Telephone Support for Metastatic Breast Cancer Patients
Phase: NA
Conditions: Metastatic Breast Cancer
Sponsor: Indiana University

                                                  IRB#: 1812850942 
 
 
 
Page 1 of 19 
 
 
 
Protocol: Randomized Controlled Trial of Acceptance and 
Commitment Therapy for Fatigue Interference with Functioning in 
Metastatic Breast Cancer 
 
Last approval date: 8/20/2024 
 

                                                  IRB#: 1812850942 
 
 
 
Page 2 of 19 
 
 
1.0 Study Objectives 
 
The primary objective of this NCI-funded Phase II RCT is to build on our pilot work by testing 
the impact of our telephone-based Acceptance and Commitment Therapy (ACT) program on 
fatigue interference (i.e., the degree to which fatigue negatively affects activities, mood, and 
cognition) in metastatic breast cancer (MBC) patients. A telephone-based approach can be 
readily disseminated to geographically dispersed patients and those with significant symptom 
burden and functional impairment that limit their ability to access in-person treatments. We will 
randomly assign MBC patients (N = 250) with significant fatigue interference to (1) six weekly 
50-minute telephone sessions of ACT or (2) six weekly 50-minute telephone sessions of an 
education/support condition. Outcomes will be assessed at baseline, 2 weeks post-intervention, 
and 3 and 6 months post-intervention. Additionally, we will assess potential theory-driven 
mediators of the ACT intervention’s effects. The study objectives are: 
 
 Primary Objective: To test the effect of telephone-based ACT on fatigue 
interference in MBC patients. 
H1: ACT will lead to an improved primary outcome of fatigue interference as compared 
to education/support. 
 
 Secondary Objectives:  
(a) To test the effects of telephone-based ACT on sleep interference, engagement in daily 
activities, and quality of life (QoL) in MBC patients. 
H2: ACT will lead to improved secondary outcomes of sleep interference, engagement         
in daily activities, and QoL as compared to education/support. 
(b) To examine change in psychological flexibility as a mediator of ACT’s effect on fatigue 
interference. 
H3: Increases in psychological flexibility will mediate the beneficial effect of ACT on   
fatigue interference. 
 
 Exploratory Objective:  
To explore changes in the two core aspects of psychological flexibility (i.e.,   
mindfulness/acceptance and commitment/behavior change processes) as mediators of 
ACT’s effect on fatigue interference. 
 
2.0 Outcome Measures/Endpoints 
All outcomes will be assessed at baseline and 2 weeks, 3 months, and 6 months post-
intervention. 
 
 Primary Outcome Measure:  
The primary outcome measure is the 7-item Fatigue Interference subscale of the Fatigue 
Symptom Inventory.1, 2 
 
 Secondary Outcome Measures: 
(1) Sleep interference will be assessed with the 8-item PROMIS sleep-related 
impairment measure.3, 4 This measure assesses the perceived interference of 
sleep problems with activities, mood, and cognition. 
(2) Engagement in daily activities will be assessed with the 6-item PROMIS short-
form measure of ability to participate in social roles and activities.5 The items, 

                                                  IRB#: 1812850942 
 
 
 
Page 3 of 19 
 
which are reverse-coded, measure difficulty engaging in social and recreational 
activities as well as usual work (including housework).  
(3) QoL will be measured with the 27-item FACT-G,6 consisting of four subscales: 
Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and 
Functional Well-Being. An overall score is computed to represent general QoL. 
 
3.0 Eligibility Criteria 
 
 Inclusion Criteria: 
 
• 
Patient is at least 3 weeks post-diagnosis of stage IV breast cancer and is receiving 
care at the Indiana University Simon Cancer Center, Eskenazi Health, IU Health 
North, IU Health Bloomington, IU Health Ball Memorial, IU Health Portland, IU 
Health Morgan, IU Health New Castle, IU Health Central-Fishers, another IU Health 
hospital or clinic, Community Health Network, or the Robert H. Lurie Comprehensive 
Cancer Center of Northwestern University. 
• 
Patient is at least 18 years of age. 
• 
Patient has adequate English fluency for completion of data collection.  
• 
Patient is willing to participate in this study. 
• 
Patient has moderate to severe fatigue interference (i.e., mean score >2.5 on the 
Fatigue Interference subscale of the Fatigue Symptom Inventory) 
 
 Exclusion Criteria: 
 
• 
Patient makes 3 or more errors on a validated 6-item cognitive screener7 or exhibits 
significant psychiatric or cognitive impairment (dementia/delirium, intellectual 
disability, active psychosis) that in the judgment of the investigators would preclude 
providing informed consent and study participation. 
• 
Patient Generated Subjective Global Assessment (PG-SGA; the patient-reported 
version of the Eastern Cooperative Oncology Group score) >2. 
• 
Patient is receiving hospice care at screening. 
• 
Patient does not have working phone service. 
• 
Patient has hearing impairment that precludes participation. 
• 
Male 
• 
Patient was randomized to a study condition in protocol #1512252646 (a pilot 
version of the current trial) 
 
Note: Patients who enroll in hospice during the trial will have the option of continuing trial 
participation. 
 
4.0 Study Design 
 
The study procedures are shown in Table 1.  MBC patients (N = 250) who meet eligibility 
criteria and provide informed consent will be randomized to receive either six weekly sessions of 
the ACT intervention or the education/support condition. Outcomes will be assessed via 
telephone at baseline and approximately 2 weeks, 3 months, and 6 months post-intervention.  
 
Table 1 
 

                                                  IRB#: 1812850942 
 
 
 
Page 4 of 19 
 
Timing 
Procedure and person(s) responsible 
At least 3 weeks after the patient’s 
Stage IV breast cancer diagnosis  
(1) The potential participant will receive a 
letter by mail notifying them about the study. 
Anyone interested will be invited to call for 
more details. The letter will have an "opt out" 
component; thus, patients who are not 
interested in the study may call the study 
team to indicate that they do not wish to be 
contacted. The mailing will also include copies 
of the recruitment brochure, study consent 
form, and authorization form. 
 
(2) A research assistant will call all those who 
do not opt out to provide an overview of the 
study and screen interested MBC patients for 
eligibility. The research assistant will obtain 
verbal informed consent for study participation 
from interested and eligible patients (see 
“recruitment process” and “informed consent 
process” below).   
Target date = within approximately 1 
week after recruitment. The baseline 
assessment can be completed up to 1 
month after recruitment.  
(3) Patients who consent to participate will 
complete a baseline assessment over the 
phone (see “interview procedures” below). 
This interview will be administered by a 
trained research assistant or a trained doctoral 
student in clinical psychology. 
Sessions will occur approximately 1 
week from each other, with the first 
session occurring about 1 week 
following the baseline assessment. 
Participants will have up to 12 weeks 
to complete the 6 sessions.  
(4) Patients will participate in six, 50-minute 
telephone-based sessions of the ACT 
intervention or education/support condition.  
Sessions will occur approximately 1 week from 
each other, with the first session occurring 
about 1 week following the baseline 
assessment. Sessions will be administered by 
a licensed therapist who will be trained and 
supervised by clinical psychologists. 
Approximately 2 weeks, 3 months, and 
6 months after the last intervention 
session. Assessments can be 
completed as early as 7 days prior to 
the target follow-up date or as late as 
21 days following the target follow-up 
date. 
(5) Patients will complete a follow-up 
assessment over the phone at approximately 2 
weeks, 3 months, and 6 months post-
intervention (see “interview procedures” 
below).  Assessments will be administered by 
a trained research assistant or a trained 
doctoral student in clinical psychology who is 
blinded to the intervention arm. 
 
5.0 Enrollment/Randomization 
 
Following baseline assessments, patients (N = 250) will be randomly assigned to the ACT 
intervention or education/support condition using a stratified block randomization scheme to 
balance the groups by patient age (<65 vs. >65 years) and performance status (Eastern 

                                                  IRB#: 1812850942 
 
 
 
Page 5 of 19 
 
Cooperative Oncology Group scores 0 or 1 vs. 2).8, 9 We will stratify randomization by 
performance status because the decision to provide chemotherapy and other cancer treatments 
is often based on performance status.10 Randomization will be performed by the IU Biostatistics 
Department. The study statistician will create the randomization procedure, and the PI will 
inform study therapists of their assigned patients. Other members of the study team will remain 
blind to participants’ group assignment. All patients will be registered with the Indiana 
University Cancer Center Clinical Trials Office. Applicable regulatory documents must be 
completed and on file prior to registration of any patients. 
 
6.0 Study Procedures 
 
Recruitment Process 
Electronic medical records for the study sites will be reviewed by a collaborating oncologist who 
is a co-investigator on this study or his or her authorized representative to identify patients who 
may be eligible for the study. Before sending a study introductory mailing to any potentially 
eligible patients, the project coordinator will discuss with the oncologist co-investigator if these 
potentially eligible patients may receive information about the study.  An introductory letter 
signed by the patient’s oncologist (the site PI, Dr. Goedde if a Community Health Network 
patient or the site PI, Dr. Addington if a Robert H. Lurie Comprehensive Cancer Center patient) 
and the PI will be sent to notify each potentially eligible person about the study (see Appendix 
A). The recruitment brochure (Appendix B), consent form, and authorization form will also be 
included in the initial mailing with the introductory letter.  Any interested patients will be invited 
to call for more details. The letter also will have an "opt out" component; thus, patients who are 
not interested in the study may call the study office to indicate that they do not wish to be 
contacted further.  
 
A research assistant will call all prospective participants who do not opt out within 
approximately 1 to 2 weeks after the letter is mailed. The research assistant will describe the 
study, review the consent form and authorization form, and ask if they would like to participate 
(see Appendix C for telephone script).  During that initial call, interested patients will complete 
the eligibility screening assessment (Appendix D).  The assessment will begin with the 
administration of the 7-item Fatigue Interference subscale of the FSI.1, 2 Eligible patients will 
have a mean score ≥ 2.5, indicating moderate to severe fatigue interference. Then patients will 
complete the 1-item Patient Generated Subjective Global Assessment (PG-SGA; the patient-
reported version of the Eastern Cooperative Oncology Group score).8, 9  Those with a score 
above 2 will be excluded from the study.  Next, patients will complete a validated 6-item 
cognitive screener.7  Patients with 3 or more errors on this screener will be excluded from study 
participation.  Those who are interested and eligible will provide verbal consent for study 
participation and verbal authorization to collect information from medical records.  Verbal 
consent was chosen in place of written informed consent to minimize the number of documents 
that link the participant with the research and therefore reduce the risk of a breach of 
confidentiality.  In addition, the entire study will be conducted via phone. Thus, we do not have 
the opportunity to obtain written consent during a face-to-face meeting with the patient.  If a 
potential participant does not answer the phone, a brief voicemail will be left (see Appendix C 
for telephone script). We will speak with the potential participant up to 5 times within 
approximately 1 to 4 weeks after the first phone call or a longer period of time if the patient 
requests a call from staff at a later date.  At least 2 weeks following the first voicemail message, 

                                                  IRB#: 1812850942 
 
 
 
Page 6 of 19 
 
we will leave a second voicemail message if we have been unable to reach the prospective 
participant.  Thus, we will leave a maximum of two voicemail messages.  
 
The research assistant will review the entire consent form and allow the potential participant to 
ask any questions they may have prior to consenting.  In addition, the authorization form will 
be reviewed with the potential participant.  If the patient needs more time or wants more 
information, an appointment to call again to obtain verbal consent will be made. If requested, a 
new consent form and authorization form will be either mailed or emailed to them (based on 
their preference).  
 
For patients who decline to participate in this study, we will ask if they would be willing to 
provide a reason for their decision.  With the patient’s permission, we will also document their 
age and race/ethnicity.  Regarding patients who agree to complete the screening assessment 
and are found to be ineligible, we will also document their age and race/ethnicity with their 
permission.  This information will be obtained solely for the purpose of determining potential 
sample selection biases.  Should non-participants decline to answer these questions, we will 
discontinue all further contact with them.  
 
Informed Consent Process 
All potential participants will be informed as to their rights as volunteers in a research study and 
will provide informed consent for research participation. The key elements of the informed 
consent procedure which will be explained to prospective participants are: 1) the research 
status of the study; 2) the potential risks and the provisions for them; 3) the lack of guarantee 
of benefit from participation; 4) the voluntary nature of the study; 5) the lack of consequence 
to medical care of the decision to consent or refuse to participate; and 6) the freedom to 
withdraw from the study or to refuse to answer specific questions or to participate in any aspect 
of the study at any time. Consenting patients will have the option of providing the name and 
contact information for an emergency contact person who may be contacted in the event that 
the study team repeatedly cannot reach the participant (see Appendix O).  
 
Interview Procedures 
MBC patients (N = 250) who are eligible and provide informed consent will complete 
assessments at baseline and approximately 2 weeks, 3 months, and 6 months following the 
final intervention session (see Table 1 in section 5.0 above for allowable assessment windows).  
The baseline assessment takes about 35 minutes, and each follow-up assessment takes about 
30 minutes.  Assessments will include questions regarding demographics, medical history, 
primary and secondary outcomes, and potential mediating variables.  Participants will be 
provided with copies of response options via email or postal mail to facilitate survey completion 
(see Appendix E). Each participant will receive $40 in Target gift cards via postal mail for each 
completed assessment (baseline and 2-week, 3-month, and 6-month follow-ups) for a possible 
total of $160 in gift cards for their time.  Participants will not receive gift cards for the 6, 50-
minute intervention sessions.  There is no cost to study participants.  Table 2 below outlines the 
assessment schedule at baseline and the three follow-ups. 
 

                                                  IRB#: 1812850942 
 
 
 
Page 7 of 19 
 
ECOG = Eastern Cooperative Oncology Group; FACT-G = Functional Assessment of Cancer Therapy-
General; FSI = Fatigue Symptom Inventory; PROMIS = Patient Reported Outcomes Measurement 
Information System; QoL = quality of life. 
 
Study Measures 
A 5-minute screening assessment to determine eligibility will be conducted with MBC patients 
using the measures described below (see Appendix D). 
 
Screening measures: Patients will first complete the 7-item Fatigue Interference subscale of the 
FSI.1, 2 Eligible patients will have a mean score ≥ 2.5, indicating moderate to severe fatigue 
interference. Then patients will complete the 1-item Patient Generated Subjective Global 
Assessment (PG-SGA; the patient-reported version of the Eastern Cooperative Oncology Group 
score).8, 9  Those with a score above 2 will be excluded from the study.  Next, patients will 
complete a validated 6-item cognitive screener.7  Patients with 3 or more errors on this screener 
will be excluded from study participation. All measures have well-established reliability and 
validity and have been studied in cancer populations.   
 
Baseline and follow-up measures: Patients will complete a 35-minute baseline assessment and 
three, 30-minute follow-up assessments using the measures described below (see Appendices 
Table 2. Measures  
 
 
Domain 
 
 
Measure 
 
#  
Items 
 
 
Baseline 
 
2-week 
follow-up 
3-month 
follow-
up 
6-month 
follow-
up 
Sociodemographics 
Sociodemographics 
7 
X 
 
 
 
Medical comorbidity 
Checklist of 9 conditions 
9 
X 
 
 
 
Functional status 
Patient-reported ECOG 
1 
X 
X 
X 
X 
Cancer information (e.g., 
date of diagnosis, cancer 
treatments) 
 
 
Chart review 
n/a 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Physical and mental 
healthcare use 
 
 
Healthcare use interview 
7 (6 at 
follow-
up) 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Medications  
Medication interview 
n/a 
X 
X 
X 
X 
Primary outcome: fatigue 
interference 
Fatigue interference subscale of 
FSI 
 
7 
 
X 
 
X 
 
X 
 
X 
Secondary outcomes: 
 
 
 
 
 
 
• Sleep interference 
PROMIS short-form sleep-
related impairment measure 
 
8 
 
X 
 
X 
 
X 
 
X 
• Engagement in 
daily activities 
PROMIS short-form measure of 
ability to participate in social 
roles and activities 
 
 
6 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
• QoL 
FACT-G 
27 
X 
X 
X 
X 
Hypothesized mediator: 
psychological flexibility 
Acceptance and Action 
Questionnaire-II 
 
7 
 
X 
 
X 
 
X 
 
X 
Exploratory mediators: 
mindfulness/acceptance 
and commitment/ 
behavior change  
Cognitive and Affective 
Mindfulness Scale-Revised; 
Value Progress subscale of 
Valuing Questionnaire 
 
 
 
15 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
Severity of symptoms: 
Fatigue severity, sleep 
disturbance, anxiety, 
depressive symptoms, 
pain, and cognitive 
symptoms 
Fatigue severity and frequency 
items from FSI; PROMIS short-
form measures of sleep 
disturbance, anxiety, 
depression, pain, hot flashes, 
and cognitive function 
 
 
 
 
 
48 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 

                                                  IRB#: 1812850942 
 
 
 
Page 8 of 19 
 
F-G).  Baseline and follow-up assessments will be audio-recorded so that the PI or a trained 
member of the study team may audit the assessments for adherence to the study protocol. 
Demographic information. The following demographic information will be assessed at 
baseline: age, race/ethnicity, marital/partner status, number of household members and their 
relationship to the patient, education, income, and employment status. Rural status will be 
determined by classifying the patient’s county of residence based on U.S. Census Bureau data.11   
Medical factors and healthcare use. As in prior NIH-funded trials with cancer patients,12, 13 
we will assess medical comorbidities, functional status, cancer information (e.g., date of breast 
cancer diagnosis, cancer treatments received), and physical and mental healthcare use.12, 14 
Medical comorbidities will be assessed at baseline only; functional status, cancer information, 
and healthcare use data will be collected at baseline and the three follow-up assessments. Self-
reported medical comorbidities will be assessed via a checklist of nine chronic health conditions. 
Functional status will be measured with the 1-item PG-SGA, a valid patient-reported version of 
the ECOG score.8 Cancer information, such as time since diagnosis and treatments received, will 
be assessed via chart review. Additionally, seven items will assess physical and mental 
healthcare use, including outpatient and emergency room visits, use of complementary and 
alternative healthcare services, and (at baseline only) prior mindfulness training.12, 14 Patients 
will also report their prescribed and over-the-counter medications. 
Primary outcome: Fatigue interference. The primary outcome measure is the 7-item Fatigue 
Interference subscale of the FSI.1, 2 Items are rated on 11-point scales (0=no interference; 
10=extreme interference) that assess the extent to which fatigue in the past week interfered 
with general level of activity, ability to bathe and dress, normal work activity (including 
housework), ability to concentrate, relations with others, enjoyment of life, and mood. This 
measure has been extensively used with cancer patients with strong evidence of construct 
validity and internal consistency reliability.15 In a review of fatigue measures for cancer patients, 
the FSI received the highest psychometric quality rating relative to other fatigue measures.16 
Cronbach’s alphas have been excellent in prior studies (αs = .91-.95)15 and our pilot research 
with MBC patients (αs = .92-.94). 
Secondary outcomes. Two secondary outcomes will be assessed with Patient-Reported 
Outcomes Measurement Information System (PROMIS) measures, which have many 
advantages. PROMIS measures were developed using sophisticated measurement techniques 
and tested with over 21,000 people.17-19 During measure development, cancer patients provided 
input to ensure their relevance for those with cancer.20 The available short-forms have strong 
evidence of reliability and validity and showed good internal consistency and convergent and 
divergent validity in our pilot research with MBC patients.21 Additionally, standardized T-scores 
facilitate comparisons with population norms. T-score distributions are standardized such that a 
score of 50 (SD = 10) represents the mean for the U.S. general population. U.S. cancer-specific 
reference values have been published for various PROMIS domains.22 A non-PROMIS measure, 
the FSI,1, 2 will be used to assess fatigue interference and severity, as the PROMIS short-form 
fatigue measures do not have subscales for these constructs. Finally, we will use another well-
validated non-PROMIS measure, the FACT-G,6 to assess QoL because many items on the FACT-
G specifically refer to the patient’s illness (e.g., “I am satisfied with how I am coping with my 
illness”), whereas PROMIS QoL items are not illness-specific. 
1) Sleep interference will be assessed with the 8-item PROMIS sleep-related impairment 
measure.3, 4 This measure assesses the perceived interference of sleep problems with 
activities, mood, and cognition. 
2) Engagement in daily activities will be assessed with the 6-item PROMIS short-form measure 
of ability to participate in social roles and activities.5 The items, which are reverse-coded, 

                                                  IRB#: 1812850942 
 
 
 
Page 9 of 19 
 
measure difficulty engaging in social and recreational activities as well as usual work 
(including housework).  
3) QoL will be measured with the 27-item FACT-G,6 consisting of four subscales: Physical 
Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. An 
overall score is computed to represent general QoL. 
Mediators. Psychological flexibility as measured by the 7-item Acceptance and Action 
Questionnaire-II (AAQ-II)23 will be assessed as a hypothesized mediator of the intervention’s 
effect on fatigue interference. Research has supported the reliability and validity of the AAQ-II 
for use with cancer patients.24-26 The two core components of psychological flexibility 
(mindfulness/acceptance and commitment/behavior change) will also be assessed as 
exploratory mediators. First, mindfulness/acceptance will be measured by the 10-item Cognitive 
and Affective Mindfulness Scale-Revised (CAMS-R).27 The scale provides a comprehensive 
assessment of mindfulness processes, including attention, present-focus, awareness, and 
acceptance/non-judgement. The measure showed strong evidence of reliability and validity in 
healthy samples,27 and our team has an ongoing study to examine its psychometric properties 
in 200 MBC and other advanced cancer patients. Data collection is finished, and we are 
currently preparing the data for analyses.  Second, commitment/behavior change will be 
measured by the 5-item Value Progress subscale of the Valuing Questionnaire.28 This subscale 
assesses progress in living consistently with personal values and showed excellent reliability and 
validity in our pilot work with MBC patients.21 
Measures of symptom severity. Fatigue severity and frequency will be measured with six 
items from the FSI,1, 2 and sleep disturbance, cognitive symptoms, anxiety, and depressive 
symptoms will each be assessed with a 6-item PROMIS measure.3, 4, 17, 22, 29, 30 Pain will be 
assessed with 3-item and 4-item PROMIS measures of severity and impact on functioning, 
respectively.17  The 10-item Hot Flash Related Daily Interference Scale will be used to assess 
the impact of hot flashes on aspects of quality of life.31 
 
ACT Intervention Procedures 
Drs. Mosher and Johns developed the ACT manual, which was informed by literature on fatigue 
and related symptoms in MBC patients,21, 32-34 the ACT model,35, 36 previous ACT trials with 
cancer patients and other populations with chronic conditions,24, 37-41 and Dr. Johns’s extensive 
experience delivering ACT to cancer patients. In the pilot trial, the intervention addressed the 
interference of any symptoms with activities. We refined the manual for the current study to 
focus on fatigue interference because it is the most common concern of MBC patients,42 and 
pilot findings were promising with respect to this outcome. The manual is found in Appendix H. 
Grounded in the ACT model,35 the intervention is designed to increase psychological flexibility 
(i.e., full awareness of the present moment, including fatigue, while persisting in actions 
consistent with personal values) and thereby reduce fatigue interference.  
     Licensed therapists will deliver the intervention. Table 3 shows a summary of the ACT 
sessions. While the therapist will aim to hold sessions on a weekly basis for 6 weeks, 
participants will have up to 12 weeks to complete the 6 sessions. According to the ACT model,43 
psychological flexibility is cultivated through the practice of six psychological skills: acceptance, 
values, defusion, contact with the present moment, self as context, and committed action. 
These skills constitute mindfulness and acceptance processes and commitment and behavior 
change processes. Each session has a primary focus on one of the six psychological skills (see 
Table 3), although in-session exercises and home practice generally promote multiple skills 
simultaneously. During the first session, the patient’s background and fatigue management 
strategies will be discussed, and the concept of mindfulness will be introduced. Participants will 

                                                  IRB#: 1812850942 
 
 
 
Page 10 of 19 
 
complete a 3-item version of the Fatigue Symptom Inventory and a 4-item standardized 
assessment of anxiety and depressive symptoms at the beginning of each session (see 
Appendix I).1, 29  Completion of this assessment will allow the therapist to monitor and respond 
to participants’ fatigue and distress.  Paper copies of the questionnaires will be provided to 
participants to facilitate survey completion. Across the six sessions, patients will practice 
mindfulness exercises, clarify their values, and set specific goals aligned with their values. 
Sessions will incorporate discussion of patients’ cancer experience, as their energy level and 
personal goals will be discussed in the context of their current medical care, functional status, 
and emotional responses to cancer. Each session will include assessing and recording the 
patient’s home practice of mindfulness and other skills and will end with a discussion of practice 
for the week ahead. Through skill practice, participants will learn new and more adaptive ways 
to respond to fatigue and other unwanted internal experiences (e.g., anxiety). Handouts 
summarizing the topics of each session (Appendix J) and a CD that our team developed to 
guide mindfulness practices will be mailed to participants. Participants will also have the option 
of receiving the mindfulness recordings via an emailed link from IU Box. 
 

                                                  IRB#: 1812850942 
 
 
 
Page 11 of 19 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 3.  ACT Session Description and Home Practice Assignments 
Topic (Targeted  
ACT model skill) 
Session and Home Practice (HP) Content 
Session 1: 
Introduction to 
Mindfulness 
(Acceptance) 
• Introductions and overview of the intervention 
• Discuss patient’s strategies for fatigue management, including control- 
vs. acceptance-based strategies and the workability of each in the 
context of coping with cancer 
• Introduce mindfulness and practice mindfulness (noticing sounds 
around her and her breathing) with therapist 
• HP1: Write a list of ways that fatigue has interfered with living a 
meaningful life; practice mindful breathing exercise daily; value-based 
goal 
Session 2: 
Exploring What is 
Most Important to 
You (Values) 
 
• Home practice review 
• Body scan mindfulness exercise and debriefing with reference to fatigue 
and the cancer experience 
• Clarify patient’s values with birthday exercise and explore how patient 
might respond to fatigue in an adaptive, values-consistent manner 
• Patient rates consistency of actions with values using the Valued Living 
Questionnaire44 
• HP2: Engage in action step in line with values; practice body scan 
exercise daily and log what is noticed 
Session 3: 
Decreasing 
Emotional Reactivity 
to Fatigue-related 
Thoughts and 
Emotions  
(Defusion) 
• Practice “leaves on the stream” mindfulness with therapist 
• Home practice review 
• Discuss the patient’s attempts to suppress the experience of fatigue and 
cancer-related thoughts and emotions (e.g., living with uncertainty) and 
the costs of these attempts in terms of reduced QoL  
• Explore the difference between “having” a thought and “buying” a 
thought 
• Further practice of mindfulness (noticing object or scene) with therapist 
• HP3: Write down two activities given up due to fatigue and any resulting 
emotions; practice “leaves on a stream” mindfulness exercise daily; 
value-based goal 
Session 4: 
Mindful Awareness 
of Fatigue (Contact 
with the Present 
Moment) 
 
• Practice mindfulness (noticing environment) with therapist 
• Home practice review 
• Practice mindful breathing 
• Introduce concept of willingness (i.e., flexibly making contact with the 
present moment, including fatigue) 
• HP4: Write down two activities that were enjoyed even while fatigued 
and resulting emotions; practice mindful breathing exercise daily; value-
based goal 
Session 5: 
Detaching from 
Fatigue  
(Self as Context or 
Perspective-Taking) 
• Practice mindfulness (self-compassion exercise) with therapist 
• Home practice review 
• Discuss observing and detaching from fatigue and related thoughts and 
emotions to cultivate a transcendent sense of self from which to observe 
and accept changing experience 
• Discuss letting go and accepting things as they are 
• HP5: Goal setting and practice; daily mindfulness practice (patient’s 
choice on CD) 
Session 6: 
Taking Steps to Do 
What Matters to You 
(Committed Action) 
• Practice mindfulness (brief body scan exercise) with therapist 
• Home practice review 
• Recap of skills and what patient learned 
• Goal setting around expanding patterns of values-consistent behavior 
after the study ends 
• Practice mindfulness (self-compassion exercise) with therapist 
• Termination and next steps in the study 
• HP6: Continue written goals 

                                                  IRB#: 1812850942 
 
 
 
Page 12 of 19 
 
Education/Support Condition Procedures 
The education/support control condition was tested in our pilot feasibility study.45 The manual is 
found in Appendix K. Patients randomized to the education/support condition will discuss their 
concerns, including symptoms and other cancer-related stressors, with a therapist providing 
psychological support. The therapist will direct patients to resources for practical and health 
information and contact information for psychosocial services. Thus, this study tests whether 
ACT is superior to supportive listening and education regarding medical center and community 
resources, consistent 
with common 
interventions in clinical 
settings. 
Licensed therapists will 
deliver the 
education/support 
intervention. Table 4 
provides a summary of 
the sessions. While the 
therapist will aim to hold 
sessions on a weekly 
basis for 6 weeks, 
participants will have up 
to 12 weeks to complete 
the 6 sessions. 
Education/support 
participants will complete 
the same weekly fatigue 
and distress assessments 
as those in the ACT 
condition. Sessions will 
include an orientation to 
the patient’s medical 
center and treatment 
team, education 
regarding common QoL 
concerns and symptoms 
experienced by cancer 
patients, and an 
overview of medical 
center and community 
resources for addressing 
these concerns. 
Therapists will also 
describe resources for 
addressing financial 
concerns and methods of evaluating health information available via the Internet and other 
modalities. Education/support participants will receive handouts summarizing the topics of each 
session and will be asked to review them as homework (Appendix L). ACT concepts will not be 
discussed in the education/support condition; thus, there is no overlap in intervention content 
between study conditions. 
Training of Therapists and Treatment Fidelity 
Training of therapists will involve didactics, live demonstrations, and role plays developed by the 
PI and her collaborators.  All intervention sessions will be audio recorded, and the PI and Dr. 
Linda Brown (study consultant and licensed clinical psychologist) will randomly review 20% of 
recorded sessions to ensure fidelity and quality control.  The PI will use therapist adherence 
checklists for the ACT and education/support conditions adapted from NIH-funded trials with 
Table 4.  Education/Support Session Description and Homework 
Topic 
Session and Homework (HW) Content 
Session 1: 
Orientation to 
medical center 
and treatment 
team; 
Overview of 
QoL issues 
• Overview of the upcoming sessions  
• Orientation to the medical center  
• Overview of components of QoL and discussion of physical 
QoL and symptoms 
• Discuss educational materials from the healthcare team 
• Overview of treatment team 
HW1: Review handouts on medical center information 
Session 2: 
Resources for 
addressing 
social 
functioning 
• Review common social challenges such as talking with 
children about cancer and employment issues 
• Contact information for resources to address social 
challenges 
HW2: Review handouts on contact information for resources 
to address social challenges 
Session 3: 
Resources for 
addressing 
role and 
emotional 
functioning 
• Tips on managing common household challenges when ill  
• Review common emotional responses to cancer, including 
anxiety and depressive symptoms, and cognitive changes 
following cancer treatment 
• Contact information for mental health services 
HW3: Review handouts on contact information for mental 
health services 
Session 4: 
Resources for 
addressing 
financial 
concerns 
• Review common financial concerns related to cancer and 
its treatment  
• Contact information for resources to address concerns 
HW4: Review handouts summarizing resources for 
addressing financial concerns 
Session 5: 
Resources for 
evaluating 
health 
information 
• Review methods of evaluating health information on the 
Internet and other modalities  
• Discuss resources for evaluating health information 
HW5: Review handouts summarizing resources for evaluating 
health information 
Session 6: 
Review and 
further 
resources 
• Review all topics discussed in prior sessions and available 
resources for addressing each topic area 
• Discuss websites for accessing cancer-related information 
HW6: Review handouts summarizing all resources  

                                                  IRB#: 1812850942 
 
 
 
Page 13 of 19 
 
cancer patients (see Appendix M).46  The PI and Dr. Brown will provide ongoing supervision of 
therapists.  During individual supervision with therapists, which will occur approximately every 
1-2 weeks, treatment adherence scores will be provided and treatment fidelity issues discussed.  
Role-plays will be conducted to correct deviations from study procedures.   
 
7.0 Statistical Considerations 
 
Design and data considerations. The primary and secondary outcomes in the proposed study 
are scaled continuously. For these outcomes, a linear mixed model using the SAS procedure 
MIXED will be employed.47, 48 Because parameter estimation in MIXED employs full information 
maximum likelihood, all data the individual provides are included in the analysis even if some of 
the data are missing. 
 
Preliminary analyses: Distributional issues. Univariate and descriptive analyses will be performed 
on all dependent variables, and if necessary, normalizing and/or variance stabilizing 
transformations will be sought in the family of power transformations and applied to the data 
before inferential analyses are undertaken. Missing data/subject attrition. We anticipate some 
missing data due to participant death, medical factors, and other reasons. For individuals who 
complete the first assessment but withdraw from the study, we will examine demographic, 
medical, and symptom factors that might be predictive of dropout using logistic regression. In 
the analyses for the primary and secondary objectives described below, all randomized 
participants will be included in intent-to-treat analyses,49 as the aims are concerned with the 
impact of the intervention on outcomes regardless of study completion status. Second, for 
participants who miss assessments, it is possible that attrition may be related to the study 
condition to which they have been assigned. We plan to use the random effects pattern-mixture 
model proposed by Hedeker and Gibbons50 to address missing data. Analyses of potential 
covariates. Because patients will be randomly assigned to the two study conditions, significant 
differences on the baseline values of all measured variables are not expected. T-tests and chi-
square analyses will be performed to determine whether there are differences between the 
groups on potential baseline covariates (e.g., demographic and medical variables), and if there 
are differences these variables will be used as covariates in subsequent analyses. 
 
Primary objective (2.1): To test the effect of telephone-based ACT on fatigue interference in 
MBC patients. A linear mixed-model repeated measures approach (SAS Proc-Mixed)48 will be 
used to test the hypothesis (#1) that ACT will improve fatigue interference as compared to the 
education/support condition. The model will include the main effect of time (as categorical) and 
study group (ACT vs. education/support) and the time-by-study group interaction. A treatment 
effect will be evidenced by a significant interaction between time and study group. If the 
treatment effect is significant, follow-up tests will be conducted to examine group differences at 
each follow-up, controlling for the outcome at baseline.  
 
Statistical power. Our sample size is calculated based on the estimated difference 
between study conditions (ACT vs. education/support) on the primary outcome of fatigue 
interference at 2 weeks post-intervention. In our pilot study, we found a moderate effect (d = -
.30) of study condition on fatigue interference at 1 month post-intervention. It should be noted 
that only about half of the pilot sample had elevated fatigue interference at baseline (unlike the 
proposed study, the pilot study did not require all eligible patients to have clinically significant 
levels of fatigue interference); thus, the effect size is likely to be higher in the proposed study 
where the sample will have uniformly elevated fatigue interference at study entry. Indeed, 

                                                  IRB#: 1812850942 
 
 
 
Page 14 of 19 
 
among patients with moderate to severe baseline fatigue interference in our pilot study, we 
found a strong effect (d = -.59) of study condition on fatigue interference at 1 month post-
intervention. Thus, we conservatively estimate a medium effect size of d = -.40 at 2 weeks 
post-intervention. With a sample size of 198 patients at 2 weeks post-intervention (assuming 
21% attrition), we will have 80% power (p = .05, two-tailed) to detect a Cohen’s d of -.40 in a 
linear mixed model.51 At the final, 6-month follow-up with a sample size of 163 (assuming 35% 
attrition), we will have 80% power (p = .05, two-tailed) to detect a Cohen’s d of -.44.51  
 
Secondary objective (2.2a): To test the effects of telephone-based ACT on secondary outcomes 
in MBC patients. Linear mixed models will be run in SAS Proc-Mixed48 to test the hypothesis 
(#2) that ACT will improve sleep interference, engagement in daily activities, and QoL as 
compared to the education/support condition. Each model will include the main effect of time 
(as categorical) and study group and the time-by-study group interaction. A treatment effect 
will be evidenced by a significant interaction between time and study group. Probabilities for 
secondary outcomes will be Sidak adjusted for correlated multiple outcomes to control the 
familywise Type I error rate. If treatment effects are significant, follow-up tests will be 
conducted to examine group differences at each follow-up, controlling for the outcome at 
baseline. 
 
Secondary objective (2.2b): To examine change in psychological flexibility as a mediator of 
ACT’s effect on fatigue interference. The PROCESS macro for SAS developed by Andrew Hayes52 
will be used to test the hypothesis (#3) that increases in psychological flexibility will mediate 
the effect of ACT on fatigue interference. This analysis employs ordinary least squares 
regression. Bootstrapped confidence intervals will be computed for the indirect effect of study 
group on fatigue interference at 2 weeks post-intervention (via change in psychological 
flexibility over the same time period). The analysis will control for baseline levels of the 
mediator and outcome. We will also compute the indirect effects of study group on fatigue 
interference at 3 and 6 months post-intervention (via change in psychological flexibility at 2 
weeks post-intervention). These analyses will also control for baseline levels of the mediator 
and outcome. 
 
Exploratory objective (2.3): To explore changes in the two core aspects of psychological 
flexibility (i.e., mindfulness/acceptance and commitment/behavior change) as mediators of 
ACT’s effect on fatigue interference. The PROCESS macro for SAS52 will be used to explore the 
extent to which changes in mindfulness/acceptance and commitment/behavior change 
processes mediate the effect of ACT on fatigue interference. Both potential mediators will be 
entered into the same model. Bootstrapped confidence intervals will be computed for the 
indirect effect of study group on fatigue interference at 2 weeks post-intervention (via change 
in mindfulness/acceptance and commitment/behavior change processes over the same time 
period). The analysis will control for baseline levels of the mediators and outcome. We will also 
compute the indirect effects of study group on fatigue interference at 3 and 6 months post-
intervention (via changes in mindfulness/acceptance and commitment/behavior change 
processes at 2 weeks post-intervention). These analyses will also control for baseline levels of 
the mediators and outcome. 
 
Other exploratory analyses. To inform future research, we will explore the extent to which 
sociodemographics (e.g., age, education) and clinical characteristics (e.g., cancer treatments, 
baseline fatigue severity) moderate the effects of ACT on primary and secondary outcomes. For 

                                                  IRB#: 1812850942 
 
 
 
Page 15 of 19 
 
these analyses, we will use linear mixed modeling at a two-sided significance level of 0.05. 
Preliminary findings or hypotheses generated from these moderation analyses will be further 
tested in a future trial. 
 
 
 
 
 

                                                  IRB#: 1812850942 
 
 
 
Page 16 of 19 
 
8.0 References 
 
1. 
Hann DM, Jacobsen PB, Azzarello LM, Martin SC, Curran SL, Fields KK, Greenberg H, Lyman 
G. Measurement of fatigue in cancer patients: Development and validation of the Fatigue 
Symptom Inventory. Qual Life Res. 1998;7(4):301-10. 
2. 
Hann DM, Denniston MM, Baker F. Measurement of fatigue in cancer patients: further 
validation of the Fatigue Symptom Inventory. Qual Life Res. 2000;9(7):847-54. 
3. 
Yu L, Buysse DJ, Germain A, Moul DE, Stover A, Dodds NE, Johnston KL, Pilkonis PA. 
Development of short forms from the PROMIS sleep disturbance and sleep-related 
impairment item banks. Behav Sleep Med. 2012;10(1):6-24. 
4. 
Buysse DJ, Yu L, Moul DE, Germain A, Stover A, Dodds NE, Johnston KL, Shablesky-Cade 
MA, Pilkonis PA. Development and validation of patient-reported outcome measures for 
sleep disturbance and sleep-related impairments. Sleep. 2010;33(6):781-92. 
5. 
Hahn EA, DeVellis RF, Bode RK, Garcia SF, Castel LD, Eisen SV, Bosworth HB, Heinemann 
AW, Rothrock N, Cella D. Measuring social health in the patient-reported outcomes 
measurement information system (PROMIS): item bank development and testing. Qual Life 
Res. 2010;19(7):1035-44. 
6. 
Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A, Silberman M, Yellen SB, 
Winicour P, Brannon J. The Functional Assessment of Cancer Therapy scale: development 
and validation of the general measure. J Clin Oncol. 1993;11(3):570-9. 
7. 
Callahan CM, Unverzagt FW, Hui SL, Perkins AJ, Hendrie HC. Six-item screener to identify 
cognitive impairment among potential subjects for clinical research. Med Care. 
2002;40(9):771-81. 
8. 
Bauer J, Capra S, Ferguson M. Use of the scored Patient-Generated Subjective Global 
Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin 
Nutr. 2002;56(8):779-85. 
9. 
Dajczman E, Kasymjanova G, Kreisman H, Swinton N, Pepe C, Small D. Should patient-
rated performance status affect treatment decisions in advanced lung cancer? J Thorac 
Oncol. 2008;3(10):1133-6. 
10. Cardoso F, Harbeck N, Fallowfield L, Kyriakides S, Senkus E. Locally recurrent or metastatic 
breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 
Ann Oncol. 2012;23(suppl. 7):vii11-vii9. 
11. United States Census Bureau. County classification lookup table: United States Census 
Bureau; 2023 [cited 2023 May 20]. Available from: https://www.census.gov/programs-
surveys/geography/guidance/geo-areas/urban-rural.html. 
12. Kroenke K, Theobald D, Norton K, Sanders R, Schlundt S, McCalley S, Harvey P, Iseminger 
K, Morrison G, Carpenter JS, Stubbs D, Jacks R, Carney-Doebbeling C, Wu J, Tu W. The 
Indiana Cancer Pain and Depression (INCPAD) trial: Design of a telecare management 
intervention for cancer-related symptoms and baseline characteristics of study participants. 
Gen Hosp Psychiatry. 2009;31(3):240-53. 
13. Kroenke K, Theobald D, Wu J, Norton K, Morrison G, Carpenter J, Tu W. Effect of telecare 
management on pain and depression in patients with cancer: a randomized trial. JAMA. 
2010;304(2):163-71. 
14. Kroenke K, Bair M, Damush T, Hoke S, Nicholas G, Kempf C, Huffman M, Wu J, Sutherland 
J. Stepped Care for Affective Disorders and Musculoskeletal Pain (SCAMP) study: design 
and practical implications of an intervention for comorbid pain and depression. Gen Hosp 
Psychiatry. 2007;29(6):506-17. 

                                                  IRB#: 1812850942 
 
 
 
Page 17 of 19 
 
15. Donovan KA, Jacobsen PB. The Fatigue Symptom Inventory: a systematic review of its 
psychometric properties. Support Care Cancer. 2011;19(2):169-85. 
16. Agasi-Idenburg C, Velthuis M, Wittink H. Quality criteria and user-friendliness in self-
reported questionnaires on cancer-related fatigue: a review. J Clin Epidemiol. 
2010;63(7):705-11. 
17. Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, Amtmann D, Bode R, Buysse D, 
Choi S. The Patient-Reported Outcomes Measurement Information System (PROMIS) 
developed and tested its first wave of adult self-reported health outcome item banks: 
2005–2008. J Clin Epidemiol. 2010;63(11):1179-94. 
18. Cella D, Yount S, Rothrock N, Gershon R, Cook K, Reeve B, Ader D, Fries JF, Bruce B, Rose 
M. The Patient-Reported Outcomes Measurement Information System (PROMIS): Progress 
of an NIH Roadmap cooperative group during its first two years. Med Care. 2007;45(5 
Suppl 1):S3-S11. 
19. Magasi S, Ryan G, Revicki D, Lenderking W, Hays RD, Brod M, Snyder C, Boers M, Cella D. 
Content validity of patient-reported outcome measures: Perspectives from a PROMIS 
meeting. Qual Life Res. 2012;21(5):739-46. 
20. Garcia SF, Cella D, Clauser SB, Flynn KE, Lad T, Lai JS, Reeve BB, Smith AW, Stone AA, 
Weinfurt K. Standardizing patient-reported outcomes assessment in cancer clinical trials: a 
patient-reported outcomes measurement information system initiative. J Clin Oncol. 
2007;25(32):5106-12. 
21. Mosher CE, Tometich DB, Hirsh A, Rand KL, Johns SA, Matthias MS, Outcalt SD, Bricker J, 
Schneider B, Mina L, Storniolo AM, Newton E, Miller K. Symptom experiences in metastatic 
breast cancer patients: relationships to activity engagement, value-based living, and 
psychological inflexibility. Psychooncology. 2017;26(11):1944-51. PMCID: PMC5359070. 
22. Jensen RE, Potosky AL, Moinpour CM, Lobo T, Cella D, Hahn EA, Thissen D, Smith AW, Ahn 
J, Luta G, Reeve BB. United States population-based estimates of Patient-Reported 
Outcomes Measurement Information System symptom and functional status reference 
values for individuals with cancer. J Clin Oncol. 2017;35(17):1913-20. 
23. Bond FW, Hayes SC, Baer RA, Carpenter KM, Guenole N, Orcutt HK, Waltz T, Zettle RD. 
Preliminary psychometric properties of the Acceptance and Action Questionnaire–II: A 
revised measure of psychological inflexibility and experiential avoidance. Behav Ther. 
2011;42(4):676-88. 
24. Feros DL, Lane L, Ciarrochi J, Blackledge JT. Acceptance and Commitment Therapy (ACT) 
for improving the lives of cancer patients: a preliminary study. Psychooncology. 
2013;22(2):459-64. 
25. Ciarrochi J, Fisher D, Lane L. The link between value motives, value success, and well-
being among people diagnosed with cancer. Psychooncology. 2011;20(11):1184-92. 
26. Hulbert-Williams NJ, Storey L. Psychological flexibility correlates with patient-reported 
outcomes independent of clinical or sociodemographic characteristics. Support Care 
Cancer. 2016;24:2513-21. 
27. Feldman G, Hayes A, Kumar S, Greeson J, Laurenceau J-P. Mindfulness and emotion 
regulation: The development and initial validation of the Cognitive and Affective 
Mindfulness Scale-Revised (CAMS-R). J Psychopathol Behav Assess. 2007;29(3):177-90. 
28. Smout M, Davies M, Burns N, Christie A. Development of the Valuing Questionnaire (VQ). J 
Contextual Behav Sci. 2014;3(3):164-72. 
29. Pilkonis PA, Choi SW, Reise SP, Stover AM, Riley WT, Cella D. Item banks for measuring 
emotional distress from the Patient-Reported Outcomes Measurement Information System 
(PROMIS(R)): depression, anxiety, and anger. Assessment. 2011;18(3):263-83. 

                                                  IRB#: 1812850942 
 
 
 
Page 18 of 19 
 
30. Choi SW, Reise SP, Pilkonis PA, Hays RD, Cella D. Efficiency of static and computer 
adaptive short forms compared to full-length measures of depressive symptoms. Qual Life 
Res. 2010;19(1):125-36. 
31. Carpenter JS. The Hot Flash Related Daily Interference Scale: A tool for assessing the 
impact of hot flashes on quality of life following breast cancer. J Pain Symptom Manage. 
2001;22(6):979-89. 
32. Aranda S, Schofield P, Weih L, Yates P, Milne D, Faulkner R, Voudouris N. Mapping the 
quality of life and unmet needs of urban women with metastatic breast cancer. Eur J 
Cancer Care. 2005;14(3):211-22. 
33. Mosher CE, Duhamel KN. An examination of distress, sleep, and fatigue in metastatic 
breast cancer patients. Psychooncology. 2012;21:100-7. 
34. Cleeland CS, Mayer M, Dreyer NA, Yim YM, Yu E, Su Z, Mun Y, Sloan JA, Kaufman PA. 
Impact of symptom burden on work-related abilities in patients with locally recurrent or 
metastatic breast cancer: Results from a substudy of the VIRGO observational cohort 
study. Breast. 2014;23(6):763-9. 
35. Hayes SC, Levin ME, Plumb-Vilardaga J, Villatte JL, Pistorello J. Acceptance and 
Commitment Therapy and contextual behavioral science: examining the progress of a 
distinctive model of behavioral and cognitive therapy. Behav Ther. 2013;44(2):180-98. 
36. Hayes SC, Strosahl KD, Wilson KG. Acceptance and Commitment Therapy, second edition: 
The process and practice of mindful change. New York: Guilford Press; 2012. 
37. Hann KEJ, McCracken LM. A systematic review of randomized controlled trials of 
Acceptance and Commitment Therapy for adults with chronic pain: Outcome domains, 
design quality, and efficacy. J Contextual Behav Sci. 2014;3(4):217-27. 
38. Hughes LS, Clark J, Colclough JA, Dale E, McMillan D. Acceptance and Commitment 
Therapy (ACT) for chronic pain: A systematic review and meta-analyses. Clin J Pain. 
2017;33(6):552-68. 
39. A-Tjak JGL, Davis ML, Morina N, Powers MB, Smits JAJ, Emmelkamp PMG. A meta-analysis 
of the efficacy of acceptance and commitment therapy for clinically relevant mental and 
physical health problems. Psychother Psychosom. 2015;84:30-6. 
40. Rost AD, Wilson K, Buchanan E, Hildebrandt MJ, Mutch D. Improving psychological 
adjustment among late-stage ovarian cancer patients: Examining the role of avoidance in 
treatment. Cogn Behav Pract. 2012;19(4):508-17. 
41. Mohabbat-Bahar S, Maleki-Rizi F, Akbari ME, Moradi-Joo M. Effectiveness of group training 
based on Acceptance and Commitment Therapy on anxiety and depression of women with 
breast cancer. Iran J Cancer Prev. 2015;8(2):71-6. 
42. Butt Z, Rosenbloom SK, Abernethy AP, Beaumont JL, Paul D, Hampton D, Jacobsen PB, 
Syrjala KL, Von Roenn JH, Cella D. Fatigue is the most important symptom for advanced 
cancer patients who have had chemotherapy. J Natl Compr Canc Netw. 2008;6(5):448-55. 
43. Hayes SC, Luoma JB, Bond FW, Masuda A, Lillis J. Acceptance and Commitment Therapy: 
Model, processes and outcomes. Behav Res Ther. 2006;44(1):1-25. 
44. Wilson KG, Sandoz EK, Kitchens J, Roberts ME. The Valued Living Questionnaire: Defining 
and measuring valued action within a behavioral framework. Psychol Record. 2010;60:249-
72. 
45. Mosher CE, Secinti E, Li R, Hirsh AT, Bricker J, Miller KD, Schneider B, Storniolo AM, Mina L, 
Newton EV, Champion VL, Johns SA. Acceptance and commitment therapy for symptom 
interference in metastatic breast cancer patients: a pilot randomized trial. Support Care 
Cancer. 2018;26(6):1993-2004. 

                                                  IRB#: 1812850942 
 
 
 
Page 19 of 19 
 
46. DuHamel KN, Mosher CE, Winkel G, Labay LE, Rini C, Meschian YM, Austin J, Greene PB, 
Lawsin CR, Rusiewicz A, Grosskreutz CL, Isola L, Moskowitz CH, Papadopoulos EB, Rowley 
S, Scigliano E, Burkhalter JE, Hurley KE, Bollinger AR, Redd WH. Randomized clinical trial of 
telephone-administered cognitive-behavioral therapy to reduce post-traumatic stress 
disorder and distress symptoms after hematopoietic stem-cell transplantation. J Clin Oncol. 
2010;28(23):3754-61. 
47. Brown H, Prescott R. Applied mixed models in medicine. 3rd ed. Chichester, West Sussex, 
United Kingdom: John Wiley & Sons; 2015. 
48. SAS Institute. SAS/STAT 9.4 User’s Guide. Cary, NC: SAS Institute, Inc.; 2016. Available 
from: https://support.sas.com/documentation/onlinedoc/stat/. 
49. Lachin JM. Statistical considerations in the intent-to-treat principle. Control Clin Trials. 
2000;21(3):167-89. 
50. Hedeker D, Gibbons RD. MIXOR: a computer program for mixed-effects ordinal regression 
analysis. Comput Methods Programs Biomed. 1996;49(2):157-76. 
51. Dong N, Maynard R. PowerUp!: A tool for calculating minimum detectable effect sizes and 
minimum required sample sizes for experimental and quasi-experimental design studies. J 
Res Educ Eff. 2013;6(1):24-67. 
52. Hayes AF. Introduction to mediation, moderation, and conditional process analysis: A 
regression-based approach. New York: Guilford Press; 2013.