Psychosocial, Behavioral, and Radiologic Changes Following Neurologic Events or Interventions: A Prospective, Non-Interventional, Observational Study
Conditions: Obsessive-Compulsive Disorder, Pain, Intractable, Depression
Sponsor: Vanderbilt University Medical Center

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Psychosocial, Behavioral, and Radiologic Changes following Neurologic 
Events or Interventions: A Prospective, Non-Interventional, Observational 
Study 
 
 
Principal Investigator 
 
Mohamed Khattab, MD 
mohamed.khattab@vumc.org 
The Vanderbilt Clinic 
2220 Pierce Avenue, B1003 PRB 
Nashville, TN 37232-5671 
 
Senior Co-Investigator 
Anthony Cmelak, MD 
The Vanderbilt Clinic 
2220 Pierce Avenue, B1003 PRB 
Nashville, TN 37232-5671 
 
 
Research Coordinator 
Alexander Sherry, BS 
The Vanderbilt Clinic 
2220 Pierce Avenue, B1003 PRB 
Nashville, TN 37232-5671 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
1. 
NAME AND ADDRESS OF Investigator ......................................................................................... 3 
2. 
Background ......................................................................................................................................... 3 
2.1 
Functional Neurologic Imaging following Interventions or Underlying Disease ......................... 3 
3.  Protocol .................................................................................................................................................. 3 
3.1. Purpose ............................................................................................................................................... 3 
3.1.1 Study Objective ............................................................................................................................ 4 
3.2. Protocol ............................................................................................................................................... 4 
3.2.1 Synopsis ........................................................................................................................................ 4 
3.2.2 Study Design ................................................................................................................................. 4 
3.2.3 Participant Selection ..................................................................................................................... 4 
3.2.4 Study Procedures .......................................................................................................................... 5 
3.2.5 Data Analysis .................................................................................................................................... 8 
3.2.6 Adverse Events ................................................................................................................................. 8 
3.2.6.1 Definitions ................................................................................................................................. 9 
3.2.6.2 Protocol Deviations ................................................................................................................. 10 
3.2.6.3 Investigator Responsibilities .................................................................................................... 10 
3.3 References .......................................................................................................................................... 10 
4.RISKS .................................................................................................................................................... 11 
5. MONITORING PROCEDURES.......................................................................................................... 12 
6. 
ADDITIONAL RECORDS AND REPORTS .................................................................................. 12 
 
 
 

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1. NAME AND ADDRESS OF Investigator 
 
Mohamed Khattab, MD 
Vanderbilt University Medical Center 
The Vanderbilt Clinic 
2220 Pierce Avenue, B1003 PRB 
Nashville, TN 37232-5671 
 
mohamed.khattab@vumc.org  
 
2. Background 
 
2.1 
Functional Neurologic Imaging following Interventions or Underlying Disease 
 
Functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTI) have rapidly 
expanded since its emergence two decades ago. fMRI is well established as the single most powerful 
method for detecting changes in neural activity in vivo, albeit indirectly by detection of changes in blood 
oxygenation level dependent (BOLD) signals that reflect hemodynamic changes subsequent to neural 
activity. A conventional fMRI experiment involves the comparison of two or more brain states followed 
by statistical tests to identify which brain regions were involved in a particular task. The identification of 
patterns of highly correlated low-frequency MRI signals in the resting brain provides a powerful approach 
to delineate and describe neural circuits, and an unprecedented ability to assess the manner in which 
distributed regions work together to achieve specific functions. Since the first reports of temporal 
correlations in BOLD baseline signals, several distinct cortical long-range networks have been identified 
and characterized in the resting state, including a default mode network. Moreover, observations of 
altered resting state connectivity in several disorders and as a function of behavior or cognitive skills 
suggest these correlations reflect an important level of brain organization and may play a fundamental 
role in the execution and maintenance of various brain functions. DTI is also an exceedingly important 
imaging modality that has elucidated the neural connectivity inherent between various cortical and 
subcortical structures. DTI is routinely used and has enhanced our understanding of functional 
connections between various parts of the brain. Prior to interventions, DTI is commonly obtained, so that 
interventionists can avoid critical circuitry. There is suggestion that both fMRI and DTI imaging is 
influenced by organic or interventional variables, however this is understudied. The neuroscientists and 
clinicians would greatly value information that would expand our working knowledge of the basic neural 
substrates and functional neural changes that occur in patients organically or after interventions. A non-
invasive, non-interventional, observational study is needed to show the changes that happen to patients 
organically or in standard of care settings. A greater working understanding of the neural connectivity and 
changes that happen in the brain is of great future benefit to patients, science, and society as well as future 
therapeutic development such as post-stroke care, rehabilitation, post-traumatic brain injury, or post-
treatment care in the brain that has previously been influenced by intervention or disease.  
3.  Protocol 
 
3.1. Purpose 
 

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A number of studies from the literature suggest important behavioral, psychosocial, or radiologic 
changes occur following significant neurologic events or interventions such as stroke, 
neurosurgery, medications, radiation, systemic therapy, or injury (ref. 1-10). The purpose of this 
study is to describe these changes with advanced neurologic imaging and targeted neurologic and 
neuropsychiatric assessments. This is a non-interventional observational study of minimal risk to 
participants as there is no medical intervention. The results of this study will be used to inform 
patients, scientists, and society in the development of future treatments. 
 
3.1.1 Study Objective 
 
Primary objective: Describe changes in radiologic, behavioral, psychosocial domains after 
neurologic events or interventions. 
 
3.2. Protocol 
 
3.2.1 Synopsis 
 
Study Title: Psychosocial, Behavioral, and Radiologic Changes following Neurologic 
Events or Interventions: A Prospective Non-Interventional Observational Study 
 
Study Design: Prospective non-interventional observational study 
 
Number of Participants: We will aim to enroll 50 patients in this observational study to 
describe broad changes in neurologic circuitry and function. 
 
Study Population: VUMC adult patients with neurologic disease or patients with 
neurologic interventions such as neurosurgical procedures or radiation therapy 
 
Study duration: We estimate that this study will accrue 50 patients over 5 years. 
 
Visit Schedule: Participants will be asked to attend zero or more assessment intervals for 
this observational study by study investigators at the convenience of the subjects. 
 
 
3.2.2 Study Design 
 
This is a prospective, observational study involving non-invasive assessments of neurologic 
function. There are no medical, therapeutic or invasive components to this study. These include 
survey-based assessments, behavioral assessments, and imaging procedures.  
 
3.2.3 Participant Selection 
 
The study population will be current patients at Vanderbilt University Medical Center identified 
by the investigators.  
 
Men and women of any ethnicity, race or socioeconomic status who meet inclusion criteria will 
be offered enrollment into the study. Patient will be greater than 18 years of age and meet 

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inclusion and exclusion criteria. Patients eligible for this study will include patients with 
neurologic events, including but not limited to stroke, depression, infections, psychiatric disease. 
Intervention is not part of this study, however, patients receiving neurologic interventions, such 
as neurosurgical procedures or radiation therapy, would be eligible.  
 
Inclusion Criteria 
 
• Age ≥ 18 years old and willing and able to sign a written informed consent.   
• Eligible for Brain MRI 
• History of neurologic event or intervention OR future planned neurologic intervention 
 
Exclusion Criteria 
• Contraindications to MRI of the brain 
• Patient declining participation in study 
• Pregnancy 
3.2.4 Study Procedures  
 
3.2.4.1 Screening procedures 
 
Potential subjects will be identified by the investigators at Vanderbilt University Medical Center. 
They will be approached by the principal investigator (PI), a co-investigator (co-I), and/or 
appropriately trained research personnel in a private setting. Those participants who express 
interest in taking part in the research study will be asked to sign a written informed consent that 
has been approved by the Vanderbilt University IRB. Subjects will have the study explained to 
them and will be given the opportunity to read and review the consent documents and have any 
questions addressed. Subjects will be given a copy of the signed informed consent document. 
 
Once informed consent is obtained, final eligibility for enrollment into the study will be 
determined based on the inclusion/exclusion criteria. We will review the patient's medical 
history. Patient registration will be managed by research coordinator to be determined. The 
following documents must be completed before enrollment in the study can be considered 
complete: (1) IRB-approved informed consent. (2) Patients will be assigned a study ID number 
at the time of registration. (3) Patient Screening using inclusion/exclusion criteria checklist on 
case report form-enrollment form, (4) No study procedure will take place prior to obtaining 
written informed consent. 
 
3.2.4.2 Assessments  
 
During the study, subjects may be asked by investigators to complete one or more of the 
following standardized surveys for behavioral assessment during various study sessions: 
i. 
Y-BOCS Survey 
ii. 
RAND 36-item Quality of Life survey 
iii. 
Mini Mental Status Exam 
iv. 
MOCA Cognitive Exam 

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v. 
QUEST 
vi. 
PDQ 39 
vii. 
PHQ2 Depression Screening 
viii. 
PHQ9 Depression Inventory 
ix. 
Beck’s Depression Inventory 
x. 
PROMIS Pain Intensity Short Form 3A 
xi. 
McGill Pain Scale 
xii. 
Visual Analog pain scale 
xiii. 
Barrow Neurologic Institute Scale  
xiv. 
Hopkins Verbal Learning Test 
xv. 
Dimensional Obsessive-Compulsive Scale 
xvi. 
Mood Disorder Questionnaire 
xvii. 
FTM (Tremor Scale) 
xviii. YGTSS (Tourette/Tic scale) 
 
Radiologic tests may include one or more of the following procedures: 
i. 
Brain MRI 1.5 or 3 Tesla 
ii. 
fMRI 1.5 or 3 Tesla 
iii. 
Diffuse tensor MR imaging with fiber tractography 1.5 or 3 Tesla 
 
During the study, medical history, including but not limited to past medical history, past surgical 
history, medications, social history, family history, immunizations, and allergies may be 
recorded from the medical record. 
Behavioral tests may include one or more of the following procedures: 
1. Upper extremity testing:  
a. Both hands with digital hand grip dynamometer. 
b. Three times 
c. There are no known risks associated with this test. 
2. Perdue Peg Board testing: 
a. This is a test to see how quickly and accurately subject can work with your hands 
b. Test is performed by each hand and both hands. 
c. Each test session takes about one minute. 
d. There are no known risks associated with this test. 
3. Hand tactile detection and discrimination test: 
a. This test is used to determine the vibration detection and spatial and temporal 
discrimination ability of both hands. 
b. A fully automatic Case IV Computer Aided Sensory Evaluator system and two manually 
administered devices are used. 
c. There are no known risks associated with this test. 
4. Temperature and pain threshold testing: 
a. These tests are used to determine the detection thresholds of temperature and pain of both 
hands. 
b. A fully automatic Case IV Computer Aided Sensory Evaluator or an Medoc computer 
system are used. These computer systems have their own risk management system which 
will automatically shut down if potential harmful temperature, pressure or duration is 
reached. The temperature, pressure, and duration limits are built-in functions of the two 

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automatic computer systems and based on a large number of studies performed with these 
FDA approved systems. A second layer of protection comes from the subject's own 
control of the stimulus delivery. Subjects can press a button to stop the session at any 
time. 
c. A hand-hold sharp probe is used to test the sharp threshold.  
5. Lower extremity Testing: 
a. Timed up and Go test (TUG) 
b. This is a simple rising from a chair, walking three meters, turning around, and walking 
back to the chair and sitting down test. This test is used to assess a person's mobility and 
requires the static and dynamic balance. 
c. There is a potential for the subject to fall during this test. If the subject and/or KSP 
administering the test suspect the possibility for a fall, the procedure will be terminated. 
6. Myomotion Inertial Motion Testing: 
a. While performing the TUG test, the Myomotion Inertial Motion Testing System (with 7 
sensors, Noraxon, Phoenix, AZ) will be used to quantify kinetics of the movement, 
including gait data (cadence, step length, single limb stance time) and 3 dimensional data 
of the hips, knees, and ankles.  
b. All data collected will be compared to established normative values for age and sex of 
each subject. 
c. There are no known risks associated with this procedure. 
 
The study investigators will determine the type and frequency of assessments for each patient 
based on their medical history. 
 
3.2.4.5 Study Participant Termination/Withdrawal 
 
Participant Termination 
• In the judgment of the investigator, further participation in the study would not be in the 
best interest of the patient 
• Substantial non-compliance by the patient with the requirements of the study 
• The patient uses illicit drugs or other substances that may, in the opinion of the 
Investigator, have a reasonable chance of contributing to toxicity or otherwise interfering 
with results. 
• The patient is lost to follow-up 
• Development of an intercurrent illness or situation which would, in the judgement of the 
investigator, affect assessments of clinical status and study endpoints to a significant 
degree 
 
Participant Withdrawal 
• Patient decision to withdraw from the study at any time. Patients will still receive 
standard medical care  
 
Screen Failure 
• Patients who sign an informed consent that are withdrawn or terminated and have already 
undergone screening procedures will be considered screening failures. A record of these 
patients will be maintained. 
 

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The Investigator will make every reasonable effort to keep each patient in the study unless it is in 
the patient’s best interests to discontinue participation.   
 
3.2.5 Data Analysis  
 
Sample size: 
For this pilot observational imaging and patient-reported outcomes study, we will enroll 50 patients. This 
is based on predicted ability to accrue and follow. Future studies will be informed by the data of this pilot 
study. 
 
Radiologic: 
 
Each measurement will be performed in a minimum of five subjects to assess its variability. Standard 
measures of image quality (e.g., image signal-to-noise ratio, image and functional contrast-to-noise ratio, 
and magnitude of artifacts) will be used to judge optimal experimental parameters for all sequences. 
 
Single-subject analyses of functional connectivity will calculate the linear correlation coefficient (r) 
between a seed region and all other regions. These correlation values will be converted to z-scores using 
the Fisher r-to-z transformation z = tanh-1(r)(dof–3)1/2 where dof is the estimated degrees of freedom for 
each voxel after correction for first-order autocorrelation. A statistical threshold of |z| > 3.29 (a two-sided 
99.9% confidence interval) will be used to protect against type I errors. A minimum cluster threshold of 
nine contiguous interpolated voxels will also be used to further protect against spurious correlations. 
 
For group-level analyses of functional connectivity, a two-tailed Wilcoxon signed rank test with p < 0.01 
will be used to identify distributions of z-scores (calculated for each subject as described above) that are 
significantly different from zero. 
 
Analysis plan for questionnaires: 
Continuous variables (e.g. patient age) will be summarized overall and by group using the 25th, 50th 
(median), and 75th percentiles or the mean and standard deviation depending on whether data can be 
assumed to follow a normal (Gaussian) distribution.  Categorical data will be summarized in frequency 
tables and percents overall and by group.  State of the art graphical analysis including trellis plots of 
bivariate scatterplots, BliP plots, and plots for the assessment of modeling assumptions (i.e., QQ plots to 
assess normality) will be constructed.  
 
Subscale and overall summary scores (SI) are sums of the scores across subscales and over all questions.   
We hope to achieve >95% complete data and we will impute missing observations of subscales if at least 
80% of the data for a given time period are observed.  We will evaluate internal consistency/reliability 
within subscales using Crohnbach’s alpha and interclass correlations (ICC).  We will use a mixed models 
analysis of variance to estimate longitudinal effects on continuous outcomes measured in this study.  For 
categorical (e.g., yes/no and ordinal) models, we will use the generalized linear model employing a 
binomial or multinomial link function to estimate effects on the odds scale or proportional odds scale as 
appropriate.  These latter models will employ the Huber-White sandwich estimator for variance 
estimation.  These modeling approaches properly account for the intra-patient correlation among repeated 
measures. 
 
3.2.6 Adverse Events 
 

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3.2.6.1 Definitions  
 
Adverse event is defined as any undesirable experience that appears or worsens during the 
clinical study  
A related adverse event is an event in which there is a reasonable possibility that study related 
procedures caused or contributed to the event. 
A serious adverse event is defined as an adverse event whereby the patient outcome meets any 
of the following criteria: 
a. Results in death as a result of the study procedures 
b. Is life-threatening (defined as an event in which the participant was at 
substantial risk of death at the time of the adverse event) 
c. Requires inpatient hospitalization due to study procedures 
d. Prolongs an existing hospitalization due to study procedures   
e. Results in new persistent or new significant disability (substantial disruption of a person’s 
ability to conduct normal life functions) 
 
A “Report of Unanticipated Problem Involving Risk to Participants or Others” is submitted to the 
IRB as soon as possible, but no later than 7 calendar days after the Investigator first learns of the 
event or problem. This form contains the Investigator’s assessment of causality (related or not 
related to the study) and a description of the actual event. The form also contains an evaluation 
of whether the event meets the following criteria: 
 
a. An event that suggests that the research places subjects or others at a greater risk of physical or 
psychological harm than was previously known or recognized; 
b. Unanticipated (i.e., the event was not foreseeable); and  
c. Related (i.e., likely to have been caused by the research procedures) and Any associated 
materials such as medical record notations or reports with the name and medical record number 
of the individual redacted (removed). 
As far as reasonably possible, data recorded about each adverse event will include the following: 
1. the severity grade according the CTCAE v5.0 
2. its relationship to the study therapy (suspected/not suspected) 
3. its duration (start and end dates or if continuing at final exam) 
4. action taken (no action taken; concomitant medication taken; non-drug therapy given; 
hospitalization/prolonged hospitalization) 
5. whether it constitutes a serious adverse event 
All adverse events should be treated appropriately. Such treatment may include starting or stopping 
concomitant treatments, changes in the frequency or nature of assessments, hospitalization, or any 
other medically required intervention 
 
AE Term Selection 
 
To facilitate proper analysis of any observed adverse events within the study, consistent and 
medically accurate standards of AE term selection will be applied.  Whenever possible, an AE 
term will be the formal diagnosis or disease term experienced by the patient per the CTCAE 
v5.0.  If the final diagnosis remains differential or is pending, then the presenting signs, 

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symptoms and/or abnormal laboratory results will be captured as AEs until a diagnostic term can 
be applied.  
 
3.2.6.2 Protocol Deviations  
 
Protocol deviations are defined as any incidents involving non-adherence to the protocol and 
may result from actions of the participant, investigator, or staff. Protocol deviations will be 
recorded and will be reported to the reviewing IRB per IRB policy. Protocol deviations 
intended to protect the life or physical well-being of a participant in an emergency situation 
and any incidence of failure to obtain informed consent will be reported to the reviewing IRB 
as soon as possible but no later than 5 working days after the emergency occurred.  
 
3.2.6.3 Investigator Responsibilities 
 
Investigators are responsible for conducting the study in accordance w i t h  applicable FDA 
regulations for protecting the rights, safety, and welfare of subjects under the investigator’s 
care, and for obtaining informed consent from each research   participant p r i o r  t o  a n y  
s t u d y -related pr oc e dur es .   
 
Abnormal findings discovered as a result of the study procedures will be communicated to the 
treating physician by the investigators. The treating physician will be advised at that time 
regarding communication of the abnormal findings to the patient.  
 
3.3 References 
 
1. Ping Y et al. Enhanced effective connectivity from ipsilesional to contralesional M1 in well-
recovered subcortical stroke patients. Front Neurol. 2019;10:909. 
2. Purcell et al. Re-learning to be different: increased neural differentiation supports post-stroke 
language recovery. Neuroimage. 2019;202:116145. 
3. Goodin P et al. Correlated resting-state functional MRI activity of frontostriatal, thalamic, 
temporal, and cerebellar brain regions differentiates stroke survivors with high compared to low 
depressive symptom scores. Neural Plast. 2019;2019:2357107. 
4. D’Souza et al. Alterations of connectivity patterns in functional brain networks in patients with 
mild traumatic brain injury: a longitudinal resting-state functional magnetic resonance imaging 
study. Neuroradiol J. 2020;1971400920901706. 
5. Coenen et al. Individual fiber anatomy of the subthalamic region revealed with diffusion tensor 
imaging: a concept to identify the deep brain stimulation target for tremor suppression. 
Neurosurgery. 2011; 68(4):1069-75. 
6. Solana et al. Modified connectivity of vulnerable brain nodes in multiple sclerosis, their impact 
on cognition and their discriminative value. Scientific Reports. 2019;9:20172.  
7. Stanley et al. Defining nodes in complex brain networks. Front Comput Neurosci. 2013;7:169. 
8. Pranckeviciene et al. Depression screening in patients with brain tumors: a review. CNS 
Oncology. 2015;4(2):71-78. 
9. Murray B et al. Risk of posttraumatic stress disorder and major depression in civilian patients 
after mild traumatic brain injury. JAMA Psychiatry. 2019;76(3):249-258. 
10. Benjamin S et al. Fusing fMRI and DTI Measures of brain function and structure to predict 
working memory and processing speed performance among inter-episode bipolar patients. J Int 
Neuropsychol Soc. 2015;21(5):330-341. 

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4.RISKS 
 
Potential Risks to Subjects (Uncommon) 
The risks of MRI include: 
1. Ferromagnetic objects brought into the room will be pulled toward the magnet. 
2. Implanted metal or medical devices may experience abnormal torques or fail to function 
properly. 
3. There is a risk of tissue heating due to power deposition of radiofrequency magnetic 
waves. 
4. There is a risk of peripheral nerve stimulation if gradients are switched too rapidly. 
5. The subjects may experience a claustrophobic reaction. 
6. There are loud banging noises with MR imaging that may be uncomfortable. 
7. The subjects may experience dizziness or nausea if very quick head movements are made 
within the scanner. 
 
During a BOLD hypercapnia scan, which is currently a clinical scan offered to patients at 
Vanderbilt University Medical Center, 5% CO2 is delivered via a facemask for brief periods of 
time. While there have been no adverse events from this protocol since its implementation at 
Vanderbilt, the risks of a controlled hypercapnia stimulus include: 
1. Slight discomfort while the mask is on, or in some cases a slight sensation of shortness of 
breath. 
 
The behavioral testing procedures involve non-invasive measurements of the test subject and 
present minimal to no risk of adverse effects. However, though not anticipated, the testing may 
make some subjects agitated and will be immediately terminated if necessary by the study team 
member and/or at the request of the subject. 
 
The risk of breach of confidentiality includes: 
1. Reputation or employment may be damaged. 
We will employ the following protections to mitigate each of the above MRI risks: 
1. The subject will be instructed not to bring metal objects into the magnet room. 
2. The use of the MRI screening form will exclude potential subjects with implanted metal 
or medical devices. 
3. The FDA has strict limits regarding power deposition. Safeguards built into scanner 
hardware and software prevent the operator from exceeding those limits. 
4. The FDA has strict limits regarding gradient strengths and rise times. Safeguards built 
into scanner software prevent the operator from exceeding those limits. 
5. Subjects will be warned of the potential for claustrophobic reactions and those with a 
prior history of such reactions will be excluded from the study. If a subject experiences 
an unexpected and severe claustrophobic reaction, the exam will be terminated. 
6. The subjects will be provided with hearing protection. 
7. Subjects will be advised not to make any quick head movements. The scanner bed 
automatically moves the subject at a rate sufficiently slow to avoid problems from 
peripheral nerve stimulation and nausea. 
 
Regarding a BOLD hypercapnia scan: 

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1. Subjects will be informed of these sensations and if they feel uncomfortable will be told 
to notify the MRI technologists so the scan can be halted. Furthermore, hypercapnia 
scans will not be performed on subjects who have respiratory deficiencies. Therefore, we 
anticipate that the risks from Aim 2 are low for the population who will be enrolled. 
 
Regarding subject confidentiality: 
1. Careful data collection and storage procedures will be followed. 
 
5. MONITORING PROCEDURES 
The Principal Investigator is responsible for overseeing the safety and responsible conduct of the 
trial. The clinical data and adverse events will be reviewed by the Principal investigator in 
conjunction with the sub-investigators, research staff, and independent data safety monitor. The 
Principal investigator will be available for sub-investigators, nurses, and research staff to answer 
questions. If non-compliance by key study personnel is discovered, the principal investigator will 
be responsible for securing compliance and for providing review of the study protocol with the 
study personnel to ensure future adherence.   
6. ADDITIONAL RECORDS AND REPORTS 
 
 
Record Retention 
The PI must retain all study records by the applicable regulations in a secure and safe facility. 
The institution must consult with the PI before disposal of any study records, and must notify the 
PI of any change in the location, disposition or custody of the study files. The PI/institution must 
take measures to prevent accidental or premature destruction of essential documents, that is, 
documents that individually and collectively permit evaluation of the conduct of a study and the 
quality of the data produced, including paper copies of study records (e.g., subject charts) as well 
as any original source documents that are electronic as required by applicable regulatory 
requirements. 
The PI/institution should retain subject identifiers for at least 15 years after the completion or 
discontinuation of the study.  Subject files and other source data must be kept for the maximum 
period of time permitted by the hospital, institution or private practice, but not less than 15 years.  
These documents should be retained for a longer period, however, if required by the applicable 
regulatory requirements.  PI must be notified and will assist with retention should institution be 
unable to continue maintenance of subject files for the full 15 years.  It is the responsibility of PI 
to inform the institution as to when these documents no longer need to be retained. 
If an Investigator moves, withdraws from an investigation, retires, requests to move records to 
another location or to assign these records to another party or (e.g. other Investigator) who will 
accept the responsibility, written notice of this transfer must be made to and agreed upon by each 
party. 
 
Records will include all correspondence relevant to the investigation, IRB and FDA approved 
study documents, device accountability records, source and case report form documentation, to 
include signed consent documentation and any medical chart information relative to the research 
and device exposure by the participant. 

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Data Storage: 
The Vanderbilt University Office of Research will be used as a central location for data 
processing and management. Vanderbilt University, with collaboration from a consortium of 
institutional partners, has developed a software toolset and workflow methodology for electronic 
collection and management of research and clinical trial data called REDCap (Research 
Electronic Data Capture). REDCap is a secure, web-based application that is flexible enough to 
be used for a variety of types of research. REDCap provides an intuitive user interface that 
streamlines project development and improves data entry through real-time validation rules (with 
automated data type and range checks). REDCap also provides easy data manipulation (with 
audit trails for reporting, monitoring and querying patient records) and an automated export 
mechanism to common statistical packages (SPSS, SAS, Stata, R/S-Plus). In addition to 
traditional data capture functionality, REDCap’s survey capabilities are a powerful tool for 
building and managing online surveys. The research team can create and design surveys in a web 
browser and engage potential respondents using a variety of notification methods. All data 
collection projects rely on a thorough, study-specific data dictionary, defined by all members of 
the research team in an iterative, self-documenting process. This iterative development and 
testing process results in a well-planned and individualized data collection strategy. REDCap 
servers are housed in a local data center at Vanderbilt, and all web-based information 
transmission is encrypted. REDCap was developed specifically around HIPAA-Security 
guidelines and is recommended to Vanderbilt researchers by both our Privacy Office and IRB. 
REDCap has been disseminated for local use at more than 600 other academic/non-profit 
consortium partners in 54 countries. Vanderbilt leads the REDCap Consortium, which currently 
supports more than 63,000 projects and 82,000 users. More information about the consortium 
and system security can be found at 
http://www.project-redcap.org/. 
 
Data Privacy/Confidentiality Issues 
The Principal investigator will collect data and enter it into password-protected computer in a 
locked office. Each patient will have a unique identifier number, with the key to the patient’s 
medical record number kept in a locked cabinet in the office. Only research associates or those 
individuals directly involved with the study will have access to data.  Information is for research 
purposes only and when used for publication purposes, all participants will have their names 
concealed. Access to identified patient information will be limited to the investigators listed 
within the IRB application. De-identified information with HIPAA identifiers removed will be 
available to other investigators following IRB approval. Confidentiality and security will be 
maintained for the database. The database is stored behind a firewall (in addition to the 
institutional firewall) with the highest level of protection, i.e. the same level of protection as the 
on-line hospital information system at Vanderbilt.  This means that users must logon to a web 
server that sits between the institutional firewall and the firewall to the database, and only this 
application server is allowed to query the database. Only users approved through our institutional 
review board will be allowed access to patient identifiers. Other levels of authorization may exist 
for future approved users following IRB approval, e.g. access to de-identified data. 
Data is initially collected in the medical record for each individual study participant. The 
information will be extracted from the patient’s medical record and then transferred into the Case 

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Report Form (CRF). The study data will be kept on site and in a securely locked room to protect 
patient confidentiality. 
 
Study personnel (PI and co-investigators) and government regulatory agencies have access to all 
research records as required by law. Others (such as law enforcement agencies) may have access 
to records as defined by law.