Willingness of Women to Undergo a Contrast-enhanced Spectral Mammography (CESM) for Breast Cancer Screening and Their Experience Before and After CESM
Phase: NA
Conditions: Mammographic Breast Density, Mammography
Sponsor: University of Virginia

IRB-HSR# 18853: Willingness of Women to Undergo a Contrast-enhanced Spectral Mammography (CESM) for 
breast cancer screening and their experience before and after CESM 
 
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IRB-HSR PROTOCOL 
Investigator Agreement 
 
BY SIGNING THIS DOCUMENT, THE INVESTIGATOR CONFIRMS: 
1. I am not currently debarred by the US FDA from involvement in clinical research studies. 
2. I am not involved in any regulatory or misconduct litigation or investigation by the FDA. 
3. That if this study involves any funding or resources from an outside source, or if you will be sharing data 
outside of UVA prior to publication that you will contact the Dean’s office regarding the need for a 
contract and letter of indemnification.  If it is determined that either a contract or letter of indemnification 
is needed, subjects cannot be enrolled until these documents are complete. 
4. The proposed research project will be conducted by me or under my close supervision.  It will be 
conducted in accordance with the protocol submitted to and approved by the IRB including any 
modifications, amendments or addendums submitted and approved by the IRB throughout the life of the 
protocol.  
5. That no personnel will be allowed to work on this protocol until they have completed the IRB-HSR On-line 
training and the IRB-HSR has been notified. 
6. That all personnel working on this protocol will follow all IRB-HSR Policies and Procedures as stated on the 
IRB-HSR Website http://www.virginia.edu/vprgs/irb/ and on the School of Medicine Clinical Trials Office 
Website:  http://knowledgelink.healthsystem.virginia.edu/intranet/hes/cto/sops/sop_index.cfm 
7. I will ensure that all those delegated tasks relating to this study, whether explicitly or implicitly, are 
capable through expertise, training , experience or credentialing to undertake those tasks.   
8. I confirm that the implications of the study have been discussed with all Departments that might be 
affected by it and have obtained their agreement for the study to take place.  
9. That no subjects will be recruited or entered under the protocol until the Investigator has received the 
signed IRB-HSR Approval form stating the protocol is open to enrollment 
10. That any materials used to recruit subjects will be approved by the IRB-HSR prior to use.  
11. That all subjects will sign a copy of the most current consent form that has a non-expired IRB-HSR approval 
stamp. 
12. That any modifications of the protocol or consent form will not be initiated without prior written approval 
from the IRB-HSR, except when necessary to eliminate immediate hazards to the subjects. 
13. Any significant findings that become known in the course of the research that might affect the willingness 
of subjects to enroll or to continue to take part, will be promptly reported to the IRB.   
14. I will report immediately to the IRB any unanticipated problems involving risk to subjects or to others 
including adverse reactions to biologics, drugs or medical devices.   
15. That any serious deviation from the protocol will be reported promptly to the Board in writing. 
16. That any data breach will be reported to the  IRB, the UVa Corporate Compliance and Privacy Office , UVa 
Police as applicable.  
17. That the continuation status report for this protocol will be completed and returned within the time limit 
stated on the form. 
18. That the IRB-HSR office will be notified within 30 days of a change in the Principal Investigator or of the 
closure of this study. 

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19. That a new PI will be assigned if the current PI will not be at UVA for an extended period of time.  If the 
current PI is leaving UVa permanently, a new PI will be assigned PRIOR to the departure of the current PI.  
20. All study team members will have access to the current protocol and other applicable documents such as 
the IRB-HSR Application, consent forms and Investigator Brochures. 
21. Signed consent forms and other research records will be retained in a confidential manner.  Records will 
be kept at least 6 years after completion of the study.  
22. No data/specimens may be taken from UVa without a signed Material Transfer Agreement between 
OSP/SOM Grants and Contracts Office and the new institution.  Original study files are considered 
institutional records and may not be transferred to another institution. I will notify my department 
administration regarding where the originals will be kept at UVa.  The material transfer agreement will 
delineate what copies of data, health information and/or specimens may be taken outside of UVa.  It will 
also approve which HIPAA identifiers may be taken outside of UVa with the health information or 
specimens. 
23. If any member of study team leaves UVa, they are STRONGLY ENCOURAGED to use Exit Checklist found on 
IRB-HSR website at http://www.virginia.edu/provost/facultyexit.pdf. 
 
The IRB reserves the right to terminate this study at any time if, in its opinion, (1) the risks of further 
experimentation are prohibitive, or (2) the above agreement is breached. 
 
Investigators Experience 
Dr. Miller has ABMS Certification in Diagnostic Radiology. His clinical practice experience and current role 
includes Breast Cancer Screening/Mammograms, Low-dose Breast Tomosynthesis (3D Mammography), 
Automated Breast Ultrasound System (ABUS), including SOM Assistant Professor and clinical director of the 
CESM program. 
 
Roger Anderson, Ph.D., is a professor of public health sciences and co-leader for cancer control and population 
health research. He is internationally known for his work in health disparities and has extensive experience in 
survey development. Dr. Anderson’s primary role in this study is survey development.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB-HSR# 18853: Willingness of Women to Undergo a Contrast-enhanced Spectral Mammography (CESM) for 
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Signatures 
 
Principal Investigator 
 
____________________________ 
____________________________ 
_______ 
Principal Investigator 
Principal Investigator 
Date 
Signature 
Name Printed 
 
 
The Principal Investigator signature is ONLY required if this is a new protocol, a 5 year update or a modification 
changing the Principal Investigator. 
 
 
Department Chair 
BY SIGNING THIS DOCUMENT THE DEPARTMENT CHAIR AGREES: 
1. To work with the investigator and with the board as needed, to maintain compliance with this 
agreement. 
2. That the Principal Investigator is qualified to perform this study. 
3. That the protocol is scientifically relevant and sound. 
 
___________________________ 
_______________________  
_________ 
Department Chair or Designee  
Department Chair or Designee 
Date 
Signature 
Name Printed 
 
 
The person signing as the Department Chair cannot be the Principal Investigator or a sub-investigator on this 
protocol. 
The Department Chair or Designee signature is ONLY required if this is a new protocol or a modification 
changing the Principal Investigator. 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB-HSR# 18853: Willingness of Women to Undergo a Contrast-enhanced Spectral Mammography (CESM) for 
breast cancer screening and their experience before and after CESM 
 
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Brief Summary/Abstract 
Contrast-enhanced spectral mammography (CESM) is an FDA approved tool for breast cancer detection. 
However, adoption into clinical practice has been slow. In this study, we will explore patient issues related to 
the use of CESM for breast cancer screening. After receiving the first 50 results from another study (IRB-HSR# 
pending, Submission #11378) survey of women with dense breasts presenting for screening mammography to 
understand issues related to convenience, risks, and benefits of advanced screening, we will proceed with this 
(CESM) study. For this study, 210 women with heterogeneous or dense breast tissue reported on a previous 
mammogram, will be recruited to undergo a screening Contrast-enhanced Spectral Mammography (CESM). 
The CESM will serve as the subject’s annual screening breast exam for clinical care.  A survey will be 
administered before and after the examination that evaluates the patient experience. Women will not be at 
high risk for breast cancer (<20% lifetime risk). All abnormal findings will be acted upon independently. Results 
of the general screening population survey will be compared with those of women who choose to undergo the 
CESM examination in order to evaluate the influence of age, education, and lifetime risk on decision making 
about advanced screening.   
Background 
1. Provide the scientific background, rationale and relevance of this project.     
Screening mammography reduces breast cancer mortality by 15-40%. However, the limitations of 
mammography have long been known regarding the ability to detect cancer in women with dense breast 
tissue. Interval cancers, presenting as a palpable or other clinical finding between screening intervals, are 5 
times more likely in women with heterogeneously dense breast tissue and 17 times more likely in women with 
extremely dense tissue compared with women with predominately fatty breasts (1). This lack of an effective 
breast cancer screening modality has prompted breast density legislation- now in effect in 19 states. In 2011, 
Virginia became the 3rd state to have a breast density law enacted. However, more than 25 million women age 
40-74 years have either heterogeneous or dense breast tissue on mammography (2). Any decisions regarding 
supplemental screening may be costly to our society.  
 
The most common ancillary screening test performed after a mammogram is a screening ultrasound (US). 
Screening US detects about 30% more breast cancers than mammography alone (3-5). However, screening US 
is associated with a high false positive rate. Whereas women undergoing screening mammography have a 1-
2% risk of undergoing biopsy, 5-7% of women undergoing screening US will be recommended to undergo 
biopsy. The positive predictive value (PPV) of biopsy recommendation for lesions identified at screening US is 
also quite low (7-9% cancers, versus 25-40% for mammography). The low specificity is the major downside of 
using US for ancillary screening of women with dense breast tissue. The cost associated with this examination 
is high- for every 100 exams performed, up to 7 biopsies will be performed, and up to 10 will have another US 
in 6 months due to an indeterminate lesion.  
 
Contrast-enhanced spectral mammography (CESM) is an emerging modality that incorporates both anatomic 
(structural) and functional (enhancement) information of the breasts. CESM is an FDA approved imaging study 
for detection of breast cancer and is frequently used for diagnostic patients in the UVa Breast Care Center. 

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There are less than 20 of these units in the U.S., and UVa Cancer Center Breast Program has one. In this exam, 
patients receive IV iodinated contrast, similar to having a CT scan. After 2 minutes, routine mammographic 
views are obtained. During the exposure, both high (45-49 KVp) and low (26-30 kVp) energy images are 
obtained (Figure 1). The low energy exposure is below the “k-edge” of iodine and so the appearance is the 
same as a conventional mammogram. This high energy exposure will “see” the iodine and the breast tissue. 
This high energy exposure is subtracted from the low energy exposure to generate an “iodine” image (Figure 
2). Because the dense tissue is subtracted out, the CESM is not limited by dense tissue. 
 
 
 
Figure 1. Timing of CESM study 
 
 
 

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Figure 2. Digital mammogram with dense tissue shows an irregular mass in the posterior right breast 
(arrows). The CESM study shows this mass as well as three other areas of invasive cancer between the mass 
and the nipple.  
 
 
At UVa, about 15 CESM studies are performed per month. The majority are performed for a 
diagnostic indication such as an abnormal mammogram or MRI, and less are performed for 
screening. However, screening CESM is often used for women at high risk that cannot undergo 
breast MRI for various reasons. Nationally, CESM has been slow to be adopted for screening 
despite the apparent high sensitivity. It is unclear if this is due to lower convenience, concern about 
IV placement or contrast reaction, or lack of knowledge of this test. The aim of this study is to 
evaluate patient attitudes related to the use of CESM as a breast cancer screening test.  
Hypothesis to be Tested 
CESM is an emerging modality that is FDA approved for clinical use. It is possible that this functional test may 
someday replace breast MRI. While only small studies have been performed to date, one study has 
demonstrated similar cancer detection, sensitivity, and specificity for CESM compared with breast MRI (6).  
CESM could be an ideal screening examination for women with dense tissue.  
 
 
 
Study Design: Biomedical 
1.  Will controls be used? No 
 
2. What is the study design?  
a) Evaluate the patient experience during a screening CESM to better understand if women find the 
experience of contrast injection to be too invasive or unpleasant to repeat or recommend to a friend.  
(“Pre-CESM” and “Post CESM” Surveys) 

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3. 
Does the study involve a placebo? No 
Human Participants 
Ages: 40-69 
Sex: 
female 
Race: all 
 
Subjects- see below 
INSTRUCTIONS: For question 1-4 below insert an exact #.  Ranges or OPEN is not allowed.  This # 
should be the maximum # you expect to need to enroll (i.e. sign consent) If you are only collecting 
specimens the number of participants should equate to the # of specimens you need.  If you are 
collecting only data from a chart review the number should designate the number of subjects whose 
medical records you plan to review.  Age/ Sex/Race criteria should designate the demographics of 
participants from whom you will obtain the specimen/data. 
1.  Provide target # of subjects (at all sites) needed to complete protocol.  
 210 CESM procedures at the Breast Care Center.   
 
2.  Describe expected rate of screen failure/ dropouts/withdrawals from all sites.   
CESM rates will be negligible due to pre-screening and study procedure involving only one visit. 
 
3.  How many subjects will be enrolled at all sites?   210 for CESM at BCC;  
 
4.  How many subjects will sign a consent form under this UVa protocol?    210 for CESM  
 
5. Provide an estimated time line for the study. 
Total 22 months. Enrollment 18 months followed by completion and data analysis 
Inclusion/Exclusion Criteria 
1.  List the criteria for inclusion for CESM 
 Female 
 40 to 69 years 
 Previous normal mammogram (BI-RADS 1 or 2) showing heterogeneous or extremely dense 
breast tissue within last 24 months 
 Scheduled for screening mammogram as part of the patient's clinical care 
 
 
2.  List the criteria for exclusion for CESM 
 No mammogram within last 24 months 
 Fatty or scattered fibroglandular tissue on last mammogram 
 History of allergy to iodinated contrast 
 History of renal disease or renal function abnormalities  
 Pregnant women  
 History of diabetes 

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 History of paraproteinemia syndromes such as multiple myeloma 
 History of collagen vascular disease 
 History of vascular disease (coronary artery disease, myocardial infarction, carotid disease, peripheral 
vascular disease, or known visceral artery disease) 
 Previously identified as high risk for breast cancer (>20% lifetime risk) 
 Asthma 
 Sickle Cell Anemia 
 Currently on Dialysis 
 If patient is age 60-69 years we will need to confirm that kidney function is normal. We will draw a 
small volume of blood and check this, unless patient has had a lab test showing normal kidney function 
in the last 30 days as part of standard of care.  
 
 
4. List any restrictions on use of other drugs or treatments. none 
Statistical Considerations 
1. 
Is stratification/randomization involved? No 
 
2.  What are the statistical considerations for the protocol?  
There are no specific statistical considerations. We are only planning to evaluate women’s experience and 
willingness to undergo CESM in the screening setting.  However, it should be noted that if modifications are 
made to the general survey questionnaire (IRB Submission #11378) after the first 50 patients have completed 
the questionnaire.  
 
 
3.  Provide a justification for the sample size used in this protocol.   
 
We have funding for 210 screening CESM subjects. This should allow us to evaluate for general attitudes 
toward CESM as well as some sub-analyses related to factors such as age, and family history.  More 
specifically, we should be able to estimate the percentage of women who have a positive attitude toward 
CESM within ± 3.5 percentage units. This includes the worst case scenario in which the percentage is 50%, 
which is the scenario in which a binomial outcome variance is maximized.        
 
4.  What is your plan for primary variable analysis? 
 
 
 
 
1. To evaluate the patient experience during a screening CESM to better understand if women find the 
experience of contrast injection to be too invasive or unpleasant to repeat or recommend to a friend.   
 
 

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breast cancer screening and their experience before and after CESM 
 
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Data summarization: Pre and post CESM survey responses that are binary or Likert scaled responses will be 
summarized by frequencies and percentages.  Pre and post CESM survey responses that are continuous scaled 
responses will be summarized by the mean and standard deviation, the median and interquartile range, and 
the range of distribution.      
 
Statistical analyses: Pre CESM procedure survey information will be utilized to predict: (a) if patients who 
undergo CESM are willing to have repeat CESM, and (b) if patients who undergo CESM would recommend 
CESM to a friend.  Multivariate logistic regression will be used to predict these two outcomes.  In the former 
case (a), the outcome variable will indicate if the patient was willing to have a repeat CESM, and in the latter 
case (b), the outcome variable will indicate if the patient would recommend CESM to a friend.  The multivariate 
logistic regression model predictor variables will include age, level of education, and breast cancer related risk 
factor variables.  Type III Wald tests will be conducted to determine which predictor variables are uniquely 
associated with outcome.  A p≤0.05 null hypothesis rejection rule will be used as the bases for identifying s 
unique partial associations.         
5.  What is your plan for secondary variable analysis?  
      1.  We will evaluate differences by age, education, and risk factors as to whether these drive willingness to  
           undergo CESM.  
 
Data summarization: Binary risk factors will be summarized by frequencies and percentages.  Continuous 
scaled risk factors will be summarized by the mean and standard deviation, the median and interquartile 
range, and the range of distribution.    
 
Statistical analyses:  Multivariate logistic regression will be utilized to determine if there is an association 
between the willingness to undergo CESM and age, level of education, and breast cancer related risk factors.  
The outcome variable will be binary and the value 1 will be assigned if the patient is willing to undergo CESM 
and the value 0 will be assigned if the patient is unwilling to undergo CESM.  Predictor variables will include 
age, level or education, and breast cancer related risk factors.   Type III Wald tests will be conducted to 
determine which predictor variables are uniquely associated with outcome.  A p≤0.05 null hypothesis rejection 
rule will be used as the bases for identifying s unique partial associations.   
 
2. A secondary endpoint will evaluate differences in recall and PPV for biopsy recommendation compared 
to our practice norms for women with dense breasts during the same time interval.  
 
 
 
 
 
Data summarization:  Recall frequencies and positive predicted values (PPV) will be summarized in the 
traditional manner by frequencies and precentages for the former, and by percentages for the latter.  
 
Statistical analyses:  Recall fequences and PPV for biopsy recommendation will be compared between the 
two study-groups by way of exact binomal methods.  
 
6. Have you been working with a statistician in designing this protocol?yes 

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IF YES, what is their name?  James Patrie, Senior Biostatistician, Department of Public Health Sciences. 
7.  Will data from multiple sites be combined during analysis?  No 
 
Biomedical Research 
1.  What will be done in this protocol?    
 
 Women age 40-69 years of age scheduled to undergo a screening mammogram at any one of our 
screening sites (Northridge, Orange, Zion Crossroads) or the UVa Breast Care Center will have their 
previous mammgoram screened to see if there is evidence of heterogeneous or dense breast tissue 
(within 2 years). If so, the study nurse will contact the patient to see if they would like to participate in 
the CESM study.  All patients having a CESM will have an appointment scheduled at the Breast Care 
Center, where CESM will be performed.  
 
 In addition, study flyers approved by the IRB will be placed at UVa Imaging sites as well as primary care 
and gynecology offices.  
 
 All women will have a urine pregnancy test at the Breast Care Center unless there has been no 
menstual cycle for at least one year (postmenopausal) or history of hysterectomy.  
 
 CESM is a mammogram performed after the injection of contrast via IV. Two images are taken almost 
simultaneously during the exam after the contrast is administered. The first image is essentially a 
standard mammogram. The 2nd image shows areas that take up the contrast (enhance) signifying 
increased blood flow. CESM studies are performed at the UVa Breast Care Center in the West Complex. 
Contrast administration is given following the same protocol of IV iodinated contrast administration as 
for CT scans elsewhere in the UVa Health System. Radiologists and technologists  in the UVa Breast 
Care Center are trained in contrast administration and treatment of contrast reaction. Women having a 
CESM will have a 30 minute period post procedure to monitor for allergy to iodine contrast as per 
department SOP. 
 
 Per department protocol, women age 60-69 will have serum creatine/GFR within 30 days or will have 
the test done prior to the CESM exam. If blood needs to be drawn prior to exam a BCC nurse or 
research nurse will draw 1 green top tube and send this to the Radiology Nursing area in main hospital. 
The blood will be precessed for Creatinine and GFR on the I-STAT machine, results will be reported 
back to BCC.The standard mammogram portion of the CESM will be billed to the patients insurance as 
per standard of care. The administration of contrast and any cost related to the contrast enhanced 
portion of the CESM, will be paid for by the research study. 
 
 All patients will undergo written consent for study participation after discussion of potential risks and 
benefits.  
 

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 Subjects who agree to participate in the CESM part of the study will complete a short survey regarding 
their interest and concerns about CESM PRIOR to the examination (Pre CESM Survey).  
 
 The patient will then undergo CESM study which will serve as her annual breast imaging screening in 
place of annual screening mammogram.  
 
 Since this is a screening exam, the study will not be interpreted immediately by the radiologist.  
 
 Following the exam, the patient will be given a short survey (Post CESM Survey) that evaluates her 
experience during the CESM examination.  
 
2. List the procedures, in bullet form, that will be done for RESEARCH PURPOSES as stipulated in this 
protocol. 
 
 Contrast-enhanced Spectral Mammography (CESM) at Breast Care Center 
 CESM pre and post surveys for women having CESM procedure only 
 Urine pregnancy test for all pre-menopausal women having a CESM at the BCC. 
 
3. Will you be using data/specimens in this study that were collected previously, with the use of a research 
consent form, from another research study? No 
 
4.  Will any of the procedures listed in item # 2 have the potential to identify an incidental finding? This 
includes ALL procedures, assessments and evaluations that are being done for RESEARCH PURPOSES that 
may or may not be considered investigational.  
Yes. Although the anticipated enhancing lesions are expected to have a high incidence of carcinoma, benign 
lesions may enhance as well that would not be otherwise detected.  
_X__The examination(s) utilize(s) the same techniques, equipment, etc., that would be used if the 
subject were to have the examination(s) performed for clinical care.  There exists the potential for 
the discovery of clinically significant incidental findings.   
 The PI takes full responsibility for the identification of incidental findings:  
 The PI will inform the subjects verbally of all incidental findings that are of clinical 
significance or are of questionable significance.   
 A follow-up letter describing the finding should be provided to the subject with 
instructions to either show the letter to their PC or if the subject has no PCP, the subject 
should be instructed to make an appointment at UVa or at the Free Clinic.   
 
5.  Do any of the procedures listed above, under question # 2, utilize any imaging procedures for RESEARCH 
PURPOSES? Yes 
IF YES, list procedures:  CESM 
_x_This imaging research examination utilizes the same imaging techniques, equipment, scanning 
sequences that would be used if the subject were to have the imaging performed for clinical care.  
There exists the potential for the discovery of clinically significant incidental findings.   

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►If checked, answer the following:  
 
Will the images be read by a licensed radiologist and the reading placed in the subject’s 
medical record?  Yes 
 
 
6. Will you be using viable embryos? No 
7. Will you be using embryonic stem cells? No 
8.  Are any aspects of the study kept secret from the participants?  No 
9.  Is any deception used in the study?    No 
  
10. If this protocol involves study treatment, explain how a subject will be transitioned from study 
treatment when they have completed their participation in the study.  N/A 
 
11. Will your study involve measures (C-SSRS/BID/SCID etc.) used to assess for depression and/or suicidality 
for research purposes? No 
      
Data and Safety Monitoring Plan 
INSTRUCTIONS: 
If you have any questions completing this section call 243-9847 for assistance. 
A Sponsor is defined as entity that will receive data prior to publication. 
1.  Definition: 
1.1 How will you define adverse events (AE)) for this study?  
_x__An adverse event will be considered any undesirable sign, symptom or medical or 
psychological condition even if the event is not considered to be related to the investigational 
drug/device/intervention. Medical condition/diseases present before starting the investigational 
drug/intervention will be considered adverse events only if they worsen after starting study 
treatment/intervention.  An adverse event is also any undesirable and unintended effect of 
research occurring in human subjects as a result of the collection of identifiable private information 
under the research.  Adverse events also include any problems associated with the use of an 
investigational device that adversely affects the rights, safety or welfare of subject s. 
1.2 How will you define serious adverse events? 
_x__A serious adverse event will be considered any undesirable sign, symptom, or medical 
condition which is fatal, is life-threatening, requires or prolongs inpatient hospitalization, results 
in persistent or significant disability/incapacity, constitutes a congenital anomaly or birth 
defect, is medically significant and which the investigator regards as serious based on 
appropriate medical judgment. An important medical event is any AE that may not result in 
death, be life-threatening, or require hospitalization but may be considered an SAE when, 
based upon appropriate medical judgment, it may jeopardize the patient and may require 
medical or surgical intervention to prevent one of the outcomes listed in the definitions of SAEs.  

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1.3 What is the definition of an unanticipated problem?  
Do not change this answer 
An unanticipated problem is any event, experience that meets ALL 3 criteria below: 
 Is unexpected in terms of nature, severity or frequency given the research procedures that 
are described in the protocol-related documents AND in the characteristics of the subject 
population being studies 
 Related or possibly related to participation in research.  This means that there is a 
reasonable possibility that the incident may have been caused by the procedures involved 
in the research study. 
 The incident suggests that the research placed the subject or others at greater risk of harm 
than was previously known or recognized OR results in actual harm to the subject or others 
 
1.4 What are the definitions of a protocol violation and/or noncompliance?  
Do not change this answer 
A protocol violation is defined as any change, deviation, or departure from the study design or 
procedures of research project that is NOT approved by the IRB-HSR prior to its initiation or 
implementation.  Protocol violations may be major or minor violations.   
 
Noncompliance can be a protocol violation OR deviation from standard operating procedures, 
Good Clinical Practices (GCPs), federal, state or local regulations.   Noncompliance may be serious 
or continuing.  
Additional Information: see the IRB-HSR website at  
http://www.virginia.edu/vpr/irb/HSR_docs/Forms/Protocol_Violations_%20Enrollment_Exceptions
_Instructions.doc 
 
1.5 If pregnancy occurs how will this information be managed? 
 
x_ Other: Pregnancy status is determined prior to mammogram. Pregnancy excludes the subject 
from the study 
1.6 What is the definition of a Protocol Enrollment Exception?   
__x__NA- No outside sponsor 
 
1.7 What is the definition of a data breach? 
Do not change this answer 
A data breach is defined in the HITECH Act (43 USC 17932) as an unauthorized acquisition, access, 
or use of protected health information (PHI) that compromises the security or privacy of such 
information. 
Additional Information may be found on the IRB-HSR Website: Data Breach 
2.  Identified risks and plans to minimize risk 
 
2.1 What risks are expected due to the intervention in this protocol? 
 

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Expected Risks related to study 
participation. 
Frequency 
 
Radiation 
____Occurs frequently 
____Occurs infrequently 
_x__Occurs rarely 
____Frequency unknown 
Allergy to contrast : 
 
Mild reactions include: 
 
nausea and vomiting 
 
headache 
 
itching 
 
flushing 
 
mild skin rash or hives 
Moderate reactions include: 
 
severe skin rash or hives  
 
wheezing 
 
abnormal heart rhythms 
 
high or low blood pressure 
 
shortness of breath or difficulty 
breathing 
Severe reactions include: 
 
difficulty breathing 
 
cardiac arrest 
 
swelling of the throat or other 
parts of the body 
 
convulsions 
 
death 
profound low blood pressure 
____Occurs frequently 
____Occurs infrequently 
__X__Occurs rarely 
____Frequency unknown 
IV site infection 
 
____Occurs frequently 
____Occurs infrequently 
__X__Occurs rarely 
____Frequency unknown 
 
2.2   List by bullet format a summary of safety tests/procedures/observations to be performed that will 
minimize risks to participants:  Adequate screening 

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2.3 Under what criteria would an INDIVIDUAL SUBJECT’S study treatment or study participation be stopped 
or modified 
__x_At subject, PI or sponsor’s request 
2.4 Under what criteria would THE ENTIRE STUDY need to be stopped.   
INSTRUCTIONS; 
 These are called stopping rules for early termination of the entire study. 
 List criteria regardless of whether the study is sponsored or not.  
 Be sure to include any criteria for which the UVa PI would halt the study at UVa. 
 Check all that apply. 
_x__Per IRB, PI, DSMB 
 
2.5 What are the criteria for breaking the blind/mask? 
__x__NA – Not blinded/masked 
 
2.6 How will subject withdrawals/dropouts be reported to the IRB prior to study completion? 
__x__IRB-HSR continuation status form  
 
3.  Adverse Event / Unanticipated Problem Recording and Reporting 
 
3.1 Will all adverse events, as defined in section 1.1, be collected/recorded? NO 
►IF NO, what criteria will be used?  
 
_x__Only adverse events that are deemed related AND serious  
 
3.2 How will adverse event data be collected/recorded?  
__x__Spreadsheet: paper or electronic 
 
3.3. How will AEs be classified/graded?  
_x__Mild/Moderate/Severe 
_X_ Serious/Not serious Required for all protocols 
 
3.4 What scale will the PI use when evaluating the relatedness of adverse events to the study 
participation?   
 
_x_The PI will determine the relationship of adverse events to the study 
 using the following scale: 
 
Related:      
 
AE is clearly related to the intervention 
Possibly related: 
AE may be related to the intervention 
Unrelated:  
 
AE is clearly not related to intervention 
 

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3.5 When will recording/reporting of adverse events/unanticipated problems begin? 
 
___X__After subject begins study intervention  
 
 
3.6 When will the recording/reporting of adverse events/unanticipated problems end? 
_x__ End of study participation  
 
3.7 How will Adverse Events, Unanticipated Problems, Protocol Violations and Data Breaches be 
reported?  Complete the table below to answer this question 
 
Type of Event 
To whom will it 
be reported: 
Time Frame for 
Reporting 
How reported? 
Any internal event resulting 
in death that is deemed 
DEFINITELY related to (caused 
by) study participation 
An internal event is one that 
occurs in a subject enrolled in 
a UVa protocol 
IRB-HSR 
Within 24 hours 
IRB Online and phone call 
 
www.irb.virginia.edu/ 
 
Internal, Serious, RELATED, 
Unexpected adverse event  
 
  
IRB-HSR 
Within 7 calendar 
days from the 
time the study 
team received 
knowledge of the 
event. 
 
Timeline includes 
submission of 
signed hardcopy 
of AE form. 
IRB Online 
 
www.irb.virginia.edu/ 
 
Unanticipated Problems that 
are not adverse events or 
protocol violations  
This would include a Data 
Breach.   
IRB-HSR 
 
 
Within 7 calendar 
days from the 
time the study 
team received 
knowledge of the 
event.  
Unanticipated Problem report 
form.  
 
http://www.virginia.edu/vprgs
/irb/HSR_docs/Forms/Reportin
g_Requirements-
Unanticipated_Problems.doc ) 
Protocol 
Violations/Noncompliance 
The IRB-HSR only requires that 
MAJOR violation be reported, 
unless otherwise required by 
your sponsor, if applicable. 
 
OR 
 
Enrollment Exceptions 
See definition- only allowed if 
IRB-HSR 
 
 
Within 7 calendar 
days from the 
time the study 
team received 
knowledge of the 
event.  
 
Protocol Violation, 
Noncompliance and 
Enrollment Exception 
Reporting Form 
 
 
http://www.virginia.edu/vprgs
/irb/hsr_forms.html 
 
Go to 3rd bullet from the 
bottom. 

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there is a commercial sponsor 
or a DSMB that has granted 
the enrollment exception.  
  
Data Breach  
The UVa 
Corporate 
Compliance and 
Privacy Office 
 
 
 
ITC:  if breach 
involves  
electronic data  
 
 
 
 
Police if breach 
includes items 
that are stolen: 
 
Stolen on UVA 
Grounds 
 
OR  
 
Stolen off UVa 
Grounds- contact 
police 
department of 
jurisdiction of last 
known location of 
PHI 
As soon as 
possible and no 
later than 24 
hours from the 
time the incident 
is identified. 
 
As soon as 
possible and no 
later than 24 
hours from the 
time the incident 
is identified. 
 
IMMEDIATELY.  
 
 
UVa Corporate Compliance and 
Privacy Office- Phone 924-9741 
 
 
 
 
ITC:  Information Security 
Incident Reporting procedure,  
http://www.itc.virginia.edu/se
curity/reporting.html 
 
 
 
 
 
 
 
 
UVa Police-Phone- (434) 924-
7166 
  
4.    How will the endpoint data be collected/recorded. Check all that apply 
__x__Source documents 
5. Data and Safety Oversight Responsibility 
 
5.1. Who is responsible for overseeing safety data for this study?  
 
_x__No additional oversight body other than PI at UVa Skip question 5.2 
 
5.2. What is the composition of the reviewing body and how is it affiliated with the sponsor? n/a   

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5.3. What items will be included in the aggregate review conducted by the PI?  
 
__x_All adverse events 
_____Unanticipated Problems 
_____Protocol violations/Issues of noncompliance 
_____Audit results 
_____Application of dose finding escalation/de-escalation rules  
These should be outlined under 2.4. 
_____Application of study designed stopping/decision rules 
_____Early withdrawals 
_____Whether the study accrual pattern warrants continuation/action 
_____Endpoint data 
 
5.4 How often will aggregate review occur? 
For additional information on aggregate review see: 
www.virginia.edu/vpr/irb/hsr/continuations.html#aggreview 
_x___Annually 
 
5.5. How often will a report, regarding the outcome of the review by the DSMB/DSMC, be sent to the 
UVa PI? n/a 
 
5.6. How will a report of the information discussed in question 5.4 OR 5.5 be submitted to the IRB?   
 
_x__Part of IRB-HSR continuation status form 
Risk/ Benefit Analysis 
1.  What are the potential benefits for the participant as well as benefits which may accrue to society in 
general, as a result of this study? 
CESM may be an ideal tool for screening women with dense breast tissue compared with screening US, which 
is currently associated with low specificity and high downstream costs due to unnecessary biopsies. However, 
there is low utilization of CESM in the screening role. This study will help identify women’s attitudes towards 
CESM as a screening tool.  
 
2.  Do the anticipated benefits justify asking subjects to undertake the risks?   
Yes. CESM is an FDA approved breast imaging study with extremely low risks. This test could potentially be 
used broadly in society for screening women with dense breasts, but we need to better understand the 
barriers to doing so.  

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Bibliography 
1.     Boyd NF, Guo H, Martin LJ, et al. Mammographic Density and the Risk and Detection of Breast 
Cancer. N Engl J Med 2007;356(3):227-236. 
2.     Sprague BL, Gangnon RE, Burt V, et al. Prevalence of mammographically dense breasts in the 
United States. J Natl Cancer Inst 2014;106(10):10.1093/jnci/dju255. Print 2014 Oct. 
3.     Weigert JM, Bertrand ML, Lanzkowsky L, Stern LH, Kieper DA. Results of a Multicenter Patient 
Registry to Determine the Clinical Impact of Breast-Specific Gamma Imaging, a Molecular Breast Imaging 
Technique. Am J Roentgenol 2012;198(1):W69-W75. 
4.     Hooley RJ, Greenberg KL, Stackhouse RM, Geisel JL, Butler RS, Philpotts LE. Screening US in 
Patients with Mammographically Dense Breasts: Initial Experience with Connecticut Public Act 09-41. 
Radiology 2012 
5.     Berg WA, Blume JD, Cormack JB, et al. Combined Screening With Ultrasound and Mammography 
vs Mammography Alone in Women at Elevated Risk of Breast Cancer. JAMA 2008;299(18):2151-2163. 
6.     Fallenberg EM, Dromain C, Diekmann F, et al. Contrast-enhanced spectral mammography: Does 
mammography provide additional clinical benefits or can some radiation exposure be avoided? Breast Cancer 
Res Treat 2014;146(2):371-381. 
 
APPENDIX:  Legal/Regulatory 
Recruitment 
The following procedures will be followed: 
 Finders fees will not be paid to an individual as they are not allowed by UVa Policy. 
 All recruitment materials will be approved by the IRB-HSR prior to use.  They will be submitted to 
the IRB after the IRB-HSR has assigned an IRB-HSR # to the protocol. 
 Only those individuals listed as personnel on this protocol will recruit and or conduct the 
consenting process with potential subjects.  
 
Retention Incentives 
Any item used by the sponsor/ study team to provide incentive to a subject to remain in the study, other than 
compensation identified in the Payment section, will be submitted to the IRB for review prior to use.  The IRB-
HSR will provide the study team with a Receipt Acknowledgement for their records.  Retention incentive items 
are such things as water bottles, small tote bags, birthday cards etc.  Cash and gift cards are not allowed as 
retention incentives.  
 
Clinical Privileges 
The following procedures will be followed:  
 Investigators who are members of the clinical staff at the University of Virginia Medical Center must 
have the appropriate credentials and been granted clinical privileges to perform specific clinical 
procedures whether those procedures are experimental or standard.  
 The IRB cannot grant clinical privileges.   
 Performing procedures which are outside the scope of the clinical privileges that have been granted 
may result in denial of insurance coverage should claims of negligence or malpractice arise. 
 Personnel on this protocol will have the appropriate credentials and clinical privileges in place before 
performing any procedures required by this protocol.  

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 Contact the Clinical Staff Office- 924-9055 or 924-8778 for further information. 
 
Sharing of Data/Specimens 
Data and specimens collected under an IRB approved protocol are the property of the University of Virginia.  
You must have “permission” to share data/ specimens outside of UVa other than for a grant application and or 
publication.  This “permission” may come in the form of a contract with the sponsor or a material transfer 
agreement (MTA) with others.  A contract/ MTA is needed to share the data outside of UVa even if the data 
includes no HIPAA identifiers and no code that could link the data back to a HIPAA identifier.   
 No data will be shared outside of UVa, beyond using data for a grant application and or publication, 
without a signed contract/MTA approved by the SOM Grants and Contracts office/ OSP or written 
confirmation that one is not needed. 
 No specimens will be shared outside of UVa without a signed contract/MTA approved by the SOM 
Grants and Contracts office/ OSP or written confirmation that one is not needed. 
 
Prisoners 
If the original protocol/ IRB application stated that no prisoners would be enrolled in this study and 
subsequently a subject becomes a prisoner, the study team must notify the IRB immediately.  The study team 
and IRB will need to determine if the subject will remain in the study.  If the subject will remain in the study, 
the protocol will have to be re-reviewed with the input of a prisoner advocate.  The prisoner advocate will also 
have to be involved in the review of future continuations, modifications or any other reporting such as 
protocol violations or adverse events.   
 
Prisoner- Individuals are prisoners if they are in any kind of penal institution, such as a prison, jail, or juvenile 
offender facility, and their ability to leave the institution is restricted. Prisoners may be convicted felons, or 
may be untried persons who are detained pending judicial action, for example, arraignment or trial. 
For additional information see the OHRP website at  http://www.hhs.gov/ohrp/policy/populations/index.html 
 
Compensation in Case of Injury  
If a subject requests compensation for an injury, the study team should notify the IRB-HSR (924-
9634/2439847) the UVa Health System Patient Relations Department (924-8315).  As a proactive courtesy, the 
study team may also notify UVa Health System Patient Safety and Risk Management (924-5595). 
 
On request, the study team should provide  the Risk Management Office with the following 
information/documents: 
 Subject Name and Medical Record Number 
 Research medical records 
 Research consent form 
 Adverse event report to IRB 
 Any letter from IRB to OHRP 
 
Subject Complaints  

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During a research study, the study team may receive complaints from a subject.  If the study team is uncertain 
how to respond to a complaint, or is unable to resolve it with the subject, the study team may contact the IRB-
HSR (924-9634/243-9847), the UVa Health System Patient Relations Department (924-8315). 
 
Request for Research Records from Search Warrant or Subpoena 
If the study team receives a request for research records from a search warrant or subpoena, they should 
notify UVa Health Information Services at 924-5136. It is important to notify them if information from the 
study is protected by a Certificate of Confidentiality.   
 
 
 
APPENDIX:  Recruitment 
Recruitment includes identifying, review of records to determine eligibility or any contact to determine a 
potential subjects interest in the study. 
 
*The UVa HIPAA covered entity is composed of the  UVa VP Office of Research, the Health System, School of 
Medicine, School of Nursing, Nutrition Services (Morrisons), the Sheila C. Johnson Center, the Exercise and 
Sports Injury Laboratory and the Exercise Physiology Laboratory.   
 
1. How do you plan to identify potential subjects? 
 To "identify" a potential subject refers to steps you plan to take to determine which individuals 
would qualify to participate in your study. This does NOT include steps to actually contact those 
individuals. 
 If your study involves more than one group of subjects (e.g. controls and cases or subjects and 
caregivers) note below which groups are being identified by the given method.  
 Check the methods you plan to utilize: 
 
a._x_ Chart Review/ Clinic Schedule Review/ Database Review from a database established for 
health care operations (departmental clinical database) or an Improvement Project (e.g.  
Performance Improvement, Practice Improvement, Quality Improvement).   
 
If you plan to obtain data from the UVa Enterprise Data Warehouse (EDW) please see option b 
below.   
 
DHHS: Study team requests Waiver of Consent to identify potential subjects.  
 
HIPAA: Allowed under Preparatory to Research if PHI to be accessed.  
 
IMPORTANT 
Keep in mind that PHI in the medical record may only be accessed by individuals who 
work under the UVa HIPAA covered entity; which means they meet one of the following 
criteria: 
--a UVa student working in the UVa HIPAA Covered Entity*   

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--a faculty or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
b____ Review of a database that was established to keep data to be used for future 
research such as the CDR, departmental research database or use of data from a separate 
current active research protocol.     
If you plan to obtain data from the UVa Enterprise Data Warehouse (EDW) you are required 
to submit your request to the CDR.  The CDR staff will work with the EDW to obtain the data 
you need.   
DHHS: Study team requests Waiver of Consent to identify potential subjects. 
 
HIPAA: Allowed under Preparatory to Research if PHI to be accessed.  
 
IMPORTANT 
Keep in mind that PHI in the medical record may only be accessed by individuals who 
work under the UVa HIPAA covered entity; which means they who meet one of the 
following criteria: 
--a UVa student working in the UVa HIPAA Covered Entity*   
--a faculty  or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
The information from which you are obtaining potential subjects must also have an IRB 
protocol approval.  If this item is checked, enter the IRB # below.  
 
IRB# ________________ 
If obtaining information from the Clinical Data Repository (CDR) insert IRB # 10797 
 
c. ____ Patients UVa health care provider supplies the UVa study team with the patients 
contact information without patients’ knowledge. 
 
DHHS: Study team requests Waiver of Consent to identify potential subjects.  
 
HIPAA: Allowed under Preparatory to Research if PHI will be shared by the health care 
provider.  
 
IMPORTANT 
Keep in mind that PHI may only be given to individuals who work under the UVa HIPAA 
covered entity; which means they meet one of the following criteria: 
--a UVa student working in the UVa HIPAA Covered Entity*   
--a faculty or staff member in a PAID appointment in the UVA HIPAA Covered Entity* 
 
d. _x_ Patient obtains information about the study from their health care provider.  The 
patient contacts the study team if interested in participating. (Health care provider may 
or may not also be the a member of the study team) 

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DHHS:  NA 
HIPAA:  Allowed under Health Care Operations 
 
If this choice is checked, check 3d-INDIRECT CONTACT below.  
 
e. __ Potential subjects will not be directly identified. They will respond to an 
advertisement such as a flyer, brochure etc.   
If this choice is checked, check 3d- INDIRECT CONTACT below.  
DHHS & HIPAA:  NA 
 
f. _____ Potential subjects have previously signed a consent to have their name in a 
registry/database to be contacted for future studies of this type.   
IRB#  of registry/ database:  ________________ 
DHHS & HIPAA:  NA 
 
If item # a, b or c is checked above and if this protocol involves the use of protected health 
information do you confirm the following to be true? yes 
 The use or disclosure is sought solely to review protected health information as 
necessary to prepare the research protocol or other similar preparatory purposes. 
 No PHI will be removed from the UVa covered entity. 
 The PHI that the researcher seeks to use or access is necessary for the research 
purposes. 
 
2. How will potential subjects be contacted? 
To "contact" a potential subjects refers to the initial contact you plan to take to reach a potential 
subject to determine if they would be interested in participating in your study.  This may include 
direct contact by such methods as by letter, phone, email or in-person or indirect contact such as 
the use of flyers, radio ads etc.  
 
If your study involves more than one group of subjects (e.g. controls and cases or subjects and 
caregivers) note below which groups are being contacted by the given method.    
 
Check the methods below you plan to utilize: 
aXDirect contact of potential subjects by the study team via letter, phone, direct e-mail. 
Members of study team ARE NOT health care providers of patients.  Information will not 
be collected from psychotherapy notes.  
Note:  Letter, phone, direct email scripts must be approved by IRB prior to use.  
See IRB-HSR Website for templates. 
 
DHHS/HIPAA: Study team requests a Waiver of Consent and Waiver of HIPAA 
Authorization to contact potential subjects.  
 
IMPORTANT:   

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Keep in mind that if PHI was collected during the identification phase that 
contact with potential subjects may only be performed by individuals who work 
under the UVa HIPAA covered entity; which means they meet one of the 
following criteria: 
 a UVa student working in the UVa HIPAA Covered Entity*   
 a faculty  or staff member in a PAID appointment in  the UVA HIPAA Covered 
Entity* 
 
b.____Potential subjects will be approached while at UVa Hospital or Health Clinic by a 
person who is NOT a member of their health care team.  Information will not be 
collected from psychotherapy notes.  
DHHS & HIPAA: Study team requests a Waiver of Consent and a Waiver of HIPAA 
Authorization to contact potential subjects.  
 
IMPORTANT:   
Keep in mind that contacting individuals in a clinical setting may only be performed by 
individuals who work under the UVa HIPAA covered entity; which means they  meet one 
of the following criteria: 
a UVa student working in the UVa HIPAA Covered Entity*   
a faculty  or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
You should share the following information with the potential subject:  
 Your name 
 Who you are:  physician, nurse etc. at the University of Virginia.    
 Why you want to speak with them 
 Ask if you have their permission to explain the study to them 
 If asked about how you obtained their information use one of the following as an 
option for response.     
o DO NOT USE THIS RESPONSE UNLESS YOU HAVE OBTAINED PERMISSION 
FROM THEIR UVa PHYSICIAN:  Your doctor, Dr. insert name wanted you 
to be aware of this research study and gave us permission to contact you.    
o We obtained your information from your medical records at UVa.   
o Federal regulations allow the UVa Health System to release your 
information to researchers at UVa, so that we may contact you regarding 
studies you may be interested in participating.  We want to assure you 
that we will keep your information confidential.  
 IF THE PERSON SEEMS ANGRY, HESITANT OR UPSET, THANK THEM FOR THEIR 
TIME AND DO NOT ENROLL THEM IN THE STUDY.  YOU MAY ALSO REFER THEM 
TO THE IRB-HSR AT 924-9634. 
 

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c._ X_Direct contact of potential subjects by the study team by approaching in person at 
UVa or via letter, phone, direct e-mail. Members of study team contacting potential 
subjects ARE health care providers of patients.  
If you are not approaching them in person but using a letter, phone call or direct email 
please note that the letter, phone, direct email scripts must be approved by IRB prior to 
use.   
See IRB-HSR Website for templates. 
 
DHHS:  Study team requests a Waiver of Consent to contact potential subjects 
HIPAA:  Allowed under Health Care Operations.  
 
d._x_ Indirect contact (flyer, brochure, TV, broadcast emails, patient provided info about 
the study from their health care provider and either the patient contacts study team or 
gives their healthcare provider permission for the study team to contact them.) 
The indirect method used (flyer, brochure, TV, broadcast emails) must be approved by 
the IRB prior to use.    The IRB does not need to review any type of script to use when 
the potential subject responds to the indirect method.   
 
DHHS & HIPAA:  NA 
 
 
e. ____  Potential subjects are not patients.  The study does not include obtaining 
subjects health information.   Subjects will be contacted directly via email, phone, 
letter or presentation in group setting with consent then obtained individually in a 
private setting.  
If you are not approaching them in person but using a letter, phone call or direct 
email please note that the letter, phone, direct email scripts must be approved by 
IRB prior to use.   
See IRB-HSR Website for templates. 
 
DHHS: Study team requests a Waiver of Consent to contact potential subjects.  
HIPPA:  NA 
 
3. Will any additional information be obtained from a potential subject during "prescreening"?   
Possibly pre-screening of potential subjects over the telephone or in person to determine their 
initial eligibility and/or interest in this study. 
 
IF YES, submit any documents that will be used to collect pre-screening information so that the IRB 
may confirm what questions will be asked. 
NOTE: To comply with HIPAA regulations only the minimum necessary information may be 
collected at this time.  This means that only questions pertaining to the Inclusion and Exclusion 
Criteria may be asked.   
 

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IF YES, 
DHHS:   study team requests a Waiver of Documentation of Consent for Pre-screening questions.  
 
HIPPA: 
HIPAA does not apply if: 
--no PHI is collected or 
--if PHI is collected from a potential subject  by an individual from a department that is not part of 
the HIPAA covered entity. 
 
HIPAA does apply if the collection occurs by individuals* who work in a department that is part of 
the HIPAA covered entity.   
 
In this case the collection will be covered under Health Care Operations/ 
 
These individuals are those that meet one of the following criteria:  
--a UVa student working in the UVa HIPAA Covered Entity*   
--a faculty  or staff member in a PAID appointment in  the UVA HIPAA Covered Entity* 
 
IF YES, Will any of the questions involve health information?yes 
 
IF YES, will you collect HIPAA identifiers with the health information? yes 
 
IF YES, which HIPAA identifiers will be recorded?MRN, name, age, email 
 
Do you confirm that health information with HIPAA identifiers will not be shared 
outside of UVa until a consent form is signed or only shared in a de-identified manner?  
yes 
 
4. Do you plan to ask the subjects to do anything, other than answering questions, for the study 
prior to signing a consent? No 
 
5. How will the consenting process take place with either the prospective subject, the subject’s 
legally authorized representative or parent/legal guardian of a minor ( if applicable)?    
HIPPA:  
If the individual, obtaining consent, works under the HIPAA Covered Entity consenting is 
covered under Health Care Operations. 
 
If the individual obtaining consent does not work under the HIPAA covered entity, HIPAA does 
not apply.  
 
The potential subject will be interviewed in a quiet and private place and may have family or 
friends with them if they choose.  If there is concern that the potential subject may not be able 
to read the potential subject will be asked to read the first sentence of the consent form to 

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determine if they are capable of reading. Depending on the response they will either be offered 
the opportunity to read the consent form or have the consent form read to them.  Once the 
consent has been read the person obtaining consent will summarize the consent form verbally, 
asking open ended questions to determine if the potential subject understands what is being 
covered in the consent form 
Potential subjects will be given an opportunity to ask questions.  Their level of understanding 
will dictate how much time will be spent covering each item.  Once all of their questions have 
been answered, if they decide to participate, they will be asked to sign the consent form.  The 
person obtaining consent will sign the form and subjects will be given a copy of the signed 
consent form. Study procedures will then begin.  The informed consent process for each 
individual subject will be documented in the subject’s medical record. 
 
6. Will subjects sign a consent form for any part of the study? yes 
 
7.  Will the study procedures be started the same day the subject is recruited for the study? Possibly, 
as an appointment will be made for the CESM and patient will sign consent before procedure and on 
day of procedure or they may go through the consent process prior to day of CESM procedure. 
 
8.  Is there the potential to recruit economically or educationally disadvantaged subjects, or other 
vulnerable subjects such as students or employees? yes 
 
IF YES, what protections are in place to protect the rights and welfare of these subjects so 
that any possible coercion or undue influence is eliminated?   
There are students, employees, and economically and educationally disadvantaged people 
among the patient population at the UVA Health System. We will ask questions to ensure all 
participants, especially those who are more vulnerable, understand their participation is 
completely voluntary 
 
9. Do you need to perform a “dry run” of any procedure outlined in this protocol?   No 
 
 
Privacy Plan 
 
The following procedures must be followed.  
 The data will be secured per the Data Security Plan of this protocol. 
 Only investigators for this study and clinicians caring for the patient will have access to data.  They will each 
use a unique login ID and password that will keep confidential.   The password should meet or exceed the 
standards described on the Information Technology Services (ITS) webpage about The Importance of 
Choosing Strong Passwords. 
 Each investigator will sign the University’s Electronic Access Agreement forward the signed agreement to the 
appropriate department as instructed on the form. 
If you currently have access to clinical data it is likely that you have already signed this form.  You are not 
required to sign it again.  

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 UVa University  Data Protection Standards will be followed 
http://www.virginia.edu/informationsecurity/dataprotection.   
 If identifiable data is transferred to any other location such as a desktop, laptop, memory stick, CD etc. the 
researcher must follow the University’s  “Electronic Storage of Highly Sensitive Data Policy”. Additional 
requirements may be found in the University's Requirements for Securing Electronic Devices.  
 If identifiable data is taken away from the UVa Health System, Medical Center Policy # 0218 will be 
followed.  
 Data will be securely removed from the server/drive, additional computer(s), and electronic media 
according to the University's Electronic Data Removal Policy.  
 Data will be encrypted or removed if the electronic device is sent outside of UVa for repair according to 
the University's Electronic Data Removal Policy. 
 If PHI will be faxed, researchers will follow the Health System Policy # 0194.     
 If PHI will be emailed, researchers will follow the Health System Policy # 0193 and University Data 
Protection Standards . 
 Data may not be analyzed for any other study without additional IRB approval.  
 If you are using patient information you must follow Health System Policy  # 0021. 
 Both data on paper and stored electronically will follow the University's Record Management policy and 
the Commonwealth statute regarding the Destruction of Public Records. 
Summary of Requirements to Comply with UVa Health System, Medical Center and University Policies and 
Guidance as noted above: 
Highly Sensitive Data is: 
-personal information that can lead to identity theft if exposed or 
-data that reveals an individual’s health condition and/or history of health services use.  
Protected Data (PHI) a type of Highly Sensitive Data, is data combined with a HIPAA identifier  
Identifiable Data under HIPAA regulations is considered to be Highly Sensitive Data at UVa. 
A Limited Data Set (LDS) under HIPAA regulations is considered to be Moderately Sensitive Data at UVa. The only 
HIPAA identifiers associated with data: dates and or postal address information limited to town or city, state, and 
zip code.   
Will not include subjects age if older than 89 or subjects DOB if older than 89.   

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Highly Sensitive Data 
(Identifiable Health Info per HIPAA )  
Moderately Sensitive Data  
(Limited Data Set and De-identified data per 
HIPAA) 
General Issues  
General Issues 
Discussions in private 
Do not share with those not on the study team or 
those who do not have a need to know. 
 
Do not share with those not on the study team or 
those who do not have a need to know 
Password protect  
Password protect 
Physically secure (lock) hard copies at all times if not 
directly supervised.  
If not supervised hard copies must have double 
protection (e.g. lock on room OR cabinet AND in 
building requiring swipe card for entrance).    
 
Physically secure (lock) hard copies at all times if 
not directly supervised.   
For electronic documents turn off File Sharing; turn 
on firewalls; use up to date antivirus and 
antispyware; delete data securely. 
 
For electronic documents turn off File Sharing; turn 
on firewalls; use up to date antivirus and 
antispyware; delete data securely. 
 
Encrypt 
See Encryption Solutions Guidance  
Files on Health System Network drives are 
automatically encrypted.  If not stored there it is study 
teams responsibility to make sure data are encrypted. 
 
If device sent out for service or repair, encrypt or 
remove data AND contract for repair using a UVa 
Purchase order. 
If device sent out for service or repair, encrypt or 
remove data AND contract for repair using a UVa 
Purchase order. 
Store files on a network drive specifically designated 
for storing this type of data, e.g. high-level security 
server/drives managed by Information Technology 
Services or the “F” and “O” managed by Heath 
Systems Computing Services.  You may access it via a 
shortcut icon on your desktop, but you are not 
allowed to take it off line to a local drive such as the 
desktop of your computer (e.g. C drive) or to an 
individual  Use Device*.  May access via VPN 
 
Do not share with sponsor or other outside group 
before consent is obtained or the IRB has granted 
appropriate approvals and contract/ MTA is in place  
Do not share with sponsor or other outside group 
before consent is obtained or the IRB has granted 
appropriate approvals and contract/ MTA is in 
place 
If collected without consent/ HIPAA authorization 
will NOT be allowed to leave UVa HIPAA covered 
entity unless disclosure is approved by the IRB and 
the disclosure is tracked in EPIC  
If collected without consent/ HIPAA authorization 
will NOT be allowed to leave UVa HIPAA covered 
entity unless disclosure is approved by the IRB and 
an MTA is in place prior to sharing of data 

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Highly Sensitive Data 
(Identifiable Health Info per HIPAA )  
Moderately Sensitive Data  
(Limited Data Set and De-identified data per HIPAA) 
Electronic Data Collection & Sharing  
Electronic Data Collection & Sharing 
(e.g. smart phone app, electronic consent using 
tablet etc.) 
MUST consult with ISPRO or Health System Web 
Development Office: 434-243-6702 
 University Side:    IT-
Security@virginia.edu  
 Health System: Web Development Center:   
 
Individual-Use Device  
Individual-Use Device 
Do not save to individual-use device* without 
written approval of your Department AND VP  
or Dean.   
If approval obtained, data must be password  
protected and encrypted. 
 
Do not save an email attachment containing 
HSD to an individual use device  
( e.g. smart phone)  
 
E Mail 
E Mail 
Do not share via email with Outlook Web/ or 
forward email using other email vendors like 
Gmail/ Yahoo  
 
Do not send via email on smart phone unless 
phone is set up by Health System  
 
Email may include name, medical record 
number or Social Security number only if 
sending email to or from a person with * HS in 
their email address. 
NOTE: VPR & IRB staff do not meet this criteria!  
In addition to sharing LDS, may include initials if 
persons sending and receiving email work within the 
UVa HIPAA covered entity.** 
FAX 
FAX 
Verify FAX number before faxing 
Verify FAX number before faxing 
Use Fax Cover Sheet with Confidentiality 
Statement 
Use Fax Cover Sheet with Confidentiality Statement 
Verify receiving fax machine is in a restricted 
access area 
Verify receiving fax machine is in a restricted access 
area 
Verify intended recipient is clearly indicated 
Verify intended recipient is clearly indicated 
Recipient is alerted to the pending transmission 
and is available to pick it up immediately 
Recipient is alerted to the pending transmission and 
is available to pick it up immediately 

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Highly Sensitive Data 
(Identifiable Health Info per HIPAA )  
Moderately Sensitive Data  
(Limited Data Set and De-identified data per HIPAA) 
Electronic Data Collection & Sharing  
Electronic Data Collection & Sharing 
(e.g. smart phone app, electronic consent 
using tablet etc.) 
MUST consult with ISPRO or Health System 
Web Development Office: 434-243-6702 
 University Side:    IT-
Security@virginia.edu  
 Health System: Web Development Center:   
 
Individual-Use Device  
Individual-Use Device 
Do not save to individual-use device* without 
written approval of your Department AND VP  
or Dean.   
If approval obtained, data must be password  
protected and encrypted. 
 
Do not save an email attachment containing 
HSD to an individual use device  
( e.g. smart phone)  
 
E Mail 
E Mail 
Do not share via email with Outlook Web/ or 
forward email using other email vendors like 
Gmail/ Yahoo  
 
Do not send via email on smart phone unless 
phone is set up by Health System  
 
Email may include name, medical record 
number or Social Security number only if 
sending email to or from a person with * HS in 
their email address. 
NOTE: VPR & IRB staff do not meet this 
criteria!  
In addition to sharing LDS, may include initials if 
persons sending and receiving email work within the 
UVa HIPAA covered entity.** 
FAX 
FAX 
Verify FAX number before faxing 
Verify FAX number before faxing 
Use Fax Cover Sheet with Confidentiality 
Statement 
Use Fax Cover Sheet with Confidentiality Statement 
Verify receiving fax machine is in a restricted 
access area 
Verify receiving fax machine is in a restricted access 
area 
Verify intended recipient is clearly indicated 
Verify intended recipient is clearly indicated 
Recipient is alerted to the pending 
Recipient is alerted to the pending transmission and 

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*  Individual Use Device – examples include smart phone, CD, flash (thumb) drive, laptop, C drive of your 
computer,  
**The UVa HIPAA covered entity is composed of the UVa VP Office of Research, the Health System, School of 
Medicine, School of Nursing, Nutrition Services (Morrison’s), the Sheila C. Johnson Center, the Exercise and 
Sports Injury Laboratory and the Exercise Physiology Laboratory.   
 
transmission and is available to pick it up 
immediately 
is available to pick it up immediately 
Highly Sensitive Data 
(Identifiable Health Info per HIPAA )  
Moderately Sensitive Data  
(Limited Data Set and De-identified data per HIPAA) 
Electronic Data Collection & Sharing 
Electronic Data Collection & Sharing 
(e.g. smart phone app, electronic consent 
using tablet etc.) 
MUST consult with ISPRO or Health System 
Web Development Office: 434-243-6702 
University Side:    IT-Security@virginia.edu  
Health System: Web Development Center:   
Contract must include required security 
measures.  
 
May NOT be stored in places like UVaBox, 
UVaCollab, QuestionPro.  
May also NOT be stored in non-UVa licensed 
cloud providers, such as Dropbox, Google 
Drive, SkyDrive, Survey Monkey, etc.  
May be stored in places like UVaBox, UVaCollab, 
QuestionPro.   
May NOT be stored in non-UVa licensed cloud 
providers, such as Dropbox, Google Drive, SkyDrive, 
Survey Monkey, etc.  
LOST OR STOLEN:  
LOST OR STOLEN: 
Must report in accordance with protocol/ in 
accordance with the Information Security 
Incident Reporting Policy. 
 
Any data breach will also be reported to the 
IRB of Record if the report meets the criteria 
of an Unanticipated Problem.   
Must report in accordance with protocol/ in 
accordance with the Information Security Incident 
Reporting Policy. 
 
Any data breach will also be reported to the IRB of 
Record if the report meets the criteria of an 
Unanticipated Problem.