ready to use, even though a film-screen is outdated technology.
>
> This is approaching two years. This is wasting both their resources
> and space for mammography. We would have replaced that unit with newer
> technology if the FDA allowed it. We also have to maintain a film
> processor that we don\'t want or need.
>
> All of the quality control tests that we do on the digital units show
> that they have much better detail on the phantom image and on
> patients, with one-third less radiation per view than the former
> state-of-the-art film-screen system that we have.
>
> Our film-screen combo is the detailed Fuji AD-M fine screen with Fuji
> AD-M film, dedicated Kodak M-35A processor with White Mountain
> chemicals, 135-second processing at 95 degrees, using GE Senographe
> DMR bi-metal tube mammogram machine maintained by GE service, but it
> cannot begin to compare with what we see with the digital system.
>
> Please get this changed immediately, so that we can provide the best
> medical care to our patients without wasting money.
>
> MS. HARVEY: Thank you.
>
> DR. FINDER: I would like to add that we are going to have some more
> talk about this entire issue later on in the afternoon.
>
> MS. HARVEY: We are a little ahead of schedule, so if Michael Divine is
> prepared, we will move on to the open committee discussion.
>
> Michael is going to talk to us on Overview of MQSA Inspection Findings
> and Current Inspection Follow-up Actions.
>
> **Overview of MQSA Inspection Findings and**
>
> **Current Inspection Follow-up Actions**
>
> MR. DIVINE: My name is Mike Divine and I work in the Inspection and
> Compliance Branch in the Division of Mammography Quality and Radiation
> Programs.
>
> \[Slide.\]
>
> My talk today is, appropriately enough, on inspections and compliance.
>
> \[Slide.\]
>
> I will be going over a summary of problems that we have found during
> our annual inspections and also an overview of the various actions FDA
> might take when facilities have serious problems or failed to correct
> these problems.
>
> \[Slide.\]
>
> For the inspection data, my talk will cover the last two complete
> fiscal years for FDA data plus most of the current fiscal year which
> will end on September 30th. While the data for this year is not
> complete, I think we have enough data for comparison purposes.
>
> \[Slide.\]
>
> While most people here today are probably familiar with our inspection
> levels, I thought a slide was needed for those who might not be
> familiar with them.
>
> Level 1 is the most serious and could result in FDA action if not
> corrected.
>
> Level 2 is less serious, but still significant enough that a facility
> is required to respond to FDA with their corrective action.
>
> Level 3 findings are considered minor.
>
> \[Slide.\]
>
> As you can see from this first slide, facilities continue to improve
> and the overall rate of problems has been declining, which is very
> good news.
>
> While this slide only shows two full fiscal years plus most of a
> third, if we extended these data back to 1995, when we started
> inspections, the trend would be even more pronounced.
>
> \[Slide.\]
>
> This slide shows Level 1 problems with personnel. While the chart
> shows a jump for some categories in 2001, the small numbers compared
> to the overall percentage of inspections doesn\'t indicate that this
> is a real problem. For the medical physicist, the number of violations
> has all but vanished.
>
> I would mention at this point that this data represents inspections of
> approximately 9,500 facilities.
>
> \[Slide.\]
>
> Processor QC problems continue to be a source of problems, but these
> numbers are also going down. The same is true for missing phantom QC
> data.
>
> \[Slide.\]
>
> On this slide, as opposed to the previous slides which showed data for
> the facility QC testing, these data come from our inspector testing.
> The number of violations for phantom image is very small, as are data
> for processor speed. Fog values are somewhat higher, although these
> numbers have been declining.
>
> \[Slide.\]
>
> For the medical physicist surveys and mammography equipment
> evaluations, the most common problems are overdue surveys, surveys
> missing specific tests or data, and failures to do evaluations on
> x-ray units and processors. These numbers are also declining.
>
> \[Slide.\]
>
> For interpreting physicians, the number of facilities cited for
> initial training or experience remains low. For continuing education
> and experience, the numbers are greater, but are declining.
>
> \[Slide.\]
>
> For radiologic technologists, we see a similar trend. The jump in
> continuing experience is probably due to this first thing checked in
> 2001. We expect these numbers will decline in the years to come.
>
> \[Slide.\]
>
> For medical physicists, the small number of facilities cited
> exaggerates the difference between the years. The missing bars for
> 2002, under the initial requirements, is due to no facilities being
> cited, as with the technologists, checking on the continuing
> experience is a relatively new assessment.
>
> \[Slide.\]
>
> For medical records, a lack of an appropriate assessment category on
> mammography reports dominates the problems, however, we have seen a
> substantial drop in the numbers in just three years.
>
> \[Slide.\]
>
> This chart shows some other requirements we check during inspections.
> The problems with x-ray units has dropped to almost nothing. For our
> first inspections with complaint and infection control procedures, the
> drop in the number of facilities with these problems has dropped
> dramatically.
>
> \[Slide.\]
>
> For the medical outcomes audit, only a small number of facilities
> still have problems. The last three sets of bars here reflect
> requirements only being checked in the last two years. As with some of
> the other cases like this, we expect these numbers will go down with
> time.
>
> \[Slide.\]
>
> This last slide from our inspection data shows a number of facilities
> that had at least one problem during their inspection for not having
> complete documentation for their personnel.
>
> \[Slide.\]
>
> Moving away from the inspection, the next few slides will focus on the
> various options FDA has when facilities have continuing problems
> complying with our regulations.
>
> \[Slide.\]
>
> These types of actions include a follow-up inspection, additional
> mammography review, patient and physician notification, which is
> actually a follow-up action in case the additional mammography review
> shows problems, a directed plan of correction, civil money penalties,
> suspension or revocation of a facility\'s certificate, an injunction,
> which is actually a court order that would shut the facility down.
>
> \[Slide.\]
>
> When facilities fail to meet specific requirements, we may need to
> reinspect the facility to see if it has corrective problems. Most of
> the time, these inspections only focus on areas where the facility has
> failed in the past.
>
> \[Slide.\]
>
> Additional mammography review is a review of mammograms and/or
> mammography reports to investigate previous or ongoing clinical
> problems at the facility. The purpose of the AMR is to look for
> serious problems where patients and physicians need to be notified. If
> there was a serious risk, there could be a possible patient and
> physician notification.
>
> \[Slide.\]
>
> For additional mammography review, we generally select certain types
> of issues that we think we want to do an AMR. One we do which is the
> most common although it has been significantly declining the last few
> years is we find a phantom image problem that is at Level 1 during an
> inspection, we will do an AMR.
>
> We could do one for an interpreting physician that would fail to be
> qualified. Clinical image quality problems would be an obvious one. If
> there was an overall failure in the quality assurance program at the
> facility, that could trigger one, and we have done a few for
> fraudulent recordkeeping situations.
>
> \[Slide.\]
>
> The extent of an AMR could range from a few films to a larger sample.
> Our most common reason for AMR, as I mentioned, is Level 1 phantom
> failure. A larger sample is usually needed if a smaller AMR shows
> serious problems or the problems at the facility to make a smaller
> review inappropriate.
>
> \[Slide.\]
>
> When an AMR shows serious problems, FDA would send the facility a
> letter requiring the patient and physician notification. These letters
> outline options referring physicians and patients have, such as
> getting their mammograms reread by another interpreting physician or
> getting a new mammogram. The letters are written in plain language,
> avoids using complicated jargon with patients.
>
> \[Slide.\]
>
> A directed plan of correction is a regulatory action FDA may take that
> imposes additional requirements on the facility. The goal of the DPC
> is to force the facility to perform mammography in compliance and
> allow FDA to easily monitor this performance.
>
> Under a DPC, the facility is usually required to send FDA copies of
> records on a monthly basis and are subject to additional inspections
> to check on their performance.
>
> \[Slide.\]
>
> For more serious problems, FDA may suspend a facility\'s certificate.
> Once a certificate has been suspended, the facility can no longer
> perform mammography. In most cases, facilities are usually given a
> hearing prior to the suspension, however, FDA may suspend prior to a
> hearing if there is a serious risk to human health or other
> substantial violations.
>
> \[Slide.\]
>
> A last list of the remaining options that FDA has is rather than
> shutting a facility down, FDA may opt for charging a facility civil
> money penalties, and this could be up to \$10,000 per violation or per
> day.
>
> We could also revoke a facility\'s certificate, which is equivalent to
> suspension, however, once a certificate has been revoked, the owner or
> operator of the facility cannot own a mammography facility or operate
> a mammography facility for at least two years after the revocation.
>
> \[Slide.\]
>
> Lastly, if everything else fails and we feel that we have to go to
> court, we have the ability to use an injunction which actually closes
> the facility down through a court order.
>
> \[Slide.\]
>
> In closing, this table shows the number of times FDA has taken
> specific regulatory actions based on problems occurring at facilities.
>
> That concludes my talk.
>
> MS. HARVEY: Thank you.
>
> DR. PISANO: I have a question.
>
> MS. HARVEY: Yes, Dr. Pisano.
>
> DR. PISANO: Is this in the history of enforcement of MQSA or is this
> one year?
>
> MR. DIVINE: This is the entire program.
>
> DR. PISANO: And what is the denominator like 900-plus facilities per
> year times 8 years, something like that?
>
> MR. DIVINE: Well, we inspect about 9,500 facilities.
>
> DR. PISANO: That is what I meant, 9,500 times about 8 or 10 years?
>
> MR. DIVINE: Yes.
>
> DR. PISANO: So, it is 95,000 facilities, and these are the numbers,
> something like that, is that right?
>
> MR. DIVINE: Yes.
>
> DR. FINDER: I would want to add that this represents actions taken by
> FDA. This does not include actions taken by the State, and in several
> cases or many cases, the State has taken action before we have, and in
> that case, we don\'t pursue it any further, so it is not the total
> number of facilities that ran into problems.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: You mentioned something about that the
> equipment-associated problems are something like very few or next to
> nothing, which is very encouraging, but I would like to comment for
> the public and for the lay press, because often we read about that
> there are no problems with the equipment or it has nothing to do with
> the equipment.
>
> The reasons that inspectors find very few problems with the equipment
> is that equipment is very well maintained. We find problems with the
> equipment all the time routinely. Almost on a weekly or monthly basis,
> technologists will walk in and will find problems with a processor, on
> occasion with the automatic exposure control, they typically call
> service or physicist depending on the situation, and the problems are
> taken care of.
>
> So, this is why you don\'t see the problems. I am sure you know that,
> but the public perhaps doesn\'t understand that.
>
> MR. DIVINE: That is a good point. We only go in once a year to do the
> inspection, and when we look at the equipment, basically, we find that
> there was a problem, but it has been fixed. It certainly is not
> something that shows up during the inspection.
>
> I would also point out that as the years have gone by, a lot of
> equipment that had problems and couldn\'t be maintained has been
> replaced or repaired to where it can meet the requirements.
>
> MS. HARVEY: Dr. Lee.
>
> DR. LEE: Amy Lee. I was wondering if you ever analyzed your data for
> specific trends, like geographical areas that tended to have more
> violations or specific kinds of equipment, and if you have, have you
> noted any kinds of trends or clusters.
>
> MR. DIVINE: I am not aware if we have done any geographic types of
> analyses.
>
> MS. HARVEY: When we look at the Level 1 phantom image violations,
> would you talk to us a little bit about the scores that that might
> represent, what is passing and what scores would be considered to be a
> serious violation, is it triggered immediately after below 10?
>
> MR. DIVINE: The criteria we use for phantom image, we have two, Level
> 1 and Level 2. Level 2 is where it fails at the accreditation body\'s
> limit, which all the accreditation bodies use the same values, which
> are 4-5ers, 3 speck groups or 3 masses. If any of the objects go below
> any of those, it\'s at least a Level 2.
>
> Now, our criteria for Level 1 is if it goes below 3, 2, or 2, which is
> one unit below the criteria. So, we do have a certain number of Level
> 2 phantom failures, and those are higher than a Level 1, but even
> those are not very high.
>
> MS. HARVEY: Equipment has become much better at resolution over the
> years. Is there a debate about raising the image score?
>
> MR. DIVINE: I am not aware of one. I have heard some people mention
> that, but there has been no urge for us or, as far as I know, the
> accreditation bodies to raise the values, but it is possible that
> there has been, I am not aware of it.
>
> MS. HARVEY: Dr. Young.
>
> DR. YOUNG: Don Young. Have you compared your data with the States that
> are accrediting bodies and certifying bodies that had the data
> required relative to the inspections?
>
> MR. DIVINE: Not that I am aware of.
>
> MS. HARVEY: Dr. Young, do you have any data?
>
> DR. YOUNG: No, I don\'t personally.
>
> MS. HARVEY: Any other questions, comments?
>
> Thank you.
>
> MR. DIVINE: Thank you.
>
> MS. HARVEY: It\'s time for a break. It\'s about 5 minutes of 10:00,
> perhaps 15 minutes, back at 10 minutes after 10:00. Thank you.
>
> \[Break.\]
>
> MS. HARVEY: Dr. Finder will provide us with information on Good
> Guidance Practices and Directions for Discussions on MQSA Guidance
> under the Final Regulations.
>
> Dr. Finder.
>
> **Good Guidance Practices and Directions for**
>
> **Discussion of the MQSA Guidance under the**
>
> **Final Regulations**
>
> DR. FINDER: Before we begin our discussion of final regulation
> guidance, I would like to briefly explain the procedures that FDA is
> following as it develops new guidance.
>
> In response to public comment regarding the use of guidance documents,
> FDA held an open meeting on April 26, 1996, and on February 27, 1997,
> they published a federal notice outlining the steps the agency needed
> to take prior to issuing guidance.
>
> In brief, it stated the following. Guidance has to be developed in an
> open manner that permitted input from the general public and the
> regulated industry. In most cases, new or controversial guidance had
> to allow for such input prior to its implementation.
>
> While the statutes and their associated regulations were binding and
> enforceable, guidance was to represent a way or ways of meeting the
> regulations, but other ways would be acceptable as long as they met
> the requirements of the underlying regulations or statute.
>
> Before we begin our discussions, I would like to emphasize the
> following. We are here to discuss the proposed guidance, not the
> underlying regulations. The regulations have already gone through
> their own extensive approval process and while they are subject to
> future change, the purpose of today\'s meeting is to address the
> proposed guidance.
>
> When you hear or see words like shall require or must, they refer to
> the underlying regulation, whereas, the words should, may, or
> recommend refer to the guidance. I also want to add that since the
> beginning of the program, we have issued a large amount of guidance to
> help facilities meet the underlying regulations.
>
> This material, this guidance has been compiled into what we call the
> \"policy guidance help system,\" which is a computerized search engine
> that is now available on the Internet to aid facilities in their
> compliance with the regulations.
>
> There is probably about anywhere from 5- to 700 pages worth of
> guidance encapsulated in that search engine and what we are in the
> process of doing right now is going through all that guidance to
> update and revise it.
>
> One of the documents that you have, which is Modification Document No.
> 5, is the first in that series where we are actually going page by
> page through all the previously issued guidance to update and add
> material as appropriate.
>
> So, with that said, I think that probably the first item that we would
> like to talk about is the issue of the agency automatic exposure
> control.
>
> With that said, I guess we are done with AEC.
>
> \[Laughter.\]
>
> DR. FINDER: Let me give a little bit of background. We did send out a
> letter to the committee for them to look at prior to the meeting, and
> basically, this raised several issues about testing of the automatic
> exposure controls in some of the newer equipment that have multiple
> different configurations and submodes.
>
> If anybody would like to start the discussion on that, I would
> appreciate it, otherwise, we are going to have a lot of time between
> now and lunch.
>
> MS. HARVEY: Yes, Dr. Karellas.
>
> DR. KARELLAS: At least I would like to start in one area of the AEC
> issues. There are certain systems that they may have various modes and
> medical physicists may be evaluating modes that they may not be
> actually used by the facility.
>
> My own view is that there should be no need to test every available
> mode of a complex AEC system if the facility does not intend to put it
> to use, and a facility should decide as to what they use, and that
> should be tested.
>
> Now, I understand that in real life, a facility will start with
> something and perhaps a month later, they will decide that they need
> to use another mode, and that will happen. Although it may be not a
> problem for a physicist to test these two or three modes and have
> that, but if they are far more complex than that, and there are too
> many combinations, it may be unrealistic to be testing all these
> modes.
>
> Then, the physicist could come back and reevaluate the system a few
> months later if that had to be, but I am not suggesting that the
> physicist should evaluate the AEC every time every minor modification
> is made, and the way it is used or some very minor repair.
>
> I am saying that it should be tested only if there is a very
> substantial departure from what the system was initially tested.
>
> MS. HARVEY: Ms. Martin.
>
> MS. MARTIN: This is Melissa Martin.
>
> I am the other medical physicist on this panel. Obviously, what we are
> discussing affects what Andrew and I do the most. As a consulting
> physicist, just to put this in perspective, I obviously provide the
> medical physics services for, at this point, around 150 facilities,
> which covers around 250 mammography units on an annual basis.
>
> We have many of the high-level, multi-mode, multi-target, multi-filter
> units in our practice. We have made great strides to test what I have
> considered all the clinical modes used for each one of these units
> when we go on site the first time.
>
> In Southern California, I cover an area I call Southern California. I
> cover sites that are about 300 miles away. It is to my benefit and the
> facility\'s benefit to make these measurements when I go out there
> initially. That is why, as Andrew said, I try to cover all what is
> going to be called clinically useful or possible clinically useful
> combinations.
>
> For those that use, as an example, the GE DMRs, I don\'t have any
> facilities that use the dose mode on a 2-cm breast, so it makes no
> sense to require the physicist to test the dose mode for a 2-cm
> breast.
>
> i think we do need to set an understanding here of what is clinically
> useful and what the physicist would be expected to test. Some of the
> newer units, the low radium 4\'s, it is not even possible to test at
> the low kVp\'s or the high kVp\'s for thin breasts, because the grid
> doesn\'t have time to move.
>
> So, if you technically looked at some of what is proposed, it can\'t
> be. The other factor is how much time are we taking a facility down.
> We do impact the access to people to get mammography. If we go in to
> perform our measurements, we are typically in a room somewhere between
> 4 and 6 hours.
>
> That is 4 to 6 hours that room is out of service and available for
> serving patients, and I think we have to be aware and very careful not
> to set measurement criteria that is not clinically relevant, but which
> will also add cost to the facility and decrease the amount of time
> that the patients can be examined.
>
> DR. KARELLAS: Melissa put that very nicely. I think the vast majority
> of medical physicists feel that way.
>
> MS. HARVEY: What percentage of the time that you are testing the
> equipment do you think the AEC testing would involve? Is it a major
> part of the testing?
>
> MS. MARTIN: At least 25 percent currently.
>
> MS. HARVEY: And there are no surrogates, there aren\'t any simple
> tests that we can go to that would be representative of larger\--
>
> MS. MARTIN: I am saying it\'s 25 percent to do what I have been
> considering the clinical modes. If one of the discussions was pursued
> here that I had to test every kVp in every mode, you are adding at
> least 2 to 3 hours of testing, so you are roughly adding somewhere
> between 3- and \$500 of additional cost and another 2 to 3 hours of
> time out of the room.
>
> MS. HARVEY: Plus your time.
>
> MS. MARTIN: Yes.
>
> MS. HARVEY: Any other comments about AEC testing?
>
> DR. FINDER: This is Dr. Finder again. I think you framed the issue.
> Now, we have got to get down to some of the specifics, and we did ask
> a couple of questions in the document that went out. We would kind of
> like some guidance on what you think that reasonable testing is under
> the various scenarios.
>
> The first issue that we talked about here is, as we have said, the
> current requirement is that a mode or configuration needs to be tested
> prior to clinical use. There are two different areas where that could
> occur. One is at the initial evaluation called the mammography
> equipment evaluation, and the other is during the annual physics
> survey.
>
> The requirements in the regulations are slightly different for those
> two types of testing. One of the issues that has been brought up is,
> is it enough to test just all the modes and configurations at the
> initial mammography equipment evaluation, and then do something lesser
> of not possibly all the clinical modes at the annual survey.
>
> This is one of the issues that we would appreciate the committee\'s
> guidance on.
>
> MS. MARTIN: I will just respond and again this is where I am coming
> from. I basically use Alternative Test No. 2, which conforms to the
> ACR\'s suggested forms that are available in the latest QC Manual for
> the physicists.
>
> That test I perform annually on all the modes with every machine. I
> personally have not skipped any of them, so I don\'t have any feel for
> what percentage of people typically only test in the contact mode. I
> always test the mag mode.
>
> DR. KARELLAS: I always test the mag mode and most people I know test
> the mag mode, because we go pretty much by the ACR guidelines, so we
> use that as a guide, and we may make one or two additional
> measurements for other things that we feel might be necessary. That is
> what we go by.
>
> MS. HARVEY: Does that help you, Dr. Finder? No?
>
> DR. FINDER: Well, it partially addresses some of the issues, but we
> also have the concept of these units that have multiple different
> AECs. As has been brought up, some of these AECs are not used over the
> entire 2 to 6 cm range.
>
> The regulations, however, say that the AECs have to be tested over
> that range, and we have some situations where a facility may say,
> well, we never use the 2 cm range for this type of submode of AEC, but
> we do use it at 4 and 6. Well, how is that going to be tested?
>
> We also have the issue of a facility that says they are going to use
> one submode at 2, another submode at 4, another submode at 6, what is
> the appropriate testing under those types of scenarios, do you just
> look at those three individual submodes at those levels, or do you
> require each one of those submodes to be tested at 2, 4, and 6?
>
> These are some of the questions that have come up, and how do you deal
> with those kind of situations.
>
> MS. MARTIN: What we have made the choices, if they are clinically
> using it, in other words, again, go back to the AOP contrast, the GE
> DMR has three different modes, well, actually several different modes,
> but three automatic modes AOP, which is contrast, standard, and dose.
>
> Typically, what Dr. Finder is saying is a 2- or 4-cm breast would be
> examined in the contrast mode, 6 could be either contrast or standard.
> I typically test 2 and 4, I don\'t test 6 under contrast unless the
> facility says that is what they use. A standard, I typically do 4 and
> 6, I don\'t do 2 unless the facility says that is what they use.
>
> I really do think you have to look at what the facility is using, but
> if those modes are set up and cross with each other, that basically is
> your test. I think it is crucial that each mode be tested at least on
> some thickness to verify that you are tracking between modes. I don\'t
> find it mandatory that you test every thickness on every mode.
>
> MS. HARVEY: So, if you are testing a unit and you look at either the
> 2, 4, or 6, and it is working properly, can you presume that it would
> be working properly at the other two thicknesses that you are not
> testing, or do you actually have to do each thickness?
>
> MS. MARTIN: I have not found a problem. If it is working properly in
> the mode for which it is pretty much designed to work in, I have not
> found a problem with it tracking between the other modes, but
> certainly I am not the only one performing these measurements.
>
> Dr. Karellas.
>
> DR. KARELLAS: We actually test at higher thicknesses than 6, but it is
> not a requirement, but we just do it because we want to see how the
> machine works, and we just draw a line there, so if it deviates, and
> sometimes they do, that then we know at least that we have bracketed
> for the requirement.
>
> Usually, the deviation may be very nominally below or above what the
> requirement is, but we know that the deviation is not really against
> any regulations, state or federal, but we are aware of it. If we see
> something and we need to adjust it, at least we know.
>
> MS. MARTIN: One of the more crucial items as far as time testing is
> for those units that are now out there, that have individual
> detectors, there is one manufacturer that has seven or eight separate
> detectors, independent detectors.
>
> I think the more crucial time thing is I have found it and what I have
> been doing is doing the full set of tests on one of the detectors and
> then cross-checking all the other detectors for the 4 cm breast. I
> have found that to be sufficient. I have not been testing all eight
> detectors for every target filter for every one.
>
> I think again, as long as you are making a reasonable attempt to
> verify at typically the 4 cm thickness, that your detectors cross with
> each other, that should be considered an acceptable test.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: Isn\'t it true\--this is a question for the
> physicists\--isn\'t it true that if there were a problem with one of
> the AECs, for example, in that eight system, it would be obvious in
> the clinical images?
>
> Wouldn\'t it be that it would be either too light or too dark over a
> certain region of the breast, so that it is not something that is
> likely to create real clinical problems? In other words, the
> radiologists, the readers, and the local physicist, if there is one,
> would be able to spot it very quickly?
>
> MS. MARTIN: You are going to spot it very quickly, right.
>
> DR. KARELLAS: It is true that eventually, it will become obvious when
> an astute radiologist or technologist will discover it, however, the
> concern is that there will be certain studies that will be done, and
> the patient will be gone, and images may be suboptimal, so eventually,
> it will be found, it will not go for very long, but it is just that
> there may be something compromised, perhaps not of great significance,
> but certainly mammography may not be done at the state-of-the-art
> level.
>
> MS. HARVEY: I have another question. Do you generally find a problem
> on the initial testing, or is this a problem that occurs over time,
> that you see that the detectors go out of whack on your annual when
> you come back, do you see problems at the annual testing, or do you
> see more problems at the initial testing?
>
> MS. MARTIN: The initial testing is usually good. I think it is
> absolutely crucial, though, that it be tested, at least sampled, again
> cross-check some way for each one of those initially.
>
> My experience is the installations are usually done very well now. I
> wouldn\'t say that was necessarily the case two years ago, being the
> installers have gotten much better, and I think part of that is
> because they are trying to make the criteria that has been set.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: The question that I have is what we should be doing when
> we have a brand-new machine and it has all these multiple modes, and
> we have not discovered how we are going to be using that machine, and
> the site needs to accept it.
>
> If you accept only two or three or four modes, and then six months
> later, you discover that you want to use all the others, and you find
> something that doesn\'t work very well, then, it is more difficult to
> go back to say that that was not done properly in the beginning,
> especially post warranty.
>
> So, it is somewhat of an issue as to whether we need to test
> absolutely everything upon installation, but that can be a very
> frustrating experience because you are testing something that may be
> so far out of the real application.
>
> So, I still maintain that upon installation, the site should define
> certain modes of use and perhaps one or two or three above and beyond
> that based on how this machine should be used, and perhaps after the
> first or second year, you could perhaps narrow it down a little
> narrower to say that we are never going to use these modes, we are
> only restricted at just to these three modes.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: I have another question for the physicists. Isn\'t it the
> case also that your phantom testing on a weekly basis would suggest
> there is an AEC problem, you would see your OD changing over time even
> with the same settings?
>
> I am trying to get a feel for how dangerous this is for patients. My
> sense of this is that it is not very because of these two things,
> these clinical images will chance and the phantom imaging will change,
> so even if you don\'t check every mode, even if they use it one or
> two, you are going to find it somehow. But I would like to hear your
> comments on that.
>
> MS. MARTIN: Again, as long as you cross-check the modes, I don\'t
> think you are going to have a problem. I have not found it a necessity
> to check the complete thickness for every single mode, and, yes, the
> idea of if you wanted to extrapolate it for those instruments that
> have eight detectors, do you want eight phantom images every week to
> verify that you have consistency. You could take it to the nth degree
> and make the same requirement, and I don\'t think any of us want to go
> there.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: I agree with Dr. Pisano. First of all, I do not feel it
> is dangerous and I feel very strongly that weekly phantom tests are
> very good, and technologists, in fact, in most situations, it is
> technologists, that they call us about problems, and they are very
> vigilant about image quality.
>
> On the down side is that if something ever might happen that shows
> okay on the 4.3 cm phantom, but it doesn\'t track very well when the
> thickness is 6 cm, that is possible, but at least in our experience,
> most of the time technologists call us and they say there is something
> wrong with my AEC, and interestingly, you may have tested it three
> months ago and everything was fine, and they alerted us.
>
> So, what radiologists and technologists see every day is extremely
> critical.
>
> DR. FINDER: One point that I would want to bring up in terms of the
> phantom testing, the phantom is one image taken under the clinical
> conditions for that thickness of breast, so you will not be checking
> or necessarily have any idea how the other submodes might operate in
> terms of the AEC.
>
> In fact, depending on how a facility sets up its protocols, if it
> does, their standard patients, say, in the typical AEC mode, and not
> the full auto mode, you won\'t have any idea what is going on with the
> full auto mode in terms of looking at the phantom.
>
> But these are the issues that we would like discussed and try to come
> to some kind of consensus.
>
> MS. HARVEY: Mr. Camburn.
>
> MR. CAMBURN: Maybe I can just relay some of the information that we
> get from our inspectors from time to time about this, especially in
> terms of your fourth question that you ask here about testing submodes
> 1, 2, and 3, when submode 1 might only be used with a 2 cm thick
> breast and submode 2 with a 4 mm, and so on.
>
> What we find from time to time is the technologists will inadvertently
> use the wrong submode especially if you have a number of technologists
> working with the same equipment, they don\'t all seem to be on the
> same page at the same time, plus there are patients whose size fall
> between 2, 4, and 6, and the technologist makes a judgment and may
> sometimes judge to use a different submode than what may have been
> initially assigned for that thickness.
>
> So, we kind of like to see, although a reasonable amount of testing,
> that the submodes are all tested.
>
> MS. MARTIN: That is why I made the comment earlier. I think each of
> the submodes needs to be tested at least at some thickness to show
> that it tracks, but if all the submodes are tested\--and I would add
> to Andrew\'s comment, we always test an 8 cm breast because at least
> in Southern California, we have several women that fall in that
> category\--so, I think the 8 cm breast is absolutely critical to be
> tested.
>
> Now, what I have found is for many of the 8 cm breasts, the 8 cm
> phantoms, it is necessary to adjust the density on some units to
> achieve the optimum density, and that option is nice to have, and I
> think that is part of the physicist\'s responsibility to give the
> facility a technique that will bring their large breasts into the same
> density range as their average breast. That is part of working with
> the facility.
>
> As long as I have tested those modes over some part of the thickness
> and they all meet the tracking, I have not found a problem with
> testing every mode for every thickness.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: I guess I want to reiterate Melissa Martin\'s point about
> the cost to facilities of having machines down for longer periods of
> time than are needed.
>
> I think the reason why I kept going back to the point of patient
> safety is I think that maybe one could make a case that at acceptance,
> all the modes and all the thicknesses should be tested and then maybe
> after acceptance, then, only the ones that are clinically used should
> be tested routinely.
>
> In that way, I really think you are probably doing the maximum at the
> beginning and then you are not going to hurt patients or I want to
> also echo Andrew Karellas\' point that the technologists are really
> right on top of those, when the AEC drifts out of calibration, we know
> about it pretty quickly, so I don\'t see that there is a practical
> real problem.
>
> It is more because the regulations say it, you have to figure out how
> to do it problem. In reality, we are on top of this AEC, and we know
> when it is not working properly in clinically relevant modes. So, I
> feel like we should probably try to make it as supportive of the
> regulations, but not hugely time-consuming for the facilities.
>
> DR. KARELLAS: I think we should also realize that the way we are
> testing it, at the various modes and the various thicknesses, we are
> using Lucite, which is really a structureless material as far as
> x-rays are concerned, and the sensors, that is not what they see. They
> see very inhomogeneous density.
>
> So, we can be testing some of these things forever and never really
> reaching perfection as far as matching it to the anatomy, and we must
> realize that. There is a point that when we go above and beyond, we
> get diminishing returns. We just do not get much better image quality.
>
> I do not want to de-emphasize the importance of the proper exposure.
> There is no question that with film-screen, the correct exposure is
> one of the most critical aspects of a good mammogram, but I think it
> can be done without going far above what we are doing today on testing
> the AEC.
>
> DR. FINDER: I just have an attempt at clarification here. Suppose a
> situation occurs where in the beginning, a full testing of all the
> equipment modes as best as possible was done for the evaluation.
>
> Then, the facility decides that they are only going to use, let\'s
> say, two of the submodes, contrast and let\'s say dose, whatever, and
> then you do your annual survey testing those submodes, but sometime
> after your survey they decide that they want to use a third submode.
>
> In your opinion, would that require you coming back to retest before
> they could use it on patients?
>
> MS. MARTIN: Not if you could actually give a cross-check, and I think
> that is where you would fall into the medical physicist oversight.
> What my advice to a facility would be is have the technologist on site
> shoot a phantom in both modes, and if they cross-check with each
> other, so you could calculate a dosage, and the dosages are reasonable
> and the technologist is trained to read out that phantom image, and so
> is the radiologist, if I get feedback that that is acceptable, that
> would be fine with me.
>
> Frankly, as far as testing all those modes, what you find is for 6 and
> 8 cm, standard and dose pull the same thing anyway, so you really only
> have to test contrast and standard, because after about 6 or 8 cm,
> they are all going to pull the high kV and high filters anyway, there
> is not that much difference in them.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: This is one point that I am not sure I am in total
> agreement with Melissa Martin. Perhaps I don\'t understand or perhaps
> she has conducted some experiment on cross-modes, and there are some
> data that we should look at.
>
> If, for example, we have tested something all in the contrast auto
> mode and somebody all of a sudden switches to the dose mode, we do
> have a very different situation in the equipment, and I am not certain
> that the system would behave the way that we would want to.
>
> Now, I wouldn\'t be surprised if it does happen with certain machines
> and when you test it across all modes and somehow everything just
> clears through and everything is fine, but if I get a call as a
> medical physicist, and they ask me is it okay to do that, then, I
> would have to ask them to conduct the measurement.
>
> But then they are performing a measurement that I should be
> performing, and we run into a gray area although theoretically, it is
> possible that somebody can send you three, four images under these
> conditions that you prescribe and measure the optical density and
> generate a report and say that, yes, it actually does conform versus
> going there on a visit and checking it on your own.
>
> MS. HARVEY: We have Question No. 2. I refer you to the document on AEC
> testing, the second page, at the bottom, which has to do with, \"Since
> some or all of the AEC configurations may share key components or
> algorithms, is it reasonable to assume that the failure of one
> configuration immediately makes the other suspect unless the cause of
> failure in one configuration can be isolated as unique to that mode.
> In that case, only the manual mode could be used as back-up until
> repairs have been made.
>
> \"An example of an isolated configuration failure would be a system
> that incorporates separate AEC detectors for different image receptor
> sizes. If one detector fails and can be identified as the cause of
> failure, then the continued use of the AEC with other image receptor
> would be appropriate.\"
>
> MS. MARTIN: I think that comes back to Dr. Pisano\'s point a while
> ago. If you have one of these instruments with eight detectors, and
> suddenly you find out that one of these is off, it doesn\'t
> necessarily mean all of them are off if you can verify that you move
> it to a different unit and it performs fine, then, obviously, you make
> a note and post something that says one unit is not usable.
>
> The same think would come down to the Siemens unit. You could very
> well have the large bucky fail or the small bucky fail, but you
> wouldn\'t necessarily fail both of them. Obviously, that can happen.
>
> Frankly, I don\'t have any facilities that, as the physicist, I allow
> them to use the manual mode of exposure. If my AEC failed, they are
> down. There is no way we use a manual technique for anything, and I
> think that is your bigger\--the idea that you are going to allow
> screen-film mammography in today\'s world to be performed with manual
> techniques is out of date.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: I totally agree with Ms. Martin. There is no way that I
> could think of mammography going on in a facility, going on in an
> manual mode. If the AEC fails, they are down, period.
>
> I would be interested to know whether anybody really would do that,
> but we don\'t, and I think most of my colleagues would not allow that
> to continue, and I think most technologists would stop.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: Just to clarify, because I don\'t understand, may have
> misunderstood, you are not saying, however, like for the Siemens unit,
> where there are two separate AECs, if one of them was down, the big
> image detector, but the smaller, you would still go ahead and allow
> imaging with the smaller detector?
>
> MS. MARTIN: Correct.
>
> DR. PISANO: Okay, because that is the way we do it at our place, and
> it seems appropriate to me.
>
> MS. HARVEY: Is this a frequent problem, that sensors go down?
>
> MS. MARTIN: No, I don\'t hear it that often.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: We have had several problems with AEC on several units.
> In some cases, we identify them, and in some cases, the technologists
> would call us. When we say \"frequent,\" it is not too frequent, but
> if you have 10, 20 or 25 mammography units, one of them, in two or
> three or four years, something will come up.
>
> MS. HARVEY: Rather infrequent.
>
> Dr. Pisano.
>
> DR. PISANO: This is a question for the physicists. In my experience,
> the AECs tend to drift a little as opposed to totally failing, so you
> notice on your phantom that the OD is changing, either going up or
> going down. That is what you notice as opposed to it\'s not working at
> all and the clinical images are really terrible, it\'s really just a
> very gradual, is that correct, is that what generally happens?
>
> MS. MARTIN: That has certainly been my experience, and that is why you
> do QC every week, and that is why you track those phantom images, and
> that is why you have PMIs on the machines, is to bring them back into
> your desired range.
>
> MS. HARVEY: Any other comments on Question No. 2?
>
> Actually, I think we have sort of answered No. 3 since we have talked
> about manual mode.
>
> \"In the event of AEC failure, the manual mode may be used for up to
> 30 days while the AEC is being repaired.\" I sense that that is not
> what the panel is recommending.
>
> MS. BUTLER: Could I ask a question from the floor?
>
> MS. HARVEY: Certainly. I recognize Ms. Butler from the floor.
>
> MS. BUTLER: This is Penny Butler from ACR.
>
> I would just like to ask for clarification on the document that was
> provided. I think it may assist the discussion that is going on.
>
> AEC failure, what exactly does that mean? Does that mean that it fails
> the physicist test or does it mean that it just doesn\'t work, because
> I think a clarification on that point may sort of influence how the
> discussion goes.
>
> The other question is what is the definition of manual mode, because
> in the current guidance that is out there, there was a discussion of
> if the AEC performance fails one of the performance tests in full
> auto, it would be appropriate to temporarily use the fixed kVp AEC
> mode in order to continue operating.
>
> I would like FDA\'s interpretation of how this plays into this
> discussion.
>
> MS. HARVEY: Thank you.
>
> DR. FINDER: I guess it plays into the discussion in the sense of as we
> are trying to get a handle on the fact that these units have multiple
> AEC modes, and if you can figure out that only one or two or three of
> these modes are affected by whatever problems is causing it to fail a
> test or to cause problems, but the other remaining AEC modes are not,
> then, obviously, you could continue to use those other AEC modes.
>
> If all those fail, the regulations do allow a manual technique for up
> to 30 days. Again, that is the way the regulations were written,
> taking into account the guidance that were received at the time the
> regs were written.
>
> But the facility certainly has flexibility in terms of if they have a
> functioning AEC that is within the limits, and they can have
> confidence that it is, they can use that if their other AEC modes
> fail, for example, the full auto mode fails in some manner, they could
> use the fixed kVp AEC mode and continue on that basis.
>
> But you do raise a good question of how do you know what it fails,
> what is the definition of failure. Obviously, there are multiple
> definitions here, and I think that they each raise their own issues.
>
> There is the failure that occurs during the physics testing, and then
> there is the failure that occurs clinically when somebody suspects
> that there is a problem and what do they do in that case.
>
> Generally, what obviously we would recommend is if they believe that
> there is a problem, they get their physicist and take a look and see
> what really is going on, so that they do have a better understanding
> of what is failing and what isn\'t.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: In our experience, failure may be gradual, as Dr. Pisano
> described, you see some drifting and the technologists may catch that
> before anybody else.
>
> The other mode of failure is when, on the annual testing, that it does
> not track with thickness, and we will notice that it is slightly off,
> and the other mode of failure is when you get a call from the
> technologists and they tell you that something is just very erratic.
>
> This is not unusual, that they will tell you that it works the first
> 30 minutes in the morning, or if I take an exposure 15 minutes after I
> turn the machine on, it doesn\'t work very well, and then it sort of
> behaves somewhat better. That is somewhat of an erratic mode, and the
> technologists pick it up.
>
> On the other part about the AEC, this is an automatic mode, so
> switching to more conventional AEC, as Ms. Butler indicated, fixed
> kVp, automatic exposure control, this is a form of an automatic mode
> versus going all manual.
>
> MS. HARVEY: Ms. Martin.
>
> MS. MARTIN: I would totally agree with what has been said, that would
> be the first option, if one of the full auto, auto mode fails, you
> would go to the next level down, which is the manual section of the kV
> and target and filter.
>
> Again, I would come back to that is why initially, we do check, at
> least cross-check for the phantom with all the modes and make sure all
> the modes are functioning properly, which certainly allows the
> facility that option, and if they lose the auto-auto mode, they can
> very well use the phototimed mode, and that has already been checked
> out by the physicist and it is ready to go, and it won\'t take them
> down.
>
> I don\'t consider the single auto mode as a manual technique. I was
> thinking of manual as totally manual where that technologist is
> setting the exposure.
>
> DR. FINDER: That is the correct interpretation of that. AEC mode, the
> fixed kVp is an AEC mode, it is not a manual mode.
>
> MS. MARTIN: Yes.
>
> DR. FINDER: Let me also ask this, follow up with this. You do the
> cross-testing both on the initial equipment evaluation and during each
> of the annual physics surveys?
>
> MS. MARTIN: Yes, I do.
>
> DR. FINDER: If a physicist didn\'t do that, would you say that if they
> hadn\'t tested it during the annual physics survey, at least at the 4
> cm cross-check level, that if the facility wanted to switch to one of
> those modes and it hadn\'t been tested, the physicist would have to
> come back out and do that testing before it could be used clinically?
>
> MS. MARTIN: If they don\'t have the data available to calculate a dose
> and image quality, some type of check I would think has to be made. I
> would think you would have to at least shoot a phantom.
>
> Not all facilities have the 2, 4, 6 cm Lucite to test, so you are
> either going to have to have a physicist on-site or some acceptable
> procedure previously outlined that the physicist is willing to accept.
>
> That could be the medical physicist oversight is what I am coming back
> to. If you have checked it out, so that you say in the auto-auto mode
> typically pull a 26 kV, and your mAs is 143, and you shoot it in
> phototime at 26, and it shoots 145, that should be perfectly
> acceptable, but you do need that cross-check done before you are going
> to use it on a patient.
>
> DR. FINDER: Just to clarify things, right now the regulations, as
> interpreted, as written, require that the physicist come on-site. What
> is being mentioned here is the possibility of doing this kind of
> remotely through physicist oversight, which would be a modification of
> what we have right now.
>
> That is what you are proposing or recommending or suggesting?
>
> MS. MARTIN: Yes, I am suggesting.
>
> DR. KARELLAS: I don\'t think this is unreasonable for providing a set
> of data for the physicists under specific conditions if it is needed
> remotely to advise the facility on something like that, on
> cross-checking, however, it raises the question whether the physicist
> should be doing one back-up mode on the annual inspection, because
> there are many physicists that they will do only one.
>
> They will ask the facility, what do you use, and they will use
> contrast auto all the time, and they will evaluate the contrast auto,
> and that\'s it.
>
> If the contrast auto does not work, then, you don\'t have any data on
> the other mode, so you don\'t have a back mode, so the option is to
> either have an evaluation done there, and you can tell them go ahead,
> you can switch to the other mode, we have the data and your other
> modes would work.
>
> But the question is how do you know now that the other modes would
> work? If one mode doesn\'t, how can you assume that the other modes
> would work. In all fairness to the patient, we do not know. So,
> somebody has to do something at that point.
>
> Now, in the more real world, a technologist is going to tell me on the
> other side, I have been using contrast auto all the time, I am not
> going to switch now to select the kVp. With three or four
> technologists doing that, they are going to get all confused, so
> chances are they are going to tell me I am calling Service right now
> and we are stopping.
>
> I think they would be very unwilling to just go and do all kinds of
> things because they would be afraid that they would be doing the wrong
> thing.
>
> MS. MARTIN: I guess maybe I have got technologists that would have no
> problems with that. I think it strictly depends on the facility, and I
> think that has to be part of the medical physicist\'s understanding
> and agreement with that facility is when they are going to be called
> and what they allow the technologists to do.
>
> MS. HARVEY: Have we completed?
>
> DR. FINDER: I just want to clarify, in the fourth one, where I think
> we had already gone over this, about the testing of the 2, 4, and 6
> cm.
>
> I just want to clarify in my own mind the consensus or at least some
> of the comments were that you would test the 2, 4, and 6, but only at
> the submodes that were used at those levels. Is that correct?
>
> MS. MARTIN: That would be my interpretation. I think that is the
> suggestion, that is certainly the training the technologists are given
> when they are given their clinical training, that it is never
> suggested that they use the dose mode for a 2 cm fatty breast. That is
> part of any technologist\'s understanding is the appropriate mode to
> select for the type of breast being examined.
>
> DR. FINDER: Just again to clarify, let\'s say the contrast is used at
> the 2, and the standard was used at the 4, and then all of a sudden
> they wanted to use the standard at the 2, any additional testing
> required or no?
>
> MS. MARTIN: It would depend on whether it is a new unit or a
> reevaluation unit. If I have checked it at 4, and it crosses its
> contrast at 2 and 4, and the standard crosses at 4, if they want to
> shoot standard at 2 and the techniques are reasonable, it is probably
> going to work.
>
> It hasn\'t been my experience that that would necessarily be a
> problem.
>
> MS. HARVEY: Any other comments?
>
> DR. FINDER: I just wanted to check. Anybody from the FDA side have any
> questions that they would like asked, or any items? Speak now or
> forever hold your peace.
>
> MS. HARVEY: Or any other members of the audience?
>
> I refer you to the Modification Document No. 5, Guidance for Industry
> and FDA. There have been quite a few changes in this document, which
> has been out for a while now for use by individuals.
>
> DR. FINDER: I just want to again bring what this document represents.
> It basically took the guidance that we had already issued on these
> items, and what we are trying to do is update and modify what needs to
> be changed. So, that is why you are looking at a lot of issues that
> deal with the same type of topics, such as accreditation and
> certification.
>
> If anybody has any comments about the changes, these actually have
> already been published and are out to the public. They are up on our
> web site. If anybody has any items that they would like to discuss,
> now is a good time to do it.
>
> I would also mention that there is quite a long, new section dealing
> with full field digital units and their certification, and explaining
> what we are doing presently with those types of units.
>
> MS. HARVEY: Does anyone see anything? Yes, Dr. Pisano.
>
> DR. PISANO: I just wanted to talk a little bit about the digital
> requirement, the digital pages 32 through 37 or so, 40, I guess. This
> ties in with what I am going to talk about a little bit this
> afternoon, so I don\'t know if you want me to wait and talk then or
> you want me to talk now.
>
> MS. HARVEY: Well, give me a hint.
>
> DR. PISANO: There is a currently active clinical trial going on for
> which I am the PI, called the American College of Radiology Imaging or
> Digital Mammographic Imaging Screening Trial, otherwise known as
> D-MIST, and we actually have a fair amount of data at this point about
> what tests, you know, we have been doing the manufacturers\'
> recommendation as is required under MQSA, under this law, plus we have
> data on other tests, plus we have been doing it for quite a while. At
> this point, we have 19 open centers and the trial has been open since
> October of 2001.
>
> So, we have a lot of information, and I would encourage the FDA to
> move forward on kind of looking at the data that exists and trying to
> perhaps pare down the requirements over what is in the manufacturers\'
> documents or their user manual, whatever it is, whatever you want to
> call it.
>
> I am concerned about spending a lot of time doing tests because we
> have always done them on film, they may not be appropriate for
> digital, and it is just that time is money and if we don\'t need to do
> it, we probably shouldn\'t have to do it.
>
> The reason I bring this up, it is going to be presented publicly at
> RSNA, the Radiologic Site of North American meeting this November, and
> Martin Yaffe, out of the University of Toronto, is the PI of the
> quality control piece of the trial.
>
> I feel that once this presentation takes place, there is going to be
> more pressure on FDA to kind of respond and maybe cut down the
> requirements, so I would like to see us kind of be proactive. I want
> to echo what Ken Crocker said from Fischer this morning in his public
> announcement.
>
> I would like to see us kind of have more specifics kind of and
> detailed recommendations for QC for digital as opposed to just what
> the manufacturers recommend. I think there are many reasons. It is in
> the interest of patients, I think, just because of the amount of time
> that we spend doing it does cost the facilities money. It is obviously
> in the interests of the facilities and people like me who run
> facilities to kind of try to keep the requirements to a minimum.
>
> Understandably, they have kind of mushroomed into a big set of
> requirements because the companies just didn\'t want to leave anything
> out that the FDA might want them to put in, but I think we now have
> really kind of\--I am not prepared to discuss today in my talk what
> things should be cut out, but I know that we will have, you know, this
> thing hardly ever drifts or once in a blue moon drifts or never.
>
> So, I just want to encourage the FDA to kind of perhaps talk to ACR. I
> am talking about the American College of Radiology Imaging Network,
> not the ACR mammography presentation program, now there is two
> separate entities, about what is available, perhaps even to hear what
> Martin has to say before the talk in November.
>
> DR. FINDER: Yes, we would appreciate any access we could get to that
> information as soon as possible.
>
> DR. PISANO: There is actually a public meeting in Washington, D.C.
> Actually, it is in Arlington, Virginia, at the Ritz Carlton in
> Pentagon City in October of the American College of Radiology Imaging
> Network where I am sure we will all get a glimpse of the information.
> I can\'t say who is going to give a polished RSNA presentation at that
> meeting, but I am sure we are going to hear about this at that
> meeting.
>
> So, I will inquire of the ACR Imaging Network folks if you all can be
> invited to listen. It is a public meeting, so you certainly are
> welcome to come to the public sessions and perhaps meet with Martin
> there and the other physicists.
>
> All the physicists for all the sites will be present or at least they
> are all supposed to be present at that meeting, so I would expect a
> very useful amount of information, you know, you will be able to get a
> lot of interesting and useful information at that setting, so I would
> encourage you to attend.
>
> DR. FINDER: I do want to kind of put this into perspective. The
> regulations dealing with full field digital, when they were written,
> obviously, there weren\'t any digital units that have been approved
> yet. We took as has been stated before the conservative approach and
> said that without any data, we would rely on the manufacturer of the
> equipment to establish a quality control system that would be adequate
> for their unit.
>
> I think the idea has always been that as more information became
> available and the ability to kind of standardize the quality control
> for these units was developed, that that is what would happen, but
> until we get enough data available, it is going to be difficult and as
> we just heard, there is some data that is going to become available
> soon and as soon as it is, we are going to certainly want to take a
> look at it and see if we can progress along that frontier.
>
> Another issue that has to be kept in mind is that some of these
> digital units are quite different from each other and that the quality
> controls that might apply to one unit may not apply to another. That
> also is an issue and the ACRIN study will be dealing with a lot of
> different units and hopefully will be able to provide us with enough
> information, so that we can start formulating the ideas for a
> standardized quality control system.
>
> I am sure that this committee is going to be directly involved when
> that information becomes available and guiding us in terms of what we
> would require.
>
> DR. PISANO: Just to follow up on that point, we will have data from
> D-MIST, as you mentioned, for manufacturers, so we will be able to
> compare the need for different tests for each manufacturer, a very
> rigorous quality control program centrally monitored also, which is
> one of the strong features of it.
>
> It is a little stronger than what MQSA does because FDA\'s inspections
> are an annual snapshot of what happens. This is literally being
> monitored by central physicists every week, so we can watch for it
> because it is so important in the trial to be sure we have the highest
> quality images, because we don\'t want people to question our results
> at the end as has happened in other clinical trials.
>
> We want to really be sure, and so this is being monitored very, very
> carefully by physicists every week, so I feel that we are going to
> have about as comprehensive data on this topic as you can get.
>
> MS. HARVEY: Very good. Thank you.
>
> Dr. Karellas.
>
> DR. KARELLAS: There is no question that they did some mammography
> units very different from each other, and it will require different
> modules for physicists and technologists who are involved in that.
>
> I find it somewhat more difficult when I deal with the manual that
> comes from the manufacturers although it is welcome that they have
> that, but I believe medical physicists will find it a lot easier if
> they have to deal with modules from an accrediting body, such as the
> American College of Radiology, and I believe that it is a lot easier
> to communicate, a lot easier to ask a question.
>
> We can always call ACR for what we want or hopefully, they feel an
> obligation that they have to do it. Frankly, the companies are
> excellent and they will give you what you want.
>
> I find it somewhat more difficult to have to call each company to find
> each person, if I have a question or the particular book or the
> version, the accrediting body provides more of a centralized area that
> I can deal with, who feel absolutely obligated that they have to
> provide that information that I need.
>
> So, if we work in that direction, and if manufacturers cooperate to
> provide the information they feel that is very important, that their
> systems need to be tested on, and that can be worked into a document
> that parallels the existing ACR guidelines that we have.
>
> Let\'s not forget that quality in mammography, at least from the
> technical point of view, has been achieved to a large degree because
> of the uniformity that we are able to achieve in quality assurance
> through these manuals that radiologists, technologists, and physicists
> have, and we refer to them all the time.
>
> MS. HARVEY: Thank you.
>
> Any other areas for comments?
>
> DR. FINDER: If nobody else has any questions about the guidance
> document per se, there are some other guidance issues that have come
> up, I just wanted to bring them to the committee\'s attention.
>
> MS. HARVEY: Hold one second.
>
> Ms. Gilbert.
>
> MS. GILBERT: I do have a question. This is Alisa Gilbert.
>
> In the documentation here, under Breast Implants, I know that there is
> not a whole lot written in this, and for a lot of the native patients
> that I work with, this is a new procedure that is being offered now,
> but I also know that there is not a whole lot of information when it
> comes to following screening after that on the remaining breast or
> even doing mammography with implant or not even implant, but other
> types of procedures have been done on tram flaps or some information
> like that.
>
> I would like to see some documentation or additional information in
> this body written on that, as well, on the procedure and protocol that
> should be developed for that, just to include it. I know that it
> wasn\'t even included in this, it just said implant, but there is
> other procedures that are now being taken that haven\'t been.
>
> Walking into the procedure and asking for follow-up, it is completely
> an unknown, and I just think that that might be something that might
> be brought to the attention.
>
> DR. PISANO: Can I ask a question? I am a little confused about what
> you are talking about, and I just want a clarification. Are you
> talking about women who have had implants placed post-mastectomy for
> reconstruction purposes?
>
> MS. GILBERT: Yes, and the follow-up for that. I know that in here, it
> just says, on page 63, there is a question, \"Is there a specific
> amount of training or number of mammograms of breast implant patients
> that the technologist must perform under direction supervision prior
> to performing these studies?\"
>
> It is requiring that 40 hours initial training for that procedure.
>
> DR. PISANO: I just have another question. I am not sure what extra
> procedure you may be referring to for patients who are
> post-reconstruction. I am not exactly sure. You said there are new
> procedures being offered, and I am not sure what you are referring to.
>
> MS. GILBERT: I just see the notation here alternative requirements or
> breast implants. Implants aren\'t the only procedures that are being
> done for women that have received mastectomies, and I was just kind of
> interested to know if that is going to be something that is going to
> be another addition to this, for women that do have just like
> one\--maybe I am not posing my question or my concern clearly.
>
> DR. FINDER: I think at the time that these regulations were written,
> there were two major issues that were being discussed, and I think
> that the idea of the implants here was more the cosmetic implant use.
>
> I think you bring up a very good point about additional training for
> patients that have undergone surgery and the correct procedures on how
> to do those examinations.
>
> That is an issue we may be able to deal with in some way through
> guidance as a recommendation, but in terms of the regulations, what we
> have got is what we have got, but I do think that we do have the
> potential to expound a little bit on the guidance and deal with some
> of these other issues that you do bring up, and I think that is a
> possibility, and if not directly in our guidance, then, referring
> people to other sources where they can get the correct procedures to
> do some of these patients, so I think that is a very good idea.
>
> MR. GOODE: I am Claude Goode from the State of California.
>
> I would like to relate a horror story. I had a patient that complained
> of a breast compression that had an implant, and the compression
> ruptured the implant. The horror story was that the woman literally
> was screaming at the technologist to release her, and she would not
> release the compression. Evidently there was significant compression
> applied although the machine was within normal operating standards.
>
> This patient has been left to suffer. There were no basic regulations
> that we could enforce, and I do believe that there is a need for FDA
> or someone to at least come forth with some standards for the
> mammography of patients with breast implants. This needs to be
> discussed at length and in depth, and presented somehow for the
> technologists, the physician who is not present, and this does present
> a major problem.
>
> I would just like to relate that horror story.
>
> MS. HARVEY: Dr. Harrison.
>
> DR. HARRISON: Miles Harrison. May I ask a similar question? This is
> someone with breast implants for cosmetic purposes, this is not
> post-mastectomy?
>
> MR. GOODE: That is correct.
>
> MS. HARVEY: Dr. Ikeda.
>
> DR. IKEDA: This is Debra Ikeda from Stanford University.
>
> I think we are talking about two different things here, I would like
> to clarify. That is a terrible story. I would like to first address
> the question about the post-mastectomy patient and the tram flap
> patient.
>
> I think if I understand correctly, you were discussing patients who
> have undergone a mastectomy and have either had latissimus dorsi flap
> reconstruction or a tram flap reconstruction with autologous material
> from the abdomen, or patients, for example, who have a mastectomy and
> may have a small amount of residual tissue, and the recommendations
> for imaging that.
>
> There are various amounts of scientific literature for stating that
> either it is not recommended, for example, there are some articles in
> which patients have had mastectomies and then looked, they have tried
> to find out if there is a breast cancer recurrence, because that is
> what everybody is concerned about, and there is varying data on that.
>
> Many places state that you should not be doing those patients
> routinely for screening, but if there is a lump, then, special views
> are often used for that, and every patient is so different, that I am
> not really sure that if there is a problem, that you can actually say
> that this is the right view to do or that is. Oftentimes, we have to
> come up with special views to address that specific patient\'s
> problem.
>
> So, it is important when the technologist is initially trained in
> their 40 hours, for example, I think guidance is\--correct me if I am
> incorrect\--but guidance states that the technologist must learn all
> of the views, as well as patients who have implants, and they must be
> doing patients with implants under supervision, so they do them
> correctly.
>
> I think we are talking about two different things.
>
> DR. FINDER: Let me just correct one thing. The regulations do require
> that technologists who qualify under the final regulations have some
> training in doing patients with breast implants. There is no
> requirement that they have to do a number of breast implant patients,
> though.
>
> DR. HARRISON: I am in complete agreement with Dr. Ikeda, we are
> clearly talking about two separate populations here, and actually, the
> standard of care in our setting is such that we don\'t do imaging
> routinely of people post mastectomy with either autologous
> reconstruction or implants.
>
> I guess I need to ask the question, are you referring to the training
> of the technologist to, in fact, be able to do mammography on women
> who have had cosmetic breast implants, are you addressing the
> training?
>
> MS. GILBERT: I guess I am addressing both. I know in the native
> population, like Alaska Native specifically, that follow-up isn\'t
> recommended after that.
>
> DR. HARRISON: Follow-up is not recommended?
>
> MS. GILBERT: It\'s just unknown, it is just one of those unknown
> procedures, and because of these procedures, it really is now, just in
> the last year, that it is being offered for native patients to have
> the reconstruction services and those provisions.
>
> I know that there is just not a whole lot of clarity when it comes to
> that, in that specific population.
>
> DR. HARRISON: It is very cloudy, because presumably, in that setting,
> in that clinical setting, you have retained all the natural breast
> tissue, you simply have implants placed, so that is someone who
> clearly would need to continue to be screened age specific. I am still
> confused.
>
> MS. HARVEY: Dr. Kopans.
>
> DR. KOPANS: Dan Kopans, Boston, Massachusetts.
>
> I just wanted to reinforce what you just said, Dr. Harrison, that the
> standard of care is to not do routine mammographic imaging of women
> who have had mastectomies on the mastectomy side.
>
> There are only two papers that I am aware of looking at women who have
> had tram flaps, and there is some debate about whether it is valuable
> when they have had trams, but women who have implants on the
> mastectomy side, if it has been a simple mastectomy or modified
> radical mastectomy, there are no data supporting doing mammography of
> the implant side.
>
> As I recall, in the discussions years ago about implants, as Dr.
> Finder was pointing out, really, the implant discussion had to do with
> augmentation, and not reconstruction.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: I just want to make a comment in reference to the story
> from California. I think that was obviously, a tragic event, and
> horrible thing for the patient, but I feel like there really is a lot
> of guidance from professional societies both for technologists and
> radiologists, and probably physicists, too, about the imaging of
> breast implants.
>
> This particular technologist obviously made an error, it sounds like
> to me from the story, but without knowing more about it, it is hard to
> be sure, but I don\'t think we should leap from one story to we need
> stronger regulatory oversight on this particular issue.
>
> There is actually a fair amount of information out there for
> technologists and radiologists already for implants for cosmetic
> purposes, and the same, in my opinion, goes for the issue of the
> reconstructed breast. There is a lot of information out there.
>
> We teach people what Dan and Debbie have already said, which is that
> you should not be imaging these people routinely after a mastectomy.
> It is too confusing and we find more false positives than negatives,
> so I feel like the regulatory guidance is sufficient, as written,
> myself.
>
> DR. HARRISON: Last comment. As many of you know, in the situation with
> mastectomies, you can have upwards of 5 to 6 percent of breast tissue
> still there after mastectomy, so that imaging of those areas, if there
> are clinical concerns, as has been pointed out, is specific.
>
> Very clearly, if something is palpated, if there is concern about
> those areas, those areas can be imaged, but routine imaging is not
> expected.
>
> DR. IKEDA: I agree and I think that if the patient has a problem that
> is a medical decision and it is a physician decision with the patient
> rather than I think something that should be seen by regulatory
> oversight.
>
> I think there is plenty about imaging the breast with FDA regulations.
>
> MS. HARVEY: Any more comments about that?
>
> DR. FINDER: If we are finished with comments about Modification
> Document No. 5, there are some issues that have come up recently
> referable to use of assessment categories, and I just wanted to kind
> of bring up the issue before the committee because I understand that
> the BIRADS Committee, the people that came up with assessment
> categories many years ago and which we have basically pretty much
> adopted into our regulations, is reviewing the current use of the
> assessment categories.
>
> I just want to bring up some issues that we have become aware of
> referable to this. Obviously, the idea behind the use of assessment
> categories was to get some standardization into the medical report, so
> that anybody who is reading these reports would have a pretty good
> idea of what was going on.
>
> I am sure that radiologists on the panel can tell you about the two-
> and three-, and four-page reports that used to be issued, and by the
> time you finished reading them, you didn\'t know where you were or
> what anybody was trying to say.
>
> In order to alleviate that problem, the use of assessment categories
> was mandated. Right now there are basically six assessment categories
> that can be used in the reports, and my understanding is, is that the
> BIRADS is looking at some of these because we have encountered
> situations where one of these assessment categories may not apply in
> some of the areas that we have been aware of. For example, people have
> raised concerns about using the currently allowed assessment
> categories when you are evaluating a postoperative breast.
>
> There really is no great assessment category that fits that type of a
> situation. It is kind of hard to say that a patient that has just been
> diagnosed with breast cancer has a negative or a benign looking breast
> when you know that they have got a diagnosis of malignancy.
>
> Other situations that have caused some concern are dealing with the
> male breast. Not a lot of patients get these, not a lot of male
> patients end up getting mammography, but when they do, they are also
> covered under the regulations, and their reports also require an
> assessment category.
>
> Other areas of concern that we have heard from the community deal with
> the use of the incomplete assessment category for situations where
> they are waiting for comparison films. Again, no great way to define
> it in terms of the current assessment categories.
>
> Other issues deal with Assessment Category 3 are probably benign. Some
> people don\'t like the recommendation that follows in BIRADS where all
> probably benign lesions are supposed to have a recommendation of
> follow up rather than in some cases where they want to recommend
> biopsy.
>
> Now, that is not a problem for the MQSA regulations because we don\'t
> tie our recommendations directly to the assessment categories, but
> that is an issue that we keep hearing about.
>
> Another issue that has come up deals with the possibility of using
> multiple assessment categories. In our requirement that if you are
> going to do that, let\'s say you have two or three lesions on the
> mammogram, you have to assign an overall assessment category, which is
> based on the worst situation.
>
> The theory behind that or the thinking behind that was that we had
> situations where there were multiple lesions on the mammogram, the
> report discussed all of them. Unfortunately, they discussed the benign
> ones first and buried the malignant one in the middle of everything,
> and they were missed.
>
> So, the idea here was to require an overall assessment category that
> was the worst one, so that people would know not to miss the cancer.
>
> Every solution creates its own problems, and there is at least a
> theoretical possibility under our system where you have to list one as
> the overall assessment category. Let\'s say there is a suspicious
> lesion and there is one that requires additional workup and
> incomplete.
>
> If you only have one assessment category, the overall assessment
> category of the suspicious one, is it possible that somebody will
> forget about the other one that needs further evaluation.
>
> So, these are some of the issues that we have encountered. We would
> like the committee\'s discussion on this a little bit, taking into
> account that the BIRADS group is looking at modifying their assessment
> categories to deal with some of these issues.
>
> DR. IKEDA: The first issue of the patient with the known cancer can be
> an issue for the current BIRADS codes in that the way that cancer is
> being treated now is much different than it was even five years ago.
> For example, a patient who has a 5 cm breast cancer in the past would
> get a mastectomy, whereas, now many of these patients are getting
> neoadjuvant chemotherapy.
>
> For those of you unfamiliar with this, this is the patient gets
> chemotherapy before the tumor is removed, and so the reason for
> imaging and for doing the chemotherapy is to watch the tumor shrink,
> so, for example, the patient may have a mammogram with a suspicious
> tumor, gets a BIRADS 5, highly suggestive of malignancy.
>
> Six months later, after four rounds of chemotherapy or three rounds of
> chemotherapy, what the oncologist wants to know is has the tumor
> shrunk.
>
> They know there is a cancer there, for example, and so we are in the
> unfortunate position of saying yes, there is a tumor there, and then
> they get another BIRADS 5 suspicious for malignancy, and everybody
> knows it is there.
>
> I think that there was movement afoot of perhaps adding another code,
> BIRAD 6, known cancer present, to address this and to reflect the
> changing of how breast cancer is being treated, and so that these
> patients aren\'t being scared to death with a letter saying, hey,
> there is a cancer, they think they have a new cancer, and then they
> are frightened, and that\'s horrible.
>
> I think that that would be something reasonable if that was approved
> by the BIRADS Committee.
>
> MS. HARVEY: Ms. Pura.
>
> MS. PURA: Linda Pura.
>
> Dr. Finder, I concur with you on the Category Zero, not only is the
> client who is very confused and very scared, but our primary care
> clinicians also interpret this in very strange ways, so I would like
> to ask for a clarification on Category Zero on the BIRAD scale.
>
> DR. PISANO: I guess I can provide it. Category Zero is intended to be,
> at least when a patient is in the process of being worked up. It is
> not intended to be the final assessment category.
>
> So, we, at UNC, only use it when we do screening mammography to say we
> read our screens in batches and we interpret them. Basically, the
> patients either get a zero or a 1 or a 2. That is just the way we have
> decided to do it, and I am sure this varies from some people use 4\'s
> and 5\'s in the screening setting, too, but we actually bring
> everybody back in for the complete workup, make sure they didn\'t have
> a biopsy there causing the spiculated mass, for example, talking to
> them one on one.
>
> So, I think in most settings, zero means we still have to do more
> tests before we are sure whether something needs a biopsy or not, but
> perhaps it is being used differently than that in some centers, I
> don\'t know.
>
> MS. HARVEY: Dr. Kopans.
>
> DR. KOPANS: I am on the BIRADS Committee and there is discussion about
> Category Zero in terms of use if someone is waiting for old films. I
> think it is going to come out that that is an inappropriate use of
> Category Zero. As Dr. Pisano just said, the categories were set up to
> you are evaluating the study now and what is your final assessment
> now.
>
> If you need additional evaluation, that is a Category Zero. If you are
> waiting for old films, you interpret the study as if you don\'t have
> the old films, and Category Zero therefore is not appropriate unless
> there is something that needs additional evaluation.
>
> So, the people who are saying they don\'t know how to use it, they are
> not using it properly if they are using Category Zero that way.
>
> MS. HARVEY: Thank you.
>
> Yes, Dr. Pisano.
>
> DR. PISANO: I just want to make another comment about it. In our
> center, it is sometimes difficult because the two breasts have
> different assessment categories, and we are supposed to dictate one
> final assessment category, and we have been cited actually on
> inspection, because we put this is a 5 on the right breast and a 3 on
> the left breast.
>
> In fact, that is kind of a good communication skill. When you were
> talking before about burying information in the report, we would like
> the final word on each breast to be in the conclusion. You know, you
> don\'t want them to forget about the 3 in the other breast, the one
> that has to be followed in six months just because you found a cancer
> in the other breast.
>
> So, I would like to see some flexibility about that built into the
> advice to clinicians, and I am looking forward to the new BIRAD scale
> because we do have all these other problems you have mentioned.
>
> DR. FINDER: The issue that you bring up has been brought up before
> about the use of assessment categories for each breast. That kind of
> shifts the problem down one level because if you still have two
> lesions in one breast, you still have the same issue.
>
> The question really I guess is, is should these assessment categories
> be for each lesion rather than overall, and if so, it would require a
> change in the regulations obviously or at least our implementation of
> them, but as I said, we did have the situation where multiple lesions
> were identified this way, and unfortunately, the malignant one was
> buried in the middle of a whole bunch of other benign processes.
>
> It is one of those things where no matter what you do, you create
> another problem somewhere else.
>
> MS. HARVEY: Dr. Kopans.
>
> DR. KOPANS: The issue again I think of multiple assessment categories,
> the report is still there, and every physician is supposed to read the
> entire report, not just the final assessment categories. The final
> assessment category is supposed to be a summary, and I think the
> BIRADS Committee would come down on the fact that it is the most
> important, which is what Dr. Finder already said.
>
> If you are just going to repeat the whole report in the assessment
> categories, it becomes a little redundant and silly, I think.
>
> DR. FINDER: Dr. Kopans, what is your feeling or do you know what the
> BIRADS group is thinking about in terms of assessment categories for
> each breast?
>
> DR. KOPANS: To be honest, I hadn\'t actually heard that as an issue.
> It may be, they are reviewing a whole bunch of things at this point.
> Again, BIRADS was designed to simplify the report, and the issue of
> what BIRADS does versus what the FDA requires, I suspect probably are
> two different things.
>
> I don\'t think that the committee is going to change to an assessment
> for each breast, but I don\'t think that has been decided.
>
> DR. PISANO: When I made my comment, I was really referring to FDA
> regulations because the BIRADS Committee, I don\'t think anybody from
> ACR would object if, in the interest of clarity, you said in your
> conclusion, you know, there is a cancer in the right breast, but there
> is also something in the left breast that needs to be followed at six
> months, it is probably benign.
>
> That just fits the way we do mammography, and I agree with Dan in
> reading the whole report, but sometimes you do need to call out the
> most important information. I am concerned because we were cited
> because we did that at an FDA inspection, so I feel like that is good
> medicine to bring out the most salient points in the conclusion, and
> yet if it conflicts with\--we actually had to change our practice, so
> we didn\'t put it in our conclusion, which seems kind of silly to me.
>
> DR. FINDER: Let me just talk about that a little bit. We do have
> guidance actually that addresses the issue of the calling or labeling
> each breast with its own assessment category. It is allowed under the
> regulations, but what we also say is if you are going to do that,
> then, you have to have one overall assessment category.
>
> But you certainly are free under the regulations to do it that way,
> but if you are, then, you have to have one overall assessment
> category. That is the way the regulations are pretty much written and
> interpreted.
>
> One thing I do want to mention is one of the reasons we came up to
> that conclusion didn\'t have to do so much with the assessment
> categories as the fact that at least in the beginning, there were
> facilities that when they divided the reports up into right and left
> breast, they were counting those as two studies, and they were using
> those to meet continuing and initial requirements by dividing up the
> mammogram into two studies that way.
>
> So, in order to stop that, we said that it is per patient, not by
> breast, and that is how we ended up where we were with the assessment
> category, so it all ties into that. There usually is a method to how
> we come up with these things.
>
> DR. KOPANS: Another way of working around this if there are multiple
> final assessments that are important, you can put just before the FDA
> statement, \"Please note there are multiple important findings, the
> most significant is,\" and then the\--
>
> DR. FINDER: Right. There is a lot of flexibility in terms of what the
> report can contain and how you write it. We don\'t mandate the makeup
> or the format of the report, but what we do say is there has to be an
> overall assessment category. That is the one thing that we pretty much
> do require.
>
> MS. HARVEY: Thank you.
>
> Any more comments? Yes, Dr. Ikeda.
>
> DR. IKEDA: I am a little concerned about adding a second assessment
> for the second breast. I am concerned about missing the most\--I
> thought the intention of FDA was that the most suspicious finding not
> be missed and be acted upon, and so if you have, instead of 10,000
> reports, you have 20,000 going out, I am concerned about that patient
> having her cancer missed.
>
> So, as far as the regulatory recommendation, I know that you can put
> down the multiple assessments, but I think the overall assessment for
> the one patient is a good idea and to keep it simple, so she gets
> treated for her cancer.
>
> MS. HARVEY: Dr. Young.
>
> DR. YOUNG: Don Young. I would emphasize that also. I still have
> referring physicians call me and say what do you mean by \"probably
> benign.\" Adding another layer, assessment layer or two or three is
> going to confuse the patients and the referring physicians.
>
> We cover these things in the body of the report, as has been brought
> out earlier, and you can phrase your report in such a way that it
> mandates see above, paragraph 2, if you get into two paragraphs. I try
> to avoid two paragraphs.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: Actually, it may be my suggestion was being interpreted
> differently than what I was really suggesting. I am not suggesting
> that we increase the number of requirements in the conclusion.
>
> I am suggesting that we not be cited if we do mention the opposite
> breast in the conclusion besides the one with the most suspicious
> finding. I mean that is what we were cited for, and I wish that the
> guidelines to the inspectors would be clearer, that it is allowed to
> use what you just said, Charlie, a few minutes ago, about the report
> has some flexibility.
>
> I feel like we should have some purview over good clinical practice in
> this area. There are times when you know the referring physician, you
> know how they read their reports. You know that you need to emphasize
> both things, and I feel like that is a doctor\'s decision, we
> shouldn\'t be told not to do it if it\'s good clinical practice.
>
> So, that is the point I was making, not that we should start doing it
> on every one, that is the last thing I want is more paperwork and more
> time spent by me. I want the ability to do it if I have to.
>
> MS. HARVEY: Any other comments? No? Thank you.
>
> I think we have come to a natural stopping point for lunch. We will
> return at 1 o\'clock. Thank you.
>
> \[Whereupon, at 11:45 a.m., the proceedings were recessed, to be
> resumed at 1:00 p.m.\]
>
> AFTERNOON PROCEEDINGS
>
> \[1:00 p.m.\]
>
> MS. HARVEY: Dr. Finder will speak first on our topic of Full Field
> Digital Mammography.
>
> DR. FINDER: I just wanted to expound a little bit about some of the
> things that were said earlier this morning about the way that full
> field digital units are currently handled and the need to have them
> hooked up to a film-screen unit.
>
> Just to give you a little bit of background and history on how we
> ended up where we are, when the first full field digital unit was
> approved by FDA for commercial use in early 2000, there was no
> accreditation body that existed in order to accredit those units.
>
> Now, we deal under the Mammography Quality Standards Act, and that Act
> requires that these units be or that the facility be accredited and
> certified. The only way we could handle this under the situation was
> to tie a full field digital unit to an otherwise already accredited
> and certified film-screen unit.
>
> That is the way that we have been handling it in the interim until an
> accreditation body is approved. It is not the optimal situation, but
> in addition to keeping us compliant with the law, it also gives us
> some assurance that the people that are involved with the full field
> digital unit also have some experience with film-screen and are
> capable of becoming fully accredited with the film-screen unit, so
> that does give us a sense of security for these people to use the FFDM
> unit.
>
> So, as has been stated in the morning, yes, we do require that
> currently, because there is no accreditation body out there, that if a
> facility wants to have a full field digital unit, it in some manner
> has to be tied to an accredited and certified film-screen unit.
>
> In order to make this as viable as possible, we have expanded out our
> ability to tie that unit to another facility, and has been stated in
> the morning, it isn\'t necessary for the two units to be actually
> physically in the same place. We have allowed some leeway there.
>
> The alternative, if we didn\'t do this, was basically to say that
> since there is no accreditation body and no other method to deal with
> this, that you can\'t use it at all, and we didn\'t find that to be
> acceptable, so we came up with this method that kept us within the
> legal constraints, also gives assurance that the people that were
> using this were capable of otherwise accrediting or capable of
> performing quality that would get them accredited for their
> film-screen unit.
>
> So, I just wanted to clarify that before we go on any further.
>
> MS. HARVEY: Thank you.
>
> Our next presentation this afternoon is Dr. Etta Pisano. She is going
> to talk to us about the ACRIN Trial of Full Field Digital Mammography.
>
> Dr. Pisano.
>
> **ACRIN Trial of Full Field Digital Mammography**
>
> DR. PISANO: Thank you.
>
> \[Slide.\]
>
> As I mentioned earlier, the National Cancer Institute has funded a
> trial, which is a screening trial for asymptomatic women, through the
> American College of Radiology Imaging Network, which some of you may
> or may not know is a new cooperative group.
>
> The trial is slated to cost about \$27.5 million. It is supposed to
> last three years total, and it is underway as of last October.
>
> \[Slide.\]
>
> A screening trial, as I mentioned, is one for asymptomatic women,
> women who do not have lumps or discharge, women who would normally
> present to the centers where the trial is open for screening
> mammography.
>
> \[Slide.\]
>
> Women undergo both digital and film mammography as part of the trial,
> and then the images, the screen-film mammogram, and the digital
> mammogram, all four views, of course, the same standard four views are
> taken for each exam are read independently, so that one reader reads
> the film exam and another reader reads the digital exam.
>
> The same reader does not read all the film exams, and the same reader
> does not read all the digital exams. The readers are split evenly
> between the two conditions, so that if you are reading on patient A,
> reader 1 will read the film and reader 2 will read the digital, and
> then for patient B, they read in the opposite conditions across all
> the images acquired at their site, so that it should be about evenly
> split across all the readers at the site.
>
> There are a variable number of readers at the different sites. Some
> sites only have two readers and some sites have as many as five to
> seven readers. It depends on the number of people that are qualified
> to read digital mammograms.
>
> If one exam is positive, the patient undergoes a workup for that exam.
> If both exams are positive in the same area that the workup occurs,
> and if they are positive in different areas, workup occurs for all
> lesions found no matter whether both exams are positive whether only
> one exam is positive, and workup occurs as per usual clinical
> protocols meaning if normally at that site, additional views and
> ultrasound are obtained after a positive mammogram, that is what will
> happen after the positive film and/or digital mammogram.
>
> A negative mammogram is treated the same way a negative mammogram is
> treated in any practice with routine imaging and clinical follow-up,
> meaning at a year for this study.
>
> We do not have a lower bound for age, we don\'t have an upper or a
> lower bound for age. We are allowing the sites to determine which
> patients they normally screen, so if a site starts screening at 35,
> the woman is eligible for screening at that site, then, she is
> eligible for the trial.
>
> Some sites don\'t open their screening to women until they are 40.
> Some women vary the first age of screening with risk, so some women
> are eligible to be screened starting at 25. If they would normally be
> screened at that site, then, they are eligible for the trial.
>
> \[Slide.\]
>
> Our outcome measures are going to be\--obviously, we don\'t have these
> yet\--are going to be ROC, assessment of the two technologies with the
> primary outcome measure being area under the ROC curve, which reflects
> both sensitivity and specificity.
>
> We are also going to measure positive and negative predictive values.
> We are both going to perform an assessment of digital mammography as a
> modality and for each individual manufacturer, because we can do that.
> We are going to have lots of patients in each condition.
>
> \[Slide.\]
>
> I mentioned this already. It is consecutive women. All women are
> approached, not all participate, of course.
>
> \[Slide.\]
>
> The total numbers are somewhat staggering - 49,500 women over a
> two-year period will be enrolled.
>
> I mentioned the trial will last for three years. That is because we
> had to build in a year of follow-up. At this point, there are 19
> centers open to accrual. Actually, this week we are opening our 20th
> center. There are 29 centers that are in the process of becoming open,
> in other words, nine more still waiting to be opened.
>
> We have 6 to 11 centers for each digital mammography manufacturer that
> has equipment available to be tested at this point. Trex is a
> subdivision of Lorad, so I have Trex there, but you can substitute
> Lorad for that.
>
> \[Slide.\]
>
> These are the names of the sites. These are for the Fischer equipment.
>
> There are a few minor changes on my slides compared to what is in the
> handout. That is because I sent it in a couple weeks ago and then I
> found some errors. So, what is up on these slides is correct, so if
> you notice changes, that is why they are changed, is because I
> corrected my slides after I sent it in.
>
> So, these are the Fischer sites, and you can see that we have a
> variety of types of sites. We have academic practices. This is a
> private practice here in D.C., Washington Radiology Associates, as
> this is LaGrange Hospital in Chicago.
>
> \[Slide.\]
>
> These are the Fuji sites. Mainly, these are academic sites, these are
> all academic sites.
>
> \[Slide.\]
>
> The GE sites. We have more GE sites than any other machine type,
> primarily because GE was the first machine type that was FDA approved,
> so we do have more machines in that category than in any other
> category.
>
> Originally, when we first opened the trial, we envisioned balancing by
> machine type, but we quickly realized that we needed more patients
> than we thought we were going to need\--well, the same number of
> patients, but we couldn\'t get as many patients per site as we were
> hoping to get, as quickly as possible, so we added sites, and so we
> ended up with this unbalanced per-machine type.
>
> \[Slide.\]
>
> These are the Lorad sites. Here is the private group, Monmouth
> Hospital in New Jersey. I think there were several in the GE sites
> that are private groups, as well, so we do have a range of types of
> settings.
>
> \[Slide.\]
>
> There will be 1,800-plus women enrolled at each center. It is going to
> vary, of course, from center to center, because our goal is to accrue
> for two years, and some of the sites don\'t even come open until after
> a year. We started out with the idea that we would have 19 or 20 sites
> and that there would be about 4 or 5 per machine type.
>
> We quickly realized that the sites could not enroll at the rate we
> were hoping, so we then added another 10 sites, so that we are in the
> process of adding those extra sites right now. So, the numbers in
> terms of per-machine or per-site is a little bit flexible.
>
> Some sites, the ones that came up early, will have higher numbers,
> some sites, the ones that came up later, will have lower numbers per
> site, so we are going to hope to accrue the 49,500 women in a two-year
> period.
>
> When we first opened, we thought we could do it in 18 months, so we
> have had two adjustments made just from the realities of accruing this
> many patients per day. It was supposed to be 6 to 8 women per day
> getting two kinds of mammograms. You can do the math and you can
> figure out how hard that would be for sites.
>
> They are doing it, they are doing quite well, but it is a lot more
> challenging than we originally thought. The interpretations are the
> least of it, getting consent, filling in forms, all the things that go
> with running a clinical trial, it is very, very labor intensive, so we
> have adjusted very rapidly to this information that sites are not able
> to accrue as fast as we had hoped they would.
>
> So, this is the current plan, which is two years of accrual. We
> started in October of 2001. We are hoping to stop accrual in October
> of 2003, more than a year from now. After that, we will have a year of
> follow-up, which you must have a year of follow-up for negative
> mammograms, at least a year, to declare the patient cancer free.
>
> In fact, probably that could be debated. You might need as much as
> three or four years to really know a patient didn\'t have cancer when
> she had her mammogram, but for purposes of this study, we are defining
> a woman\'s mammogram as a true negative after one year of follow-up if
> she does not have a diagnosis of cancer. Actually, the exact range for
> follow-up is 10 to 15 months.
>
> So, if a woman presents within 15 months of that mammogram, the entry
> mammogram with the cancer, we will consider the original mammogram a
> false negative. I should say\--I didn\'t make that quite clear.
>
> Anytime up to 15 months, the 10-month period is when we must have, we
> are mandating a follow-up mammogram of some sort. The earliest after
> the original mammogram that can count as being appropriate is at 10
> months.
>
> \[Slide.\]
>
> Patients are excluded if they have a lump or they have a bloody or
> clear nipple discharge. If they have implants, they are excluded.
>
> Implants require extra views of the breast, and we didn\'t think it
> was appropriate to include them because they would require four views
> per breast times 2, so a lot of images, and we thought it was too much
> radiation and we wouldn\'t have enough numbers in that category to
> really get statistical validity or statistical power, so we excluded
> them rather than including them.
>
> Anyone who is pregnant or thinks she may be pregnant or if a woman
> can\'t undergo follow-up mammography. We are not requiring that they
> come back to the same institutions for their follow-up mammograms
> because we wanted to open the trial to as many people as we could, but
> they at least have to provide the follow-up mammograms for review by
> study radiologists.
>
> \[Slide.\]
>
> As I mentioned, we are doing two standard views of each breast, and
> there is some tiling needed sometimes, women sometimes have larger
> breasts and the detector size for films and for digital, so if a woman
> is too large for the detector, for just one view in each projection,
> she might have to have inners and outers, uppers and lowers, just as
> we do with film mammography in standard practice right now, and the
> same technologist does both exams, and so she is supposed to do both
> exams the same way.
>
> If she has done inners and outers on the film, she will do inners and
> outers on the digital. We are not doing any extra diagnostic views
> during the screening part of the trial. You can do diagnostic workup
> with the digital system if it is FDA approved, but some of the systems
> are not, at least one of the systems now, just the Fuji system, is not
> yet FDA approved, so they cannot do diagnostic workup using a
> non-FDA-approved system.
>
> In addition, there are no extra views done during the screening study.
> That is just not what a screening study is. So, we are studying just
> the screening exam in this study.
>
> \[Slide.\]
>
> I mentioned that the technologist is the same. She has to be eligible
> to take mammograms under MQSA. She is supposed to be using the same
> degree of compression and the same angle with both systems. That is
> definitely the case for the Fuji systems since it is an image plate
> system where the film is just replaced with the plate.
>
> It is more challenging when you have to move the patient between
> rooms, but they are supposed to try to replicate the exams as much as
> possible.
>
> In addition, we are randomizing the order of acquisition. We were
> worried about the technologist being able to kind of tweak her
> technique a little, if she saw the film mammogram, she always did the
> film first and then did the digital, she would then know that it was a
> dense-breasted woman or something about the patient, the way she
> compressed or something, and make the other exam better.
>
> So, that is why we are randomizing the order of acquisition. That is
> assigned centrally. When you register the patient for the study, you
> are assigned a randomization, so you either perform digital first or
> film first for all 49,500 women in the study, that will happen.
>
> We are trying to standardize the dose between the two systems and if
> the AEC is available, try to use it in the same manner for both
> systems.
>
> \[Slide.\]
>
> As I mentioned, there are two radiologists per patient, one to
> interpret each exam, one for digital, one for screen-film. They are
> not supposed to talk to each other. They are not supposed to be aware
> of each other\'s interpretation.
>
> We have been careful at the sites to take any little hints they might
> get about what the other person thought. Every place has their own way
> of making sure the patients are called and so we have to inform them
> if they have a positive mammogram. We have to pay a lot of attention
> to that.
>
> We go there to make sure that the second radiologist can\'t figure out
> what the first thought. We have no fellows or residents in the room
> during the interpretation of these exams.
>
> They are certainly free to be taught on the images after the
> interpretations are completed, but not until then, not until the
> radiologist has entered his or her final interpretation, because we
> were afraid of increasing the sensitivity of the study if even a
> second person was reading, we don\'t want that to happen across the
> study, so it is just reader for the final reading for each set of
> images.
>
> \[Slide.\]
>
> As I mentioned, we are splitting the radiologists. I am a reader for
> this study, so I am reading equally in film and digital, as is every
> other reader. We started out with a requirement that there would only
> be five readers per site, and we soon found, because of people
> retiring and quitting, and doing all the other things, that we
> couldn\'t stick with this requirement, so this has been dropped, there
> is no more than five readers allowed at each site.
>
> We have an executive committee that meets weekly by conference call,
> and it consists of myself, Ed Hendrick, who is the co-PI of the study,
> and four radiologists, who are one for each machine type, who has
> experience with each machine type, plus the ACR personnel, plus Martin
> Yaffe, who runs our QC program for this.
>
> We meet weekly and we discuss issues such as this, and five readers,
> it soon became apparent that some of the sites started with five
> readers and then lost people, and we didn\'t lost penalize them, so we
> now require that all readers read equally in each condition, and we
> try to have every reader read more than 50 mammograms, which even that
> is difficult to definitely require because of the fact that we have
> had people start reading and say I can\'t stand doing this, I am not
> doing it anymore, and so you can\'t really penalize the site, you
> can\'t throw those patients out because a reader only wanted to read
> 20 cases, so we are keeping those readings in the study.
>
> \[Slide.\]
>
> I mentioned already that we have no trainees, just MQSA-qualified or
> would be, some are Canadians, so would be qualified if they were
> living in this country, or practicing in this country, physicians.
>
> We enter all data on-line, into a web site, where the data forms are
> kept, so it\'s on-line data entry for a lot of the data of the trial.
>
> There also are worksheets that radiologists can fill out because you
> can imagine. I am a busy person, I don\'t want to sit there at the
> computer all day entering data, so we have forms that a person can
> fill out, instead of going on line and entering directly themselves,
> and then it can be entered later by someone.
>
> You can enter on line, but you have some flexibility about that. As I
> mentioned, if either exam is abnormal, the workup should take place
> according to the standard clinical protocols, and even if only one
> exam is abnormal, even if you think the other exam kind of clears the
> first exam, you are supposed to work up the lesion, because, you know,
> you might be interpreting the digital mammogram differently or the
> film mammogram differently given the first study. So, it is best to
> just go ahead as if it is a regular clinical workup on that patient,
> not refer to the other exam.
>
> \[Slide.\]
>
> We use usual equipment and practices at the different sites. At most,
> especially when we first opened the trial, most of the cases were
> worked up with screen-film mammography, but as I mentioned, as they
> become FDA approved, we have allowed people to be worked up with
> digital mammography. Often senographe is used. Some sites are using
> MRI and other imaging tests.
>
> We are keeping track of all the downstream costs of the positive
> exams, and of course, biopsy is one of the most important outcome
> measures of the trial. That is how we find out who has cancer or not
> for the positive mammograms, the BIRADS 4 and 5 lesions.
>
> \[Slide.\]
>
> I already mentioned this. You can consult widely with other experts if
> that is your normal clinical practice for the workup. We don\'t
> control the workup at the sites, so that if you want to show it to
> three or four other radiologists before you make a decision to biopsy,
> if that is your normal clinical practice, that is not controlled in
> the protocol. We want to know the truth about these patients, so we
> are allowing people to do whatever they normally do, and that might
> include consultation with many others.
>
> \[Slide.\]
>
> We use the standard BIRAD scale, but that is not the scale we are
> using for the primary outcome measure in the trial. We are collecting
> that for every patient for both digital and film.
>
> We are also collecting the probability of malignancy on a 7-point
> scale\--I think I have it up in the next few slides\--and a call-back
> scale, which is the probability that you think that the patient needs
> to be called back with, how worried are you basically.
>
> \[Slide.\]
>
> Here is the probability of malignancy scale. It is just words, as you
> can see. We also ask for the actual percent probability of malignancy
> as a separate item, which I don\'t know what good that is going to do
> us for sure, but we definitely have collected that. There was a lot of
> discussion of whether we just use the 7-point scale or the 100-point
> scale. We are collecting both.
>
> This is the scale that you must choose on every single patient, you
> must give one of these 7 points. You give it for individual findings,
> and then you do it for the overall assessment, similar to what FDA
> requires, so you are supposed to classify each individual finding and
> then classify the whole mammogram.
>
> So, this is the scale for that, definitely not malignant, all the way
> to definitely malignant. You can see there are gradations in between.
>
> \[Slide.\]
>
> The call-back scale is a similar idea. We are trying to get an idea of
> the level of uncertainty that radiologists have in deciding whether
> the patient should come back or not.
>
> So, you might call something BIRADS 1\--I am just making this up, I am
> not thinking of a particular case\--you might decide to call something
> BIRADS 1 or maybe 2, but you think to yourself, well, maybe there is
> some evidence the patient should be called back for diagnostic workup,
> but I am not going to call them back, I think it is below my
> threshold, so you might give that a 2.
>
> In other words, you are noting there is something there, but something
> that is below your threshold. The only things you have to give more
> information on is the things you actually do call back.
>
> So, you can see all the way down from no evidence to overwhelming
> evidence the patient should be called back.
>
> \[Slide.\]
>
> We have, of course, follow-up, because that will help us determine
> truth about the vast majority of patients who have negative
> mammograms. Patients are supposed to keep in touch with us.
>
> We have a system where we are sending out newsletters and keeping in
> touch with the patients. The local sites have the contact information
> for the patients, and they can contact the patients by phone and mail.
>
> Obviously, we would like them to all come in for follow-up
> mammography. If they don\'t come in, we have a way of calling them and
> finding out whether they have been diagnosed with breast cancer or
> not.
>
> In addition, we plan, for the patients who are lost to follow-up, make
> sure we check their medical record at the hospital where they are
> imaged and search tumor registries, and things like that. I am hoping
> we don\'t have huge numbers of women lost to follow-up because it is
> included in the consent form that we expect them to come back in a
> year and we are doing our best to keep up with them, but some women
> will be lost to follow-up, of course.
>
> We are going to code follow-up information on the mammograms. We need
> to know whether there are new findings on the follow-up mammogram.
> Basically, we are going to collect the BIRAD status on the follow-up
> mammograms primarily because that will help us determine the truth
> about that first year\'s mammogram.
>
> Obviously, if they have had any biopsies in the meantime, we are going
> to collect information on that, as well. We have central over-read of
> all pathology.
>
> It says 9 to 15. We have had a huge debate about this. What I said
> earlier was 10 to 15 months, and I believe, I mean I wish I could
> remember really straightforwardly right now, but I think we actually
> changed it to 11 to 15 recently, so I would have to check on that, but
> the reason is because you want to be\--obviously, if a patient has
> breast cancer anytime up to 15 months, we are going to call the first
> one a false negative.
>
> The question is when do you allow yourself to call it a true negative,
> how soon follow-up can you have to call it a true negative, so there
> has been a lot of discussion about that, and my recollection now is
> that it is 11 to 15 months, so this is slide is not correct.
>
> \[Slide.\]
>
> I mentioned this earlier, that there is the team of physicists headed
> by Martin Yaffe at the University of Toronto, and then helped by Ed
> Hendrick who is the co-PI on the study. He is at Northwestern
> University. They are overseeing quality control at all these centers.
>
> They are doing the MQSA requirements for the screen-film units, and
> they are also sending all the digital data and the screen-film data up
> to Toronto where it is looked at centrally, as well.
>
> In addition, we had a very comprehensive acceptance testing protocol.
> Some of these machines are not FDA approved yet. So, we are making
> sure that they are functioning at a minimum standard, what we have
> determined in advance prior to the entry of patients into the study.
>
> We have had no real glaring problems with quality, no reasons to shut
> sites down or anything like that during the\--let\'s see, 10 months we
> have been open at this point.
>
> \[Slide.\]
>
> We are also doing a cost effectiveness analysis, which is, as I
> mentioned, we are keeping track of all the downstream tests, and if
> someone has both a positive digital and a positive film, then, you
> can\'t really pull out which test caused which, you know, which
> downstream cost, but you will know that both would have caused those
> downstream costs.
>
> One of the hypotheses is that digital actually has fewer false
> positives. That has been shown in the other large screening trial that
> has been performed by John Lewin and Ed Hendrick and Carl Dorsey,
> which has been published already. They did find a statistically
> significant lower call-back rate and lower false positive rate, lower
> false positive and lower biopsy rate.
>
> So, that has been shown before with the GE system in their big study,
> so we are hypothesizing that will be shown again in our study, so we
> are trying to figure out what that means in terms of medical costs.
>
> We are asking the radiologists to record what additional tests are
> done on these patients, and Dr. Anna Tosteson, who is a health care
> economist at Dartmouth Medical School, will be doing modeling to look
> at the cost effectiveness issue.
>
> \[Slide.\]
>
> In addition, we have a patient telephone survey that will be done on a
> subset of patients in the trial. That was developed by Dr. Danny
> Fryback of the University of Wisconsin, which we expect fewer false
> positives, so we are trying to find out how important that is to
> patients by interviewing patients who had false positive mammograms
> versus the control group.
>
> Those are being done centrally, but through telephone surveys, so it
> is a very short, few-item questionnaire, and it is being done out of
> UNC.
>
> \[Slide.\]
>
> All pathology reports will be reviewed by one of two breast pathology
> experts. In addition, the specimens of any breast tissue that is
> obtained on patients during the course of the follow-up period will be
> reviewed by the breast pathologist, these same two breast
> pathologists, one of the two of them.
>
> In addition, if there is a disagreement between a local pathologist
> and a central pathologist, then, the other central pathologists will
> be called in to give a tiebreaker vote, and hopefully, there won\'t be
> a three-way disagreement, but we may even have one of those, so we
> will have to find a fourth person to kind of help us.
>
> I don\'t have any data about how often this is happening. I did just
> see the data from R.5 on this, which was a multicenter clinical trial
> of stereotactic and ultrasound guided core biopsy for nonpalpable
> lesions, and the rate of disagreement in that study was only 4
> percent, which is very good actually for a kappa number. It is 96
> percent, 0.96 kappa is extremely high for any technology.
>
> So, I am hoping we have numbers like that for this study.
>
> \[Slide.\]
>
> What I have described just now was what we are doing to achieve our
> primary aims and I also described some of the secondary aims because I
> talked about quality of life and cost effectiveness, but what I just
> described are the main aims of the study or how we are achieving the
> main aims of the study.
>
> We are also planning additional studies during year 3, after all the
> patients have been acquired, all the images have been acquired, we are
> going to run reader studies to assess other aspects of digital
> mammographic performance, diagnostic performance.
>
> For example, a big issue is softcopy display versus printed film
> display, does the technology perform equivalently in both conditions.
> Just as an aside, I didn\'t say this, but we have assigned reader
> methods for each system. For example, GE, all readers are reading in
> softcopy. For Fuji, all readers are reading in hardcopy.
>
> For Fischer, all readers are reading in both conditions, both soft and
> hard copy, and for Lorad, right now they are reading in hardcopy, but
> they may be switching to softcopy. The point is that we have
> standardized it across sites, so we really can\'t answer this
> question, softcopy versus printed film, within the study.
>
> Really, it wouldn\'t be appropriate because each system has its own
> softcopy system to really make a statement across digital mammography
> for soft versus hard copy, so what we are going to do is run reader
> studies in the third year where we compare digital softcopy to digital
> hardcopy for each machine type, so that each new manufacturer will
> give us their best version of their softcopy system and will run
> reader studies comparing soft to hardcopy for each manufacturer to
> determine the diagnostic accuracy.
>
> In addition, I am going to skip over the second bullet for a second
> because it is kind of an arcane statistical thing that I think the
> statisticians will be happy we did them, it will take me a few
> minutes, so we are going to look at breast density and its effect on
> diagnostic accuracy and compare digital film for that, because the
> hypothesis is that obviously, people believe digital may be better
> than film in dense-breasted women, and so we are going to have a lot
> of data on that by the end of this trial.
>
> You know, this trial is costing \$28 million and doesn\'t even include
> all the systems that exist in the world for digital mammography.
>
> I am personally aware of two other systems that didn\'t make it in
> time for this trial, there may be others out there, as well, and we
> can\'t keep running \$28 million studies every time we have a new
> system, so the statisticians and those of us who do clinical trials
> are very interested, isn\'t there some other way we could do this
> without having to run a full-fledged clinical trial, so we are
> actually going to look at the use of a reader study in predicting, and
> I know the FDA statisticians at least over in the Device Approval
> Branch are going to be interested in the result of this study, is
> there any way to predict the results of the full-fledged trial with
> carefully controlled reader studies, can we estimate the diagnostic
> accuracy.
>
> We are going to do this study with that percent prevalence in the
> reader sets to see if any particular mix, case mix is most predictive
> of the outcome.
>
> I talked about this already as the secondary aim. Each unit may have
> different performance versus film-screen mammography. It is possible
> that one unit really performs extremely well and better than film. It
> is possible that another unit performs less well than film, so we
> really need to divide them up.
>
> We have the whole technology kind of lumped together in the overall
> aim, but we will divide them up and look at them that way, as well.
>
> Obviously, we have much less power for this aim than we do for the
> overall aim of comparing digital to film, but we do what we can and
> obviously, we will have a lot of power for the GE because they have a
> lot of systems out there being tested in the trial.
>
> We will have less power for the other manufacturers because we only
> have six machines. In addition, all these other characteristics will
> be tested, digital versus film. Obviously, we have less power against
> any of these than we do against the main objectives - age, lesion
> type, pathologic diagnosis, et cetera.
>
> \[Slide.\]
>
> We also have a lot of technical aims in this trial. We have a big
> quality control program going on, collecting a huge amount of data on
> a daily, weekly, monthly basis. We are hopefully going to have a
> pretty good handle at the end of the trial on the effect of spatial
> and contrast resolution on diagnostic accuracy, if there is such an
> effect.
>
> We have a range of image detectors in the trial on the Lorad system
> that was available until recently, which is getting discontinued,
> which is the one that is FDA approved at this point, has a 41-micron
> pixel size, and the GE system has 100-micron pixel size.
>
> In addition, we have a range of contrast resolutions, 10 to 14 bits,
> and so we will have some idea, we hope, about the importance of those
> factors. We are going to have a good idea of whether image quality
> varies tremendously across sites and we hopefully will know about
> dose, as well, and we are going to know about the range over time,
> whether things change a lot, drift a lot, so far there haven\'t been
> major surprises, but we will have lots and lots of information about
> that.
>
> \[Slide.\]
>
> I just wanted to show you a few pictures. It may be too bright in here
> to really appreciate this. This is an image from the University of
> Pennsylvania, and there is really two lesions here. There is a big,
> obvious spiculated mass, and then right next to it is a little
> smaller, indistinct, irregular mass, which both were cancers. I assume
> one was invasive ductal and the other was invasive lobular, but I am
> not sure about that.
>
> \[Slide.\]
>
> Here is another example of an infiltrating ductal carcinoma with DCIS,
> which was on the Fischer unit. The first image I showed you was from a
> GE system. This one is at the University of Toronto.
>
> So, I am happy to answer any questions. We have a lot of times still,
> I only took 40 minutes. Does anybody have any questions about the
> trial?
>
> MS. HARVEY: Dr. Harrison.
>
> DR. HARRISON: You mentioned in getting pathology read that you were
> hoping that there was not a necessity to break a three-way tie, you
> either have malignancy or you don\'t. How can there be a three-way
> tie?
>
> DR. PISANO: Well, we have a 5-point scale from pathology. There is
> malignancy, there are obviously malignant, invasive ductal cancers,
> there are obviously benign lesions like fibroadenomas and things like
> that, but there are kind of gray lesions like\--
>
> DR. HARRISON: It was rhetorical.
>
> DR. PISANO: Oh, I know you know the answer. You want me to clarify.
>
> DR. HARRISON: Right.
>
> DR. PISANO: LCIS and the lobular neoplasias, lobular carcinoma in
> situ, the other lobular neoplasia lesions. There can be quite a bit of
> disagreement between pathologists around those kind of high-risk
> lesions.
>
> That is where we found disagreement in the R.5 data is right at that
> point. We did very well overall, but that group had a higher rate of
> disagreement, and then DCIS, of course, sometimes there is
> disagreement in classifying a lesion as ductal carcinoma in situ, so
> we do have a range of possibilities.
>
> Hopefully, the pathologists will agree most of the time, but we don\'t
> want it to be too high a rate. I don\'t expect a very high rate.
> Frankly, the R.5 data was better than we expected.
>
> It was earlier studies that indicated as much as 7 to 10 percent
> disagreement rate between pathologists with open biopsy. So, we were
> pleasantly surprised to see it was smaller than that for R.5, and
> presumably that suggests a training effect over time. Maybe people are
> learning, they are not so unfamiliar with these border cases.
>
> MS. HARVEY: Dr. Lee.
>
> DR. LEE: I was wondering if you had a sense of out of the women who
> are eligible for the study, what percentage actually are
> participating.
>
> DR. PISANO: I don\'t really know for sure. I can tell you about my
> site. We actually have two machines going in two different buildings,
> and we have more women, we have lots of women who want to participate.
> It is mainly the rate limiter is not the number of women who want to
> participate, it is more just physically, how many mammograms can you
> do a day.
>
> You know, you are using these machines for clinical work, and you have
> to kind of fit in the research into the clinical day, and there is
> only so much you can do. We are taking all comers who want to do it,
> but you can\'t keep working until midnight.
>
> So, that is really not the issue that patients aren\'t willing to do
> it. We have lots of patients willing to do it. That has not been our
> problem at all. It is more just physically being able to handle that
> much per day. It is very, very labor intensive.
>
> MS. HARVEY: Dr. Ramos.
>
> DR. RAMOS-HERNANDEZ: Because of the disparities among different
> ethnicities and the new tendency for African-Americans and Latinos to
> be diagnosed at younger ages, in the general information that you are
> getting, some sense, or are you collecting specifically age and
> ethnicity, so when we get results, we have a sense, see if this is
> more accurate for specific groups?
>
> DR. PISANO: Yes, we are collecting age and ethnicity, and, in fact, we
> have been monitoring very carefully our African-American and Hispanic
> and Asian enrollment in the trial.
>
> We noticed in the first six months of the trial that we had fewer than
> we would like both in African-American and Asian and Hispanic women.
> We had appropriate percentages of white women and Asian women.
>
> So, we actually have targeted interventions directed toward the
> minority populations that we have put in place at specific sites. What
> we did was we looked at the demographics at the sites that had more
> African-American and Hispanic women, and we have asked those sites to
> target those populations in specific ways.
>
> We have noticed already that we are getting reports from the Data
> Safety and Monitoring Board and the Statistical Center, we get monthly
> reports, and the ethnicity report we got in April, we have already
> seen a correction, so we have gotten the numbers back up to where we
> want them to be or I should say up to where we want them to be already
> from where they were, which was not acceptable or below what we
> thought it should be in April just by getting a couple sites to make
> outreach into the community.
>
> Actually, Washington Radiology is one of the sites that we targeted,
> and Denver, the University of Colorado, both those sites. Washington
> Radiology and Denver both had large numbers of Hispanic patients, and
> so we improved the enrollment for Hispanic patients by basically
> having translation of consent and available person at the site who can
> speak Spanish, things like that, simple things like that.
>
> In addition, the NCI has a communications kind of guru, someone who
> could help clinical trials recruit patients and target certain
> populations, and they have been quite helpful in coming up with
> strategies. So, we have dealt with that issue. I don\'t know whether
> there will be a difference, but we will look at it, the ethnicity of
> the patients as one of the factors affecting the outcome of the trial,
> we will look for it.
>
> DR. RAMOS-HERNANDEZ: Since the beginning of the trial, did you set up
> specific percentages of special populations that you wanted to
> achieve?
>
> DR. PISANO: What we did was we looked at the U.S. population and we
> are trying to reproduce the percent of the population studied that
> reflects what Hispanic, African-American, Asian, white, are in the
> population.
>
> We probably are not going to succeed in doing that exactly, but we are
> going to come as close as possible to it as we can with these
> interventions that we have created or are undertaking.
>
> MS. HARVEY: Dr. Harrison.
>
> DR. HARRISON: Along the same lines, historically, African-American
> participation in clinical trials has been very low, down around 1
> percent. What are the numbers that you are seeing right now?
>
> DR. PISANO: Well, we are seeing much better than that, but I don\'t
> remember the exact figure off the top of my head, but my memory is it
> is closer to 10 or 15 percent African-American, maybe even higher than
> that. I really don\'t remember the exact numbers, but we are coming
> close to the percent in the population at the different sites.
>
> For example, Alaska, Native American, we don\'t have any sites that
> are really in places where there are Native Americans, so we can\'t
> possibly achieve the percent that really exists in the population of
> that particular subset of the population. We are doing what we can.
>
> I will say at my site, we are definitely getting a percent of women
> who exist in our population. At UNC, it is about 30 percent
> African-American, and we are getting about 30 percent
> African-Americans at our site, but I don\'t remember the exact numbers
> at the rest of the sites overall. I would have brought the figures, I
> mean I can provide them if you are interested, but I don\'t have them
> with me today.
>
> DR. HARRISON: Are you allowing people with previous cancer diagnoses
> to be screened?
>
> DR. PISANO: The answer is if a woman has had a mastectomy, and she
> would normally get screening mammography for the opposite breast,
> then, she is eligible to participate in the trial. Some sites do not
> image women as screening mammograms who have ever had a cancer
> diagnosis, so those sites, those women are never screened\--
>
> DR. HARRISON: Right, they are always defined as diagnostic at that
> point.
>
> DR. PISANO: They are always diagnostic. Now, women who have had
> lumpectomy and radiation or without radiation are not eligible because
> those women, we define them as needing diagnostic mammograms as
> opposed to screening mammograms, but women who have had mastectomy can
> participate if that center performs those patients as screening
> mammograms.
>
> DR. HARRISON: Right, because presumably, the contralateral breast does
> not have architectural disturbances that we have created.
>
> DR. PISANO: Exactly.
>
> MS. GILBERT: I know that you did address this earlier. What are some
> of the strategies that you are using to recruit these women? 49,000
> women are a lot of women. Can you just give me some idea of what you
> are doing?
>
> DR. PISANO: Well, the centers that are, first, the centers that are
> participating in this trial are all high-volume centers. We don\'t
> have anybody who does five mammograms a day or anything like that, so
> we are not talking about centers that have no population to recruit
> from.
>
> The primary thing we do is publicize the trial at the centers where
> there already are screening mammograms happening in large numbers per
> day. At my site, it is over 70 screening mammograms per day. So
> recruiting 15 of those women, you know, 10 to 15, some number like
> that every day has been no problem.
>
> On top of that, there has been local publicity at the local sites. I
> mean it is kind of a tradeoff. You don\'t want to distort the
> population at the site away from the screening population. You know,
> it is a little bit of a mixed blessing getting other women in who
> don\'t normally come to that site for screening.
>
> Certainly, you want people to know about the trial, but perhaps people
> will come to get screened who wouldn\'t ordinarily or should not be
> screened. So, we want to make sure that women who will come to the
> center for screening, we want to be able to make sure they come back
> in a year for follow-up, so we publicized it locally.
>
> Each center has brochures they can distribute to local primary care
> physicians or to women\'s groups locally. We send it out. At UNC, for
> example, they sent it to local PTAs, we have sent these brochures out,
> we have done all sorts of things like that.
>
> I am not sure how many patients for sure come in because of that, but
> we do have some publicity. There is a web site for the trial, which is
> a very attractive, nice place to come visit, and it gives very
> explicit instructions to patients on how to get a mammogram
> appointment at the site if they are interested in participating, or to
> women, I should say, these are screening women, they are not really
> patients.
>
> If women want to come in to the centers for screening, they can come
> in based on the instructions at that site, but occasionally, patients,
> you know, we have to be vigilant that patients who aren\'t eligible
> for screening might get into the trial. We don\'t want that to happen
> with this trial, as it has happened in other clinical trials.
>
> We want patients to really be asymptomatic patients or women\--I am
> getting my terminology mixed up\--but we want women to come in who
> have no problems, and if they are symptomatic, they shouldn\'t be part
> of the trial.
>
> We have done a lot of stuff, but, as I said, you have to be careful
> that you don\'t almost overpublicize it to the point where people who
> ordinarily aren\'t getting screened are coming in, maybe 20-year-olds.
> I did have a 20-year-old come up to me after I gave a talk on it and
> asked me how she could be part of it, and I had to tell her, sorry,
> you are too young to be screened.
>
> MS. GILBERT: Is there an age range that you are looking at?
>
> DR. PISANO: Well, as I said, the centers screen a population of women,
> and there are some women who are eligible for screening below the age
> of 40, and so those women, if they come normally to that center for
> screening mammography, for example, if you are at high risk for breast
> cancer, your mother had breast cancer at age 40, at UNC, we start
> screening those women annually at age 30.
>
> So, those women come to UNC for routine appointments now, they show up
> on our schedule for screening mammography now, they are recruited to
> the trial, we don\'t exclude them.
>
> Obviously, we don\'t want to have too many women that are at low risk,
> and some women are worried about their breasts and start screening on
> their own at a young age, and we are kind of leaving that up to the
> local sites to make the decision would they normally screen these
> patients.
>
> If they would normally screen these patients, they are eligible for
> the trial. We don\'t really have a lower age cutoff.
>
> There is a long discussion about that. We talked about cutting it off
> at 40, but there are really high-risk women who wanted to participate
> in the trial, so we decided we would err on the side of including them
> as opposed to cutting them off because of their age.
>
> MS. HARVEY: Ms. Rigsby.
>
> MS. RIGSBY: Do you charge the ladies that come in for the screening?
>
> DR. PISANO: We do charge them for film mammography. They get the
> digital mammogram for free, so it is really their insurance, most of
> them have insurance, some don\'t. The ones who don\'t, they have to
> pay for their film mammogram out of their pocket or whatever way they
> normally pay for it. We don\'t have, believe it or not, \$27.5
> million, enough to pay for the full mammogram, too. It\'s a huge
> undertaking with this many thousands of women.
>
> MS. HARVEY: This is a phenomenal amount of data that you are
> collecting. When will we expect to see the first reports of your
> findings?
>
> DR. PISANO: If we wait until all the follow-up is in, that would be
> October\--it will probably be December, you know, given a few extra
> months there, the 15 months as opposed to the 12 months, it will be
> December of 2003. That is until all the data is in from follow-up.
>
> Obviously, we will have some preliminary idea before then, at least
> the statisticians will. My guess is sometime in 2003, there will be
> something, but I don\'t know exactly what month that would be.
>
> MS. HARVEY: Thank you. Any other questions? Dr. Karellas.
>
> DR. KARELLAS: I have two questions. If a patient asks for her original
> films because she is going somewhere, moving somewhere, how do you
> handle that?
>
> DR. PISANO: In the consent form for this study, we ask their
> permission to keep the films centrally, so the women relinquish their
> films to the study. That is so that we can do these reader studies
> during the third year of the trial.
>
> If they need the films back for clinical purposes, which is quite
> possible, they can be requested, and we ask them to send them back
> after they are finished with them. So, the patients aren\'t keeping
> their own films right now, they are all being stored.
>
> The digital images, a copy of them is being stored in ACR Imaging
> Network Headquarters in Philadelphia, and the original film mammograms
> are being stored in ACR Imaging Network Headquarters in Philadelphia.
>
> I had recently a patient who came in with a problem about three months
> after her film mammogram, and we got it by FedEx, her old films,
> within 24 hours. That happened to me at UNC, so I know it is working.
> It has worked for that one case anyway.
>
> That is an experience we have had in the past, that we can get the
> cases pretty quickly back if need be.
>
> DR. KARELLAS: Have you thought of how you and all the sites would
> handle if a percentage of these patients want a copy of their digital
> mammograms at some point?
>
> The reason I am asking you that is that I am finding it very difficult
> to deliver digital mammograms to people who want them, and it is okay
> when they want one or two or three a year, but it is very difficult to
> envision if we have 100 patients in a week ask for their digital data,
> it is very time-consuming.
>
> DR. PISANO: I don\'t know if I have any information from within the
> trial, but I will talk from my own personal experience as someone who
> has digital mammography in my practice. I have not found this to be a
> big problem where patients are asking for their images a lot.
>
> As I mentioned, we have two digital units doing clinical work plus we
> have another one participating in the trial, so I have not had a real
> problem with patients requesting their images.
>
> What we have done when they have requested, we have a printer and we
> just print out another copy and hand it to them. If everybody were
> asking for it, it would be exorbitant, but we haven\'t had that many
> patients, just as most patients don\'t want to keep their film
> mammograms, we haven\'t had that many people request that, so it
> hasn\'t been a problem in our practice.
>
> DR. KARELLAS: The reason I am asking about that, it is very easy if
> they request it at the time of examination. It is always more
> difficult of they come back a year later, because the images are not
> just all neatly packed in one place on patients, so there can be
> various CDs or various locations, so that is something for the sites
> to think about as to how this could be handled in the future.
>
> DR. PISANO: That is a good point. I haven\'t had anybody ask me for
> the mammogram except at the visit where we did the mammogram, but you
> are right, if it is even a week or two later, and it has already been
> archived, it is a little bit of a challenge to get that case back and
> printed, but it wouldn\'t be impossible.
>
> Of course, you could always hand them the one you have in the jacket,
> knowing you could print another one in a few days or something while
> you search for it.
>
> We don\'t have a good pack solution at UNC, I wish I did, but I
> don\'t.
>
> MS. HARVEY: Thank you. Excellent talk.
>
> We have a few minutes while we prepare for Dr. Kopans\' computer to
> get set up, which might be a good opportunity for us to discuss any
> questions that any of the board members might have up to this point or
> any other issues that you would like to talk about. There is lots to
> think about with the digital. It is going to be the wave of the
> future.
>
> Dr. Harrison.
>
> DR. HARRISON: When, in fact, a suspected malignancy is found in these
> clinical trials, the clinical handling of that is done by the local
> clinicians?
>
> DR. PISANO: I should have mentioned that in the talk probably. Each
> site handles the identification of abnormal mammograms and the
> biopsies and everything else as per their usual clinical protocol.
>
> For example, at my site, we wait until both mammograms are
> interpreted, and we have a nurse who contacts the patients and tells
> them about the positive exams, so that person makes the phone call.
>
> Instead of just saying you had an abnormal screening mammogram, you
> need to come back for additional views, she says you had an abnormal
> digital or you had an abnormal film or you had both, an abnormal
> digital and film, and you need additional views.
>
> Then, the letters they get include both, I mean everything has been
> adapted for the trial. The primary care physician gets a dictation
> that says, in our case, I am talking about UNC\--each site had to do
> what their IRBs would let them do or wanted them to do\--so, at UNC,
> first, they get a report, the primary care physicians get a report
> that says film mammogram report with a signature, digital mammogram
> report with a report and a signature, and somewhere in the report, put
> on by a secretary at the top, is this patient participated in digital,
> she received both a digital and film mammogram, so that the primary
> care physician gets both reports, knows what is going on.
>
> When we get the patient back for workup, the radiologist dictates into
> the final report, this patient had both, was part of this study, had
> an abnormal whatever, and we did the workup of this, this way, we did
> the workup of that, that way, and the final interpretation category.
>
> So, we have adapted everything to this trial.
>
> DR. HARRISON: One corollary question. Do you certify a letter to the
> patient?
>
> DR. PISANO: No, we don\'t send our letters certified mail right now,
> we just send them regular mail.
>
> DR. RAMOS-HERNANDEZ: Is there anything in the study or what would you
> do with people that actually couldn\'t afford to pay the screening
> mammography, but they are diagnosed, they get something, an
> abnormality, and they are going to get help to pay?
>
> DR. PISANO: I am sorry, I am not sure I understand your question.
>
> DR. RAMOS-HERNANDEZ: Is there any support for payment when finding an
> abnormal mammogram?
>
> DR. PISANO: So, if the abnormal mammogram occurs, is there any way to
> pay for the downstream costs?
>
> DR. RAMOS-HERNANDEZ: Yes.
>
> DR. PISANO: There is no money allocated at present in the trial to pay
> for downstream test costs. That is part of the consent process, that
> the patient would be responsible for those downstream test costs.
>
> That is the way we have dealt with it, is just inform the patient
> upfront that she may have additional costs if she is not insured. We
> have had no insurance company refuse to pay for the downstream costs
> that I am aware of.
>
> MS. HARVEY: Thank you.
>
> Dr. Kopans will talk to us about tomosynthesis.
>
> DR. KOPANS: And a few other things. I come from Boston. I have to
> admit I am a little anxious to not be standing with my back to the
> wall, which is the way we are taught, so if something is coming from
> behind, I wish you would let me know and have me duck.
>
> **Potential New Applications of FFDM**
>
> \[Slide.\]
>
> DR. KOPANS: I suspect that the committee is well versed in digital
> mammography, but before I get into tomosynthesis, which is really the
> main thrust of my comments this afternoon, I just wanted to briefly
> kind of review just so that everybody understands digital mammography
> and why there are multiple advantages to digital that are going to be
> coming along.
>
> I am going to actually speak about two other aspects of digital other
> than tomosynthesis, but I will do that briefly.
>
> \[Slide.\]
>
> Basically, a digital mammogram, the way I think of it is a spreadsheet
> where you have got rows and columns, and each row can be labeled with
> a number and each column can be labeled with a number, and then the
> x-rays that are collected at each cell, if you will, or pixel, can be
> labeled with a number.
>
> So, for example, 60 photons\--I am just making these up\--but 60 x-ray
> photons come through and are collected in this cell, then, we know
> that this is cell 5-5, and there are 60 photons, so we can define the
> location and the number of x-rays at that point in space by numbers,
> and hence, the term digital, so that the whole image can be described
> as rows, columns, and numbers of x-ray photons.
>
> Then, we can manipulate that image because we can assign different
> levels of gray or color if we really want to, to help whoever is
> looking at the image appreciate things that may not be obvious with
> one sort of presentation.
>
> So, a digital mammogram is just an image made up of numbers, and, of
> course, that allows the computer also to be brought to bear.
>
> \[Slide.\]
>
> I suspect the committee knows the basic advantages of digital
> mammography - higher contrast resolution, greater dynamic range than
> the film-screen systems, because you are not exposing the image to
> meet the parameters of the detector, for example, the film-screen, you
> have to have specific exposure values, otherwise, when you process the
> image, it won\'t be a satisfactory image.
>
> With digital, you are actually uncoupling the detector from the
> display, and you can adjust the image afterward in any one of an
> infinite number of display characteristics, but that way you can image
> the breast, so that you get the imaging characteristics, and you
> don\'t have to worry about the display.
>
> You can manipulate the image. We use digital for real-time procedure
> guidance, I think you probably know that, with stereotactic devices.
> The areas where I think digital is really going to have an impact over
> and above conventional film-screen mammography are in the areas that I
> have listed below.
>
> I am not going to talk about telemammography, but I heard you
> discussing issues of some underserved women, and certainly being able
> to transmit images from areas where there may be remote access,
> digital mammography will permit that.
>
> We have actually sent images between New York and Boston, the short
> way, 22,000 miles out to a satellite and 22,000 miles back again. We
> did that over 70,000 times without a single loss of information. So,
> that is doable. You could be in some remote area in, say, the western
> part of the country and transmit images anywhere in almost real-time.
>
> \[Slide.\]
>
> We use digital now, of course, for procedure guidance. I am not going
> to spend any time on this.
>
> \[Slide.\]
>
> There are multiple ways of doing digital imaging. This is the image of
> a prototype slot-scanning device that we actually had back in the
> 1980s.
>
> \[Slide.\]
>
> It was way before its time, and unfortunately, the company didn\'t
> have the staying power, but the Fischer system works in a similar way
> with x-rays coming through a pre-breast slot and then a post-breast
> collimator, and then detected as a detector.
>
> This is the system we had in the 1980s, but it is similar to the
> Fischer where the detector moves, it is a linear detector and it moves
> across as the exposure is made. This has the advantage of being very
> good at scatter rejection.
>
> \[Slide.\]
>
> This is just for historical purposes. I think probably the first very
> high-resolution digital study, again done in the 1980s with the
> American Science and Engineering system, this is 9 line
> pairs/millimeter of a high-grade ductal carcinoma in situ.
>
> \[Slide.\]
>
> Just one of the quick things you can do with digital is if you don\'t
> like white dots on a black background, you can just push a button and
> it will be black dots on a white background.
>
> Although this is more than a parlor trick, sometimes just changing the
> image presentation can make things more visible to the human eye than
> other manipulations, so that sometimes just breaking up our pattern
> recognition allows us to see things that maybe we wouldn\'t have
> appreciated in the conventional way.
>
> With digital, this is just a push of a button.
>
> \[Slide.\]
>
> There are other technologies. This is the Fuji approach, which is a
> stored phosphor system where a plate is stimulated by the radiation to
> a higher energy level, and then that is read with a laser. I am not
> going to go into the details of the different technologies.
>
> \[Slide.\]
>
> This is just a mastectomy study we did a number of years ago with the
> Fuji system.
>
> \[Slide.\]
>
> There are charge coupled devices, which basically convert the x-ray
> photons into light photons, and then the light is channeled down to a
> charge coupled device, which converts the light into an electrical
> signal, and that then goes to the computer.
>
> \[Slide.\]
>
> This is actually the system that the Fischer unit uses in somewhat of
> a linear array. The initial Trex, Lorad, Bennett, I don\'t know how
> many other companies, had this system, and then as I think everyone
> knows now, Lorad has converted to a selenium system, which I will
> mention again in a second.
>
> \[Slide.\]
>
> These generally have to be put together in some form of mosaic,
> because the charge coupled devices aren\'t big enough to cover the
> entire breast.
>
> \[Slide.\]
>
> This was the old Lorad system with 12. Each one of these is a CCD
> camera with fiberoptics in the screen that converts the x-ray photons.
>
> \[Slide.\]
>
> This is just from Lorad, a slide from Lorad using selenium to convert
> the x-ray photon directly to electrical signal without going through a
> light conversion approach.
>
> \[Slide.\]
>
> Again from Lorad.
>
> \[Slide.\]
>
> This is from General Electric, which is their system converts the
> x-ray photon to light and then, in an electronic array behind the
> light conversion level, they convert the light into electrical signal,
> and this is actually the reverse of what we do with most of our
> computer displays where there is literally a wire to every point in
> the area.
>
> The difference between this and the selenium detector is that the
> x-ray photon is converted directly to electrical signal in the
> selenium detector, and in this, there is a light conversion factor
> first.
>
> \[Slide.\]
>
> Again, you can imagine somebody having to stretch these little, tiny
> wires to each one of these points, so the manufacturing of these
> systems is tricky, but I gather the companies are doing pretty well
> with it.
>
> \[Slide.\]
>
> You have probably seen digital images. Notice how different the ACR
> phantom looks on a digital image than an x-ray film-screen image. The
> answer is it doesn\'t.
>
> \[Slide.\]
>
> This is just so you can see the ACR phantom really is obsolete for
> digital images. You can see just about everything in the ACR phantom
> with a digital system, and I gather there are new phantoms. I know
> there are phantoms under construction, I don\'t know if any of them
> have been accepted yet, but I guess this committee is going to have to
> face those kind of issues as to how to test the digital systems.
>
> \[Slide.\]
>
> Again, you can see the major difference between film-screen and
> digital is no difference in terms of if you want to print the digital
> image or present the digital image the exact same way as the
> film-screen image, you can do that.
>
> \[Slide.\]
>
> The advantage, of course, with the digital image is that you can
> manipulate the image, and you are not just stuck with what you have
> got in terms of with a film-screen image, what you get is what you
> get. You get one shot. If the film isn\'t exposed properly, you have
> to do it again.
>
> With the digital image, you can manipulate the image, and another
> advantage for those of us who are always looking for magnifying
> glasses in our divisions, someone in this country is collecting
> magnifying glasses because I bet if you asked every radiologist in the
> audience, they are all disappearing from our departments. I don\'t
> know where they go.
>
> But the joke is going to be on that person because we won\'t need
> magnifying glasses. With digital, you just make the image larger, and
> that is a major advantage just by itself.
>
> \[Slide.\]
>
> Now, digital mammography, and D-MIST is going to I think confirm what
> most of us who have looked at digital and obviously are experienced
> with film-screen mammography know, and that is that digital mammograms
> are as good as film-screen mammograms.
>
> Are they better? Just by themselves, I don\'t know. I think there are
> advantages, and D-MIST may be able to tease that out, we will have to
> see, but what really makes digital better than film-screen are the
> things that you can do with digital that you just can\'t do with
> film-screen.
>
> I am just going to mention three of them today and finish with the one
> that we are most excited about, which is tomosynthesis.
>
> \[Slide.\]
>
> There is a technique called dual energy subtraction. I hope everyone
> on the committee knows that one of the things that we look for on
> mammograms are calcium deposits.
>
> In every mammogram there is probably at least one calcium deposit, so
> calcium, by itself, doesn\'t mean a whole lot, but it is patterns of
> calcium deposition that worry us, and ductal carcinoma in situ
> frequently will cause the deposition of calcium whether it is from
> dead cancer cells or actual secretion of the calcium.
>
> One of the things that we look for on mammograms are so-called
> clustered calcifications. Well, they are hard to see because these
> calcium deposits are under a millimeter in size, virtually all the
> time in cancers, and down around 500 microns, that is about a half a
> millimeter particles, and trying to see them against the background of
> the very heterogeneous breast parenchyma can be difficult.
>
> One of the things that the computer-assisted detection units, one of
> the things that they do well is to find these white spots on the
> mammogram.
>
> There is another approach which is dual energy, which we think will
> allow us to see them very easily. What is dual energy? Well, you take
> a high-energy mammogram, and at a high-energy/high kV, the difference
> between soft tissue attenuation and calcium attenuation is not as
> great as when you do a low kV image, where the calcium attenuation
> becomes significantly higher.
>
> With a computer, if you have taken these basically simultaneously, you
> can adjust the soft tissue attenuation numbers, so that you change the
> image, so that the soft tissue in the high kV and low kV image match
> up exactly, and you can then subtract those, so that there is no soft
> tissue image left.
>
> Because the calcium doesn\'t subtract exactly with these two changes,
> then, the calcifications will show up as a separate signal.
>
> \[Slide.\]
>
> This is just schematically how this would work. You take a low kV
> image, you take a high kV image, subtract the two.
>
> \[Slide.\]
>
> If it works, the tumor calcifications will stand out and the breast
> will disappear.
>
> \[Slide.\]
>
> This is from an article in the Journal of Radiographics from many
> years ago where they did this in a chest x-ray. Just to show you, this
> is the heart and the mediastinum, and the ribs have been subtracted
> out.
>
> \[Slide.\]
>
> That is not quite as impressive as when they subtracted out the heart
> and mediastinum and left the ribs, and this was done without a
> scalpel, which is kind of impressive.
>
> This is sort of what you can do potentially with dual energy
> subtraction, and this is a fairly crude subtracted study we think that
> we can do better.
>
> \[Slide.\]
>
> This is a breast tissue sample with high grade ductal carcinoma in
> situ, that we did a dual energy image with just a standard General
> Electric digital mammography system, and this isn\'t just window and
> leveling, this is actually subtracting out the soft tissue and leaving
> only the calcium.
>
> \[Slide.\]
>
> Here is another one with calcifications from a cancer, and you can
> imagine if, on a mammogram, when you push the button, you saw nothing
> but where the calcifications are, that would make the radiologist\'s
> search a lot easier for finding calcifications.
>
> This is not available on digital systems yet, so you don\'t have to
> worry about it yet as the MQSA Committee, but this is one of the
> things that you can do with digital system that really would be next
> to impossible with a conventional film-screen system.
>
> \[Slide.\]
>
> Another sort of corollary to this is digital contrast subtraction
> angiography. This is a technique that we use all the time in the rest
> of the body, and now that we have digital detectors for the breast,
> investigators are starting to look at it in the breast.
>
> This is a way of looking at only the vascularity. I think most of you
> know that breast cancers or cancers in general, solid tumors can only
> grow to a certain size and then they need a blood supply.
>
> They can\'t just continue to grow unless they call in a blood supply,
> and that is called angiogenesis, a neo-, a new vascularity that\'s
> developed, and this, of course, is one of the areas that people are
> looking at to try and kill cancers if you can get rid of the blood
> supply, then, maybe you can kill the cancer, but it is also the way we
> confine cancers.
>
> \[Slide.\]
>
> In magnetic resonance imaging, here, on a CT scan, this is back from
> the 1980s when Chang in Kansas pointed out that cancers will enhance
> with iodinated contrast on CT. This is a pre-contrast scan and a
> post-contrast scan, you can see the cancer has taken up the contrast,
> and is much more visible with contrast.
>
> \[Slide.\]
>
> This is on magnetic resonance imaging, actually, a little cancer that
> we found in a study. Actually, we were studying her left breast
> because she had a known cancer there, and we found an unexpected and
> unsuspecting cancer in the other breast, that was found because it
> enhanced with contrast because of these new blood vessels that had
> formed, and this was not visible on a mammogram, ultrasound, we could
> only see it on MRI and CT.
>
> \[Slide.\]
>
> Here is another case, not that one, but a similar one, where we found
> it on MRI and then located it on CT because of the contrast
> enhancement.
>
> \[Slide.\]
>
> Well, this is a potentially powerful tool if we could do it in
> mammographic, with mammographic resolution. The CT scan doesn\'t have
> nearly the resolution that an x-ray mammogram has, and so if we could
> take the advantage of seeing small blood vessels at high resolution,
> we may have a very powerful tool.
>
> \[Slide.\]
>
> So, again schematically, we would do a pre-contrast mammogram\--this
> is before injecting any contrast\--then, intravenous administration of
> iodinated contrast. This is the same material that is used every day
> in departments for CT scans and just about anything that we do that
> needs what are called contrast agents. It is generally iodine.
>
> Then, you subtract the pre- and post-contrast, and the only thing that
> is left after subtracting is the vascularity, and in this nice
> schematic, it works beautifully.
>
> \[Slide.\]
>
> This is an animal model that we did a number of years ago. This is
> bone. There is a tumor that has been implanted right here. It is a
> little hard to see because we haven\'t done the subtraction.
>
> \[Slide.\]
>
> When you do the subtraction, now you can actually see the nest of
> blood vessels that has developed around this tumor. This was done with
> a digital mammography detector, so that the spatial resolution is
> quite exciting.
>
> \[Slide.\]
>
> Other folks are now looking at this in the human breast. Martin Yaffe
> and his group up at the University of Toronto, using the Fischer
> system, has shown contrast enhancement of a cancer, and just as we can
> with magnetic resonance, they can track the contrast as it flows
> through the tumor, so as the contrast gets to the tumor, there is a
> sudden increase in contrast in the tumor.
>
> Some of the contrast actually leaks out, so it stays in the tumor, so
> the tumor contrast stays high, but some of it leaks out, and this is a
> fairly characteristic curve for a cancer, which this turned out to be.
>
> We have seen this on magnetic resonance. We should be able to do this
> less expensively and at higher resolution with iodine and digital
> mammography.
>
> \[Slide.\]
>
> John Lewin has also done some work in this and loaned me these slides,
> where he is dealing with the issue of registering these images.
>
> One of the big problems that the radiologists and physicists in the
> audience know about is to do accurate subtraction, where you subtract
> one image from another, they have to line up perfectly, otherwise, you
> get all kinds of artifacts.
>
> John has taken another approach where he takes a high-energy image and
> then a low-energy image, and subtracts them, and that can be done very
> quickly, just like the calcium that I just showed you.
>
> That leaves the iodine, which blocks x-rays at much greater rate than
> soft tissue, so then you can have the iodine image, if you will, of
> the cancer left behind.
>
> \[Slide.\]
>
> Here is just another case that John gave me, sort of a subtle lesion,
> and then much more obvious following the contrast.
>
> \[Slide.\]
>
> Now, what I was sort of asked to talk about today is a technique that
> we are developing at Mass. General, and I should issue the disclosure
> that I am, number one, biased because this was our idea for the breast
> and we hold patents at Mass. General on it, so that I am not totally
> objective, although I will try to be as objective as I can here.
>
> Three-dimensional digital mammography, I think is going to be the
> first technique that really sets digital mammography off from
> conventional film-screen, and there are a lot of advantages that I
> will show you.
>
> \[Slide.\]
>
> What do I mean by 3-dimensional mammography? Well, there is a
> technique that was actually written about back in the late 60s, early
> 70s, called tomosynthesis. What is tomosynthesis?
>
> In conventional x-ray\--and we will talk about mammography, which is
> an x-ray technology\--the breast is between the x-ray beam and the
> detector, and x-rays come through the entire structure of the breast,
> and something that is in this plane, superimposes on something that is
> in this plane, and they project on top of one another on the
> mammogram.
>
> One of the challenges that radiologists face is to try to separate the
> structures that are overlapping, and one of the reasons we take views
> from the side and from top to bottom is to help the radiologist
> understand the 3-dimensional location of structures, so that we are
> not fooled by overlapping structures.
>
> I should tell you, though, that in our practice, and Ed Sickles, I was
> talking with Ed, and he has the same experience at the University of
> California at San Francisco, about 25 percent of the women that we
> recall because we think there is a problem on their mammogram, are
> recalled because of overlapping structures. It turns out to be
> nothing, but the radiologist, just looking at the two films, can\'t be
> sure of that, and so the patients are recalled.
>
> \[Slide.\]
>
> Now, this just an example of a very subtle tumor. It is not so subtle
> because we have got a spot compression panel on it, and I wanted you
> to be able to see it. Here, you can see a spiculated, fairly
> high-density mass that is partially hidden because of the rest of the
> breast, the normal breast structures.
>
> \[Slide.\]
>
> Now, once this is taken out at surgery, this is following needle
> localization, it is easy to see. Why is it easy to see? Well, first of
> all, it is a thinner structure, and so there is less scatter, and so
> on, but we have taken away what is called the structure noise of the
> breast, which is what is in front of it and behind it on the
> mammogram.
>
> \[Slide.\]
>
> I liken that to looking for a birch tree in a pine forest, couldn\'t
> find a birch tree in a pine forest, but this is a deciduous, but it is
> close anyhow. Here is the birch tree. It is pretty easy, everyone can
> see it. It is white, it stands out against the green background.
>
> But as you start walking along\--I had to go all the way to Norway to
> do this, by the way, it was a tough experience, but I did\--as you
> walk along, it starts getting hidden, and after a while you really can
> just barely see the birch tree, if at all.
>
> \[Slide.\]
>
> Here, my diagram of a birch tree in a pine forest, it is very hard to
> see the birch tree even if it were just one row back behind these pine
> trees. Well, how does this compare to the breast?
>
> The breast, you all know about dense breast tissue. Dense breast
> tissue are the fibroglandular structures, principally the fibrous
> structures although the glandular tissue is also dense, that are
> highly attenuating of the x-ray beam, and cancers have very similar
> x-ray attenuation to fibroconnective tissue.
>
> So, it is sometimes very hard and often\--not often\--but not
> infrequently impossible to differentiate a cancer from the normal
> tissue, and this is the reason why cancers don\'t show up on
> mammogram. They are hidden by the dense tissues.
>
> This can happen at any age, and the density of the breast, just as a
> quick aside, has nothing to do with how firm it feels on clinical
> breast exam. The density is an x-ray attenuation phenomenon, you can
> only tell density by doing a mammogram, and the density changes
> gradually with increasing age. It is nothing that happens at menopause
> or age 50, as we have been led to believe.
>
> Women at age 30, about 90 percent of them have dense breast tissue,
> and that changes by about 1 to 2 percent with each increasing year of
> age, so that the percent of women with fatty breast increases. Fat is
> like window glass or having a birch tree out in the middle of a field.
> The density of the breast is like the pine trees.
>
> \[Slide.\]
>
> So, if we could just get rid of the pine trees without having the
> environmentalists against us here, we would be able to see the birch
> trees.
>
> \[Slide.\]
>
> So, the trick really is to make slices through the breast, and I think
> many of you are probably familiar with CT scans, which make slices
> through the breast tissue\--again, the radiologists are all well
> familiar with cross-sectional imaging\--and what that does is it gets
> rid of what is in front and what is in back, so that you can see the
> birch trees.
>
> \[Slide.\]
>
> Well, how can you do this in the breast? In the days when I was very
> young, we used to move the x-ray tube in one direction, and the
> detector, in this case it was film, in the other direction, and they
> would move in tandem, and you can probably imagine that as you move
> the x-ray tube in one direction and the detector in the other
> direction, only the things that are at the fulcrum of the motion will
> not look like they are moving, everything else will look blurred. I
> will come back to that in a minute.
>
> But this is the old way of doing conventional tomography, move the
> tube in one direction, the detector in the other, and you could blur
> everything but the plane that you were interested in. If we were doing
> this in the breast, it would be in the breast.
>
> The problem with this is for every slice that you want to make through
> the tissue, you have to repeat this sequence at full dose. So, to go
> through the breast, say, get 60 slices through the breast, would
> require 60 mammographic exposures. Clearly, we are not going to do
> that, so this approach to making slices through the breast isn\'t
> going to work.
>
> \[Slide.\]
>
> It turns out that using a computer, you can move the x-ray tube
> through an arc, and what we do in our system is move the x-ray tube
> through an arc of 50 degrees. That is just what we started with. We
> think that there are better arcs to choose.
>
> We are moving it through 50 degrees, and as we move it, it is stopping
> and taking a picture 11 times from 11 different angles. We can do that
> in 7 seconds. The breast stays stationary and the detector doesn\'t
> move, so the breast and the detector are stationary, just like a
> conventional mammogram.
>
> It takes a little bit longer. It takes 7 seconds as opposed to
> conventional mammogram is anywhere from half a second to a couple of
> seconds, and we take 11 images. You say, well, gee, that must be a lot
> of dose.
>
> Each individual image is a fraction of the total x-ray dose of a film
> mammogram or, for that matter, a digital mammogram at the same dose.
> So, the dose for these 11 images adds up to about 1.5 film-screen
> mammogram exposures, so the dose is actually less than the tubular
> mammogram.
>
> \[Slide.\]
>
> Now, why are we doing this? Well, if you look at again our objects
> that are in the breast here, when we take a conventional x-ray, they
> are lined up and they are hard to tell apart.
>
> As we move the x-ray tube through an angle, you can see\--and I will
> do this back again, so you can see it\--that at different angles,
> something in one plane moves differently than something in the other
> plane.
>
> Again, we move through the angles, and if you watch, the structures
> start moving apart. That is called parallax, and if you close one eye
> and point to an object on the wall, and then change, your eyes closed,
> the first eye, and open the other eye, you will see the object seems
> to shift. That is because your eyes are looking at it from a different
> angle, and it is that shift that is called parallax.
>
> \[Slide.\]
>
> We can take advantage of that with tomosynthesis to make slices
> through the breast, because we can then take these images that we have
> put together, and line them up, and this is why we need digital
> systems because you really can\'t do this certainly efficiently with
> film images. You need a computer image, it is much easier.
>
> \[Slide.\]
>
> Here, in the synthesized images, now the spiculated, the irregular
> abnormality, or anything in that plane will register on all the
> images. The other ones won\'t because they are in a different
> location. They will misregister and you will have blurring by the
> misregistration.
>
> Now, let\'s say we wanted to see the plane that had this irregular
> shape in it. Well, we just shift the images and add them again, and
> now what is in the plane of the irregular shape adds up and is sharply
> defined, and everything else is misregistered. That is called
> tomosynthesis, that was named tomosynthesis.
>
> \[Slide.\]
>
> Well, we have taken it several steps beyond now. We don\'t do that
> so-called shift and add, but we accomplish the same thing, and this is
> just to acknowledge the people that we have worked with from Brandeis
> University to develop advanced algorithms, and I have to tell you that
> this was done under a grant from the Army.
>
> \[Slide.\]
>
> General Electric built the machine for us, and basically, the x-ray
> tube moves up in this housing. This is just here so we don\'t whack
> the patient in the head as the x-ray tube moves, but it is a standard
> digital mammography system, digital detector right here, compression
> system. This just has to do with counterbalancing the movement of the
> x-ray tube.
>
> Again, this is a prototype and not as elegant as a finished system
> would be, but to the patient, it is like having a mammogram. Now, I
> will say just quickly as an aside, we are collecting data to see if we
> can reduce the compression needed for doing mammography. I know most
> women don\'t care much about that, but we would like to reduce the
> amount of compression that is needed.
>
> We are not sure we can get away with that. Right now we are using the
> standard mammographic compression, but another advantage of
> tomosynthesis will be that we think we can just do one compression,
> that we won\'t need to do the two projections because, as I will show
> you, we will have 3- dimensional information.
>
> So, the x-ray tube moves up here. The exposure, as I say, takes 7
> seconds. I think we have had one case out of over 250 that we have
> done where we think there was some movement by the patient, but they
> seem to be okay, and again, 11 images in 7 seconds for 1.5 film-screen
> dose, not film-screen study, but film-screen image.
>
> \[Slide.\]
>
> Now, it is not going to be great here in this room because the
> lighting isn\'t terrific, and I will also give you the caveat that
> this looks much better on a workstation which is designed for this,
> but here is a conventional film-screen mammogram, and I am sure all
> the radiologists picked out this cancer. Actually, it is a very subtle
> cancer.
>
> I think we picked it up because there is some calcium that just
> happened to be nearby and drew the radiologist\'s eye. This is a very
> subtle lesion.
>
> \[Slide.\]
>
> Here it is up close, a little better, but you can see you have got all
> the structure noise of the breast that is getting in the way.
>
> \[Slide.\]
>
> Here it is from the cranio-caudal projection, again pretty subtle.
>
> \[Slide.\]
>
> Even when you get up close, it is still pretty subtle.
>
> \[Slide.\]
>
> This is the tomosynthesis image, and, of course, it takes getting used
> to. What I am going to do, we are going to be paging through. We have
> reconstructed this at 1-millimeter thick slices. We actually can go
> down to\--we have done half-millimeter, we can go to thinner, it just
> requires much greater computer calculations.
>
> That is right now the rate-limiting step. It takes about two hours to
> process one of these images. That cuts your throughput down a little
> bit, but we know how to do it actually within a minute or two, so that
> is really more the computational power, and computers get cheaper and
> cheaper by the second, so that is not an issue.
>
> \[Slide.\]
>
> Now, what I am going to do is just page through, and we are starting
> to move into the breast, and you will start seeing structures. I am
> going to stop it here. You can start seeing Cooper\'s ligaments coming
> into view, these curved lines.
>
> \[Slide.\]
>
> If you watch right here\--it is hard here to stop and start with
> PowerPoint\--but now you can see the cancer without the noise of the
> breast in the way. I will show you this up close in a second. Then, we
> will page through the cancer and out to the other side.
>
> \[Slide.\]
>
> Just to show you, this is a little easier to appreciate, these are the
> blood vessels just under the skin on the other side. Notice that we
> just saw them at the end of the paging through, because they are not
> in the slices that preceded them.
>
> \[Slide.\]
>
> Let me just show you this up close. Again, on a workstation, it is
> much easier to deal with this. Here we go, just looking at the tumor.
> Now you can see I think with much greater sharpness, the spiculations
> of the lesion, its irregular margins, and just the conspicuity of it.
>
> \[Slide.\]
>
> We will go to the next. I tried to put them side to side, and adjust
> them the same. This is the conventional mammogram on the left. Here is
> the tomosynthesis on the right. I think the ability to see this tumor
> is much greater than trying to pick it out of the background there.
>
> \[Slide.\]
>
> Here is another patient. This was a great pickup by one of my
> associates. There is some funny architecture right in here. It is
> actually not this, it is up in here. Let me see close up. You can see
> there is some funny\--again, the radiologists I think can appreciate
> some funny architecture there, everyone else is going what is he
> talking about. Anyhow, this is a good pickup.
>
> \[Slide.\]
>
> Here, in just the projection, I am going to show you in this area, I
> don\'t even think I see it on the conventional mammogram, but anyhow,
> here is the tomosynthesis. I think you can now see pretty easily the
> spicules coming out of this tumor, and then somewhat to our surprise,
> here is a second lesion.
>
> To get into our study, you have to have an abnormality on the
> film-screen image to begin with, so that this is tying tomosynthesis
> one hand behind its back, but this we have had now three cases where
> we picked up a lesion that was not visible on the conventional
> mammograms. We actually thought there might be a third one up here,
> but the surgeon wasn\'t willing to biopsy that, so we will just have
> to wait and see, hopefully, it is not.
>
> Just to put them side by side, the conventional image here, and then
> we will run the tomosynthesis for you here. You start seeing this
> condensation of tissue, I mean it just makes it much easier to see
> these things.
>
> \[Slide.\]
>
> There is the spiculate of the first one and then the second one right
> there, and just in case you don\'t believe me, we got both of them on
> the biopsy. Actually, I think they are easier to see almost on the
> tomosynthesis than there on the specimen, which is a switch.
>
> \[Slide.\]
>
> This is another case of a patient who came with a palpable
> abnormality, that we just don\'t really see on the mammogram, we
> couldn\'t see it in the cranio-caudal view.
>
> \[Slide.\]
>
> Here, on the tomosynthesis, if you watch right where I have got it
> labeled, you will see the cancer\--this was an invasive cancer come
> into view, and I am not sure what they were feeling. We looked with
> ultrasound, and they were close together, but there is a second
> lesion, a fibroadenoma, which again shows up on tomosynthesis.
>
> Now, we haven\'t looked at trying to differentiate benign from
> malignant at this point, but we think that we will have probably have
> a better shot. We have done some preliminary reader studies that, in
> fact, suggest\--and I can\'t give you all the data, because we are
> presenting it at the RSNA\--but that suggests that we see the margins,
> as you might imagine, of lesions much better with tomosynthesis than
> conventional, so we think we should be able to differentiate benign
> from malignant more accurately.
>
> \[Slide.\]
>
> Just a couple more cases here and then I will wind it up. This is the
> case of a patient who came in and had this asymmetry deep in her
> breast, and she didn\'t have it on the other side, so we were
> concerned. It really wasn\'t that dense, but invasive lobular cancer
> can do funny things, so we were going to biopsy this if we didn\'t
> have any other information.
>
> \[Slide.\]
>
> The problem was that we couldn\'t see it on the cranio-caudal view. We
> did extra views, and we really had a little bit of a quandary. She
> agreed to have the tomosynthesis. I put this in motion, you watch up
> here, you will see the lesion come into view.
>
> Then, for the radiologists in the audience, you will notice\--I don\'t
> know if you can see from the angle you are sitting up there, the
> panel\--you will notice that there is a nice capsule around the
> abnormality, which we could not see on the conventional imaging.
>
> We know exactly where this is now, because we know it was a 6-cm thick
> breast, and this was at millimeter 33, so not only do we know where it
> is 3-dimensionally, which we couldn\'t tell from the conventional
> mammography, but we also know that it is a mixed density lesion. It
> has got a pseudocapsule around it with fat and dense tissue, and that
> to a radiologist means it\'s a benign hamartoma.
>
> We were able to get this patient\'s old mammograms from California
> from eight years go, much to our surprise, and this was there eight
> years ago, so we are comfortable in just leaving this alone. Just
> based on the tomosynthesis, we would have been comfortable leaving it
> alone, but knowing it has been there for eight years unchanged, that
> confirms our suspicion.
>
> \[Slide.\]
>
> I think this is the last case. This is a patient who came in with a
> palpable abnormality. These are the mammograms that you take off the
> pile and you put down below that you are not going to get to that day,
> so that your associate can read them the next day.
>
> Very dense breast tissue and just very hard to tell what is going on.
> Someone thought they felt something. There actually is a little
> architectural distortion here, and again you can sort of see it in
> here. Everyone is going yeah, right.
>
> Here, just a little bit digitized representation. Something up in here
> maybe, hard to tell on a cranio-caudal view.
>
> \[Slide.\]
>
> Here is the tomosynthesis. As we page through, just showing the whole
> breast for a second here. I think you can all see the strands coming
> out and the lesion right here.
>
> \[Slide.\]
>
> Just make it a little bigger and side by side. It is very hard to see
> much on the conventional mammogram, page through. Again, with the
> workstation, you can go back and forth, so it is not hard to see, but
> here, you can see the spiculations that really aren\'t even\--I don\'t
> think you can see them there\--much easier lesion to see.
>
> We actually thought that there is another lesion here, and we are in
> the process of going through the pathology. This turned out to be an
> 8-mm invasive cancer with DCIS, and I think what we are actually
> seeing is DCIS as ductal extension here. We have got to confirm that
> with more detailed pathological review. This is just the lesion on
> ultrasound.
>
> \[Slide.\]
>
> Just one more case to show you some of the other features with
> tomosynthesis. Vary again, another one you put to the bottom of the
> pile, there is just all kinds of stuff going on here. There is some
> funny architecture right here.
>
> \[Slide.\]
>
> Here is the tomosynthesis. As we page through, you will notice that
> some of these are coming into very sharp detail with very sharp
> margins, and these turn out to be cysts. There is another one here
> again as you page back and forth, very easy to see.
>
> Then, we come into this spiculated architectural distortion. Again, in
> this room, with this light, it may be hard to see, but much easier to
> see with all the structure noise moved out of the way or cut out of
> the way with tomosynthesis as we page through.
>
> \[Slide.\]
>
> I will skip that.
>
> \[Slide.\]
>
> We have actually done reader studies now with tomosynthesis and the
> lesions are much more conspicuous with tomosynthesis. The borders of
> the lesions are more clearly defined. We virtually can eliminate
> recall for superimposed structures because there aren\'t any. When you
> are slicing through, you have eliminated everything that is in front
> or in back, so anything that is there is in a plane, and is not
> superimposed structure.
>
> \[Slide.\]
>
> The problem of where is it 3-dimensionally will go away because if you
> can see it in one view, you can figure out by what slice it is on
> where it is 3-dimensionally. We think\--we haven\'t proved this
> yet\--but we think we will be able to better differentiate benign from
> malignant. That, to me, would be nice, but it has got to be at least
> as good as a needle biopsy before I would rely on it, but that may be
> another feature of tomosynthesis.
>
> The issues that we have to deal with, of course, are two hours for
> reconstruction per study is a little bit too long, but we have already
> done the math, if you will, and the computer design that will allow us
> to reconstruct these in just a few minutes, probably one to three
> minutes per image, which would be like the old days of processing a
> mammogram, and with faster computers, we can get that down even more.
>
> \[Slide.\]
>
> The difficulty now is that instead of one to look at, the radiologist
> has 60 more, or 120, or whatever, you know, your slice thickness is,
> and we think that there are ways of dealing with that.
>
> It is actually not that bad. You can go through these very quickly in
> a workstation, you know, you can go back and forth instantaneously or
> slow it down, whatever you want, or once you have\--and this is great
> after lunch, we will have people barfing in the corridors\--what you
> can do is take these slices and put them back together as a
> 3-dimensional projection. This is what is called a maximum intensity
> projection. There are different ways of doing this.
>
> This is just a patient who had actually a previous biopsy. You can see
> where her skin is thinned right here. It is a benign biopsy. This is
> just some postsurgical change from the biopsy.
>
> But you can get an appreciation of how you could take these slices and
> put them together, so that the radiologist could very quickly look at
> this image and the computer programs are available today where you can
> just sit there and turn the breast as you want it.
>
> Whether this is the way we will look at them, whether the slice is the
> way we look at them, I am not exactly sure, but having worked with
> this system now for several years, I am convinced that this is the way
> we are going to be doing mammographies.
>
> If you think you had problems regulating conventional and the digital,
> wait until you get to tomosynthesis. I can imagine the issues that we
> are going to face in terms of quality assurance, but there is little
> doubt in my mind that the sensitivity of tomosynthesis\--I mean I am
> biased, you know that\--but I think everyone who has looked at it has
> agreed that the sensitivity of tomosynthesis will be higher than
> conventional and digital mammography, and the specificity will be
> higher, as well.
>
> We know we can eliminate 25 percent of the call-backs, so that right
> there is pretty desirable, and then the other points that I made.
>
> Again, I appreciate your inviting me here, and I would be happy to
> take any questions.
>
> DR. PISANO: Dan, do you do all the images always in the oblique
> projection?
>
> DR. KOPANS: Yes. So far we have only done them in the oblique
> projection. Our thinking has been that one of the advantages of
> tomosynthesis would be that we could eliminate having to do two
> compressions, which in and of itself, I think women would appreciate.
>
> So, we have really done most of our work that way. We have talked
> about it, maybe it would be even better doing it in two projections,
> and we will look at that in the future.
>
> MS. HARVEY: Dr. Ikeda.
>
> DR. IKEDA: How are you archiving these, and how big are the files?
>
> DR. KOPANS: That is a good question. The files are whatever a digital
> mammogram is times 60. I should have pointed that out, and thanks for
> the question. These are done at the same spatial resolution as the
> General Electric detector 100 micron pixel size, so it is a very big
> file.
>
> Right now we are archiving them on CD. That is a good point, but
> archive gets cheaper and cheaper every year, too.
>
> DR. IKEDA: And you are displaying them on a regular GE Advantage
> workstation?
>
> DR. KOPANS: We are displaying them on a 2K by 2K monitor. I have
> forgotten whose monitor it is. It is not GE\'s.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: Dr. Kopans, we have also done tomosynthesis, and we see
> your excitement in that area. I would like to ask you, how do you
> envision that we would be using tomosynthesis in a few years as the
> technology matures, because it is very difficult between diagnostic or
> there are certain groups of patients that you might say I want to go
> to tomosynthesis straight, bypassing the normal mammogram?
>
> DR. KOPANS: It is a good question, and of course, the question. In my
> mind, finding early cancers is the only reason to image the breast. I
> mean all the diagnostic imaging that we do, I think does have some
> benefit for patients, but the real benefit is in finding cancers early
> and saving lives.
>
> As we look at tomosynthesis, we see it as the screening test. It was
> interesting, I thought, well, it is only going to be in the dense
> breast, but even lesions in fatty breasts, small lesions in fatty
> breasts are much more conspicuous on tomosynthesis than they are on
> conventional mammography.
>
> So, I don\'t have a feel yet as to whether you do the fatty breast
> with conventional digital and you do the tomosynthesis in the dense
> breast. My prediction is\--again, I am biased, but I think I am going
> to be right\--is that it will become the screening mammogram.
>
> Now, proving that is a monumental task.
>
> MS. HARVEY: Dr. Ikeda.
>
> DR. IKEDA: Have you been able to display side by side, left and right
> breasts, because oftentimes we look for symmetry. Probably\--I don\'t
> know if the computing power is there yet\--but many people are
> thinking about, instead of unilateral MRI\'s, doing bilateral studies
> to look for symmetry, which can be a help sometimes.
>
> DR. KOPANS: Absolutely. We have put them up, but what we end up doing
> is that everyone concentrates, you see so much detail that it is kind
> of like you almost forget about the other breast, but that is clearly
> a study.
>
> Another thing that I didn\'t mention that we think is going to be very
> valuable is that computers now, and computer-aided detection, can look
> for morphologic features. They look for white spots, which are
> calcifications. They look for certain linear projections to look for
> spiculation. They are not very good at looking at masses, but they
> can\'t look at last year\'s mammogram and see if there has been a
> change to this year\'s mammogram, you just can\'t do that with
> 2-dimensional imaging.
>
> We think with 3-dimensional imaging, we will be able to teach
> computers to look for changes between last year\'s tomosynthesis and
> this year\'s tomosynthesis, because you have a 3D dataset that can be
> warped and registered, so you can see what has actually changed.
>
> So, we think that having 3-dimensional datasets is going to open the
> door even further for computer-assisted detection and diagnosis. I
> hesitate to talk about diagnosis because our needle biopsy techniques
> and even localization and surgery are so accurate and safe, that you
> really have to have a diagnostic system that was like 98 percent
> accurate to do away or even more than that, 99 percent accurate to do
> away with biopsies.
>
> But in terms of finding cancers, having a 3-dimensional dataset and
> then adding, for example, contrast agents to the tomosynthesis, adding
> ultrasound to the tomosynthesis, which we think we can do in exactly
> the same position, so that everything is perfectly registered, a lot
> of opportunity for investigation.
>
> That is why I say that, you know, digital is just in its infancy, and
> all the different things that digital is going to allow us to do are
> what are going to make it beneficial, not just that it is as good as a
> film-screen mammogram.
>
> MS. HARVEY: Dr. Ramos.
>
> DR. RAMOS-HERNANDEZ: Can you talk about cost, speculated cost?
>
> DR. KOPANS: It hasn\'t cost me a cent.
>
> \[Laughter.\]
>
> DR. KOPANS: Cost, again, you really don\'t know until the companies
> really get involved, and we are trying to get the companies involved.
> It will be more than a digital mammogram, but the real expense in
> digital mammography is the detector.
>
> So, once you have the detector, what we are doing is actually, we
> asked for \$25,000 from one of the companies to motorize the x-ray
> tube, we are going to do it ourselves, and they sent all kinds of
> people to talk to us. They must have spent well over \$25,000 visiting
> us, didn\'t give us the \$25,000, and then we went out and got a
> grant, and the company got a million dollars to do it, so they were
> smarter than we were.
>
> But it is just moving the tube, that doesn\'t cost much. The computers
> are getting cheaper and cheaper and cheaper, so if a digital
> mammography system retails for, what, \$400,000 or something, this
> might add \$100,000 to it, but that will come down as the computers
> get less expensive and more systems are purchased.
>
> We really haven\'t done an in-depth cost analysis because we are
> really in the very early study phase of this, but I don\'t think it is
> going to add that much expense, I mean per patient, that actually
> doesn\'t, that is a few dollars per patient.
>
> MS. HARVEY: Dr. Henderson.
>
> DR. HENDERSON: Jessica Henderson.
>
> Just out of curiosity, the patient who had three suspicious places\--
>
> DR. KOPANS: No, two, we don\'t know about the third one.
>
> DR. HENDERSON: Why did the surgeon only biopsy two?
>
> DR. KOPANS: Well, it gets to be tricky when you are doing research
> protocols, can you use the research to take care of the patient, and
> there are Institutional Review Board policies that start getting in
> the way of taking data from\--I mean no one has ever done this
> before\--so, we can\'t say to the surgeon, you know, we have got a
> track record, we know that is a cancer, and have the surgeon do a
> second biopsy.
>
> So, it becomes an ethical problem. There was enough debate in the
> group, that no, it isn\'t, yes, it is, no, it isn\'t, that we felt it
> was reasonable to follow her. She has got two cancers anyhow, she is
> being radiated and treated.
>
> The issue of finding additional foci of cancer, I mean my excitement
> in finding those two cancers is that tomosynthesis found a cancer we
> didn\'t know about. You know, the whole issue of do you really need to
> know all the cancer that is in a breast, this is going to sound a
> little strange, but that may not be a good thing.
>
> For example, with magnetic resonance imaging, people are finding more
> cancers or more foci of cancers in a breast than they originally
> thought, so the patient, instead of having her breast conserved, is
> having a mastectomy.
>
> Yet, at least in our practice, the recurrence rates for conservation
> therapy are incredibly low now. Our radiation therapists just looked
> at their data, and it is 2 percent at eight years, which is very, very
> low. So, maybe those cancers that we don\'t find now are being killed
> by the radiation, and finding them may be doing a disservice to the
> patients.
>
> There is a lot of issues that come up in the issue of multifocality or
> multicentricity in terms of cancer, so it gets, you know, when you are
> doing a research project, it gets even more complicated as to how you
> deal with that information.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: Just as a follow-up to that, you probably did all the
> other things you would normally do with that area, right? I mean just
> to clarify that.
>
> DR. KOPANS: Yes.
>
> DR. PISANO: You probably did extra views and ultrasound and all the
> things, and that is why the surgeon didn\'t want you to go after it.
>
> DR. KOPANS: Right.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: We often look at the cost of the procedure and the
> technology, but, Dr. Kopans, what do you think about the utilization
> or are there any potential costs to be saved if cancers are detected
> earlier, or of equal importance, if cancers or lesions are managed
> better, if you have better specificity, that way you might avoid
> procedures?
>
> DR. KOPANS: I think those are all very good points. As I said, 25
> percent of our recalls are for women who turn out to just have
> superimposed tissue, and we just have to get some extra mammographic
> views to kind of look around the trees to make sure that those are
> just superimposed, and not an actual abnormality.
>
> So, eliminating 25 percent of recalls is a desirable thing from a
> cost-benefit point of view. Then, better management of patients, those
> are sometimes hard to quantitate, but I think that my impression based
> on the work we have done so far is that our sensitivity will go up, so
> we will find smaller cancers, more small cancers, which I hope will
> translate into more lives saved. We are already seeing the decreased
> death rate in the United States from screening.
>
> I think that will help us with some of the cancers that we don\'t find
> now by mammography, and certainly don\'t find early enough, and then
> having the specificity improve will reduce some of the secondary costs
> of screening, as you point out.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: I have another question. What is the time line or what is
> the status of this technology in terms of FDA approval?
>
> DR. KOPANS: Oh, FDA approval. It has to be approved by the FDA?
>
> \[Laughter.\]
>
> DR. KOPANS: That will be up to the FDA, and I don\'t want to speak for
> them.
>
> DR. PISANO: Well, it has been submitted.
>
> DR. KOPANS: My guess would be it\'s at least a year for\--I am being
> optimistic\--a year for approval if we can get everything going very
> quickly, probably more like two years, and then approval for what is
> going to be the issue. Obviously, it will be approval as a diagnostic
> device. You can\'t do a screening test with it.
>
> We will have to sit down with the FDA and figure out how we decide
> whether it\'s used for screening, because this really is different. I
> mean I think most people who know me, know that I think making digital
> mammography have to go through a PMA process was a major mistake that
> the FDA has done, and it is going to make it very difficult to improve
> the conventional digital technology.
>
> The reason I argued against it was that digital mammography is the
> same as film-screen mammography. I think D-MIST is going to show that.
> The other studies that have been available have shown that they are
> really the same.
>
> This is different, so this is going to need a PMA and all the things
> that go along with that. I mean I would like to see it out there in
> between three to five years, shorter if possible, I am not optimistic
> it can be shorter, but we will see.
>
> MS. HARVEY: Dr. Harrison.
>
> DR. HARRISON: This is fascinating. You made a comment that you
> envision getting to a point where resolution of malignancy, if it gets
> up around 99 percent, we could proceed without tissue.
>
> Do you really think we are ever going to get there, considering that
> many of the subsequent management decisions are based on histologic
> findings?
>
> DR. KOPANS: No, I think that is a good point. I think that histology,
> although there are technologies that are now looking at this, spectral
> analysis using lasers, we fiddled around with this a number of years
> ago, where you put a needle in and try and get the spectral analysis.
>
> All of our therapy, as you point out, is based on histologic analysis
> and margin analysis, and that is also going to get in the way of in
> vivo ablation, you know, what is the margin analysis, and so on.
>
> That is why I am almost discouraged that we have to go through the
> diagnostic route to get technologies approved, when it is really
> screening that is going to be beneficial, but I understand the
> reasons, and they are good ones.
>
> MS. HARVEY: Thank you.
>
> DR. KOPANS: Thank you.
>
> I believe we will have a break now, come back about 10 minutes after
> 3:00. Thank you.
>
> \[Break.\]
>
> MS. HARVEY: We are having a talk on the Inspection Demonstration
> Project. It\'s an update by Charles Gunzburg of the Division of
> Mammography Quality and Radiation Program.
>
> Welcome.
>
> **Inspection Demonstration Project**
>
> DR. GUNZBURG: Thank you very much.
>
> I am going to hopefully walk through this pretty quickly and let you
> know what our program is and I guess the who, what, when, and where of
> the program.
>
> \[Slide.\]
>
> When Congress first passed this Act, they included the requirement
> that there be annual inspections of all certified facilities.
> Initially, the compliance rate, not the noncompliance rate, but the
> compliance rate was relatively low, but as soon as the facilities
> became aware of what we expected and became more familiar with the
> regulations, the compliance rate rose pretty dramatically.
>
> Many facilities and some professional organizations were concerned,
> that were actually hopeful that we could inspect on a less frequent
> basis and actually save them some money and time.
>
> We pointed back to the Act and said no, we can\'t do that, we have to
> do this annually.
>
> \[Slide.\]
>
> So, they went to Congress and they talked to them, and asked them to
> do something about it. Congress listened and when they passed the
> Reauthorization Act in 1998, they kept the annual requirement, but
> they added a provision for an inspection demonstration program, and
> that would be a test program under which certain facilities could be
> inspected less frequently than annually.
>
> \[Slide.\]
>
> It couldn\'t be implemented before April 2001, so that was easy.
> Facilities had to be substantially free of noncompliances, and the
> number of facilities had to be a statistically significant sample of
> the facilities available.
>
> They didn\'t specify an inspection frequency, but they said that it
> had to be one that was capable of reasonably assuring compliance with
> the standards.
>
> \[Slide.\]
>
> So, FDA took that guidance and came up with some criteria of their
> own, and that was that the States and facilities would be selected
> according to a specific written criteria. We would include both study
> and control groups, and conduct inspection of the study group every
> two years or at least two years on the first basis, and annual
> inspections of the control groups.
>
> \[Slide.\]
>
> The participation criteria for the States, first of all, the State had
> to be willing to do it, they had to agree to do it. They couldn\'t
> have any laws or policies or requirements that meant they had to go to
> the facility more frequently than we were specifying in our project or
> our plan, and that was going to be two years again.
>
> They had to agree to inspect at the frequency designated by FDA.
>
> \[Slide.\]
>
> They also had to be able to accept modifications to their contract,
> all these States that have contracts with us, about how many
> facilities they would inspect annually, and they had to be able to
> absorb the loss of income from not inspecting these facilities, and be
> willing to do that. They had to notify us if they found any problems
> that were important.
>
> \[Slide.\]
>
> That left us with 14 participating groups. We have 11 states and 3
> other testing jurisdictions.
>
> \[Slide.\]
>
> For a facility to be included, they had to have undergone at least two
> inspections under the final regulations, two annual inspections. They
> had to have no citations in the last two inspections under the final,
> and they had to have never been considered, received, or being
> considered for any regulatory action by FDA.
>
> \[Slide.\]
>
> They also had to anticipate providing services throughout the length
> of the program, and they had to maintain their accreditation and
> certification, and lastly, they had to be kicked out of the program,
> the random selection process as being one of the facilities to be
> included.
>
> \[Slide.\]
>
> That left us with this. It varies between one facility in some states
> to 24 in Ohio, and if you lump New York together, 35 facilities in New
> York State.
>
> \[Slide.\]
>
> Currently, we have notified everybody that we could think of that
> needed to know about this program, that it was in process. We have 155
> facilities, about 155, and approximately 155 facilities in the study
> and the control group.
>
> Those numbers are approximate because we never know when somebody is
> going to drop out. So, we don\'t know what we are going to finally end
> up with, but somewhere in that region we hope.
>
> We actually began this process in May of this year.
>
> \[Slide.\]
>
> Where are we going with it? We are going to continue the annual
> inspection of control groups. The changes that this necessitates means
> we are going to have to make some changes in the procedure and the
> software. We hope to have those changes in place by January, and we
> hope to have them tested shortly thereafter, and begin testing the
> study group facilities about the middle of the year.
>
> Hopefully\--this is not a real firm number\--but we hope that it
> works. It should finish about July of 2004 and begin data analysis at
> that point.
>
> That is all I have. Questions?
>
> MS. HARVEY: Any questions?
>
> DR. GUNZBURG: Good. Thank you.
>
> MS. HARVEY: Thank you.
>
> Dr. Chakrabarti and Ms. Butler will talk to us about full field
> digital mammography, accreditation and certification update.
>
> **Full Field Digital Mammography**
>
> **Accreditation and Certification Update**
>
> \[Slide.\]
>
> DR. CHAKRABARTI: By now you have heard this several times, that GE\'s
> system was approved first by Office of Device Evaluation followed by
> Fischer and then Lorad, and you also know that there is no accrediting
> body, Dr. Finder explained that at the beginning of previous session,
> and we provide approval based on extending the existing screen-film
> certificate.
>
> I will briefly discuss and summarize the approval process here.
>
> \[Slide.\]
>
> Until otherwise notified by FDA, an FFDM unit will be exempt from the
> MQSA accreditation requirement, and until FDA issues such
> notification, a facility must request FDA to extend its screen-film
> certification to cover its FFDM units.
>
> Requests for FFDM certification extension need to supply all the
> information listed in the document MQSA Facility Certification
> Requirements. This is on our web site, also the facility request has
> to provide application form, application package. There is that
> information about the facility certification requirements. I will give
> the gist of that here.
>
> \[Slide.\]
>
> In that requirement, the facility needs to furnish facility status
> information, FFDM Unit identification, digital image receptor
> identification, identification of printers for hardcopy output,
> monitor identification if softcopy display is available, phantom
> identification, personnel qualifications.
>
> \[Slide.\]
>
> Phantom image, personnel information, Report of Mammography Equipment
> Evaluation, manufacturer\'s quality control program. I will take a
> brief pause and I will mention that we need, in FDA, we reviewed this
> with a phantom image, we need to have a phantom image.
>
> Also, this third bullet, which says the Report of Mammography
> Equipment Evaluation, and that is 900.12(e)(10) of the final
> regulation, that is applicable to all modalities, but in case of
> digital, a new modality, the No. 4 bullet, which is very, very
> important, that means all QC programs, equipment evaluation must be
> performed according to the manufacturer\'s requirement. That is the
> 900.12(e)(6). That is in the final regulation.
>
> So, when we review the Mammography Equipment Evaluation Report, we
> look at whether the facility has performed their tests according to
> the manufacturer\'s requirement of that FFDM system. That is very
> important.
>
> Also, we need the signature of the lead interpreting physician. That
> signature tells us that all the information provided are true. We
> don\'t need to have all the documentation about personnel
> qualifications.
>
> We need the list of the personnel who will be working on the FFDM
> system, but whether that person is qualified to perform and have
> additional 8 hours of training, that is being sort of guaranteed by
> the signature when the inspector goes to the facility, inspector
> verifies those documentation or at the station of the personnel.
>
> Now, once all this informations are furnished, we review the equipment
> evaluation report and phantom image, everything is satisfactory, we
> send a facility a letter of approval mentioning that your FFDM system
> is included with the conventional screen-film mammography
> certification, and that letter goes out in the name of our division
> director, and then the facility can perform using efficient imaging
> with the FFDM system.
>
> \[Slide.\]
>
> If a facility receives a letter of acceptance, the approved FFDM unit
> will be added to the facility\'s certificate.
>
> The facility must maintain its accreditation status for at least one
> screen-film unit in order to keep its certification alive and then can
> continue to utilize FFDM unit.
>
> The facility is also subject to an annual on-site MQSA inspection of
> its FFDM unit at the same time its screen-film units are being
> inspected.
>
> \[Slide.\]
>
> The FFDM unit must be located within the same inspection jurisdiction
> as the certified screen-film unit. In most cases, this means that the
> FFDM unit must be located in the same state as the certified
> screen-film facility.
>
> The lead interpreting physician must oversee the quality assurance
> program for both the screen-film and the off-site FFDM units. That is
> very important. We want to make sure that we make one person, who is
> the lead interpreting physician, responsible for overseeing the QA
> program in both screen-film and the FFDM system.
>
> In general, we respond in three to five days from the time we get the
> application. If the application is complete, I showed you the gist of
> the information that they have to furnish, plus if the mammography
> equipment evaluation report is complete and perform according to the
> manufacturer\'s requirement.
>
> Indeed, there is the problem that we see, that for the first time
> facilities and first time medical physicists, there is physicists
> having a number of problems providing the proper MEE for FFDM system.
>
> \[Slide.\]
>
> I will go over a few tests where we see the problem. Now, here is a GE
> system, GE Senographe 2000D. If you look at that, you see that GE
> requires that signal-to-noise ratio should be over 50 in an AOP mode,
> standard mode and SNR check.
>
> Now, if the facility does not, the medical physicist does not perform
> the test and do not use the raw image, they use process image, they
> get more than 100 percent inflated value of SNR. So, it does not tell
> us whether the SNR will pass the minimum of 50 requirement or not.
>
> So, then, I call the physicist, they have to come back and redo the
> test, and this has happened a number of times.
>
> Then, there is another one in this, that if you look at that, the GE
> requires the kV must not change, kV should be same if you are in the
> 2.5, 4, and 6 cm thickness, kV should be the target filter, and kV
> should not change.
>
> There can be a range of mAs value, however, kV should be 27, 28, 32,
> depending on what thickness you use. We have seen in some cases, that
> that has changed, and we have to discuss with GE, and then that took a
> little more time for approval process.
>
> \[Slide.\]
>
> Another thing that I will mention in this regard is that the dose has
> to be performed in the AOP mode, three OP modes, and many first-time
> physicists haven\'t done that, have simply provided the dose value,
> but we are finding out that that is creating problem also, creating
> problem for us to give approval on time, which we believe we can do it
> within three to five days if the report is complete and tests are
> performed according to the manufacturer\'s specification.
>
> \[Slide.\]
>
> Now, these are the three tests which must be performed with raw
> images. Very recently I am seeing even the signal-to-noise tests are
> different values than what is coming forth with the raw images,
> because some physicists have done it with process image.
>
> So is MTF measurement and AOP mode and SNR check, all three tests must
> be performed in raw images, and it is very clear in the manual, and
> some physicists are missing it.
>
> \[Slide.\]
>
> I will mention here there is another reason that MTF values, some
> physicists have reported MTF value more than 100 percent. One way you
> can do that, if you do not put your elliptical region of interest
> tightly within the bar pattern, if it goes beyond that, then, your
> value would be very incited \[ph\], and we can look at the number, and
> you can see that these are not done properly.
>
> \[Slide.\]
>
> Another thing that is very important and that physicists are missing,
> these are the list of things that GE wants and must be performed -
> room layout, room description, why this is important, because if all
> these things are moved around, then, particularly the dark level from
> the monitor will change drastically and the calibration would be
> disrupted. So, you want to see that this information is provided
> properly as mentioned in the manual.
>
> \[Slide.\]
>
> Now, there is new change, there is revision of GE\'s manual is out,
> and I am seeing that many physicists are still using the older manual.
> In the new manual, the physicists are not supposed to be doing any
> calibration, performing calibration, but they will check the
> calibration as performed by the service engineer, and they will
> perform the records of five reference luminance levels as given by
> this curve.
>
> Many physicists are missing that, they are not giving those values or
> they are getting wrong numbers.
>
> So, these are the things that are necessary for GE system to get
> approval within the proper time.
>
> \[Slide.\]
>
> This is the Fischer system. Here, I see that many physicists are not
> performing the system resolution test properly. They are using simply
> bar pattern and then counting the number. They must be following what
> the manufacturer says in their manual.
>
> \[Slide.\]
>
> Also, I see that artifacts are not far from recording the window width
> that is specified in the manual, and this flat field tests are not
> performed at the region, at the corner and the center that the
> manufacturer requests. Thirdly, the Fischer system has a contrast
> disc, unlike the GE system where GE prohibits use of a contrast disc
> with their phantom.
>
> So, those are the things that there is a difference from one
> manufacturer to another manufacturer, and even for the same
> manufacturer, there are changes in the manual, the physicists and the
> facility must be aware of that and must be performing mammography
> equipment evaluations and the QC according to that, and that is the
> cause of the delay many times.
>
> Sometimes facilities call us as soon as they send this thing, and says
> we are already schedule patients, and unless they have their report
> properly done, we cannot give approval.
>
> Any question or should Penny speak first?
>
> MS. HARVEY: Any questions?
>
> Thank you.
>
> Sorry, Dr. Karellas has a question.
>
> DR. KARELLAS: Kish, according to FDA, are facilities required to have
> a printer? I know the use of the printer and I realize that without a
> printer, it is going to be very difficult to operate, but does FDA
> require it?
>
> DR. CHAKRABARTI: Yes, we require for the foreseeable future, we
> require the original mammogram must be provided in the form of hard
> copy. The facility has to have a printer available for a hard copy
> printout when the patients ask for the original image.
>
> DR. KARELLAS: What if the facility has an option of printing off site
> upon request, does the printer have to be on site, or what if the
> printer is within the broader institution, another building or
> something like that?
>
> DR. CHAKRABARTI: That will work out fine, but when you apply, there
> was a prior mention of the list, the printer, you have to mention that
> that printer number is this, we have to make sure that the same
> printer as manufacturer, is comfortable with the manufacturer\'s
> system, and if it is available off-site, then you mention it is
> available there, and that will work out.
>
> MS. HARVEY: Thank you.
>
> Ms. Butler. Good afternoon.
>
> MS. BUTLER: Good afternoon.
>
> I am Penny Butler from American College of Radiology, Senior Director
> for Breast Imaging Accreditation Programs.
>
> I thought I would give everybody an update on where the ACR is with
> full field digital mammography accreditation.
>
> \[Slide.\]
>
> The last time we spoke, the full field digital accreditation module,
> it is not a new accreditation program, but it is a supplement or a
> module to the mammography accreditation program that has been in place
> since 1987.
>
> It was complete and it was midway through our internal ACR leadership
> approval. We had really hoped it was going to be out, be approved by
> the ACR leadership by September of 2001. I think you all know perhaps
> what has slowed that down.
>
> The module that we developed was manufacturer-specific. GE was the
> first FDA-approved FFDM system, and the reason for this were
> multifaceted. First, the exposure control mechanisms are different,
> meaning that our instructions to facility in order to make phantom and
> dosimetry measurements had to be unique to the manufacturer, and due
> to the FDA regulations, the required quality control is different.
>
> \[Slide.\]
>
> Since that time, in early October, ACR sent the full field digital
> mammography module document to the Executive Committee of our Board of
> Chancellors, and also at the same time, to the FDA for review.
>
> In mid-October, these documents were approved by the Executive
> Committee. In mid-November, FDA had instructed us to submit a formal
> application for approval of the full field digital mammography
> accreditation module, and this formal application needed to include a
> number of requirements that we hadn\'t addressed when we sent them the
> documents. We weren\'t aware that we needed a formal application, and
> these were basically to address the elements that were in Part A of
> the regulations, similar to what we addressed in the accreditation
> body approval application that they approved on December 20th, 2000.
>
> \[Slide.\]
>
> At the beginning of July 2002, we submitted a complete formal full
> field digital mammography accreditation module application to the FDA.
> At the end of July, after initial review of the application, FDA
> advised us that there was some of the information provided with an
> alternative standard request that we had submitted was insufficient.
>
> This alternative standard request had to do with the exposure of the
> phantom and acquisition of dosimetry data during our mailed
> accreditation process.
>
> In early August, I worked with some members of the Digital
> Subcommittee to collect some additional data to supplement this
> alternative standard request, and right now the material is under
> revision internally before we forward this to the FDA.
>
> \[Slide.\]
>
> So, that is the current status of the accreditation program. I would
> like to review some of the proposed accreditation process for full
> field digital mammography.
>
> \[Slide.\]
>
> In general, our process is not going to differ than what we do for
> film-screen mammography. The paperwork that a facility submits to us
> is going to depend, just like film-screen, on how much time the
> facility has left on their MQSA certification and their accreditation.
>
> In general, if they have less than 13 months left on their
> accreditation, all the units at the facility go through an early
> renewal process at the usual fee.
>
> If they have greater than 13 months left on their accreditation, they
> will complete what we call a mid-cycle, we call it the New Unit
> Addendum Process at a reduced fee. The fee for accreditation for full
> field digital is not going to be any different from film-screen.
>
> At that time, once the program is approved, the facilities will be
> able to have stand-alone digital systems and no screen-film will be
> required within the facility or associated with the facility as Kish
> has just described.
>
> Keep in mind that right now, since the first application is for GE,
> right now we are talking about GE systems.
>
> \[Slide.\]
>
> The clinical image quality evaluation will not differ. Our Digital
> Subcommittee and our Committee on Clinical Image Review have
> determined that they will be evaluating the same eight attributes in
> exactly the same way, and that is position and compression, exposure,
> contrast sharpness, noise, artifacts, and labeling.
>
> All images will be submitted on hard copy at this time, and all of the
> ACR reviewers are qualified in digital mammography under the MQSA
> requirements.
>
> \[Slide.\]
>
> Phantom image quality evaluation is not going to differ. Again, they
> have to be submitted on hard copy. The scoring is going to be the same
> as with screen-film, that is, fibers, specks, masses, and the
> subtraction of artifacts.
>
> We have made a minor revision to how we evaluate the phantom image
> quality to take into consideration some of the very special artifacts
> that you might see for digital, but they were relatively minor, so we
> could just supplement our standard evaluation form.
>
> Also, as with clinical review, the ACR reviewers are qualified in
> digital under MQSA.
>
> \[Slide.\]
>
> So, if all these things are the same, why do we need a separate
> accreditation program or a separate module to accredit digital? Well,
> most of this falls down to 900.12(e)(6), as Kish had described and let
> me just read this to you. \"For systems with image receptor modalities
> other than screen-film, the QA program shall be substantially the same
> as the quality assurance program recommended by the image receptor
> manufacturer except that the maximum allowable dose shall not exceed
> the maximum allowable dose for screen-film.\"
>
> \[Slide.\]
>
> So, we are working with the screen-film dose limit, but the QC program
> as specified by the manufacturers. So, let\'s talk about the phantom
> exposure and dosimetry.
>
> As you aware, ACR has a male dosimetry program. We tried to get
> radiation dose estimates concurrently with the phantom image quality,
> and so these are done at the same time, so we can provide better
> information back to the facility of what possible causes for poor
> image quality may be, and certainly a dose that is too low is a strong
> reason for why image quality may be poor.
>
> We do this currently through a mailed TLD. The TLD dosimeter is in a
> little holder, it is several millimeters thick, and it is placed
> typically upon the phantom. With the GE system, the exposure control
> mechanism that is typically used under an AOP is very different from
> what is used for a film screen.
>
> The exposure control mechanism is different among the different
> manufacturers. Some of the manufacturers are using just strictly
> manual techniques right now. Consequently, our instructions to the
> facility have to be unit-specific, and we are very conscious about
> sending written instructions out to facilities because it is very easy
> for the technologists, who are usually the ones doing all the work, if
> the instructions are too technical or too physics like, it could be
> not clear enough. We can get some very strange numbers back.
>
> The GE exposure is impacted by the thickest or the densest part of the
> breast, and if you use the routine phantom, the plastic rim around the
> wax block that is in that phantom, and on top of that, the TLD holder
> that we use, it can result is a significantly higher exposure than one
> would anticipate under film-screen conditions, for example, for the
> 4.2 cm breast.
>
> So, we have revised our instructions for GE to have the facility first
> expose an acrylic block, and that acrylic block is equivalent to the
> 4.2 cm tissue, which is what the center part of the ACR phantom is
> equivalent to under AEC to determine the appropriate technique.
>
> Then, we asked the facility to exposure the accreditation phantom, and
> a dosimeter with the manual technique which is closest to the
> technique that came up under AOP mode. This is one of the items that
> we are working with FDA on to revise, to make sure that it is
> appropriate under the regulations.
>
> \[Slide.\]
>
> In addition, we have tests listed in our application materials that
> the facility must submit either information on or a checklist showing
> that they do these tests, and these are specific to GE.
>
> \[Slide.\]
>
> Likewise the medical physicist test, they must submit equipment
> evaluation and if it is an annual survey, the annual survey report
> showing that they have performed all of these tests and all the tests
> appropriately meet the regulations.
>
> \[Slide.\]
>
> Once we receive FDA approval for the first manufacturer\'s module, the
> GE module, we are going to complete development of the modules for the
> other FDA-approved units.
>
> This is my last slide, but I would like to add that some of the
> comments that were brought up here earlier regarding harmonizing the
> QC test among the different manufacturers wherever possible is
> something that would enable us to operationally make evaluation of
> applications submitted by facilities under the accreditation program a
> whole lot easier, and we fully support that effort.
>
> Any questions?
>
> MS. HARVEY: Do we have an idea how long it will be before there is
> going to be an approval, like within the next six months, a lifetime?
> This is the question I probably get most frequently these days.
>
> DR. FINDER: I would like to give you an answer. It is a process that
> is ongoing. Obviously, both sides here are trying to accomplish this
> as quickly as possible. We all understand the implications of having
> an accreditation body or not having an accreditation body.
>
> I cannot give you a specific date or a time, but I can tell you that
> everybody is working as hard as they can to get this done as quickly
> as humanly possible.
>
> MS. BUTLER: Obviously, FDA, the next step, well, FDA is concurrently
> reviewing our full application that we sent in, and we are working to
> provide the supplemental material to them as quickly as possible for
> the alternative standard.
>
> MS. HARVEY: Thank you.
>
> Any other questions? Dr. Gray.
>
> DR. GRAY: Joel Gray with Lorad Corporation.
>
> I have two questions, one for Penny and I believe one for Charlie or
> somebody.
>
> You indicated that your image quality test is going to remain and the
> same, and the question is will the requirements for fibers, specks,
> and masses, 4, 3, and 3, remain the same, and the question for Charlie
> or someone, does this mean that each accrediting body is now going to
> have to go through and complete this process that ACR is, so you are
> going to have to go through this process of approval four more times?
>
> MS. BUTLER: I will take the easy question. For GE, the standard was 4,
> 3, and 3. That is what is in their QC manual. That is what we were
> moving forward with.
>
> DR. FINDER: With respect to the accreditation bodies, the
> accreditation bodies are free to apply for FFDM. If they do, they will
> have to go through a process similar to what we are requiring of
> everybody else. It is the same process. So, the answer is yes.
>
> MS. HARVEY: Ms. Martin.
>
> MS. MARTIN: Penny and I both spent the last couple of days going to a
> class on the physics of digital mammography and how to do all these
> wonderful tests. One comment that I got consistently from most of the
> attendees, and I would just pass this along, I am not sure where it
> will go, is that from what we could see, most of the units could do a
> 5-4-4 score, and we were wondering why that was not set. If the
> digital is capable of being better, why are we setting the score so
> low for the phantom image, because if you can\'t get a 5-4-4 out of
> it, you really don\'t have your digital set up right.
>
> I mean why was it set so low?
>
> MS. BUTLER: Well, we are going with the GE Quality Control Manual as
> far as meeting the specifications. That was outlined in that.
>
> DR. PISANO: I know Penny knows about this, and maybe some of you also
> do. There is a phantom that has been developed for D-MIST, for digital
> mammography, which they are calling MISTY, which is really a much more
> challenging phantom for digital mammography, and we are going to have
> a lot of data on its performance across the trial through the D-MIST,
> that same presentation that I referred to earlier.
>
> I think Dan Kopans commented that really, this technology makes the
> ACR phantom somewhat archaic, it\'s not challenging enough for
> digital, so perhaps over time there can be a evolution to another
> standard or any other phantom. I like what Penny has done or what the
> ACR has done, it is just adopt what GE did before this phantom became
> available, and I think that is a reasonable first step myself.
>
> MS. BUTLER: To expand on that a little bit more, what the subcommittee
> has been talking about is the current phantom the appropriate one, and
> I think there is a prevalent thought that there probably could be a
> better phantom out there, but being involved with developing new
> phantoms in the past and having them adopted is not something that
> happens overnight. You think this process is long, try to develop a
> phantom.
>
> To get going, we are staying with the ACR phantom the way it is right
> now and then hopefully look at this in the long term.
>
> MS. HARVEY: Dr. Karellas.
>
> DR. KARELLAS: The issue about the various phantoms was discussed, as
> the ACR is well aware, with Dr. Yaffe. Dr. Yaffe is very familiar with
> that phantom. I believe he developed it. So, I just wanted to inform
> you that this decision was not totally arbitrary, and it has been
> decided, according to my understanding, and as Penny pointed out, that
> at this time, a decision was made to stay with the existing phantom.
>
> I have no idea as to when we will be going to a new phantom. Chances
> are at some point, something will change.
>
> The other issue, though, that I think is of some importance, is to
> consider the minimum score required for these phantoms, that we cannot
> make an arbitrary decision, and frankly, I cannot tell you that if we
> increase the score one notch, something is going to change all of a
> sudden.
>
> I find often on a phantom review, that some of my objections may not
> be as much with scoring, Pugh scoring of all the features in the
> phantom, but with the overall impression of the image, like excessive
> noise. Although you see everything, you just don\'t like the noise and
> the image artifacts, that they are excessive and bothersome, and I
> would like to see something that addresses all these issues, giving a
> little more latitude for the reviewers to be a little more critical.
>
> There is latitude right now, but perhaps to the point that we can
> actually reject something a little more easily in the future.
>
> MS. HARVEY: Another question?
>
> CPT THOMAS: My name is Jerry Thomas. I am at the Uniformed Services
> University. Kind of a comment and a question at the same time.
>
> It has been clearly pointed out that there are substantial differences
> between quality assurance programs for each of the three approved
> digital systems. Our current training requirements are eight hours for
> a new modality.
>
> Do we have three different new modalities? I think maybe eight hours,
> in my experience, and I ran this program, it was this past weekend
> that Melissa talked about, I think maybe eight hours is not enough
> training.
>
> I would suggest you may want to consider what the impact of these new
> modalities are going to be on both the training requirements for the
> technologist, as well as the medical physicist. I think probably the
> radiologist training could meet the eight-hour requirement without
> additional training, but probably not the other two.
>
> I would like to hear other thoughts, as well.
>
> MS. HARVEY: Ms. Martin.
>
> MS. MARTIN: I guess my first response would be again coming from some
> of the other physicists, too, or their training, I think we have to
> look at it. I guess I don\'t have a problem with the eight hours of
> the initial training. The first time any of us have to go through one
> of these machines, you are going to have to go through it with the
> manufacturer\'s representative.
>
> Certainly, eight hours of general training would not qualify you to
> walk in cold and do a different manufacturer\'s unit with absolutely
> no assistance, but eight hours of basic training in digital
> mammography imaging would qualify you to go with the engineer.
>
> That is just an opinion, but I would agree with Captain Thomas, you
> are not going to be ready to do it without anyone around.
>
> DR. PISANO: I just have a comment about the technologists. Does
> anybody who is a technologist want to comment about the technologist
> training? Did you want to comment? I really wanted a comment from a
> technologist if that is possible.
>
> MS. ELLINGSON: I am not working in the field myself, but we do have a
> lot of questions coming in to ASRT. They seem to think we know all the
> answers, but it is not very specific as to what eight hours of
> training is, is it applications training, is it a CE course where you
> heard a lecture on digital.
>
> The questions that I am getting leads me to believe that it is not
> very clear what is intended for them to count as the eight hours of
> initial training.
>
> MS. HARVEY: Dr. Pisano.
>
> DR. PISANO: I just want to comment that in my experience, as I
> mentioned earlier, I have three different machines, and I find that
> the eight hours is more than adequate for the technologists to learn
> how to use the equipment and the tests that they are required to do.
>
> I have probably been through this process with about, I would
> guesstimate 20 technologists at this point, because we have these
> three units, and we have a turnover in our place, so we have done it
> quite a bit. I haven\'t found too big of a need for additional
> training ever, in fact, out of all those techs.
>
> DR. FINDER: Going back to the question about what types of training
> are involved, again, we have to go back to the history behind this. At
> the time the regulations were written, these units didn\'t exist, so
> we tried to get the best opinions and expert advice that we could to
> try and settle on some type of initial training that was required, and
> we came up with the eight hours for the various personnel categories.
>
> In our guidance, we have enumerated some of the things that can be
> used to meet this eight hours of training, and again, we were fairly
> flexible and general in the statement, so yes, hands-on experience can
> count in terms of training programs, CME courses, CEU courses would
> all, if they added up to the eight hours, would meet the requirement.
>
> DR. PISANO: I think the technologists are highly motivated also to
> learn how to use the equipment, and if they need more time, they are
> not shy about saying to the equipment manufacturer representative, who
> is present, that they need more time learning.
>
> I haven\'t found it to be a real problem. I can also say from the
> radiologist perspective, many radiologists have said to me\--I
> actually run one of these programs for CME credits\--and while it is a
> very nice way for our program to make some money, I have had many
> people say that they don\'t think eight hours is appropriate, that
> probably four would do, so maybe that could be shortened at some point
> for radiologists. It is really not that different.
>
> The main difference is reading on softcopy, so that is just another
> viewpoint on that.
>
> MS. HARVEY: Mr. Crocker.
>
> MR. CROCKER: This is Ken Crocker from Fischer Imaging again.
>
> I just wanted to kind of reiterate that I think we need some urgency
> in developing some uniformity. You know, if you look at some of the
> times lines here, GE had their PMA approval in December of 2000, and
> we are here today yet, and for one manufacturer and with one
> accrediting body, we don\'t yet have the process moved over to the
> accrediting bodies.
>
> The other thing I would like to point out is that it appears that the
> approach that is being taken is very linear or sequential rather than
> in parallel. I think as Penny mentioned, they are working very hard to
> work with one accrediting body, with one manufacturer, to get one
> approval.
>
> If we continue that approach into the future, it is going to really
> tie a lot of people up and a lot of users up not having achieved their
> transfer over to what the regulation really intended.
>
> That is just a comment.
>
> MS. HARVEY: Thank you.
>
> Another question?
>
> MS. MARTIN: As a consulting physicist, I can only support Penny\'s
> comment and Ken Crocker\'s comment. If there is one set of forms, one
> set of measurements that we are all expected to make, that is to the
> benefit of all the physicists.
>
> MR. VASTAGH: My name is Steven Vastagh. I am with the NEMA, National
> Electrical Manufacturers Association. I am pleased to recognize that
> it is wonderful that we have, not one, but three or four different
> solutions for digital mammography, so there are two sides for each
> issue, but I am pleased to tell you that NEMA and the manufacturers
> will begin to make an effort to harmonize QC tests. I am real pleased
> to hear that the accreditation bodies are supportive of that and hope
> that this will contribute to speeding up the process.
>
> MS. HARVEY: Thank you.
>
> Any further questions? No? Thank you.
>
> Let\'s move on now to Dr. Burkhart, who will tell us a little bit
> about States as Certifiers.
>
> **States as Certification Agencies Update**
>
> DR. BURKHART: I am going to give a brief update. The way I should
> start is to point out that these activities all originate from
> Subsection Q of the original Mammography Quality Standards Act of
> 1992.
>
> Subsection Q permits FDA to authorize State agencies to carry out some
> of the functions under our oversight. Perhaps most visible of these
> functions is the actual issuance of the certificates to the
> facilities, the certificates that they need to be able to do
> mammography, and because of the visibility of this particular
> function, that is why we refer to the whole effort as State\'s
> certifiers or we commonly use the acronym SAC to refer to these
> activities.
>
> But it shouldn\'t be forgotten that this is not the only function that
> the States can be authorized to carry out. Among other functions is
> administrative control of the inspection activities within their
> borders. As I think probably everybody knows, the great bulk of the
> inspections are performed by State personnel under contract to FDA,
> under general FDA oversight and administrative control, but a SAC
> State can have the function of that general administrative control.
>
> With this comes any associated follow-up actions to the inspections,
> any follow-up on the Level 1 or Level 2 citations can become the
> responsibility of the SAC State.
>
> To go a step further, if compliance actions are necessary, these also
> can be a function which the State can be authorized to carry out
> although I should mention in connection with that, FDA still has the
> right, the authority to carry out compliance functions within a SAC
> State, as well as the State itself.
>
> On the other hand, I should point out that perhaps a major function
> that can\'t be delegated to a SAC State is the function of developing
> the standards for the accreditation bodies or for the facilities.
>
> This is specifically prohibited by law being delegated to a SAC State,
> and we define this as including not only the regulations, but also the
> guidance which interprets the regulations. This remains an FDA
> function again the SAC States.
>
> Before we could open up the possibility nationwide of States becoming
> SAC States, we needed to have implementing regulation, and to help us
> develop these regulations, about three years ago now, a SAC
> demonstration project was established, which the idea was that a
> limited number of States, for a limited period of time, would be given
> SAC functions to carry out.
>
> They would be authorized to carry out the functions that I mentioned.
> So, for about three years now, the States of Iowa and Illinois have
> been recognized as SAC States, and they have been carrying out the
> functions that I mentioned, and from this experience, we have gained a
> great deal of information which has been useful to us in developing
> regulations.
>
> It has also been useful to use in our thinking about the long-term
> oversight activities, but now we are ready to move on to another plane
> because on February 6 of 2002, SAC regulations were published as
> final, and they became effective on May 7th.
>
> So, now we have a third subpart to the MQSA regulations. Subpart A is
> accreditation bodies. Subpart B is the facilities. Now we have Subpart
> C for the SAC States.
>
> So, as new States enter the program, they will be looked at, their
> applications will be looked at under these new regulations, and the
> maintenance of activities also will be the oversight will be directed
> by the new regulations.
>
> Probably one question which may come to your mind is are there other
> States that are interested in becoming in SAC States, and several
> States have mentioned some interest to us. This interest is buried in
> inquiries in some cases, and in other cases, the States have gone
> further.
>
> Probably the most time-consuming part of becoming a SAC State is in
> the development of regulations because it is required by the law that
> a SAC State have regulations in the mammography area equivalent to the
> MQSA regulations for the facilities.
>
> On the State level, as on the national level, it takes time to develop
> regulations, so a State that is interested in becoming a SAC State,
> seriously interested, that is a logical first process to get started
> to begin developing their regulations.
>
> It is also prudent if they are going to go this way, it is prudent for
> them to talk to us about their plans to begin with rather than go
> through the process, if the regulation is final, and then discover
> that they are not satisfactory and have to go through it again.
>
> So, this is a prudent first step to discuss the regulation plans with
> us. There have been States that have discussed regulations that they
> are working on with us, have discussed with us the regulations they
> are working on for this purpose.
>
> But at the present time, we have no active applications in-house under
> review to produce SAC States, so at the present time, the only SAC
> States which exist are the two which we active under the demonstration
> project, the States of Iowa and Illinois are our current SAC States.
>
> So, this brings us up to date to where we stand today. The big news
> again since the last time this committee met was the publication of
> the regulations as final. That has been the major change.
>
> If there are any questions, I would be happy to try to answer them.
>
> MS. HARVEY: Any questions? Dr. Pisano.
>
> DR. PISANO: In the guidance document, what about Arkansas, California,
> and Texas, that are listed in the guidance document? I am a little
> confused maybe.
>
> DR. BURKHART: Arkansas, California, Texas, and Iowa, I think what you
> are referring to as accreditation bodies. This is different from
> becoming a State\'s Certifier.
>
> For a facility to become certified, as you know, it has to be
> accredited, and we can approve as accreditation bodies, we can approve
> States or private, nonprofit bodies, and we have the four State AB\'s
> plus ACR, of course, as accreditation body.
>
> But this is the next step, issuing the certificates once a facility is
> accredited and making sure that they are inspected properly and, as I
> said, carrying out any compliance actions and follow-up which is
> necessary.
>
> DR. PISANO: So, Illinois is a certifying State, but not an accrediting
> State.
>
> DR. BURKHART: Right, Iowa is both. California, Texas, and Arkansas are
> just accreditation bodies at the present time.
>
> MS. HARVEY: Thank you.
>
> I think we have come to the last part of our meeting. Dr. Finder.
>
> DR. FINDER: Just before we go and review the summary minutes, some
> issues again were brought up just the last few minutes, again about
> accreditation for FFDM, and I just wanted to clarify a few things.
>
> One is FDA only can deal with what we get in-house. The accreditation
> bodies obviously have to make their own decisions whether they are
> going to go ahead and accredit under FFDM or not. That is their
> decision. We can\'t force anybody to do anything.
>
> We certainly are willing to look at any comments that an accreditation
> body wants to submit to us if they want to apply for FFDM. The same is
> true for alternative standards and some other aspects of the FFDM
> program. Manufacturers are certainly free to submit materials to us if
> they believe that they are appropriate for us.
>
> Just to go back to one of the earlier statements in terms of approved
> alternative standards, one manufacturer did come in to us for an
> alternative standard regarding, not the frequency, but the amount of
> time that a unit could be still used depending on the QC test that was
> failed.
>
> Other manufacturers are certainly free to apply for the same thing.
> That is their decision, and if they don\'t want to, facilities, if
> they want to, can also apply for an alternative standard.
>
> We are certainly open to comments and suggestions and efforts by
> manufacturers and other entities with this process, we are certainly
> open to that, so the more, the merrier.
>
> **Review of Summary Minutes of August 2001**
>
> DR. FINDER: Next, in terms of the review of the summary minutes, if
> anybody has any comments.
>
> MS. HARVEY: Are there any corrections or additions that any members of
> the committee found when they reread the summary minutes of our last
> meeting?
>
> \[No response.\]
>
> MS. HARVEY: Very good. Excellent.
>
> Dr. Finder, do you want to talk to us a little bit about future
> meetings?
>
> DR. FINDER: Yes, but before I talk about future meetings, I do want to
> make mention of one fact. Dr. Amy Lee has served on our committee, and
> her term is expiring in January of next year, so chances are we will
> not be having another meeting before her term expires, so we just want
> to thank her for all her efforts and hope that this has been an
> enjoyable experience.
>
> We know that we have gained a lot from her insights into this area,
> and we thank her for her participation here.
>
> MS. HARVEY: Thank you, Dr. Lee.
>
> **Future Meetings**
>
> DR. FINDER: As for future meetings, the plan probably is going to be
> to have a meeting sometime in the spring. This is going to be somewhat
> based on what happens. As many of you are aware, the Mammography
> Quality Standards Act is in the process of reauthorization. It
> terminates in October of 2002. Hopefully, we will have some action by
> Congress to reauthorize the program for another five years.
>
> When they reauthorize it, it is not uncommon\--I shouldn\'t say
> uncommon\--they reauthorized once and did put in specific items that
> required immediate attention from that reauthorization.
>
> Depending on what is included in the reauthorization this time around,
> we may have to take some immediate actions to generate some new
> regulations depending on what they say. So, the plan is to have a
> meeting sometime in the spring, and the topics may be dictated by what
> happens in the reauthorization process.
>
> I would expect that if they do reauthorize and put in a few new items,
> we might be talking about a two-day meeting rather than a one-day
> meeting, so just to get everybody informed.
>
> As for the exact timing, I will try and do the same thing that I did
> for this meeting, which is send out requests for days that are
> available from everybody and try and generate a suitable time that is
> applicable to everyone.
>
> I will mention the fact that this was the first time that we tried to
> send out all the materials electronically. It was quite an experience.
> I got a lot of e-mails that were bounced back at me and a lot of
> comments about it, but I think we are going to work through that
> process and hopefully, this time around it will be smoother.
>
> For those people who got their e-mails, but no attachments, I think it
> may be that your systems have recognized my name and are stripping off
> the attachments immediately. I am on your spam list I guess.
>
> MS. HARVEY: Any other further comments, questions?
>
> I wish you all a safe trip home and we will meet again. The meeting is
> closed.
>
> \[Whereupon, at 4:10 p.m., the meeting was adjourned.\]
>
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