Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis Compared to Mammography (ADAPT Trial) ADAPT-SCR: Recruitment Plan for Asymptomatic Women Undergoing Screening Mammography
Phase: NA
Conditions: Breast Cancer, Tumors, Breast, Cancer Screening
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: 2.0
Page 1 of 51
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Version Date: 15/Jun/2016
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Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
ADAPT-SCR: Recruitment Plan for Asymptomatic Women Undergoing
Screening Mammography
Study Number: 124.03-2014-GES-0010
Revision/Amendment: 2.0
Version Date: 15/Jun/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: 2.0
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Assessment of Diagnostic Accuracy and Performance of Digital Breast Tomosynthesis
Compared to Mammography (ADAPT Trial)
ADAPT-SCR: Recruitment Plan for Asymptomatic Women Undergoing Screening
Mammography
GEHC Study Number: 124.03-2014-GES-0010
Revision/Amendment: 2.0
Version Date: 15/Jun/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: 2.0
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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....................................................................................22
7.1.
Number of Subjects ........................................................................................ 22
7.2.
Subject Population.......................................................................................... 22
7.3.
Protection of Vulnerable Subjects .................................................................. 22
7.4.
Procedures for Enrollment.............................................................................. 22
7.5.
Inclusion Criteria............................................................................................. 23
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: 2.0
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8. Procedures for Research Study...........................................................25
8.1.
Pre-Study Imaging Procedures........................................................................ 25
8.2.
Baseline (Month 0) Digital Breast Tomosynthesis (DBT) and Full Field Digital
Mammography (FFDM) Examinations............................................................ 25
8.3.
Post-Study Imaging Procedures...................................................................... 26
8.4.
Biopsy Procedures........................................................................................... 27
8.5.
Follow-up (Month 10-16) Procedures ............................................................ 28
8.6.
Incidental Findings .......................................................................................... 28
8.7.
Withdrawal and Discontinuation Criteria....................................................... 29
9. Training Plan ......................................................................................29
9.1.
Training Plan for Research Device/Product.................................................... 29
9.2.
Training Plan for Protocol ............................................................................... 29
9.3.
Reader Training............................................................................................... 30
10.Data Analysis and Statistics................................................................30
10.1.
Statistical Analysis Methods ........................................................................... 30
10.2.
Interim Analysis............................................................................................... 32
10.3.
Handling of Missing Data................................................................................ 32
There will be no imputation of missing data and collected data will be analyzed as is.
......................................................................................................................... 32
10.4.
Pass/Fail Criteria of the Study......................................................................... 32
11.Deviations..........................................................................................32
11.1.
Management of Protocol Deviations.............................................................. 32
12.Complaint Handling and Adverse Event Reporting .............................33
12.1.
Foreseeable Adverse Events and Device Effects ............................................ 33
12.2.
Adverse Event Definitions............................................................................... 33
12.3.
Management of Adverse Event Reporting ..................................................... 34
12.4.
Management of Serious Adverse Event and Unanticipated Adverse Device
Effect Reporting .............................................................................................. 35
12.5.
Management of Device Complaints ............................................................... 36
13.Early Termination or Suspension ........................................................36
13.1.
Criteria for Early Termination or Suspension ................................................. 36
13.2.
Withdrawal of EC/IRB Approval...................................................................... 37
14.Ethics Committee (EC) and Regulatory Filings.....................................37
14.1.
Regulatory Authority Approval Requirements (Global) ................................. 37
14.2.
Ethics Committee Approval Requirements..................................................... 37
14.3.
Management of Protocol Revisions/Amendments ........................................ 37
14.4.
Informed Consent and Privacy Requirements................................................ 37
15.Data and Quality Management ..........................................................38
15.1.
Management of Data...................................................................................... 38

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: 2.0
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15.2.
Subject De-identification ................................................................................ 38
15.3.
Completion of Case Report Forms (CRFs)....................................................... 39
15.4.
Record Retention at the Site........................................................................... 39
16.Monitoring Plan .................................................................................39
16.1.
Brief Description ............................................................................................. 39
16.2.
Reference to Approved Monitoring Plan........................................................ 40
17.Publication Policy...............................................................................40
18.Additional Country-Specific Regulatory Requirements .......................40
References ..............................................................................................41
Appendix A: Amendment to Protocol Version 1.0 to 2.0 .........................44

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: 2.0
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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
10/Sep/2014
Sara Lam
Initial Protocol
2.0
15/Jun/2016
Carrie Lauer
Clinical Writer – Updated protocol per amendments detailed in
Appendix A: Amendment to Protocol Version 1.0 to 2.0

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: 2.0
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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-SCR: Recruitment Plan for Asymptomatic Women Undergoing Screening Mammography
Protocol Number (Study Number): 124.03-2014-GES-0010
Investigators and Study Center(s): Two (2) centers in the United States (US) will collect cases as part of this
study protocol.
Murray Rebner, MD
Beaumont Health System
Address:
3581 W 13 Mile Road,
Royal Oak, Michigan 48073 US
Telephone:
248-551-5122
E-mail:
mrebner@beaumont.edu
William Poller, MD
Allegheny General Hospital
Address:
320 E North Ave
Pittsburgh PA 15212, US
Telephone:
412-359-8366
E-mail:
wpoller@wpahs.org
Objective: The aim of this recruitment plan (ADAPT-SCR) is to collect image and other data on both digital
breast tomosynthesis (DBT) and full-field digital mammography (FFDM) from asymptomatic women
undergoing screening mammography. 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 screening images from up
to 250 asymptomatic women aged ≥30 years undergoing routine breast cancer screening will be conducted.
CC and MLO views from bilateral GE DBT and GE FFDM (conducted before or after enrollment) within a 30 day
window will be collected and assessed on-site by qualified radiologist(s) for clinical management purposes. BI-
RADS® scores will be recorded. Results of biopsy(ies) and histopathology, including lesion characteristics, will
be recorded.
Subjects with negative or benign imaging findings will be followed for approximately one year (10-16 months)
by standard of care imaging to determine 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 or evidence of negative one-year follow-up will be considered truth for
non-cancer status. A positive histology result will be considered truth for cancer.
Accrual DBT and FFDM data will be pooled for evaluation by independent blinded readers in a subsequent
reader study. The detailed information on the blinded image evaluation will be provided in a separate
Independent Review Charter (IRC) detailed in the ADAPT-BIE (Blinded Image Evaluation) protocol. This study’s
primary endpoint is collection of data to compare the diagnostic accuracy of two-view SenoClaire® - GE Breast
Tomosynthesis (DBT) verses 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.

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: 2.0
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Selection of Subjects: The subject population consists of asymptomatic adult women (>30 years of age)
scheduled for routine screening mammography.
Inclusion Criteria:
Subjects may be included that meet the following criteria:
1.
Women aged 30 years or older (≥30 years old);
2.
Asymptomatic women scheduled for screening mammography or have completed a screening
mammogram within the past 30 days;
3.
Mammography completed on a GE FFDM system (with CC and MLO views) at the site or another
clinical facility 1 2;
4.
Are able and willing to comply with study procedures;
5.
Have signed and dated the informed consent form;
6.
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, a negative
urine pregnancy test (if subject requests one).
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 a history of breast cancer and are in active treatment.  However, subjects with a prior
lumpectomy (> 5 years prior) who receive only routine screening mammography views can be
included;
3.
Have breasts too large to be adequately positioned on 24 x 31 centimeter (cm) FFDM digital receptor
without anatomical cut off during either FFDM or DBT 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)
Asymptomatic Women Scheduled for Screening Mammography
Pre-Clinical (animal)
External Bench
1 If prior mammographic examinations were not conducted at the recruiting site, review of those images by the Investigator must confirm that
the subject is qualified for this study (CC and MLO views present) and access to the images in DICOM digital format by GE must be granted.
2Subjects who had prior imaging on non-GE equipment may be enrolled if they agree to undergo repeat imaging on a GE FFDM system.
3Post-Menopausal is defined as documented 12 months of spontaneous amenorrhea.

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: 2.0
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Brief Description of Study Purpose: This study is being conducted to accrue breast cancer screening cases of
asymptomatic women for a subsequent blinded reader study comparing the diagnostic accuracy and
performance of digital breast tomosynthesis (DBT) performed with the GE SenoClaire® - GE Breast
Tomosynthesis (DBT) compared to conventional GE full-field digital mammography (FFDM) in asymptomatic
women. The study also provides data 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 (hereinafter
referred to as the “sponsor”)
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 (DBT)
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).
Regulatory Status:
Pre-Market
Post-Market
DBT, FFDM, and IDI MammoWorkstations used in this study are considered post-
market in the US. 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 site’s diagnosis of cancer status (positive or
negative/benign) for each subject based on DBT and FFDM at baseline (0 months) and 10-16 months, and/or
(if clinically indicated) histology and surgical findings. Histologic concordance with imaging will be assessed for
benign lesions, when applicable, and DBT and FFDM image sets will be assessed using BI-RADS® scores.
Characteristic Endpoints: Characteristic endpoints for all subjects will include histology findings and size,
lesion type, and other lesion characteristics based on image appearance. Technical factors of 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 as needed, repeat FFDM) that occur during the study
will be collected. No other clinical safety assessments will be performed.
Sample Size: 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), for which accrual of 200 biopsy cases
(ADAPT-BX and other sources) and 250 screening mammography cases (ADAPT-SCR and other sources) are
required.
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: 2.0
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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: 2.0
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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

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: 2.0
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US
United States
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: 2.0
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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

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: 2.0
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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 some 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

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: 2.0
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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 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 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

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: 2.0
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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).

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: 2.0
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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. 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), the SenoClaire® - GE Breast Tomosynthesis (DBT) is considered to be
Class III, as defined by the US FDA CFR 1020.30-33. FFDM devices without tomosynthesis or
computed tomography breast imaging devices are considered to be Class II, as defined by the US
FDA 21 CFR 892.1715. In Europe, the SenoClaire® - GE Breast Tomosynthesis (DBT) is considered
to be Class IIb as defined by the French National Agency for the Safety of Medicine and Health
Products regulations in accordance with the European Medial 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 are commercially available. Unique identifying information (e.g. model, serial
number, etc.) of each device used in this study will be recorded.

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: 2.0
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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.

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: 2.0
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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 screening
mammography subjects in this study is determined to provide sufficient accrual of non-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-SCR) is to collect image and other data on both digital
breast tomosynthesis (DBT) and full-field digital mammography (FFDM) from asymptomatic
women undergoing screening mammography. 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 site’s diagnosis of cancer status (positive or negative/benign)
for each subject based on DBT and FFDM at baseline (0 months) and 10-16 months, and/or (if
clinically indicated) histology and surgical findings. Histologic concordance with imaging will be
assessed for benign lesions, when applicable, and DBT and FFDM image sets will be assessed
using BI-RADS® scores.
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 factors of 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 as needed, repeat FFDM) that occur during
the study will be collected. No other clinical safety assessments will be performed.

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: 2.0
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6. DESIGN OF RESEARCH STUDY
6.1.
Type of Research Study
6.1.1. Study Type
This study (ADAPT-SCR) is an open-label, multi-center, within-subject crossover, randomized,
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 asymptomatic
adult women aged ≥30 years undergoing routine screening mammography.
The data from this study will be pooled with data from
other subjects who will have been
recruited under other GEHC protocols (including ADAPT-BX), for a blinded reader study and
analysis described in a separate protocol (ADAPT-BIE). Figure 1 depicts the study design and
procedures.
Figure 1:  Study Design and Procedures
Asymptomatic women ≥30
undergoing screening
full-field digital
mammography
(n = 250)
GE
FFDM*
GE DBT
≤30 days
1 yr F/U (10-16 mo)
imaging
AND applicable
Standard of Care
Follow-up
Suspicious
findings?
No
Yes
Standard of
Care Imaging
Work-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
Benign/
Negative
BX
Positive
BX
Positive
Image &
Histopathology
Concordance
Review**
Benign/
Negative
*FFDM may be collected prior to enrollment if conducted within 30 days of DBT.
** Concordant histological and imaging findings for benign lesions or evidence of negative 1-year follow-up will serve as truth for non-cancer.

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: 2.0
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6.1.2. Study Design Details:
Open-Label
Interventions are known to researchers and subjects
Blinded
Double-Blinded
Single-site
Multi-site
Data will be pooled from multiple studies (e.g. ADAPT-SCR & ADAPT-BX) at
multiple sites
Randomization
Procedure:
Reading order of DBT and FFDM will be random
Not randomized:
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 the last subject is imaged in the one-year follow-up. Total participation for each
subject is expected to be 10-16 months, unless completed early due to truth determination of
cancer status. The Investigator shall not begin study until the applicable EC/IRB approval has
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; subjects may be recalled for further
work-up based on positive screening interpretations on either FFDM or DBT.
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.
c.
Interpretation bias will be managed by randomizing the order that DBT and FFDM are
read for subjects as these will usually occur during the same visit.

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: 2.0
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7. STUDY SUBJECTS
7.1.
Number of Subjects
Up to 250 routine screening mammography (Enrollment ceiling per site will be 150 subjects)
subjects will be enrolled from two (2) centers in the US. Data will be pooled with other sources
to achieve the target number of positive cancer and non-cancer cases required for analysis, 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 scheduled for routine screening
mammography that are 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). Each subject will be assigned a randomized order for reading of their DBT and FFDM
images such that approximately half of the subjects will have their DBT images interpreted first
and the other half will have their FFDM images interpreted first. A subject will be considered
enrolled when determined eligible, informed consent is signed, and randomized read order is
assigned, whether or not the subject undergoes study procedures.

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: 2.0
1 If prior mammographic examinations were not conducted at the recruiting site, review of those images by the Investigator must confirm that
the subject qualified for this study (CC and MLO views present) and access to the images in DICOM digital format by GE must be granted.
2 Subjects who had prior imaging on non-GE equipment may be enrolled if they agree to undergo repeat imaging on a GE FFDM system
3 Post-Menopausal is defined as documented 12 months of spontaneous amenorrhea.
ADAPT-SCR
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7.5.
Inclusion Criteria
Subjects may be included that meet the following criteria:
1.
Women aged 30 years or older (≥30 years old);
2.
Asymptomatic women scheduled for screening mammography or have completed a
screening mammogram within the past 30 days;
3.
Mammography completed on a GE FFDM system (with CC and MLO views) at the site or
another clinical facility 1 2;
4.
Are able and willing to comply with study procedures;
5.
Have signed and dated the informed consent form;
6.
Are either surgically sterile or post-menopausal3 or, if of childbearing potential, the
possibility of pregnancy is remote based on a documented negative patient history and,
optionally, a negative urine pregnancy test (if subject requests one).
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 a history of breast cancer and are in active treatment.  However, subjects with a
prior lumpectomy (> 5 years prior) who receive only routine screening mammography
views can be included;
3.
Have breasts too large to be adequately positioned on 24 x 31 centimeter (cm) FFDM
digital receptor without anatomical cut off during either FFDM or DBT 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 recruited from asymptomatic populations undergoing routine screening
mammography at each site, in accordance with local EC/IRB recruitment policy. Enrollment
decisions will be based on 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

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: 2.0
1 If prior mammographic examinations were not conducted at the recruiting site, review of those images by the Investigator must confirm that
the subject qualified for this study (CC and MLO views present) and access to the images in DICOM digital format by GE must be granted.
2 Subjects who had prior imaging on non-GE equipment may be enrolled if they agree to undergo repeat imaging on a GE FFDM system
3 Post-Menopausal is defined as documented 12 months of spontaneous amenorrhea.
ADAPT-SCR
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compliance with applicable laws, regulations, and standard procedures at the investigational
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: 2.0
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8. PROCEDURES FOR RESEARCH STUDY
Table 1: Study Schedule of Events for Study Subjects
Variables
Pre –
Study Imaging
Study Imaging
Post - Study
Imaging
Informed Consent
X
Entry Criteria
X
Demographic Information a
X
Review Relevant Medical/Surgical History
X
Randomized Read Order Assigned
X
DBT Imaging
X
Collection of Prior Screening FFDM Imaging
X
Screening FFDM Imaging b
X
Safety   Assessments   (AE,   SAE,   device malfunctions)
c
X
Image assessment by site radiologist
X
Histopathology (if applicable)
X
DBT = Digital Breast Tomosynthesis; FFDM = Full-field digital mammography; AE = adverse event; SAE = serious adverse event;
a: Including age, menopausal status and history of surgical breast intervention. b: Only if prior images are not available or were not
obtained on a GE FFDM system. c: Device-related AEs and SAEs
8.1.
Pre-Study Imaging Procedures
All enrolled subjects will undergo the following procedures prior to receiving their study-specific
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 the subject had her
questions answered, read, signed and dated and has 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 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 and randomized reading order will be assigned.
There is no special subject preparation required to perform DBT or FFDM screening
mammography.
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 images will be collected from each
subject’s medical record or, if necessary (because prior screening mammography images are not
available or were not performed with GE FFDM equipment), a subject may also need to undergo

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: 2.0
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repeat FFDM; if so, this will be 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 FFDM image acquisition (both CC and MLO views) will be performed within 30 days of
each other, regardless if FFDM was performed before or after the subject 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 FFDM (if repeated) to be recorded in the
source document 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 imaging 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 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.
8.3.
Post-Study Imaging Procedures
The following assessments will be performed:
•
DBT and FFDM images will be assessed at the study site in randomized order by one or
more MQSA-qualified radiologists, as per institutional standard practice;

If clinically indicated based on screening imaging results, subjects will undergo
institution’s standard practice of diagnostic work-up of findings seen, which may include
surgical intervention and breast tissue histopathological analysis.

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: 2.0
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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.
8.3.1. 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 radiologist(s) on an IDI MammoWorkstation. The 2-D FFDM or 3-D DBT results
may result in a recommendation that breast lesions be worked-up by diagnostic evaluation or
biopsied.
The results of DBT alone, however, will not be used as a basis to cancel plans for biopsy of any
lesion that would be otherwise recommended based on routine mammography with FFDM.
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 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
8.3.2. Additional Diagnostic Imaging
If a subject is called back for further diagnostic assessment, the additional FFDM views will be
recorded on the CRF. In addition, any other imaging which the subject undergoes will be
recorded (e.g., ultrasound or magnetic resonance imaging [MRI]).
8.4.
Biopsy Procedures
Biopsy(ies) will be completed for subjects whose screening mammography (DBT and/or FFDM)
and subsequent diagnostic work-up results provide a clinical indication for biopsy. No biopsies
will be performed solely for research purposes as part of this study.
Percutaneous and/or 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 on 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. 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, 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

Study Title: Assessment of Diagnostic Accuracy and Performance of Digital
Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
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concordance between imaging and histopathology, the resulting histopathology from surgical
excision may be collected as part of the study. If available, one-year follow-up data will be used
to determine truth status in lieu of concordance assessments.
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, the subject will be followed at approximately
one year (10-16 months).
8.5.
Follow-up (Month 10-16) Procedures
All subjects will be followed at approximately one year (10-16 months) unless positive cancer
status is histologically determined or imaging and histology are deemed concordant prior to one
year follow-up. For any subject who undergoes one-year follow-up procedures, the follow-up
results will be considered truth for non-cancer or cancer status.
Applicable 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 images 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.
If the initial GE FFDM and/or DBT imaging or incidental standard of care procedures conducted
prior to one-year follow-up reveals suspicious findings that could indicate breast cancer, the
subject will undergo standard of care diagnostic work-up (e.g. clinically indicated MRI,
ultrasound, biopsy, or other exams). Cancer status should be reported using all available clinical
information, according to the Investigator’s medical judgment. Positive cancer results from
diagnostic work-up, biopsy and histology will be considered truth of positive cancer status, and
no additional follow-up will be required once truth is established.
8.6.
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.

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8.7.
Withdrawal and Discontinuation Criteria
8.7.1. 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 determined during the exam that the research imaging will in
any way 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.
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.
Subjects withdrawn after consent is signed and randomized read order is given 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 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.

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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 dates 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 recording of data on case report forms
(CRFs) prior to 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-BX and ADAPT-Enrich).
In this study, for an enrollment of 250 screening subjects, it is assumed, based on the GE-190-
001 experience, that 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.
Based on the GE-190-003 experience, for an enrollment of 275 subjects recommended for
breast biopsy, approximately 33% are expected to have a proven cancer and 33% will have a
benign lesion. So, at least 90 cancer cases and 90 benign cases are expected to be accrued in the
ADAPT-BX study.
In the ADAPT-ENRICH study, for a target enrollment of 200 subjects recommended for breast
biopsy, it is assumed, based on the GE-190-003 experience, that approximately 33% are
expected to have a proven cancer. Thus, at least 66 cancer cases are expected from the ADAPT-
ENRICH study.
In the combined protocols (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.
The data from this study will be pooled with data from other subjects who will be recruited from
other sources (e.g. ADAPT-BX). If necessary, data from other sources may also be included to

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Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
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achieve the required number of cancer and non-cancer cases. The accrued screening 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 the data collected in this study.
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 evaluated 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/randomized, 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.
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

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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.
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 data 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:
Critical deviations are protocol 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.

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If an Investigator uses a device without obtaining informed consent, 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:
Non-critical deviations are 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.
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
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 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.
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.

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Protocol: 2.0
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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
(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 subject’s 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)

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­
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)

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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Study Number: 124.03-2014-GES-0010
Protocol: 2.0
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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 Affairs 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 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 that the subject has
ample time to review the ICF and has all questions answered to her 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 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. These data and images collected as part of this research study may also be transported
to countries outside of the United States 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 that is used to
provide a means for subject randomization and de-identification. The Site Principal Investigator

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(PI) or authorized 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.

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: 2.0
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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.

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: 2.0
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dying-from-cancer. Accessed Sep 25, 2013.
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1990;73(5):335-8.
7. Cuomo M. Mammography: A Limited Tool for Early Detection of Breast Cancer: Huffington Post; 2013.
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13. Tabar L, Vitak B, Chen H, Yen M, Duffy S, Smith R. Beyond randomized controlled trials: organized
mammographic screening substantially reduces breast carcinoma mortality. Cancer. 2001;91(9):1724-1731.
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organized service screening with mammography: 1. Further confirmation with extended data. Cancer
Epidemiol. 2006;15(1):45-51.
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.
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.

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Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 2.0
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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).
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).

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Breast Tomosynthesis Compared to Mammography (ADAPT Trial)
Study Number: 124.03-2014-GES-0010
Protocol: 2.0
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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/ucm107552.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 Med.
2013;32(1):93-104.
41. Dorfman D, Berbaum K, Metz C. Receiver operating characteristic rating analysis: generalization to the
population of readers and patients with the jackknife method. Investigative Radiology. 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: 2.0
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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, which are
not expected to impact the safety profile or scientific integrity of the study. Changes made to the
protocol include:

Addition of documented concordance assessments for truth determination of negative/benign
histology cases;

Inclusion of data collection for non-cancerous lesions;

Updates to accrual target for the overall GEHC DBT program; and

Discussion of additional ADAPT case collection study (ADAPT-ENRICH).
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
screening images from up to 250 asymptomatic women aged ≥30
years undergoing routine breast cancer screening will be conducted.
CC and MLO views from bilateral GE DBT and GE FFDM (conducted
before or after enrollment) within a 30 day window will be collected
and assessed on-site by qualified radiologist(s) for clinical
management purposes. BI-RADS® scores will be recorded. Results of
biopsy(ies) and histopathology, including lesion characteristics, will
be recorded.
A positive histology result will be considered truth of cancer.
Subjects with negative or benign imaging findings (histological
and/or imaging) will be followed for approximately one year (10-16
months) by FFDM and any additional standard of care imaging to
determine cancer status performed per standard of care. 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 or
evidence of negative one-year follow-up will be considered truth for
non-cancer status. A positive histology result will be considered truth
for cancer.
…
Added assessment of
histologic concordance
with imaging for truth
status of
negative/benign
histology cases.
Clarified how truth will
be determined for
cancer and non-cancer
status.
2.
Section 1. Study Synopsis
– Brief Description of
Study Purpose
This study is being conducted to accrue breast cancer screening cases
of asymptomatic women for a subsequent blinded reader study
comparing the diagnostic superiority, accuracy and performance, and
reading time of digital breast tomosynthesis (DBT) performed with
the GE SenoClaire® - GE Breast Tomosynthesis (DBT) compared to
conventional GE full-field digital mammography (FFDM) in
asymptomatic women. The study also provides data for exploratory
analysis of cancerous and non-cancerous lesion characteristics
detected by DBT and FFDM systems. This statistically powered study
Revised to accurately
reflect intent of the
blinded reader study.
Updated to include
non-cancerous lesion
characteristics.

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: 2.0
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Item
Section
Revision or Clarification
Justification
is being conducted to support regulatory claims to expand the
labeling of the DBT system.
3.
Section 1. Study Synopsis
– Primary Endpoints
The primary endpoint will be the site’s diagnosis of cancer status
(positive or negative/benign) for each subject based on DBT and
FFDM at baseline (0 months) and 10-16 months, and/or (if clinically
indicated) histology and surgical findings. Histologic concordance
with imaging will be assessed for benign lesions, when applicable,
and at any point after enrollment. I DBT and FFDM image sets will be
assessed using BI-RADS® scores.
Revised to include
histologic concordance
with imaging for
determining truth
status of benign
lesions.
Clarified that FFDM
and DBT image sets
will be assessed.
4.
Section 1. Study Synopsis
and 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
factors of 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 will be
collected based on
image appearance.
5.
Section 1. Study Synopsis
and 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 as needed, repeat FFDM) that occur during the study will
be collected. No other clinical safety assessments will be performed.
Reporting period
defined for safety
endpoint.
6.
Section 1. Study Synopsis
– Sample Size
Sample size is determined by the need to accrue at least 70 120
cancer cases and 250 non-cancer cases for the overall GE Healthcare
(GEHC) DBT program (ADAPT-BIE), for which accrual of 200 biopsy
cases (ADAPT-BX and other sources) and 250 screening
mammography cases (ADAPT-SCR and other sources) are required.
Revised accrual target
based on power
analysis for the overall
GEHC DBT program.
Updated to clarify that
other sources may be
pooled for subsequent
BIE study.
7.
Section 1. Study Synopsis
– Research Manager
Address:
3562 Lookout Court #478
Oceanside, CA 92056-5259, US
3200 N Grandview Blvd
Waukesha, WI 53188-1678
Telephone: +1-414-379-4201 1-414-721-4393
E-mail:
Tanya.Carrillo@ge.com
Updated Research
Manager’s contact
information.
8.
Section 1. Study Synopsis
– Medical Monitor
Address:
1100 Technology Park Drive
Billerica, MA 01821-4111, US
3200 N Grandview Blvd
Waukesha, WI 53188-1678
Telephone: +1-617-669-3200 781-262-5579
Updated Medical
Monitor’s contact
information.

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: 2.0
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Item
Section
Revision or Clarification
Justification
E-mail:
Ron.VonJako@med.ge.com
9.
Section 2.1. Literature
Review – Introduction
…
This protocol is one of two 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 two 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 some who have been
recommended for breast biopsy because of one or more
radiographically detected suspicious lesions.
Updated to clarify that
other sources may be
pooled for subsequent
BIE study.
Clarified that all
subjects are not
expected to be
recommended for
biopsy.
10.
Section 5.2.2.
Characteristic Objectives
An exploratory aim is to describe positive cancer and non-cancer
cases identified in this accrual study based on cancer characteristics
histology findings and lesion type.
Updated to include
non-cancerous lesion
characteristics.
11.
Section 5.3.1. Primary
Endpoints
The primary endpoint will be the site’s diagnosis for each patient of
cancer status (positive or negative/benign) for each subject based on
DBT and FFDM at baseline (0 months) and 10-16 months, and/or (if
clinically indicated) histology and surgical findings. Histologic
concordance with imaging will be assessed for benign lesions, when
applicable, and DBT and FFDM image sets will be assessed using BI-
RADS® scores.
Revised to include
histologic concordance
with imaging for
determining non-
cancer truth status of
benign lesions.
Revised to mirror
language in Section 1.
Study Synopsis –
Primary Endpoints.
12.
Section 6.1.1. Study Type
This study (ADAPT-SCR) is an open-label, multi-center, within-subject
crossover, randomized, 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. Study subjects will be asymptomatic adult
women aged ≥30 years undergoing routine screening
mammography.
…
Figure 1:  Study Design and Procedures
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
lesions. Clarified that
1-year follow-up will

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: 2.0
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Item
Section
Revision or Clarification
Justification
Asymptomatic women ≥30
undergoing screening
full-field digital
mammography
(n = 250)
GE
FFDM*
GE DBT
≤30 days
1 yr F/U (10-16 mo)
FFDM
AND applicable
Standard of Care
Follow-up
Suspicious
findings?
No
Yes
Standard of
Care Imaging
Work-up
Histopathology
Standard of
Care Imaging
Work-Up
Histopathology
Suspicious
findings?
No
Yes
Truth
Cancer
(Positive for Cancer)
Positive
Truth
Non-Cancer
(Negative for Canc
Benign/
Negative
Positive
Benign/
Negative
BX
Positive
BX
Positive
Asymptomatic women ≥30
undergoing screening
full-field digital
mammography
(n = 250)
GE
FFDM*
GE DBT
≤30 days
1 yr F/U (10-16 mo)
imaging
AND applicable
Standard of Care
Follow-up
Suspicious
findings?
No
Yes
Standard of
Care Imaging
Work-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
Benign/
Negative
BX
Positive
BX
Positive
Image &
Histopathology
Concordance
Review**
Benign/
Negative
*FFDM may be collected prior to enrollment if conducted within 30 days of DBT.
** Concordant histological and imaging findings for benign lesions or evidence of
negative 1-year follow-up will serve as truth for non-cancer.
include standard of
care imaging.
Added footnote
clarifying non-cancer
truth determination.
13.
Section 6.1.2. Study
Design Details
…
Multi-site: Data will be pooled from 2 multiple studies (e.g. ADAPT-
SCR & ADAPT-BX) at multiple sites
Comparator: Diagnostic accuracy of DBT vs FFDM is will be assessed
in a separate protocol (ADAPT-BIE)
…
Clarified that other
sources may be pooled
for analyses.
Clarified that ADAPT-
BIE will be conducted
subsequently.
14.
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 the last subject is imaged in the one-year follow-
up. Total participation for each subject is expected to be 10-16
months, unless completed early due to incidental cancer finding
truth determination of cancer status. The Investigator shall not begin
study until the applicable EC/IRB approval has been obtained.
Revised to reflect
update to non-cancer
truth determination.

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: 2.0
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Item
Section
Revision or Clarification
Justification
15.
Section 7.1. Number of
Subjects
Up to 250 routine screening mammography (Enrollment ceiling per
site will be 150 subjects) subjects will be enrolled from two (2)
centers in the US. Data will be pooled with other sources to achieve
the target number of positive cancer and non-cancer cases required
for analysis, as described in Section 10.1.1 Sample Size Justification
9.1.1 – Sample Size Justification.
Updated section
reference.
16.
Section 8. Procedures for
Research Study
Table 1: Study Schedule of Events for Study Subjects
Variables
Pre – Study
Imaging
Mammograp
hy
Study
Imaging
Mammograp
hy
Post - Study
Imaging
Mammograp
hy
Informed Consent
X
Entry Criteria
X
Demographic Information a
X
Review Relevant Medical/Surgical
X
Randomized Read Order Assigned
X
DBT Imaging
X
Collection of Prior Screening
X
Screening FFDM Imaging b
X
Safety   Assessments   (AE,   SAE,
device malfunctions) c
X
Image assess,emt assessment by
X
Histopathology (if applicable)
X
Revised table headers
to clarify procedures
are related to study-
specific imaging.
Corrected
typographical error.
17.
Section 8.1. Pre-Study
Imaging Procedures
8.1. Pre-Mammography Study Imaging Procedures
All enrolled subjects will undergo the following procedures prior to
receiving their study-specific 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 the subject had her questions
answered , read, signed and dated and has 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 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 and randomized reading order will be
assigned.
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 screening mammography. Subjects undergoing a
Revised section title
for consistency with
Table 1 headings.
Clarified procedures
relate to study-specific
imaging.
Deleted language
regarding Investigator
comments to reflect
approved format of
CRFs.
Deleted
inconsequential
language for the study
protocol. Appropriate
language presented in
the informed consent
forms.

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: 2.0
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Item
Section
Revision or Clarification
Justification
mammography examination often feel apprehensive because of the
examination and the ensuing diagnosis. Consequently, a simple but
precise explanation of the procedure is provided to reassure the
subject. The subject should be comfortably positioned to remain
motionless throughout the examination.
18.
Section 8.2. Baseline
(Month 0) Digital Breast
Tomosynthesis (DBT) and
Full Field Digital
Mammography (FFDM)
Examinations
…

Positioning the breast properly in FFDM 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.
Generalized statement
since CC views apply to
both DBT and FFDM.
19.
Section 8.3. Post-Study
Imaging Procedures
8.3 Post-Mammography Study Imaging Procedures
Revised section title
for consistency with
Table 1 headings.
20.
Section 8.3.1. 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 radiologist(s) on an IDI
MammoWorkstation. The 2-D FFDM or 3-D DBT results may result in
a recommendation that breast lesions be worked-up by diagnostic
evaluation or biopsied.
…
Added FFDM to
accurately reflect
study procedures.
21.
Section 8.4. Biopsy
Procedures
Biopsy(ies) will be completed for subjects whose screening
mammography (DBT and/or FFDM) and subsequent diagnostic work-
up results provide a clinical indication for biopsy. No biopsies will be
performed solely for research purposes as part of this study.
Percutaneous and/or 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 on 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. 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, 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. If available,
one-year follow-up data will be used to determine truth status in lieu
of concordance assessments.
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
Added procedure for
histologic concordance
with imaging for
negative/benign
histology cases.

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: 2.0
Page 50 of 51
ADAPT-SCR
DOC1601442 (Rev. 2.0)
Version Date: 15/Jun/2016
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Item
Section
Revision or Clarification
Justification
concordance assessment of the rebiopsy will be used to determine
the subject’s cancer status. If rebiopsy is not recommended, the
subject will be followed at approximately one year (10-16 months).
22.
Section 8.5. Follow-up
(Month 10-16)
Procedures
All subjects will be followed at approximately one year (10-16
months) unless positive cancer status is histologically determined or
imaging and histology are deemed concordant prior to one year
follow-up. For any subject who undergoes one-year follow-up
procedures, the follow-up results will be considered truth for non-
cancer or cancer status.
Applicable Ssubjects 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 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 diagnostic work-up, and results will be considered truth for
non-cancer or cancer status.
…
Added histologic
concordance with
imaging for
negative/benign
histology cases.
Specified that one-
year follow-up results
will be used for truth
determination, when
available.
Clarified that standard
of care imaging will be
conducted at follow-
up.
23.
Section 10.1.1. Sample
Size Justification
The projected sample size is determined by the need to accrue at
least 70 120 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-BX and ADAPT-Enrich).
In this study, for an enrollment of 250 screening subjects, it is
assumed, based on the GE-190-001 experience, that 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.
Based on the GE-190-003 experience, for an enrollment of 200 275
subjects recommended for breast biopsy, approximately 33% are
expected to have a proven cancer and 33% will have a benign lesion
with normal 1-year follow-up. So, at least 66 90 cancer cases and 66
90 benign cases with normal 1-year follow-up are expected to be
accrued in the ADAPT-BX study.
In the ADAPT-ENRICH study, for a target enrollment of 200 subjects
recommended for breast biopsy, it is assumed, based on the GE-190-
003 experience, that approximately 33% are expected to have a
proven cancer. Thus, at least 66 cancer cases are expected from the
ADAPT-ENRICH study.
Thus, inIn the combined protocols (ADAPT-SCR and, ADAPT-BX, and
ADAPT-ENRICH), it is expected that at least 70 120 cancer cases and
Updated total accrual
targets for the overall
GEHC DBT program.
Revised to include
ADAPT-ENRICH and to
clarify strategy for
combining cancer and
non-cancer cases from
different sources to
achieve the overall
program targets.
Updated enrollment
targets for ADAPT-BX
(protocol version 4.0,
dated 08/Mar/2016).

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: 2.0
Page 51 of 51
ADAPT-SCR
DOC1601442 (Rev. 2.0)
Version Date: 15/Jun/2016
GE Healthcare Confidential
Item
Section
Revision or Clarification
Justification
250 non-cancer cases will be accrued for the overall GEHC DBT
development program.
The data from this study will be pooled with data from other subjects
who will be recruited from other sources, such as the separate
protocol (e.g. ADAPT-BX). If necessary, data from other sources may
also be included to achieve the required number of cancer and non-
cancer cases. The accrued screening 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.
…
End of Document