**SUMMARY MINUTES**

**OF THE**

RADIOLOGICAL DEVICES PANEL MEETING

**Open Session**

**December 10, 2002**

**Gaithersburg Holiday Inn**

Gaithersburg, MD

RADIOLOGICAL DEVICES PANEL MEETING

December 10, 2002

## Panel Participants

> Minesh P. Mehta, M.D. Chair
>
> Harry K. Genant, M.D. Voting Member
>
> Geoffrey S. Ibbott, Ph.D. Voting Member
>
> Alicia Y. Toledano, Sc.D. Voting Member
>
> Prabhakar Tripuraneni, M.D. Voting Member
>
> Emily F. Conant, M.D. Temporary Voting Member
>
> Regina J. Hooley, M.D. Temporary Voting Member
>
> Marilyn R. Peters, M.N., M.P.H. Consumer Representative
> (**non-voting**)
>
> Ernest L. Stern Industry Representative (**non-voting**)

**FDA Participants**

> Robert J. Doyle Panel Executive Secretary
>
> Nancy Brogdon Division Director, DRARD
>
> Stanley Stern, Ph.D. Health Physicist, CDRH
>
> John Monahan Biologist, DRARD
>
> William Sacks, Ph.D., M.D. Medical Officer, DRARD
>
> Harry Bushar, Ph.D. Statistician, CDRH
>
> Robert A. Phillips, Ph.D. Branch Chief, DRARD

## Morning Session 

## 

## Administrative Items

**CALL TO ORDER**

**Panel Chair Minesh P. Mehta, M.D.,** called the meeting to order at
8:32 a.m. He noted that the voting members present constituted a quorum
and asked the panel members to introduce themselves.

**Robert A. Phillips, Ph.D., Branch Chief, Radiology Branch, ODE,
CDRH,** updated the panel on the devices FDA had approved since the
panel's March 2001 meeting. FDA approved the Sirtex SirSpheres
brachytherapy product; the Deus Technologies RapidScreen computer-aided
detector (CAD) device for chest radiographs; the Diagnostic Medical
Systems bone sonometer; the Fischer Imaging SenoScan (a full-field
digital mammography \[FFDM\] device); the Hologic Lorad Digital Breast
Imager FFDM device; the CADx Medical Systems SecondLook CAD system for
mammograms; and the Intelligent Systems Software \[now iCAD\]
MammoReader CAD system for mammograms. In addition, FDA approved PMA
supplements for soft-copy imaging for digital mammography systems.

**Panel Executive Secretary Robert J. Doyle** read the appointment to
temporary voting status for panel consultants Emily F. Conant, M.D., and
Regina J. Hooley, M.D. He then read the conflict of interest statement:
Full waivers had been granted to Regina J. Hooley, M.D., Geoffrey S.
Ibbott, Ph.D., and Prabhakar Tripuraneni, M.D., for their interests in
firms that could be affected by the panel's recommendations. Mr. Doyle
noted that the Agency had taken into consideration other matters
concerning Drs. Hooley, Ibbott, and Tripuraneni, all of whom reported
interests in firms at issue that were not related to the day's agenda.
Finally, Mr. Doyle noted that FDA encourages comments from the public
concerning guidance documents.

# FDA PRESENTATION

**Stanley Stern, Ph.D., Health Physicist, CDRH,** presented information
on the development of amendments to the U.S. radiation safety standard
for diagnostic x-ray computed tomography (CT). \[He noted that proposed
amendments to the Performance Standards for Ionizing Radiation Emitting
Products were published in the *Federal Register* on December 10,
2002.\] Current regulations covering CT have not kept pace with
technological developments. Public health concerns include the total CT
dose to the population as well as high radiation doses associated with
CT exams of children and small adults and asymptomatic self-referrals
for CT screening (whose radiation doses are among the highest of all
modalities). In addition, CT fluoroscopy, which visually guides
interventional procedures and has applications in a broad range of
specialties, carries the additional risk of radiation-induced skin
injury.

Dr. Stern described the current standards for CT equipment radiation
safety performance, which are 20 years old and predate electron beam and
multislice devices. The current regulations do not fully address these
modalities. Consequently, FDA is considering amendments that involve
dose-index standardization, automatic exposure control, and field-size
limitations. Dose-index standardization would require each new CT system
to display and/or record values of standardized dose indices for each
patient's exam. This requirement could reduce patient CT dose by an
average of about 15 percent. Automatic exposure control would
automatically reduce the dose as the x-ray beam scanned a thinner part
of the anatomy; this requirement would reduce patient CT dose by about
30 percent.

FDA is concerned that a number of multislice models use radiation
inefficiently. Although the amount of radiation applied to construct one
image or a set of images is the same for each configuration, the
radiation distribution is much wider than for single-slice system, and
radiation falls beyond the detectors and is not used for image
construction. FDA is therefore considering regulations to limit the
x-ray field to a size no larger than that needed to construct multislice
images. This requirement could reduce the patient CT dose by about 30
percent. If all CT equipment were to include the proposed features,
8,700 radiation-induced cancer mortalities per year could be avoided;
the projected collective dose savings are 193,000 person-Sieverts per
year. FDA has developed a framework for analysis that will lead to a
concept paper. The Agency expects industry professional groups and
States to contribute to the regulatory development process and expects
to update the panel in June 2003.

# 

# OPEN PUBLIC HEARING

No comments were made.

# OPEN COMMITTEE DISCUSSION of the PMA

Panel Chair Minesh P. Mehta, M.D., stated that the purpose of the
meeting is to discuss, make recommendations on, and vote on a PMA
(P010035) for a device that produces a computerized thermal image of the
breast of women recommended for biopsy.

# SPONSOR PRESENTATION---P010035

**John Brenna, president and CEO, Computerized Thermal Imaging (CTI),**
described the CTI BCS2100 device as a noninvasive adjunct device
designed to work with mammography to eliminate the need for biopsy of
benign masses. The device uses infrared (IR) technology to provide
physiological information that supplements the anatomical information
provided by mammography. The device is painless and noninvasive. CTI
plans to market the device exclusively to MQSA-certified facilities
under the control of board-certified radiologists.

**Yuri Parisky, M.D., professor of radiology, University of Southern
California School of Medicine and principal investigator at USC/Norris
and USC/LAC,** provided background information on the development of
breast imaging devices. The introduction of diagnostic mammography did
not add significant specificity or sensitivity and did not reduce biopsy
rates. Ultrasound led to a drop in biopsies. Other modalities have been
introduced; all have high sensitivity but low specificity. Every year,
approximately 1.3 million women have biopsies, of which 80 percent are
benign. Breast biopsy procedures cause discomfort, carry risks of
complications, and create physical and emotional stress. The sponsor's
device has good sensitivity and specificity that can permit the
avoidance of some biopsies.

**Kevin Hughes, M.D., FACS, surgical director of breast screening,
Massachusetts General Hospital/Harvard Medical School, and principal
investigator, Lahey Clinic, Boston,** provided a clinical perspective on
how the CTI device will be used. Patients who are identified through
mammography as having suspicious growths will first go to IR imaging
rather than biopsy. If the IR image is negative (i.e., indicates that
the growth is likely to be benign), the patient can go to follow up
instead of biopsy; however, the patient will still go to biopsy if other
clinical information warrants the procedure. If the IR image is positive
the patient goes on to biopsy. The IR image is not visually interpreted;
the computer determines whether an image represents a suspicious lesion
in a region chosen by the radiologist.

**Lynn Satterthwaite, vice president of engineering, CTI,** provided
details on the mechanism of the CTI device. The body emits IR radiation
as a result of heat produced by physiologic processes. The device
passively senses IR radiation and records it as temperature. Mr.
Satterthwaite described the data acquisition system, including the
camera, which detects differences in temperature of 0.1°C between any
two pixels. Six mirrors ensure that the entire breast is imaged; the
mirrors do not contact the breast, therefore, they do not interfere with
temperature measurements. Thirty seconds into the imaging process, the
computer turns on a cooling system that continues through the remainder
of the 3-minute imaging session. The cooling challenge, which is
computer controlled, elicits a physiological response and enhances the
temperature contrast between benign and malignant tissue. Once the IR
data are processed, two composite images are generated.

The second part of the process is evaluation of the data. The
technologist outlines the margins of the breast on the composite image;
the physician confirms, or changes the outline if necessary. The
physician then determines a region of interest (ROI) and marks it on the
image. The device analyzes the ROI as well as an expanded area around it
comprising about 1/12 of the total breast area; it then scans 8.3
million temperature data points per breast. An index of suspicion (IOS)
calculation is then generated; if the IOS is below the threshold of
20.59, it is considered a negative result, and the patient is referred
to short-term follow up rather than biopsy. In summary, the BCS 2100
performs computerized analysis to differentiate between malignant and
benign tissue. The device comprises noninvasive, safe components and is
designed to be an adjunctive medical device.

**Karleen Callahan, Ph.D., director of clinical research, CTI,**
described the clinical study. The objective was to determine whether the
CTI BCS 2100, when used in conjunction with mammography, increases the
ability of physicians to differentiate benign from malignant breast
abnormalities. The hypothesis was that the device could differentiate
benign from malignant breast lesions on the basis of the relatively
lower strength of the IR signal in benign tissue, thereby reducing the
number of benign biopsies.

The study was a blinded investigation that began at one site with 600
subjects and was later expanded to five sites in order to obtain enough
malignancies for analysis purposes. Effectiveness was determined on the
basis of area-under-the-curve (AUC) analyses as well as sensitivity,
specificity, and subpopulation analyses. Subjects were identified and
enrolled, had IR imaging, and then proceeded to biopsy. The pathology
was sent to an independent research organization. After a panel of
independent evaluators completed the trial read of the IR image (i.e.,
determined the ROI), the data were unblinded and sent to CTI for
analysis along with the mammogram data and patient information on case
report forms.

The evaluator panel consisted of seven currently practicing
mammographers; each image was randomly assigned to three evaluators, who
were blinded to all lesion pathology results. The clinical research
organization Quintiles monitored the investigative sites, held the
blinded pathology results, and was provided with a locked database of IR
testing outcomes prior to unblinding the pathology data.

Included subjects were those with lesions recommended for surgical or
core biopsy on the basis of mammography or clinical findings. Exclusion
criteria consisted of previous breast surgery, radiation exposure in the
breast of interest, breast implants or breast reduction, weight of
greater than 300 lbs, pregnancy, and previous cancer in the breast of
interest. Two mild adverse events were reported that were related to the
device, both of which involved patient discomfort from lying on the bed.
Two other adverse events were found not to be related to the device.

The sponsor amended the protocol several times over the course of the
study. In November 1998, the evaluation method of the mammographic and
IR image was changed. In June 1999, the sponsor reduced the breast
surgery exclusion period to 1 year. Amendment 5 involved unvaulting of
additional data (69 subjects with 78 lesions) that had been collected
under the same protocol but not yet analyzed. This was done in response
to deficiencies noted by FDA.

**Steve Rust, Ph.D., senior research leader, Battelle Statistics and
Data Analysis Systems,** provided details on the sponsor's statistical
analysis, focusing on the confirmatory study. The study involved 275
subjects who were in the pipeline at the time the dataset was "frozen"
and used the same evaluation process as the initial study. A target
population of masses was selected after the pathology for the original
study subjects was unblinded; the target was based on results from
prospectively planned subset analyses by lesion type. Subset analysis
could have resulted in seven possible target populations: masses;
calcifications; distortions; masses and calcifications; masses and
distortions; calcifications and distortions; and masses, calcifications,
and distortions.

Dr. Rust stated that two options for reaching valid statistical
conclusions for the mass subset were possible: (1) Perform a new study
and draw conclusions from only the new study data, or (2) apply a
correction that validates the statistical conclusions drawn from the
original study data. Either approach is correct. CTI thus conducted the
confirmatory study using a subset of 78 masses, added the data to that
of the original study population, and applied a Bonferroni correction to
the results for the combined data. He stated that the conclusions are
valid for any of the seven target populations.

Dr. Parisky summarized the sensitivity and specificity data. The 769
original subjects had a total of 875 lesions, 688 of which were benign;
of those, 96 were correctly assigned a negative IR result (resulting in
14 percent specificity). Of 187 malignant lesions, 180 lesions were
correctly assigned a positive IR result, and 7 were falsely assigned a
negative IR result. Of the seven false negatives, all were
microcalcifications. Pathology results found four ductal carcinomas in
situ (DCIS), two DCIS with focal microinvasion; and 1 intraductal and
infiltrating ductal carcinoma were found. No invasive malignancies were
described as false negatives. The confirmatory study of 78 masses
included 63 benign masses; of those, 16 were correctly assigned a
negative IR result, resulting in 25 percent specificity. Of 15 malignant
masses, 14 were correctly assigned a positive IR result, and 1 was
assigned a false negative IR result, resulting in 93 percent
sensitivity. The combined data (confirmatory study plus the masses from
the original study; *N* = 490) resulted in 19 percent specificity and 99
percent sensitivity.

Dr. Rust then provided data on health care costs and benefit. He
estimated that the device could save \$94 million to \$183 million
annually and prevent 89,329 biopsies.

Finally, Mr. Satterthwaite read the proposed indication for use and
described aspects of the device's regulatory history. He stated that FDA
approved combining the confirmatory study results with those from the
original study and that the original study protocol was developed with
advice from FDA. Results of the clinical study found 99 percent
sensitivity and 19 percent specificity; the device is therefore safe and
effective.

# Panel Questions for Sponsor

Panel members asked many questions about the study methodology as well
as the device. Their methodological concerns included the lack of
ultrasound data, the definition of mass, variability among readers and
the reproducibility of results, the rationale for stopping enrollment
before the target of 3,000 patients was reached, the statistical
validity of pooling reader results, and the exclusion criteria. Sponsor
representatives provided clarification in response to the panel's
questions. Device-related concerns included calibration of the device
and procedures for quality assurance. Mr. Satterthwaite noted that the
device is calibrated before each imaging session. Finally, panel members
observed that the cost--benefit data seemed a bit high, but Dr. Rust
said that the numbers were based on surgical as well as needle biopsy
costs.

# FDA PRESENTATION

**John Monahan, biologist and lead FDA reviewer,** noted that the PMA
was a modular submission. The first module, which contained preliminary
information, was received in 1999. Modules 2 through 4 provided data on
the device's software, manufacturing, and engineering.

**William Sacks, Ph.D., M.D., medical officer, CDRH,** described the
sponsor's clinical study. He noted that the device was a new type of
thermographic device intended for use as an adjunct to mammography. It
renders a value on the basis of an IOS score. In its intended use the
device can only decrease the number of biopsies (i.e., increase
specificity); it cannot increase detection of cancers (i.e., increase
sensitivity).

**Harry Bushar, Ph.D., statistician, CDRH,** reviewed the clinical study
protocol and the sponsor's statistical analysis. He pointed out that
diagnostic mammography, not just clinical examination, is required for
use of the device. The sponsor's AUC analysis loses statistical
significance when mammography level of suspicion (LOS), in terms of the
American College of Radiology Breast Imaging Reporting and Data System
(BIRADS) score, is expanded by just two additional intermediate
categories, after excluding calcifications alone. Further, the sponsor's
initial rejection of ROC, followed by rejection of calcification-alone
sensitivity, indicates exploration (of the database). The sponsor\'s
attempted Bonferroni adjustment to correct for this exploration, by
widening sensitivity and specificity confidence interval estimates, is
not statistically acceptable. Therefore, the submission requires the
results of a new study.

Dr. Sacks followed and stated that safety has two aspects: adverse
events and accuracy of output. Only four minor adverse events were
reported. Safety is more closely related to sensitivity (i.e., false
negatives though also false positives); effectiveness is more closely
related to specificity. The sponsor provided four clinical submissions:
the PMA and three amendments (Amendments 4, 5, and 7) which were
provided in response to FDA deficiency letters. The FDA reviewed each
submission and raised numerous questions concerning the adequacy of the
data. He noted that, based on the data, if the device were used on *all*
585,000 women with mammographic masses each year, 5 to 7 percent of 1.3
million biopsies would be obviated; however, 1 to 6 percent of the
malignant masses and 0.5 to 3 percent of all breast cancers might be
delayed in diagnosis.

## Afternoon Session 

## 

## Administrative Item

**Nancy Brogdon, Director of DRARD,** noted that Marilyn R. Peters,
M.N., M.P.H., consumer representative, and Alicia Y. Toledano, Sc.D.,
are completing their terms on the panel at the end of January, 2003. She
thanked them for their service.

# OPEN COMMITTEE DISCUSSION of the PMA

Panel members were concerned about the study methodology, including
disagreement among readers, handling of unreadable images, missing
readings, and exclusion criteria. Sponsor representatives explained that
the study attempted to get three reader evaluations for each lesion. In
those cases, all three results were used in the analysis. If two
evaluations were obtained, they each were weighted 50 percent, and the
analysis statistically accounted for the missing reading. Any lesions
that did not show up on a mammogram could not be used. Panel members
noted that women who did not have biopsies were excluded, as were those
who had a biopsy that found fluid-filled cysts. The exclusion criteria
may have opened up the results of the trial to significant bias. They
also noted the lack of data on inter- and intrareader reliability,
effects of breast size, and the rationale supporting the cooling
challenge.

Panel members expressed concern about the primary efficacy findings and
the robustness of the data. The primary efficacy endpoints did not reach
significance or demonstrate a trend. They only reached significance in
post hoc analysis. It is important to know the reproducibility from one
reader to the next. Is a trained panel of readers necessary, or can a
single reader assess the image? Dr. Rust noted that the sponsor allowed
itself to be statistically penalized for reader-to-reader variability.
Dr. Genant responded that because of the way the sponsor handled the
issue, it is not clear that three trained readers are any more reliable
than a single reader.

Many panel members noted that the sponsor did not collect ultrasound
data, even though in clinical practice, almost all masses will undergo
ultrasound to help determine whether biopsy is needed. It is unclear
whether the device will be useful in masses with BIRADS scores of 3 or 4
on ultrasound as opposed to BIRADS 5. Also, many lesions with BIRADS
scores of 0, 1, 2, or 3 were included in the biopsy group. Dr. Parisky
said that in those cases, the patient wanted biopsy, but Dr. Conant
noted that even so, the numbers were still high.

The panel expressed doubts about the feasibility of using the device in
clinical practice. They repeatedly raised concerns about patient flow
and suggested that the ability to demonstrate clinical usefulness was
negated by the use of the readers in the clinical study. Dr. Hughes
stated that he uses the device successfully in his clinic. Mr.
Satterthwaite noted that the device has been improved; the cooling
challenge is now automated, for example.

Dr. Toledano asked whether the sponsor could reanalyze the existing data
in an exploratory manner, as though masses had been separated by type
from the start. Dr. Callahan said that it was possible; the data are in
case report form. No data are available on why any biopsy was not
performed, though.

Panel members asked for clarification on how the sponsor determined the
threshold for positive IR findings (i.e., the IOS score). Dr. Parisky
said that the threshold was determined prior to unblinding in the
original study, so the sponsor kept that threshold. The objective was to
try to achieve 99.3 percent sensitivity with 75 percent confidence. It
was never intended to be a hypothesis for performance evaluation.

# PANEL DISCUSSION QUESTIONS 

1(a) The data in Amendment 4 were selected retrospectively from the
original PMA dataset, albeit based on lesion type analyses that were
prospectively planned for in the clinical trial protocol. Are the data
from Amendment 4 applicable for the assessment and determination of
effectiveness of the BCS 2100?

The panel agreed that the data are not valid in and of themselves for
documenting effectiveness. They are encouraging, but they represent a
post hoc analysis. The sponsor prospectively planned to analyze
performance by lesion type but had no plan to exclude certain lesion
types from the indications. The current indications are based on masses.
The data and analysis for masses cannot come from the data indicating
that the sponsor should limit the indications to masses.

1(b) The additional data in Amendment 5 consist of 78 masses. Are these
additional data by themselves sufficient for the assessment and
determination of effectiveness of the BCS 2100?

The panel concurred that the additional data are insufficient; they do
not include enough patients.

1(c) When combined, Amendment 4 provides 84 percent (412) of the masses
and Amendment 5 provides 16 percent (78). What is the validity of
combining these data to assess and determine effectiveness of the BCS
2100?

The panel concurred that combining the data is not a valid approach to
analysis.

2\. Please discuss the same questions for safety.

2(a) The data in Amendment 4 were selected retrospectively from the
original PMA dataset, albeit based on lesion type analyses that were
prospectively planned for in the clinical trial protocol. Are the data
from Amendment 4 applicable for the assessment and determination of
safety of the BCS 2100?

The panel concurred that use of the device is physically safe, although
the possibility of false negatives raises a different type of safety
concern. The panel felt that it sufficiently addressed questions 2(b)
and (c) in its answers to the previous questions. The data and the
analysis methods are not sufficient to determine safety and
effectiveness.

3\. Please discuss whether safety and effectiveness has been
established. As part of this, please discuss the risk/benefit trade-off
whereby a false negative results in a 6-month delay of cancer diagnosis
and a true negative obviates biopsies that would otherwise turn out
benign.

The panel concurred that the risk/benefit tradeoff was high. A false
negative could result in a 6-month delay in cancer diagnosis, but not
enough is known about the natural history of DCIS to establish whether 6
months is the appropriate follow up interval. Patients with false
positives are subjected to additional tests, emotional turmoil, and
expense. For DCIS, delayed diagnosis might not be of too much concern,
but it would be a problem if the cancer were infiltrating.

** **

4\. Is the proposed labeling adequate to ensure safe and effective use
of the BCS 2100? Please include in your discussion the following
specific items (a) and (b):

4(a) Given that only 2 of 105 cancers were smaller than 5 mm, should the
labeling specify a lower size limit for an eligible mammographic mass?
If so, what size limit?

The panel concurred that the labeling should specify a lower size limit,
but the data are insufficient to determine that limit.

4(b) Should the labeling address lesion depth? If so, in what way?

The panel agreed that data were insufficient to answer the question.

5\. Should the labeling be revised to address any potential
psychological impact of a positive mammogram, followed by a positive BCS
2100 result, on a woman who does not, in fact, have cancer (i.e., false
positive)?

The panel said that clinicians do not always take time to reassure
patients that a positive finding does not mean that the patient has
cancer, but it is unclear how labeling could help that situation.

6(a) Do the above, or any other, issues require resolution before
approval of the PMA?

The panel felt that several important issues need to be addressed before
approval. The existing data may not be able to resolve those issues,
which include reproducibility of results and the stability of the
instrument. Equilibration is a concern because not every clinic will
maintain the proper temperature for a successful cooling challenge.
Establishment of the IOS threshold is also an issue---several panel
members felt that it should be determined based on masses, not a wide
variety of lesions. Effectiveness needs to be established in a target
population that is directly relevant to the proposed indications for
use, taking into account the clinical flow of patients. Several panel
members stated that it might be possible to resolve the issues without
additional clinical trial data.

6(b) Do the above, or any other, issues suggest the need for a
post-market study?

The panel concurred that if the device were approved, then a postmarket
clinical trial would be needed.

# OPEN PUBLIC HEARING

No comments were made.

# FINAL SPONSOR COMMENTS

Dr. Parisky reminded the panel that the ideal threshold for false
negatives cannot be met by any existing modalities, including PET scan,
MRI, and ultrasound has high rate. The panel has set a standard that
will only allow existing technologies to enter the marketplace. Mr.
Brenna noted that the sponsor worked closely with FDA during the
clinical study. He said that the product is noninvasive, adjunctive, and
safe and shows high promise with sensitivity.

# VOTE

Mr. Doyle read the voting instructions. A motion was made to recommend
that the PMA was "Approvable with Conditions." This motion failed on a
3-4 vote. Another motion was then made to recommend "Not Approvable."
The panel voted in favor of this motion on a 4-3 vote with the panel
chair casting a tiebreaking vote in each case. When asked to state the
reasons for their votes, panel members voting for "Not Approvable"
stated that although the device is safe, its clinical effectiveness was
not demonstrated by the study. Members expressed concerns about quality
assurance issues and the sponsor's clinical trial design. They felt that
a prospective study that better defined masses and included ultrasound
data would be helpful. They also felt that the relevant population of
interest should be women with masses seen on mammography or found by
clinical exam. In addition, the sponsor's study did not provide data on
inter- and intrareader variability.

Panel members voting against "Not Approvable" stated that the device is
noninvasive and has utility. They felt that as the data are fine-tuned
and the company gets more experience, use of the device would be more
compelling. They also felt that the device could help spare tens of
thousands of women the psychological trauma of biopsy. In addition,
postmarket research could provide the information many panel members
felt was lacking in the sponsor's data.

### ADJOURNMENT

Dr. Mehta thanked the participants and adjourned the open session at
3:35 p.m.

> I certify that I attended this open session of the Radiological
> Devices Advisory Panel on December 10, 2002, and that these minutes
> accurately reflect what transpired.
>
> \_\_\_\_\_\_\_\_\_\_\_\_\_[/S/]{.underline}\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
>
> Robert J. Doyle
>
> Executive Secretary

I approve the minutes of the December 10, 2002,

open session as recorded in this summary.

\_\_\_\_\_\_\_\_\_\_\_\_\_[/S/]{.underline}\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Minesh P. Mehta, M.D.

Chairperson

Summary prepared by

Caroline G. Polk

Polk Editorial Services

1112 Lamont St., NW

Washington, DC 20010

\(202\) 265-8271

<cpolk@earthlink.net>

Edited by FDA