Assessment of Cancer Related Brain Fog Using the Test of Strategic Learning
Conditions: Brain Fog
Sponsor: Inova Health Care Services

ACT I: Assessment of Cancer Related Brain Fog using the Test of Strategic Learning 
 
 
Principal Investigator 
 
Adam L. Cohen, MD, MS 
 
 
Sub-Investigator(s) 
 
Ebtahal Al Shami B.A. 
Michelle Ferretti, MSW, LCSW, OSW-C 
 
Patient Advocate 
Deriece Harrington 
 
Sponsor 
 
Inova Schar Cancer Institute 
Inova Neurosciences  
 
 
April 20, 2022 
 
Version 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ABSTRACT 
 
Title:   ACT I: Assessment of Cancer Related Brain Fog using the Test of Strategic Learning 
 
Short Title:  ACT I. 
 
Rationale:  To determine the ability of the Test of Strategic Learning (TOSL) to detect cognitive 
impairment in people complaining of brain fog. 
 
Objectives: We hypothesize that we can recruit 3 people per month and that the TOSL will have high 
correlation with PAOFI higher level cognition subscore.  The primary objectives are:  Time to recruit 
the first 10 patients and the correlation of TOSL Synthesizing Summary score with PAOFI score at 
time 0 
 
Study Type:  This is a prospective observational cohort 
 
Study Design:  55 people will be recruited who are 18 years of age and older and diagnosed with 
stage I-III breast cancer within the last 5 years and who can operate a computer and read and 
understand English. 
 
Study Methodology:  Participants will complete the TOSL, the PAOFI, and the FACT-COG at 
enrollment and then 3 months later.  Completion can be done in person or on a computer.   
 
Statistical Methodology: After the 1st 10 people we will pause to consider the recruitment rate and 
feasibility.   If we can recruit 10 people in 4 months (recruitment rate 2.5 people/month) that will be 
considered sufficient recruitment rate to proceed to the full study. If the recruitment rate and 
dropout rate are sufficient for completing the main study in the allotted time, we will proceed to 
stage 2, which is the full study. We will use a Spearman correlation coefficient to compare the 
TOSL subscales with the PAOFI subscales.  50 people will also give 80% power to reject the null 
hypothesis of 0 correlation if the actual correlation is at least 0.4, at a significance level of 0.05.  
Assuming 10 percent drop out, we will recruit 55 people. 
 
 
                                                                                                                                                              

                           
INTRODUCTION 
 
1.1. Specific Aims 
 
Aim 1:  To demonstrate the feasibility of recruiting patients to a brain fog study at Inova 
Aim 2:  To correlate BHI gist reasoning and complex narrative memory domains with overall Patient 
Reported Outcome measures at baseline 
Aim 3: To correlate change in BHI gist reasoning and complex narrative memory domains with change 
in Patient Reported Outcome Measures 
 
1.2. Hypothesis  
We hypothesize that the Brain Health Index domains of gist reasoning and complex narrative memory 
will negatively correlate with higher cognitive subscale of the PAOFI and changes in BHI will negatively 
correlate with changes in the higher cognitive subscale of the PAOFI 
 
1.3. Background and Significance   
 
1.3.1. BACKGROUND 
Breast cancer remains the most common cancer in women, with an estimated incidence of 2,261,419 new cases 
reported globally in 2020.  Breast cancer in men is rare; in 2019 in the United States, less than 1% of new 
breast cancer diagnosis occurred in men.  Cancer-related cognitive impairment (CRCI) in breast cancer 
patients, sometimes called “brain fog” is now a recognizable concern, and an important problem to address. In 
2018, 3.1 million women were reported to live with breast cancer in the United States and up to 75% experience 
CRCI.  CRCI in patients with breast cancer causes problems with attention, working memory, executive 
function linked to a region in the brain called the prefrontal cortex, as well as processing speed.  CRCI has a 
negative impact on quality of life (QOL) and detrimental effects on daily activities.     The etiology of CRCI 
is not yet well understood, it can be related to the disease or treatments, such as surgery, chemotherapy, 
radiation, hormone therapy, and immunotherapy.   
 
Patient complaints of CRCI symptoms have been reported and documented mostly by Self-Assessments, 
directly from patients, and Patient-reported outcomes (PROs). One of the few formal neuropsychological tests 
that assesses a spectrum of cognitive abilities in breast cancer patients is the Patient’s Assessment of Own 
Functioning Inventory (PAOFI).  PROs have consistently documented brain fog. However, there is a lack of 
evidence of detected concordance between CRCI self-reported complaints and formal neuropsychological 
assessments that are currently being implemented. In addition, the specific attribution of PAOFI to 
standardized neurocognitive metrics is not well examined and understood.  Further, analyses the correlation of 
PAOFI to “objective” standardized neurocognitive assessments. The study also aims to examine the ability of 
standardized psychometrics to detect CRCI complaints, thus establishing a strong agreement between cognitive 
complaints and neuropsychological performance. 
 
1.3.2. 
BACKGROUND ON PAOFI and FACT-COG 
 
The Patient Assessment of Own Functioning Inventory (PAOFI) is a subjective measure of cognitive function. 
PAOFI is a widely used application in a diverse set of clinical population. The PAOFI was developed in 
reflection of commonly reported complaints and the cognitive domains typically assessed in 
neuropsychological evaluations. The PAOFI consists of 33 categories designed to assess the different aspects 
of cognitive function with the goal of capturing the diverse characteristics of self-assessed cognitive 
complaints. Categories are aggregated into four subscales: Higher Level Cognitive and Intellectual Functions 
(HLC) tapping executive functioning (nine questions); Memory (ten questions); Language (nine questions); 
and Motor/Sensory-Perceptual (five questions).   Items are rated on a Likely scale from 1 (“almost always”) to 
6 (“almost never”). The scoring system involves summing only the items with high severity number (i.e., 
scores of 1, 2, or 3) into a domain score. There have been limited studies evaluating the psychometric properties 

and reliability/validity of PAOFI.  To better understand its usefulness in this patient population, a study 
conducted by Van Dyk et al. examined the scaling structure, reliability, and construct validity of the PAOFI in 
breast cancer survivors. The study found that certain aspects of the assessment, such as the scoring method are 
not sensitive enough to detect the more subtle cognitive changes that are frequently reported by breast cancer 
patients.   
 
Self-reporting instruments have been widely administered across a diverse range of clinical settings. This 
approach has been regularly applied in experimental studies and is validated by clinicians to be a practical and 
effective method for collecting data (Van Dyk et al., 2017). The Functional Assessment of Cancer Therapy-
Cognitive (FACT-Cog) is a certified method for identifying patients’ cancer-related cognitive impairments. 
FACT-Cog is a self-reported questionnaire designed for cancer patients to assess perceived cognitive function 
and its impact on quality of life (Costa et al., 2018). The FACT system was first developed in 1980 by David 
Cella, a postdoctoral student in Memorial Sloan Cancer Center (www.facit.org). FACT has now become a 
licensed measurement system with many categories of assessments, one being the FACT-COG.  The FACT-
COG consists of 37 questions evaluating four different components of perceived cognitive function; perceived 
cognitive impairments (CogPCI: 20 items); perceived cognitive abilities (CogPCA: 9 items); comments from 
others (CogOth: 4 items); and the impact of perceived cognitive impairments on quality of life (CogQOL: 4 
items). It is aimed at assessing patients’ memory, attention, concentration, language, and thinking skills and 
the impact of cognition disturbances on the quality of life. Participants’ rate the question based on how many 
times a given situation has occurred the past week. This is constructed on a five-point scale, from never/not at 
all (0) to several times a day/very much (4).  The total FACT-Cog score is the sum of the four subscales and 
ranges from 0-148. The higher the total score, the better the cognitive function, and the lower the impact on 
patients’ quality of life (Hajj et al. 2020, Costa et al. 2018).  Studies evaluating the FACT-Cog found 
appropriate construct validity for the total score of neuropsychological weaknesses in cancer patients and 
survivors. The assessment has specific strengths in detecting signs of depression and anxiety rather than 
cognition function, such as memory. (Hajj et al. 2020) Thus in orders to detect cognitive dysfunction, 
suggestions have been made to refine the assessment. A recommended best approach is incorporating assessing 
cognitive abilities (Dyk et al., 2017). Others found the calculation structure uncertain, and a big consideration 
was tailored to future efforts focusing on scoring specific cognitive domains separately (Van Dyk et al., 2020). 
Overall, there are significant concerns in regard to the FACT-Cog lacking targeted subjective abilities. 
 
1.3.3.       BACKGROUND ON BHI 
 
The Brain Health Index (BHI) is a standardized performance benchmark that was developed by scientists at 
the Universities of Edinburgh and Glasgow.  BHI was designed to assess whole brain deterioration and help 
predict cognitive function. BHI has been successful in detecting cognitive decline in stroke patients 
significantly more accurate than methods that were previously established.  This performance benchmark 
allows an effective observation of changes in key cognitive abilities over time. BHI includes various 
assessment domains that incorporate a series of written and verbal tasks, specifically targeting the frontal lobe. 
It aims at to determining the performance of critical frontal lobe processes, which are responsible for executive 
functions such as planning, decision making, and problem solving. 
 
An assessment domain of BHI called the Test of Strategic Learning (TOSL) measures gist reasoning, an 
assessment that directs participants to construct as many abstract ideas as possible from a lengthy text. The 
scoring is based on the number of abstract ideas the participants cultivated.  TOSL also includes a measurement 
of memory for text details called the Memory for Details. Participants are asked to recall specific details of the 
text used to assess gist. Previous studies have found that the gist reasoning test may be sensitive enough to 
help clinicians identify previously undedicated subtle cognitive changes that could explain the difficulties of 
daily life experienced by patients with cognitive impairments. This was found to be true in patients with 
traumatic brain injury. Gist reasoning is also found to be a subsequently guide for appropriate therapies.  
 
The Visual Selective Learning Task (VSLT) is a selective learning task in which the participant’s ability to 
learn select information among other items is assessed (Hanten et al., 2004; Hanten, Zhang, & Levin, 2002). 
Individuals are presented with multiple trials of single words, 20 words each, 10 of which are a high-point 
value and 10 of which are a low-point value. Individuals are instructed to remember as much as they can, with 

the goal being to earn points. The ability to filter low-value and focus on high-value information is reliant on 
attention, working memory, and inhibition and has been shown to be sensitive to frontal lobe dysfunction, 
including attention deficit disorders and traumatic brain injury. 
 
1.3.4.      Rationale of ACT1 
 
Prior studies have found a lack of association between neuropsychological performance and documentation of 
subjective cognitive complaints in breast cancer patients. This could be reflective to the lack of specificity and 
sensitivity of the self-reported tools.  Gist reasoning is predicted to be a better evaluator of frontal lobe 
cognitive function. Thus, it provides us with a better way to detect cognitive complaints in breast cancer 
patients. Cognitive complaints indicate neuropsychological decline but efforts to establish this relationship in 
cancer survivors have produced ambiguous results.  It is believed that subjective cognitive assessment is not a 
substitute for objective performance. Cognitive complaints in breast cancer survivors are unique, expressive 
symptoms that alert clinicians of threats to poor cognitive functioning. Future research should focus on the 
effects of objective instruments to assess neurocognitive performance in breast cancer population. Establishing 
a strong correlation between neurocognitive performance and cognitive complaints will allow increased 
awareness of cognitive decline in breast cancer patients. This is imperative in the quest of studying this adverse 
event. There are a few studies that assess CRCI in a heterogeneous matter using an adequate size of sample 
population and diverse set of breast cancer patients. This study hypothesizes that TOSL is an objective indicator 
of brain fog which yields increased sensitivity and superior results.  
 
2. 
STUDY DESIGN AND SUBJECT SELECTION  
 
2.1. Study Type 
This is an observational prospective cohort study 
 
2.2. Setting/Location 
Subjects will be recruited from clinics at ISCI, LWC sessions, and community groups. 
 
Consenting: A study team member to contact patient, introduce the study, and schedule a convenient time to 
consent. Consent can be done in one of the consult rooms and /or CTO conference rooms or over the phone. 
 
Assessments:  Assessments can be done either in person or on computer from home. If they are done in 
person they will be done: 
 
BHI , PAOFI  and FACT-COG can be done Clinic consult rooms/various rooms in ISCI or in the life with 
cancer lounge rooms on floor 2. All assessments will be done on a computer. 
 
 
2.3. Duration of Study 
There will be two assessments, three months apart.  The expected duration of recruitment is 18 months. 
 
2.4. Number of Subjects  
55 people 
 
2.5. Study Population 
 
2.5.1. 
Gender of Subjects 
Men or women with stage I-III breast cancer. 
 
2.5.2. 
Age of Subjects 
>18 years 
No upper limit 
 
2.5.3. 
Racial and Ethnic Origin  

No restrictions.  To increase the recruitment of a diverse subject population, all assessments are available 
both online or on paper.  We have also involved a patient advocate on the leadership committee to help with 
community outreach. 
 
2.5.4. Vulnerable Populations 
 
As this study is no more than minimal risk, vulnerable populations will not be excluded. 
 
2.6. Inclusion Criteria 
 
1. 18 years of age or older 
2. ECOG performance status ≤ 2 
3. Patients diagnosed or with a history of breast cancer within the last 5 years.  
4. Life expectancy of at least 3 months 
5. Subject reports experiencing brain fog or cognitive impairment that the subject attributes to cancer or 
cancer therapy 
6. Able to sit for one hour and attend and respond to verbal and written instructions.  
7. Able to use a computer 
 
 
2.7. Exclusion Criteria 
 
1. 
Brain metastases from breast cancer 
2. 
Severe hearing or visual impairment 
3. 
Unable to give informed consent 
4. 
Unable to read and write in English 
5. 
Those diagnosed with history of neurologic injuries or disorders (e.g. seizures, strokes, traumatic brain 
injury, brain surgery, neurodegenerative disorders) other than those attributable to cancer or cancer 
therapy. 
 
 
STUDY METHODS AND PROCEDURES 
 
3.1. Setting/Location 
 
3.2.   Recruitment 
 
In close collaboration with ISCI breast clinical physicians (Dr. Mauro, Dr. Harnden, and Dr. Pennisi) and 
breast surgery clinic (Dr. Wiley). CRC can also prescreen physician schedule and contact patients directly. 
The patient advocate will also assist in outreach efforts to community organizations. 
 
3.3. Study Treatment/Intervention 
 
This is a non-interventional study. 
 
At both time points, patients will be administered the TOSL, the PAOFI, and the FACT-COG. Testing will take 
approximately 30-50 minutes to complete. Each participant will be tested individually in a quiet room by a 
trained examiner or at home via computer. Subjects will complete the PAOFI and FACT-COG before the VSLT 
and TOSL.  The PAOFI and FACT-COG are included in the appendix. 
 
The Visual Selective Learning Test: 
The VSLT will be administered to examine the ability to filter low-value and select high value information. 
In the VSLT the examinee is presented with a series of words, one at a time. Some words are in all caps and 
some are in all lower case.  There are three rounds. In two of the rounds, words in all caps are valued at 10 

points and words in lower case are valued at 1 point. In the third round, the values are reversed.  The 
examinee is instructed to remember the words to maximize their point value. 
 
The Test of Strategic Learning: 
The Test of Strategic Learning (TOSL, Chapman, Gamino, & Cook, under review; S. Chapman, J. Hart, H. 
Levin, L. Cook, J. Gamine, unpublished data, 2009) will be administered to examine the higher-order cognitive 
control function of gist reasoning (the ability to abstract novel integrative interpretations from complex 
information) and to examine memory for core details/facts.   
 
The TOSL consists of a one-page text in the form of an expository, biographical narrative. The narrative is 
dense with details of the person’s life. Taken beyond the surface level, the texts contain multiple high-level 
themes that encapsulate the key concepts within the story. For example, one of the TOSL texts was about a 
man (John Pierpoint’s) life and the eight jobs he attempted throughout his life in an effort to improve life for 
others (Chapman et al. 2002). The text also contained detailed information about the reasons for his failure in 
each career.  There are 3 different TOSL text narratives which can be used alternately: Malcolm Muggeridge, 
Sarah Hale, John Pierpont. One of the texts can be used at time point 1 and a different text can be used at 
time point 2 to minimize practice effects.  
 
The three components of the TOSL are:  
1) A high-level overview of the text.   
2) Life lessons or take-away messages that could be learned from the text (Interpretive statements) 
3) Detail-level questions about the text 
The first two components yield two measurements of the ability to use gist reasoning to abstract the central 
message and glean interpretations from complex information. The third component provides a measure of the 
ability to recall the important facts/details.  
 
Participants will be tested individually in a quiet room by a trained examiner. Before presenting the text, the 
examiner familiarizes participants with the task. The participants are informed: “The text conveys a lot of high-
level meanings. After reading the passage, I will first ask you to write a high-level overview. Then I will ask 
you to generate numerous lessons that can be learned. So be thinking about the bigger ideas as you read the 
text. Also, I will ask you some specific questions.” 
 
Participants are then provided with a copy of the narrative text to read. Participants read the text silently. The 
participant is allowed to re-read the narrative and may underline or take notes if they desire, but they are 
informed they will not be allowed to refer back to the text once they are done reading.  Upon completion, the text 
is removed from sight so that participants do not have the option to refer to it further. The participant is then 
asked to write a condensed version of the passage they just read that includes as many high-level ideas as 
possible within a 6-minute time limit. They are instructed they do not need to include all of the details, but 
instead to write highlights that convey ideas of substance from the text. If participants begin making a list or 
writing down bullet points of information, they are cued to instead write down their ideas in the form of a 
paragraph. In addition to the abstracted overview/synopsis, to further assess the ability to abstract meaning, 
participants derive one-sentence interpretive statements from the text. The participant is next asked to write 
down as many lessons or take-home messages that can be gleaned from the information as he or she can 
think of within a 6-minute time limit.  
 
Subsequently, the participant is given the “memory for detail” recall measure of the TOSL, which entails a 
series of cued questions to assess recall of specific details from the complex narrative text that was used to 
assess gist reasoning. Participants are first asked a question that requires listing key points from the text. 
They are then asked 8 cued questions that require short answers regarding detail information about 8 key 
points from the text.  For example, for participants given the TOSL text about John Pierpoint, participants are 
first asked to recall all the careers that John Pierpont had. They are then asked cued questions to specify what 
happened in each of the 8 careers.  
 

The TOSL has a manualized objective scoring system in which written overviews/synopses conveying 
abstracted gist meanings receive a higher score than those that focused on the stated details of the text. 
Participants receive 1 point for each key thematic concept/abstracted idea conveyed in their overview of the 
text in their own words; verbatim or paraphrased ideas receive no points. With regard to scoring the 
interpretive statements, concrete interpretations of the text that were directly tied to the explicit content also 
receive no points. Abstract interpretations that express a generalized takeaway that can be inferred from the 
narrative and are stated in the client’s own words rather than via a cliché or rote saying receive 1 point. When 
scoring the “memory for detail’ recall measure of the TOSL, a cumulative score can range from 0 to 24 total 
points possible, with 24 points representing the best possible score. One point is given for each of the 8 
possible key points recalled. In addition, for each prompt to provide more specific detail about the key 
points, participants can receive a score from 0 to 2 points depending on the accuracy and completeness of the 
response. Participants receive 2 points for providing 2 or more details specific to the given prompt, 1 point 
for accurately capturing one detail, and no points for incorrectly recalled details. For example, on the TOSL 
text about John Pierpoint, participants receive 1 point for each of the eight careers they recall and 2 points for 
giving a complete reason for each career’s failure, 1 point for giving a partial reason, or 0 points for giving 
an incorrect reason.  
 
Two trained raters independently score the TOSL overviews, interpretative statements, and responses to probes 
about their memory for details. Disagreements between raters are resolved through discussion and mutual 
consensus. The scoring will be discussed with a clinician from the Center for BrainHealth at UT Dallas over 
telephone or video call, with no identifying patient information provided. Raters are blinded to the participants’ 
scores on the patient-reported outcome measures.  
 
Responses to detail-level questions about the text (TOSL Part 3) will be tape-recorded and later transcribed 
for verbatim scoring for all participants. Written responses will be elicited for the overviews/synopses and 
interpretive statements (TOSL Parts 1 and 2) for all participants except for those who are unable to write their 
responses due to physical constraints. For these participants, oral responses on these tasks will also be audio-
recorded and later transcribed for verbatim scoring. Participants will also be asked to read aloud their written 
overviews/synopses and interpretive statements for audio-recording and later transcription if their handwriting is 
difficult to read. Audio recordings will be deleted after transcription.  
 
 
Brief Description of Variables from Cognitive Testing   
Name of Measure 
Variables/what 
is being assessed 
by the measures 
Description  
Scoring  
Scoring 
information:   
Test of Strategic Learning 
(TOSL) Part 1:  Synthesizing 
summary 
Gist reasoning 
 
Participant 
construct as many 
abstracted ideas 
as possible (in a 
summary format) 
from a 1-page 
text  
 
Number of 
abstracted ideas 
Performance 
ranges: 
0 – 1: 
Lower 30% 
2 – 3: 
Middle 40% 
4+ Upper 
30% 
 
Test of Strategic Learning 
(TOSL) Part 2: Lessons/one-
sentence interpretative 
statements 
 
Gist Reasoning  
Patient provides 
as many one-
sentence 
interpretations as 
possible from a 
1-page text  
Number of 
interpretation 
statements  
 
0-1: Lower 
25% 
2-3: Middle 
50% 
4-10+: Upper 
25% 

 
Test of Strategic Learning 
(TOSL) Part 3: Memory for 
Details 
Memory for 
details/facts from 
a complex 
narrative text 
Participant recalls 
(on cued 
questions) 
specific details of 
the text used to 
assess gist 
reasoning 
Recall of facts  
 
0-24 
0-8 points: 
Lower 25% of 
clients 
 
9-16: Middle 
50% of clients 
 
17-24: Upper 
25% of clients 
 
 
 
 
 
3.4. Endpoints/Outcomes Measurements 
 
3.4.1. Primary outcomes. 
 
Primary Outcome:  
Stage 1: Time to recruit the first 10 patients 
Stage 2: Correlation of TOSL Synthesizing Summary score with PAOFI score at time 0 
 
Primary end-points: 
Stage 1:  Number of months between opening of recruitment and recruitment date of the 10th subject 
Stage 2: Spearman correlation coefficient between the TOSL Lessons score and the PAOFI higher level 
cognition subscale score. 
 
3.4.2.  Secondary outcomes 
 
1. Correlation of the TOSL Lessons score with the PAOFI total score and the FACT-COG cognitive 
impairments subscore and total score 
2. TOSL synthesizing summary score and TOSL memory for details score and the PAOFI higher level 
cognition score, PAOFI total score, and FACT-COG cognitive impairments subscore and total score at 
time 0 
3. Correlation of the change in the TOSL Lessons score, synthesizing summary score, and memory score 
with the change in PAOFI total score, higher level cognition subscore, and FACT-COG cognitive 
impairment subscore and total score between session 1 and session 2, 3 months apart 
3.5.    Consent/Assent 
 
Delegated study investigators who received consent training will approach eligible subjects for enrollment 
into the study. A copy of the signed consent form will be given to the patient, the original signed consent will 
be kept in a study binder. No study procedures will occur prior to obtaining informed consent.  
 
 
3.6.   Monitoring Subjects and Criteria for Withdrawal of Subjects from the Study.    
 
Subjects may voluntarily stop at any time. 
 
STATISTICAL CONSIDERATIONS/DATA ANALYSIS 
 
4.1.   Sample Size   

 
Stage 1 (internal pilot): 
 
After the 1st 10 people we will pause to consider the recruitment rate and feasibility.   
 
10 people with also give 80% confidence that we will encounter in the pilot study at least one incident of 
some unanticipated problem that may arise with a probability of 15%. (Vichtbauer 2015)  
We will estimate the recruitment rate as 10 divided by the number of months to recruit 10 people.  For the 
full study to recruit 55 people in 18 months requires an average recruitment of 3 people per month.  If we can 
recruit 10 people in 4 months (recruitment rate 2.5 people/month) that will be considered sufficient 
recruitment rate to proceed to the full study. 
 
10 people will also allow an estimate of the dropout/noncompletion rate. If the observed dropout rate is 10%, 
a sample size of 10 people will provide an 80% two-sided confidence interval of 1 to 34%. 
 
If the recruitment rate and dropout rate are sufficient for completing the main study in the allotted time, we 
will proceed to stage 2, which is the full study. 
 
Stage 2 
The TOSL lessons score is a numeric score from 0 to 10 that can then be split in quartiles.  In cognitively 
normal seniors, the mean score is 3.35 with SD 1.29.  The complex narrative memory subscale is a numeric 
score from 0 to 24.  In cognitively normal seniors, the mean score is 16.35 with SD 3.88. (Anand 2010) The 
PAOFI has 33 questions, each measured on a 1-6 score. The higher cognitive learning subscale has 12 items, 
and the reported score is an average of these items. In healthy controls the mean was 1.32 with SD 0.40.  In 
women with breast cancer with cognitive complaints, the mean score was 2.68 with standard deviation 0.9.  
The Higher Level Cognition subscore has a Spearman correlation of ~ 0.47-0.71 with other memory tests in 
women with breast cancer without cognitive complaints.  We will use a Spearman correlation coefficient to 
compare the BHI subscales with the PAOFI subscales.  If the correlation coefficient is 0.7, to have 95% 
confidence interval width of 0.33 or less, we need 50 people.  50 people will also give ~85% power to reject 
the null hypothesis of 0 correlation coefficient if the actual correlation is at least 0.4, at a one-sided 
significance level of 0.05.  Assuming a 10 percent drop out, rate we will recruit 55 people. 
 
Given the small number of evaluations, the coordinator will confirm there are no missing items on the 
FACT-COG and PAOFI. 
 
FACT-COG will be scored using the version 3 scoring document (https://www.facit.org/measures-scoring-
downloads/fact-cog-scoring-downloads) without scoring the 4 items indicated as “NOT CURRENTLY 
SCORED.” 
 
Study participants’ VSLT score, TOSL score, the PAOFI score, FACT-COG score and their subscale score 
at baseline and follow-up will be summarized using descriptive statistics (N, min, max, mean, median, SD). 
  
The following Spearman’s correlation coefficients will be calculated  
between the TOSL Lessons score/VSLT score and the PAOFI higher level cognition subscale score  
between the TOSL lessons score/VSLT score and the PAOFI total score, the FACT-COG cognitive 
impairment subscale score and total score 
between TOSL synthesizing summary score, TOSL memory for details score and the PAOFI higher level 
cognition score, PAOFI total score, FACT-COG cognitive impairments subscale score and total score at 
baseline. 
between the change (from baseline to follow-up assessments) in the VSLT score, TOSL Lessons score, 
synthesizing summary score, memory score and the change (from baseline to follow-up assessments) in 
PAOFI total score, higher level cognition subscale score, the FACT-COG cognitive impairment subscale 
score and total score. 
 
4.2.   Data Storage   

 
4.2.1. Data Management 
 
Information about patients will be kept confidential and managed according to the requirements of the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA).  Privacy and confidentiality of all patients 
enrolled must be maintained.   
  
Study data will be collected and managed using REDCap electronic data capture tools hosted at Inova Health 
System. REDCap (Research Electronic Data Capture) is a secure, web-based application designed to support 
data capture for research studies, providing 1) an intuitive interface for validated data entry; 2) audit trails for 
tracking data manipulation and export procedures; 3) automated export procedures for seamless data 
downloads to common statistical packages; and 4) procedures for importing data from external sources. 
 
The VSLT and TOSL will be administered through Qualtrics hosted on the UT Dallas server.  This Qulatrics 
server is password protected and HIPAA compliant.  The subject records on that server will be coded by 
subject ID number, and the key will be kept at Inova in the REDCap EDC, so no identifiable information will 
be stored at UT Dallas. 
 
4.2.2.   Records Retention 
 
Data will be stored for three years following study completion and then destroyed. If data is used for future 
research and analysis, all identifiers will be removed.   
 
HUMAN SUBJECTS PROTECTION (RISKS, BENEFITS, AND    ALTERNATIVES) 
 
5.1. Risks 
 
Potential loss of privacy. The risk will be minimized by shielding the participant’s by unlinking his or her 
identity from his or her personal health information. 
 
Psychological risk. Patients may experience potential anxiety, stress, and depression as well as uncomfortable 
emotions such as anger, fear, sadness, discomfort.  
 
5.2. Benefits   
 
There are no direct benefits to the patient. All subjects will be informed about Life With Cancer free resources 
for brain fog. 
 
5.3.  Alternatives 
 
The alternative is not to participate in the research. 
 
5.4. Confidentiality 
 
Confidentiality of the data will be ensured as follows: 
• 
Only the research team will have access to electronic databases with the patient data. The electronic 
database will be held on a password-protected server within the Inova Health System firewall. 
• 
Data will be made available only to the investigators and staff working on this database, all of whom are 
appropriately trained. 
• 
Data for participants who take the Test of Strategic Learning electronically will have their responses stored 
on Qualtrics. Access to systems is restricted to specific individuals who have a need-to-know such 
information and who are bound by confidentiality obligations. Access is monitored and audited for 
compliance. Qualtrics uses Transport Layer Security (TLS) encryption (also known as HTTPS) for all 
transmitted data. Surveys may be protected with passwords. Qualtrics’ services are hosted by trusted data 
centers that are independently audited using the industry standard SSAE-18 method.  

 
 
SUBJECT COMPENSATION    
6.1. Costs 
 
There are no costs to participants. 
 
6.2. Payment  
 
$25 gift card at completion of second assessment. 
 
ADVERSE EVENT REPORTING   
 
As this is a minimal risk, non-interventional study, adverse events will not be recorded. 
 
FUNDING 
 
Inova Schar Cancer Institute and Inova Neurosciences Service Line. 
 
CONFLICTS OF INTEREST  
 
The research group has no conflicts of interest. 
 
  FACILITIES AND EQUIPMENT       
 
Inova Schar Cancer Institute 
8081 Innovation Park Drive 
Fairfax, Virginia 22031 
                                                   
 

 
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https://doi.org/10.1007/s10549-017-4376-4  
 
 

 
  APPENDIX  
 
 
FACT-Cognitive Function (Version 3) 
 
Below is a list of statements that other people with your condition have said are important. 
Please circle or mark one number per line to indicate your response as it applies to the 
past 
7 
days. 
  
 
  
  
  
  
  
  
  
  
PERCEIVED COGNITIVE 
IMPAIRMENTS 
Neve
r 
Abou
t once 
a 
week 
Two to 
three 
times a 
week 
Nearl
y 
every 
day 
Severa
l times  
a day 
CogA1 I have had trouble forming thoughts0 
  
0 
1 
2 
3 
4 
CogA3 My thinking has been slow0 
  
0 
1 
2 
3 
4 
CogC7 I have had trouble concentrating0 
  
0 
1 
2 
3 
4 
CogM9 I have had trouble finding my way to a familiar 
place0 
  
0 
1 
2 
3 
4 
CogM1
0 
I have had trouble remembering where I put 
things, like my keys or my wallet0 
  
  
0 
  
1 
  
2 
  
3 
  
4 
CogM1
2 
I have had trouble remembering new 
information, like phone numbers or simple 
instructions 0 
0 
1 
2 
3 
4 
CogV13 I have had trouble recalling the name of an 
object while talking to someone  
0 
1 
2 
3 
4 
CogV15 I have had trouble finding the right word(s) to 
express myself0 
  
0 
1 
2 
3 
4 
CogV16 I have used the wrong word when I referred to 
an object0 
  
0 
1 
2 
3 
4 
CogV17
b 
I have had trouble saying what I mean in 
conversations with others0 
  
0 
1 
2 
3 
4 
CogF19 I have walked into a room and forgotten what I 
meant to get or do there0 
  
0 
1 
2 
3 
4 
CogF23 I have had to work really hard to pay attention 
or I would make a 
mistake................................................................
................. 0 
  
0 
1 
2 
3 
4 

CogF24 I have forgotten names of people soon after 
being introduced0 
  
0 
1 
2 
3 
4 
 
 
  
 
Please circle or mark one number per line to indicate your response as it applies to  
the 
past 
7 
days. 
  
 
  
  
Neve
r 
Abou
t once 
a 
week 
Two to 
three 
times a 
week 
Nearl
y 
every 
day 
  
Severa
l times 
a day 
CogF25 My reactions in everyday situations have been 
slow0 
  
0 
1 
2 
3 
4 
CogC31 I have had to work harder than usual to keep 
track of what I was doing0 
  
0 
1 
2 
3 
4 
CogC32 My thinking has been slower than usual0 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
0 
1 
2 
3 
4 

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CogC33
a 
I have had to work harder than usual to express 
myself clearly0 
  
0 
1 
2 
3 
4 
CogC33
c 
I have had to use written lists more often than 
usual so I would not forget things0 
  
0 
1 
2 
3 
4 
CogMT
1 
I have trouble keeping track of what I am doing 
if I am interrupted0 
  
0 
1 
2 
3 
4 
CogMT
2 
I have trouble shifting back and forth between 
different activities that require thinking0 
  
0 
1 
2 
3 
4 
  
 
Please circle or mark one number per line to indicate your response as it applies to  
the past 7 days. 
  
  
  
  
  
COMMENTS FROM OTHERS 
Neve
r 
Abou
t once 
a 
week 
Two to 
three 
times a 
week 
Nearl
y 
every 
day 
  
Severa
l times 
a day 
CogO
1 
Other people have told me I seemed to have 
trouble remembering information0 
  
0 
1 
2 
3 
4 
CogO
2 
Other people have told me I seemed to have 
trouble speaking 
clearly...................................................................
................ 0 
  
0 
1 
2 
3 
4 
CogO
3 
Other people have told me I seemed to have 
trouble thinking 
clearly...................................................................
................ 0 
  
0 
1 
2 
3 
4 

CogO
4 
Other people have told me I seemed confused 
  
0 
1 
2 
3 
4 
  
Please circle or mark one number per line to indicate your response as it applies to  
the past 7 days. 
  
  
  
PERCEIVED COGNITIVE ABILITIES 
Not 
at 
all 
A 
little 
bit 
Some
-
what 
Quite
a bit 
Very 
much 
  
Cog
PC1 I have been able to concentrate 
0 
1 
2 
3 
4 
Cog
PV1 I have been able to bring to mind words that I wanted 
to use while talking to someone 
 
0 
 
1 
 
2 
 
3 
 
4 
Cog
PM
1 I have been able to remember things, like where I left 
my keys or wallet 
 
0 
 
1 
 
2 
 
3 
 
4 
Cog
PM
2 I have been able to remember to do things, like take 
medicine or buy something I needed 
 
0 
 
1 
 
2 
 
3 
 
4 
Cog
PF1 I am able to pay attention and keep track of what I am 
doing without extra effort 
 
0 
 
1 
 
2 
 
3 
 
4 
Cog
PC
H1 My mind is as sharp as it has always been 
0 
1 
2 
3 
4 
Cog
PC
H2 My memory is as good as it has always been 
0 
1 
2 
3 
4 
Cog
PM
T1 I am able to shift back and forth between two 
activities that require thinking 
 
0 
 
1 
 
2 
 
3 
 
4 
Cog
PM
T2 I am able to keep track of what I am doing, even if I 
am interrupted 
 
0 
 
1 
 
2 
 
3 
 
4 
  
  
Please circle or mark one number per line to indicate your response as it applies to  
the past 7 days. 
    
IMPACT ON QUALITY OF LIFE 
Not  
at all 
A 
little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
CogQ
35 I have been upset about these problems0 
  
0 
1 
2 
3 
4 
CogQ
37 These problems have interfered with my ability 
to work0 
  
0 
1 
2 
3 
4 
CogQ
38 These problems have interfered with my ability 
to do things I 
enjoy....................................................................
............... 0 
  
0 
1 
2 
3 
4 
CogQ
41 These problems have interfered with the quality 
of my life0 
 
0 
1 
2 
3 
4