# Presentation: 718138

## BCS 2100Radiological Device Panel  December 10, 2002

- Computerized Thermal Imaging
**Two Centerpointe Drive, Suite 450**
**Lake Oswego, Oregon 97035**
**Main office: (503) 594-1210**
**Email: **_**[info@cti-net.com](mailto:info@cti-net.com)**__**	**__**	**_
_**[www.cti-net.com](http://www.cti-net.com/)**__** **_

## 
JOHN BRENNA
President
Computerized Thermal Imaging (CTI)

Former Director – Phillips Medical Systems
Former President - LORAD

- JOHN BRENNA
- President
- Computerized Thermal Imaging (CTI)
- Former Director – Phillips Medical Systems
- Former President - LORAD

## CTI appreciates the opportunity to introduce the BCS 2100 to the Panel.

A noninvasive adjunct device designed to work with mammography to obviate biopsy of benign masses

The system provides ‘physiological’ information based on infrared technology that supplements the ‘anatomical’ information provided by mammographic x-ray.

**A noninvasive adjunct device designed to work with mammography to obviate biopsy of benign masses**
**The system provides ‘physiological’ information based on infrared technology that supplements the ‘anatomical’ information provided by mammographic x-ray.**

- PANEL PRESENTATION

## BCS 2100 HIGHLIGHTS

**Painless noninvasive patient procedure**
**Less than 10 minutes**
**Captures over 100 dynamic images**
**Collects over 8.3 million temperature values per imaged breast**
**Adjunctive to mammographic x-ray**
**Provides physiological information**

## PROFESSIONAL REVIEW

**The peer-reviewed journal, American journal of Roentgenology (AJR), accepted a clinical manuscript for publication describing the results of the clinical trials of the BCS 2100.**
**December 2002 release on AJR website**
**Article to appear in January 2003 edition**

## PRODUCT FOCUS

**CTI plans to market the BCS 2100 exclusively to**
**MQSA certified facilities **
**Under the control of board certified radiologists**

## INTRODUCTIONS

**CTI staff**
**Lynn Satterthwaite**
**Vice President of Engineering, CTI**
**Karleen Callahan, Ph.D.**
**Director of Clinical Research, CTI**

## INTRODUCTIONS

**CTI Principal Investigators**
**Yuri Parisky, M.D.**
**Associate Professor of Radiology, University of Southern California School of Medicine**
**Director of Breast Imaging Services, USC/Norris Comprehensive Cancer Center in Los Angeles**
**Principal Investigator at USC/Norris and USC/LAC**
**Kevin S. Hughes, MD, FACS**
**Assistant Professor of Surgery, Harvard Medical School**
**Surgical Director of Breast Screening, Massachusetts General Hospital, Harvard Medical School**
**Principal Investigator at Lahey Clinic, Boston**

## INTRODUCTIONS

**CTI advisors**
**Kathy Plesser, M.D.**
**Former Chief of Breast Imaging Section, St. Vincent’s Comprehensive Cancer Center**
**Assistant Professor of Radiology, New York Medical College and State University of New York, Downstate Medical Center**
**A. Pat Romilly, M.D.**
**Assistant Professor of Radiology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida**

## INTRODUCTIONS

**CTI advisors**
**Steve Rust, Ph.D.**
**Senior Research Leader, Battelle Statistics and Data Analysis Systems**
**Loraine Sinnott, Ph.D.**
**Research Scientist, Battelle Statistics and Data Analysis Systems**
**Elizabeth Nelson**
**Senior Regulatory Consultant, The Catalyst Group, LLC**

## AGENDA

**Dr. Parisky – Current clinical environment**
**Dr. Hughes – Patient management / case presentation**
**L. Satterthwaite – Device description and operation**
**Dr. Callahan – Clinical trial processes and statistical procedures**
**Dr. Parisky – Efficacy results and Indications for Use**

## INTRODUCTION

**Yuri Parisky, M.D.**
**Director of Breast Imaging Services, USC Norris**
**Associate Professor of Radiology, USC School of Medicine**

## BREAST IMAGING

**Historical progression**
**Introduction of standard mammography**
**Diagnostic mammography**
**Additional views**
**Ultrasound**
**Other**

## ETHICAL IMPERATIVE

**“****DO NO HARM”**

## CURRENT STATISTICS

**Every year, approximately 1.3 million women undergo breast biopsies to determine if they have cancer of the breast.**
**80% are benign**** **
**Approximately 1 million biopsies with benign outcomes**

## PATIENT NEED

**Breast biopsy procedures cause**
**Discomfort**
**Inconvenience**
**Procedural complications (e.g., bleeding)**
**Trauma (i.e., physical and emotional stress)**
**Possible interference with future mammographic interpretation**
**A need exists to**
**Reduce the number of benign tissue biopsies without preventing biopsies of malignant tissue**

## CURRENT PATIENT FLOW

**Mammography**

**Yes**

**Follow-up**

**Biopsy**

**No**

**No**

**Yes**

**Suspicious by additional diagnostic workup?**

**Normal Screening Interval**

## Kevin Hughes, M.D.
Assistant Professor of Surgery, Harvard Medical School
Surgical Director of Breast Screening, Massachusetts General Hospital
Principal Investigator at Lahey Clinic, Boston

**Assistant Professor of Surgery, Harvard Medical School**
**Surgical Director of Breast Screening, Massachusetts General Hospital**
**Principal Investigator at Lahey Clinic, Boston**

## CURRENT PATIENT FLOW

**Mammography**

**Yes**

**Biopsy**

**No**

**Yes**

**Lesion**
**suspicious by**
**US, PE**

**Normal Screening Interval**

**No**

## CLINICAL FLOW WITH BCS 2100

**Mammography**

**Lesion**
**suspicious by**
**US, PE**

**Yes**

**Follow-up**

**Biopsy**

**Normal screening interval**

**Negative**
**IR**

**Positive **
**IR**

**No**

**No**

**Yes**

**IR Imaging**

## CASE SA0258: Female, age 39

- CASE SA0258: Female, age 39

- CC View

- MLO View

## CASE SA0258: Female, age 39

- CASE SA0258: Female, age 39

- ML Compression View

- MLO Compression View

## BCS 2100 PROCEDURE

**Patient with suspicious solid lesion (mass as descriptor)**

##  BCS 2100 IMAGE

-  BCS 2100 IMAGE

**Notes:**
Isn’t the top right photo upside down?

## CASE SA0258: Female, age 39

***Not visual interpretation***

## CASE SA0258: Female, age 39

- CASE SA0258: Female, age 39

***Identify region of interest***

## CASE SA0258: Female, age 39

## IR TEST RESULT

**Notes:**
“Version used in clinical trial”; Explain IOS (see EN notes)

## CASE SA0258: Female, age 39

**Pathology result    Benign**
**Periductal and stromal fibrosis**

## Lynn Satterthwaite

## WHAT IS INFRARED (IR)?

**Heat energy emitted from the body at wavelengths longer than those of visible light.**

**Notes:**
My objective today is to discuss the technology and the equipment and how produces adjunctive 

## INFRARED (IR)

**IR radiation is emitted by the body as a result of heat produced by the body’s internal physiologic processes.**
**IR camera **_**passively**_** senses IR radiation and records as temperature.**
**Therefore, there is no risk to the patient.**

## BCS 2100 SYSTEM

*Data Acquisition System*

*Data Evaluation System*

*Technologist*

*Physician*

## IR IMAGING

**Data Acquisition**

- Acquire IR Images

- Process
- IR Data

- Produce
- Composite Image

- Place ROI on Composite Image

- Calculate IR value

- Place Breast Outline on Composite Image

**Notes:**
The point’s temperature through time during the static phase and during the active cooling phase
The point’s temperature compared to the temperatures of the surrounding points over time 
The IOS is a numerical representation of the algorithm treatment of IR image information.

## KEY COMPONENTS

**Data acquisition system**
**Patient support unit**
**Optical system**
**Infrared camera**
**Computer controlled cooling**
**Computerized data collection**

## OPTICAL ASSEMBLY

**Mirror array**
**6 mirrors ensure entire breast is imaged.**
**Mirrors do not contact breast, therefore do not interfere with temperature measurements.**

## COMBINED IR IMAGES

## IR CAMERA

## BCS 2100 IR CAMERA

- 3

- 11

- 12

- 10

- 13

- 9

- 8

- 7

- 6

- 4

- 5

- Early Cameras

- BCS 2100

- IR Spectrum – Wavelength in Microns

- Human skin emission
- pattern

## CAMERA FEATURES

**Detects differences in temperature between any 2 pixels of 0.1****o**** C**
**Area of resolution of 1-2 mm**

**Notes:**
Change temperature?

## CAMERA BENEFITS

**BCS 2100 captures IR evidence of human body’s physiological activity in the form of temperatures**
**Physiological information supplements anatomical x-ray information**

## IR DATA ACQUISITION

**Cooling Challenge Sequence**

- Patient Positioned

- CAMERA IMAGING

- TIME  in Minutes

- 0

- 1

- 2

- 3

- COOLING

**Notes:**
The point’s temperature through time during the static phase and during the active cooling phase
The point’s temperature compared to the temperatures of the surrounding points over time 
The IOS is a numerical representation of the algorithm treatment of IR image information.

## COOLING CHALLENGE

**Accurate and precise (computer controlled)**
**Elicits physiological response**
**IR images provide a physiological view as compared to the anatomical view provided by mammographic x-ray**

## IR IMAGE DATA CAPTURE

- direct image

- surrounding
- mirror
- images

- cooler

- warmer

- Right Breast

*Click to play*

**Notes:**
Note that this is “sped up”; no visual clues

## DATA PROCESSING

**IR data processed**
**Single composite image developed             **

## Data Evaluation System

- Acquire IR Image

- Process
- IR Data

- Produce
- Composite Image

- Place ROI on Composite Image

- Calculate IR value

- Place Breast Outlines on Composite Image

**Notes:**
The point’s temperature through time during the static phase and during the active cooling phase
The point’s temperature compared to the temperatures of the surrounding points over time 
The IOS is a numerical representation of the algorithm treatment of IR image information.

## BREAST DEFINITION

**Technologist places outline on breast**
**Physician confirms and changes outline if necessary**

## DEFINE ROI

**   ****Based on mammographic information, the physician places a region of interest (ROI) marker on the composite image.**

- Region of
- Interest Marker

## ROI SEARCH

**Search localization adjustment**

*Approx 1/12 of breast area*

- Region of
- Interest marker

## IR DATA ANALYSIS

**8.3 million temperature data points collected per breast**
**IR images NOT visually interpreted**
**IR images interpreted by analysis intensive approach**

## IOS CALCULATION

## IR TEST RESULT

## TRAINING BY CTI

**Technologist**
**Proper patient positioning**
**Proper procedure performance**
**Proper breast outline placement**
**Device upkeep and maintenance**

## TRAINING BY CTI

**Physician**
**Lesion localization**
**ROI placement on composite image**
**Utilization of IR result**

## TECHNICAL SUMMARY

**BCS 2100 performs computerized analysis to differentiate between malignant and benign tissue.**
**BCS 2100 is comprised of safe components that do not expose patients to risk.**
**The BCS 2100 is designed to be a non-invasive adjunctive medical device.**

## Karleen Callahan, Ph.D.

## CLINICAL STUDY

**Study objective**
**Study hypothesis**
**Study design **
**Study procedures**

## CLINICAL STUDY

**Study flow**
**Subject enrollment / demographics**
**Safety results**
**Efficacy groups and statistical analyses**

## STUDY OBJECTIVE

**To determine if the CTI BCS 2100 when used in conjunction with mammography increases the ability of physicians to differentiate benign from malignant breast abnormalities**
**  **

## STUDY HYPOTHESIS

**“****The CTI**** BCS 2100 could differentiate benign breast lesions from malignant breast lesions based on the relatively lower strength of the IR signal in benign tissue****”**
**Reduce the number of benign ****biopsies**

## STUDY DESIGN

**Blinded investigation **
**Initial protocol – one site / 600 subjects**
**Protocol expanded to 5 sites**
**Effectiveness evaluation criteria**
**Area under the curve**
**Sensitivity**
**Specificity**
**Subpopulation analysis**

**Notes:**
Expanded to speed recruitment, especially of malignants to ensure adequate evaluation of sensitivity.

## CLINICAL SITES

**Norris Cancer Center / LA County Hospital,  University of Southern California, Los Angeles, California, ****Yuri Parisky, M.D. **
**Providence Hospital,  Washington D.C.,                   Robert Hamm, M.D. **
**Mt. Sinai Medical Center, Miami, Florida,                      Lisa Esserman, M.D. **
**St. Agnes Health Care, Baltimore, Maryland, ****Armando Sardi, M.D. **
**Lahey Clinic, Boston, Massachusetts, ****Kevin Hughes, M.D**

## STUDY FLOW

**Subject **
**Enrollment**

**IR Imaging**

**IR Image Data**

**CRF**
**X-Rays**

**Biopsy**

**Pathology**

**Independent **
**Research **
**Organization**

**Trial Read**

**Pathology**

## EVALUATOR PANEL

**Mammographers**
**Seven (each subject randomly assigned to three)**
**Currently practicing**
**Independent from sites**
**Blinded to all lesion pathology results**

## CRO

**Quintiles**
**Monitored investigative sites**
**Held blinded pathology results**
**Provided with locked database of IR testing outcomes prior to unblinding pathology data**

## STUDY INCLUSION

**Subjects with lesions recommended for surgical or core biopsy based on **
**Mammography and/or**
**Clinical findings**
**IRB approved informed consent**

## STUDY EXCLUSION

**Previous breast surgery**
**Radiation in breast of interest**
**Breast implants or breast reduction**
**Weight > 135 kg (table weight limit)**
**Pregnancy**
**Previously diagnosed cancer in breast of interest (histologically proven)**

## PROTOCOL AMENDMENT 1

**November 1998**
**Changed method of evaluating mammogram and IR image**
**Initial protocol – IR IOS and mammographic LOS assigned by site investigator in “real time”**
**Amendment 1 – IOS and LOS assigned by reference radiologist after all data collected from sites**
**Comparison of IR IOS to mammographic LOS became problematic**

## PROTOCOL AMENDMENT 2

**June 1999**
**Prior breast surgery exclusion period reduced from 3 years to 1 year**

## STUDY PROCEDURES

**Investigator**
**Screen and enroll subjects**
**Perform IR data acquisition**
**Record subject data, including**
**Lesion descriptor**
**Lesion size**
**Pathology outcome**

## STUDY PROCEDURES

**Reference radiologist – LOS determination**
**LOS based on radiology report and over-read of mammography films**
**Performed by independent physician evaluators**
**Problematic issues**
**LOS not measured “real-time” by original site investigator**
**LOS not based directly on mammography**
**Contribution of adjunctive testing, e.g., ultrasound, in establishing LOS impossible to establish**
**Led to comparison to biopsy decision**
**Ground truth**

**Notes:**
Karleen to work on presentation of this slide

## STUDY PROCEDURES

**Physician evaluator**
**Reviewed mammogram**
**Checked breast outline and modified if necessary**
**Placed ROI marker on IR image**
**BCS 2100 assigned ROI a negative or positive IR result**

## SUBJECT ENROLLMENT

**	****	****	****	****	**** ****# Subjects**
**Norris/LAC****	****	****   ****	****369**
**Providence****	****	****   ****	****626**
**Mt Sinai****	****	****	****   ****	****428**
**St Agnes****	****	****	****   ****	****814**
**Lahey ****	****	****	****   ****	**_**170**_
**       ****Total****	****	****	****        2407**

**Notes:**
Note that this is overall, not efficacy sets.

## LESION SIZE

**  **
**	****	**_**Number**_**	****      **_**Size**_**	****	****	**
**	****	****14 masses       < 0.5 cm**
**   ****238 masses        0.5 to 1.0 cm**
**   ****238 masses        > 1.0 cm**

**Notes:**
Note that this is overall, not efficacy sets.

## SAFETY RESULTS

**2,407 subjects enrolled:**
**2 mild adverse events related to device**
**1)  Minor discomfort due to lying on abdomen**
**2)  Exacerbation of previously diagnosed hip sciatic nerve pain**
** **
**2 adverse events not related to device**

**Notes:**
Safety reported as number of AEs -- Adverse events few and minor

## LESIONS AND SUBJECTS

** ****Original study – Withdrawn cases**

**Notes:**
Note that this is overall, not efficacy sets.

## LESIONS AND SUBJECTS

**Original study – Withdrawn cases**

**Notes:**
Note that this is overall, not efficacy sets.

## LESIONS AND SUBJECTS

**Original study – retained cases**

**Notes:**
Note that this is overall, not efficacy sets.

## LESIONS WITHDRAWN

**Prior to IR evaluation**
**After IR evaluation and prior to unblinding**
**Analyses performed comparing retained lesions to withdrawn lesions showed no statistically significant differences in subject demographics and lesion characteristics.**

**Notes:**
Note that this is overall, not efficacy sets.

## MASS SELECTION

**Original study**
**Good performance for all lesion types**
**As prospectively planned in protocol, efficacy analyses by lesion type performed**
**Performance in masses better than non-masses**
**To minimize risk and maximize benefit, target population focused on masses**
**FDA requested a study confirming the Amendment 4 results for masses**

**Notes:**
Note that this is overall, not efficacy sets.

## EFFICACY GROUPS

**Original study – all lesion types**
**Original study – masses**
**Confirmatory study – masses**
**Combined studies – masses**

**Notes:**
Note that this is overall, not efficacy sets.

## MASS SELECTION

**Confirmatory study plan focused on masses with FDA review and agreement**
**CTI submitted to FDA a confirmatory study plan consistent with Amendment 4 procedures**
**FDA reviewed and agreed to confirmatory study plan**

## LESIONS AND SUBJECTS

**Confirmatory study**
**275 patients**
**Identical evaluation process **
**78 masses**
**	****	**

**Notes:**
Note that this is overall, not efficacy sets.

## SUBSETTING

**Target population was subset to masses after unblinding pathology for original study subjects**
**Based on results from **_**prospectively planned**_** subsetting analyses by lesion type**
**That could have resulted in 7 possible target populations**
**Masses**
**Calcifications**
**Distortions**
**Masses and calcifications**
**Masses and distortions**
**Calcifications and distortions**
**Masses, calcifications and distortions**

**Notes:**
Note that this is overall, not efficacy sets.

## SUBSETTING

**There are 2 options for reaching valid statistical conclusions for the mass subset.**
**Perform a new study and draw statistical conclusions from only the new study data**
**Apply a correction that validates statistical conclusions drawn from the original study data**
**Either approach is scientifically correct.**

**Notes:**
Note that this is overall, not efficacy sets.

## SUBSETTING

**CTI approach**
**Added data from a new confirmatory study**
**Conservatively applied a Bonferroni correction to results for the combined data**
**Result is that the statistical conclusions drawn for any of the 7 possible target populations are valid**

**Notes:**
Note that this is overall, not efficacy sets.

## SUBSETTING

**Uncorrected performance results for masses**
**Sensitivity (95.6, 100)**
**Specificity (16.0, 22.8) **
**Corrected performance results for masses**
**Sensitivity (93.5, 100)**
**Specificity (14.5, 24.6) **

**Notes:**
Note that this is overall, not efficacy sets.

## Dr. Parisky

## EFFICACY RESULTS

| STUDY | TYPE | n | SENS | SPEC | NPV | PPV |
| --- | --- | --- | --- | --- | --- | --- |
| Orig. | All | 875 | 97 | 14 | 97 | 24 |
| Orig.(A4) | Mass | 412 | 100 | 18 | 100 | 25 |
| Conf.(A5) | Mass | 78 | 93 | 25 | 94 | 23 |
| Comb. (A5) | Mass | 490 | 99 | 19 | 99 | 25 |

## SPECIFICITY

**Original 875 Lesions**
**14 % Specificity**
**Of 688 benign lesions, 96 were correctly assigned negative IR result**

## SENSITIVITY

** ****Original 875 Lesions****	****	**
**97% Sensitivity**
**Of 187 malignant lesions**
**180 correctly assigned positive IR result**
**7 falsely assigned negative IR result**
**Of 7 false negative**
**All were microcalcifications**
**Pathology**
**4 DCIS**
**2 DCIS with Stage 1 focal microinvasion**
**1 intraductal and infiltrating ductal carcinoma**

## EFFICACY RESULTS

| STUDY | TYPE | n | SENS | SPEC | NPV | PPV |
| --- | --- | --- | --- | --- | --- | --- |
| Orig. | All | 875 | 97 | 14 | 97 | 24 |
| Orig.(A4) | Mass | 412 | 100 | 18 | 100 | 25 |
| Conf.(A5) | Mass | 78 | 93 | 25 | 94 | 23 |
| Comb. (A5) | Mass | 490 | 99 | 19 | 99 | 25 |

## SPECIFICITY

**  ****Original set of 412 masses**
**18% Specificity**
**Of 322 benign masses, 58 were correctly assigned a negative IR result**

## SENSITIVITY

**  ****Original set of 412 masses**
**100% Sensitivity**
**Of 90 malignant masses**
**90 correctly assigned positive IR value**
**0 falsely assigned negative IR result**

## EFFICACY RESULTS

| STUDY | TYPE | n | SENS | SPEC | NPV | PPV |
| --- | --- | --- | --- | --- | --- | --- |
| Orig. | All | 875 | 97 | 14 | 97 | 24 |
| Orig.(A4) | Mass | 412 | 100 | 18 | 100 | 25 |
| Conf.(A5) | Mass | 78 | 93 | 25 | 94 | 23 |
| Comb. (A5) | Mass | 490 | 99 | 19 | 99 | 25 |

## SPECIFICITY

** ****Confirmatory set of 78 masses**
**25% Specificity**
**Of 63 benign masses, 16 were correctly assigned a negative IR result**

## SENSITIVITY

** ****Confirmatory set of 78 masses**
**93% Sensitivity**
**Of 15 malignant masses**
**14 were correctly assigned a positive IR result**
**1 false negative**
**DCIS**

## EFFICACY RESULTS

| STUDY | TYPE | n | SENS | SPEC | NPV | PPV |
| --- | --- | --- | --- | --- | --- | --- |
| Orig. | All | 875 | 97 | 14 | 97 | 24 |
| Orig.(A4) | Mass | 412 | 100 | 18 | 100 | 25 |
| Conf.(A5) | Mass | 78 | 93 | 25 | 94 | 23 |
| Comb. (A5) | Mass | 490 | 99 | 19 | 99 | 25 |

## SPECIFICITY

** ****Combined set of 490 masses**
**19% Specificity**
**Of 385 benign masses, 74 were correctly assigned a negative IR result**

## SENSITIVITY

** ****Combined set of 490 masses**
**99% Sensitivity**
**Of 105 malignant masses, **
**104 were correctly assigned a negative IR result**
**1  false negative, non-invasive cancer**

## PATHOLOGY (MALIGNANT)

**Malignant masses (n=105)**
**Invasive Masses**
**69 Invasive Carcinomas**
**9  Invasive Lobular Carcinomas**
**4  Tubular**
**5  Mucinous Carcinomas**
**2  Papillary Carcinomas**
**1  Lymphoma**
**Non-Invasive****	**
**11 DCIS**
**4 LCIS**** **

## PATHOLOGY (BENIGN)

**Benign masses (n=385)**
**153 Fibrocystic disease (not cysts)**
**89 Fibroadenoma**
**46 Fibrocystic and fibroadenoma**
**18 Atypical hyperplasia**
**79 Other**

## CLINICAL USE

**Intended population**
**Role in practice**
**Patient counseling**

## CLINICAL USE

**Intended population**
**Masses**

## CLINICAL USE

**Role in practice**
**Enables further workup of breast masses that are**
**Mammographically defined**
**Sufficiently suspicious to warrant workup**
**Device test result may be used to obviate need for biopsy**

## CLINICAL USE

**Patient counseling**
**Use IR imaging data analysis information, along with all other available information, when counseling the patient regarding recommendations for treatment and follow-up**

## CLINICAL FLOW WITH BCS 2100

**Mammography**

**Lesion**
**characterized as solid mass?**

**Yes**

**Consider follow-up**

**Consider biopsy**

**IR Imaging not recommended**

**Negative**
**IR test result**

**Positive **
**IR test**
**result**

**No**

**No**

**Yes**

**IR Imaging**

## PERFORMANCE

** ****In study subjects, BCS 2100 offered opportunity to **
**Avoid biopsy of 74 benign masses of 385 biopsies with a benign outcome**
**At risk of delaying 1 biopsy of a non-invasive malignant mass of 105 biopsies that were cancer **

## Steve Rust, Ph.D.

## STUDY PERFORMANCE

|  | Positive
IR result | Negative
IR result |  |
| --- | --- | --- | --- |
| Malignant mass | 104 | 1 | 105 |
| Benign mass | 311 | 74 | 385 |
|  | 415 | 75 | 490 |

## APPLIED PERFORMANCE

|  | Positive IR result | Negative IR result |  |
| --- | --- | --- | --- |
| Malignant mass | 125,543 | 1,207 | 126,750 |
| Benign mass | 375,421 | 89,329 | 464,750 |
|  | 500,964 | 90,536 | 591,500 |

## HEALTHCARE COST / BENEFIT

**Cost**
**IR procedure cost ($225) x 591,500 procedures  = $133M**
**Cancer** diagnoses delayed = 1,207**
**Benefit**
**Biopsy cost ($3,000) x 89,329 biopsies prevented = $268M**
**Benign mass biopsies prevented = 89,329**
**Net **
**Cancer** diagnoses delayed = 1,207**
**Net healthcare cost savings = $135M*** annually**
**Benign mass biopsies prevented = 89,329**
***   Cost of IR procedure anticipated to be between $150 and $300**
****  Single delayed cancer diagnosis in trial was noninvasive**
*****Net savings between $90M and $179M, depending on IR**
**    ****procedure cost**

## SUMMARY

**John Brenna**
**President, CTI**

## PROPOSED INDICATION

**	****The CTI BCS 2100 is a dynamic computerized infrared (IR) based image acquisition and analysis system ****intended for use as an adjunct to mammography to safely avoid biopsy of benign breast masses that would otherwise have undergone biopsy****. A physician should not base a decision for patient care solely on the results of testing with this device, but rather on the results of this test in combination with all other findings and risk factors associated with a specific patient. The CTI BCS 2100 provides additional information to guide a breast biopsy recommendation.**

## PROPOSED INDICATION

**	****Because demonstration of device effectiveness was limited to breast lesions that included “mass” as a lesion descriptor, use of ****the BCS 2100 should be limited to the evaluation of breast lesions that include “mass” as a lesion descriptor****. Presence of another lesion descriptor does not contraindicate use of the CTI BCS 2100, if the lesion is also described as a mass.**

## PROPOSED INDICATION

**	**
**	****It is recommended that the appropriate recommendation for care for ****all patients receiving a negative IR test result be similar to the recommendation for care of a mass that is assigned to a mammographic category 3.**** That is, a short interval follow-up is recommended in order to establish the stability of the finding.**

## MODULE 5 HISTORY

**Original Module 5 submission / All lesion types -  June 15, 2001**
**Amendment 4 submission / Masses - February 28, 2002**
**FDA issued deficiency letter with approvability criteria**
**CTI discussed and submitted written plan for adding confirmatory data**
**FDA reviewed and indicated that FDA reviewers “were fine” with the described plan**
**Amendment 5 submission / Confirmatory study results – May 2002**
**FDA site audits successfully completed – June 2002 **
**CTI invited to 16 October panel – July 2002**
**FDA sponsor audit successfully completed – September 2002**
**FDA and CTI mutually agreed to postpone panel date for administrative and logistical reasons – October 2002**

**Notes:**
What happened to Modules 1 through 4? Need dates.

## PMA HISTORY

**Original study protocol developed with the FDA**
**Confirmatory study plan approved by FDA**
**Plan targets lesions with mass as a descriptor**
**Confirmatory study results were combined with original study results**
**FDA scheduled panel meeting**

**Notes:**
What happened to Modules 1 through 4? Need dates.

## PMA HISTORY

**In summary the BCS 2100 is:**
**Painless, non-invasive and safe**
**Adjunctive to mammography x-ray**
**Provides physiological information**
**Clinical study performance**
**99% sensitivity**
**19% specificity improvement when compared to the biopsy decision**
**Health care cost reduction benefit**
**We believe CTI has demonstrated that the BCS 2100 is a safe and effective medical device for the proposed Indication for Use.**

**Notes:**
What happened to Modules 1 through 4? Need dates.

## 	

The CTI team appreciates your time, 
attention, and consideration of 
our BCS 2100 PMA application.

Thank you.

**The CTI team appreciates your time, **
**attention, and consideration of **
**our BCS 2100 PMA application.**
**Thank you.**