Assessment and Treatment of Cognitive Functioning Deficits in Veterans With PTSD
Phase: NA
Conditions: Posttraumatic Stress Disorder
Sponsor: VA Office of Research and Development

Assessment and Treatment of Cognitive Functioning Deficits in Veterans with 
PTSD
NCT03696225
01/09/2024

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Research Protocol 
Title 
“Assessment and treatment of cognitive functioning deficits in Veterans with PTSD” 
Investigators  
Maya E. O’Neil, PhD 
Specific Aims/Purpose 
PTSD is common in Veterans of wartime service eras, particularly those who receive VHA 
services: Over 500,000 Veterans receive VHA PTSD treatment each year. PTSD is associated 
with both objective cognitive impairment and subjective (self-reported) cognitive problems. A 
recent meta-analysis provides strong support for associations between PTSD and worse 
performance on cognitive tests of verbal learning/memory, attention/working memory, executive 
functions, and processing speed, language, and visual learning/memory. The effect of PTSD on 
cognition is often independent of mental health comorbidities or TBI history. Although robust 
research suggests that evidence-based psychotherapy (EBP) for PTSD results in significant 
improvement in PTSD symptoms, cognitive impairment is associated with reduced PTSD 
treatment response. Fortunately, Veterans with comorbid PTSD and TBI can benefit from EBP 
for PTSD, including standard and modified versions that accommodate cognitive impairment. 
However, some Veterans continue to experience cognitive problems even after completing 
evidence-based PTSD treatment. Therefore, the VA needs a rehabilitation intervention to 
address this clinical service gap. 
Our research team (including Drs. Huckans, Twamley, and Storzbach) developed 
Compensatory Cognitive Training (CCT). This manualized intervention teaches methods for 
managing and compensating for cognitive symptoms, thereby reducing suffering and functional 
limitations. Many aspects of PTSD can influence cognition (e.g., decreased motivation, 
avoidance, medication side effects). CCT is promising due to its focus on teaching 
compensatory strategies regardless of the etiology of cognitive deficits. Our studies have 
demonstrated CCT efficacy for mild TBI and for schizophrenia. Compared to treatment as usual 
(TAU), CCT significantly improves learning, memory, executive functioning, and 
attention/working memory, as well as self-reported cognitive, social, and vocational functioning; 
use of compensatory strategies; and quality of life (QOL). CCT efficacy is not moderated by 
depression or PTSD, suggesting that CCT might be effective for treating cognitive impairment 
and improving functioning in Veterans with PTSD, even if they do not have a history of TBI. To 
test this, we need to study the efficacy of CCT in Veterans without other conditions (e.g., TBI or 
severe mental illness) that could confound results. 
Aim 1: Evaluate recruitment feasibility and participant acceptability and characteristics in a pilot 
Randomized Controlled Trial of CCT vs. TAU in Veterans who previously engaged in PTSD 
treatment and report current cognitive functioning deficits.  
Aim 2: Estimate effect sizes to calculate needed sample size for a fully powered RCT of CCT 
vs. TAU for improving objective and subjective cognitive functioning deficits, mental health, 
other aspects of functioning, and QOL. 
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Hypotheses: (1) CCT will be feasible and acceptable to participants in a pilot RCT of CCT 
versus TAU for Veterans who have previously participated in PTSD treatment and report current 
cognitive functioning deficits. (2) We will be able to collect adequate feasibility, acceptability, 
and participant characteristics data to inform a future, fully powered RCT of CCT versus TAU for 
Veterans with PTSD-related cognitive functioning deficits. (3) Effect size data from this pilot 
RCT of CCT versus TAU will allow us to estimate effect sizes and needed sample size for a fully 
powered RCT comparing CCT versus TAU on outcomes including objective and subjective 
cognitive functioning, mental health symptoms, social functioning, and QOL in Veterans with 
PTSD-related cognitive functioning deficits. 
 
Scientific Rationale and Significance  
Posttraumatic stress disorder (PTSD) is common among Veterans of all wartime service 
eras, particularly those who receive VHA services (Harpaz-Rotem & Hoff, 2015). Over 
500,000 Veterans each year have received PTSD treatment through the VHA since 2011 (US 
Department of Veterans Affairs, 2016). PTSD is a mental health disorder resulting from 
exposure to one or more traumatic events. According to the Diagnostic and Statistical Manual of 
Mental Disorders fifth edition (DSM-5), PTSD is characterized by symptoms of intrusive re-
experiencing of a traumatic event, avoidance of associated stimuli and reminders, alteration in 
mood and cognitions, and persistent physiological arousal and reactivity which impact 
functioning and persist for at least one month (APA, 2013). Approximately 50% of women and 
60% of men in the US will experience one or more traumatic events in their lifetimes, and an 
estimated 8,000,000 people in the US meet criteria for PTSD in a given year (NCPTSD, 2015). 
Up to 20% of Veterans from the Operation Enduring Freedom/Operation Iraqi Freedom 
(OEF/OIF) service era screen positive for probable PTSD compared to 10-12% from the Gulf 
War era and around 15% from the Vietnam era (Dohrenwend, 2006; Hoge et al., 2004; Kang et 
al., 2003; NCPTSD, 2015; Terhakopian et al., 2008).  
 
While research has historically emphasized mental health symptoms of PTSD such as 
flashbacks, nightmares, avoidance, and hypervigilance, PTSD is also associated with objective 
and subjective (self-reported) cognitive functioning deficits (Roca & Freeman, 2010). Subjective 
deficits are not surprising given that concentration difficulties are a core symptom of PTSD 
(DSM-5, 2013). PTSD symptoms include self-reported cognitive problems such as intrusive 
memories; inability to recall details of the trauma; hypervigilance or attentional bias toward 
trauma reminders, threats, or extraneous environmental details; and concentration difficulties 
including moderating control over trauma-related thoughts (Brewin 2007; Litz et al., 1996). 
 
A recent meta-analysis of cohort studies provides strong support for associations between 
PTSD and objectively assessed cognitive functioning deficits (Scott et al., 2015). Effect sizes for 
impairment across cognitive domains were generally of medium magnitude (Cohen, 1988; 
Borenstein et al., 2009). Effect sizes ranged from d values of -,62 (verbal learning), -.59 (speed 
of information processing), -.50 (attention/working memory), -.46 (verbal memory), -.45 
(executive functions), -.43 (language), -.38 (visuospatial functioning), -.32 (visual learning), to -
.29 (visual memory). These effects were mediated by PTSD symptom severity for verbal 
learning but not for attention/working memory or speed of information processing. Even in 
Veterans with a history of mild traumatic brain injury (TBI), objectively assessed and self-
reported cognitive functioning deficits are largely explained by PTSD, and not due to long-term 
consequences of mild TBI (e.g., Vasterling et al., 2012; O’Neil et al., 2014; Storzbach,* O’Neil,* 
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et al., 2015 [shared first authorship]). Research confirms the links between PTSD and both 
functional and structural brain changes related to cognitive functioning (Morey et al., 2012; Shin 
et al., 2006). While underlying neurobiological mechanisms for associations between PTSD and 
cognitive impairment need further investigation, some theories have been supported by recent 
imaging research. For example, PTSD has been associated with biological differences in 
numerous areas of the brain including the amygdala, hippocampus, dorsolateral and 
ventromedial regions of the prefrontal cortex, and the cingulate cortex (Brown & Morey, 2012). 
These regions of the brain are associated with many PTSD-related functions (e.g., emotions, 
memory, and fear) as well as functions not traditionally associated with PTSD such as episodic 
memory, affective and cognitive control, processing of ambiguous information, attention, 
working memory, and decision making. 
 
Cognitive functioning deficits associated with PTSD often interfere with other aspects of 
functioning and quality of life (QOL; e.g., Pittman et al., 2012; Vasterling & Verfaellie 2009). 
Wrocklage et al. (2016) report that executive functioning deficits in Veterans with PTSD is 
associated with poorer occupational functioning; both executive functioning and speed of 
information processing deficits are associated with poorer physical health-related QOL. 
Similarly, Gueze et al. (2009) report that PTSD in a Veteran sample is associated with memory 
deficits which in turn predict impairments in social and occupational functioning. A very recent 
study (Silverberg et al., 2017) examined relationships among PTSD and depression symptom 
severity, cognitive functioning, and QOL in Veterans and US Service Members with PTSD. This 
study found that cognitive functioning was independently associated with QOL (beta = -.204). 
This relationship was not related to TBI history, though was related to depression. 
 
A robust body of research suggests that evidence-based psychotherapy (EBP) for PTSD results 
in clinically significant improvement in PTSD symptoms for many individuals with PTSD, 
including Veterans (Cusack et al., 2016). Some recent research suggests that Veterans with 
comorbid PTSD and mild to severe TBI can benefit from EBP for PTSD, while other preliminary 
research suggests that cognitive impairment is associated with reduced PTSD treatment 
response. Despite reducing PTSD symptoms for many Veterans, it is common for others to 
have significant PTSD symptoms even after participating in EBP. For example, in some studies, 
less than half of Veterans receiving EBP for PTSD achieved loss of diagnosis (e.g., not meeting 
diagnostic criteria on the Clinician Administered PTSD Scale [CAPS] or scoring less than 50 on 
the PTSD Checklist [PCL]; Yehuda et al., 2014; Schnurr et al., 2015). While some Veterans may 
see improvement in cognitive functioning after EBP reduces related PTSD symptoms (e.g., re-
experiencing, hyperarousal, avoidance, and numbing), others may have engrained cognitive 
functioning deficits or other residual symptoms such as sleep difficulties that affect cognition 
(Schnurr et al., 2015, Verfaellie et al., 2015). 
 
Given that PTSD-related cognitive functioning deficits persist for some Veterans even 
following PTSD treatment, interventions should be developed to effectively treat them. 
The VA/DoD PTSD Clinical Practice Guideline (CPG, 2010) recommends that if residual 
symptoms follow EBP, adjunctive therapies targeting individual symptoms should be 
considered. However, the CPG does not cover any treatments specifically targeting PTSD-
related cognitive functioning deficits. Similarly, the National Center for PTSD (NCPTSD) website 
section on “Assessment and Treatment of PTSD with Co-Occurring Neurocognitive Disorder,” 
notes that “PTSD commonly co-occurs with neurocognitive disorders (NCD), yet specific 
assessment techniques and treatments for patients with both diagnoses have not been 
established” (2015).  
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Compensatory Cognitive Training (CCT) is a promising intervention for treating cognitive 
functioning deficits in Veterans. CCT draws from the theoretical literature on compensatory 
strategy training for other cognitively impaired populations (e.g., Huckans et al., 2013; Twamley 
et al., 2010; Storzbach et al, 2016). It is a rehabilitation model that aims to teach individuals 
strategies that allow them to work around cognitive deficits. Consistent with this model and the 
expert recommendations for civilians and Service members with TBI (Cicerone, 2011), 
manualized CCT treatment provides training in compensatory attention and learning/memory 
skills, formal problem-solving strategies applied to daily problems, and the use of external aids 
such as calendar systems and assistive devices to promote completion of daily tasks 
(Storzbach et al., 2016). CCT is a promising intervention for PTSD-related cognitive problems 
due to its focus on teaching and practicing compensatory strategies regardless of the etiology of 
cognitive functioning deficits. CCT sessions focus on practical and generalizable compensatory 
strategies such as organizing home and work life and priorities from daily goals and check lists 
to physical layout changes to facilitate ease of functioning. Veterans also work on implementing 
a calendar support system, most often through a smart phone or small day planner, to help 
them use efficient and repeated reminders about activities and behaviors that support their 
larger goals. Examples include weekly reminders for support groups, social activities, work or 
school meetings and assignments, and medical appointments. Daily reminders are used for 
physical activities, family check-ins, meal preparation, pet or childcare, and medications. Stress 
management strategies such as progressive muscle relaxation or circle breathing, with VA 
smartphone app support when appropriate, are also incorporated into daily and weekly 
schedules, which supports common mental health treatment goals. Specific memory, learning, 
executive functioning, processing speed, working memory, attention, and concentration 
strategies are also taught as part of this intervention, with specific examples tailored to each 
Veteran’s goals and unique circumstances in ways that are relevant to everyday functioning 
(e.g., returning to school, attending multiple medical appointments, overcoming challenges at 
work, etc.). The strategies used in CCT are all taught and rehearsed in sessions. CCT is 
applicable to many scenarios involving cognitive functioning deficits associated with mental 
health and chronic stress, and helpful for Veterans who are managing common transitions (e.g., 
job changes, returning to school, managing conflicting family demands). This pragmatic 
treatment focused on improving the ability to compensate for cognitive deficits and improve 
functioning and QOL is therefore very likely to be applicable to individuals with a range of 
mental health diagnoses including PTSD. 
 
Although not yet formally studied, it is likely that Veterans with PTSD will benefit from CCT even 
if they do not have a history of TBI. Our team’s recent trial of CCT for Veterans with a history of 
mild TBI provides relevant preliminary data to support this hypothesis. Post hoc analyses of 
these CCT clinical trial data and examined whether mental health, including PTSD, depression, 
and substance dependence, moderated the efficacy of CCT for Veterans with a history of mild 
TBI. None of the mental health factors moderated CCT efficacy in Veterans with a history of 
mild TBI, suggesting that a further investigation of CCT for Veterans with PTSD, but without a 
history of TBI, is appropriate (Pagulayan,* O’Neil,* Storzbach, et al., in press [*shared first 
authorship]). Currently, a small trial of CCT in Veterans with comorbid PTSD and TBI is ongoing 
(Jak, 2015), though results of this trial are not yet available. Finally, Walter et al. (2015) 
examined the impact of PTSD symptoms on CCT effectiveness for OEF/OIF Veterans with mild 
to moderate TBI history who received supported employment services. The presence of PTSD 
did not diminish improvement associated with CCT. No current research is examining the 
effectiveness of CCT for Veterans who have PTSD but who do not have comorbid TBI history. 
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Because recent research has confirmed that cognitive functioning deficits are present for 
Veterans who have PTSD but do not have a history of TBI, it is likely that these Veterans will 
also benefit from an intervention designed to target cognitive functioning deficits, such as CCT. 
CCT emphasizes the cognitive domains most impacted by PTSD (Scott et al., 2015), and 
therefore the intervention is well-suited to this population. 
 
Summary: We know that many Veterans experience cognitive functioning deficits associated 
with PTSD and that, in some Veterans, these persist after PTSD treatment (including EBP). 
CCT is a promising treatment for mild TBI that can be tailored to Veterans with PTSD. We need 
to pilot test CCT to determine the feasibility and appropriateness of future research on its 
effectiveness for reducing cognitive functioning deficits and improving compensatory strategy 
use in Veterans with PTSD but without TBI. The central hypothesis is that though PTSD 
treatment will reduce cognitive functioning deficits for some Veterans with PTSD, others will 
benefit from CCT to address residual cognitive functioning deficits. 
 
Preliminary Studies 
Cognitive functioning, mild TBI, and PTSD in Veterans: Dr. O’Neil’s research focus derives 
from clinical neuropsychology practice, in which she assesses and treats Veterans who have 
PTSD and associated cognitive functioning deficits. Recently completed projects include a VA-
funded RCT of CCT for Veterans with mild TBI (Storzbach, Twamley, et al., 2016), a VA-funded 
RCT of behavioral activation efficacy for PTSD symptom reduction (Storzbach et al., in 
progress), and a VA-funded study of the affects blast exposure on cognitive outcomes 
(Storzbach,* O’Neil,* et al., 2015 [shared first authorship]; O’Neil et al., 2016; Callahan et al., 
2016; and 2 additional manuscripts in progress). The blast exposure study demonstrated that, 
though blast exposure was a stronger predictor of cognitive deficits than mild TBI, PTSD 
symptoms mediated this relationship. This project solidified Dr. O’Neil’s focus on PTSD as a 
relatively unstudied driver of cognitive impairment. The CCT for TBI study provided preliminary 
support for CCT intervention efficacy for cognitive symptom reduction in Veterans with mild TBI 
history, and Dr. O’Neil co-led a follow-up paper on mental health moderators of CCT efficacy 
with Drs. Twamley and Pagulayan, recently published in Archives of Physical Medicine and 
Rehabilitation. This paper shows that neither PTSD symptom severity nor PTSD diagnosis 
moderates the efficacy of CCT for Veterans with TBI history, suggesting that investigating 
whether it improves cognitive functioning in Veterans with PTSD but without TBI history is an 
appropriate next step to advance VA rehabilitation research related to PTSD.  
 
Research Design and Methods  
Overview: CCT will be pilot tested with Veterans who have residual cognitive functioning 
deficits following PTSD treatment to determine the effectiveness of this treatment for reducing 
cognitive functioning deficits associated with PTSD. These Veterans will be either identified in 
Dr. O’Neil’s concurrent CDA study assessing cognitive functioning in Veterans completing EBPs 
for PTSD, referred by mental health providers if they received PTSD treatment in the past and 
are reporting ongoing cognitive functioning deficits, or through the VA CDW, if needed. 
 
Aim 1: Evaluate recruitment feasibility and participant acceptability and characteristics in a pilot 
RCT of CCT vs. TAU in Veterans who previously engaged in PTSD treatment and report current 
cognitive functioning deficits. Aim 2: Estimate effect sizes to calculate needed sample size for a 
fully powered RCT of CCT vs. TAU for improving objective and subjective cognitive functioning 
deficits, mental health, other aspects of functioning, and QOL. 
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Study Design: The proposed study is a single site, pilot RCT comparing 10-session CCT (one 
session per week) to 10 weeks of TAU as the control condition. 
 
Intervention: TAU will consist of routine, weekly mental health psychotherapy as all participants 
must have a referring mental health provider to be eligible for this pilot RCT. The CCT 
rehabilitation model aims to teach individuals strategies that allow them to work around 
cognitive deficits. CCT provides training in compensatory attention and learning/memory skills, 
formal problem-solving strategies applied to daily problems, and the use of external aids, such 
as calendar systems and assistive devices to promote completion of daily tasks (Storzbach et 
al., 2016). CCT sessions consists of interactive didactic information and discussion, and 
activities that introduce a variety of cognitive strategies and external aids. Participants are given 
a copy of the treatment manual and a paper calendar or day planner if requested, or they may 
request training on a smartphone or electronic calendar system instead. They will receive 
extensive graduated training in and practice with their chosen calendar system across sessions 
with a focus on how the day planners can facilitate the use of compensatory strategies taught 
each week. Dr. O’Neil will supervise the CCT groups run by the study coordinator, co-facilitating 
early groups as needed for training purposes. They have an ongoing relationship with local 
psychology doctoral programs which may provide clinical trainees who may provide supervised 
group facilitation. The current CCT Treatment Manual (Twamley, Huckans, et al., 2016) is 
included as an Appendix, though aspects of structure and content will be changed before this 
pilot RCT for PTSD to tailor the intervention to PTSD rather than TBI. We have successfully 
tailored CCT to other similar Veteran populations in the past, and we expect to be able to refine 
it for Veterans with PTSD prior to CDA initiation. We have also had success training a variety of 
master’s level research associates and providers to administer the intervention, and similar 
training and fidelity monitoring protocols (e.g., recorded sessions, 20% random fidelity checks) 
previously utilized by Drs. Storzbach, Twamley, and Huckans will be implemented in this 
proposed efficacy study. The following table outlines the CCT structure and content. 
 
 
 
Feasibility and Acceptability: A goal of pilot studies is to assess feasibility of proposed methods 
for a larger trial (e.g., recruitment, retention, resource capacity, and data and personnel 
management). We will examine the feasibility of recruiting and retaining Veterans with recent 
history of PTSD treatment (past year) and current cognitive functioning deficits for a CCT for 
PTSD RCT; establish study protocols to ensure adequate recruitment, intervention delivery, and 
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intervention fidelity; and maximize participant retention. Detailed records on recruitment, session 
attendance, and homework completion will be kept throughout the intervention. Consistent with 
Consolidated Standards of Reporting Trials (CONSORT) guidelines, we will obtain data to 
determine (1) the number of participants who reported moderate or greater symptom ratings, or 
who have impairments in one or more cognitive domain, from the baseline assessment; (2) the 
number of participants referred to the study, (3) the number of participants screened by 
research staff for study eligibility, and (4) the number enrolled in and completing all aspects of 
the study including treatment sessions and assessments. We will ascertain reasons for 
unsuccessful recruitment, ineligibility, and unsuccessful enrollment of eligible Veterans. In 
addition, we will collect data on the intensity of outreach needed to recruit and enroll participants 
(e.g., number of phone calls required before Veterans complete eligibility screening, number of 
“no shows” for eligibility screening appointments) and length of time between initial recruitment 
attempt, eligibility screening, and completion of the pre-intervention assessment. Participant 
Retention will be measured by the proportion of participants who complete follow-up 
assessments within two weeks of the target date. Treatment satisfaction will be assessed by the 
Client Satisfaction Questionnaire (CSQ8). 
 
Functional and Clinical Variables: We will use similar assessment procedures as in the Aim 1 
study to assess cognitive and functional domains most strongly associated with PTSD (details 
listed in the table below). We will examine sleep and mental health symptoms (including PTSD 
and depression) not directly targeted by CCT to examine comparability to TAU. Assessments 
will take approximately 1.5 hours and will occur at baseline, post-treatment, and 6-month follow-
up for both groups. 
 
Measure 
Construct Assessed 
Objective Cognitive Functioning (Neuropsychological Tests) 
Test of Premorbid Functioning (ToPF) 
Verbal abilities; estimate of premorbid cognitive 
functioning 
California Verbal Learning Test (CVLT-II; Delis et al., 2000) 
Verbal learning and memory, forced choice 
validity 
Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span & Coding 
subtests (Wechsler, 2008) 
Attention, working memory, processing speed, 
reliable digit span validity 
Controlled Oral Word Association Test (Benton, Hamsher, & Sivan, 
1983) 
Word generation, verbal fluency, executive 
functioning 
Halstead Reitan Trailmaking Test (Trails A & B; Reitan & Wolfson, 
1985) 
Visual tracking, processing speed, executive 
functioning 
Medical symptom Validity Test (MSVT) 
Validity 
Functional Outcomes (Patient-Reported) 
World Health Organization Disability Assessment scale (WHODAS 
2.0) 
QOL, global functioning 
Neuro-QOL Cognitive Scale 
Cognitive functioning and QOL 
Neuro-QOL Ability to participate in Social Roles and Activities Scale 
Social functioning and QOL 
Neuro-QOL Sleep Scale 
Sleep-related functioning and QOL 
Memory Compensation Questionnaire (MCQ; de Frias & Dixon, 
2005) 
Compensatory cognitive strategy use 
Portland Cognitive Strategies Scale 2.0 (PCSS) 
Compensatory cognitive strategy use 
Clinical Outcomes (Patient-Reported) 
Mini International Neuropsychiatric Interview (MINI; Sheehan et al., 
2006) 
Mental health diagnoses 
PTSD Checklist (PCL-5; Weathers et al., 2013) 
PTSD symptoms and severity 
Patient Health Questionnaire (PHQ-9; Spitzer, Kroenke, & Williams, 
1999) 
MDD symptoms and severity 
Prospective-Retrospective Memory Questionnaire (PRMQ; Crawford 
et al. 2006) 
Cognitive symptoms 
Multiple Sclerosis Neuropsychological Screening Questionnaire – 
Patient Version (MSNQ; Venedict et al. 2003) 
Cognitive symptoms  
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All assessments will be administered by the trained study coordinator/assessors supervised by 
Dr. O’Neil, who is a licensed, credentialed, and privileged VA neuropsychologist.  
 
Randomization and Blinding: All eligible participants will be randomized to either the CCT or 
TAU group. Randomization tables will be prepared by the study statistician at the beginning of 
the study and assignments to CCT or TAU will be based on the randomization table. New 
participants will be allocated to the current group awaiting randomization. Once group 
membership reaches 6 participants, the group will be randomized by the statistician. We will 
employ a system of adaptive randomization, weighted to achieve the desired proportion of 
participants in each condition, managed by the statistician. Randomization will be implemented 
by the study coordinator in coordination with the statistician who will monitor randomization 
procedures. Because of the small sample size and number of study personnel in this pilot RCT, 
it might not be feasible to blind the assessor to participant group status if the assessor is also 
co-facilitating CCT groups with Dr. O’Neil, though this type of blinding will be implemented if 
possible. 
 
Data Analysis: Rates of recruitment, retention, and participation will be calculated, and we will 
compare participant characteristics at baseline by group (CCT vs. TAU). We will conduct intent-
to-treat analyses to compare change from baseline to 3-month follow-up within and between 
groups. 
 
Study Feasibility Analyses: Descriptive statistics will characterize the feasibility of recruiting and 
retaining Veterans. Recruitment will be deemed feasible if we successfully screen for eligibility 
50% of Veterans referred to the study and enroll 75% of screened Veterans who meet all study 
inclusion criteria. Retention will be deemed successful if we achieve 80% completion for post-
treatment assessments. Chi-square tests of association for categorical variables and t-tests for 
continuous variables will compare demographic and clinical characteristics of successfully 
versus unsuccessfully recruited and retained Veterans to identify characteristics of participants 
who may require more intensive recruitment or retention efforts in a future trial. 
 
Clinical and Functional Outcome Analyses: An additional goal of clinical and functional outcome 
data from this pilot RCT is to obtain effect size estimates to prepare for a future fully powered 
RCT. Because estimating effect sizes in small pilots is fraught with limitations and should not be 
used as a sole estimate (e.g., Kraemer et al., 2006), we will compare obtained effect sizes to 
those obtained for participants with PTSD in our CCT for mild TBI trial. We are not relying on the 
TBI data alone, however, because of the potentially significant differences in Veterans who do 
and do not have a history of TBI. Therefore, though we will conduct multivariate analyses of pilot 
data and examine the statistical significance of within and between group differences, we will 
focus on obtaining effect size estimates to prepare for a future trial. Because of the small 
sample size, we will examine data for trends to plan for future analyses in a fully powered RCT. 
To evaluate the proportion of Veterans with early discharges from CCT, we will conduct mixed 
models for binary outcomes. We will plan for an underpowered pilot trial, though will use the 
obtained effect sizes to estimate statistical power and needed sample size for the fully powered 
RCT RR&D Merit proposal in year 4 of the CDA. We will also use appropriate assumptions for 
planned statistical tests when calculating estimated power. 
 
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In this pilot study, we will first examine descriptive statistics, and conduct tests of normality and 
homogeneity of variance for variables included in repeated measures analyses. We will 
examine missing data for all variables and dropout rates in order to plan for a future RCT, 
though will not conduct multiple imputation or other missing data techniques for this pilot study. 
We will, however, conduct intent to treat analyses, analyzing data from all randomized 
participants assigned to CCT versus TAU groups, rather than only including completers. 
Primary outcome analyses will be multilevel models to compare the change over time in 
cognitive, mental health, functioning, and QOL outcomes for Veterans in the CCT versus TAU 
groups. If the sample size is too small to run multilevel models, we will run alternative methods 
such ANOVAs which are more feasible with smaller samples. We will examine how much 
symptoms change, comparing changes across groups, and also examine clinically significant 
change in self-reported functional and clinical outcomes. We will compare the change in 
proportions of Veterans who fall within in “clinically significant impairment” ranges on objective 
cognitive performance measures before and after CCT versus TAU, characterizing cognitive 
functioning deficits according to cognitive domains. Because of the small sample size in this 
pilot RCT, these analyses will rely heavily on descriptive statistics including identifying 
individuals who score within clinically impaired ranges on objective testing, and who score 
above clinical cutoffs on self-report measures. Multilevel models or repeated measures analysis 
of covariance (ANCOVA) models will examine potential moderators including validity tests, 
service connection status and percent, number of sessions attended, comorbid mental health 
diagnosis such as PTSD, and demographic variables. 
 
Study Population and Subject Identification/Recruitment 
 
Study setting, sample size, and recruitment feasibility: The proposed study is conducted at 
a single site. We propose to enroll at least 36, and up to 48, total Veterans in this pilot RCT. 
Because our primary purposes are to examine feasibility of this clinic-based research and 
acceptability to Veterans with PTSD and estimate effect sizes for a future fully powered RCT, 
achieving adequate statistical power is not a primary concern of this pilot clinical trial. Results 
from this pilot RCT with a sample size of 36 to 48, combined with comparisons to similar studies 
of CCT with other Veteran groups (e.g., those with mild TBI history), will provide adequate 
information on expected effect size to allow for estimations of statistical power for a future 
RR&D Merit proposal of a fully powered RCT. VHAPORHCS Mental Health and PTSD clinics 
will serve as primary sites for study recruitment, assessment, and intervention activities. We will 
work with the Public Affairs Office to post IRB approved study flyers in VHAPORHCS Mental 
Health and PTSD clinics and nearby elevators as well as the main hospital. The flyers provide 
information about the study and will help notify Veterans of the opportunity to participate in this 
study. Eligibility and recruitment procedures used to identify Veterans who report residual 
cognitive functioning deficits following recent (past year) treatment for PTSD at the Portland VA 
will be used to recruit Veterans for this pilot trial. Veterans who have participated in PTSD 
treatment and report cognitive functioning deficits on the Neurobehavioral Symptom Inventory 
(NSI; moderate cognitive symptoms or greater on any cognitive functioning item), will be 
recruited from the clinics. 
 
CDW: If needed to achieve recruitment goals, we will also access the VA’s Corporate Data 
Warehouse (CDW) and use ICD-10 codes to identify Veterans with recent (past year) Portland 
VA mental health or PTSD clinic treatment for PTSD. NSI data is also available for some 
Veterans in CPRS and Veterans with elevated NSI scores or neuropsychological evaluations 
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will be prioritized for recruitment. The CDW will be used to identify potentially eligible Veterans. 
The Veterans’ clinicians will be contacted to ask them if they would like to refer these identified 
Veterans to the study. If the clinician wants to refer a Veteran to the study, this will be 
documented and the IRB approved recruitment procedures for a referred Veteran will then be 
followed.  
 
Enrollment and Assessment Procedures: Prior to enrollment, interested Veterans will be pre-
screened. The study coordinator will conduct a medical record review to document cognitive 
symptoms, medical and psychiatric history, and recent treatments and medications. The 
Neurobehavioral Symptom Inventory (NSI) will be used as a screening tool to determine the 
presence of moderate or greater cognitive symptoms for eligibility purposes. A brief phone 
interview will ensure that Veterans are interested in participating and meet eligibility criteria. All 
participants will be screened to ensure their ability to comprehend study procedures, risks and 
benefits. We anticipate that up to 500 Veterans will need to be screened in order to achieve the 
desired sample size of 36-48 Veteran participants in the study. Veterans will be provided the 
opportunity to have the informed consent materials mailed to them. After the Veteran receives 
the informed consent materials, a trained study team member will call the Veteran to go through 
the informed consent procedures and answer any questions. If the Veteran chooses to 
participate, he or she will sign the informed consent documents and mail them back to Dr. 
O’Neil using a pre-addressed and stamped envelope. The study assessment will only be 
scheduled after the hard copy informed consent is received back from the Veteran. Following 
determination of eligibility, provision of informed consent, and enrollment into the pilot trial, 
Veterans will initiate the pilot RCT assessments, and, when assigned to the CCT condition, the 
10-week CCT group intervention (weeks 2-11). Cognitive assessments and symptom 
questionnaires will be completed at baseline, post-treatment (approximately 3-months following 
baseline), and follow-up (6-months following baseline). Veterans will have the option to 
complete all study activities, including the 10-week CCT intervention and the 3 cognitive 
assessments via the VA’s telehealth system, VA Video Connect (VVC), or via telephone.  
 
If a Veteran chooses to complete intervention activities via VVC or telephone, a study team 
member will mail the Veteran the CCT session materials. If a Veteran chooses to complete the 
intervention activities via VVC, Dr. O’Neil or another trained, IRB-approved study team member 
will explain how VVC works and ensure that the Veteran has the appropriate technology and 
accommodations to ensure VVC will work (i.e., internet connected device with video chat 
capabilities, internet connection, private space to engage in the intervention). A study team 
member will schedule intervention sessions with the Veteran and then the Veteran a link for 
VVC through Virtual Care Manager. If a Veteran chooses to complete intervention activities via 
VVC or telephone, Dr. O’Neil or another trained, IRB-approved study team member will conduct 
the intervention via VVC or telephone. If a Veteran chooses to complete assessments via VVC 
or telephone, a study team member will administer all cognitive tests over the phone by reading 
the instructions and questions to the Veteran and recording their response. All responses will be 
recorded directly into electronic files maintained in the IRB-approved VA folders behind the VA 
firewall. No hard copy or other electronic files will have any study data. All assessment activities 
can be completed via VVC or telephone with the exception of the Halstead Reitan Trailmaking 
Test parts A and B and the Wechsler Adult Intelligence Scale Coding subtest. If a Veteran 
chooses to complete an assessment via VVC or telephone these tests will not be administered.  
 
Participant retention/ Dropout Minimization: Retention activities will include offering the option to 
complete study activities via VVC or telephone, inviting participants who discontinue treatment 
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to complete follow-up assessments, advance participant reminders of upcoming assessments, 
scheduling assessments near the target date at times that are convenient for participants, 
providing reminder calls 1-3 days prior to the scheduled assessment, and promptly rescheduling 
missed assessment appointments. We will attempt to retain all enrolled Veterans in the study, 
regardless of ongoing participation in CCT or other interventions as part of TAU. In our prior 
research, all Veterans who initiated CCT completed the intervention. For Veterans who 
discontinue treatment and who express discomfort returning to the clinic to complete follow-up 
assessments, accommodations will be made to ensure Veterans have the opportunity to 
continue study participation (e.g., assessment completion via VVC or telephone or at other 
VAPORHCS locations). We will ensure that participants are appropriately reimbursed for time 
and travel, paying participants $50 for each assessment. Recent trials of CCT in VA clinics 
conducted by Drs. Storzbach, Twamley, and O’Neil have exceeded 90% retention. 
 
Inclusion/Exclusion Criteria 
Participants will be at least 36 (and up to 48) Veterans weighted with more CCT participants 
(approximately 4-5 CCT groups with 6 Veterans each) than controls (12-18 TAU participants, 
grouped for randomization piloting purposes into 6-Veteran participants in each of 2 groups). 
Veterans of all genders, races, and ethnicities will be eligible for this study. We have estimated 
enrollment for gender, race, and ethnicity based on the recent CCT for mild TBI study, assuming 
similar demographic proportions. Eligibility will be established by current Mental Health or PTSD 
Clinic provider and CPRS chart review and will be confirmed by the Veteran during the initial 
phone call. Eligible Veterans (1) must meet DSM-5 criteria for PTSD based on PTSD or Mental 
Health Clinic intake assessment or PTSD diagnosis at most recent Mental Health/PTSD clinic 
visit if intake was completed over 6 months prior to study participation; (2) are patients in the 
PTSD specialty clinic or Mental Health clinic with a current mental health provider who is willing 
to provide TAU if randomized as such; (3) prior EBP treatment within the past 2 years confirmed 
by patients, their current Mental Health or PTSD clinic provider, and a review of CPRS records; 
(4) do not have a history of TBI of any severity; (5) are able to provide informed consent; (6) are 
English speaking; (7) are able to travel to the clinics for appointments; (8) do not have auditory 
or visual impairments that would compromise assessments; (9) do not meet criteria for a 
substance dependence disorder with less than 30 days abstinence; (10) do not meet criteria for 
bipolar disorder or psychotic disorders; (11) do not have active suicidal intent indicating 
significant clinical risk (which would suggest that a treatment specifically targeting this intent 
was indicated); (12) do not have a major medical condition likely to significantly impact cognitive 
functioning such as stroke, multiple sclerosis, Parkinson’s, brain tumor, or congestive heart 
failure; (13) are not currently participating in any type of brain stimulation treatment; and (14) are 
between the ages of 18 to 75 years old. To maximize the generalizability of the study and 
ensure that we are testing CCT with a typical PTSD Veteran population, exclusion criteria are 
minimized (e.g., there are no medication exclusion criteria, and Veterans with comorbid 
depression or anxiety disorders will be included). Current cognitive functioning deficits are also 
required for participation, and chart review and NSI screening will be implemented for this study. 
  
Informed Consent & HIPAA Authorization 
For all studies, written informed consent will be obtained from all Veteran participants who 
attend in-person visits and electronic informed consent will be obtained through DocuSign for 
those Veterans who participate by phone or VVC. The consent process will be conducted by 
trained research team members. Eligible participants will be Veterans with a current diagnosis 
of PTSD who have been referred for PTSD mental health treatment in the VA Portland mental 
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health clinics. With approval of the clinical providers, additional eligibility screening will take 
place for up to 120 Veterans; the Veterans who meet eligibility criteria will be contacted until the 
desired sample size of 36-48 participants are enrolled in the study. There is currently a waiver of 
informed consent to be able to review Veterans’ medical records to ensure medical inclusion 
and exclusion criteria are met prior to contacting potentially eligible Veterans. This may reduce 
time and travel burden for Veterans who do not meet these minimum study criteria. Dr. O’Neil or 
another study member will let VA mental health clinicians know about the study and 
inclusion/exclusion criteria and request their assistance in recruiting eligible Veterans. This 
information will be provided to clinicians in the form of an email, in person conversation, team 
meeting presentation, or phone call using the attached email letter/script. Veterans meeting 
these study criteria will be informed of the study by their clinician from the mental health clinic in 
which they receive mental health treatment. If they are willing to participate, the clinician will 
notify Dr. O’Neil through CPRS, encrypted email, or in person meeting, or phone call that the 
Veteran agreed to be contacted about the study. Veterans who express interest in participating 
will be called to schedule a meeting to discuss and obtain informed consent and to conduct the 
90-minute baseline assessment and be randomized to CCT or TAU group if they consent to 
study participation. During the initial scheduling call, Veterans will be given the option to conduct 
the baseline visit (i.e., discuss and obtain informed consent and conduct the 90-minute baseline 
assessment) in person, via VVC, or via telephone; staff will follow current VA guidance about in-
person visits and will allow for participant preference when permitted by the VA (e.g., if the 
Portland VA does not recommend in-person for non-essential visits, then this option will not be 
offered, and only VVC or telephone appointments will be offered).  
 
If the Veteran chooses to conduct the meeting via telephone or VVC, the study team will 
schedule a telephone or VVC appointment to go over study documents (i.e., Informed Consent 
Form and HIPAA Authorization) using DocuSign. An approved study team member will send a 
DocuSign envelope (an email containing links to the study documents) to the potential 
participant. The email will contain a reminder for the Veteran to not sign the documents prior to 
the scheduled contact time, when study staff will review the documents with the Veteran and 
answer any questions. At the scheduled appointment, approved study staff will contact the 
potential participant via phone or VVC and use the e-consenting script to walk the Veteran 
through the DocuSign process, including opening and reviewing the documents. For reference, 
staff will have opened a copy of the documents on his/her own computer. If the Veteran agrees 
to be in the study, staff will direct the Veteran to fill in any required fields and sign the document. 
Once the Veteran has signed the documents, the Veteran will click “Finish” to finalize the 
documents. While still in the appointment with the Veteran, study staff will verify that the signed 
documents have been completed accurately and completely as well as signed. Study staff will 
sign the documents and then direct the Veteran on how to save a copy for his/her own records. 
After the appointment, study staff will print a copy of the signed documents to be delivered for 
review to the privacy officer, following the same procedure as in-person visits. The study staff 
will document the consenting process in CPRS. 
 
If the Veteran chooses to conduct study activities in person and this modality is allowed by the 
Portland VA at the time, the Veteran will be scheduled for an in-person meeting to discuss and 
obtain informed consent and to conduct the 90-minute baseline assessment. At all stages of 
eligibility determination and study involvement, all Veteran participants will be provided an 
opportunity to have their questions answered. 
 
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Risks and Side Effects: 
The proposed study poses no serious risks to participants. The study involves direct contact with 
participants, and there is a slight risk that participants could become upset during groups or 
assessments or while completing questionnaires. There is also a slight risk that a Veteran could 
report suicidal thoughts during these contacts, although clinician-patient discussions about 
mental health or possible suicidal ideation have not been shown to increase the risk of suicide 
attempts. Participants will be participating in an intervention that has been shown to be 
acceptable to similar Veteran patients (e.g., those with TBI history), and effective for reducing 
cognitive problems; however, it is possible that the intervention will not be effective with this 
population or will produce iatrogenic effects. The risk to participants is minimal but may include 
breach of confidentiality via inadvertent disclosure of PHI and identifiers and distress upon 
participating in the CCT intervention. 
 
Protection Against Risk & Participant Safeguards:  
Prior to consenting procedures, a waiver for HIPAA will be used to collect Veteran names and 
email addresses for those who choose to complete study procedures remotely or, in the case of 
hospital guidance, are unable to complete in-person visits. E-mail addresses will be obtained 
through the veteran’s medical record and verified with the potential participant during the initial 
phone call. Study staff will not keep a record of Veteran’s e-mail address. With the exception of 
Veteran’s name and e-mail address for utilization of DocuSign, no personally identifying 
information will be released outside of the VA, and all study participants will be assigned unique 
study ID numbers. Keys linking participant identifiers with study ID numbers will be kept in 
locked file cabinets in VA research offices or on a password-secure network server, separate 
from study data. Identifying information will be removed from datasets prior to analyses. All 
investigators and team members who will have access to the data will have received 
appropriate VA background checks as part of VA hiring and/or credentialing and will have 
completed Data Security Training within the prior 12 months. All data will be maintained and 
analyzed within the secure VA computing system. For all study activities that involve direct 
contact with participants, all precautions will be taken to ensure confidentiality. For study 
activities that involve contact with participants via VVC or via telephone, study team members 
will only contact Veterans from a private area so no one outside of the study team can overhear 
the conversation or have access to research information or protected health information. The 
study team member that conducts a study activity via VVC or via telephone will obtain the 
address of the Veteran's location where they will participate and the contact information of a 
person at or near the Veteran's location who can be called in the case of emergency. If there is 
not a person at or near the Veteran’s location available in case of emergency, the study team 
member will notify the Veteran that they will call 911 if there is an emergency and provide the 
911 dispatch with the Veteran’s address.  Veterans will participate via VVC or via phone only if 
they have a safe, private location from which to participate. No phone, video, or audio contact 
will be recorded in any way. No research information or protected health information will be 
written down when conducting the intervention or assessments via VVC or via telephone. These 
are standard telehealth appointment procedures routinely implemented by Dr O'Neil and other 
study staff (e.g., Dr. Jason Chen) as part of their clinical service on the rural tele-mental health 
team at the Portland VA. 
 
Data from Veteran surveys and assessments will similarly be stored in the network file and 
coded with unique study IDs. Only study personnel will have access to assessment data. Any 
hardcopies of study survey and assessment data will be kept in locked files in the principal 
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investigator’s office. Special precautions will be taken to minimize Veterans becoming upset and 
to maximize safety.  
 
During the informed consent process and during ongoing study interactions, members of the 
study team will ensure that Veterans understand they do not have to answer any question or 
discuss any topic that they do not wish to answer or discuss. Participants will be provided with 
emergency contact numbers. All participants will be clearly informed of their right to withdraw 
from the study at any point without adversely impacting their routine medical, psychiatric, or 
psychotherapeutic care. 
 
Dr. O’Neil has developed individualized safety plans for use in case patients report active 
suicidal ideation during interviews. If a Veteran reports current suicidal ideation during an 
assessment session, interview, or other interactions with members of the study team, study 
personnel will seek immediate consultation per the safety plan, and work with the patient’s 
referring mental health clinician to ensure that appropriate follow-up assessment is conducted. If 
a Veteran does not have a current suicide safety plan, the local suicide protocol will be activated 
if necessary, which involves calling the VA National Suicide Hotline. Hotline staff will be given 
the caller's name, telephone number, and last four digits of the Social Security Number or as 
much information that is known at the time of warm transfer. If the VA National Suicide Hotline 
warm transfer telephone number is busy, study personnel will call 1-800-273-TALK (8255) and 
press 1 to be routed to the VA National Suicide Hotline. If appropriate and necessary, Veterans 
with acute suicidal ideation or intent will be escorted to the local VA emergency room and 
evaluated there by licensed clinicians who will take over their care. Dr. O’Neil has trained many 
research personnel in procedures for addressing and responding to potential suicidal ideation; 
all involved study personnel will receive supplemental training in these procedures. For all 
studies, the study coordinator and the Portland Center’s IRB specialist will conduct a review of 
study files every 6 months to assure compliance with approved procedures, and the local VA 
research and Development Office will conduct a similar audit annually. In accordance with VA 
guidelines, a data safety monitoring board will be established. 
 
Adults without decisional capacity will be excluded from this study. 
 
Suicidality: 
If participants present with high risk for suicide (e.g., report suicidal plans or intentions), study staff 
will follow the following protocol, one step at a time until the participant is transferred to an 
appropriate provider for follow-up assessment and care: 1) Contact Dr. O’Neil (PI) or other IRB-
approved responsible clinician of the study (e.g., Dr. Jason Chen) to assess the participant and 
determine if follow-up care is needed (i.e., transfer the participant to the responsible clinician before 
ending the study visit). 2) Work with the participant to identify and contact their primary VA mental 
health care provider or medical provider so that s/he can conduct an assessment and provide 
follow-up care as needed (i.e., transfer the participant to that provider in person before ending the 
study visit).  3) Walk the participant to the VA emergency room and have emergency personnel 
conduct an assessment and provide follow-up care as appropriate.  4)  If suicide risk becomes 
apparent while on the phone with a participant and the above steps are not possible, then study 
staff will follow procedures for a “warm transfer” to VA National Suicide Prevention Hotline staff, 
using a nationally disseminated protocol described here:  
http://www.portland.va.gov/research/documents/hrpp/warm-transfer.doc. (VA Central Office has 
arranged with the VA National Suicide Prevention Hotline ((585) 393-7938 OR 1-800-273-8255, 
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then press “1”) to provide suicide prevention support in cases that a researcher is on the phone 
with a participant who indicates that they are suicidal. When this occurs, a “warm transfer” 
should be conducted, which is defined as transferring a call and giving the referring party an 
opportunity to share information over the phone prior to the call transfer. A warm transfer also 
allows for all three parties to be on the line at the same time if needed. Instructions for how to 
conduct a warm transfer if needed during the course of a research study are provided in the 
above-mentioned website.)  
 
Benefits:   
This study will determine whether PTSD-related cognitive symptoms can be treated effectively 
with CCT, an evidence-based intervention that is effective in other, similar Veteran subgroups, 
but not yet tested in Veterans who do not have a history of TBI. This study will help determine 
strategies to facilitate the implementation of CCT in VA mental health clinics. The risk to 
Veterans, as described above, is low and the proposed study has the potential to considerably 
improve Veteran care experiences and health outcomes. 
 
Protected Health Information: 
As part of the study, we will collect the following individually identifiable health information from 
each participant: information from their VA Health Records such as diagnoses, progress notes, 
medication, lab and radiology findings; demographic information such as name, race, gender, 
age, birthdate, address, phone number, email address, and clinic and research visit dates; 
social security number and medical record number; questionnaires and neuropsychological 
measures. This information is necessary for our research, because we plan to use medical 
record information to identify potential participants and to confirm eligibility for participation in 
the study.  We will use contact information to reach participants and for scheduling.  We will use 
names and email addresses to obtain consent through DocuSign but will not keep a record of 
email addresses. We will use demographic information to describe our sample (i.e., sample 
characteristics) and to determine if they moderate study outcomes.  
 
Multi-Site Study Concerns  
 
This is not a multi-site study.  
 
 
Resources Available 
   
The principal investigator (PI) Dr. Maya O’Neil is a full time, permanent VA clinician, with .5 FTE 
protected research time (.75 protected research time after initiation of the CDA in January of 
2019). Dr. Maya O’Neil and her research team are housed at the VA RR&D National Center for 
Rehabilitative Auditory Research (NCRAR) and HSR&D Center of Innovation, the “Center to 
Improve Veteran Involvement in Care” (CIVIC), at the VA Portland Health Care System 
(VAPORHCS). Dr. O’Neil and Portland mentors and consultants also all have faculty 
appointments at Oregon Health & Science University, Oregon’s only academic health center, 
which is physically connected to VAPORHCS. The CIVIC has several PhD-level biostatisticians 
who support the research of investigators, including Dr. O’Neil; all will be available to her for 
training and consultation throughout the course of the CDA award. Similar resources will also be 
available to Dr. O’Neil through the NCRAR. In addition, the VAPORHCS Research & 
Development Office has dedicated staff to further assist with grant preparation and submission 
and coordination of travel for research activities. 
 
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The PI and her study staff will use the PI’s existing personal office (Building 6, Rm 217) and 
research space as well as Building 104 Neuropsychology Clinic rooms to conduct this research. 
 
Costs To Subjects:  
Cost to subjects include their time during study visits, and any costs related to transportation to 
and from the research visits.  
 
Subject Compensation:  
Veteran participants will be compensated with $50 for time and transportation costs associated 
with completing each of the three 90-minute assessments. Participants’ assessment results will 
also be reported in their VA medical records so that this clinical information can be accessed by 
them and by their clinicians in the future if needed. There are generally no other direct benefits 
to participants. However, knowledge obtained from the study may benefit other Veterans in the 
future. Payment amounts and terms of payment are also listed in the informed consent form.  
 
Participants will be paid the appropriate compensation after the completion of each assessment 
visit in the study, either by direct deposit (EFT), debit card, gift card, or cash. 
 
Privacy and Confidentiality: 
We will take multiple steps to protect participants’ privacy and confidentiality. All data will be de-
identified, labeled with a code number that is unique to each patient in the study, and 
maintained in a Subject Data File. All hard copy subject data will be stored in locked filing 
cabinets in locked rooms, while all electronic data will be stored in password-protected files in a 
limited access folder on the secure VA network drive. Only IRB-approved study personnel will 
have access to the Master List key code, Subject Data Files or Informed Consent Forms. We 
will analyze and report subject data in aggregate form and no PHI will be entered into these 
analyses or reports. Audio recordings of treatment sessions will be stored on a VA secure 
server and will be accessed by Dr. O’Neil or her staff for the purposes of rating the group 
leader’s adherence to the treatment manuals. 
 
The PI or project manager will conduct a review of study files every six months to assure 
compliance with approved procedures. The research team will work closely with the 
VAPORHCS Information Security Officer to ensure that any data transfer, storage, and handling 
by non-VA entities adhere to VA security policies. 
 
Participant Routing 
As participants are seen within clinical spaces for research visits, and to ensure that 
participants are in the right area for study visits, participants will check-in with front desk 
staff/MSAs of the appropriate clinic. Study staff will send appropriate MSAs an encrypted 
e-mail with participant name, date, and time of study visit to allow MSAs to perform normal 
clinical duties and assist participants in being routed to study staff. 
 
Information and/or Specimen Management 
Study staff is trained on the protocols to ensure that procedures are being conducted within the 
scope of the approved protocols. Recruitment and enrollment for clinical projects are reviewed 
regularly at Dr. O’Neil’s meetings. At the meetings, staff provide enrollment updates, and the 
research team problem solves recruitment issues to ensure that projected enrollment numbers 
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are obtained. The PI or project manager checks procedures (at least monthly) to verify that they 
are being conducted per the approved protocol, including the responsibilities and roles for 
gathering and monitoring data. Assessment data are recorded by research staff as it is 
collected, and data accuracy is verified by double scoring, data entry and visual verification.   
 
All recruitment data containing PHI will be stored on VINCI servers at the Austin Information 
Technology Center, 1615 Woodward St., Austin, TX 78772-0001. The specific server where the 
data will be stored will be chosen by VINCI personnel. The server name and location within the 
Austin Information Technology center may be changed at any time at the discretion of VINCI 
personnel.  
 
In addition, all recruitment data containing PHI downloaded from the VINCI server will be stored 
in a password protected file on the PI’s secure research folder and only approved study 
personnel will have access to this folder. This data will be used for recruitment purposes only. 
Research staff will use an audited VINCI download utility to move these data from VINCI 
servers to local storage media on the VA servers behind the VA firewall. Only study team 
personnel explicitly authorized by data stewards will have access to the recruitment data. The 
study principal investigator has the responsibility for security of the study. VINCI data managers 
and VA OI&T personnel not under the purview of the study principal investigator control the 
servers, network, processors, firewall, and software in the VINCI environment, including access 
rights granted to study personnel. 
 
 
Data Management: We will use Microsoft Excel to record and store study data, track subject 
screening, enrollment and participation, create surveys, generate reports, and enhance project 
management. Project computers are served by the VAPORHCS local area network and all 
database and qualitative analysis software are licensed. All information linking study data to 
personal health information will be stored on a password-secure server behind the VA firewall, 
or in hardcopy form in locked file cabinets which reside in a locked office in a secure research 
building (Building 6). All records will be maintained according to the VHA records control 
schedule. Audio recordings will be made to ensure that the study team member who is running 
the CCT group is adhering to the CCT manual (fidelity monitoring). Once audio recordings have 
been reviewed by study staff for the purpose of fidelity monitoring, the recordings will be stored 
according to the VAPORHCS records control schedule. 
 
We are also asking participants to allow their data and contact information including identifiers 
to be stored (‘banked”) in the Neuropsychology Data Repository (MIRB# 3508) located at the 
VA Portland Health Care System (VAPORHCS) and managed by Dr. Maya O’Neil. These data 
will include data resulting from the cognitive test battery and identifiers including name, 
telephone number, the last four digits of social security number, and study participation dates 
that will be used in future research. Contribution to the repository is optional.  
 
Transfer of Data Ownership 
N/A 
 
Data and Safety Monitoring Plan (DSMP)  
Safety Monitoring: The PI or anyone else who has contact with study participants during study 
activities have the responsibility to monitor for any potential adverse events and protocol 
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deviations. Any adverse participant event will be reported immediately to PI Dr. O’Neil, who will 
contact the participant and determine if additional intervention is needed to ensure participant 
safety. Protocol deviations will also be immediately reported to Dr. O’Neil who will ensure that 
adverse events deemed to be unanticipated problems and protocol deviations are properly 
reported to the IRB in a timely manner. Detailed written documentation will be kept for all 
adverse events that occur over the course of the study. PI Dr. O’Neil holds weekly meetings 
with lab personnel where they will discuss adverse events and protocol deviations associated 
with this project and ways to reduce repeat occurrences. Research staff will examine all 
cumulative adverse events quarterly to determine if there are any systematic problems and to 
implement protocol corrections as needed after receiving IRB approval. 
 
Data Monitoring: All information linking study data to PHI will be kept within VHA electronically in 
secure computer files stored behind firewalls requiring password access, or in hardcopy form in 
locked file cabinets in locked offices. All patient identifiers will be removed prior to analysis. All 
investigators and team members who will have access to the data will have received 
appropriate background checks as part of hiring and/or credentialing and will have completed 
Data Security Training within the prior 12 months. The PI or project manager will conduct a 
review of study files every six months to assure compliance with approved procedures. The 
research team will work closely with the VAPORHCS Information Security Officer to ensure that 
any data transfer, storage, and handling by non-VA entities adhere to VA security policies. 
 
Per VHA guidelines, data resulting from this study will be stored locally on VHA password-secure 
folders until enterprise-level resources become available for long-term storage and access. 
Requests for data access will be considered and responded to within one month of the request and 
datasets will be made available electronically. Requests must be made in writing to the study PI 
and provide information on the purpose for accessing the data.  
 
All data used in final, published results will be made available for sharing. Published data will be 
available upon request to any investigator in order to enable independent validation and 
interpretation of published data. 
 
Once the current study is closed, we will store de-identified, anonymized dataset in an approved 
data repository consistent with policies in 1200.12 (Use of Data and Data Repositories in 
Research). A sharing agreement will prohibit the recipient from identifying or re-identifying (or 
taking steps to identify or re-identifying (or taking steps to identify or re-identify) any individual 
whose data are included in the dataset. 
 
Step-by-Step Guidance on Conducting the Study 
See section above on study methods which includes step by step guidance on study conduct and 
procedures. 
 
References & Literature Cited   
1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental 
disorders (5th ed.). Washington, DC: American Psychiatric Publishing. 
2. Brewin, C. R. (2007). Autobiographical memory for trauma: update on four controversies. 
Memory, 15(3), 227-248. doi: 10.1080/09658210701256423 
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3. Brown, V. M., & Morey, R. A. (2012). Neural systems for cognitive and emotional processing 
in posttraumatic stress disorder. Front Psychol, 3, 449. doi: 10.3389/fpsyg.2012.00449 
4. Chard KM, Schumm JA, McIlvain SM, Bailey GW, Parkinson RB. Exploring the efficacy of a 
residential treatment program incorporating cognitive processing therapy-cognitive for 
veterans with PTSD and traumatic brain injury. J Trauma Stress. 2011;24:347-351. 
5. Cicerone KD, Langenbahn DM, Braden C, et al. Evidence-based cognitive rehabilitation: 
updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil. 
2011;92:519-530. 
6. Cusack, K., Jonas, D. E., Forneris, C. A., Wines, C., Sonis, J., Middleton, J. C., . . . Gaynes, 
B. N. (2016). Psychological Treatments for Adults With Posttraumatic Stress Disorder: A 
systematic review and meta-analysis. Clinical Psychology Review, 43, 128-141. doi: 
10.1016/j.cpr.2015.10.003 
7. Dohrenwend BP, Turner JB, Turse NA, Adams BG, Koenen KC, Marshall R. The 
psychological risks of Vietnam for U.S. veterans: a revisit with new data and methods. 
Science. 2006;313:979-982. 
8. Geuze, E., Vermetten, E., de Kloet, C. S., Hijman, R., & Westenberg, H. G. (2009). 
Neuropsychological performance is related to current social and occupational functioning in 
veterans with posttraumatic stress disorder. Depress Anxiety, 26(1), 7-15. doi: 
10.1002/da.20476 
9. Haaland, K. Y., Sadek, J. R., Keller, J. E., & Castillo, D. T. (2016). Neurocognitive correlates 
of successful treatment of PTSD in female veterans. J of the International 
Neuropsychological Society, 22, 643-651.  
10. Harpaz-Rotem, Ilan & Hoff, Rani (2015). FY2015 Overview of PTSD Patient Population Data 
Sheet. VA Office of Mental Health Operations. West Haven, CT: Northeast Program 
Evaluation Center. 
11. Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. Combat duty in Iraq 
and Afghanistan, mental health problems, and barriers to care. N Engl J Med. 2004;351:13-
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Appendix – Supporting Documents List 
 
 
 
 
 
• 
CCT Manual  
• 
Phone/In Person Recruitment Script 
• 
Email Message for Recruitment 
• 
Participant Recruitment flyer 
 
VA Portland IRB
Effective Date:
February 2, 2024