Neural Bases of Cognitive Rehabilitation for Brain Injury
Phase: NA
Conditions: Brain Injury
Sponsor: VA Office of Research and Development

IRB (Institutional Review Board/Human Studies Subcommittee) 
DEPARTMENT OF VETERANS AFFAIRS 
NORTHERN CALIFORNIA HEALTH CARE SYSTEM 
MAT 5th Floor CR / MTZ Directors CR 
IRB APPROVAL 
- Continuing Review 
Date: May3l,2017 
From: Jary Larsen, PhD, IRE Chairperson 
Investigator: Anthony J.W. Chen, MA, MD 
Protocol: MERIT: Neural Bases of Cognitive Rehabilitation for Brain Injury 
ID: 00599 
Prom#: 4257 Protocol#: 10-08-00599 
Expiration Date: 05/14/2018 
The following items were reviewed and approved through Expedited Review: 
s * Continuing Review Application - Amendments (05/05/20 17) 
i . Remove Brian Cunan, Jason Deitch, Matthew Schalles and Diane Swick from the research team. 
2. Close study to enrollment. 
3 . Update recruitment totals for individuals enrolled between 20 1 5-20 1 6 (see enrollment table). 
4. Increase the length of the study 1 year for a total of 8 years. 
. * Human Subject Enrollment Form - From 03/14/2014 to 1 1/28/2015 (02/24/2017) 
. * Human Subject Enrollment Form - From i 1/28/2015 to 03/08/2017 (02/24/2017) 
. 
Proj ect Data Sheet (04/03/2017) 
. 
Research Security Plan (04/03/20 17) 
s 
Research Proj ect Abstract (03/22/2017) 
. 
Research Data Use and Security Plan - Investigator (04/03/2017) 
s 
Offsite Data Storage Waiver (04/03/2017) 
s 
Research Financial Conflict of Interest Statement - 2017 
Anthony Chen (03/08/2017); Mark D'Esposito (03/08/2017); Tajana Novakovic-Agopian (03/08/20 17) 
Continuing Review Application - Amendments (05/05/2017) was returned to you with stipulations. The 
following revised items incorporate the stipulations and are now approved: 
s 
Continuing Review Application - Amendments (05/22/20 17) 
1 . Remove Brian Cunan, Jason Deitch, Matthew Schalles and Diane Swick from the research team. 
2. Close study to enrollment. 
3 . Update recruitment totals for individuals enrolled between 20 1 5-20 1 6 (see enrollment table). 
4. Increase the length ofthe study i year for a total of 8 years. 
Human Subject Enrollment Form - From 03/14/2014 to 1 1/28/2015 (02/24/2017) was returned to you with 
stipulations. The following revised items incorporate the stipulations and are now approved: 
s 
Human Subject Enrollment Form - From 03/14/2014 to 1 1/28/2015 (05/22/2017) 
Human Subject Enrollment Form - From 1 1/28/2015 to 03/08/2017 (02/24/2017) was returned to you with 
Page 1 of2 
The Northern Cal VAMC IRB is not connected with, has no authority over, and is not responsible for human research conducted at 
any other institution, except where a Memorandum ofUnderstanding specifies otherwise. Separate consent forms, initial reviews, 
continuing reviews, amendments, and reporting of serious adverse events are required ifthe same study is conducted at multiple 
institutions. 

stipulations. The following revised items incorporate the stipulations and are now approved: 
Human Subject Enrollment Form - From 11/28/2015 to 03/08/2017 (05/22/2017) 
Expedited Approval [Expedited under Federal Regulation: 45 CFR 46.11O(b)(1)(4) I VA Regulation: 38 
CFR 16.11O(b)(1)(4)1 was granted on 05/31/2017 for a period of 12 months and will expire on 
05/14/2018. Your Continuing Review is scheduled for 04/03/2018. This Expedited review will be 
reported to the fully convened IRB (Institutional Review Board/Human Studies Subcommittee) on 
06/06/20 17. 
Since this continuing review was done after the current expiration date, the continuing review approval 
period changes to 05/31/2017 to 05/14/2018. 
The following other committee reviews are scheduled: 
Research & Development Committee [06/28/2017] 
Approval by each ofthe following is required prior to study continuation (unless Exempt): 
IRB (Institutional Review Board/Human Studies Subcommittee) 
Research & Development Committee 
Approval for study continuation is contingent upon your compliance with the requirements ofthe Research 
Service for the conduct of studies involving human subjects. 
Diqitally signed by Jary Larsen 
Jary Larsen 
DN: cn=Jary Larsen, o=VANCHCS, ou=lnstitutional Review 
Board, email=Jary.Larsen@va.gov, c=US 
Date: 2017.05.31 16:02:34-0700 
Jary Larsen, PhD, IRB Chairperson 
Page 2 of 2 
The Northern Cal VAIVIC IRE is not connected with, has no authority over, and is not responsible for human research conducted at 
any other institution, except where a Memorandum ofUnderstanding specifies otherwise. Separate consent forms, initial reviews, 
continuing reviews, amendments, and reporting of serious adverse events are required ifthe same study is conducted at multiple 
institutions. 

DEPARTMENT OF VETERANS AFFAIRS 
NORTHERN CALIFORNIA HEALTH CARE SYSTEM 
10535 Hospital Way 
Mather & Martinez, CA 
Conditions of IRB Approval 
What Are the Conditions of IRB Approval? 
Adhere to ethical principles: (1) Respect for persons - consent, privacy, confidentiality, (2) 
Beneficence - maximize possible benefits to the subject and minimize possible harms, and (3) Justice - 
equitable selection. 
2. Obtain informed, written consent from each human subject or his legally qualified guardian or next-of- 
kin, unless specifically waived by the IRB. If the subject lacks decision making capacity or has been 
declared incompetent, surrogate consent is required. You are required to place the original, signed 
consent form in the medical record (and document it in the electronic record), provide a copy to the 
subject, provide a copy to the Research Office (if applicable), and keep a copy for your files. 
3. Promptly report all Serious Adverse Events or Serious and Unexpected Events to the IRB (both events 
at the VA and sponsor reports ofevents at other sites). The FDA defines Serious Adverse Events as: 
(1) death, (2) life-threatening, (3) hospitalization - initial or prolonged, (4) disability, (5) congenital 
anomaly, (6) required intervention to prevent permanent impairment/damage, or (7) serious and 
unexpected severity or frequency of expected events. 
4. Promptly report all deviations (including error and accidents) from the approved protocol and do not 
initiate any unapproved changes (amendments, consent form modifications, advertisements) without 
IRB review and approval, except where necessary to eliminate apparent immediate hazard to human 
subjects. 
5. Report Emergency Use ofunapproved test articles to the IRE within 5 days. 
6. If applicable, provide a copy ofeach subject's consent form and the Investigational Drug Information 
Record (VA Form 90 1 2) to the Investigational Pharmacist prior to your request to receive, store, and 
dispense study medications. (The Investigational Pharmacist is responsible for the storage and 
dispensing of investigational drugs.) 
7. Submit Continuing Review information to the IRB by the date specified and inform the [RB when your 
study is completed (federal law requires that every protocol must be reviewed a minimum of once per 
year). File a final report upon completion or termination of a study. 
What Are the Penalties for Non-Compliance? 
Non-compliance may result in suspension of approval or a particular project. Serious or continuing 
non-compliance may result in suspension of your privilege to conduct research at this VAMC. 
Printed:05/31/2017 
Pagel of i 

\ Department of 
Veterans Affairs 
NORTHERN CALIFORNIA HEALTH CARE SYSTEM 
CONTINUING REVIEW APPLICATION 
Principal Investigator: Anthony Chen, MD. 
Title of Study: 
MERIT: Neural bases of cognitive rehabilitation for brain injury 
VA File Number: i O-08-00599 
PRINCIPAL INVESTIGATOR PREFERS APPROVAL NOTIFICATION DOCUMENT 
SENT TO: 
Principal Investigator 
OR 
Contact Person 
SENT BY: Z VA Inter-Office Mail 
OR 
United States Postal Service 
Principal Investigator: 
Anthony Chen, MD. 
Contact Person 
(if different from PI): 
Phone: 
925-372-2000 ext 2530 
Phone: 
Pager or Cell Phone: 
41 5-71 9-3824 
Pager or Cell Phone: 
Email: 
anthony.chen@va.gov 
Email: 
Fax: 
510-666-3440 
Fax: 
Martinez VA 
US Mailing Address: 
Research Service/i 51 
US Mailing Address: 
150 Muir Rd 
Martinez, CA 94553 
VA Site and VA Inter- 
Martinez 127 
VA Site and VA Inter- 
Office Mail Code: 
Office Mail Code: 
A. RESEARCH STUDY STATUS 
r! 
DESCRIPTION OF STUDY 
a. 
Is this study open to enrollment of new subjects, samples or charts? 
LIYes ZNo 
b. Are any subjects in the process of receiving research related interventions or study procedures? 
LIYes ZNoLIN/A 
c. Are any subjects being tracked for long term follow-up? 
LlYes ZNoN/A 
d. Are any of the remaining research activities ongoing, including data analysis? 
ZYes LINo 
(If the answer to all of the above questions is "NO" or "N/A, " complete the "Application for Study Closure" instead of 
thisforim) 
VO4/17/14 
Page 1 of 25 

e. . 
Is an original signed consent form in the study file for each subject entered into this study? 
EYes LINo 
. 
If "NO", is a waiver of consent and authorization approved for all subjects, samples or charts being used in 
this study? 
LIYes LINo 
f. 
Is a progress note ¡n the medical record of eachVA subject entered into this study? 
ZYes LINo LIN/A 
I 2. Information from the Prior Approval Period 
I 
. 
a. 
Total number of subjects, samples or charts entered into study since the last IRB Initial or Continuing 
Review: 6 
b. 
Have one or more subjects claimed injury from participating in this study? 
LlYes 
INNo LINfA 
c. 
Have any unanticipated problems, and/or adverse events related to the research occurred at this site? 
LIYes 
No 
d. 
Have any serious adverse events related to the research occurred at this site? 
LIYes ZN0 
e. 
Have any participants withdrawn from this site since the last IRB review? 
LIYes ZN0 
f 
Have there been any complaints about the research at this site since the last IRB review? 
LIYes IZN0 
g. 
Has there been any recent literature that may be relevant to the research since the last IRB review? 
LIYes ZNo 
h. Have there been any relevant multi-center trial reports since the last IRB review? 
LlYes 
LI No 
NIA 
i. 
Has there been any other relevant information, especially information about risks associated with the 
research (updated Investigator's Brochure, etc.) since the last IRB review? 
LIYes 
LI No 
I 
NIA 
j. 
Have there been any research findings since the last IRB review? 
LIYes 
ZNo 
k. 
Has this study received any monitoring visits from the sponsor or other external compliance agencies? 
LlYes INNo 
If "YES": 
1) 
How many monitoring and/or compliance visits were conducted? 
2) 
Were all monitoring and/or compliance visits reported to Research Service? LI Yes LI No 
3) 
Please provide dates and outcome of monitoring/compliance visits. 
3. Additional IRB Ove 
Has the Pl submitted this study to another IRB or IRBs? 
IYes LINo 
If "YES": 
a. 
Provide name(s) of IRB(s): UC San Francisco Committee onHuman Research (for UC Berkeley, per NOITR) 
1) Federal Wide Assurance Number: 00000068 
b. Status of study: 
z Under Review 
Approved 
LI Disapproved 
, 
If Disapproved: 
1) 
Provide details: 
V.04/17/14 
Page2of25 

B. CONFLICT OF INTEREST 
i . 
Describe any personal or financial interest of the investigators and research staff in the study. 
nia 
2. 
Research Financial Conflict of Interest Statement submitted for all members of the research team. 
ZYes 
LINo 
C. INVESTIGATORS AND RESEARCH PERSONNEL 
. 
. 
. 
i . Principal Investigator 
Check if research personnel will perform 
. 
. 
informed consent process independently 
________________________________________________________________ 
Anthony Chen 
LII 
2. Co-Investigator(s) 
None LI 
Mark D'Esposito 
Z 
Tatjana Novakovic-Agopian 
Z 
3. Research Staff 
None LI 
Diane Swick 
Z 
Matthew Schalles 
Z 
Nicholas Rodriguez 
Z 
Fred Loya 
Z 
LI 
LI 
**NOTE: Delegation of informed consent must be to an appropriate, suitably qualified member of the research team 
with a comprehensive understanding of the study and the ability to answer all research-reláted questions including those 
regarding risk, alternative treatments and therapies. 
4. 
Current number of open studies for this Pl at VANCHCSNACCHCS: 
LI o 
Z 
i -5 
LI 6-20 
LI over 20 
a. Current number of open studies for this PI at other institutions: 
LI o 
Z 
i -5 
LI 6-20 
LI over 20 
5; Describethe experience and training of the investigators and research staff. (Do notanswer with Refer to GV") 
a. 
Expertise with study procedures. 
_Mark D'Esposito, M.D., is Staff Neurologist at the VA, Director, Neurobehavioral Clinic and Brain Injury Rehabilitation 
Unit at the Martinez VA, Director of the Brain Imaging Center, UC Berkeley, Professor of Psychology, UC Berkeley, and 
Professor of Neurology, UCSF with extensive experience performing investigations of cognitive processes using 
functional MRI and other testing methods. 
_Anthony Chen, M.A., M.D., is a Staff Neurologist at the VA, with fellowship training in performing investigations of 
cognitive neuroscience and cognitive rehabilitation, development of functional MRI methods for these investigations, 
Assistant Professor at UCSF, directing studies of cognition, recovery and rehabilitation of patients with brain injuries. 
_Tatjana Novakovic-Agopian, Ph.D., is a specialist in Rehabilitation Neuropsychology, fellowship trained at UCSF and 
with extensive experience in clinical practice, Clinical Instructor in Neurology at UCSF, with expertise in the development 
of assessment measures for cognitive dysfunction affecting patients with brain injuries. 
_Fred Loya, PhD is a psychologist with expertise in neurocognitive assessment and clinical interventions who will 
conduct neurocognitive assessments and will be involved in research design and cognitive training. 
_Nicholas Rodriguez, BA is a research associate who will screen potential subjects, explain research activities to 
subjects, assist in research design and manage study data. 
V.04/17/14 
Page3of 25 

b. 
Provide information on how the training and expertise of the principal investigator, sub-investigators 
and other research personnel are relevant to the study. 
The study addresses how executive control functions such as selective attention may be improved through 
clinically-relevant cognitive training in patients with brain injury, as well as which neural changes support such 
improvements in executive control functions. The investigators and other research staff all have training and 
experience relevant to the study's purpose and design, including: cognitive rehabilitation of patients with brain 
injury and the development of clinical research protocols for assessment (using imaging, functional, and 
cognitive outcomes) of patients with brain injury. 
C. Describe the qualifications (training and experience) of all individuals who will be involved in the informed 
consent process. 
Mark D'Esposito, MD, is a staff neurologist at the VA. Co-investigators who will obtain informed consent include 
Anthony Chen, MD (staff neurologist at the VA) and Tatjana Novakovic-Agopian, PhD (rehabilitation 
neuropsychologist). Fred Loya, PhD, Nicholas Rodriguez, BA, and Erica Pool, BA are study staff who will also 
be involved. All have extensive experience working with patients and performing neuroscience studies. Drs. 
D'Esposito and Chen are trained in neurology, behavioral neurology and neurologic rehabilitation and cognitive 
neuroscience. Dr. Novakovic-Agopian is trained in neuropsychology and cognitive neuroscience. Fred Loya is 
a psychologists with extensive experience in neurocognitive assessment and research. Erica Pool, and Nicholas 
Rodriguez have BAs in Psychology and over 2 years research experience. Brian Curran has a BS in 
Physiological Psychology and is a Health Research Specialist with over 30 years experience in neuroscience 
research, with extensive experience screening and consenting subjects. 
d. 
If applicable, include information about relevant licenses/medical privileges. 
Mark D'Esposito and Anthony Chen are licensed physicians. Tatjana Novakovic-Agopian is a licensed 
neuropsychologists. 
D. STUDY DESIGN AND MERIT 
i . 
Estimated length of study: (in years or months) 
S 
7years 
S 
2. 
Length of each participant's time in this study: (in hours, days, weeks, months, or years) 
i day to 9 months 
3. 
Purpose of study: 
a. 
State the research hypothesis. 
Participation in the experimental interventions will enhance functioning in complex 'real-life' settings, result in 
improvements in attention and working memory (reflecting protection from distraction) and improvements on 
measures of sustained attention. 
b. 
Describe the research objectives. 
To dtermine the neural, neurocognitive and functional effects of attentional training protocols. We will use fMRI 
coupled with behavioral interventions to address the following questions: Question i : What are the neural 
changes caused by brain injury that underlie behavioral changes in executive cognitive control? Question 2: 
What specific neural changes support improvements in cognitive abilities of executive control and attention in 
with brain injury? The studies will also investigate to what extent effects transfer to higher and lower 
levels of function and domains of cognitive functioning that are not explicitly trained; to what extent neural 
measures help to explain variability in behavioral effects; and to what extent effects are maintained at 6 months 
follow-ui. 
c. 
Describe in detail the purpose of this study. 
Aim i . To determine the neural, neurocognitive and functional effects of a theory-driven, strategy-based 
intervention that trains goal-oriented attention with intensive application through accomplishment of personally 
relevant projects. Hypothesis: Participation in the experimental intervention will enhance functioning in complex 
'real-life' settings, relative to an educational intervention matched for time and attention. 
2. To determine the neural, neurocognitive and functional effects of a computer-assisted game-based 
protocol designed to intensively trainthe target process of re-direction of selective attention when distracted. 
V.04/17/14 
Page 4 of 25 

Participation in the experimental intervention will result in improvements in attention and working 
memory (reflecting protection from distraction), relative to a comparison intervention matched for time and 
computer usage. 
Aim 3. To determine the neural, neurocognitive and functional effects of a computer-assisted training task that 
targets basic tonic and phasic attention functions. Hypothesis: Participation in the experimental intervention 
improves sustained attention, relative to a comparison intervention matched for time and computer usage. 
Each study will also investigate to what extent effects transfer to higher and lower levels of function and 
domains of cognitive functioning that are not explicitly trained; to what extent.neural measures help to explain 
variability in behavioral effects: and to what extent effects are maintained at 6 months follow-un 
Describe the importance of resulting knowledge from this study. 
d. This research is designed to contribute to improving care by (1 ) providing a neuroscientific framework for 
understanding neurorehabilitation therapies and their effects on brain functions, (2) aiding in the development of 
informative fMRI biomarkers that will be useful in rehabilitation treatment studies and (3) aiding in the design of 
novel therapeutic interventions that more directly target the underlying neural bases of dysfunction. Completion 
of the proposed studies will provide an essential foundation for the immediate next steps -- directly targeting the 
elucidated neural pathways using improved behavioral, physiological and pharmacologic modulation treatment 
interventions. 
4. 
Check types of study design 
z Chart/Medical Records Review 
z Prospective 
Retrospective 
Observational (the investigator observes the events without altering them): 
Cross-sectional study (each participant examined only once) 
Longitudinal study (each participant followed over a period of time) 
z Experimental Intervention (the investigator observes the effect of the intervention on outcome): 
z Randomized 
z Blinded 
LI Retrospective 
5. Describe statistical methods (For example: sample size estimation, power calculation, statistical tests or 
descriptive statistics, data analysis tools, etc.) 
Analyses of cross-sectional data will include (a) across-group comparisons using univariate statistics and (b) within 
group correlational analyses testing the relationships between behavioral and neural measurements. Tests of 
repeated measures will be used to assess the effects of the training interventions on pre- and post- intervention 
measurements. Intervention group x time interactions will be assessed using ANOVA and specific relationships will 
be tested using paired T-tests. 
6. 
Describe appropriateness and rationale for elements warranting special attention (placebo, washout period, 
challenge study, radiation exposure, deception study, deviation from accepted standard of care). 
n/a 
7. 
Have there been IRB approved protocol amendments modifying the study (including sponsor amendments) 
since the last review? 
Yes LINo 
V.04/17/14 
Page 5 of 25 

e 
If "YES", list approval date and summarize the nature and purpose of all protocol amendments made sínce the 
time of last Initial or Continuing Review: 
Approval Date 
Amendment Description 
1011/04/2016 
Approved letter to request signed authorization 
E. AMENDMENT REQUEST AT CONTINUING REVIEW 
1. Are any protocol amendments modifying the study (including sponsor amendments) being proposed at the 
time of this continuing review? 
IYes LINo 
e 
¡f "YES' complete the rest of this section, If No, skip the rest of this section 
2. Purpose andíor reason for modifying the protocol. 
Remove personnel from research team, close study to enrollment, update recruitment totals 
3. Brief Description of Amendment. 
- 
Remove Brian Curran and Jason Deitch from protocol 
- 
Close studyto enrollment 
- 
Update recruitmenttotals for individuals enrolled between 2015-2016 (see enrollment table) 
F. 
SUBJECT POPULATION 
1. 
Human Subject Enrollment 
a. 
How many total participants did VANCHCS IRB oriciinally approve for accrual (sign consent forms) at 
VANCHCSNACCHCS? 210 
b. 
How many total participants are currently approved for accrual at VANCHCSNACCHCS? 
jQ 
C. 
How many total participants did VANCHCS IRB originally approve for accrual at other sites under your 
responsibility? 
List other initial site names 
d. 
How many total participants are currently approved for accrual at other sites under your responsibility? jí 
List other current site names 
e. 
If this is a Multicenter trial with different sites and different PIs, how many total participants are currently planned 
to be enrolled for the entire project? 
f. 
No contact with participants, authorization and consent waived: LI 
1) 
Enter total number of samples or charts originally approved jL 
2) 
Enter total number of samples or charts currently approved 
3) Enter total number of records extracted from VA Data Mart or VA Data Warehouse (National, Regional, or 
VISN) originally approved j 
4) 
Enter total number of records extracted from VA Data Mart or VA Data Warehouse (National, Regional, or 
VISN) currently approved 
V.04/17/14 
Page 6 of 25 

2. 
Status of subjects 
a. 
Number of subjects, samples or charts entered into study since project began? 
b. 
Number of subjects, samples or charts entered into study since last report to the IRB? 
3. 
Since the last report, to the IRB indicate: 
a. 
Number of female subjects:Q 
b. 
Number of male subjects 
c. 
Number of subjects in each of the following groups: 
Caucasian: 4 
African-American: i 
Hispanic: i 
Asian: 
Other: (indicate minority status and number) 
d. 
Number of subjects in each of the following vulnerable groups: 
z None 
Children: 
. 
Persons with HIV: 
Economically Disadvantaged: 
Employees: 
Prisoners:' 
Educationally Disadvantaged: 
Homeless/Shelter: 
Students/Trainees: 
Impaired Decision Making Capacity: 
Mentally Disabled: 
Terminally Ill Patients: 
Pregnant Women & Fetuses: 
Non-English Speaking: 
Others: 
e. 
Number of subjects who signed consents but were dropped from study ("screen failures"):l 
f. 
Total number of patients who withdrew or were withdrawn from the study: Q 
i ) Summarize the reasons for withdrawal. 
g. 
Did all research subjects give written informed consent? 
Yes 
No 
N/A - consent waived 
1) 
If no, provide explanation: 
4. Which of the following groups will be recruited for this study? (check all that apply) 
z lnpatients 
Outpatients 
Pre-Operative patients 
V.04/17/14 
Page 7 of 25 

5. 
Are you recruiting and enrolling Non-VA participants? 
ZYes LINo 
e 
/f 'YES", complete the following information: 
a. 
Document how you will attempt to enroll veterans 
Veterans are being referred by VA clinicians. Recruitment activities will also be extended to VA Outpatient 
Clinics, Veteran Centers, State of California Department of Rehabilitation veteran services programs, 
Employment Development Department disabled veterans outreach programs, community college disabled 
student programs and veteran affairs offices, adult school programs for individuals with brain injury, University of 
California and California State University programs for veterans, Travis AFB TransitionService Center, and 
neurology clinics at local hospitals. Recruitment activities will include presentations to individuals or groups 
associated with these service providers, distribution of approved letters, brochures and flyers, and posting of an 
approved advertisement on Craigslist. 
b. Outline how you will provide verification to Research Service that recruitment resulted in insufficient 
veteran enrollment. 
Researchers will make extensive efforts to enroll veterans, including providing IRB-approved recruitment 
material to VA Outpatient clinics, Veteran Centers, State of California Department of Rehabilitation Veteran 
services programs, State of California Employment Development Department disabled veterans outreach, State 
of California County veterans services, community college veteran affairs offices, University of California and 
California State University programs for veterans, Travis AFB Transition Service Center, and a Craigslist 
advertisement. 
6. 
Selection Criteria 
a. 
What are the inclusion/exclusion criteria? 
Inclusion criteria: Patients with acquired brain injuries at the VANCHCS will be studied. Patients will be age i 8- 
75 and have a clinical history of brain injury from stroke, brain tumor, surgery or trauma. Patients will be 
screened for evidence of mild residual dysfunction in executive control functions based on reports of real-world 
difficulties by self and/or significant other (Cognitive Failures Questionnaire, Patient Competency Scale, Mayo- 
Portland Adaptability Inventory) and/or evidence of executive cognitive deficits on neuropsychological tests 
(Auditory Consonant Trigrams, Trailmaking B, D-KEFS Stroop, Strategy application). All patients will be in the 
chronic, stable phase of recovery (>1 week from initial injury), and able to consent for themselves. Only patients 
who are deemed to have capacity for decision making by physicians caring for the patients will be asked to 
participate. If there is additional uncertainty, the clinicians on the research staff, Mark D'Esposito, MD, Anthony 
Chen, MD, or Tatjaña Novakovic-Agopian, PhD will interview the patients, provide information on the risks and 
benefits of the study and ascertain whether the patient understands and has the capacity to make an informed 
decision. 
Exclusion criteria: Severely apathetic/abulic,aphasic,orunable to participate with the training tasks, history of 
neurodevelopmental abnormalities, illicit drug use, severe depression. Pacemakers, electronic or metallic 
implants, shrapnel, claustrophobia, that render MRI unsafe will exclude patients from participating in MRI 
studies. There will be no restriction in regard to gender, race and socioeconomic status. As safety for MRI 
during pregnancy is not well established, patients who are pregnant will be excluded. Only English-speaking 
subjects will be recruited as the neurocognitive tests are only available in English. 
HealthyVolunteers: Allheaithy volunteers will be screened for past psychiatric problems, severe medical 
disorders and drug or alcohol abuse history. Screening will be self-report and/or significant other-report. Healthy 
volunteers will also be screened for evidence of executive cognitive deficits on neuropsychological tests 
(AuditoryConsonant Trigrams, Trailmaking B, D-KEFS Stroop, Strategy application). 
tests (Auditory 
Consonant Trigrams, Trailmaking B, D-KEFS Stroop, Strategy application). 
V.04/17/14 
Page 8 of 25 

b. 
How do the inclusion/exclusion criteria reflect the purpose of the study? 
The study seeks to investigate neural changes associated with clinically relevant cognitive training of patients 
with acquired brain injury. Variability in cognitive performance is a significant problem in the interpretation of 
many rehabilitation studies. Limiting the study to patients with stable, chronic deficits will facilitate the detection 
of changes related to the parameters of interest. Acute recovery presents a phase of high variability and 
ongoing neural and vascular changes, therefore only patients in chronic stages will be included. Studies at this 
stable phase will facilitate detection of otherwise subtle changes in these 'proof-of-principle' studies. Findings 
are less likely to be confounded by 'sDontaneous' recovery or vascular chanaes. 
C. How do inclusion and exclusion criteria impose fair and equitable burdens and benefits? 
The purpose of the inclusion/exclusion criteria is to limit the study to patients with stable, chronic deficits who 
are not severely abulic or aphasic, as the results of this research might benefit individuals in the general 
population who meet the inclusion criteria and is not expected to benefit individuals who are severely abulic or 
aphasic. Patients who are severely abulic or aphasic are already burdened by other factors (e.g., major 
difficulty in activities of daily living) and should not also be burdened by participating in research tasks they will 
not be able to perform. In addition, the informed consent process requires capable decision makers and patients 
who are severely abulic or aphasic are likely to be decisionally impaired. 
d. 
Describe the science and ethics of excluding groups that might benefit from the research. (If women or 
minorities are excluded, explain reasons for exclusion.) 
Patients who are severely abulic or aphasic will not be able to perform the tasks involved in these studies and 
are therefore excluded. 
7. 
Research Setting: 
a. 
Describe the research setting in context of equitable selection of subjects. 
The research will be conducted at the Martinez VA and the University of California, Berkeley. 
b. 
Where will participants be screened, enrolled, and followed? 
VANCHCS Outpatient Clinics - Check all that apply: 
Chico VA Outpatient Clinic - Specify Clinic: 
Fairfield VA Outpatient Clinic - Specify Clinic: 
Mare Island VA Outpatient Clinic - Specify Clinic: 
McClellan VA Outpatient Clinic - Specify Clinic: 
z Martinez VA Outpatient Clinic - Specify Clinic: Neurobehavioral Neurology 
Oakland VA Outpatient Clinic - Specify Clinic: 
Oakland VA Mental Health and Substance Abuse Clinic - Specify Clinic: 
Redding VA Outpatient Clinic - Specify Clinic: 
LII Sacramento VA Mental Health Clinic - Specify Clinic: 
L Sacramento VA Medical Center - Check all that apply: 
LII Outpatient Clinic: Specify: 
III Inpatient Ward: Specify: 
UC Davis CTSC Clinical Research Center (CCRC) 
VANCHCS Martinez: Center for Rehabilitation and Extended Care (CREC) 
LI VANCHCS Martinez: UC Davis Alzheimers Disease Center (UCD ADC) 
z VANCHCS Research Space - Specify Site: Martinez Research Building 4 and Brain Health Building 
E UC Davis Medical Center - Specify: 
University or College Campus - Specify: UC Berkeley Neuroscience Institute 
VACCHCS Outpatient Clinic - Specify Clinic: 
VACCHCS Research Space - Specify Site: Martinez VA Research Building 4; Martinez VA Center for 
Integrated Brain Health and Wellness 
Other - Specify: 
V.04/17/14 
Page 9 of 25 

8. 
How will participants be recruited for taking part in the study? Please review 'important Information for 
Researchers" for more information about acceptable recruitment methods. 
a. Check all that apply: 
Investigator's patient population: Study investigators recruit their own patients directly in person and/or nurses 
working with researchers approach patients. 
z Scheduled visit: Study investigators provide their colleagues with an IRB approved "Dear Patient" letter 
describing the study. This letter can be signed by the treating health care provider and would inform the patients 
about how to contact the study investigators. The study investigators may not have access to patient names 
and addresses. 
z Physician referral: Study investigators send an IRB approved letter to colleagues asking for referrals of eligible 
patients interested in the study. The investigators may provide the referring physicians an IRB approved 
Information Sheet about the study to give to patients. If interested, the patient will contact the PI. Or, with 
documented permission from the patient, the Pl may be allowed to talk directly with patients about enrollment. 
Direct advertising: Interested participants will initiate contact with study investigators. (Submit an electronic 
copy of all recruitment media listed in this section to the IRB Coordinator who will forward it to VANCHCS Public 
Affairs Officer (PAO) for reviewpjJçr to IRB review and approval.) 
LII Newspaper: Name(s) 
LI Bulletin Board Poster: Posting Location(s) 
Flyers: Posting Location(s) VA Clinics , Vet Centers, Dept of Rehab offices, Community Colleges 
veteran services offices, Employment Development Department Disabled Veterans Outreach offices, 
Travis Transition Service Center, UC and CSU Veteran services offices, adult schools with classes 
for brain-injured students, community bulletin boards, County Veterans Service Offices and 
community organizations that provide services to disabled veterans. 
Internet: Web site address Advertisements on http://sfbay.craigslist.org 
If using the media above, see VANCHCS Policy Statement PS-OO9 "Local Publications" or call VANCHCS 
HRPP at 916 366-5369. 
LI Radio: Station Name(s) 
LI Television: Station Name(s) 
; 
If using the media above, see VANCHCS Policy Statement P5-00-7 "Public Affairs Program." 
Other: Letter to Potential Subjects, Letter to Clinicians, Brochure, Letter to Service Provider, 
Craïgslist advertisement 
Waiver of Authorization and Consent for recruitment purposes: This waiver is an exception to the policy but 
may be requested in exceptional circumstances such as: 
L Minimal risk studies in which participants willnot be contacted, for example chartldatabase review only 
(Describe who and how): 
Review of charts/database is needed to identify prospective participants who will then be contacted 
(Describe who nd how): Drs. Chen and Novakovic-Agopian will review medical charts of prospective 
participants. 
Large-scale epidemiological studies and/or other population-based studies when participants may be 
contacted by someone other than personal health care provider (Justify and describe by who and how): 
Direct contact: Potential participants have previously given consent to be contacted for participation in 
research. Clinic or program develops an IRB approved recruitment protocol that asks patients if they agree to 
be contacted for research (a recruitment database) or consent for future contact was documented using the 
consent form from a different study that was approved by the IRB. 
z Potential participants unknown to investigators: Study investigators recruit potential participants who are 
unknown to them. Examples include direct approach in public situations, random digit dialing, use of social 
networks, Please explain here: In the case of physician referral or self-referral, investigators may not know 
the potential participants. 
V.04/17/14 
Page 10 of 25 

NO contact: This study does not involve participant contact for recruitment. Examples include record review, 
use of specimens. 
b. Are participants being paid (includes all types of reimbursement, such as parking fees, etc) for 
participation? 
Yes LINo 
Note: VA policy prohibits paying human subjects to participate in research when the research is integrated with 
a patient'à care and when it makes no special demands on the patient beyond those of usual medical care. 
e 
If "YES", continue to question 1), 2), 3), 4), 5) and 6) below. 
e 
If "NO", skip to Section F9. 
1) 
Payment may be permitted in the following circumstances 
Check all that apply 
No Direct Subject Benefit: When the study to be performed is not directly intended to enhance the 
diagnosis or treatment of the medical condition for which the volunteer participant is being treated, and 
when the standard of practice in affiliated non-VA institutions is to pay participants in this situation. 
LI Others Being Paid: In multi-institutional studies, when human participants at a collaborating non-VA 
institution are to be paid for the same participation in the same study at the same rate proposed. 
LI Comparable Situatïons: In other comparable situations in which payment of participants is 
appropriate. Describe: 
Transportation Expenses: When transportation expenses are incurred, by the participant that would 
not be incurred in the normal course of receiving treatment and which are not reimbursed by any other 
mechanism. 
2) 
Payment Amount: 
Total Amount $ 120-780 
Prorated as follows: $20/hour 
3) Method of Payment: 
Cash 
LI Check 
Gift certificate 
Other: 
4) Payment Schedule: 
LII Each visit 
Z Study completion 
Other: 
5) Substantiate that proposed payments are reasonable and commensurate with the expected 
contributions of the participant. 
are being compensated for the inconvenience and time spent in a study that may provide no 
direct benefit to them. They will undergo 6 - 36 hours of cognitive, functional, and imaging assessments, up 
to 3 hours at a time. 
6) Substantiate that proposed payments are fair and appropriate and that they do not constitute undue 
pressure or influence to participate. 
Participation in the study will require a substantial amount of time. During the Informed Consent process, 
participants will review the nature, risks, benefits, alternatives, and requirements of the study. The rate of 
$20/hour is not excessive, given wage rates in the local vicinity, and therefore would not constitute an undue 
inducement to participate in the study. 
V.04/17/14 
Pagell of 25 

9. 
Which of the following vulnerable populations will be recruited for this study? (Check all that apply). 
None 
Li Children* 
Non-English Speaking 
LI Economically Disadvantaged* 
j Employees 
LII Persons with HIV 
LI Educationally Disadvantaged* 
Fetuses* 
Prisoners* 
LI Impaired Decision Making Capacity* 
Homeless/Shelter 
E StudentsìTrainees 
LI Pregnant Women* 
J Mentally Disabled* 
Terminally Ill Patients 
LI Others: 
* listed in the Federal regulations; VHA Handbook 12OO5 Appendix D lists special requirements 
a. 
Describe the scientific and ethical reasons for including vulnerable populations in the research. (Why 
are vulnerable populations necessaty in this research study?) 
n/a 
b. 
Describe the extra protections and additional safeguards that protect the rights and welfare of 
vulnerable groups. (How are the vulnerable populations being protected?) 
n/a 
C. 
Describe the procedures that you have devised to ensure that participant's representatives are well 
informed regarding their roles and obligations to protect incompetent participants or persons with 
impaired decision-making capacity. 
n/a 
G. RESEARCH PROCEDURES 
i . 
Check all procedures to be performed on human participants, samples or charts: 
III Analysis of Existing Biological Specimens 
Z Interview 
Analysis of Existing Data 
Invasive Procedures - Diagnostic (e.g. biopsy, catheters, etc4 
LIII Biological Specimen Collection (urine, sputum, 
tissue, etc.) 
Invasive Procedures - Therapeutic (e.g. infusions, catheters, 
etc.) 
LII Blood Collection 
fMRI: Clinical Research 
Chart Review 
MRI: Clinical Research 
Cognitive or Perceptual Experiment 
MRI: Diagnostic 
LI Commercial Product Development Potential 
. 
. 
. 
from_Human_Biological_Specimens 
Placebo 
LI Deception 
Physical Measurements: Non-Invasive (e.g. vitals signs) 
LII Device(s): FDA approved 
LII Public Behavior Observation 
LI Device(s): Investigational 
Questionnaire 
LI Drug(s): FDA approved 
LIJ Radiation: Clinical Research (e.g. PET) 
LI Drug(s): FDA approved Controlled Substance 
Radiation: Diagnostic (e.g. X-ray) 
Drug(s): Investigational 
LII Radiation: Therapeutic 
Drug(s): Investigational Controlled Substance 
LII Specimen Collection for Future Use (tissue banking) 
LII ECG 
LI Specimen Use from Tissué Bank (stored samples) 
I 
EEG 
LI Surgery 
LI EMG 
LI Survey 
LII Evaluation of Program or Services 
Taste Test 
V.04/17/14 
Page 12 of 25 

LI Gene therapy 
LI VA Data Record Search (Data Mart, Data Warehouse, etc.) 
LI Genetic/DNA Research 
Other neurocognitive testing and cognitive task training 
2. 
Describe research procedures to be performed on participants, samples or charts. 
a. 
Describe all interactions with participants or their identifiable samples or data in detail. 
Patients and Healthy Volunteers: The research involves (1) neurocognitive testing, (2) practice on cognitive 
tasks, and (3) performing MRI scans. All study procedures described will be done at the Martinez VA Research 
Building 4, Outpatient Clinic, Brain Health Building, and/or Center for Rehabilitation and Extended Care (CREC) 
except that patients will be referred either to the Brain Imaging Center, UC Berkeley or to Martinez VA for 
functional MRI scans. 
_Neurocognitive measurements: Subjects (patients and healthy volunteers) will be asked to participate in a 
focused battery of neurocognitive (neuropsychologic) tasks. This testing Will be done at the Martinez VA 
Outpatient Clinic, Brain Health Building and/or Center for Rehabilitation and Extended Care (CREC). During 
this session, subjects will sit in front of a computer screen and respond to visual stimuli using a keyboard or 
button press. The subjects will also be asked to do written tests and answer written questionnaires about their 
cognitive and emotional status. 
_Cognitive task practice: Subjects (patients and healthy volunteers) participate in cognitive task practice 
requiring attention and memory. These may be of short, medium and long-term duration in 3 separate stages. 
In the first stage, subjects may be asked to practice tasks for a single session. The short-term practice tasks 
involve presentations of images or words on a computer during one session lasting up to 90 minutes. In the 
second stage, subjects may be asked to practice tasks over 2-4 weeks. This medium-term training also 
involves practicing computerized cognitive tasks that involve attention and memory for 30-60 minutes a day. 
Subjects will be randomized into groups doing the same tasks, but in a different order. In the third stage, 
subjects will be asked to participate in cognitive task practice that is designed to be a form of cognitive 
rehabilitation training. This long-term training includes computer-assisted and therapist-guided practice 1-2 
hours each day for up to 6 weeks working on cognitive tasks that engage attention, working memory, goal 
management and other executive functions, and may also include up to 6 weeks attending education sessions 
about brain health, with a therapist on an individual basis and in groups. The long-term training will include 
sessions with staff at the Martinez VA Outpatient Clinic, Brain Health Building and/or Center for Rehabilitation 
and Extended Care (CREC) on a weekly basis. Subjects in this third stage are also randomized into groups that 
do the same tasks, but in a different order. Assignments and materials for practicing at home will be given to 
patients and healthy volunteers. For computerized tasks, software for practicing tasks at home will be offered to 
participants. Subjects may stop participating at any time. Typically, neurocognitive testing and fMRI studies are 
performed before and after training. 
_Functional MRI measurements: In the MRI test, subjects (patients and healthy volunteers) are asked to lie on 
their backs in the MRI scanner and perform a cognitive task. When the subjects are ready to be scanned, an 
MRI imaging coil will be placed around the subject's head. The subject will not come into contact with the coil 
during the experiment. Foam pads will be placed around the subject's head to limit head movement during the 
study. Functional MRI will involve scanning during the performance of a cognitive task and during rest. The 
cognitive task will involve presentation of images or words on a computer monitor or sOunds through 
headphones. The subjects are asked to respond to certain stimuli by pressing a button. Basic structural images 
will be taken for reference to align with the functional images (these are separate from the clinical structural MRI 
imaging done as standard of care). Scanning will be performed using a 3 Tesla Siemens or 4 Tesla Varian 
scanners under the supervision of the Director of the Brain Imaging Center, Dr. Mark D'Esposito or co- 
investigator Dr. Anthony Chen.. All MRI studies performed at the Brain Imaging Center are part of research 
protocols and are not intended to provide comprehensive clinical MRI examinations of the brain. If a potential 
abnormality is identified on an MRI scan, the PI will immediately notify the subject and the family physician. 
_EEG studies: In EEG studies, EEG is recorded while concurrently monitoring behavior. Subjects (patients 
and healthy volunteers) are asked to sit in a soundproofed room and have EEG electrodes placed on their scalp 
with conducting paste. The experiments involve presentation of images on a computer monitor, sounds 
V.04/17/14 
Page 13 of 25 

through headphones, or taps to fingers. The subject is asked to respond to certain stimuli by pressing a button. 
All stimuli are presented at a comfortable level. A recording session typically takes 60-90 minutes. The subject 
is given breaks every 5-1 0 minutes, but may request a break or stop the experiment at any time. These will be 
done in Research Building 4 at VANCHCS Martinez. 
Follow-up contact: Researchers will contact 
subjects by telephone 6 months after other study activities to ask standardized questions about their post- 
participation level of functioning in various life domains. Telephone contact takes 30-60 minutes. Subjects may 
also be asked to return six months after their first visit for follow-up neurocognitive testing and MRI. 
b. 
Describe the research methods, including how the study will be implemented locally. 
The research involves (1) neurocognitive testing, (2) practice on cognitive tasks, and (3) performing MRI scans. 
(1 ) Neurocognitive testing will be done at the Martinez VA Research Building 4, Outpatient Clinic, Brain Health 
Building and/or Center for Rehabilitation and Extended Care (CREC); (2) practice on cognitive tasks will be 
done at the Martinez VA Research Building 4, Outpatient Clinic, Brain Health Building and/or Center for 
Rehabilitation and Extended Care or at home; and (3) perlorming fMRl scans will be done at the Brain Imaging 
Center. 
C. Provide detailed information about all study procedures, including the approximate duration and 
frequency of each procedure. lt is not necessary to repeat descriptions of non-human related 
procedures from the protocol narrative (e.g. you should describe how much and how frequently blood is 
drawn, but not the methods for performing tests on the blood, if already stated elsewhere) 
Neurocognitive measurements: This part of the experiment takes approximately 2 - 3 hours. The subject 
is free to take breaks throughout the session. 
Subjects may undergo neurocognitive measurements once if 
they do not undergo cognitive training, twice if they participate in short-term or medium-term training (pre- and 
post-training), and three times if they participate in long-term training (at baseline, 5 weeks, and i 0-weeks) 
_Cognitive task practice: These may be of short, medium and long-term duration in 3 separate stages. In the 
first stage, subjects may be asked to practice tasks for a single session. The short-term practice tasks involve 
presentations of images or words on a computer during one session lasting up to 90 minutes. In the second 
stage, subjects may be asked to practice tasks over 2-4 weeks. This medium-term training also involves 
practicing tasks that involve attention and memory for 30-60 minutes a day. Subjects will be randomized into 
groups doing the same tasks, but in a different order. In the third stage, subjects may be asked to participate in 
cognitive task practice that is designed to be a form of cognitive rehabilitation training. This long-term training 
includes practicing i -2 hours each day for up to i O weeks working on cognitive tasks that engage attention, 
working memory, goal management and other executive functions, or education sessions about brain health, 
with a therapist on an individual basis and in groups. 
- fMRI scanning: A session typically takes 60-90 minutes and the subject is given frequent breaks. The 
subject may stop the experiment at any time. Subjects may undergo fMRI once if they do not undergo cognitive 
training, twice if they participate in short-term or medium-term training (pre- and post-training), and three times if 
they participate in long-term training (at baseline, 5 weeks, and i 0-weeks) 
_EEG studies: A recording session typically takes 60-90 minutes. The subject is given breaks every 5-10 
minutes, but may request a break or stop the experiment at any time. These will be done in Research Building 
4 at VANCHCS Martinez. 
Follow-up contact: Researchers will contact subjects by telephone 6 months after other study activities to 
ask standardized questions about their post-participation level of functioning in various life domains. Telephone 
contact takes 30-60 minutes. Subjects may also be asked to return six months after their first visit for follow-up 
neurocognitive testing and MRI. 
d. Distinguish procedures that are for research from those that are clinically indicated and/or standard of 
care. All theprocedures are for research. 
V.04/17/14 
Page 14 of 25 

e. 
Will any study procedures (mc/ud/ng ana/ysis of subject samples or data) be conducted at any site other 
than VANCHCSNACCHCS? 
ZYes Lili No 
. 
If "YES", complete the following information: 
1) Site(s): University of California, Berkeley and outpatient subjects' homes 
2) What study procedures will be performed there? fMRI at UC Berkeley Brain Imaging Center. Outpatient 
subjects will have option to participate in computer-assisted cognitive training at home or in Research Building 4 
at VANCHCS Martinez or the Martinez VA Cente r forintegrated Brain Health and Wellness. 
H. RISK 
1. 
Expected risks 
Describe all known risks to subjects of study-related procedures and products and their expected frequency and 
severity. 
, 
Assess the likelihood and seriousness of identified risks. 
a. 
Physical Risks: The research procedures involved in this study present minimal physical risk to the subjects. 
MRI Studies: Subjects will be repeatedly queried about metal in their bodies and claustrophobia before 
undergoing MRI. The risks for 3T and 41 MRI are the same as for clinical MR! scans, typically at i .5T. The 
risks of this procedure will be attenuated for those patients who have undergone acute MRI as verified by thé 
acute images or notes in their charts. If CT rather than MRI was taken acutely, the reasons will be established 
before considering that patients participation in the MRI portion of this project. Although MRI scanning is 
painless, subjects may experience discomfort. In particular, subjects may be bothered by the beeping and 
hammering sounds made when the scanner is collecting measurements. Some people become claustrophobic 
inside the magnet. Subjects may also experience peripheral stimulation, manifested as a gentle tap or 
sensation of mild electric shock. Because the MRI scanner attracts certain metals, it could move metallic 
objects within the MRI room which could possibly harm a subject. Further, because of the high magnetic field, 
people with pacemakers, heart rhythm disturbances, permanent cosmetics or certain metallic implants will be 
excluded. Finally, because the risks to a fetus from MRI are unknown, all women will have a pregnancy test 
immediately prior to scanning. Disposable earplugs will be provided to diminish the noise. Subjects with a 
history of claustrophobia will be excluded. Precautions have been taken to prevent metallic objects from moving 
within the MRI room. If a subject is uncomfortable for any reason, the experiment will be stopped. They will be 
warned about claustrophobia and will be given earplugs or headphones in fMRI study to reduce the noise 
intensity. They will also be given a hand held buzzer that sounds in the exterior room when pressed to indicate 
that they are uncomfortable or want to disbontinue the imaging procedure. When this occurs subjects will be 
immediately removed from the scanner. 
EEG Studies: Conventional EEG recording with standard subject grounding procedures are always employed. 
Subjects may become bored or anxious during the course of EEG measurements. The anxiety infrequently 
encountered can be immediately addressed and the EEG recordinçi will be aborted, if reQuested. 
b. Psychological Risks: The research procedures involved in this study present minimal psychological risk to the 
subjects. The primary risk in this study is the potential for anxiety, discomfort or boredom associated with 
completing neuropsychological testing, fMRI or EEG testing, and treatment intervention. The behavioral test 
battery is relatively brief and is non-invasive. lt consists of instruments (neuropsychological and functional 
assessments, and self-report questionnaires) that have been previously administered to different patient 
populations, thus the potential for creating undue anxiety or frustration is minimal. There is a possibility of 
fatigue or boredom from performance of cognitive tasks. Participants are allowed frequent breaks during 
training. For patients, training will be adjusted for the fatigue level, and training sessions will stop if patients are 
frustrated or fatigued. 
V.04/17/14 
Page 15 of 25 

C. Social Risks: There are no perceived social risk. 
d. Economic Risks: There are no perceived economic risks. 
e. 
Legal Risks: There is a real, but small risk of breach of confidentiality. This risk will be minimized by controlling 
data storage. 
2. 
Risk minimization 
a. 
Describe the impact of study design on risk. (e.g. does observational design impact on risk; or does 
observatíonal design only impact privacy risks; or does placebo controlled design impact risk, or do all patients 
receive therapy; or does single blind placebo washout period increase risk of uncontrolled symptoms?) 
The study is designed ¡n a series of parts. First, participants are enrolled in a cross-sectional study involving 
neurocognitive and functional MRI testing. Risks associated with this portion are related to time consumption, 
potential boredom and risks to privacy. Additional portions of the study include an experimental cognitive task 
practice interventions, in which participants are randomized prospectively to different groups which do the same 
tasks. but in different orders. The risks of boredom and faticiue increase. 
b. Describe study procedures that minimize risks. 
Psychological: 
_The behavioral test battery is relatively brief and is non-invasive. lt consists of instruments 
(neuropsychological and functional assessments, and self-report questionnaires) that have been previously 
administered to different patient populations, thus the potential for creating undue anxiety or frustration is 
minimal. 
_Cognitive training: There is a possibility of fatigue or boredom from performance of cognitive tasks. 
Participants are allowed frequent breaks during training. For patients, training will be adjusted for the fatigue 
level, and training sessions will stop if patients are frustrated or fatigued. 
Physical: 
_MRI: The risks of this procedure will be attenuated for those patients who have undergone acute MRI as 
verified by the acute images or notes in their charts. If CT rather than MAI was taken acutely, the reasons will be 
established before considering that patients participation in the MRI portion of this project. Although MRI 
scanning is painless, subjects may experience discomfort. In particular, subjects may be bothered by the 
beeping and hammering sounds made when thé scanner is collecting measurements. Some people become 
claustrophobic inside the magnet. Subjects may also experience peripheral stimulation, manifested as a gentle 
tap or sensation of mild electric shock. Because the MRI scanner attracts certain metals, it could move metallic 
objects within the MRI room which could possibly harm a subject. Further, because of the high magnetic field, 
people with pacemakers, heart rhythm disturbances, permanent cosmetics or certain metallic implants will be 
excluded. Finally, because the risks to a fetus from MRI are unknown, all women will have a pregnancy test 
immediately prior to scanning. Disposable earplugs will be provided to diminish the noise. Subjects with a 
history of claustrophobia will be excluded. Precautions have been taken to prevent metallic objects from moving 
within the MRI room. If a subject is uncomfortable for any reason, the experiment will be stopped. They will be 
warned about claustrophobia and will be given earplugs or headphones in fMRI study to reduce the noise 
intensity. They will also be given a hand held buzzer that sounds in the exterior room when pressed to indicate 
that they are uncomfortable or want to discontinue the imaging procedure. When this occurs subjects will be 
immediately removed from the scanner. 
_Conventional EEG recording with standard subject grounding procedures are always employed. Subjects 
may become bored or anxious during the course of EEG measurements. The anxiety infrequently encountered 
can be immediately addressed and the EEG recording will be aborted, if requested. 
_Privacy: We recognize the need to guaranteed participants confidentiality in order to protect individual 
participants from potential embarrassment, as well as to obtain maximally valid data. All information will be kept 
confidential in accordance with all regulations as specified by the Department of Veterans Affairs. All patient 
data will be depersonalized after initial screening and enrollment into the study. All personally identifying 
information will be kept in locked cabinets or password protected files. 
V.04/17/14 
Page 16of25 

C. Describe standard of care procedures that minimize risks. 
There is no clear national standard of care for rehabilitation treatments for patients with brain injuries. However, 
most of our subjects receive high quality medical care at the VANCHCS by qualified professionals including 
physicians, psychologists and therapists. Neurologic and neuropsychologic evaluation, CT and/or MRI scans 
are all part of standard of care in our practice. 
J. 
RISK BENEFIT RATIO 
i 
Risks in Relation to Benefits 
a. 
What are the direct benefits to the participants? 
There are no definite direct benefits to the subjects. The findings from these studies may potentially make a 
major impact in improving rehabilitation for patients with brain injuries, leading to a direct benefit to society. 
b. 
Why do you believe the risks are reasonable in relation to the potential benefits to the participants? 
The risks of this research to subjects are minimal. There are no definite direct benefits to the subjects. 
c. 
What are the benefits to society? 
As noted in the introduction, improved treatments for executive control dysfunction would potentially make a 
major impact in improving outcomes after brain injuries. The findings from these studies will be presented to 
health care workers and to other scientists in the field, and this is expected to influence both clinical care and 
future scientific investigations. 
Why do you believe the risks are reasonable in relation to the potential benefits to society? The risks of 
this research to subjects are minimal, and therefore the risk is reasonable in relation to the potential benefits to 
society. 
: Alternatives to participation 
a. 
Describe appropriate alternative procedures or courses of treatment, if any, which might be 
advantageous to the participant. (Ifno alternatives exist or ifthis is not a treatment study, state so.) 
This is not a treatment study. Subjects may decline participation in these studies, or discontinue participation at 
any time. Declining to participate in the studies will not have any effect onstandard clinical care. 
J 
MONITORING SAFETY 
i . 
Describe the Data and Safety Monitoring Plan that ensures the safety of participants in this research study 
(eg. what labs to monitor for abnormalities, what questionnaire responses to monitor for suicide) 
All patients will be seen by the Pl or his research staff. Research subjects will continue to receive usual care. 
Although this is a minimal risk study, the Pl and investigators will monitor study subjects for adverse events during 
the study. Monitoring will occur continuously during study activities. Although the only interventions are behavioral, a 
standard grading scale will be used to describe AEs if the need arises: Onone, i =mild, 2=moderate, 3=severe, 
4=life-threatening, 54atal. The attribution scale is i =definitely not related, 2=probably nöt related, 3possibly 
related, 4probably related, 5=definitely related to the study interventions. The Pl will promptly report any serious 
adverse events or unanticipated problems involving risks to study subjects in accordancewith regulations: 
reportable adverse effects arising from any of the research procedures will be submitted promptly to the IRB. 
Although they are not anticipated to occur, unanticipated problems (involving risks to subjects) or Serious Adverse 
Events in subjects will be reported to the IRB within 5 working days of awareness of the event. Copies of reports will 
be submitted to the IRB so that they are received no later than i 5 calendar days after the event. In addition, adverse 
events in all categories will be included in the Pis reports to the RB as required by the federal regulations. Ail 
reportable adverse events will be compiled, and reported in summary form, on an annual basis to the IRB, and at the 
conclusion of the study. The Pl reviews and reports on the progress of the study on an annual basis. The Pl will 
monitor study progress, outcomes and participant safety, and may make recommendations on changes to the study 
protocol. The Pl will review safety on an ongoing basis. Dr. Anthony Chen will perform the safety monitoring. 
V.04/17/14 
Page 17 of 25 

2; Does this study have a Data and Safety Monitoring Board (DSMB)? 
LuYes ZN0 
If "YES': 
a. What is the nature and expected role of the DSMB? 
b. 
How often will the findings of the DSMB be reported to the IRB? 
3. 
Explain how researchers will manage adverse events and research-related injuries. 
All research staff have been directed to document adverse events and to notify the Principal Investigator of any 
adverse event. Investigators will follow up with subjects until the resolution of the adverse event and will ensure that 
appropriate medical care is provided. 
4. 
Describe the circumstances under which a participant may be withdrawn prematurely from the study and 
the potential risks of such early withdrawal. 
A participant may decide to withdraw or be withdrawn for a variety of medical and personal reasons, such as lack of 
interest, non-participation, or change in medical condition. A potential risk of early withdrawal would be the possible 
adverse effect on the participant's self-esteem (e.g., feeling like a failure). This risk would be addressed by 
supportive counseling of participants who are withdrawn prematurely. 
5. Describe the procedures for reporting adverse events. 
Researchers will complete an adverse event report and notify the Principal Investigator, who will report the event to 
VANCHCS. All unanticipated problems involving risk to subjects or others related to participation in the study will be 
promptly reported by phone (301-619-2165), by email (hsrrb@det.amedd.army.mil), or byfacsimile (301-619-7803) 
to the USAMRMC, Office of Research Protections, Human Research Protection Office. A complete written report 
will follow the initial notification. In addition to the methods above, the complete report will be sent to the U.S. Army 
Medical Research and Materiel Command, AUN: MCMR-ZB-PH, 504 Scott Street, Fort Detrick, Maryland 21702- 
5012. 
K. SAFETY REPORT 
i . Adverse Events 
a. 
Local (Internal) Adverse Events and Serious Adverse Events (AEISAE): Have ALL complications, untoward 
side effècts, or adverse events related or possibly related to research at this site been reported to the IRB since the 
last review? 
Li Yes 
No 
N/A 
none occurred 
e 
¡f "YES": 
Attach a Local Adverse Event spreadsheet summarizing all AEISAE's which occurred at this site since 
the last report to the IRB. 
e 
(f "NO": 
Submit the missing report to the IRB and attach a Local Adverse Event spreadsheet summarizing all 
AE/SAE's which occurred at this site since the last report to the IRB. 
b. Global (External) Adverse Events and Serious Adverse Events (AE/SAE): Have any complications, 
untoward side effects, or adverse events been reported at other sites (SAE or IND Safety Reports) since last 
report? 
V.04/17/14 
Page l8of 25 

2. 
Have unanticipated problems* (localórgiobal) involving risks to subjects or others, or significant new findings 
(that have not been previously reported) been discovered since the previous IRB review that might affect the 
subject's willingness to continue participation? 
LlYes ZNo 
If "YES", complete the following: 
a. 
Attach a spreadsheet summarizing all unanticipated problems which occurred siñce the last report to the 
IRB. 
b. 
Explain the risks or findings in detail: (a clear explanation of why the adverse event or series ofadverse events 
has been determined to be an unanticipated problem) 
C. Describe any proposed protocol changes or other corrective actions to be taken by the investigators in 
response to the unanticipated problem: 
Do these risks or findings require modification of the informed consent form? 
LjYes Lili No 
If 'YES", have the modifications been submitted to the IRB? 
LlYes LINo 
e. Were subjects notified of these risks or findings? 
LuYes LINo 
f. 
Were subjects re-consented? 
LlYes LINo 
3. 
Have other unantiòipated problems (not related to adverse events) been discovered since the previous IRB 
review? 
luYes !No 
If "YES", complete the following: 
a. Attach a spreadsheet summarizing all unanticipated problems which occurred since the last report to the 
IRB. 
b. 
Explain the findings in detail: 
C. Describe any proposed protocol changes or other corrective actions to be taken by the investigators in 
response to the unanticipated problem not related to an adverse event: 
* NOTE: Unanticipated problems are any incident, exp.rie-nce, or outcome that meet 
of the following criteria: 
Is unexpected in terms of nature, severIty, or frequency 
Is related or possibly related to partfciloation in the research 
Suggests that the research places the subject or others at a greater risk of harm than wa previously known or 
4. Describe any complaints about the research since the last IRB review. 
N/A - none occurred 
5. Describe anyunanticipated protocol deviations (including errors and accidents) since the last review. 
z N/A-noneoccurred 
V.04/17/14 
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L. 
PRIVACY AND CONFIDENTIALITY 
1. 
Research Data 
a. 
Identifiers: Please indicate all identifiers that may be used by researchers or included in study research 
records. 
LI NO identifiers used by researchers (skip to item L. 1.d. "Medical Records or Health Information') 
Check all that apply: 
z Names 
Social Security Number 
LII Device Identifiers 
z Dates 
Medical Record Number 
Web URLs 
z Postal Addresses 
LI Health Plan Numbers 
IP Address Numbers 
z Phone Numbers 
Account Numbers 
LI Biometric Identifiers 
LI Fax Numbers 
License/Certificate Numbers 
Photos and Comparable Images 
Email Addresses 
LI! Vehicle ID Numbers 
Any Other Unique Identifier 
b. Source of Identifiers Listed Above: Please indicate the sources of the information listed in part i (a) above 
Check all that apply: 
Medical Records (created as part of health care, collected as part of health care, added to the medical 
record, extracted from the medical record, or used to make health care decisions) 
Directly from the Participant, including Interviews, Questionnaires 
LI Records Open to the Public 
LI Other: 
c 
Describe how identifiers will be used to screen and/or recruit participants for the trial. 
Referring providers may provide information to patients on how to contact research staff, but may also ask 
permission for research staff to contact the patient. This includes permission by the patient to release basic 
information, including name and contact information, to research staff. To accomplish this, the study will use a 
Partial Waiver of Authorization and Consent for recruitment. PHI will be accessed by the PI, co-investigators, 
and research staff in order to contact participants for screening. Screening and eligibility data will initially be 
reviewed with personal identifiers included. 
d. 
Medical Records or Health Information: Please indicate all information that may be used by researchers or 
included in study research records. 
till NO medical record or health information used by researchers (skip to Section M. 'Research Data Security') 
Check all that apply: 
History and Physical Exam 
Progress Notes 
Operafive Report(s) 
Discharge Summary(ies) 
Diagnoses 
Drugs/Medications 
Radiology Images 
Z Radiology Reports 
Pathology Reports 
Laboratory Reports 
LI ECG Reports 
Z Consult Reports 
z Drug Abuse 
Alcoholism dr Alcohol Abuse 
Testing for or Infection with HIV 
LI Sickle Cell Anemia 
z Psychological Tests 
Mental Health (not psychotherapy notes) 
Patient Demographics 
Only the following records of types of health information: 
e 
Describe who will access protected health information (PHI) (i.e. medical record) and for what purpose. 
PHI will be accessed by the PI, co-investigators, and research staff in order to contact participants for screening 
as well as scheduling of studies (e.g. making appointments for neur000gnitive testing). 
V.04/17/14 
Page 20 of 25 

f. 
Disclosure of Protected Health Information (Pl-li): Please indicate to whom or where you may disclose any 
of the information listed above as part of the study process. 
Check all that apply: 
LI We do not plan to share any of the PHI listed above outside the research team. 
VANCHCSNACCHCS Research & Development Committee and Subcommittees 
LI VANCHCSNACCHCS Designated Non-Profit Corporation 
LI U.S. Food and Drug Administration (FDA) 
U.S. Department of Health and Human Services Office for Human Research Protection (OHRP) 
U.S. Government Accounting Office (GAO) 
Participant's Medical Record 
Study Sponsor: 
l51 Others UC Berkelev liC San Francisco. VA San Francisco 
g. Identify who will disclose information 
Anthony Chen, MD and authorized members of the research team. 
2. 
Data Protection 
a. 
Describe the provisions that exist to protect participant privacy during and after the research. 
We will collect only the minimum amount of the individual's private information required to complete our study. 
To protect privacy, we will advise potential subjects of the minimum amount of personal information that would 
be required of them in order to participate in our study. Furthermore, we will provide information about the 
logistics of participating in our research study (e.g., location of testing) to ensure that each subject can decide 
whether logistics will impinge on his/her privacy. Finally, all participants will be informed regarding how 
information is secured and stored to protect confidentiality. Based on this information, the potential subject can 
determine for him/herself if he/she wishes to provide this information to us and whether he/she wishes to 
participate in our research study. 
Subjects are contacted with discretion. Consenting and testing take part in private settings. To protect privacy, 
all subject interviews will be held in a closed room. Information will be discussed between the subject, 
interviewer, and PI only. None of the information reported by the interviewee will be discussed outside of the 
enclosed room and all information will be kept confidential. 
b. Describe the provisions in place to protect participant confidentiality during and after the research. 
Patient data will be kept confidential after initial screening and enrollment into the study. No personally 
identifying information will be used for data analyses. Collected datawill include questionnaire results, 
neurocognitive testing data, and MRI data. Data will be stored in a database with personally identifying 
information removed. All personally identifying information, including patient name, and contact information will 
be kept in locked cabinets or password protected files. A key will be kept to match personal information with 
data in the case that patients need to be identified and contacted. Patients who receive computer-assisted 
training at home will be provided with a training website link as well as a secure login (divorced from personal 
information) and password once their training phase has begun. 
M. INTERIM FINDINGS 
t Provide a summary description of study progress, subject experiences, research results obtained thus far, 
and any new information since the IRB's last review. 
i . Training goal-oriented attention self-regulation amongst Veterans with chronic TBI. Twenty-two Veterans with 
history of chronic TBI (> 6 months) and functional complaints have completed this research protocol after having 
been randomized into active training (GOALS) or a comparison intervention involving brain health education (BHE). 
Results. GOALS participants demonstrated improvements on composite measures of attention and executive 
functions (p <0.01) and a simulated, ecologically-valid 'real world' task (p < 0.01), as well as reported improvements 
on multiple aspects of cognition as it relates to daily functioning (i.e., within domains of working memory, sequencing 
and switching of attention, and awareness, self-monitoring, planning, task execution, learning, managing 
fatigue/energy, andanxiety;_p<O.05).BHE_participants_did not_demonstrateorreport sirnUar changes.. 
V.04/17/14 
Page2l of 25 

2. Development and preliminary testing of a cognitive training system for goal-directed self-regulation: "From Startup- 
to-CEO". We developed a fully manualized cognitive training system consisting of therapist-administered training and 
specially designed game scenarios to help illustrate, practice, and develop training concepts. 
3. Preliminary data lend support to the plausibility of the hypothesized moderation and medication mechanisms under 
investigation in this protocol. Data also support that these approaches to training goal-oriented self-regulation are 
feasible and may help with transfer of skills to daily life contexts and individual goals. 
Provide a summary of any relevant recent literature since the IRB's last review. (Attach copies ofany relevant 
publications.) 
2. Attach any relevant multi-center trial reports. 
N. INFORMED CONSENT PROCESS 
1. 
Will all participants taking part in this study be consented on VA Form 10-1086? 
Yes 
No 
If 'YES', continue to question #2 and #3 below. 
If 'WO", submit the document entitled 'Request to Waive Consent and Authorization for a Research Study" and 
skip Sections 02 and 03. 
2. 
Describe the process of obtaining informed consent. 
a. 
Describe who conducts the consenting process. 
Chen, MD, Tatjana Novakovic-Agopian, PhD, Fred Loya, PhD, MA, Erica Pool, Sahar Yusef, and 
. 
Nicholas Rodriguez will conduct the consenting process. 
b. 
Describe when it occurs. 
After a preliminary determination that a candidate meets the inclusion/exclusion criteria, the candidate is 
contacted by the Pl or Co-investigators, who explain the study in great detail. The contact may be at the 
Martinez VA Outpatient Clinic and/or Center for Rehabilitation and Extended Care, or if necessary, by 
telephone. The explanation of the study includes a description of the behavioral studies and MRI scanning. The 
participants are explicitly told that there are no treatment benefits to the proposed research and all participants 
are told that they can withdraw from the research at anytime. Risks of the behavioral testing, task practice and 
functional MRI imaging are explained. 
Candidates are given as much time as needed to consider participation 
in the study and ask questions. If they are agreeable to the study after initial discussions, candidates are 
brought to VANCHCS and the studies are again described in detail, with risks and benefits explained. Informed 
consent is then obtained. 
c. 
Describe where it occurs. 
At the Martinez VA Outpatient Clinic, Center for Integrated Brain Health and Wellness, Research Building R-4, 
Center for Rehabilitation and Extended Care, or UC Berkeley Brain Imaging Center. 
d. Describe how you will assure an acceptable level of comprehension before consent. 
In order to meet eligibility criteria, patients need to be able to demonstrate understanding of the potential risks, 
potential benefits, and voluntary nature of the study. Only patients deemed to have capacity by the patient's 
clinicians will be accepted into the study. 
V.04/17/14 
Page 22 of 25 

e. 
For participants who may have impaired decision-making capacity to give înformed consent: 
1) Describe the likely range of impairment 
nia 
2) Describe how the participants' decision-making capacity to consent will be determined. 
The Pl (Anthony Chen) and clinician co-investigators (Mark D'Esposito, Novakovic-Agopian), all of whom are 
experienced clinicians, will interview the patients and ascertain whether the patient understands and has the 
capacity to make an informed decision. Candidates are given as much time as needed to consider participation 
in the study and ask questions. Potential participants are asked to restate the description of the study, risks, 
and benefits. Informed consent is then obtained. 
3) Who will determine whether or not the participant has decision-making capacity to consent? 
The PI (Anthony Chen) and clinician co-investigators (Mark D'Esposito, Novakovic-Agopian). 
f. 
If any vulnerable populations will be recruited, describe what precautions will be taken to insure their 
protection from undue influence. 
No vulnerable populations will be recruited. Patients with brain damage of the types that are described in this 
study typically retain the ability to make informed decisions. They are able to understand and repeat study 
procedures, risks, and benefits. Patients with severe damage may not retain this capacity, but as we are only 
including patients with mild problems this will not be an issue. 
g. 
If surrogate consent is likely to be required, describe your procedure for obtaining consent from the 
legally authorized representative. 
n/a 
3. After Hours Contact Information (to be included in the consent form) 
a. The VA approved after-hours telephone number for research studies is (91 6) 843-7000 extension 6051. 
b. This study will use the VA approved after-hours telephone number for research studies. 
LuYes ZNo 
If "YES", complete the following: 
1) 
Designated Service (department): 
OR 
1) 
Designated Contact Person: 
2) After-hours telephone number for the designated contact person (to be given to the VA after-hours 
operator): 
b. This study will use a Designated Contact Person. 
YesLINo 
. 
e 
If 'YES", complete the following: 
1) Designated Contact Person: Anthony Chen, MD 
2) After-hours telephone number for the designated contact person: 925-580-2806 
V.04/17/14 
Page 23 of 25 

O. PRINCIPAL INVESTIGATOR'S KNOWLEDGE ATTESTATION 
Initial beside each statement to confirm your knowledge and agreement. 
T:i;-i . i assure that the rights and welfare of human subjects participating in this research project will be 
protected at all times and that the benefits to be gained from this study are commensurate with the 
risks involved. 
ì:-2. I will obtain, (unless a waiver of consent and authorization is approved) an authorization to use PHI for 
research and a fully documented research informed consent on a VA Form i O-1 086 for each subject 
enrolled. 
:iii:i:i I will document the consent process in the progress notes for each research subject, unless a waiver of 
consent and authorization is approved. 
Tì4_ 
I certify that I will report all serious adverse events and unexpected adverse experiences as required. 
T:?:: 
I acknowledge that I will immediately report any complications arising from this study to the Human 
Studies Subcommittee/IRB through the Research Office. 
T:& 
I understand that any research project utilizing VA resources (i.e. space, personnel, services) must be 
approved by VANCHCSNACCHCS Research and Development (R&D) Committee prior to 
commencement of the project. 
::L 
I understand that any research involving VANCHCSNACCHCS patients must be approved by 
VANCHCSNACCHCS R&D Committee. 
:::8 I will not begin any research project using human subjects before it has been fully approved by 
VANCHCS IRB and VANCHCSNACCHCS R&D Committees. 
____9. I understand that I am required to annually complete an educational course or web-based training on 
both the protection of human subjects in research and Good Clinical Practice (GCP). ORD and 
Collaborative IRB Training Initiatives (CITI) have developed a VA training curriculum to satisfy this 
annual training requirement. (http:llwww.appcl ,va.gov/resdev/fr/PRIDE/training/) 
:iiì:ìç:io. I understand that the research staff working for me who are involved in human studies are required to 
annually complete an educational course or web-based training on both the protéction of human 
subjects in research and Good Clinical Practice. A single combined course will satisfy this 
requirement. 
-.- i i . I understand that there may be specific training requirements for me and my research staff regarding 
animal research, laboratory safety, and security. 
t2.l understand that I am to cooperate fully with VANCHCS Research Compliance Officer regarding 
compliance in research. 
TZI understand that any research involving radiation must be approved by VANCHCS Radiation Safety 
Committee. 
TIÇI-4. I agree to abide by the requirements of VRA Handbook i 200.1 8, Intellectual Property. 
(http://www.va.gov/publ/direc/health/Handbook/1 200-1 8hk.pdf) 
agree to abide bythe requirements of VANCHCS P5-151-9, Publication ofProfessiona! Papers 
(http://vaww.northern-california.med.va.aov/policies/Researchlndex.htrnl) and VHA Handbook i 200.19 
Presentation of Research Results Handbook. 
(http:Ilwww.va.govlpubl/direclhealthlhandbookll 200.1 9hk.pdf) 
TTiß. 
I agree to abide by the requirement of VANCHCS P5-i 51 -7, Administration of Non-VA Funded Research 
Grants. (http:llvaww.noherncaIifornia.med.va.gov/poIicies/Researchlndex.htmI) 
I agree to abide by the requirements of VANCHCS PS-i 51 -2, Detecting and Managing Conflicts of 
Interest in Research 
ttp:llvaww.northerncaIifornia.med.va.gov/policies/ResearchIndex.html). 
i8. I agree to abide by the requirements of VHA Handbook 1200.8, Safety ofPersonnel Engaged in 
Research and the Chemical Hygiene Plan for Medical Research. 
V.04/17/14 
Page 24 of 25 

P. PRINCIPAL INVESTIGATOR'S ASSURANCE 
As the Principal Investigator, I have ultimate responsibility for the performance of this study, the protection of 
the rights and welfare of the human subjects, and strict adherence by all co-investigators and research 
personnel to all requirements of the Human Subjects Subcommittee (IRB), the Research and Development 
Committee, federal regulations, and state statutes for human subjects research. 
I hereby assure the following: 
All named individuals on this project have read and understand the procedures outlined in the protocol. All 
experiments and procedures involving human subjects will be performed under my supervision or that of another 
qualified professional listed on this protocol. 
I understand that, should I use the project described in this application as a basis for a proposal for funding (either 
intramural or extramural), it is my responsibility to ensure that the description of human subjects used in the funding 
proposal(s) is identical in principle to that contained in this application. 
I will submit modifications and/or changes to the IRB as necessary to ensure these are identical 
I and all the sub-investigators and research personnel agree to comply with all applicable requirements for the 
protection of human subjects in research including, but not limited to, the following: 
. 
Obtain legally effective informed consent of all human subjects or their legally authorized representatives, and use 
only the currently approved, stamped consent form (if applicable); 
u 
Make no changes to the approved protocol or consent form without first having submiffed those changes for 
review and approval by VANCHCS Institutional Review Board; 
. 
Within 24 hours of investigator awareness, communicate any Local Research Subject Deaths to the IRB and 
submit a written follow-up report to the IRB within 5 working days; 
. 
Communicate other Local Serious Adverse Events, except death, in writing to the IRB within 5 working days after 
investigators learn of the event; 
. 
Promptly provide the IRB with any information requested relative to the project; 
. 
Promptly and completely comply with an IRB decision to suspend or withdraw its approval for the project; 
. 
Submit an application for continuing review within 60 days prior to the date on which the approval for the study 
expires. 
I understand if I fail to apply for continuing review, approval for the study will automatically expire, and 
study activity múst cease until IRB current approval is obtained; 
. 
Submit a final report, within 60 days, to VANCHCS Research Office at the conclusion of this project; 
. 
If I am unavailable to direct this research personally, I will arrange for an investigator to assume direct 
responsibility as principal investigator in my absence. 
I will submit a protocol amendment to the IRB in advance of 
such arrangements requesting th is modification. 
I understand my obligations as an investigator and agree to fulfill them 
The information contained in this application is complete to the best of my knowledge. 
By signing this document, I attest that all the information I have provided is accurate to the best of my knowledge 
Principal Investigator 
Date. 
05/2212017 
V.04/17/14 
. 
Page 25 of 25