Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis Compared to Mammography (ADAPT Trial) ADAPT-BX: Recruitment Plan for Initially Asymptomatic Women Referred for Breast Biopsy
Phase: NA
Conditions: Breast Cancer, Tumors, Breast
Sponsor: GE Healthcare

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
ADAPT-BX: Recruitment Plan for Initially Asymptomatic Women Referred for
Breast Biopsy
Study Number: 124.03-2014-GES-0010
Revision/Amendment: 4.0
Version Date: 08/Mar/2016
Confidentiality Statement
This protocol is provided for conducting a research study. The information contained in this document is
confidential and, except to the extent necessary to obtain informed consent or EC/IRB approval, cannot be
disclosed unless required by governmental regulation. Persons to whom any portion of the contents of this
document is disclosed must be informed that the information is confidential and may not further be disclosed by
them.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis
Compared to Mammography (ADAPT Trial)
ADAPT-BX: Recruitment Plan for Initially Asymptomatic Women Referred for Breast Biopsy
GEHC Study Number: 124.03-2014-GES-0010
Revision/Amendment: 4.0
Version Date: 08/Mar/2016
Investigator’s Signature Page
I have read this protocol and study related documents and agree to conduct this study in full accordance
with the stipulations of the protocol described herein, and any subsequent amendments.
Investigator Signature
Date
Print Name
Site Name
Site Address

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Table of Contents
This document contains the following sections:
Topic
Page
Investigator’s Signature Page ....................................................................2
Table of Contents......................................................................................3
Document and Version Control .................................................................6
1. Study Synopsis .....................................................................................7
List of Abbreviations ...............................................................................11
2. Preliminary Investigations and Justification .......................................13
2.1.
Literature Review............................................................................................ 13
2.2.
Pre-Clinical (animal) Trials and Previous Clinical (human) Experience........... 14
2.3.
Device Risk Analysis ........................................................................................ 15
3. Research Device/Product ...................................................................15
3.1.
SenoClaire® - GE Breast Tomosynthesis (DBT)................................................ 15
3.2.
Full-field digital mammography (FFDM)......................................................... 16
3.3.
IDI MammoWorkstation ................................................................................. 16
4. Regulatory Status...............................................................................17
4.1.
Risk Category and Rationale (US Only) ........................................................... 17
4.2.
Device Classification and Rationale ................................................................ 17
4.3.
Device Issuance and Replacement ................................................................. 17
4.4.
Disposition of the Device/Product.................................................................. 18
5. Objectives of Research Study .............................................................19
5.1.
Hypothesis....................................................................................................... 19
5.2.
Study Objectives ............................................................................................. 19
5.3.
Study Endpoints .............................................................................................. 19
6. Design of Research Study ...................................................................20
6.1.
Type of Research Study................................................................................... 20
6.2.
Study Timeframe............................................................................................. 21
6.3.
Controls and Minimization of Bias.................................................................. 21
7. Study Subjects....................................................................................21
7.1.
Number of Subjects ........................................................................................ 21
7.2.
Subject Population.......................................................................................... 22
7.3.
Protection of Vulnerable Subjects .................................................................. 22
7.4.
Procedures for Enrollment.............................................................................. 22
7.5.
Inclusion Criteria............................................................................................. 22
7.6.
Exclusion Criteria............................................................................................. 23
7.7.
Screening Subjects for Enrollment.................................................................. 23

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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8. Procedures for Research Study...........................................................23
8.1.
Digital Breast Tomosynthesis (DBT) and Full Field Digital Mammography
(FFDM) Examinations...................................................................................... 23
8.2.
Post-Mammography Procedures.................................................................... 24
8.3.
Biopsy Procedures........................................................................................... 25
8.4.
Follow-up Procedures..................................................................................... 26
8.5.
Incidental Findings .......................................................................................... 26
8.6.
Withdrawal and Discontinuation Criteria....................................................... 26
9. Training Plan ......................................................................................27
9.1.
Training Plan for Research Device/Product.................................................... 27
9.2.
Training Plan for Protocol ............................................................................... 27
9.3.
Reader Training............................................................................................... 27
10.Data Analysis and Statistics................................................................28
10.1.
Statistical Analysis Methods ........................................................................... 28
10.2.
Interim Analysis............................................................................................... 30
10.3.
Handling of Missing Data................................................................................ 30
10.4.
Pass/Fail Criteria of the Study......................................................................... 30
11.Deviations..........................................................................................30
11.1.
Management of Protocol Deviations.............................................................. 30
12.Complaint Handling and Adverse Event Reporting .............................31
12.1.
Foreseeable Adverse Events and Device Effects ............................................ 31
12.2.
Adverse Event Definitions............................................................................... 31
12.3.
Management of Adverse Event Reporting ..................................................... 32
12.4.
Management of Serious Adverse Event and Unanticipated Adverse Device
Effect Reporting .............................................................................................. 33
12.5.
Management of Device Complaints ............................................................... 34
13.Early Termination or Suspension ........................................................34
13.1.
Criteria for Early Termination or Suspension ................................................. 34
13.2.
Withdrawal of EC/IRB Approval...................................................................... 35
14.Ethics Committee (EC) and Regulatory Filings.....................................35
14.1.
Regulatory Authority Approval Requirements (Global) ................................. 35
14.2.
Ethics Committee Approval Requirements..................................................... 35
14.3.
Management of Protocol Revisions/Amendments ........................................ 35
14.4.
Informed Consent and Privacy Requirements................................................ 35
15.Data and Quality Management ..........................................................36
15.1.
Management of Data...................................................................................... 36
15.2.
Subject De-identification ................................................................................ 36
15.3.
Completion of Case Report Forms (CRFs)....................................................... 37

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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15.4.
Record Retention at the Site........................................................................... 37
16.Monitoring Plan .................................................................................37
16.1.
Brief Description ............................................................................................. 37
16.2.
Reference to Approved Monitoring Plan........................................................ 38
17.Publication Policy...............................................................................38
18.Additional Country-Specific Regulatory Requirements .......................38
References ..............................................................................................39
Appendix A: Amendment to Protocol Version 1.0 to 2.0 .........................42
Appendix B: Amendment to Protocol Version 2.0 to 3.0..........................48
Appendix C: Amendment to Protocol Version 3.0 to 4.0..........................55

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Document and Version Control
This section records all changes made to the protocol for a specific study. In the table below, record
each and every relevant change by indicating what changes were made.
Revision
Date
(DD/Mmm/YYYY) Revision Author
Comments/Changes
1.0
17/Sep/2014
Sara Lam
Initial Version
2.0
08/Mar/2016
Carrie Lauer
Clinical Writer – Updated protocol per amendments detailed in
APPENDIX A: Amendment to Protocol Version 1.0 to 2.0
3.0
08/Mar/2016
Carrie Lauer
Clinical Writer – Updated protocol per amendments detailed in
Appendix B: Amendment to Protocol Version 2.0 to 3.0
4.0
08/Mar/2016
Carrie Lauer
Clinical Writer – Updated protocol per amendments detailed in
Appendix C: Amendment to Protocol Version 3.0 to 4.0

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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1. STUDY SYNOPSIS
Title of Study: Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis
Compared to Mammography (ADAPT Trial)
ADAPT-BX. Recruitment Plan for Initially Asymptomatic Women Referred for Breast Biopsy (ADAPT-BX)
Protocol Number (Study Number): 124.03-2014-GES-0010
Investigators and Study Center(s): Up to 3 centers in the United States (US) and France (FR)
Corinne Balleyguier MD
Gustave Roussy
Address:
114, rue Édouard Vaillant,
Villejuif, 94805
France
Telephone:
+33 01 42 11 51 89
E-mail: Corinne.balleyguier@gustaveroussy.fr
Lydia Liao, MD
Cooper Health - Cooper Breast Imaging Centers
Address:
900 Centennial Blvd. Suite B
Voorhees, NJ, 08043
US
Telephone:
+1-856-325-6591
E-mail:
liao-lydia@cooperhealth.edu
Kathy Schilling, MD
Boca Raton Regional Hospital
Christine E. Lynn Women’s Health and Wellness
Institute
Address:
690 Meadows Road
Boca Raton, FL, 33486
US
Telephone:          +1-561-955-5000
E-mail:
kschilling@brrh.com
Objective: The aim of this recruitment plan (ADAPT-BX) is to collect image and technical data on both digital
breast tomosynthesis (DBT) and full-field digital mammography (FFDM), along with other subject data
including histology results from biopsy specimen examination and cancer classification data from initially
asymptomatic women referred for biopsy after recall from screening and diagnostic work-up. These data
will be included in a subsequent and prospectively planned pooled analysis described in a separate protocol
(ADAPT-BIE) examining superiority of DBT to FFDM for breast cancer diagnosis and other clinical
performance measures.
Study Design: An open-label, multi-center, accrual study collecting DBT and FFDM images from up to 275
initially asymptomatic women aged ≥30 years referred for clinically indicated breast biopsy based on
suspicious breast imaging results will be conducted. CC and MLO views from bilateral GE DBT and GE
screening and/or diagnostic FFDM taken within a 30 day window of each other will be collected and
assessed on-site by qualified radiologist(s) for clinical management purposes. Results of biopsy(ies) and
histopathology, including lesion characteristics, will be recorded and considered as truth if positive for
cancer status. Subjects with negative or benign histological findings will have their images and
histopathology reviewed for concordance, per the site’s standard procedures. Histologic concordance with
imaging will be considered truth for non-cancer status.
Accrual DBT and FFDM data will be pooled for evaluation by independent blinded readers in a subsequent
reader study. The detailed information for the blinded image evaluation will be provided in a separate
Independent Review Charter (IRC) detailed in the ADAPT-BIE (Blinded Image Evaluation) study. This study’s

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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primary endpoint is collection of data to compare the diagnostic accuracy of two-view SenoClaire® - GE
Breast Tomosynthesis and two-view FFDM based on difference in receiver operating characteristic (ROC)
area under the curve (AUC) detailed in the separate ADAPT-BIE protocol.
Device-related Adverse Events (AEs), serious adverse events (SAEs), and device malfunctions will be
recorded and reported to Sponsor’s medical monitor and applicable authorities.  No other clinical safety
assessments will be performed.
Selection of Subjects: The subject population consists of initially asymptomatic adult women (>30 years of
age) referred for breast biopsy.
Inclusion Criteria:
Subjects may be included that meet the following criteria:
1.
Women aged 30 years or older (≥30 years old);
2.
Initially asymptomatic women who underwent routine bilateral screening FFDM, breast ultrasound
(U/S), breast magnetic resonance imaging (MRI), and/or DBT, followed by diagnostic work-up
showing one or more abnormalities and referred for breast biopsy 1,2;
3.
Are able and willing to comply with study procedures;
4.
Have signed and dated the informed consent form;
5.
Documented as non-pregnant based on the investigator’s medical judgment and in consideration
of local clinical practice standards for evidence of non-pregnancy.
Exclusion Criteria:
Subjects must be excluded from participating in this study if they meet any of the following criteria:
1.
Have been previously included in this study;
2.
Have undergone diagnostic or surgical intervention(s) or procedure(s) on either breast, including
mastectomy and cytopunction, before study-related imaging;
3.
Have breasts too large to be adequately positioned on 24 x 31 centimeter (cm) FFDM digital
receptor without anatomical cut off during a DBT or FFDM examination;
4.
Have participated in (within the prior 30 days), another trial of an investigational product expected
to interfere with study procedures or outcomes;
5.
Have breast implant(s);
6.
Have reconstructed breast(s).
Research Type:
Clinical (human)
Initially Asymptomatic Women Referred for Breast Biopsy
Pre-Clinical (animal)
External Bench
1 Subjects who had screening DBT or screening/diagnostic FFDM imaging on non-GE equipment may be enrolled if they agree to undergo repeat
imaging on a GE system; If the prior screening and diagnostic DBT or mammographic examinations were not conducted at the recruiting site,
review of those images by the investigator must confirm that breast biopsy recommendation is warranted and GE access to the images in DICOM
digital format must be granted.
2 Screening FFDM and DBT image acquisitions must be within 30 days of each other.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Brief Description of Study Purpose: This study is being conducted to accrue cancer cases for a subsequent
blinded reader study comparing the diagnostic accuracy and performance of digital breast tomosynthesis
(DBT) performed with the GE SenoClaire® GE Digital Breast Tomosynthesis compared to conventional GE
full-field digital mammography (FFDM) in asymptomatic women. The study also provides for exploratory
analysis of cancerous and non-cancerous lesion characteristics detected by DBT and FFDM systems. This
statistically powered study is being conducted to support regulatory claims to expand the labeling of the
DBT system.
Sponsor Name:
GE Healthcare (GEHC)
Sponsor contact: Sara Lam, Senior Clinical Affairs
Project Manager III
Address:
3000 N Grandview Blvd
Waukesha, WI 53188-1696 US
Telephone: +1 262-409-0828
E-mail:
Sara.J.Lam@ge.com
Device/Product GEHC Modality:
Detection and Guidance Solutions (DGS)
Device/Product GEHC Class:
SenoClaire® - GE Breast Tomosynthesis
Device/Product Description: Commercially available SenoClaire® - GE Breast Tomosynthesis is a Digital
Breast Tomosynthesis (DBT) device available for commercial full-field digital (FFDM) mammography systems
(GE Senographe® Essential Full-Field Digital Mammography) and read on IDI MammoWorkstation with
Volume-Preview Synthetic 2-D Mammography (V-Preview).
Regulatory Status:
Pre-Market
Post-Market
DBT, FFDM, and IDI MammoWorkstations used in this study are considered post-
market in the US and Europe. V-Preview for DBT is a commercially available tool on the
IDI MammoWorkstation not currently indicated for breast cancer diagnosis use.
Primary endpoints: The primary endpoint will be the respective site’s diagnosis for each subject of cancer
status (positive or negative/benign) based on histology of biopsy/surgical findings and histologic
concordance with imaging for benign lesions.
Characteristic Endpoints: Characteristic endpoints for all subjects will include histology findings and size,
lesion type, and other lesion characteristics based on image appearance. Technical characteristics of
electronic image data collected from subjects, such as information related to radiation dose, may be
extracted and analyzed by the Sponsor for the purposes of this study.
Safety endpoint: Device-related adverse events (AEs), serious adverse events (SAEs), and device
malfunctions by overall occurrence and imaging modality (DBT and FFDM) that occur during the study will
be collected. No other clinical safety assessments will be performed.
Sample Size: Up to 275 subjects referred for breast biopsy (Enrollment ceiling per site will be 165 subjects)
will be enrolled in this recruitment plan until at least 90 histopathology-confirmed cancers have been
accrued. Sample size is determined by the need to accrue at least 120 cancer cases and 250 non-cancer
cases for the overall GE Healthcare (GEHC) DBT program (ADAPT-BIE).
Research Manager Name: Tanya Carrillo
Research Manager – Women’s Health
Address:
3562 Lookout Court #478
Oceanside, CA 92056-5259, US
Telephone: +1-414-379-4201
E-mail:
Tanya.Carrillo@ge.com
Medical Monitor Name: Ron von Jako, MD, PhD
Medical Director, GEHC Quality-Medical Affairs
Address:
1100 Technology Park Drive
Billerica, MA 01821-4111, US
Telephone: +1-617-669-3200

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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E-mail:
Ron.VonJako@med.ge.com

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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LIST OF ABBREVIATIONS
2-D
Two-dimensional
3-D
Three-dimensional
ACR
American College of Radiology
ACRIN
American College of Radiology In Network
AE
Adverse Event
ALARP
As Low as Reasonably Practicable
ASF
Artifact Spread Function
AUC
Area Under the Curve
BIE
Blinded Image Evaluation
BI-RADS®
Breast Imaging Reporting and Data System
CC
Craniocaudal
CFR
Code of Federal Regulations
CHF
Clinical History File
CRF
Case Report Form
DBT
Digital Breast Tomosynthesis
DCF
Data Clarification Form
DGS
Detection and Guidance Solutions
DMP
Data Management Plan
EC
Ethics Committee
FDA
US Food and Drug Administration
FFDM
Full-field Digital Mammography
GCP
Good Clinical Practices
GE
General Electric Company
GEHC
General Electric Healthcare
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IRB
Institutional/Independent Review Board
IRC
Independent Review Charter
MLO
Mediolateral Oblique
MQSA
Mammography Quality Standards Act
MRI
Magnetic Resonance Imaging
PI
Principal Investigator
Reader
Interpreting Physician, as defined under 21CFR §900.12(a)(1)(i)(B)(2)
ROC
Receiver Operating Characteristics
SAE
Serious Adverse Event
SFM
Screen-film Mammography
US
United States

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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V-Preview
Volume-Preview Synthetic 2-D Mammography

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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2. PRELIMINARY INVESTIGATIONS AND JUSTIFICATION
2.1.
Literature Review
Introduction
Mammography screening is an important tool for reducing the rate of breast cancer mortality,
reported to reduce mortality in women aged 39 to 69 years by up to 14-32%. 1 In the United
States, women have a 12.29% lifetime risk (1 in 8 women) of developing breast cancer and
2.74% lifetime risk (1 in 36 women) of death due to breast cancer according to the American
Cancer Society (ACS) 2008-2010 US National Cancer Institute’s Surveillance Epidemiology and
End Results (SEER) database. 2 The ACS Cancer Facts and Figures report (2013) 3 predicts that
232,340 new diagnoses and 39,620 deaths occur each year due to breast cancer, though
progress in early breast cancer detection, improved treatment, and decreased use of
menopausal hormone therapy have steadily decreased breast cancer mortality rates over the
past three decades, with the most notable decreases in younger women. From 2005 to 2009,
death rates decreased 3.0% per year in women younger than 50 and 2.0% per year in women 50
and older. 3 False-positive mammography results and additional imaging are, however, common.
2 Thus, there remains a need for more effective tools for breast cancer screening and diagnosis
to further improve breast cancer patient outcomes.
Screening with conventional screen-film mammography (SFM) became widely used by the 1980s
4, 5 and has been considered the gold standard for early detection of breast cancer since the
1980s. 6, 7, 8, 9 Numerous sizable randomized trials have demonstrated that regular
mammographic screening reduces breast cancer mortality. 10, 11, 12, 13, 14 There remains
controversy, however, as to the benefit of conventional mammography alone, owing to
relatively high false positive rates and risks associated with repeat ionizing radiation exposure. 7,
15, 16, 17 A ten-year study of the risk of false positives in 9,762 screening mammograms conducted
by Elmore et al. 16 estimated that the cumulative risk of a false positive results was 49.1% (95%
CI; 40.3-64.1%) after 10 mammograms, resulting in a $33 cost of evaluating false positives for
each $100 spent in breast cancer screening. Furthermore, overdiagnosis has been reported to
occur in 1% to 10% of women that undergo screening mammography, and both overdiagnosis
and overtreatment risks increase dramatically as women age, particularly above age 70. 2 Thus,
there is currently an urgent need for improved breast cancer screening technology and care
pathways that will enable early detection and minimize the risk of overdiagnosis and
overtreatment, particularly in aging and high risk patient populations.
While age was previously considered the key determinate characteristic for false positive risk in
mammographic screening, recent evidence, including the AGE trial of 53,884 mammographic
screening patients in the UK, has refuted the value of age as the sole determinate of abnormal
interpretation rate in mammographic screening for breast cancer. 19, 20, 21, 22A study of 73,247
patients (46,340 mammograms) from the Washington State Mammography Tumor Registry
further indicated that breast density rather than age, is the paramount factor in prediction of
false positive screening mammograms, necessitating increased emphasis on breast density as a
defining characteristics in clinical breast cancer screening strategies and patient education for

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Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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patients with dense breasts. 23 Analysis of data collected from 1994 to 2008 in a group of 11,474
women with breast cancer and 922,624 without breast cancer that underwent mammography
at facilities that contribute to the Breast Cancer Surveillance Consortium (BCSC) mammography
registries indicated that the cumulative probability of false-positive mammography results was
highest among women undergoing annual mammography with extremely dense breasts who
were either aged 40 to 49 years (65.5%) or used estrogen plus progestogen (65.8%) and was
lower among women aged 50 to 74 years with scattered fibroglandular densities (30.7% and
21.9%, respectively) or fatty breasts (17.4% and 12.1%, respectively). 22 Further work is still
required to achieve optimal mammographic screening results, including reduction of false
positive rates, in women with dense breasts. The wide implementation of full-field digital
mammography (FFDM) has incrementally improved mammographic breast cancer screening, as
demonstrated by the significantly improved diagnostic accuracy of digital mammography
compared to screen-film mammography in pre-menopausal women and women with dense
breasts in the National Cancer Institute-sponsored and American College of Radiology Imaging
Network (ACRIN) Digital Mammographic Imaging Screening Trial (DMIST) (335 mammograms) 24,
25 and in other recent studies. 26, 27
Digital breast tomosynthesis (DBT) has been reported to achieve superior accuracy in a variety
of breast tissues types, potentially reducing false positives and increasing cancer detection rates
when applied as an adjuvant to mammography. 28, 29, 30, 31 Compared to conventional
mammography, DBT has also been reported to reduce false positives in noncalcified breast
tissues by up to 10% and to provide superior information on mass lesions, focal asymmetries,
and architecture distortions. 32, 33 Further evidence is required, however, to determine the most
advantageous clinical pathways for DBT in clinical breast cancer screening and diagnosis.
This protocol is one of multiple GEHC protocols designed to collect data from asymptomatic
women who have been referred to 1) screening mammography and 2) breast biopsy following
diagnostic work-up. The data from these protocols will be pooled for analysis to compare
diagnostic accuracy of DBT to FFDM for detecting breast cancers in asymptomatic women. This
protocol will recruit initially asymptomatic women who have undergone clinically recommended
mammography procedures and who have been recommended for breast biopsy because of one
or more radiographically detected suspicious lesions.
2.2.
Pre-Clinical (animal) Trials and Previous Clinical (human) Experience
There is previous clinical evidence that combined 3-D DBT images with 2-D synthetic images can
improve diagnostic performance and confidence in cancer detection using DBT. The first
combination 2-D synthetic and 3-D DBT system, Hologic C-View, was cleared by the US FDA in
May 2013. 34 Using this device, the Oslo study revealed that DBT with 2-D synthetic and 3-D
capabilities resulted in approximately 30% improvements in breast cancer detection over 2-D
FFDM alone. 34 The Sponsor previously tested the GE SenoClaire® DBT system in GE190-004 BIE
(Blinded Imaging Evaluation) study – US. A Multicenter Study to Test the Non-Inferiority of
Digital Breast Tomosynthesis Compared to FFDM in Detecting Breast Cancer. 35

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2.3.
Device Risk Analysis
2.3.1. Device Risk Analysis
DBT has not been reported to have additional side-effects or radiation exposure compared to
conventional 2-D FFDM of similar views, and subjects that have DBT plus FFDM have been
shown to have lower recall rates than those that have FFDM alone. 36 The Sponsor has
completed a risk analysis (GEHC Breast Tomosynthesis Risk Analysis, GEHC internal document
DOC0890254). Having both DBT and FFDM exams in a short time and possibly having repeat
FFDM and/or DBT on GE equipment can result in additional ionizing radiation exposure, not to
exceed doses that are considered to be As Low as Reasonably Practicable (ALARP) for the
purpose of this research and are not expected to exceed risks of routine clinical breast cancer
screening and follow-up. As a result of participating in this study, the subject may be exposed to
additional radiation compared to having only routine mammography on FFDM or DBT only. No
additional medications will be administered beyond those regularly required for the subject’s
medical care outside of this study, and regular medication should not be adversely impacted or
delayed by study participation.
2.3.2. Benefits
Having both DBT and FFDM may benefit subjects by improving identification of suspicious
findings, and providing access to DBT imaging otherwise unavailable to some subjects. A benefit,
however, cannot be guaranteed.
3. RESEARCH DEVICE/PRODUCT
3.1.
SenoClaire® - GE Breast Tomosynthesis (DBT)
The SenoClaire® - GE Breast Tomosynthesis is a digital breast tomosynthesis (DBT) device
capable of generating digital mammographic images for use in screening and diagnosis of breast
cancer. The SenoClaire® - GE Breast Tomosynthesis is intended for the same clinical applications
as traditional screen film and digital mammography systems. GE Digital Breast Tomosynthesis is
an add-on device for Senographe® Essential standard FFDM systems. SenoClaire® - GE Breast
Tomosynthesis is a DBT hardware and software option available for new and existing
Senographe Essential platforms.
DBT reconstructed three-dimensional (3-D) imaging technology uses multiple individual low-
dose views acquired in a limited-angle, around a compressed breast in a step-and-shoot
acquisition mode. The acquired projection images are processed electronically to reconstruct
multiple in-focus planar views through the entire breast, with blurring of out-of-plane tissues.
DBT is designed to reduce the structured noise of superimposed, out-of-plane tissues, which is a
limiting factor in standard 2-D mammography.
To allow acquisition in a step-and-shoot mode, using partial isocentric motion, the standard
breast holder is replaced by a tomosynthesis module. Once the breast is compressed, the
system acquires a sequence of 9 projection views, each acquired with the X-ray tube located at a

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different angle along a linear arc. The reconstruction software and review workstation allows for
reconstruction and display of a stack of planar DBT image through the breast, parallel to the
breast support. Several refined processing algorithms used in FFDM are applicable in the DBT
reconstruction process, including FineView processing. These processing algorithms, along with
100 micron pixel size, yield high spatial resolution DBT images through the entire breast that can
be viewed by the radiologist with minimal manual image adjustment.
Information pertaining to the specific design differences between the SenoClaire® - GE Breast
Tomosynthesis and conventional mammography were included in the approved Pre-Market
Application (PMA), which has been approved by the US FDA (refer to PMA module 1) and
European CE mark. Most notably, the tomosynthesis technique used by the DBT system employs
improved artifact correction based on the artifact spread function (ASF). The ASF is the impulse
response of the tomosynthesis system along the z-axis. It is sometimes used as a figure of merit
for the assessment of out-of-plane artifacts, according to the theoretical approach described by
Hu et al. 37
3.2.
Full-field digital mammography (FFDM)
GE Full-field digital mammography (FFDM) devices are integrated systems that include both the
X-ray delivery system and integrated (non-removable) detector. These systems are intended to
be used on existing X-ray systems where the removable detector, such as a computed
radiography cassette, replaces the film/screen detector. 39 These systems, such as the GE
Senographe® Essential standard FFDM platform, are widely commercialized and routinely used
for breast cancer screening and diagnosis.
3.3.
IDI MammoWorkstation
The IDI MammoWorkstation system will be used in this study to enable readers to view FFDM
images, as well as 3-D DBT and synthetic 2-D DBT images.
The IDI MammoWorkstation can be used to review FFDM, 3-D DBT images, and mammographic
images from other modalities.  IDI MammoWorkstation allows radiologists to smoothly navigate
through the DBT dataset using dedicated 2-D/3-D hanging protocols and specific ergonomic
features: 35

Straightforward visual identification of all series of tomosynthesis planes and slabs

Dedicated tools to review tomosynthesis data sets: cine loop, bookmarks, breast
localizer, breast height ruler

V-Preview reconstructed images from tomosynthesis
3.3.1. Volume-Preview Synthetic 2-D Mammography (V-Preview)
Volume Preview Synthetic 2-D Mammography (V-Preview) is the algorithmic software
developed by GE Healthcare for use on the IDI MammoWorkstation to reconstruct a synthetic 2-
D view from tomosynthesis images, producing image quality designed to be similar to that of
conventional full-field digital mammography (FFDM).

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4. REGULATORY STATUS
The SenoClaire® - GE Breast Tomosynthesis (DBT) system, GE Senographe® Essential Full-Field
Digital Mammography system, and workstations (including software components) used in this
study are commercially available as determined by the United States (US) Food and Drug
Administration (FDA) and European CE mark. The IDI MammoWorkstation version 4.7.0, with
the ability to interpret DBT images using V-Preview as a navigation tool is CE Marked and FDA
cleared for use under US 510(k) K123575, however the V-Preview images are currently labeled
not for diagnostic purposes and cannot be stored, printed or transmitted outside of the IDI
MammoWorkstation.
4.1.
Risk Category and Rationale (US Only)
The SenoClaire® - GE Breast Tomosynthesis (DBT) and mammography devices under
investigation are considered non-significant risk devices per the 21 CFR 812. 3 definition:
1) it is not intended as an implant;
2) it is not purported or represented to be for a use in supporting or sustaining human life;
3) it is not for a use of substantial importance in diagnosing, curing, mitigating, or treating
disease, or otherwise preventing impairment of human health;
4) and it does not otherwise present a potential for serious risk to the health, safety, or
welfare of a subject.
This designation of non-significant risk is supported by the study design in which DBT data will
not be used as the sole measure of diagnosis without distinct confirmation from conventional
methods, such as mammography or other standard of care procedures (e.g., breast ultrasound,
breast magnetic resonance imaging (MRI), or biopsy) at the investigational site.
4.2.
Device Classification and Rationale
In the United States (US) and France, the SenoClaire® - GE Breast Tomosynthesis (DBT) is
considered to be Class III, as defined by the US FDA CFR 1020.30-33 and French National Agency
for the Safety of Medicine and Health Products regulations in accordance with the European
Medical Directive 93/42/EEC. FFDM devices without tomosynthesis or computed tomography
breast imaging devices are considered to be Class II and Class IIa (special controls), as defined by
the US FDA 21 CFR 892.1715 and French National Agency for the Safety of Medicine and Health
Products regulations in accordance with the European Medical Directive 93/42/EEC.
The IDI MammoWorkstation is a Class II medical device under 21 CFR 892.2050 Picture Archiving
and Communications Systems (product Code LLZ) and Class IIa (special controls) in Europe.
4.3.
Device Issuance and Replacement
SenoClaire® - GE Breast Tomosynthesis (DBT), FFDM, and IDI MammoWorkstation devices used
in this study will be commercially available. Unique identifying information (e.g. model, serial
number, etc.) of each device used in this study will be recorded.

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Ancillary equipment, including safety equipment such as protective vests, and surgical
equipment necessary for biopsy(ies) procedure(s) will be used in this study according to the
standard of care at the investigational site. These devices will be owned and maintained by the
investigational site.
Sites will be encouraged to use equipment owned by the site, if available. For sites that do not
own required mammography equipment (DBT, FFDM, and/or IDI MammoWorkstation) or
component software versions necessary to complete study procedures, the Sponsor may
provide devices for study use.
4.3.1. Maintenance of Research Devices
Devices used in this study will be maintained, calibrated, and ensured to be functioning correctly
during the study, in accordance with applicable site policy and state and federal requirements.
The Site Principal Investigator (PI) should inform the Sponsor of any known or anticipated issues
with device functionality or availability that could impact the conduct or outcomes of this
research study.
4.3.2. Concurrent Use of Research Devices
The DBT and FFDM devices used in this study are commercially available, multiple-use devices.
Devices owned by the site may be used concurrently in this research and for standard of care
procedures outside of this study. Devices provided to the site by GE shall be limited to use only
for this protocol. The site is responsible for completing routine care, such as prevention of
cross-contamination, between procedures that could impact study subjects.
4.3.3. Device Software and Configuration Management
The most current commercial configuration and software version for SenoClaire® - GE Breast
Tomosynthesis (DBT) will be used during this study, and the site(s) should use an IDI
MammoWorkstation with software version 4.7 MR2 or higher (capable of viewing V-Preview
images). In the event of commercial release of software versions or configuration changes that
will be implemented on devices used in this study, changes shall not increase risk classification
of the study. The Site Principal Investigator (PI) is responsible for notifying the Sponsor of any
current or planned software or configuration changes, including the date of implementation on
a per-device basis. The Sponsor may, at its discretion or upon site request, require additional
training or quality control procedures (e.g. calibration or other routine engineering maintenance
activities) following software or configuration changes.
4.4.
Disposition of the Device/Product
Devices and associated accessories, provided to the site for the purposes of this clinical trial, will
be collected at the end of the study and returned to GE Healthcare.

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5. OBJECTIVES OF RESEARCH STUDY
5.1.
Hypothesis
No statistical hypothesis is tested in this data collection study. The sample size for breast biopsy
subjects in this study is determined to provide sufficient accrual of cancer cases for a
subsequent statistically powered analysis as part of a separate protocol (ADAPT-BIE).
5.2.
Study Objectives
5.2.1. Primary Objective(s)
The aim of this recruitment plan (ADAPT-BX) is to collect image and technical data on both
digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM), along with other
subject data, including histology results from biopsy specimen examination and cancer
classification data, from initially asymptomatic women referred for biopsy after recall from
screening and diagnostic work-up. These data will be included in a subsequent and prospectively
planned pooled analysis described in a separate protocol (ADAPT-BIE) examining superiority of
DBT to FFDM for breast cancer diagnosis and other clinical performance measures.
5.2.2. Characteristic Objectives
An exploratory aim is to describe cancer and non-cancer cases identified in this accrual study
based on histology findings and lesion type.
5.3.
Study Endpoints
5.3.1. Primary endpoints
The primary endpoint will be the respective site’s diagnosis for each subject of cancer status
(positive or negative/benign) based on histology of biopsy/surgical findings and histologic
concordance with imaging for benign lesions.
5.3.2. Characteristic Endpoints
Characteristic endpoints for all subjects will include histology findings and size, lesion type, and
other lesion characteristics based on image appearance. Technical characteristics of electronic
image data collected from subjects, such as information related to radiation dose, may be
extracted and analyzed by the Sponsor for the purposes of this study.
5.3.3. Safety endpoint
Device-related adverse events (AEs), serious adverse events (SAEs), and device malfunctions by
overall occurrence and imaging modality (DBT and FFDM) that occur during the study will be
collected. No other clinical safety assessments will be performed.

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6. DESIGN OF RESEARCH STUDY
6.1.
Type of Research Study
6.1.1. Study Type
This study (ADAPT-BX) is an open-label, multi-center, within-subject crossover, prospective,
clinical research study, collecting images and associated data from bi-lateral two-view DBT and
FFDM exams conducted with GE systems. Study subjects will be initially asymptomatic adult
women ≥30 years of age presenting for breast biopsy based on prior breast imaging.
The data from this study will be pooled with data from other subjects, who will have been
recruited under other GEHC protocols (including ADAPT-SCR and ADAPT-ENRICH), for analysis
described in a separate protocol (ADAPT-BIE). Figure 1 depicts the study design and procedures.
Figure 1:  Study Design and Procedures
Initially asymptomatic
women ≥30 referred for
breast biopsy
(n = 275)
Histopathology
Truth
Cancer
(Positive for Cancer)
Positive
BX
Benign/
Negative
Truth
Non-Cancer
(Negative for Cancer)
SOC Histologic
Concordance
Concordant
SOC re-Bx
recommended?**
Discordant
GE
FFDM*
GE DBT*
≤30 days
Yes
*Images may be collected from FFDM and/or DBT performed on GE equipment prior to enrollment, if conducted within 30 days of each other.
** If rebiopsy is not recommended or if histopathology remains discordant with imaging findings after rebiopsy, the subject will be withdrawn
from the study.
6.1.2. Study Design Details:
Open-Label
Interventions are known to researchers and subjects
Blinded
Double-Blinded

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Single-site
Multi-site
Data will be pooled from multiple studies (e.g. ADAPT-SCR, ADAPT-BX, &
ADAPT-ENRICH) at multiple sites
Randomization
Procedure:
Not randomized:
Treatments occur as clinically indicated, not according to randomization
Single arm
Comparator
Diagnostic accuracy of DBT vs FFDM will be assessed in a separate protocol
(ADAPT-BIE)
Parallel
Crossover
This is a within-subject crossover study
Prospective
Subjects are enrolled and then undergo study procedures
6.2.
Study Timeframe
The study is expected to begin in the fourth quarter of 2014, and last for approximately two
years (24 months), or until the target subject population is enrolled or the Sponsor otherwise
indicates in writing that enrollment should be terminated. The end of the study shall be defined
as the date when the last subject undergoes biopsy procedures and concordance is established,
if applicable. Subject participation will be from the point of enrollment until truth determination
of cancer status. The Investigator shall not begin the study until the applicable EC/IRB and
necessary regulatory authority (when required) approval have been obtained.
6.3.
Controls and Minimization of Bias
The following bias control methods are being employed in this study:
a.
Selection bias in allocating subjects to interventional groups will be limited by attempting
to enroll consecutively eligible subjects. To reduce bias introduced from this study by
subjects who are expected to be referred for biopsy primarily based on FFDM screening,
other sources (e.g. ADAPT-ENRICH) may be pooled to include cancer cases reaching biopsy
through a DBT screening program.
b.
Spectrum bias will be limited by using a population expected to be representative of the
general population at the investigational site, without regard for race, or ethnicity.
7. STUDY SUBJECTS
7.1.
Number of Subjects
Up to 275 subjects referred for breast biopsy (Enrollment ceiling per site will be 165 subjects)
will be enrolled from three (3) centers located in the US and Europe (France) until at least 90
histopathology-confirmed cancers have been accrued. Enrollment will be closed once the
required number of cancers has been histologically identified. Data will be pooled with other

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sources to achieve the target number of positive and negative cancer cases, as described in
Section 10.1.1 Sample Size Justification.
7.2.
Subject Population
Study subjects will be adult women (>30 years of age) clinically referred for breast biopsy due to
abnormalities on routine screening Mammography, breast ultrasound (U/S), breast Magnetic
Resonance Imaging (MRI) or Digital Breast Tomosynthesis (DBT); subjects must have been
asymptomatic at the time of screening.
7.3.
Protection of Vulnerable Subjects
This study does not intend to enroll vulnerable subject populations.
7.4.
Procedures for Enrollment
All subjects must satisfy all the inclusion criteria and none of the exclusion criteria defined in the
protocol. Subjects must sign and date the informed consent form prior to completing protocol
specific procedures. The Investigator may discuss with the Sponsor any subject who does not
strictly meet the inclusion/exclusion criteria but who is thought to be otherwise appropriate for
the study; if the Sponsor and Investigator agree that inclusion of the subject would not affect
the scientific or ethical aspects of the study, the Sponsor may provide a written exception for
the subject. In this case, the details of the exception will be recorded on the Case Report Form
(CRF). A subject will be considered enrolled when determined eligible and informed consent is
signed, whether or not the subject undergoes study procedures.
7.5.
Inclusion Criteria
Subjects may be included that meet the following criteria:
1.
Women aged 30 years or older (≥30 years old);
2.
Initially asymptomatic women who underwent routine bilateral screening FFDM, breast
ultrasound (U/S), breast magnetic resonance imaging (MRI), and/or DBT, followed by
diagnostic work-up showing one or more abnormalities and referred for breast biopsy 1, 2;
3.
Are able and willing to comply with study procedures;
4.
Have signed and dated the informed consent form;
5.
Documented as non-pregnant based on the investigator’s medical judgment and in
consideration of local clinical practice standards for evidence of non-pregnancy.
1 Subjects who had screening DBT or screening/diagnostic FFDM imaging on non-GE equipment may be enrolled if they agree to undergo repeat
imaging on a GE system; If the prior screening and diagnostic mammographic examinations were not conducted at the recruiting site, review of
those images by the investigator must confirm that breast biopsy recommendation is warranted and GE access to the images in DICOM format
must be granted
2 Screening FFDM and DBT image acquisitions must be within 30 days of each other.

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7.6.
Exclusion Criteria
Subjects must be excluded from participating in this study if they meet any of the following
criteria:
1.
Have been previously included in this study;
2.
Have undergone diagnostic or surgical intervention(s) or procedure(s) on either breast,
including mastectomy and cytopunction, before study-related imaging;
3.
Have breasts too large to be adequately positioned on 24 x 31 centimeter (cm) FFDM digital
receptor without anatomical cut off during a DBT or FFDM examination;
4.
Have participated in (within the prior 30 days), another trial of an investigational product
expected to interfere with study procedures or outcomes;
5.
Have breast implant(s);
6.
Have reconstructed breast(s).
7.7.
Screening Subjects for Enrollment
Subjects will be screened for recruitment from initially asymptomatic populations referred for
breast biopsy due to imaging findings at each site, in accordance with local EC/IRB recruitment
policy. Enrollment decisions will be based upon the Investigator’s judgment. Final screening will
include confirmation that each subject meets all inclusion and no exclusion criteria. All screening
will be conducted in compliance with applicable laws, regulations, and standard procedures at
the investigational site.
8. PROCEDURES FOR RESEARCH STUDY
All enrolled subjects will undergo the following procedures prior to receiving study-specific imaging
(if required) and/or undergoing their clinically indicated biopsy procedure:
•
A notation will be made in the subject’s medical chart that the subject is participating in the
clinical trial.  Additionally, the notation should indicate that the subject had her questions
answered, and that she read, signed and dated, and had been given a copy of the Informed
Consent Form (ICF);
•
Study entry criteria, demographic information (including age), relevant reproductive
medical/surgical history such as oophorectomy, hysterectomy, or other reproductive
surgeries and pregnancy/menopausal status will be reviewed;
•
A subject number will be assigned.
There is no special subject preparation required to perform DBT or FFDM mammography.
8.1.
Digital Breast Tomosynthesis (DBT) and Full Field Digital Mammography
(FFDM) Examinations
Prior screening and/or diagnostic FFDM and/or DBT images will be collected from each subject’s
medical record. If necessary (e.g. because prior screening and/or diagnostic FFDM and/or DBT

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mammography images/views are not available or were not collected with GE equipment), a
subject may undergo study-specific FFDM and/or DBT imaging. Study-specific imaging will
include a bilateral two-view (both CC and MLO views) FFDM and/or DBT performed using the GE
FFDM and/or DBT system available at the site and according to the hospital’s standard
procedure.
Two-view DBT and FFDM image acquisition (both CC and MLO views) shall be performed within
30 days of each other, regardless if FFDM or DBT was performed before or after the patient
agreed to participate in the study. Subjects requiring study-specific imaging will undergo the
following procedures:
•
Enter a changing room to prepare for their mammogram;
•
Each subject of child-bearing potential will wear a lead apron or have equivalent
shielding during the FFDM and/or DBT procedures;
•
Undergo FFDM and/or DBT procedure(s);
•
Will be monitored for AEs and SAEs from study-specific DBT and FFDM and will be
recorded in the source documents and CRF.  Device malfunctions shall be sent to the
Sponsor as per Section 12.5 Management of Device Complaints.
All scanning should be performed within the standard range of scan parameters, as per the
manufacturer-provided operator’s manual(s) for GE FFDM and DBT devices. The scan operator
should conduct DBT and FFDM exam according to the standard clinical practice at the site with
consideration for:
•
Subjects with large breasts, because perspiration under the breast can cause the skin to
soften, and become paper-thin;
•
Any condition that exists which may cause unusual discomfort or tearing of the skin,
which could include telling the subject the importance of correct positioning. The
subject should be positioned carefully to avoid any discomfort to abnormalities such as
warts, scarring, or skin which is not intact;
•
Warmth of the front part of the breast support, which can be warm to the touch, as it
contains electronic components that generate heat;
•
Positioning the breast properly in FFDM and DBT in the CC position, where it is essential
that the breast is lifted away from the chest wall and gently pulled forward, in order to
visualize the maximum amount of breast tissue.
8.2.
Post-Mammography Procedures
The following assessments will be performed:
•
DBT and FFDM images will be assessed at the study site by one or more MQSA-qualified
radiologists, as per institutional standard practice;

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
If clinically indicated based on imaging results, subjects will undergo biopsy or surgical
intervention and breast tissue histopathological analysis, as per institutional standard
practice.
The IDI MammoWorkstation permits 3-D-reconstruction and 2-D-reconstruction (V-Preview).
The evaluating radiologist should use the image reconstruction views appropriate for diagnostic
evaluation, per his or her medical judgment, and handle diagnostic evaluations in accordance
with the standard of care at the investigational site.
8.2.1. On-Site Image Interpretation
DBT and FFDM images of all included subjects will be assessed at the study site by one or more
MQSA-qualified radiologists on an IDI MammoWorkstation. The DBT results may result in a
recommendation that additional breast lesions be biopsied (in addition to that/those already
planned when the patient entered the study). If so, biopsy plans may be changed accordingly.
The results of DBT alone, however, will not be used as a basis to cancel plans for biopsy of any
lesion.
The evaluating radiologist(s) at the site will record for each subject, the following parameters:

Breast density (as defined by BI-RADS®density categories)

Finding characteristics, to include breast laterality, lesion type, depth, quadrant and size.
In the case of multiple findings, a maximum of three (3) most suspicious findings will be
scored and localized.
8.2.2. Additional Diagnostic Imaging
If a subject is called back for further diagnostic assessment, the additional breast imaging that
the subject undergoes will be recorded on the CRF.
8.3.
Biopsy Procedures
Percutaneous and open surgical breast interventions will proceed as per standard of care at the
recruiting site. The interpretation of the local pathologist will be recorded on the CRF.
If the subject does not complete the biopsy procedure as scheduled or if the biopsy procedure is
not successful or produces indeterminate results that are not able to be resolved by clinically
indicated procedures, such as repeat biopsy(ies), the subject will be withdrawn.
For benign/negative histopathology results, the site radiologist will review the subject’s imaging
and histopathology findings for concordance, per the site’s standard of care, and results will be
captured on a CRF. Histologic concordance with imaging for negative or benign lesions will be
considered truth for non-cancer status. If surgical excision is recommended even after
concordance between imaging and histopathology, the resulting histopathology from surgical
excision may be collected as part of the study.

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Protocol: 4.0
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Subjects who have negative or benign histology findings that are discordant with imaging shall
be followed-up per the site’s standard of care. If rebiopsy is recommended, the histology
findings and concordance assessment of the rebiopsy will be used to determine the subject’s
cancer status. If rebiopsy is not recommended or if histopathology remains discordant with
imaging findings after rebiopsy, the subject will be withdrawn from the study.
8.4.
Follow-up Procedures
Results from surgical intervention and/or any additional follow-up resulting from biopsy(ies)
(e.g., breast ultrasound or magnetic resonance imaging [MRI]) will be considered in determining
truth of cancer status.
No additional follow-up appointments will be required for subjects that have completed
biopsy/surgical intervention with positive findings or documented histologic concordance with
imaging.
8.5.
Incidental Findings
If any unexpected atypical or abnormal findings unrelated to the study aims (breast cancer
identification) are identified during this study that may incidentally indicate other diseases or
other unknown conditions, these cases will be reported to the Site Principal Investigator. If the
Site Principal Investigator determines that these findings are medically significant in his or her
medical judgment, he or she will notify the subject and refer her for further follow-up outside of
this study according to the standard of care at the investigational site. Follow-up for incidental
findings is not required by this study, but relevant images and data resulting from examinations
related to incidental findings may be provided to the Sponsor, at the discretion of the Principal
Investigator, if determined to be relevant to study conduct or integrity of study results.
8.6.
Withdrawal and Discontinuation Criteria
8.6.1. Subject Withdrawal Rules
The subject’s medical care shall take precedence over any research imaging or other procedures
associated with the study.  If it is discovered during the study (any time after consent has been
signed or study procedures have begun) that any study procedure will negatively impact
required clinical care, the subject shall be withdrawn from the study.
Each subject is free to withdraw from the study at any time. Investigator(s) also have the right to
withdraw subjects from the study in the event of illness, AEs, SAEs, or other reasons concerning
the health or well-being of the subject, or in the case of lack of cooperation.
If a subject withdraws (or is withdrawn), all efforts will be made to complete and report the
observations up to the time of withdrawal. A complete final evaluation at the time of the
subject’s withdrawal should be made and an explanation given on the CRF given as to why the
subject is withdrawing or being withdrawn from the study. If the reason for withdrawal is a
clinical AE or SAE, monitoring will continue until the outcome is evident. The specific event or
test result(s) must be recorded on the CRF.

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In the event the subject experiences pain, undue discomfort, or destabilizing vital signs that is
observed by visual inspection or via monitoring equipment, or requests to discontinue study
procedures, the study procedures will be stopped immediately, and the appropriate response
will be taken according to the standard of care at the investigational site.
A subject may withdraw from study participation at any time, for any reason without
consequence. The study staff may withdraw a subject at any time for any reason. There shall be
no negative repercussions to the subject. The reasons for withdrawal and discontinuation for
any subject shall be recorded. These will be reported to the Sponsor. The EC/IRB should be
notified per their notification of subject withdrawal policy.
As described in Section 8.3 Biopsy Procedures, subjects with initial benign/negative
histopathology results that are discordant with imaging findings will be withdrawn from this
study if no rebiopsy or histopathology occurs, or if histopathology remains discordant with
imaging findings following rebiopsy.
Subjects withdrawn after consent is signed will be counted as enrolled subjects up until the time
of withdrawal, and will be considered in reporting total enrolled subjects in this study per the
populations defined in Section 10.1.2. - Study Populations.
9. TRAINING PLAN
9.1.
Training Plan for Research Device/Product
Training will be provided to study staff on the use of device system(s), as needed. Study staff
that will be operating the device(s) during subject procedures may be required to receive
additional training above that is required by other study staff. The Sponsor will provide
instructions for use of the device and, as necessary, subsequent training, at the Sponsor’s
discretion or upon request by the site.
9.2.
Training Plan for Protocol
Study staff will be trained on the study protocol and study procedures, including completion of
Informed Consent Forms (ICFs), Case Report Forms (CRFs), and other study documentation.
Training will also be provided to ensure appropriate storage and handling of images and data. All
study staff will be required to be trained on Good Clinical Practice (GCP) guidelines per ISO
14155: 2011.
A record of all formal training attendance and date conducted will be stored in the Site
Regulatory Binder and provided to the Sponsor for inclusion in the Sponsor’s Clinical History File
(CHF).
9.3.
Reader Training
All study staff assessing images for this study will be qualified radiologists at the investigational
site(s), and reads will be performed according to the standard of care at the investigational site.
All readers will be trained on the study protocol and on recording of data on CRFs prior to

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reading images. Determinations made by site radiologists based on DBT and FFDM images
collected in this study may be included in the subject’s regular medical record.
10.DATA ANALYSIS AND STATISTICS
10.1. Statistical Analysis Methods
10.1.1. Sample Size Justification
The projected sample size is determined by the need to accrue at least 120 cancer cases and 250
non-cancer cases for the overall GE Healthcare SenoClaire® - GE Breast Tomosynthesis (DBT)
development program. To achieve these overall accrual targets, the data from this study will be
pooled with data from other studies (e.g. ADAPT-SCR and ADAPT-ENRICH).
In this study, for an enrollment of 275 subjects recommended for breast biopsy, it is assumed,
based on the GE-190-003 experience, approximately 33% are expected to have a proven cancer
and approximately 33% will have a benign lesion. So, at least 90 cancer cases and 90 non-cancer
cases are expected to be accrued in this study. Up to 275 subjects referred for breast biopsy
(Enrollment ceiling per site will be 165 subjects) will be enrolled from three (3) centers located
in the US and Europe (France) until at least 90 histopathology-confirmed cancers have been
accrued.
Based on the GE-190-001 experience, for an enrollment of 250 subjects having screening
mammography, about 185 (75%) will complete the study with a normal 1-year follow-up.
Approximately 2% are expected to have a proven cancer either at screening or during follow-up,
which will provide an estimated 6 cancer cases that are expected to be accrued in the ADAPT-
SCR study.
In the ADAPT-ENRICH study, for a target enrollment of 90 subjects recommended for breast
biopsy, it is assumed, based on the GE-190-003 experience, approximately 33% are expected to
have a proven cancer. Thus, at least 30 cancer cases are expected from the ADAPT-ENRICH
study.
With the combination of these studies (ADAPT-SCR, ADAPT-BX, and ADAPT-ENRICH), it is
expected that at least 120 cancer cases and 250 non-cancer cases will be accrued for the overall
GEHC DBT development program. If necessary, data from other sources may also be included to
achieve the required number of cancer and non-cancer cases.
The accrued DBT and FFDM images will be used in a blinded image evaluation to analyze the
diagnostic performance of SenoClaire® - GE Breast Tomosynthesis (DBT) compared to FFDM
through receiver operating characteristic (ROC) analysis, sensitivity, specificity, recall rate, and
other analyses.
No statistical analyses are included as part of this study. A descriptive summary will be provided
for data collected in this study.

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10.1.2. Study Populations
The Efficacy Population will consist of those subjects meeting the study inclusion/exclusion
criteria with no protocol violations judged to affect the ability to evaluate the subject whose
DBT and FFDM images are diagnostically evaluable, and whose mammography images are
available for the independent blinded evaluation regardless of the image quality. Non-available
images will include:

those lost due to corrupted media or inability of site to transport to image review
center;

subjects where no images are acquired.
The Sponsor will make any decisions regarding whether any subjects or any individual values
belonging to a subject will be excluded from the evaluations when a protocol violation is
considered to have a negative impact on the scientific aspects and interpretation of the study
results. The reason(s) for any exclusion(s) will be documented in the study report.
The Safety Population will include all subjects enrolled into the study.
10.1.3. Subject Disposition and Characteristics
Subjects enrolled, imaged, and withdrawn will be summarized overall and by site and imaging
modality.  Descriptive statistics and summaries will be provided for demographics, medical
histories, image acquisition, lesions and findings.
Specific subgroups of interest include stratification by the following variables:
•
Age;
•
Menopausal status; and
•
Breast density.
10.1.4. Adverse Events
Adverse events will be reported from the time the subject enters the imaging suite for study
procedures until the time the subject leaves the imaging suite after the study procedure. Device-
related adverse events (AEs) and serious adverse events (SAEs) reported by subjects within 30
days of imaging (only those reported by subjects will be considered, and no separate 30-day
follow-up is planned), and device malfunctions occurring in the safety population will be
summarized with subject counts overall and by modality (DBT and FFDM).  Additionally,
individual subject listings will be provided to detail all AE/SAE information collected.
10.1.5. Methods
All descriptive analyses will be performed using SAS V9 (SAS Institute, Inc. Cary, North Carolina,
USA).
Any deviations, changes, or additions to the statistical analysis outlined in the protocol will be
described with reasons for the deviations in the final Clinical Study Report.

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10.2. Interim Analysis
No interim analysis is prospectively planned. The Sponsor may, however, review and monitor
data collected to date at any point during the study for purposes of monitoring study conduct
and completion.
10.3. Handling of Missing Data
There will be no imputation of missing data and collected data will be analyzed as is.
10.4. Pass/Fail Criteria of the Study
No statistical criteria for success are defined for this accrual study, which will be considered
successful if subject number and truth accrual targets are met, without consideration for
subsequent analysis results.
11.DEVIATIONS
11.1. Management of Protocol Deviations
Deviations to the protocol may occur when necessary to protect the life or physical well-being of
a subject. Except in an emergency, prior approval by the Sponsor is required for changes in, or
planned deviations from this protocol. If these changes affect the scientific soundness or the
safety and welfare of the subject, prior EC/IRB approval is also required. Planned Protocol
Deviation documentation must be filed in the Site Study Regulatory Binder. There are two types
of unplanned protocol deviations, critical deviations and non-critical deviations. All deviations
must be documented and reported, the criticality of the deviation will determine the reporting
path.
Critical Deviations:
Deviations that significantly affect the safety, efficacy, integrity or conduct of the study.
These deviations must be reported to the Sponsor no later than 5 working days from awareness
of occurrence and reported to the EC per the deviation reporting policy.
If an Investigator uses a device without obtaining informed consent, per Section 14.4 Informed
Consent and Privacy Requirements, the Investigator shall consider this a critical deviation and
report the event to the Sponsor and the EC/IRB within 5 working days of the occurrence.
Non-Critical Deviations:
Protocol deviations that DO NOT significantly affect the safety, efficacy, integrity or conduct of
the trial.
These deviations must be documented on the Case Report Form Protocol Deviation page and
will be reviewed by the study monitor.

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12.COMPLAINT HANDLING AND ADVERSE EVENT REPORTING
12.1. Foreseeable Adverse Events and Device Effects
There are no known additional medical risks or side effects from digital breast tomosynthesis
(DBT) beyond those of conventional mammography. Expected AEs that apply to mammography
and are also applicable to digital mammography using the Senographe Essential system may
include but are not limited to:

Bruising;

Discomfort;

Skin irritation, abrasions, bruising or tears.
There is also the risk that imaging studies will falsely indicate an abnormality that could cause
extra procedures to be done, and cause unnecessary anxiety for subjects.
The radiation dose for a two-view DBT acquisition is approximately the same as for conventional
two-view FFDM mammography. In this study, subjects must have previously undergone FFDM
and/or DBT on GE equipment. If they have not, they must have FFDM and/or DBT (CC and MLO
views) repeated on GE equipment.
Patients will thus get approximately twice (four-times if repeat FFDM and DBT is required) the
radiation dose that they normally would if they underwent mammography outside of the clinical
trial, a dose within expected limits for routine mammography procedures and considered ALARP
to complete this study.
It is generally agreed that the risk to a fetus of radiation from a screening mammography is
extremely low; however, clinical practice is to try to determine pregnancy status of women
referred for mammography and not allow women known or suspected to be pregnant to
undergo screening mammography or other elective radiologic procedures.
12.2. Adverse Event Definitions
Adverse Event (AE): As defined by EN ISO 14155-2011: any untoward medical occurrence,
unintended disease or injury, or untoward clinical signs (including abnormal laboratory findings)
in subjects, users or other persons, whether or not related to the investigational medical device.
Serious Adverse Event (SAE): As defined by EN ISO 14155 – 2011: an adverse event that
(a) led to death;
(b) led to a serious deterioration in the health of the subject, that either resulted in:
(1) a life-threatening illness or injury, or
(2) a permanent impairment of a body structure or a body function, or
(3) in-patient or prolonged hospitalization, or

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(4) medical or surgical intervention to prevent life-threatening illness or injury or
permanent impairment to body structure or a body function;
(c) led to fetal distress, fetal death or a congenital abnormality or birth defect.
Anticipated: Any adverse event and/or reaction, the specificity or severity of which is consistent
with the EC/IRB approved informed consent, protocol, investigator brochure, or product
labeling.
Unanticipated Adverse Device Effect (UADE): As defined by 21 CFR 812. 3: means any serious
adverse effect on health or safety or any life-threatening problem or death caused by, or
associated with, a device, if that effect, problem, or death was not previously identified in
nature, severity, or degree of incidence in the investigational plan or application (including a
supplementary plan or application), or any other unanticipated serious problem associated with
a device that relates to the rights, safety, or welfare of subjects.
12.3. Management of Adverse Event Reporting
Any adverse events will be recorded in the subjects study record and the Adverse Event Case
Report Form. The following information should be obtained:

Description of Event

Date of onset and resolution

Intensity (mild, moderate, severe)
­
Mild: Symptom(s) barely noticeable to the subject or does not make the subject
uncomfortable. The AE does not influence performance or functioning. Prescription
drugs are not ordinarily needed for relief of symptom(s).
­
Moderate: Symptom(s) of a sufficient severity to make the subject uncomfortable.
Performance of daily activities is influenced. Treatment of symptom(s) may be needed.
­
Severe: Symptom(s) of a sufficient severity to cause the subject severe discomfort.
Treatment for symptom(s) may be given.

Serious (yes/no)

Relationship to device (unrelated, possibly related, probably related)
­
Unrelated: The adverse event is reasonably expected to be related to (or caused by) a
concurrent illness, effect of another device/drug or other cause, and is unlikely related
to the investigational product
­
Possibly related: The adverse event is reasonably expected to be related to the
investigational product, and an alternative etiology is equally or less likely compared to
the potential relationship to investigational product
­
Probably related: There is a strong relationship to investigational product, or recurs on
re-challenge, and another etiology is unlikely, or there is no other reasonable medical
explanation for the event.

Treatment given and/or action taken (procedure stopped, withdrawn from study, no action)

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
Anticipated (yes/no)
Adverse events will be reported to the local EC/IRB per their policy.
12.4. Management of Serious Adverse Event and Unanticipated Adverse Device
Effect Reporting
All SAEs and or UADEs will be documented as above and reported in writing to the Sponsor
within 72 hours of knowledge of the event The Investigator shall submit the Adverse Event Case
Report Form and GEHC_GQP_10. 07. 005_F002 Site Notification and Assessment of Serious and
Unexpected Adverse Events (DOC0910335) with redacted supporting documentation to SAE
mailbox.
If the event resulted in the death of a subject, the event shall also be reported via telephone to
the Sponsor within 24 hours of knowledge of the event. SAEs will be reported to the local EC/IRB
per their policy.
Sponsor contact for SAEs and/or UADEs:
Ron von Jako, MD, PhD
Fax: 800-888-3983
E-mail: SAE@ge.com
If additional information (i.e. outcome of event, date event resolved, additional treatments) is
required to submit a follow-up report, the Investigator shall update the AE CRF and resubmit to
GE Healthcare.
The Investigator shall submit the follow-up SAE and/or UADE report to the local EC/IRB per their
policy.

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12.5. Management of Device Complaints
Any complaints regarding the operation of the device or software or any malfunctions are to be
reported to the Clinical Affair Project Manager.
Sponsor Contact for Device Complaints:
Sara Lam, Senior Clinical Affairs Project Manager III
Phone: +1-262-409-0828
Email: Sara.J.Lam@ge.com
13.EARLY TERMINATION OR SUSPENSION
13.1. Criteria for Early Termination or Suspension
There are no formal termination criteria for this study. The Sponsor reserves the right to
terminate the study at any time. Investigators have the responsibility to comply with
International Conference on Harmonisation (ICH) E6-Good Clinical Practice (GCP) guidance. The
Sponsor, the Institutional/Independent Review Board (IRB) or Ethics Committee (EC), or the
health authorities may terminate a center for the following (but not limited to) reasons:
1.
If any SAEs or other technical safety issues occur;
2.
Failure of the investigator to comply with pertinent ICH E6-GCP guidelines and
regulations;
3.
If serious protocol violations occur;
4.
Submission of knowingly false information from the research facility to the Sponsor,
clinical monitor, or other party involved in the study;
5.
Failure of the investigator to enroll subjects into the study at an acceptable rate as
agreed to with the Sponsor;
6.
Repeated failure to have imaging data transferred or CRF completed and ready for
submission to the Sponsor in the agreed time frame.
7.
If the Sponsor determines that unanticipated adverse event(s) presents an unreasonable
risk to subjects or for any other reason as Sponsor determines to be appropriate.
The Sponsor will promptly notify the Investigators of any determination to terminate the study
outside of the protocol timeframe.
Termination shall occur no later than 5 working days after the Sponsor makes the determination
and no later than 15 working days after Sponsor first received notice of the effect.
The Sponsor will provide each Investigator with written guidelines/instructions on termination
processes and timelines.
The Investigator is responsible for reporting the early termination to their local EC/IRB.

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13.2. Withdrawal of EC/IRB Approval
The Investigator will notify the Sponsor of any withdrawal of EC/IRB approval within 5 working
days of such occurrence.
If the EC/IRB terminates or suspends its approval of the Study, the Investigator will promptly
notify Sponsor and provide a detailed written explanation of the termination or suspension.
Upon receipt, the Sponsor will provide written guidelines/instructions on subject
withdrawal/termination processes and timelines.
14.ETHICS COMMITTEE (EC) AND REGULATORY FILINGS
14.1. Regulatory Authority Approval Requirements (Global)
All regulations for the local country at the investigational site will be followed.
14.2. Ethics Committee Approval Requirements
This study is to be submitted to the EC/IRB for review and approval prior to enrolling subjects.
The Investigator is responsible for keeping approval current and maintaining appropriate
correspondence and reports.
Copies of all EC/IRB applications, approval letters, ICFs and other correspondence are to be sent
to the Sponsor, with originals kept in the Site Study Regulatory Binder.
14.3. Management of Protocol Revisions/Amendments
All protocol amendments will be approved and released by the Sponsor and receive approval
from applicable local and, if necessary, central EC/IRB prior to implementation at the
investigational site(s).
14.4. Informed Consent and Privacy Requirements
In accordance with US FDA and the French National Agency for the Safety of Medicine and
Health Products regulations in accordance with the European Medical Directive 93/42/EEC
regulations, informed consent will be obtained from all subjects prior to participation in the
study, per the determination of the local EC/IRB.
Informed consent will be documented in the source record of each subject. The Investigator or
designee will consent the subject per regulatory guidelines which include the subject has ample
time to review the ICF and have all questions answered to their satisfaction; the subject may
take the ICF home to review with family members or others prior to agreeing to participate in
the study; upon agreeing to participate in the study, the subject signs and dates the document,
and the person who consented the subject signs and dates the document.
The subject will be given a copy of the signed informed consent form and the original will be
retained with Subject Files at the investigational site(s).

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15.DATA AND QUALITY MANAGEMENT
15.1. Management of Data
Images acquired during imaging (DBT and FFDM) examinations will be stored on an internal or
external disk system for preliminary assessment, before permanent archiving.
The digital technology used by the devices in this study may provide the ability to transfer
acquired images between workstations, and to store them on hard disk. However, the hospital
should utilize devices that are intended or approved as archiving devices for permanent storage
of images.
Electronic image data (scan files) and associated data will be collected from subjects enrolled in
this study and labeled with de-identified subject identification designation (SID) that will not
contain any identifiable personal information. Images acquired by device procedures in this
study will be handled by approved third-party contract research organizations (CROs).
FFDM and DBT images in this study will be collected from participating subjects in electronic
format, which contains information about technical characteristics of the scan session. The
Sponsor may extract and analyze electronic image data to determine technical information
about the subject’s scan session, including radiation dose information and other factors
determined by the Sponsor. Applicable data extracted from electronic image files and calculated
values based on such image data may be extracted and summarized by the Sponsor at an
authorized engineering facility separate from the clinical site for the purposes of this study.
During this study, data and images from clinically indicated 2-D and/or 3-D mammography
occurring prior to the beginning of the subject’s participation (date of consent) in this study
period may be collected and provided to the Sponsor for research purposes. In the event of
adverse event (AE) and serious adverse event (SAE) occurrence or appearance of incidental
findings that initiate clinical follow-up, information about other interventions, including any
diagnostic imaging results, will be recorded in the CRF and source images and/or other
associated data may be provided to the Sponsor as part of this research study.
GE Healthcare (GEHC) may use image data for regulatory claims, future technology
development, marketing purposes, publications or any other possible use. Specifically, the
image data obtained in this study is intended for use as part of a regulatory submission
supplementing the approval of SenoClaire® - GE Breast Tomosynthesis (DBT) in the United
States and in Europe. This data and images collected as part of this research study may also be
transported to countries outside of the United States and France for purposes of future
research, engineering development, and global regulatory submissions in other countries.
The approved Data Management Plan (DMP) will be located in the study’s Clinical History File
(CHF) maintained by the Sponsor.
15.2. Subject De-identification
Each enrolled subject will be assigned a unique Subject Identification number which is used to
provide a means for subject de-identification. The Site Principal Investigator (PI) or authorized

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delegate will capture the subject information in the Enrollment Log and assign a corresponding
Subject Identification number. These numbers will be assigned in consecutive order of
enrollment with numbering format provided by the Sponsor.
15.3. Completion of Case Report Forms (CRFs)
Data will be collected using paper CRFs. To ensure the quality and integrity of the data, it is the
responsibility of the Principal Investigator or designee to complete CRFs in a timely manner for
each subject who is enrolled in this study. The Sponsor will provide CRFs and any applicable the
instructions for their completion, if necessary.
CRFs shall be completed as information becomes available. If errors or omissions are found in
the course of monitoring, a query will be raised and the site shall make the correction per Good
Clinical Practice (GCP) on the CRFs. In the event of a CRF audit, or data review once the CRFs
have been pulled from the site, a Data Clarification Form (DCF) will be generated and the error,
omissions, or clarifications will be corrected on these forms.
The Sponsor may additionally request copies of any clinical imaging datasets (including FFDM
and/or DBT scan datasets and other clinically indicated imaging examinations) or biopsy results
that are conducted during the study period.
15.4. Record Retention at the Site
All records pertaining to the conduct of the study, including CRFs, ICFs, EC/IRB correspondence
and other study documentation, must be retained at the investigational site for inspection at
any time by the GEHC Study Monitor or authorized Sponsor agent. These records will be
maintained according to GEHC Retention Policies. Elements should include the following:

Subject Files – containing the completed subject CRFs and possibly signed ICFs

Regulatory Binder – containing the protocol and amendments, EC/IRB submissions and
approvals, blank and possibly signed/dated ICF(s), and Site study logs

Reference Manuals – containing the resource list, responsibilities of the Investigator,
Sponsor, adverse event and informed consent guidelines, study aids (training material,
device screen shots), and central supplier instructions.
No records will be destroyed without first notifying and receiving approval from the Sponsor.
16.MONITORING PLAN
16.1. Brief Description
In collaboration with the investigational site, the Sponsor will ensure proper monitoring of the
study to confirm that all the clinical requirements are met. Monitoring visits will ensure
adherence to the protocol, completion of ICFs, EC/IRB review of the study, maintenance of
records, primary outcomes review, and review of CRFs and source documentation for accuracy
and completeness.

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16.2. Reference to Approved Monitoring Plan
The approved monitoring plan will be located in the study’s Clinical History File (CHF)
maintained by the Sponsor.
17.PUBLICATION POLICY
The Sponsor will reach consensus with each investigational site regarding publication of work
relating to the study that will allow both parties and their authorized representatives to
promote publication of such material as appropriate through journals, meetings, and symposia.
To ensure adequate patent protection for any inventions or discoveries and to protect any other
commercial interests of both parties, specific guidelines for submission and review of
publications will be determined in a separate contractual agreement between the Sponsor and
the Site, which governs publications of this work by the Investigators and any persons at the
investigational site with knowledge of this study.
18.ADDITIONAL COUNTRY-SPECIFIC REGULATORY REQUIREMENTS
Applicable reporting processes for AEs and device issues will be followed at each site, in
compliance with applicable local laws and regulations and with local and (if applicable) central
EC/IRB policies. The clinical investigation shall be conducted in accordance with the ethical
principles that have their origin in the Declaration of Helsinki.
In France, applicable study documents will be submitted and, as necessary, approved by the
Comité de Protection des Personnes (CPP) and Health Authorities, including Agence Nationale
de Sécurité du Médicament et des Produits de Santé (ANSM). Sites in France will comply with
Privacy law (Loi “informatique et libertés”).

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8. Onega T, Anderson M, Miglioretti D, et al. Establishing a gold standard for test sets: variation in
interpretive agreement of expert mammographers. Acad Radiol. 2013;20(6):731-9.
9. Randal J. ter 40 Years, Mammography Remains as Much Emotion as Science. JNCI J Natl Cancer
Inst. 2000;92(20):1630-1632.
10. Shapiro S, Strax P, Venet L. Periodic breast cancer screening in reducing mortality from breast
cancer. JAMA. 1971;215(11):1777-1785.
11. Thurfjell E, Lendgren J. Breast cancer survival rates with mammographic screening: similar
favorable survival rates for women younger and those older than 50 years. Radiology.
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13. Tabar L, Vitak B, Chen H, Yen M, Duffy S, Smith R. Beyond randomized controlled trials: organized
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14. The Swedish Organized Service Screening Evaluation Group. Reduction in breast cancer mortality
from organized service screening with mammography: 1. Further confirmation with extended
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15. Stewart K, Neumann P, Fletcher S, Barton M. The Effect of Immediate Reading of Screening
Mammograms on Medical Care Utilization and Costs after False-Positive Mammograms. Health
Serv Res. 2007;42(4):1464–1482.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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16. Elmore J, Barton M, Moceri V, Polk S, Arena P, Fletcher S. Ten-year risk of false positive screening
mammograms and clinical breast examinations. N Engl J Med. Apr 1998;338(16):89-96.
17. Heywang-Köbrunner S, Hacker A, Sedlacek S. Advantages and Disadvantages of Mammography
Screening. Breast Care (Basel). 2011;6(3):199-207.
18. Gøtzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst
Rev. 2011;19(1):CD001877.
19. Johns L, Moss S, Group ATM. False-positive results in the randomized controlled trial of
mammographic screening from age 40 ("Age" trial). Cancer Epidemiol Biomarkers Prev. Nov
2010;19(11):2758-64.
20. Boyd N, Rommens J, Vogt K, et al. Mammographic breast density as an intermediate phenotype
for breast cancer. Lancet Oncol. 2005;6(10):798-808.
21. Checka C, Chun J, Schnabel F, Lee J, Toth H. The relationship of mammographic density and age:
implications for breast cancer screening. AJR Am J Roentgenol. 2012;198(3):W292-5.
22. Kerlikowske K, Zhu W, Hubbard R, et al. Outcomes of screening mammography by frequency,
breast density, and postmenopausal hormone therapy. JAMA Intern Med. May 2013;173(9):807-
16.
23. Lehman C, White E, Peacock S, Drucker M, Urban N. Effect of age and breast density on screening
mammograms with false-positive findings. AJR Am J Roentgenol. Dec 1999;173(6):1651-5.
24. Pisano E, Acharyya S, Cole E, et al. Cancer cases from ACRIN digital mammographic imaging
screening trial: radiologist analysis with use of a logistic regression model. Radiology.
2009;252(2):348-57.
25. Pisano ED, Hendrick RE, Yaffe MJ, et al. Diagnostic accuracy of digital versus film mammography:
exploratory analysis of selected population subgroups in DMIST. Radiology. 2008;246(2):376-83.
26. Lewin J, Hendrick E, D'Orsi C, et al. Comparison of Full-Field Digital Mammography with Screen-
Film Mammography for Cancer Detection: Results of 4,945 Paired Examinations. Radiology.
2001;218:873-880.
27. Skaane P, Skejennald A. Screen-Film Mammography versus Full-Field Digital Mammography with
Soft-Copy Reading: Randomized Trial in a Population-based Screening Program—The Oslo II
Study1. Radiology. 2004;232:197-204.
28. Houssami N, Skaane P. Overview of the evidence on digital breast tomosynthesis in breast cancer
detection. Breast. 2013;22(2):101-8.
29. Bernardi D, Ciatto S, Pellegrini M, et al. Prospective study of breast tomosynthesis as a triage to
assessment in screening. Breast Cancer Res Treat. 2012;133(1):267-71.
30. Houssami N, Skaane P. Overview of the evidence on digital breast tomosynthesis in breast cancer
detection. Breast. Apr 2013;22(2):101-8.
31. Gur D, Abrams G, Chough D, et al. Digital breast tomosynthesis: observer performance study. AJR
Am J Roentgenol. Aug 2009;193(2):586-91.
32. Zuley ML, Bandos AI, Ganott MA, et al. Digital breast tomosynthesis versus supplemental
diagnostic mammographic views for evaluation of noncalcified breast lesions. Radiology.
2013;266(1).

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Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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33. Yang T, Liang H, Chou C, Huang J, Pan H. The Adjunctive Digital Breast Tomosynthesis in Diagnosis
of Breast Cancer. Biomed Res Int. 2013:597253.
34. Brosky J. JFR 2013: Challengers emerge as Hologic advances tomo for screening. Medical Device
Daily. October 2013.
35. GEHC. SenoClaire. Waukesha, WI: GE Healthcare; 2013.
36. Destounis S, Arieno A, Morgan R. Initial Experience with Combination Digital Breast
Tomosynthesis Plus Full Field Digital Mammography or Full Field Digital Mammography Alone in
the Screening Environment. J Clin Imaging Sci. 2014;4(9).
37. Yue-Houng H, Bo Z, Wei Z. Image artifacts in digital breast tomosynthesis: Investigation of the
effects of system geometry and reconstruction parameters using a linear system approach. Med
Phys. 2008;35(12):5242.
38. Suryanarayanan S, Karellas A, Vedantham S, Waldrop SM, D'Orsi CJ. Detection of Simulated
Lesions on Data-compressed Digital Mammograms. Radiology. 2005;236:31-36.
39. FDA. Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Full Field
Digital Mammography System. Medical Devices. April 2012, 2012. Available at:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm10
7552.htm. Accessed August 9, 2013.
40. Padilla F, Roubidoux MA, Paramagul C, Sinha SP. Breast mass characterization using 3-dimensional
automated ultrasound as an adjunct to digital breast tomosynthesis: a pilot study. J Ultrasound
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41. Dorfman D, Berbaum K, Metz C. Receiver operating characteristic rating analysis: generalization to
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1997;27:723-731.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
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Protocol: 4.0
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APPENDIX A: AMENDMENT TO PROTOCOL VERSION 1.0 TO 2.0
Purpose: This amendment document describes the changes from protocol version 1.0 to 2.0, including:

Discussion of additional cancer case collection study (ADAPT-ENRICH);

Clarification to inclusion and exclusion criteria; and

Updates to enrollment and accrual targets.
The following amendments were made to version 1.0 to produce version 2.0. Point-by-point revisions in
this amendment are shown with additions in double-underline (double-underline) and deletions in
strikethrough (strikethrough).
Item
Section
Revision or Clarification
Justification
1.
Section 1. Study Synopsis
– Study Design
An open-label, multi-center, accrual study collecting DBT and FFDM
images from up to 200 275 initially asymptomatic women aged ≥30
years referred for clinically indicated breast biopsy based on
suspicious breast imaging results will be conducted.
Accrual DBT and FFDM data will be pooled for evaluation by
independent blinded readers in a subsequent reader study. The
detailed information for on the blinded image evaluation will be
provided in a separate Independent Review Charter (IRC) detailed in
the ADAPT-BIE (Blinded Image Evaluation) protocol study. This
study’s primary endpoint is collection of data to compare the of
diagnostic accuracy of two-view SenoClaire® - GE Breast
Tomosynthesis and two 2-view FFDM based on difference in receiver
operating characteristic (ROC) area under the curve (AUC) detailed in
the separate ADAPT-BIE protocol.
Enrollment target
adjusted to
accommodate accrual
redistribution based
on the capacities of
sites participating in
this study and other
studies contributing to
the overall GEHC DBT
program.
Revised for
clarification.
2.
Section 1. Study Synopsis
and Section 7.5. Inclusion
Criteria
5.
Documented as non-pregnant based on the investigator’s
medical judgment and in consideration of local clinical practice
standards for evidence of non-pregnancy. Are either surgically
sterile or postmenopausal3 or, if of childbearing potential, the
possibility of pregnancy is remote based on a documented
negative patient history and, optionally, has a negative urine
pregnancy test (if subject requests one).
3Post-menopausal is defined as documented 12 months of
spontaneous amenorrhea.
Clarified criterion to
ensure the sites’
standard practices and
investigators’
judgements are
utilized when
determining
pregnancy status.
Removed inessential
footnote.
3.
Section 1. Study Synopsis
and Section 7.6.
Exclusion Criteria
2.
Have undergone diagnostic or surgical intervention(s) or
procedure(s) on either breast, including mastectomy and
cytopunction, before study-related imaging; Have a history of
any symptoms and/or physical signs of breast cancer in either
breast (or if she has had a mastectomy, have signs or symptoms
of breast cancer in the remaining breast)
Revised to clarify
intent of criterion,
which is to reduce bias
in subsequent BIE
study.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Item
Section
Revision or Clarification
Justification
4.
Section 1. Study Synopsis
– Brief Description of
Study Purpose
This study is being conducted to accrue cancer cases for a
subsequent blinded reader study comparing the diagnostic accuracy
and, performance, and reading time of digital breast tomosynthesis
(DBT) performed with the GE SenoClaire® GE Digital Breast
Tomosynthesis compared to conventional GE full-field digital
mammography (FFDM) in asymptomatic women. The study also
provides for exploratory analysis of cancerous lesion characteristics
detected by DBT and FFDM systems. This statistically powered study
is being conducted to support regulatory claims to expand the
labeling of the DBT system.
Clarified purpose of
subsequent BIE study.
5.
Section 1. Study Synopsis
– Device/Product
Description
Commercially available SenoClaire® - GE Breast Tomosynthesis is a
Digital Breast Tomosynthesis (DBT) device available for commercial
full-field digital (FFDM) mammography systems (GE Senographe®
Essential Full-Field Digital Mammography or equivalent GE FFDM)
and read on IDI MammoWorkstation with Volume-Preview Synthetic
2-D Mammography (V-Preview).
Removed equivalent
option to ensure that
GE Senographe®
Essential Full-Field
Digital Mammography
systems are used.
6.
Section 1. Study Synopsis
and Section 5.3.1.
Primary endpoints
The primary endpoint will be the respective site’s diagnosis for each
subject of cancer status (positive or negative/benign) based on
histology and surgical findings or 10-16 month imaging (if applicable).
for both DBT and FFDM, and l Lesion appearance and characteristics
on imaging will also be collected.
Clarified for this multi-
site study.
Omitted BI-RADS score
from primary endpoint
data collection.
7.
Section 1. Study Synopsis
– Sample Size
Up to 200 275 subjects referred for breast biopsy (Enrollment ceiling
per site will be 120 165 subjects) will be enrolled in this recruitment
plan until 70 90 (max. 75 95) histopathology-confirmed cancers have
been accrued. Sample size is determined by the need to accrue at
least 70120 cancer cases and 250 non-cancer cases for the overall GE
Healthcare (GEHC) DBT program (ADAPT-BIE).
Revised enrollment
and accrual targets
based on power
analysis for the overall
GEHC DBT program.
8.
Section 2.1. Literature
Review – Introduction
This protocol is one of multiple two GEHC protocols designed to
collect data from asymptomatic women who have been referred to
1) screening mammography and 2) breast biopsy following diagnostic
work-up. The data from these two protocols will be pooled for
analysis to compare diagnostic accuracy of DBT to FFDM for
detecting breast cancers in asymptomatic women.
Updated to clarify that
other sources may be
pooled for subsequent
BIE study.
9.
Section 4. Regulatory
Status
The SenoClaire® - GE Breast Tomosynthesis (DBT) system, GE
Senographe® Essential Full-Field Digital Mammography or equivalent
GE FFDM system, and workstations (including software components)
used in this study are commercially available as determined by the
United States (US) Food and Drug Administration (FDA) and
European CE mark.
Removed mention of
equivalent system.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Item
Section
Revision or Clarification
Justification
10.
Section 6.1.1. Study Type
The data from this study will be pooled with data from
other
subjects, who will have been recruited under other GEHC protocols
(including ADAPT-SCR and ADAPT-ENRICH), for analysis described in a
separate protocol (ADAPT-BIE). Figure 1 depicts the study design and
procedures.
Included a third case
collection study,
ADAPT-ENRICH, which
was developed to
provide additional
cancer cases for the
overall GEHC DBT
program. Similar
language added
throughout version 2.0
of this protocol to
clarify this update.
11.
Section 6.1.1. Study Type
– Figure 1.
Initially asymptomatic
women ≥30 referred for
breast biopsy
(n = 200 275)
Updated “n” to reflect
change in enrollment
target.
12.
Section 6.1.2. Study
Design Details
Multi-site: Data will be pooled from 2 multiple studies (e.g. ADAPT-
SCR, & ADAPT-BX, & ADAPT-ENRICH) at multiple sites
Comparator: Diagnostic accuracy of DBT vs FFDM is will be assessed
in a separate protocol (ADAPT-BIE)
Clarified that more
than two (2) studies
may be pooled for
analyses.
Clarified that ADAPT-
BIE will be conducted
subsequently.
13.
Section 6.3. Controls and
Minimization of Bias
a.
Selection bias in allocating subjects to interventional groups will
be limited by attempting to enrolling consecutively eligible
subjects, however despite inclusion of subjects referred from
DBT, US or MRI screening, as most subjects in this study are
expected to be biopsy referrals based on FFDM, a selection bias
in favor of FFDM is possible. To reduce bias introduced from this
study by subjects who are expected to be referred for biopsy
based on FFDM screening, other sources (e.g. ADAPT-ENRICH)
may be pooled to include cancer cases reaching biopsy through
a DBT screening program.
Revised with efforts to
reduce FFDM
screening bias.
14.
Section 7.1. Number of
Subjects
Up to 200 275 subjects referred for breast biopsy (Enrollment ceiling
per site will be 120 165 subjects) will be enrolled from two (2)
centers located in the US and Europe (France) until 70 90 (max. 7595)
histopathology-confirmed cancers have been accrued. Enrollment
Updated enrollment
and accrual targets.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Item
Section
Revision or Clarification
Justification
will be closed once the required number of cancers has been
histologically identified.
15.
Section 8. Procedures for
Research Study – Table 1
Amendment to footnote – a: Including age, menopausal status and
history of surgical breast intervention.
Revised due to change
in exclusion criterion
#2.
16.
Section 8.1. Pre-
Mammography
Procedures
An area also will be allowed on the CRFs for additional notes or
comments relevant to the subject’s study procedures, to be
completed by the Investigator .
There is no special subject preparation required to perform DBT or
FFDM mammography.
Deleted to reflect
approved format of
case report forms.
17.
Section 8.2. Baseline
(Month 0) Digital Breast
Tomosynthesis (DBT) and
Full Field Digital
Mammography (FFDM)
Examinations
Study subjects will undergo two-view DBT (both CC and MLO view) of
both breasts or of one breast if they have had prior mastectomy.
Prior screening and/or diagnostic FFDM images will be collected from
each subject’s medical record or, if necessary (because prior
screening and/or diagnostic mammography images are not available
or were not collected with GE FFDM equipment), a subject may also
need to undergo repeat FFDM; if so, this will be a bilateral two-view
FFDM (both CC and MLO views) performed on the GE FFDM system
available at the site and according to the hospital’s standard
procedure.
DBT and two-view FFDM image acquisition (both CC and MLO views)
shall be performed within 30 days of each other, regardless if FFDM
was performed before or after the patient agreed to participate in
the study. Each subject will undergo the following procedures:
• Enter a changing room to prepare for their mammogram;
• Each subject of child-bearing potential will wear a lead apron or
have equivalent shielding during the DBT (and, if necessary, FFDM)
procedures;
• Undergo DBT (and, if necessary, FFDM) procedure(s);
• Will be monitored for AEs, SAEs from DBT and repeated FFDM (if
required) and will to be recorded in the source documents and CRF.
Device malfunctions shall be sent to the Sponsor as per Section 12.5
Management of Device Complaints.
Revised due to change
in exclusion criterion
#2.
Clarified that FFDM
may be repeated, if
necessary.
18.
Section 8.3.1. On-Site
Image Interpretation
The evaluating radiologist(s) at the site will record for each subject,
the following parameters:
• Breast density (as defined by BI-RADS® density categories)
• Finding characteristics, to include breast location, lesion type,
depth, quadrant and size.  In the case of multiple findings, a
Omitted screening BI-
RADS score per change
to primary endpoint
data collection.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Item
Section
Revision or Clarification
Justification
maximum of three (3) most suspicious findings will be scored
and localized.
• Screening BI-RADS® score (BI-RADS 1, 2, 3, 4, 5), scores of 0
(indeterminate) should be approximated to the closest
definition score of 1 to 5 for each breast based on DBT and
FFDM separately.
19.
Section 8.4. Biopsy
Procedures
Subjects who undergo biopsy(ies) may feel apprehensive because of
the pending diagnosis. Consequently, a simple but precise
explanation of all study procedures should be provided to reassure
the subject .
If the subject does not complete the biopsy procedure as scheduled
or if the biopsy procedure is not successful or produces
indeterminate results that are not able to be resolved by clinically
indicated procedures, such as repeat biopsy(ies) the subject will be
withdrawn.
Deleted
inconsequential
language for the study
protocol. Appropriate
language presented in
the informed consent
form.
20.
Section 10.1.1. Sample
Size Justification
The projected sample size is determined by the need to accrue at
least 70120 cancer cases and 250 non-cancer cases for the overall GE
Healthcare SenoClaire® - GE Breast Tomosynthesis (DBT)
development program. To achieve these overall accrual targets, the
data from this study will be pooled with data from other studies (e.g.
ADAPT-SCR and ADAPT-ENRICH).
In this study, for an enrollment of 200 275 subjects recommended
for breast biopsy, it is assumed, based on the GE-190-003
experience, approximately 33% are expected to have a proven
cancer and approximately 33% will have a benign lesion with normal
1-year follow-up. So, at least 66 90 cancer cases and 66 90 non-
cancer cases with normal 1-year follow-up are expected to be
accrued in this study. Up to 200 275 subjects referred for breast
biopsy (Enrollment ceiling per site will be 120 165 subjects) will be
enrolled from two (2) centers located in the US and Europe (France)
until 70 90 (max. 95) 75) histopathology-confirmed cancers have
been accrued.
Based on the GE-190-001 experience, for an enrollment of 250
subjects having screening mammography, about 185 (75%) will
complete the study with a normal 1-year follow-up. Approximately
2% are expected to have a proven cancer either at screening or
during follow-up, which will provide an estimated 6 cancer cases;
that are expected to be accrued in the ADAPT-SCR protocol study.
In the ADAPT-ENRICH study, for a target enrollment of 90 subjects
recommended for breast biopsy, it is assumed, based on the GE-190-
003 experience, approximately 33% are expected to have a proven
Updated enrollment
and accrual targets.
Clarified total accrual
targets for the overall
GEHC DBT program.
Revised to include
ADAPT-ENRICH and to
clarify strategy for
combing cancer and
non-cancer cases from
different sources to
achieve the overall
program targets.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Item
Section
Revision or Clarification
Justification
cancer. Thus, at least 30 cancer cases are expected from the ADAPT-
ENRICH study.
Thus, in the combined protocols (ADAPT-SCR and ADAPT-BX), it is
expected that at least 70 cancer cases and 250 non-cancer cases will
be accrued.
The data from this study will be pooled with data from other subjects
who will be recruited from other sources, such as the separate
protocols (ADAPT-SCR). If necessary, data from other sources may
also be included to achieve the required number of cancer and non-
cancer cases. With the combination of the protocols (ADAPT-SCR and
ADAPT-BX) and other sources, it is expected that at least 120 cancer
cases and 250 non-cancer cases will be accrued for the overall GE
Healthcare SenoClaire® - GE Breast Tomosynthesis (DBT)
development program. If necessary, data from other sources may
also be included to achieve the required number of cancer and non-
cancer cases.
21.
Section 10.1.3. Subject
Disposition and
Characteristics
Subjects enrolled, imaged, and withdrawn will be summarized overall
and by site and imaging modality.  Descriptive statistics and
summaries will be provided for demographics, medical histories,
image acquisition, lesions and findings and BI-RADS® assessments.
Removed screening BI-
RADS score per change
to primary endpoint
data collection.
22.
Section 11.1.
Management of Protocol
Deviations
Critical Deviations:
If an Investigator uses a device without obtaining informed consent,
per Section 14.4 Informed Consent and Privacy Requirements, the
Investigator shall consider this a critical deviation and report the
event to the Sponsor and the EC/IRB within 5 working days of the
occurrence.
Specified section that
defines requirements
for obtaining informed
consent.
23.
Section 12.1.
Foreseeable Adverse
Events and Device Effects
The radiation dose for a two-view DBT acquisition is approximately
the same as for conventional two-view FFDM mammography.  In this
study, subjects must have previously undergone FFDM on GE
equipment. If they have not, they must have FFDM CC and MLO
views repeated on GE equipment. They will then undergo DBT, which
has radiation dose similar to FFDM.
Patients will thus get approximately twice (three-times if screening
repeat FFDM is required) the radiation dose that they normally
would if they underwent mammography outside of the clinical trial, a
dose within expected limits for routine mammography procedures
and considered ALARP to complete this study.
Deleted redundant
statement.
Clarified that FFDM
may be repeated, if
necessary.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
Page 48 of 59
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APPENDIX B: AMENDMENT TO PROTOCOL VERSION 2.0 TO 3.0
Purpose: This amendment document describes the changes from protocol version 2.0 to 3.0, including:

Updates to the participating study centers;

Clarification to inclusion and exclusion criteria;

Addition of documented concordance assessments for negative/benign cases; and

Clarification to the type of study-specific imaging that may be required.
The following amendments were made to version 2.0 to produce version 3.0. Point-by-point revisions in
this amendment are shown with additions in double-underline (double-underline) and deletions in
strikethrough (strikethrough).
Item
Section
Revision or Clarification
Justification
24.
Section 1. Study Synopsis
– Investigators and Study
Center(s)
Up to 3 2 centers in the United States (US) and France (FR)
Kathy Schilling, MD
Boca Raton Regional Hospital
Christine E. Lynn Women’s Health
and Wellness Institute
Address:
690 Meadows Road
Boca Raton, FL, 33486
US
Telephone: +1-561-955-5000
E-mail:
kschilling@brrh.com
Updated the number
of participating
centers and added
new site’s contact
information.
25.
Section 1. Study Synopsis
– Study Design
An open-label, multi-center, accrual study collecting DBT and FFDM
images from up to 275 initially asymptomatic women aged ≥30 years
referred for clinically indicated breast biopsy based on suspicious
breast imaging results will be conducted. CC and MLO views from
bilateral GE DBT and GE screening and/or diagnostic FFDM
(conducted before or after enrollment) taken within a 30 day
window of each other will be collected and assessed on-site by
qualified radiologist(s) for clinical management purposes. Results of
biopsy(ies) and histopathology, including lesion characteristics, will
be recorded and considered as truth if positive for cancer status.
Subjects with negative or benign histological findings will have their
images and histopathology reviewed for concordance and will be
followed at for approximately one year (10-16 months) by FFDM and
any additional standard of care practice.
Clarified language
regarding the 30-day
window.
Added assessment of
image and
histopathology
concordance for
negative/benign cases.
26.
Section 1. Study Synopsis
and Section 7.5. Inclusion
Criteria
2. Initially asymptomatic women who that underwent routine
bilateral screening FFDM, breast ultrasound (U/S), breast magnetic
resonance imaging (MRI), and/or DBT, followed by diagnostic work-
up showing one or of more abnormalities and referred for breast
biopsy 1,2 within of 30 days before study entry;
Footnote:
2 30 day window requirement is between the Screening FFDM and DBT image
acquisitions must be within 30 days of each other.
Clarified that the
screening must be
bilateral and removed
30-day requirement
prior to study entry.
Corrected minor
typographical errors.
Clarified in footnote
that FFDM and DBT
image acquisitions

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Justification
have a 30-day window
requirement.
27.
Section 1. Study Synopsis
and Section 7.6.
Exclusion Criteria
3. Have breasts too large to be adequately positioned on 24 x 31
centimeter (cm) FFDM digital receptor without anatomical cut off
during a DBT or FFDM examination (or FFDM, if required);
Clarified that the
criterion applies to
both DBT and FFDM.
28.
Section 1. Study Synopsis
– Primary endpoints
The primary endpoint will be the respective site’s diagnosis for each
subject of cancer status (cancer positive or negative/benign) based
on histology and surgical findings or 10-16 month imaging (if
applicable) /or follow-up of suspicious findings. Lesion appearance
and characteristics on imaging will also be collected
Revised to mirror
language in Section
5.3.1 Primary
endpoints.
29.
Section 1. Study Synopsis
and Section 5.3.3 Safety
endpoint
Device-related adverse events (AEs), serious adverse events (SAEs),
and device malfunctions by overall occurrence and imaging modality
(DBT and repeated FFDM) that occur during the study will be
collected. No other clinical safety assessments will be performed.
Removed unnecessary
term (“repeated”).
Reporting period
defined for safety
endpoint.
30.
Section 1. Study Synopsis
– Research Manager
Address: 3562 Lookout Court #478 3200 N Grandview Blvd
Oceanside, CA 92056-5259, US Waukesha, WI 53188-1678
Telephone: +1-414-379-4201 721-4393
Updated contact
information.
31.
Section 1. Study Synopsis
– Medical Monitor
Address: 1100 Technology Park Drive Billerica, 3200 N Grandview
Blvd
MA 01821-4111, US Waukesha, WI 53188-1678
Telephone: +1-617-669-3200 781-262-5579
Updated contact
information.
32.
Section 2.3.1.Device Risk
Analysis
Having both DBT and FFDM exams in a short time and possibly
having repeat FFDM and/or DBT on GE equipment can result in
additional ionizing radiation exposure, not to exceed doses that are
considered to be As Low as Reasonably Practicable (ALARP) for the
purpose of this research and are not expected to exceed risks of
routine clinical breast cancer screening and follow-up. As a result of
participating in this study, the subject may be exposed to additional
radiation compared to having only routine mammography on FFDM
or DBT only.
Clarified that both
repeat FFDM and DBT
may be required for
the study, if the
subject’s
screening/diagnostic
FFDM and/or DBT
mammography do not
fulfill the study criteria
outlined in the
protocol. Similar
language was
amended throughout
revision 3.0 to clarify
this point.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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33.
Section 6.1.1. Study Type
This study (ADAPT-BX) is an open-label, multi-center, within-subject
crossover, prospective, clinical research study, collecting images and
associated data from bi-lateral two-view DBT and FFDM exams
conducted with GE systems comparing DBT and FFDM in the
detection of breast cancer.
Figure 1. Study Design and Procedures
1 yr F/U (10-16 mo)
FFDM
AND applicable
Standard of Care
Follow-up
Histopathology
Benign/
Negative
Image &
Histopathology
Concordance
Review**
Concordant
** In the event of discordant histopathology and imaging findings, rebiopsy and resulting
histopathology results will be acquired to establish concordance. If no rebiopsy or
histopathology occurs, or if histopathology remains discordant with imaging findings, the
subject will be withdrawn from the study.
Revised to represent
this study’s objective
and to clarify that the
comparison of the two
modalities will be
conducted under a
separate protocol.
Figure 1 updated to
include assessment
and documentation of
concordance for
negative/benign cases.
Added language
describing the process
for discordance.
34.
Section 6.3. Controls and
Minimization of Bias
a. Selection bias in allocating subjects to interventional groups will be
limited by attempting to enroll consecutively eligible subjects. To
reduce bias introduced from this study by subjects who are expected
to be referred for biopsy primarily based on FFDM screening, other
sources (e.g. ADAPT-ENRICH) may be pooled to include cancer cases
reaching biopsy through a DBT screening program.
Clarified that the
majority of subjects
are expected to be
referred from an FFDM
screening population.
35.
Section 7.1. Number of
Subjects
Up to 275 subjects referred for breast biopsy (Enrollment ceiling per
site will be 165 subjects) will be enrolled from three two (3 2) centers
located in the US and Europe (France) until at least 90 (max. 95)
histopathology-confirmed cancers have been accrued.
Updated number of
participating sites.
Clarified the minimum
accrual target for
histopathology-
confirmed cancers and
removed the
maximum limit to
allow for meeting the
target.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Justification
36.
Section 7.5. Inclusion
Criteria
1 Subjects who had screening DBT and diagnostic FFDM imaging on non-GE
equipment may be enrolled if they agree to undergo repeat imaging on a GE
FFDM system; If the prior screening and diagnostic mammographic
examinations were not conducted at the recruiting site, review of those
images by the investigator must confirm that breast biopsy recommendation
is warranted and GE access to the images in DICOM format must be granted
Revised to mirror
footnote in Section 1.
Study Synopsis,
Inclusion Criteria
37.
Section 8. Procedures for
Research Study
Table 1: Study Schedule of Events for Study Subjects
Variables
Pre – Mammography
Mammography
Post-
Mammography
Informed Consent
X
Entry Criteria
X
Demographic Information a
X
Review relevant
X
DBT Imaging
X
Collection of Prior two-view
X
Repeat of FFDM Imaging b
X
Safety   Assessments   (AE,
SAE,   device malfunctions) c
X
Image assessment by site
X
Histopathology (if
X
DBT = Digital Breast Tomosynthesis; FFDM = Full field digital mammography; AE
adverse event; SAE = serious adverse event;
a: Including age, menopausal status. b: Only if prior two-view screening and/or
diagnostic images are not available or were not obtained on a GE FFDM system
Device-related AEs and SAEs reported.
8.1.
Pre-Mammography Procedures
All enrolled subjects will undergo the following procedures prior to
receiving study-specific imaging (if required) and/or undergoing their
clinically indicated biopsy procedure their DBT (and, if necessary,
FFDM) mammogram(s):
•
A notation will be made in the subject’s medical chart that
the subject is participating in the clinical trial.  Additionally,
the notation should indicate that the subject had her
questions answered, and that she read, signed and dated,
and has had been given a copy of the Informed Consent
Form (ICF);
•
Study entry criteria, demographic information (including
age), relevant reproductive medical/surgical history such as
oophorectomy, hysterectomy, or other reproductive
surgeries or breast surgeries (e.g. aspiration, core biopsy,
breast reduction, implant removal surgery, or other
surgery) and pregnancy/menopausal status will be
reviewed;
•
A subject number will be assigned.
There is no special subject preparation required to perform DBT or
FFDM mammography.
Removed Table 1 to
clarify study
procedures and pre-
study versus study-
specific image
acquisition.
Clarified the
procedures that will be
conducted prior to
study-specific imaging
and biopsy.
Modified
typographical errors.
Removed
documentation of
breast surgeries due to
exclusion criterion #2.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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38.
Section.8.1. Baseline
(Month 0) Digital Breast
Tomosynthesis (DBT) and
Full Field Digital
Mammography (FFDM)
Examinations
Study subjects will undergo two-view DBT (both CC and MLO view) of
both breasts. Prior screening and/or diagnostic FFDM and/or DBT
images will be collected from each subject’s medical record. or, i If
necessary (e.g. because prior screening and/or diagnostic FFDM
and/or DBT mammography images/views are not available or were
not collected with GE FFDM equipment), a subject may also need to
undergo study-specific repeat FFDM and/or DBT imaging. Study-
specific imaging ; if so, this will be a include a bilateral two-view
(both CC and MLO views) FFDM and/or DBT (both CC and MLO views)
performed on using the GE FFDM and/or DBT system available at the
site and according to the hospital’s standard procedure.
Two-view DBT and two-view FFDM image acquisition (both CC and
MLO views) shall be performed within 30 days of each other,
regardless if FFDM or DBT was performed before or after the patient
agreed to participate in the study. Subjects requiring study-specific
imaging Each subject will undergo the following procedures:
•
Enter a changing room to prepare for their mammogram;
•
Each subject of child-bearing potential will wear a lead
apron or have equivalent shielding during the FFDM and/or DBT
(and, if necessary, FFDM) procedures;
•
Undergo DBT (and, if necessary, FFDM) and/or DBT
procedure(s);
•
Will be monitored for AEs and , SAEs from study-specific
DBT and FFDM (if required) and will be recorded in the source
documents and CRF.  Device malfunctions shall be sent to the
Sponsor as per Section 12.5 Management of Device Complaints.
Proper equipment checks as noted in the SenoClaire® - GE Breast
Tomosynthesis Operators Manual will be performed prior to treating
any subject. All scanning should be performed within the standard
range of scan parameters, as per the manufacturer-provided
operator’s manual(s) for GE FFDM and DBT devices. The scan
operator should conduct DBT and FFDM exam according to the
standard clinical practice at the site with consideration for:
•
Subjects with large breasts, because perspiration under the
breast can cause the skin to soften, and become paper-thin;
•
Any condition that exists which may cause unusual
discomfort or tearing of the skin, which could include telling the
subject the importance of correct positioning. The subject should be
positioned carefully to avoid any discomfort to abnormalities such as
warts, scarring, or skin which is not intact;
•
Warmth of the front part of the breast support, which can
be warm to the touch, as it contains electronic components that
generate heat;
•
Positioning the breast properly in FFDM and DBT in the CC
position, where it is essential that the breast is lifted away from the
Clarified criteria for
use of images acquired
prior to enrollment.
Clarified that subjects
will undergo study-
specific DBT and FFDM
imaging only if
required, per the
defined criteria.
Corrected
typographical errors.
Removed SenoClaire-
specific check, as the
equipment checks are
appropriately
described for both
FFDM and DBT
systems.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Justification
chest wall and gently pulled forward, in order to visualize the
maximum amount of breast tissue.
39.
Section 8.2.2. Additional
Diagnostic Imaging
If a subject is called back for further diagnostic assessment, the
additional FFDM views breast imaging that the subject undergoes
will be recorded on the CRF. In addition, any other imaging which the
subject undergoes will be recorded (e.g., breast ultrasound or
magnetic resonance imaging [MRI]).
Generalized statement
to include any
additional breast
imaging during the
study.
40.
Section 8.3 Biopsy
Procedures
Percutaneous and open surgical breast interventions will proceed as
per standard of care at the recruiting site. A record of breast lesion
characteristics, including the type of lesion and approximate size
based upon histology and surgical findings, and location of the lesion
by left or right breast and within a breast quadrant will be recorded
on the CRF for all subjects. The interpretation of the local pathologist
will be recorded on the CRF.
For benign/negative histopathology results, the site radiologist will
review the subject’s imaging and histopathology findings for
concordance and document the assessment on a CRF. If the findings
are concordant, then the subject will continue with the 1-year
follow-up procedure in approximately 10-16 months. If surgical
excision is recommended even after concordance between imaging
and histopathology, the resulting histopathology from surgical
excision will be collected and used to establish the subject's cancer
status. If breast cancer status is negative, 1-year follow-up will be
used to establish final cancer status.
If the imaging and histopathology findings are discordant, rebiopsy
and resulting histopathology will be required to establish
concordance, per the site’s standard of care. Once concordance is
achieved and histopathology continues to be negative for cancer, the
subject will continue with the 1-year follow-up procedure in
approximately 10-16 months from initial study imaging. If no
rebiopsy or histopathology occurs, or if histopathology remains
discordant with imaging findings following rebiopsy, the subject will
be withdrawn from the study.
Modified to accurately
represent data being
collected.
Added procedure and
documentation for
assessing concordance
of negative/benign
cases.
41.
Section 8.4. Follow-up
(Month 10-16)
Procedures
No additional follow-up appointments will be required for subjects
that have completed biopsy with positive findings. Subjects with
negative or benign histology findings will be followed at
approximately one year (10-16 months) by FFDM in addition to any
additional imaging as required by standard of care imaging.
Subjects should be scheduled to complete one year follow-up by
month 15, allowing for one month (until month 16) to reschedule
subjects unable to attend or to collect previously completed one-
year follow-up FFDM images imaging completed at another clinical
site. If no suspicious findings are observed at one-year FFDM follow-
up, this will be considered truth of non-cancer status. If suspicious
findings are observed, the subject will undergo standard of care
Modified to allow for
standard of care
imaging without
requiring FFDM.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Justification
diagnostic work-up, and results will be considered truth for non-
cancer, benign, or cancer status.
42.
Section 8.6.1. Subject
Withdrawal Rules
As described in Section 8.3 Biopsy Procedures, subjects with initial
benign/negative histopathology results that are discordant with
imaging findings will be withdrawn from this study if no rebiopsy or
histopathology occurs, or if histopathology remains discordant with
imaging findings following rebiopsy.
Added withdrawal
rules for discordance.
43.
Section 10.1.1 Sample
Size Justification
In this study, for an enrollment of 275 subjects recommended for
breast biopsy, it is assumed, based on the GE-190-003 experience,
approximately 33% are expected to have a proven cancer and
approximately 33% will have a benign lesion with normal 1-year
follow-up. So, at least 90 cancer cases and 90 non-cancer cases with
normal 1-year follow-up are expected to be accrued in this study. Up
to 275 subjects referred for breast biopsy (Enrollment ceiling per site
will be 165 subjects) will be enrolled from three two (3 2) centers
located in the US and Europe (France) until at least 90 (max. 95)
histopathology-confirmed cancers have been accrued.
Updated number of
participating sites.
Clarified the minimum
accrual target for
histopathology-
confirmed cancers and
removed the
maximum limit to
allow for meeting the
target.
44.
Section 12.1.
Foreseeable Adverse
Events and Device Effects
The radiation dose for a two-view DBT acquisition is approximately
the same as for conventional two-view FFDM mammography.  In this
study, subjects must have previously undergone FFDM and/or DBT
on GE equipment. If they have not, they must have FFDM and/or DBT
(CC and MLO views) repeated on GE equipment.
Patients will thus get approximately twice (three four-times if repeat
FFDM and DBT is required) the radiation dose that they normally
would if they underwent mammography outside of the clinical trial, a
dose within expected limits for routine mammography procedures
and considered ALARP to complete this study.
Updated to reflect the
potential for repeated
mammography with
both modalities.
45.
Section 15.1.
Management of Data
During this study, data and images from clinically indicated 2-D
and/or 3-D mammography occurring prior to the beginning of the
subject’s participation (date of consent) in this study period may be
collected and provided to the Sponsor for research purposes.
Clarified that both
FFDM and DBT image
may be collected.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
Page 55 of 59
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APPENDIX C: AMENDMENT TO PROTOCOL VERSION 3.0 TO 4.0
Purpose: This amendment document describes the changes from protocol version 3.0 to 4.0, including:

Replacement of one-year follow-up with histologic concordance for truth determination of non-
cancer status of negative/benign cases; and

Inclusion of data collection for non-cancerous lesions.
The following amendments were made to version 3.0 to produce version 4.0. Point-by-point revisions in
this amendment are shown with additions in double-underline (double-underline) and deletions in
strikethrough (strikethrough).
Item
Section
Revision or Clarification
Justification
46.
Section 1. Study Synopsis
– Study Design
Subjects with negative or benign histological findings will have their
images and histopathology reviewed for concordance, per the site’s
standard procedures. Histologic concordance with imaging will be
considered truth for non-cancer status. and will be followed at
approximately one year (10-16 months) by FFDM and any additional
standard of care practice.
Added assessment of
image and
histopathology
concordance for non-
cancer truth status of
negative/benign cases.
Removed one-year
follow-up for non-
cancer truth
determination.
47.
Section 1. Study Synopsis
– Brief Description of
Study Purpose
The study also provides for exploratory analysis of cancerous and
non-cancerous lesion characteristics detected by DBT and FFDM
systems. This statistically powered study is being conducted to
support regulatory claims to expand the labeling of the DBT system.
Updated to include
non-cancerous lesion
characteristics.
48.
Section 1. Study Synopsis
and Section 5.3.1 –
Primary endpoints
The primary endpoint will be the respective site’s diagnosis for each
subject of cancer status (positive or negative/benign) based on
histology and of biopsy/surgical findings and histologic concordance
with imaging for benign lesions.. or 10-16 month imaging (if
applicable). Lesion appearance and characteristics on imaging will
also be collected.
Revised to include
histologic concordance
with imaging rather
than one-year follow-
up for truth of non-
cancer status.
Removed lesion
characterization from
primary endpoint
because data are
included in
characteristic
endpoints.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
Page 56 of 59
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Revision or Clarification
Justification
49.
Section 1. Study Synopsis
and Section 5.3.2 –
Characteristic endpoints
Characteristic endpoints for all subjects with positive cancer status
will include invasive/non-invasive characteristics and histology
findings and size, lesion type, and other lesion characteristics based
on image appearance and other lesion characteristics.  Technical
characteristics of electronic image data collected from subjects, such
as information related to radiation dose, may be extracted and
analyzed by the Sponsor for the purposes of this study.
Revised to include
non-cancerous
findings and to clarify
lesion data being
collected based on
image appearance.
50.
Section 5.2.2.
Characteristic Objectives
An exploratory aim is to describe cancer and non-cancer cases
identified in this accrual study based on cancer characteristics
histology findings and lesion type.
Clarified to include
non-cancerous lesion
characteristics.
51.
Section 6.1.1. Study Type
Figure 1. Study Design and Procedures
Initially asymptomatic
women ≥30 referred for
breast biopsy
(n = 275)
1 yr F/U (10-16 mo)
FFDM
AND applicable
Standard of Care
Follow-up
Histopathology
Standard of
Care Imaging
Work-Up
Histopathology
Suspicious
findings?
No
Yes
Truth
Cancer
(Positive for Cancer)
Positive
Truth
Non-Cancer
(Negative for Cancer)
Benign/
Negative
Positive
BX
BX
Positive
Benign/
Negative
GE
FFDM*
GE DBT*
≤30 days
Image &
Histopathology
Concordance
Review**
Concordant
Initially asymptomatic
women ≥30 referred for
breast biopsy
(n = 275)
Histopathology
Truth
Cancer
(Positive for Cancer)
Positive
BX
Benign/
Negative
Truth
Non-Cancer
(Negative for Cancer)
SOC Histologic
Concordance
Concordant
SOC re-Bx
recommended?**
Discordant
GE
FFDM*
GE DBT*
≤30 days
Yes
*Images may be collected from FFDM and/or DBT performed on GE equipment prior to
enrollment, if conducted within 30 days of each other.
** In the event of discordant histopathology and imaging findings, rebiopsy and resulting
histopathology results will be acquired to establish concordance If rebiopsy is not
recommended or if histopathology remains discordant with imaging findings after
rebiopsy, the subject will be withdrawn from the study.
Figure 1 updated to
represent histologic
concordance as truth
for non-cancer and to
remove one-year
follow-up procedures
for negative/benign
cases.
Updated language in
footnotes, clarifying
the 30-day image
acquisition
requirement and
describing the process
for discordance.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Justification
52.
Section 6.2. Study
Timeframe
The study is expected to begin in the fourth quarter of 2014, and last
for approximately two years (24 months), or until the target subject
population is enrolled or the Sponsor otherwise indicates in writing
that enrollment should be terminated. The end of the study shall be
defined as the date of when the last subject undergoes biopsy
procedures and concordance is established, if applicable is imaged in
the one-year follow-up. Total Subject participation will be from the
point of enrollment until truth determination of cancer status. for
each subject is expected to be 10-16 months, unless completed early
due to positive cancer diagnosis. The Investigator shall not begin the
study until the applicable EC/IRB and necessary regulatory authority
(when required) approval have been obtained.
Updated to reflect the
revised non-cancer
truth determination.
53.
Section 7.1. Number of
Subjects
Up to 275 subjects referred for breast biopsy (Enrollment ceiling per
site will be 165 subjects) will be enrolled from three (3) centers
located in the US and Europe (France) until at least 90
histopathology-confirmed cancers have been accrued. Enrollment
will be closed once the required number of cancers has been
histologically identified. Subjects awaiting one-year follow-up will
continue to be followed for truth. Data will be pooled with other
sources to achieve the target number of positive and negative cancer
cases, as described in Section 10.1.1 Sample Size Justification.
Removed one-year
follow-up language.
54.
Section 7.5. Inclusion
Criteria
Footnote:
1 Subjects who had screening DBT and or screening/diagnostic FFDM
imaging on non-GE equipment may be enrolled if they agree to
undergo repeat imaging on a GE system; If the prior screening and
diagnostic mammographic examinations were not conducted at the
recruiting site, review of those images by the investigator must
confirm that breast biopsy recommendation is warranted and GE
access to the images in DICOM format must be granted
Revised to match
footnote presented
with Inclusion Criteria
in Study Synopsis.
55.
Section 8.1. Digital Breast
Tomosynthesis (DBT) and
Full Field Digital
Mammography (FFDM)
Examinations
8.1. Baseline (Month 0) Digital Breast Tomosynthesis (DBT) and Full
Field Digital Mammography (FFDM) Examinations
Revised section title to
reflect omission of
one-year follow-up.
56.
Section 8.2 Post-
Mammography
Procedures
• If clinically indicated based on imaging results, subjects will
undergo biopsy or surgical intervention and breast tissue
histopathological analysis, as per institutional standard practice.
Clarified types of
procedures.
57.
Section 8.2.1. On-Site
Image Interpretation
DBT and FFDM images of all included subjects will be assessed at the
study site by one or more MQSA-qualified radiologists on an IDI
MammoWorkstation.  The DBT results may result in a
recommendation that additional breast lesions be biopsied (in
Clarified that both
modalities will be
assessed at the study
site.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
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Justification
addition to that/those already planned when the patient entered the
study). If so, biopsy plans may be changed accordingly.
The results of DBT alone, however, will not be used as a basis to
cancel plans for biopsy of any lesion.
The evaluating radiologist(s) at the site will record for each subject,
the following parameters:
• Breast density (as defined by BI-RADS® density categories)
• Finding characteristics, to include breast location laterality, lesion
type, depth, quadrant and size.  In the case of multiple findings, a
maximum of three (3) most suspicious findings will be scored and
localized.
Specified that breast
laterality will be
recorded.
58.
Section 8.3. Biopsy
Procedures
Percutaneous and open surgical breast interventions will proceed as
per standard of care at the recruiting site. A record of breast lesion
characteristics, including the type of lesion and location of the lesion
by left or right breast and within a breast quadrant will be recorded
on the CRF for all subjects. The interpretation of the local pathologist
will be recorded on the CRF.
If the subject does not complete the biopsy procedure as scheduled
or if the biopsy procedure is not successful or produces
indeterminate results that are not able to be resolved by clinically
indicated procedures, such as repeat biopsy(ies), the subject will be
withdrawn.
For benign/negative histopathology results, the site radiologist will
review the subject’s imaging and histopathology findings for
concordance and document the assessment on a CRF. If the findings
are concordant, then the subject will continue with the 1-year
follow-up procedure in approximately 10-16 months, per the site’s
standard of care, and results will be captured on a CRF. Histologic
concordance with imaging for negative or benign lesions will be
considered truth for non-cancer status. If surgical excision is
recommended even after concordance between imaging and
histopathology, the resulting histopathology from surgical excision
may be collected as part of the study. will be collected and used to
establish the subject's cancer status. If breast cancer status is
negative, 1-year follow-up will be used to establish final cancer
status.
Subjects who have negative or benign histology If the imaging and
histopathology findings that are discordant, rebiopsy and resulting
histopathology will be required to establish concordance, with
imaging shall be followed-up per the site’s standard of care. Once
concordance is achieved and histopathology continues to be
negative for cancer, the subject will continue with the 1-year follow-
up procedure in approximately 10-16 months from initial study
imaging. If rebiopsy is recommended, the histology findings and
concordance assessment of the rebiopsy will be used to determine
the subject’s cancer status. If no rebiopsy is not recommended or
Modified to accurately
represent data being
collected.
Clarified procedure for
histologic concordance
with imaging for
negative/benign cases.
Removed one-year
follow-up language.

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 4.0
Page 59 of 59
ADAPT- BX
DOC1601455 (Rev. 4.0)
Version Date: 08/Mar/2016
GE Healthcare Confidential
Item
Section
Revision or Clarification
Justification
histopathology occurs, or if histopathology remains discordant with
imaging findings following after rebiopsy, the subject will be
withdrawn from the study.
59.
Section 8.4. Follow-up
Procedures
8.4 Follow-up (Month 10-16) Procedures
Results from surgical intervention and/or any additional follow-up
resulting from biopsy(ies) (e.g., breast ultrasound or breast MRI) will
be considered in determining truth of positive cancer status.
No additional follow-up appointments will be required for subjects
that have completed biopsy/surgical intervention with positive
findings or documented histologic concordance with imaging.
Subjects with negative or benign histology findings will be followed
at approximately one year (10-16 months) by standard of care
imaging.
Subjects should be scheduled to complete one year follow-up by
month 15, allowing for one month (until month 16) to reschedule
subjects unable to attend or to collect previously completed one-
year follow-up imaging completed at another clinical site. If no
suspicious findings are observed at one-year follow-up, this will be
considered truth of non-cancer status. If suspicious findings are
observed, the subject will undergo standard of care diagnostic work-
up, and results will be considered truth for non-cancer or cancer
status.
Revised section title to
reflect omission of
one-year follow-up.
Clarified follow-up
procedures to account
for revised truth
determination of
negative/benign cases.
Clarified types of
procedures.
Removed one-year
follow-up language.
60.
Section 10.1.1. Sample
Size Justification
In this study, for an enrollment of 275 subjects recommended for
breast biopsy, it is assumed, based on the GE-190-003 experience,
approximately 33% are expected to have a proven cancer and
approximately 33% will have a benign lesion with normal 1-year
follow-up. So, at least 90 cancer cases and 90 non-cancer cases with
normal 1-year follow-up are expected to be accrued in this study. Up
to 275 subjects referred for breast biopsy (Enrollment ceiling per site
will be 165 subjects) will be enrolled from three (3) centers located in
the US and Europe (France) until at least 90 histopathology-
confirmed cancers have been accrued.
Removed one-year
follow-up language.
61.
Section 18. Additional
Country-Specific
Regulatory Requirements
The clinical investigation shall be conducted in accordance with the
ethical principles that have their origin in the Declaration of Helsinki
could be added.
Deleted inessential
language.
End of Document