A Phase III, Randomized, Single Blind, Attention Controlled, Multi-center Study of the Effects of a Rehabilitation Intervention on Participation Restrictions of Female Breast Cancer Survivors
Phase: NA
Conditions: Breast Cancer Female
Sponsor: MGH Institute of Health Professions

 
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Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
 
Principal Investigator: 
Kathleen Lyons, ScD 
 
Project Title: 
A Phase III, randomized, single blind, attention controlled, multi-center 
study of the effects of a rehabilitation intervention on participation restrictions of female breast cancer 
survivors  
 
Version Date: 
1.11.23 
 
NCT Number: NCT03915548 
 
For Intervention/Interaction studies, submit a Detailed Protocol that includes the following sections.  If 
information in a particular section is not applicable, omit and include the other relevant information.   
 
1. 
 Background and Significance 
 
 Definition of participation. This study is focused on breast cancer survivors’ ability to engage in life, 
fulfill social roles, and perform activities and daily routines. Disability scholars use various labels for this 
construct. We are using the language of the World Health Organization, where the word “participation” 
describes a state of health and functioning in which a person can fully engage in roles and life 
situations.[1]     
   
Operationalization. The construct of participation is multidimensional.[2] The objective aspects of 
participation include whether and how often an activity is performed; the subjective aspects include the 
level of difficulty and satisfaction with activity engagement.[3] Most measures of participation focus on 
activities that fulfill social roles within particular environments, according to personal, societal, and 
cultural standards.[2] As such, measures of participation generally privilege the individual’s perspective 
as he or she has the best vantage point from which to judge the degree to which he or she is fulfilling 
various roles within home and community settings.   
 
Prevalence. A population-based study (in which the most common diagnosis for women was breast 
cancer) reported 31% of both recent and long-term cancer survivors reported restrictions in their ability 
to participate in roles and life activities. This proportion was significantly more than the 13% of age-
matched controls without cancer reporting participation restrictions.[4] In a 2017 study of 245 breast 
cancer survivors, 90% reported at least some difficulty completing work activities, 87% reported 
difficulty doing strenuous activities, 78% reported difficulty doing moderate activities, and 74% reported 
difficulty completing household activities.[5]  
 
Persistence. There is no compelling evidence to suggest that participation restrictions resolve naturally 
over time. While the studies cited above did not use a longitudinal design, the proportions of recent and 
long-term survivors reporting participation restrictions are remarkably similar.[4] Research indicates 
that even after underlying physical impairments have resolved, limitations in recreational activities, 

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sexual activities, work, and daily activities can persist two[6] to six[7] years after breast cancer 
treatment.  
 
Causes and consequences. Multiple factors interact to restrict activity participation, and co-
morbidities play a large role in generating disability for cancer survivors.[8, 9] Regardless of the etiology, 
participation restrictions affect both quantity and quality of life. Lower participation in valued activities 
predicts shorter overall survival in women treated for breast cancer.[10-12] In samples of women living 
with or recovering from breast cancer, self-reported disruption in daily activities is associated with 
greater depression[13] and is predictive of less positive mood over time.[14] As such, optimizing 
participation and promoting functional recovery are important aspects of cancer survivorship.[15, 16]   
Scientific Premise 
Gap. We lack evidence-based interventions that directly target participation in roles and life 
activities.[17] Self-management interventions and multidimensional survivorship programs improve 
symptom management, distress, and quality of life, yet they do not consistently or conclusively improve 
the outcomes of social functioning or role functioning that are most similar to participation.[18, 19] 
Rehabilitation interventions primarily address physical impairments. While important, impairment 
reduction alone may not improve activity participation. For example, a recent meta-analysis[20] found 
that exercise improves social and emotional well-being of breast cancer survivors, but does not have a 
significant effect on functional well-being (the aspect of quality of life that is most similar to the 
construct of participation[21]). Further, because not all underlying impairments can be remediated, 
adaptive approaches directly targeting activity participation are needed.  
 
 Premise. Cheville and colleagues found that the number of physical impairments explained only half 
of the variance in participation restrictions reported by women with advanced breast cancer.[22] Recent 
models of cancer rehabilitation acknowledge that participation in roles and activities is influenced not 
only by physical impairments, but also by other personal factors, environmental factors, and activity 
demands.[23] We assert that a structured intervention can increase breast cancer survivors’ active 
coping and proficiency in manipulating the environment and adapting activities and that weekly 
application of those skills can lead to enhanced activity participation. Support for this assertion is 
presented below, where we describe our preliminary studies. Our approach is designed to catalyze 
functional recovery by encouraging women to take strategic, incremental actions to optimize activity 
engagement, without waiting for symptoms and side effects to fully resolve.   
 
Changing the Field. This Behavioral Activation/Problem-solving (BA/PS) intervention could be utilized 
by rehabilitation therapists, nurses, and social workers in clinical or workplace environments. 
Occupational therapists, in particular, provide billable services with the ultimate goal of maximizing the 
ability to function at home and in the community.[24] The BA/PS intervention provides a standardized 
way to move beyond treating impairments and to directly optimize the ability to engage in activities 
related to valued roles. 
 
Preliminary Studies Supporting the Scientific Premise 
Overview. Our team has conducted pilot studies to establish the feasibility of our methods and 
demonstrate the intervention’s acceptability and potential efficacy. We describe below how we 
addressed issues that allow us to feel confident that the proposed RCT will be successful.  
 

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Acceptability of randomization. In our first pilot study, 31 women undergoing chemotherapy for 
breast cancer were randomized to the intervention or usual care.[25] We learned that our participants 
would accept randomization and those assigned to usual care had adequate retention in the 3-month 
study (94%). Additionally, in our team’s larger studies of similar interventions (two RCTs of a supportive 
care intervention each with >250 participants[26, 27] and an RCT of a home-based BA/PS intervention 
for 61 older adults with cancer[28]) we have successfully randomized participants and kept data 
collectors blind to group assignment. 
   
Potential efficacy. After completing the first pilot RCT,[25] we enrolled 32 women who had completed 
breast cancer treatment and were experiencing participation restrictions (per the screening tool that 
will be used in this study) into two studies, each using a single arm study design.[29] One of the studies 
included a no-treatment run-in phase to assess the stability of functional limitations after cancer 
treatment. There was no change in quality of life during the 6-week no-treatment run-in phase. A 
longitudinal analysis showed a main effect of time for overall quality of life (as measured by the 
Functional Assessment of Cancer Therapy-Breast; FACT-B; F(5, 43.1) = 5.1, p = 0.001), including a 
significant improvement in functional well-being. Women reported an average increase of 10 points on 
the FACT quality of life measure immediately after the intervention. A change in 5 points has been found 
to signal clinically meaningful improvement on the FACT total score.[30, 31] There were also significant 
improvements in adaptive coping (as measured by the Brief COPE), namely active coping (F (3, 31.7) = 
4.9, p = 0.007), planning (F (3, 36.0) = 4.1, p = 0.01), and reframing (F (3, 29.3) = 8.5, p < 0.001).[29]  
 
Use of BA/PS to address various activities. A content analysis of session data from the first pilot study 
indicated that participants did not rely exclusively on one type of adaptive strategy, but brainstormed 
diverse strategies that changed what activities were done (32% of solutions), and where (10%), when 
(21%), with whom (16%), and how (21%) they were done.[32] The content analysis also revealed that 
women used the intervention to address 11 types of challenging activities (e.g., exercise, instrumental 
activities of daily living, work, socializing). In the subsequent two studies using the BA/PS structure, we 
similarly demonstrated that one parsimonious structure could address up to 13 different types of 
activities[28, 33] according to the participant priorities. When analyzing the types of goals set by 
participants in those two studies, we demonstrated that BA/PS targets both the ability to perform 
activities as well as satisfaction with performance.[33] 
 
Feasibility of telephone delivery. We delivered the intervention by telephone in our three pilot studies 
involving women with breast cancer[25, 29] because of feedback from participants in our previous 
studies[26, 34, 35] who consistently appreciated that our interventions do not require them to return to 
or extend their stay at the cancer center. In our Alabama site, Dr. Bakitas has been able to recruit 
participants to similar studies of individually-tailored, telephone-delivered interventions and has found 
that having a local recruiter and interventionist (e.g., with a local accent) has allowed for successful 
recruitment and retention.   
 
Summary. Our pilot studies used a structured, problem-solving and action planning approach to find 
ways to increase participation in valued daily activities. We have used participant feedback to create a 
standardized treatment manual that flexibly addresses the individual needs of cancer survivors. 
Definitive efficacy testing is warranted as the studies demonstrate the feasibility, acceptability, and 
potential efficacy of our approach. 
 
Case Example of BA/PS to Illustrate the Significance and Scientific Premise  

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“Amy” was a 53-year old woman enrolled in our third pilot study. She had a mastectomy to treat her 
Stage II breast cancer followed by 18 weeks of chemotherapy and 8 weeks of radiation. She was seen by 
physical therapy to address her severe fatigue, peripheral neuropathy, and lymphedema in her right 
arm.  
Amy reported three challenges with daily activities. First, she was working 24 hours a week, but felt 
exhausted and overwhelmed at work. Her long-term goal was to resume full-time work, but was 
currently calling in sick and coming in late and was “burning out the good will” of her employer. Second, 
she had lived in a large home since divorcing and now felt it was too much for her to take care of 
properly. She wanted to get back to regular cleaning and start to downsize her possessions. Third, 
because her physical challenges absorbed her coping resources, she was finding it difficult to reengage 
with her previous practice of meditation.  
In the first BA/PS session, Amy’s goal was to re-establish her daily meditation practice. She knew how 
to meditate, so the session focused on identifying an achievable goal and constructing an action plan 
that would be manageable, given the barriers of fatigue and time management she had identified. In the 
second session, she was happy to report that she had meditated six out of the seven days and had 
enjoyed the experience. In subsequent sessions, she updated her action plan to accommodate any new 
barriers to meditating. 
In the second session, she set a goal to downsize some items in the attic. Using the BA/PS framework, 
she set an achievable goal and identified modifications that would help her make enough progress to 
feel successful, but not become exhausted. For example, she brainstormed bringing up a lawn chair to 
avoid sitting on the floor, setting the alarm on her phone to encourage rest periods, gathering packing 
supplies on the day before starting the project, and stretching her arm that morning to help her be 
limber. She also identified where in the attic she would start (i.e., objects that were not too heavy, not 
likely to stir up unhappy memories, etc.). 
In the third session, Amy said she met her goals. However, she was distraught because she was 
meeting with her boss at the end of the week due to poor work attendance and performance. She used 
the BA/PS framework to explore the work challenges and brainstorm options for how to improve 
performance in targeted areas (e.g., organize her work files over the weekend and gather her work 
supplies and lunch the night before). As part of her action plan, she figured out how she would share 
this analysis and action plan with her boss.  
In the fourth session, Amy said she shared her plan with her boss who was grateful that she had come 
to the meeting with a plan instead of simply an intention to do better. As a result of the meeting, she 
was not put on probation and she used her identified solutions to function better at work. Over the 
remaining sessions, she continued to set achievable goals for functioning better at work, organizing her 
home, and meditating. She said that planning out manageable steps to reach her long-term goals had 
been invaluable and had “saved her job. 
 
2. 
Specific Aims and Objectives  
 
Aim 1: To test the effect of BA/PS on participation in roles and activities of breast cancer survivors. 
Hypothesis 1a (primary: participation satisfaction): Compared to attention control participants, 
BA/PS participants will report greater participation as measured by the Patient-reported Outcomes 
Measurement Information System (PROMIS) Satisfaction with Social Roles and Activities Short Form 
8a.[36, 37]  
Hypothesis 1b (secondary: participation ability and productivity): Compared to attention control 
participants, BA/PS participants will report higher activity performance as measured by the PROMIS 
Ability to Participate in Social Roles and Activities Short Form 8a[36, 37] and higher productivity as 

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measured by the Disability Days Section of the Medical Expenditure Panel Survey[38] and the Work 
Limitations Questionnaire-Short Form.[39] 
 
Aim 2: To test the effect of BA/PS on quality of life of breast cancer survivors. 
Hypothesis: Compared to attention control participants, BA/PS participants will report higher quality 
of life as measured by the Functional Assessment of Cancer Therapy- General (FACT-G).[21, 40, 41] 
 
Exploratory Aim: To test the effect of BA/PS on the outcomes of coping, goal adjustment, and distress. 
Hypothesis: Compared to attention control participants, BA/PS participants will report greater 
adaptive coping (Brief COPE[42]), greater goal adjustment (Goal Disengagement and Goal 
Reengagement Scale[43]), and less distress (Hospital Anxiety and Depression Scale[44, 45]). 
 
3. 
General Description of Study Design 
 
Overview. This is a single Institutional Review Board (IRB) study where the Massachusetts General 
Hospital (MGH) IRB will provide oversight for all sites. The sites include a) MGH Institute of Health 
Professions (MGH IHP); b) Dartmouth-Hitchcock Medical Center (D-H) which includes the Norris Cotton 
Cancer Center and its affiliated oncology practices and c) University of Alabama at Birmingham (UAB).  
• 
The principal investigator, Dr. Lyons, is Professor of occupational therapy at MGH IHP. Dr. 
Lyons will oversee all aspects of the study (e.g., train and supervise team of coordinators and 
interventionists, monitor participant recruitment, data collection, and data analysis, and lead 
the writing and publication of results). Dr. Lyons will not recruit participants from MGH and 
will not deliver the intervention.  
• 
The D-H research team will recruit and enroll participants, will collect all of the outcome data, 
and will deliver the intervention to participants. Data collection activities will be conducted 
from MGH IHP once enrollment has been completed in 2022. 
• 
The UAB research team will recruit and enroll participants and will deliver the intervention to 
participants. The UAB-based statistician and data analyst will lead the data analysis. 
Research question. This RCT was designed to answer the question “Is BA/PS efficacious in enhancing 
activity participation and quality of life of breast cancer survivors?” The primary aims are to assess the 
efficacy of BA/PS over time (Aims 1 and 2). We will also explore other potential effects of BA/PS on 
adaptive coping, goal adjustment, and distress (Exploratory Aim). 
 

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Design Overview. The study team will recruit 300 women over 
the age of 18 reporting participation restrictions after completing 
curative treatment for Stage 1-3 breast cancer within the past 
year. Half of the participants will be randomized to the 4-month 
BA/PS intervention which consists of 6 weekly telephone calls 
followed by 3 monthly telephone calls. BA/PS is designed to teach 
problem-solving and action planning to promote functional 
recovery. The other half of participants will be assigned to an 
attention control condition providing education about survivorship 
topics. This control condition will allow us to account for the effect 
of time and history, and the non-specific effects of attention.  
 
Assessments. Assessments will be administered via telephone by 
a D-H research assistant blind to group assignment. Participants 
will complete outcome assessments upon enrollment (T1) and at 8 
weeks (T2), 20 weeks (T3) and 44 weeks (T4) later. The T2 
assessment captures the short-term outcomes of the most 
intensive part of the intervention (i.e., after six weekly sessions). 
The T3 assessment will capture the short-term outcomes at the 
end of the full intervention. The T4 assessment explores the 
sustained effect of BA/PS (six months after BA/PS ends). Our 
decision to include the T4 assessment was influenced by a 
systematic review that indicated it often takes six months to see maximum effects of interventions 
targeting participation in adults with physical disabilities.[46] The study aim is to test whether the BA/PS 
intervention affects the “slope” of functional recovery over time. With the longitudinal data, we will also 
be able to explore the pace of improvement and whether the two groups differ at these clinically 
relevant time points.   
 
4. 
Subject Selection 
 
Inclusion Criteria with justification 
1. Age of 18 years or older. 
2. Experiencing reduced participation (i.e., a score of > 10 on the modified Work and Social Adjustment 
Scale[47]). 
3. Females diagnosed with Stage 1-3 breast cancer and within one year of completion of locoregional 
treatment and/or chemotherapy with curative intent and absence of disease recurrence. 
Biological variables of age and gender. In our pilot studies, the intervention has been flexible enough 
to be used with various challenges that occur across the age range.[25, 29] This proposal’s focus upon 
female breast cancer survivors reflects our pilot research population and allows us to focus recruitment 
resources with a smaller, closely aligned number of providers. We have decided to focus on females 
with breast cancer because of the very low prevalence rate of breast cancer in males. Because the D-H 
and UAB  sites see a mean of 3.8 males each year with breast cancer, we will not enroll enough males to 
allow us to draw sound conclusions that are generalizable to a male population. 
 
Medical co-morbidities. We considered the advantages and disadvantages of excluding women who 
have medical co-morbidities that affect their daily activities. Cancer survivors report an average of five 

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co-morbidities[48] that interact with cancer treatment and affect activities. The most prevalent co-
morbidities are hypertension, eye or ear problems, and arthritis.[48] Excluding people with such co-
morbidities is conceptually appealing in that it would allow a focus on only “cancer-related disability.” 
However, in practice it is difficult to determine whether disability is caused by cancer, a comorbidity, or 
an interaction of the two. Further, comprehensive cancer rehabilitation must address both pre-existing 
and treatment-related conditions.[49] Because we ultimately want to develop a generalizable 
intervention that has broad applicability for cancer survivors experiencing disability (i.e., strong external 
validity), it is necessary to develop and test interventions that can address any type of participation 
restriction, regardless of its source. Therefore, we will not exclude potential participants solely because 
of medical co-morbidities.  
  
Time since treatment. We are targeting survivors who are within one year of completing curative 
therapy because we are interested in supporting the middle phase of survivorship (i.e., the transition 
from active treatment toward extended survival).[50] We recognize that interest in and readiness for 
the intervention can come at different times for survivors. In our pilot studies, semi-structured 
interviews revealed that some women would have preferred to begin the intervention immediately after 
treatment ended (i.e., when they were experiencing the most difficulty re-establishing routines). Other 
women felt the need for intervention after 6 months had gone by (i.e., when they had a sense of their 
residual participation restrictions). While a one-year window of time may add heterogeneity, we think it 
will enhance the generalizability of the findings if BA/PS can address varying needs over time. 
 
Exclusion Criteria with justification 
 
1. Non-English speaking.  
2. Non-correctable hearing loss. 
3. Moderate-severe cognitive impairment indicated by a score < 3 on a 6-item cognitive screener.[51] 
4. History of severe mental illness (i.e., schizophrenia, bipolar disorder), current major depressive 
disorder, active suicidal ideation, or active substance misuse documented within the medical record or 
by self-report. 
Rationale. While the intervention is amenable to translation to other languages and modification for 
use with a hearing-impaired population, these adaptations are beyond the scope of the current 
proposal. Similarly, the highly structured program has been able to accommodate subtle cognitive 
difficulties[52] that are often reported after cancer treatment, but we need to exclude survivors with 
gross cognitive deficits that would impede safe and independent application of the action plan. Also, the 
needs of women with schizophrenia, bipolar disorder, major depressive disorder, suicidal ideation, and 
substance misuse disorders are greater than can be adequately provided by our telephone-delivered 
intervention. People who are excluded according to these criteria will be referred to clinic-based 
rehabilitation or behavioral services. 
 
Strategies to minimize bias in sampling. Our eligibility criteria are clearly defined so that the sample is 
not biased by relying upon a clinician’s determination of a given patient’s “appropriateness” or need for 
the study. Our use of the telephone for study and intervention procedures, along with our flexible 
staffing (i.e., staff available during early evening hours), allows us to reduce barriers to participation that 
may be experienced by working women or mothers with small children. 
 

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Procedures to identify potential participants. Our research team has established a successful 
mechanism in which we collaborate with clinicians to identify eligible patients each week. We apply for 
a Health Insurance Portability and Accountability Act (HIPAA) waiver to allow research staff to screen 
clinic schedules and/or use the i2b2 portal to identify potential study participants. The project 
coordinator consults with the clinicians to confirm eligibility based upon clinical characteristics. 
Clinicians deliver the brochure describing the study to patients. Our project coordinator is available in 
the clinic or by telephone to further explain the study to patients, screen for eligibility, and initiate 
informed consent procedures. If a patient is unable to be approached in clinic, we have an IRB-approved 
letter template describing the study and asking patients to contact us if they are interested or await a 
courtesy phone call from our team to see if they would like to hear more about the study. The letter is 
signed by the treating clinician(s), accompanied by a study recruitment brochure, and mailed out by the 
study team.  
In order to maximize recruitment, we will bring our recruitment brochures to events that may include 
breast cancer survivors such as wellness fairs, support groups, and cancer survivorship events. Screening 
and consenting after these events will follow the established procedures and scripting that have been 
approved by the Committee for the Protection of Human Subjects (CPHS) at Dartmouth College. We also 
run a Facebook advertising campaign, posting IRB-approved information about the study on Facebook 
with a link so that interested people can provide their email or phone number so that we can tell them 
more about the study and screen for eligibility. If necessary, we will post advertisements on print and 
other social media platforms (e.g., local newspapers, Instagram, Twitter), cancer center platforms (e.g., 
waiting room screens, websites), and online support group or advocacy platforms (e.g., Army of 
Women). Any inquiries resulting from our registration in ClinicalTrials.gov will be fielded by the D-H 
project coordinators, using our telephone procedures to screen and initiate informed consent 
procedures as appropriate. 
 
5. 
Subject Enrollment 
In our previous studies, we have found that many people like to take the study materials home 
and take some time to decide whether or not to enroll.  This study will be recruiting survivors, people 
who have completed treatment and may not be returning to the cancer center frequently. Additionally, 
we are recruiting participants via Facebook, where we need to conduct all screening and consenting via 
telephone. In these situations, we use telephone consent procedures that have been approved by the 
Dartmouth Committee for the Protection of Human Subjects previously. It should be noted that our 
telephone procedures mirror our in-person procedures. We train our study staff to give the person 
ample opportunity to feel comfortable, express concerns, and ask you any questions he or she might 
have and to pause more often and ask if they have questions to make up for the absence of non-verbal 
signals that help assess the degree to which a person is paying attention and understanding. We also 
train study staff that they can only proceed with the informed consent discussion only when the person 
has a copy of the consent form in front of them so that they can follow along.  
The project coordinators use a study brochure to describe the study and if the person is interested 
in learning more they use a template to screen participants according to the eligibility criteria. If the 
person is eligible, the project coordinators proceed with informed consent, explaining each section of the 
consent form (which has either been given to them in paper form if in the clinic or sent via Docusign at D-
H or Adobe esign at UAB if enrolling remotely or from self-referral). Participants who decide to enroll 
either sign the paper copy of the consent form (signing two copies, as does the project coordinator; one 
copy is given to the participant and one copy is retained by the project coordinator) or use the 
Docusign/Adobe esign link to electronically sign and return the informed consent document; once co-
signed by the project coordinator, a copy is sent to the participant. No study activities are initiated until 

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the signed consent form is in the hands of the project coordinator. At that time, the baseline assessment 
is scheduled. 
 
6. 
STUDY PROCEDURES 
Data Collection 
A clinical research coordinator blind to group assignment will administer standardized telephone 
interviews, scheduled at the participants’ convenience. On the rare occasion that a woman is unable to 
complete the surveys by telephone, the coordinator will send a link to a secure electronic Redcap survey 
or mail a hard copy of the surveys with a postage paid envelope in order to do everything we can to 
minimize missing data.  Data is directly entered into the Redcap software system. Recap is programmed 
with quality controls that facilitate rigorous data collection, such as not allowing interviewers to skip 
questions.  
Data Collection Schedule 
Measures and Data Collection Schedule 
Aim 
Construct 
Instrument 
# of 
Items 
T1 
Week 
0 
T2 
Week 
8 
T3 
Week 
20 
T4 
Week 
44 
 
Characteristics 
Demographics and Clinical Characteristics 
9 
X 
 
 
 
Aim 1 
Participation 
&  
Productivity 
PROMIS® (Satisfaction and Ability to Participate 
in Social Roles and Activities) 
Disability Days and WLQ-SF 
Individual activity targets 
16 
 
25+2 
3-9 
X 
X 
X 
X 
Aim 2 
Quality of Life 
FACT-G 
28 
X 
X 
X 
X 
Exploratory 
Aim  
Adaptive 
Coping 
Brief COPE subscales  
6 
X 
X 
X 
X 
Exploratory 
Aim 
Goal 
Adjustment 
GDGRS 
10 
X 
X 
X 
X 
Exploratory 
Aim 
Distress 
Hospital Anxiety and Depression Scale (HADS)  
14 
X 
X 
X 
X 
 
Perceived 
benefit 
Perceived Benefit Questions 
5 
 
X 
 
 
The coordinators will administer the outcome assessment battery by telephone upon enrollment (T1), 
after completion of the most intensive portion of the intervention (T2), after completion of the full 
intervention (T3) and six months after completion of the intervention (T4). Coordinators begin to call 
participants up to three weeks before the survey target date to schedule the survey; they will continue 
to call participants until either the survey is completed or four weeks passes beyond the target date. If 
participants are unable or unwilling to complete the outcome assessments by telephone, we will offer 
them the opportunity to complete the measures on paper (mailed with a hard copy and postage paid 
return envelope) or electronically (a link to a Redcap survey will be sent by email). 
Measures  
Eligibility Assessment 
Participation restrictions and gross cognitive impairments: The Work and Social Adjustment Scale 
(WSAS). The WSAS is a five-item scale of participation restrictions related to work, home management 
(e.g., cleaning, shopping, childcare), leisure, and relationship activities.[47, 53] Items are rated from 0-8 
(0 = not at all impaired, 8 = very severely impaired). Test-retest reliability is acceptable at r = 0.73.  As in 
the preliminary studies, we will use a WSAS cutoff score of > 10 as a way to identify people with at least 
a moderate level of participation restrictions.  
Sociodemographic and Clinical Characteristics to Describe the Sample 

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Enrolled participants will report their age, race, ethnicity, employment status, education level, marital 
status, insurance status, number of dependent children living at home, and household income. We will 
ask three questions related to COVID-19 status from the PhenX toolkit 
(https://www.phenxtoolkit.org/covid19/) related to whether a participant has been diagnosed with 
COVID-19, whether a family member was diagnosed with COVID-19, and the degree to which their work 
is impacted by COVID-19. We will use data from the medical record to describe stage, treatment and co-
morbidities or self-report if the participant is recruited outside of D-H or UAB.[54] 
Participation 
Participation satisfaction (primary outcome): Participation is a construct with two dimensions: 
satisfaction and ability. Disability scholars have argued that the subjective assessment of satisfaction 
with daily routines and activities is a defining feature of participation.[55] As such, we will use the 
PROMIS Satisfaction with Social Roles and Activities Short Form 8a[36, 37] as our primary outcome. 
Initial validation studies used exploratory and confirmatory factor analysis and two-parameter item 
response theory modeling to explore differential item functioning and to increase the precision of the 
PROMIS participation items.[36, 37] The resulting 8-item subscales (i.e., satisfaction and ability) address 
routine, work, leisure, family, and social activities. The scales were used in a recent large study of cancer 
survivors.[45] 
Participation ability (secondary outcome): We will use the second 8-item PROMIS scale entitled Ability to 
Participate in Social Roles and Activities Short Form 8a[36, 37] to measure the ability aspect of 
participation. The scale was developed in conjunction with the satisfaction scale, as described above. 
We added an item to solicit participant perceptions of the degree to which their challenges are related 
to cancer or its treatment so that we can determine if the source of the restrictions moderates the 
effect of the intervention. 
Productivity (secondary outcome): We will use relevant questions from the Disability Days section of the 
Medical Expenditure Panel Survey (MEPS) [38, 56] to capture days missed from work and lost household 
productivity. Missed days of work have been defined as half or more of a day missed from work due to a 
physical illness, or injury, or mental or emotional problem (including those missed because of 
hospitalizations). MEPS questions can be used to measure missed days of school if survivors are enrolled 
in school or training. For all participants, including those who are not employed or are on leave, we will 
assess lost household productivity by measuring days spent in bed, defined in MEPS as half days or more 
spent in bed because of physical illness or injury, or mental or emotional problems. We will also use the 
Work Limitations Questionnaire-Short Form (WLQ-SF)[39] to assess productivity. The WLQ has 25 items, 
and 4 subscales that assess limitations in 4 job dimensions (time, physical, 
mental/interpersonal/output). The subscale scores represent the percentage of time in the previous 2 
weeks that participants may be limited in performing in the specific dimension.  An overall WLQ 
Productivity Loss Score is the weighted sum of the 4 subscale scores and indicates the percentage 
decrement in productivity. The WLQ demonstrated high validity and reliability[39, 57] and has been 
used in cancer survivor populations.[58-60] While developed to assess productivity at paid work, it has 
been used with homemakers as well.[61]  
Individual Activity Targets (secondary outcome): During the first session of the intervention and control 
conditions, the occupational therapist elicits the participant’s individual recovery goals. The participant 
rates each activity with Likert scales for three characteristics: frequency of current performance (very 
often, often, once in a while, almost never, never), importance of the activity (1-10), and satisfaction 
with the activity (1-10). These ratings were used in a similar study by our team and provided a simple 
and pragmatic tool for assessing individualized outcomes.[62]   
Quality of Life 

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Quality of Life: The Functional Assessment of Cancer Therapy- (FACT-G) is a 28-item self-report measure 
of health-related quality of life specifically designed for breast cancer patients.[40, 41]  The items of the 
tool assess perceived well-being in physical, social, emotional, and functional domains.  Subscale scores 
are derived in each domain as well as a total score. [41] 
Exploratory Outcomes 
Coping: Brief COPE.[42]  Our pilot research has suggested that BA/PS increases participants’ use of active 
coping, planning and positive reframing.[29] These coping styles are measured by three subscales of the 
Brief COPE. The Brief COPE has been shown to have excellent psychometric properties among cancer 
patients including evidence of construct, convergent and concurrent criterion validity.[63] To minimize 
respondent burden, we will not administer the 28-item Brief COPE, but will instead utilize the three 
subscales of interest. 
Goal adjustment: Goal Disengagement and Goal Reengagement Scale (GDGRS).[43] The GDGRS is a 10-
item scale that measures two aspects of goal adjustment. Four items measure dispositional goal 
disengagement (i.e. the general inclination to relinquish untenable goals). Six items measure 
dispositional goal reengagement (i.e., commit to new goals). The internal consistency of the scales is 
generally high.[64] We will use the GDGRS to explore the potential efficacy of BA/PS on goal adjustment. 
Distress. Hospital Anxiety and Depression Scale (HADS)is a 14-item self-report measure of depressive 
and anxiety symptoms specifically designed for medical patients.[44] [45]The HADS contains only the 
cognitive symptoms of depression and anxiety, thus eliminating the somatic symptoms that are poor 
indicators of psychiatric distress in the medically ill. Items are rated on a four-point scale from 0 (not at 
all) to 3 (very often) and yield subscale scores for both depression and anxiety.  Higher scores indicate 
more severe symptoms. Because breast cancer survivors can experience significant distress regarding 
their ability to perform social roles and life activities, we will use this scale to explore the potential 
efficacy of BA/PS on this outcome. 
Perceived benefit. We have developed six questions modeled after those uses in a recent rehabilitation 
RCT.[65] The questions will help us to describe the credibility and utility of the intervention versus 
control conditions. Using a three-point scale (not at all, some, a great deal), participants will rate the 
degree to which the program helped them gain confidence, reduce distress, adjust habits and routines, 
set goals, and exercise. These reflect the areas that participants in the pilot studies reported were 
affected by the intervention. It should also function as a manipulation check in that the intervention is 
hypothesized to work by setting goals and the control condition does not include goal setting as active 
component. At minimum, the intervention participants should report higher levels of benefit on the goal 
setting item. 
Subject Stipends or Payments 
Participants will be paid $25 for completion of each of the Time 1, Time 2, and Time 3 assessments and 
will be paid $30 upon completion of the Time 4 assessment (total = $105 per participant). Participants 
who wish to accept the payments are required to complete a W9 form that will be submitted to 
Massachusetts General Brighamby the project coordinator along with the payment request. The W9 
form will be completed on paper if the participant is recruited within clinic or will be completed via 
Docusign software if recruited outside of the clinic (e.g., social media). Docusign is HIPAA compliant and 
has been approved for use in this project by Dartmouth-Hitchcock. 
 

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Method for Assigning Subjects to Treatment Groups 
Scheme. Participants will be randomly assigned to group (1:1) using a computer-generated program 
overseen by Dr Azuero. The randomization scheme will be stratified by site (D-H and UAB), time since 
treatment completion (i.e., <6 months and >6 months), and receipt of chemotherapy (yes versus no) and 
will be blocked within strata (block lengths of 2 and 4 varied randomly).  
 
Process and blinding. The PI or project managers will manage the randomization process, looking up 
the id number in an established excel file and assigning the local interventionist to communicate 
assignment to the participant and initiate treatment activities. The project coordinators will remain blind 
to group assignment and participants will be instructed not to discuss their assignment with the project 
coordinator collecting the outcome assessments.  
When and How to Withdraw Subjects 
Participants will be withdrawn from the study at their request (e.g., lack of interest in or perceived need 
for intervention, lack of time for study assessments). 
Data Collection and Follow-up for Withdrawn Subjects 
Our team continues to attempt to contact participants for each session and study assessment unless and 
until they ask us to stop/express the desire to withdraw. Each study contact is an extension of informed 
consent where participants are told what is occurring, what happens next, and that their participation is 
voluntary. When we are unable to reach participants by telephone for at least 30 days we send a letter 
conveying our attempts to reach them and ask them to contact us to continue with study activities or 
withdraw, as they prefer. 
Treatment Regimen 
 
Theoretical Background of BA/PS   
Our approach to improving activity participation reflects self-regulation models that emphasize 
alignment between goals and circumstances.[66-69] Recognition of a discrepancy between one’s goals 
and circumstances leads to either adaptive or maladaptive coping. Adaptive coping can be viewed as 
efforts to change the activity, environment, or self. These efforts manifest themselves in active coping 
(i.e., taking action instead of waiting for problems to disappear), planning (strategically deciding what 
actions to take), and positive reframing (adjusting expectations and interpretations of events).[29] Goal 
adjustment is another self-regulation strategy with two components.[70] The first component, goal 
disengagement, prevents the negative emotional consequences of pursuing a futile goal. The second 
component, goal reengagement, directs renewed energy towards attainable goals. BA/PS is designed to 
promote adaptive coping and goal adjustment through a process of strategic goal-setting, problem-
solving, and action planning centered on increasing the ease and enjoyment of activity participation and 
life roles, which leads to lower distress, improved productivity, and higher quality of life. 
The BA/PS Intervention (Experimental condition) 
Framework (Figure 3). BA/PS teaches survivors to a) systematically examine the reasons an activity is 
challenging, b) set achievable short-term goals that have the potential to improve participation, c) 
brainstorm solutions including activity adaptations and environmental modifications, d) construct and 
implement a detailed action plan, and e) evaluate the results and level of goal attainment. The 
structured process gives participants repeated practice in goal reengagement that leads them 
progressively closer to their long-term functional goals. The BA/PS framework integrates the cognitive-

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behavioral therapies of Behavioral Activation[71, 
72] and Problem-solving Treatment[73, 74] and 
incorporates concepts from an occupational 
therapy theory called the Person-Environment-
Occupational Performance Model.[75]    
 
Non-prescriptive. The BA/PS interventionist 
does not directly give advice or prescriptions.  
Behavioral Activation and Problem-solving 
Treatment were developed to treat depression 
and one active ingredient of those therapies is to 
teach patients to actively identify their own 
solutions to problems in living. We have found this 
technique is also beneficial when addressing 
participation because the cancer survivor is the 
expert in his or her lifestyle, routines, and 
environment. A participant in a pilot study of 
Behavioral Activation that we are conducting at 
Johns Hopkins (K23HL138206; PI: Parker) noted this emphasis was refreshing and in stark contrast to his 
post-hospitalization experiences of rehabilitation (i.e., “they mostly told me what I should do.”). 
 
Session 1. The interventionist presents the rationale for BA/PS, promotes a positive problem 
orientation, and educates about the framework for problem-solving and action planning. The 
interventionist then administers the Canadian Occupational Performance Measure[76] to elicit 
participant priorities, motivation, and long-term goals. The interventionist then guides the participant in 
using the BA/PS framework to set a goal, brainstorm solutions to challenges, and create a detailed 
action plan for the coming week.  
 
Subsequent sessions (once a week for five more weeks, then once a month for three months). The 
interventionist begins by reviewing the rationale for BA/PS and the previous action plan and elicits 
information about goal attainment and satisfaction with effort and outcome. If the goal for that week 
was met, then the interventionist guides the participant to identify another short-term goal for the 
coming week that would continue the progress towards the long-term goal. If the goal was not met, 
then the interventionist troubleshoots with the participant to determine whether the challenge was not 
fully described, whether the goal was too hard, whether the chosen solution or action plan was not 
effective, or whether more practice is needed. The framework is then used to create a goal and action 
plan for the coming week.  
 
Dose. The therapies that BA/PS is built upon typically show that six sessions allow sufficient exposure 
for participants to meet many of their goals and independently utilize the framework.[77, 78] The 
theoretical rationale for the three monthly sessions comes from the Transtheoretical Model[79] that 
suggests there is a maintenance stage of intentional behavior change where people need to actively 
solidify habits and develop confidence in their ability to sustain gains in activity engagement. As such, 
the three monthly follow-ups are booster sessions to enhance motivation, provide feedback, and keep 
the focus on continued incremental gains.    
 
Attention Control Condition 

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Rationale for an attention control. This proposal explores the question, ““Is BA/PS efficacious in 
enhancing activity participation and quality of life of breast cancer survivors?” Using randomization and 
a usual care control condition would allow us to eliminate the threats to internal validity that arise with 
time and history (i.e., participants might improve naturally as time goes by or because of an event 
occurring at the sites). However, the BA/PS participants would be receiving more attention and support 
than would the usual care participants. We recognize that the attention experienced within a weekly 
telephone call from a warm and supportive therapist could lift the spirits of participants and it is 
theoretically plausible that feeling more hopeful or supported could allow and encourage participants to 
become more active and engaged in life. We feel it is important to control for this possibility so that we 
can determine that it is our specific BA/PS intervention and not general support or attention that drives 
any effects seen in our data.  
    
Rationale for education within the attention control condition. Increased attrition can occur if 
participants feel that an attention placebo is not a meaningful use of time.[80] As such, we decided to 
provide education regarding nine cancer survivorship topics (i.e., healthy diets, physical activity, 
lymphedema management, smoking cessation, stress management, communication with providers, 
body image and sexuality, communication with social supports, work accommodations) during the 
control telephone contacts. The control condition will match the intervention in terms of the number of 
sessions, the delivery by telephone, use of an occupational therapist, and the use of “homework” 
between sessions (i.e., reading the education materials for the control condition versus executing the 
action plan for the BA/PS condition). This will allow us to determine the effect of the specific BA/PS 
elements (i.e., strategic goal setting, problem-solving, activity adaptation, environmental modification, 
and action planning) on participation and quality of life. 
 
7. 
Risks and Discomforts 
There are three potential risks involved in this study: (1) the risk of hurting oneself when trying to 
increase activity level (e.g., falling while exercising or performing home management tasks); (2) the risk 
of distress while talking about challenges with functional recovery after cancer treatment; and (3) risk of 
loss of confidentiality. The level of risk is generally quite low and strategies to minimize risks are 
incorporated into the BA/PS treatment manual. 
 
Risk of injury: The goal of the BA/PS intervention is to assist participants in optimizing functional 
recovery and activity participation after cancer treatment. BA/PS may help the participant to change 
aspects about themselves, the task, or how it is performed in order to engage in valued activities. In 
general, there is a very low level of risk involved in the intervention. Regarding the risk of injury, the 
BA/PS program includes action planning in order to increase the safety and success of activity 
engagement to minimize the chances of this risk. Furthermore, we instruct participants to schedule 
the outcome assessments and the intervention sessions at times when they can be seated 
comfortably while writing in the workbook or looking at the response choice sheet during outcome 
assessment administration. We have found that staffing in evening hours as needed and using these 
clear instructions helps us to discourage and counteract some participants’ desire to complete study 
procedures by telephone while driving. 
    Risk of distress: This is somewhat of a self-correcting problem because the objective of BA/PS is to 
provide a structured process to help people find ways to increase activity engagement. The 
interventionists are trained to validate feelings of frustration and distress while re-directing the 
participant to actionable ways to make immediate progress. Likewise, the coordinators who 
administer the outcome assessment are also trained in listening for signals of distress (e.g., long 

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pauses, weeping) and are trained handle distress tactfully (e.g., do not indicate verbally or non-
verbally that they are uncomfortable with participant distress) and to remind the participants that 
they can discontinue the surveys at any time. If a participant is experiencing significant emotional 
distress, either because of their disease and its treatment or participation in the study, Mark Hegel, 
PhD (Co-investigator and licensed clinical psychologist) will be available for consultation and mental 
health services are available at both study sites (D-H and UAB).  
Risk of privacy loss: Finally, to address a low-level risk of loss of privacy, participant 
confidentiality will be strictly protected. Hard copies of data will be maintained in locked files that 
can only be accessed by study personnel. Data forms will be identified using an identification (ID) 
number only. Access to the list cross-tabulating ID numbers with participant names will be kept in a 
password-protected data file behind the firewalls of D-H and UAB, accessible only to the project 
manager and coordinators. Hard copies of data files will likewise be kept in a locked file cabinets in 
locked offices and will include the ID number but no other unique identifier. All computer systems 
and programs will be password protected, and all electronic communications of study and other 
confidential information will be encrypted. Good computer security practice (shutting down 
computers after work hours, restricting physical access to machines, prohibition of password 
sharing) will be required of all study personnel. Virus protection software is installed on each study 
computer. The virus detection tools are used, maintained, audited and, if necessary, updated on all 
computers and pathways into the system.  Redundant backups allow for quick restoration of data in 
the unlikely event that a hardware failure or security breach occurs. Data sharing between sites 
occurs via the secure Sharefile storage system housed behind the Dartmouth-Hitchcock firewall. 
 
8. 
Benefits 
Potential benefit. Participants who are randomized to the BA/PS intervention arm will receive 
elements of a problem-solving intervention that has been shown to improve function and quality of 
life in other populations. Therefore, participants may benefit from their participation in the study. If 
shown to be efficacious, the intervention model could be used to improve health outcomes for 
cancer patients across the country. 
 
9. 
Statistical Analysis 
Sample Size Determination 
Minimally important differences. The minimally important differences (MID) between the two study 
arms are taken to be 10% of the practical range of the outcome variable[31] and thus the MIDs are 3.94, 
3.95 and 11.2 for satisfaction with participation, ability to participate, and quality of life, respectively. 
Note that these MIDs are not data dependent, although standard deviations might change for different 
data sets. We will assume the standard deviation for the two PROMIS scales are both 10 according to 
the scoring manual and the standard deviation for FACT-B is 24, as estimated from our third pilot 
study.[29]  
 
Estimated attrition. To estimate attrition, we examined the attrition seen in our three preliminary 
studies. One of the preliminary studies was an RCT,[25] two studies used a single arm design,[29] and 
each of the studies had at least three assessments. On average, 80% of our participants completed all 
study activities, and thus we expect an attrition of ~20% (if 300 people enroll, at least 240 participants 
will complete the study). 
 

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Power. Using a Time-Averaged Difference approach,[81] at a corrected significance level of 
.05/3=.017, and with three time-points post baseline, the required sample size to test for the minimally 
important effects of BA/PS on participation (PROMIS scales) ranges from 63 to 117 in each arm to 
achieve 80% power for within subject correlations ranging from 0.2-0.8. The required sample size to test 
for the minimally important effect of BA/PS on quality of life (overall FACT-B score) ranges from 45 to 83 
in each arm to achieve 80% power for within subject correlations ranging from 0.2-0.8. An FDR 
correction (see section C.7.3) will be used at the time of analysis which will provide more power than a 
Bonferroni correction and adequate control to the number of Type I errors. 
Statistical Methods 
Data analysis will begin with descriptive statistics for baseline participant characteristics and 
outcomes by study group. We will calculate means, standard deviations, and percentiles for continuous 
variables (e.g., participation, quality of life, coping, goal adjustment, distress, age, etc.) and frequencies 
and proportions for categorical variables (e.g., clinical characteristics), at each time point as appropriate. 
We will plot and inspect the distributions of the outcome variables, and examine the validity of any 
extreme values (data entry errors will be minimized by logic checks in the Velos data collection system, 
and inspection of scheduled reports during data collection). We will examine balance between study 
groups with respect to baseline characteristics using effect sizes such as the standardized mean 
difference for numerical variables and Cramer's V for categorical variables. We will examine patterns of 
missing data due to dropout, and whether baseline characteristics are associated with dropout. Baseline 
factors showing non-trivial imbalances between groups or that are predictive of dropout, will be then 
used as adjusting covariates in the longitudinal group comparisons. We will use the latest versions of 
standard statistical packages (SAS and R) for all analyses.    
 
Group Comparisons (Aim 1, Aim 2, and Exploratory Aim) 
Objective. Our objective is to compare the two groups’ functional recovery over time in terms of 
participation (PROMIS scales; Aim 1), productivity (Disability Days and WLQ; Aim 1), quality of life (FACT-
B; Aim 2) and coping style, distress, and goal adjustment (Brief COPE, HADS, and GDGRS; Exploratory 
Aim). All measures are collected at conceptually relevant time points of enrollment (T1), completion of 
the most intensive part of the intervention (T2), completion of the full intervention (T3) and six months 
after treatment completion (T4). The methods described below will be conducted upon each outcome 
variable.  
 
Modeling. A longitudinal model fitted with linear mixed methods will be used for each outcome. 
Numerical outcomes with markedly non-normal distributions, if any, will be modeled with more 
appropriate error distributions than the default normal (e.g., lognormal or generalized beta 
distributions). The focus of inference will be the between-group difference in outcome trajectories over 
the study time points, modeled by a time by group interaction. A random effect for subject will be fitted 
to account for covariance among repeated measures on the same individuals. If necessary, we will 
conduct covariate adjustment for baseline factors unbalanced between the groups or predictive of 
dropout. Time will be modeled as a categorical variable, to avoid the strong assumption of linear 
trajectories, and therefore the single test for the interaction effect will be a multiple-degree of freedom 
test. Model-predicted outcome means (a.k.a. LS-Means) by group at each time point will be computed 
to facilitate interpretation. The overall treatment effect will be computed as the between-group 
difference in change from baseline (change from T1 averaged over T2 to T4) estimated with a linear 
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Handling of Missing Data 
Mixed modeling techniques and covariate adjustment will reduce the impact of missing data, as the 
missingness is not assumed completely at random (MCAR) but conditionally (on the covariates) at 
random (i.e., MAR, a milder assumption).[82]  Should dropout exceed the 20% allowed by the sample 
size (section C.7.5), non-parametric multiple imputation[83] will be employed to determine the 
robustness of the conclusions for the main analyses under the milder MAR assumption. Because missing 
data due to non-ignorable or non-random drop out (i.e., MNAR) does not depend on the observed data, 
it presents the most complex situation to handle. Because of the non-invasive, supportive nature of the 
BA/PS intervention, as well as the attention control condition, a priori, we do not expect to encounter 
non-random dropout (and therefore MNAR). However, we will examine the tracking system records and 
logs with regard to dropout, to determine the main reasons for dropout. If sufficient indication of an 
MNAR mechanism is found, sensitivity analyses under different assumptions for the missing data 
mechanism will be conducted, following the methodology described by Molenberghs and Kenward[84] 
in which the missing data mechanism needs to be modeled explicitly.   
 
Adjustment for Multiple Inference 
A False Discovery Rate (FDR) approach[85] will be utilized to adjust inferential results for multiple 
inferences on the same body of data, separately for the primary analyses and the exploratory analyses. 
The FDR is the expected proportion of true null differences among those that are declared “significant”. 
The FDR will be set at 10%. All research products will disclose the number of inferences conducted and 
whether outcomes were primary or exploratory. As shown above , the sample is well powered to detect 
relevant effect sizes on the primary outcomes, even after multiplicity adjustment.  
 
Heterogeneity of Intervention Effects 
Rationale. We have developed the intervention to be flexible and responsive to the needs of a 
diverse group of breast cancer survivors. However, our diverse sample will give us the opportunity to 
identify any unanticipated moderator effects. Therefore, we will explore whether there are subgroups of 
participants who benefited most and least during the study, as per the primary outcomes.  
 
Recursive partitioning. The classical approach to moderator or subgroup analysis consists of 3 steps: 
1) pre-specifying some population characteristics of interest (e.g., site: UAB vs. D-H; race: minority vs. 
white; age: <65 vs. ≥65; source of participation restriction: primarily related to or unrelated to cancer; 
relapse vs. not, etc.); 2) analyzing one characteristic at a time, conducting inferences on differential 
intervention effects based on the characteristic's subgroups, using interaction tests adjusted for 
subgroup imbalances in other characteristics; and 3) applying an adjustment for multiple inference to 
account for the multiple analyses on the same body of data. Instead of implementing the classical 
approach, we propose using recursive partitioning, a.k.a. CART[86] (Classification and Regression Trees), 
a non-parametric modeling approach that allows extracting multivariate profiles from a sufficiently large 
dataset under minimal modeling assumptions, based on values of an outcome and participant 
characteristics. We propose this approach instead of the classical approach because multiple patient 
characteristics might be simultaneously associated with benefitting from the BA/PS intervention, 
therefore the multivariate approach can potentially provide more information and be more useful than 
the classical approach. Because CART is data-driven, these analyses will be considered exploratory. To 
avoid assuming that missing outcome data due to dropout is missing completely at random (i.e., MCAR), 
a Random Forest-based algorithm[83, 86] will be used to generate 3 imputed datasets comprising 

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baseline characteristics, group assignment, and longitudinal outcome variables. CART modeling will be 
implemented on each imputed dataset and results will be compared as a form of sensitivity analysis. The 
target variables for the CART modeling will be the average change from baseline in each primary 
outcome. Regression tree models for these target variables will be fitted using as predictors the group 
assignment and selected baseline characteristics. These baseline characteristics will include indicators of 
pertinent subpopulations of interest: site, race, income, age, etc. We will implement the conditional 
inference approach[87] to fit the tree models and use repeated 10-fold cross-validation to determine 
the final tree size. The tree model is a decision-tree-like structure that is interpreted based on the 
characteristics of the resulting groups of participants. 
Intent to treat. Our main analyses will utilize an intention-to-treat approach. As the BA/PS 
intervention is not part of standard practice, cross-over events are not expected to occur. All available 
data from all participants who undergo randomization will be included in the analyses according to the 
group assigned, regardless of any post-randomization protocol deviations. 
 
10.   Monitoring and Quality Assurance 
Safety and Adverse Events 
Definitions 
Unanticipated Problems Involving Risk to Subjects or Others 
Any incident, experience, or outcome that meets all of the following criteria:  
• Unexpected in nature, severity, or frequency  (i.e. not described in study-related documents such 
as the IRB-approved protocol or consent form, the investigators brochure, etc) 
• Related or possibly related to participation in the research (i.e. possibly related means there is a 
reasonable possibility that the incident experience, or outcome may have been caused by the 
procedures involved in the research) 
• Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm). 
 
Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
• results in study withdrawal 
• is associated with a serious adverse event 
• is associated with clinical signs or symptoms 
• leads to additional treatment or to further diagnostic tests 
• is considered by the investigator to be of clinical significance 
 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
• fatal 
• life-threatening 
• requires or prolongs hospital stay 
• results in persistent or significant disability or incapacity 
• a congenital anomaly or birth defect 

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• an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of 
major clinical significance.   They may jeopardize the subject, and may require intervention to prevent 
one of the other serious outcomes noted above.  For example, drug overdose or abuse, a seizure that 
did not result in in-patient hospitalization, or intensive treatment of bronchospasm in an emergency 
department would typically be considered serious.  
 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious 
adverse events.  
 
Adverse Event Reporting Period 
The study period during which adverse events must be reported is normally defined as the period from 
the initiation of any study procedures to the end of the study treatment follow-up.   
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition should be 
recorded as an adverse event if the frequency, intensity, or the character of the condition worsens 
during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the 
end of the study, any new clinically significant findings/abnormalities that meet the definition of an 
adverse event must also be recorded and documented as an adverse event.  
 
Post-study Adverse Event 
All unresolved adverse events should be followed by the investigator until the events are resolved, the 
subject is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the 
investigator should instruct each subject to report any subsequent event(s) that the subject, or the 
subject’s personal physician, believes might reasonably be related to participation in this study.  The 
investigator should notify the study sponsor of any death or adverse event occurring at any time after a 
subject has discontinued or terminated study participation that may reasonably be related to this study.   
 
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization should be documented 
and reported as a serious adverse event unless specifically instructed otherwise in this protocol.  Any 
condition responsible for surgery should be documented as an adverse event if the condition meets the 
criteria for and adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an adverse 
event in the following circumstances: 
• Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for a 
preexisting condition.  Surgery should not be reported as an outcome of an adverse event if the 
purpose of the surgery was elective or diagnostic and the outcome was uneventful. 
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• Hospitalization or prolonged hospitalization for therapy of the target disease of the study, unless 
it is a worsening or increase in frequency of hospital admissions as judged by the clinical 
investigator. 
Recording of Adverse Events 
At each contact with the subject, the investigator must seek information on adverse events by specific 
questioning and, as appropriate, by examination.  Information on all adverse events should be recorded 
immediately in the source document, and also in the appropriate adverse event module of the case 
report form (CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures results 
should recorded in the source document, though should be grouped under one diagnosis. 
 
All adverse events occurring during the study period must be recorded.  The clinical course of each event 
should be followed until resolution, stabilization, or until it has been determined that the study 
treatment or participation is not the cause.  Serious adverse events that are still ongoing at the end of 
the study period must be followed up to determine the final outcome.  Any serious adverse event that 
occurs after the study period and is considered to be possibly related to the study treatment or study 
participation should be recorded and reported immediately. 
Reporting of Serious Adverse Events and Unanticipated Problems 
 
Investigators must conform to the adverse event reporting timelines, formats and requirements of the 
various entities to which they are responsible, but at a minimum those events that must be reported are 
those that are: 
• related to study participation, 
• unexpected, and  
• serious or involve risks to subjects or others  
(see definitions, section 8.1).   
If the report is supplied as a narrative, the minimum necessary information to be provided at the time of 
the initial report includes: 
• 
Study identifier 
• 
Study Center 
• 
Subject number 
• 
A description of the event 
• 
Date of onset 
• 
Current status 
• 
Whether study treatment was discontinued 
• 
The reason why the event is classified as serious 
• 
Investigator assessment of the association 
between the event and study treatment 
 
Investigator reporting: notifying the IRB 
The  IRB requires reporting of those events related to study participation that are unforeseen and 
indicate that participants or others are at increased risk of harm.  The IRB requires researchers to submit 
reports of any incident, experience, or outcome that meets each of the following criteria: 
• Unanticipated in terms of nature, severity, or frequency given: (a) the research procedures that 
are described in the protocol-related documents, such as the IRB-approved research protocol and 
consent document; and (b) the characteristics of the subject population being studied; and 
• Possibly related to participation in the research means there is a reasonable possibility that the 
incident, experience, or outcome may have been associated with research participation; and 

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• The problem suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, emotional, economic, legal, or social harms) than was 
previously known or recognized. 
 
Reporting Process 
Unanticipated problems posing risks to subjects or others as noted above will be reported to the  IRB 
using the form: “Unanticipated Problem Involving Risks to Subjects or Others (UPR).” 
 
Copies of each report and documentation of IRB notification and receipt will be kept in the Clinical 
Investigator’s study file. 
 
Other Reportable events: 
For clinical trials, the following events are also reportable to the IRB: 
• Any adverse experience, defined as an untoward or unfavorable medical occurrence in a human 
subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the subject’s participation in research, whether 
or not considered related to the subject’s participation in the research), that is considered: 
– Serious: Death; a life-threatening adverse drug experience; inpatient hospitalization or 
prolongation of existing hospitalization; a persistent or significant disability or incapacity; or a 
congenital anomaly or birth defect; and 
– Unexpected:  Any adverse experience, the specificity or severity of which is not consistent with 
the current investigator brochure or consent form; and 
– Possibly related:  There is a reasonable possibility that the incident, experience, or outcome 
may have been associated with the procedures involved in the research; and 
– Is experienced by a participant in a trial open at a site subject to Dartmouth IRB review 
• Information that indicates a change to the risks or potential benefits of the research, in terms of 
severity or frequency. For example:  
– An interim analysis indicates that participants have a lower rate of response to treatment than 
initially expected. 
– Safety monitoring indicates that a particular side effect is more severe, or more frequent than 
initially expected. 
– A paper is published from another study that shows that an arm of your research study is of 
no therapeutic value. 
• Change in FDA safety labeling or withdrawal from marketing of a drug, device, or biologic used in 
a research protocol. 
• Breach of confidentiality 
• Change to the protocol taken without prior IRB review to eliminate apparent immediate hazard to 
a research participant. 
• Complaint of a participant when the complaint indicates unexpected risks or the complaint cannot 
be resolved by the research team. 
• Protocol deviation (meaning an accidental or unintentional deviation from the IRB approved 
protocol) that in the opinion of the investigator placed one or more participants at increased risk, 
or affects the rights or welfare of subjects. 

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Stopping Rules  
Significant risk is not anticipated in this study due to the supportive and non-invasive nature of the 
intervention. However, we will summarize adverse event data annually to the D-H Data Safety 
Monitoring and Accrual Committee for consideration of study continuation. The study design does not 
include planned interim analyses to identify the need to stop early due to significant benefit, i.e., 
inferential analyses will be conducted when data collection has been completed.  
Internal Data and Safety Monitoring Board 
 
This project will involve enrolling 300 breast cancer survivors into a randomized controlled trial within 
the year after they complete their treatment. After enrollment, participants will complete a baseline 
assessment. Participants randomized to the BA/PS intervention arm will engage in 9 individual sessions 
delivered via telephone by an interventionist (who is an occupational therapist or nurse). Participants 
randomized to the attention control arm will engage in 9 individual education sessions delivered via 
telephone by an interventionist. The intervention and assessments are not invasive and do not involve 
pharmacological agents. The informed consent process, the recruitment process, and the timeliness and 
quality of the data will be monitored by the principal investigator, the Institutional Review Board, and 
the Data Safety Monitoring and Accrual Committee (DSMAC) of the D-H.  The DSMAC meets quarterly to 
review accrual rates and information for studies that have accrued participants.  The Clinical Cancer 
Review Committee (CCRC) determines the frequency of DSMAC review. The DSMAC has the authority to 
suspend or to recommend termination to the CCRC of all research activities that fall within its 
jurisdiction.  In the event that a study is suspended or terminated, that information will be forwarded to 
the MGH IRB office. The last DSMAC report will be filed in January 2023 as all enrollment and 
intervention activities have been completed and the only remaining study activity is data collection. 
.  
11.   Privacy and Confidentiality 
 
☒ Study procedures will be conducted in a private setting 
☒ Only data and/or specimens necessary for the conduct of the study will be collected 
☒ Data collected (paper and/or electronic) will be maintained in a secure location with appropriate 
protections such as password protection, encryption, physical security measures (locked 
files/areas) 
☐ Specimens collected will be maintained in a secure location with appropriate protections (e.g. 
locked storage spaces, laboratory areas) 
☒ Data and specimens will only be shared with individuals who are members of the IRB-approved 
research team or approved for sharing as described in this IRB protocol 
☒  Data and/or specimens requiring transportation from one location or electronic space to 
another will be transported only in a secure manner (e.g. encrypted files, password protection, 
using chain-of-custody procedures, etc.) 
☒   All electronic communication with participants will comply with Mass General Brigham secure 
communication policies 
☒ Identifiers will be coded or removed as soon as feasible and access to files linking identifiers 
with coded data or specimens will be limited to the minimal necessary members of the research 
team required to conduct the research 
☒ All staff are trained on and will follow the Mass General Brigham policies and procedures for 
maintaining appropriate confidentiality of research data and specimens 

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☒ The PI will ensure that all staff implement and follow any Research Information Service Office 
(RISO) requirements for this research 
☒ Additional privacy and/or confidentiality protections 
 
Data sharing between D-H, MGH IHP, and UAB will occur via the D-H Sharefile site, as described in 
the  data use agreements as part of the subcontracting award process. Data sharing will be bi-
directional between D-H and UAB (e.g., UAB sends participant enrollment information to D-H 
and receives outcome data from D-H for analysis) and bi-directional with MGH IHP as Dr. Lyons 
will provide a de-identified data set to UAB where the statistician is located..  
 
12.   References 
 
1. 
World Health Organization, International Classification of Functioning, Disability, and Health 
(ICF). 2002, World Health Organization: Geneva, Switzerland. 
2. 
Chang, F.-H. and W.J. Coster, Conceptualizing the Construct of Participation in Adults With 
Disabilities. Archives of Physical Medicine and Rehabilitation, 2014. 95(9): p. 1791-1798. 
3. 
Chang, F.-H., et al., Validation of the Participation Measure–3 Domains, 4 Dimensions (PM-
3D4D). Archives of Physical Medicine and Rehabilitation, 2017. 98(12): p. 2498-2506. 
4. 
Ness, K.K., et al., Physical performance limitations and participation restrictions among cancer 
survivors: a population-based study. Ann Epidemiol, 2006. 16(3): p. 197-205. 
5. 
Letellier, M.-E. and N. Mayo, Assessment of breast cancer disability: agreement between expert 
assessment and patient reports. Disability and Rehabilitation, 2017. 39(8): p. 798-808. 
6. 
Yang, E.J., et al., Discrepant trajectories of impairment, activity, and participation related to 
upper-limb function in patients with breast cancer. Archives of Physical Medicine and 
Rehabilitation, 2015. 96(12): p. 2161-2168. 
7. 
Jones, J.M., et al., Cancer-related fatigue and associated disability in post-treatment cancer 
survivors. Journal of Cancer Survivorship, 2016. 10(1): p. 51-61. 
8. 
Deimling, G.T., et al., Factors Affecting Perceptions of Disability and Self-Rated Health Among 
Older Adult, Long-Term Cancer Survivors. Journal of Aging and Health, 2017. 0(0): p. 
0898264317745745. 
9. 
Kenzik, K.M., et al., Chronic condition clusters and functional impairment in older cancer 
survivors: a population-based study. Journal of Cancer Survivorship, 2016. 10(6): p. 1096-1103. 
10. 
Braithwaite, D., et al., Long-term prognostic role of functional limitations among women with 
breast cancer. J Natl Cancer Inst, 2010. 102(19): p. 1468-77. 
11. 
DiSipio, T., et al., Patterns, correlates, and prognostic significance of quality of life following 
breast cancer. Psychooncology, 2011. 20(10): p. 1084-91. 
12. 
Sehl, M., et al., Decline in physical functioning in first 2 years after breast cancer diagnosis 
predicts 10-year survival in older women. Journal of Cancer Survivorship, 2013. 7(1): p. 20-31. 
13. 
Williamson, G.M., Extending the activity restriction model of depressed affect: evidence from a 
sample of breast cancer patients. Health Psychol, 2000. 19(4): p. 339-47. 
14. 
Low, C.A. and A.L. Stanton, Activity disruption and depressive symptoms in women living with 
metastatic breast cancer. Health Psychology, 2015. 34(1): p. 89-92. 
15. 
Feuerstein, M., Cancer survivors need evidence on how to optimize physical function. J Cancer 
Surviv, 2009. 3(2): p. 73-4. 
16. 
Nekhlyudov, L., et al., Going Beyond Being Lost in Transition: A Decade of Progress in Cancer 
Survivorship. Journal of Clinical Oncology, 2017. 38(18): p. 1978-1981. 

Mass General Brigham Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
Version 2021.06.10 
 
Page 24 of 28 
17. 
Egan, M.Y., et al., Rehabilitation following cancer treatment. Disability and Rehabilitation, 2013. 
35(26): p. 2245-2258. 
18. 
Howell, D., et al., Self-management education interventions for patients with cancer: a 
systematic review. Supportive Care in Cancer, 2017. 25(4): p. 1323-1355. 
19. 
Cheng, K.K.F., et al., Home-based multidimensional survivorship programmes for breast cancer 
survivors. Cochrane Database of Systematic Reviews, 2017(8). 
20. 
Zhu, G., et al., Effects of exercise intervention in breast cancer survivors: a meta-analysis of 33 
randomized controlled trials. OncoTargets and therapy, 2016. 9: p. 2153-2168. 
21. 
Cella, D.F., et al., The Functional Assessment of Cancer Therapy scale: development and 
validation of the general measure. Journal of Clinical Oncology, 1993. 11(3): p. 570-9. 
22. 
Cheville, A.L., A.B. Kornblith, and J.R. Basford, An examination of the causes for the 
underutilization of rehabilitation services among people with advanced cancer. Am J Phys Med 
Rehabil, 2011. 90(5 Suppl 1): p. S27-37. 
23. 
Campbell, K.L., et al., A prospective model of care for breast cancer rehabilitation: Function. 
Cancer, 2012. 118(S8): p. 2300-2311. 
24. 
American Occupational Therapy Association, Occupational Therapy Practice Framework: Domain 
and Process (3rd Edition). American Journal of Occupational Therapy, 2014. 68(Supplement_1): 
p. S1-S48. 
25. 
Hegel, M.T., et al., Feasibility study of a randomized controlled trial of a telephone-delivered 
problem-solving-occupational therapy intervention to reduce participation restrictions in rural 
breast cancer survivors undergoing chemotherapy. Psychooncology, 2011. 20(10): p. 1092-101. 
26. 
Bakitas, M.A., et al., The Project ENABLE II randomized controlled trial to improve palliative care 
for rural patients with advanced cancer: Baseline findings, methodological challenges, and 
solutions. Palliative and Supportive Care, 2009. 7: p. 75-86. 
27. 
Bakitas, M.A., et al., Early versus delayed initiation of concurrent palliative oncology care: Patient 
outcomes in the ENABLE III randomized controlled trial. Journal of Clinical Oncology, 2015. 
33(13): p. 1438-1445. 
28. 
Lyons, K.D., et al., Content Analysis of a Participant-Directed Intervention to Optimize Activity 
Engagement of Older Adult Cancer Survivors. OTJR: Occupation, Participation and Health, 2018. 
38(1): p. 38-45. 
29. 
Lyons, K.D., et al., Development and initial evaluation of a telephone-delivered, Behavioral 
Activation and Problem-solving Treatment Program to address functional goals of breast cancer 
survivors Journal of Psychosocial Oncology, 2015. 33(2): p. 199-218. 
30. 
Cella, D., E.A. Hahn, and K. Dineen, Meaningful change in cancer-specific quality of life scores: 
Differences between improvement and worsening. Quality of Life Research, 2002. 11: p. 207-
221. 
31. 
Ringash, J., et al., Interpreting clinically significant changes in patient-reported outcomes. 
Cancer, 2007. 110(1): p. 196-202. 
32. 
Lyons, K.D., K.S. Erickson, and M.T. Hegel, Problem-solving strategies of women undergoing 
chemotherapy for breast cancer. Canadian Journal of Occupational Therapy, 2012. 79(1): p. 33-
40. 
33. 
Lyons, K.D., et al., A content analysis of recovery strategies of breast cancer survivors enrolled in 
a goal-setting intervention. OTJR: Occupation, Participation and Health, 2015. 35(2): p. 73-80. 
34. 
Bakitas, M.A., et al., Effects of a palliative care intervention on clinical outcomes in patients with 
advanced cancer: The Project ENABLE II randomized controlled trial. JAMA, 2009. 302(7): p. 741-
749. 

Mass General Brigham Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
Version 2021.06.10 
 
Page 25 of 28 
35. 
Bakitas, M.A., et al., Project ENABLE: A palliative care demonstration project for advanced cancer 
patients in three settings. Journal of Palliative Medicine, 2004. 7(2): p. 363-372. 
36. 
Castel, L.D., et al., Content validity in the PROMIS social-health domain: a qualitative analysis of 
focus-group data. Qual Life Res, 2008. 17(5): p. 737-49. 
37. 
Hahn, E.A., et al., Measuring social health in the patient-reported outcomes measurement 
information system (PROMIS): item bank development and testing. Qual Life Res, 2010. 19(7): p. 
1035-44. 
38. 
Zheng, Z., et al., Annual medical expenditure and productivity loss among colorectal, female 
breast, and prostate cancer survivors in the United States. J Natl Cancer Inst, 2016. 108(5). 
39. 
Lerner, D., et al., The Work Limitations Questionnaire's validity and reliability among patients 
with osteoarthritis. Journal of Clinical Epidemiology, 2002. 55(2): p. 197-208. 
40. 
Brady, M.J., et al., Reliability and validity of the functional assessment of cancer therapy - Breast 
Quality-of-Life instrument. Journal of Clinical Oncology, 1997. 15(3): p. 974-986. 
41. 
Coster, S., K. Poole, and L.J. Fallowfield, The validation of a quality of life scale to assess the 
impact of arm morbidity in breast cancer patients post-operatively. Breast Cancer Res Treat, 
2001. 68(3): p. 273-82. 
42. 
Carver, C.S., You want to measure coping but your protocol's too long: consider the brief COPE. 
Int J Behav Med, 1997. 4(1): p. 92-100. 
43. 
Wrosch, C., et al., Adaptive self-regulation of unattainable goals: goal disengagement, goal 
reengagement, and subjective well-being. Personality and Social Psychology Bulletin, 2003. 
29(12): p. 1494-508. 
44. 
Zigmond, A. and R. Snaith, The Hospital Anxiety and Depression Scale. Acta Psychiatrica 
Scandinavica, 1983. 67: p. 361-370. 
45. 
Jensen, R.E., et al., Responsiveness of 8 Patient-Reported Outcomes Measurement Information 
System (PROMIS) measures in a large, community-based cancer study cohort. Cancer, 2017. 
123(2): p. 327-335. 
46. 
Hammel, J., A systematic literature review of participation-focused interventions for people with 
physical disabilities: American Occupational Therapy Foundation (AOTF) Research Colloquium, in 
American Occupational Therapy Association Annual Conference and Expo. 2016: Chicago, IL. 
47. 
Mundt, J.C., et al., The Work and Social Adjustment Scale: a simple measure of impairment in 
functioning. Br J Psychiatry, 2002. 180: p. 461-4. 
48. 
Leach, C.R., et al., The complex health profile of long-term cancer survivors: prevalence and 
predictors of comorbid conditions. Journal of Cancer Survivorship, 2015. 9(2): p. 239-251. 
49. 
Alfano, C.M., et al., Cancer survivorship and cancer rehabilitation: revitalizing the link. J Clin 
Oncol, 2012. 30(9): p. 904-6. 
50. 
American Cancer Society, Cancer Treatment and Survivorship Facts and Figures 2014-2015. 
2015, Atlanta: American Cancer Society. 
51. 
Callahan, C.M., et al., Six-item screener to identify cognitive impairment among potential 
subjects for clinical research. Medical Care, 2002. 40(9): p. 771-781. 
52. 
Ahles, T.A., J.C. Root, and E.L. Ryan, Cancer- and cancer treatment–associated cognitive change: 
An update on the state of the science. Journal of Clinical Oncology, 2012. 30(30): p. 3675-3686. 
53. 
Marks, I.M., Behavioural Psychotherapy; Maudsley Pocketbook of Clinical Management, ed. J. 
Wright. 1986, Bristol. 
54. 
Charlson, M., et al., A new method of classifying prognostic comorbidity in longitudinal studies: 
Development and validation. Journal of Chronic Diseases, 1987. 40: p. 373-383. 

Mass General Brigham Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
Version 2021.06.10 
 
Page 26 of 28 
55. 
Martin Ginis, K.A., et al., Broadening the conceptualization of participation of persons with 
physical disabilities: A configurative review and recommendations. Archives of Physical Medicine 
and Rehabilitation, 2017. 98(2): p. 395-402. 
56. 
Ekwueme, D.U., et al., Medical costs and productivity losses of cancer survivors--United States, 
2008-2011. MMWR Morb Mortal Wkly Rep, 2014. 63(23): p. 505-10. 
57. 
Lerner, D., et al., Relationship of employee-reported work limitations to work productivity. Med 
Care, 2003. 41(5): p. 649-59. 
58. 
Tamminga, S.J., et al., Measurement properties of the Work Limitations Questionnaire were 
sufficient among cancer survivors. Qual Life Res, 2014. 23(2): p. 515-25. 
59. 
Leensen, M.C.J., et al., Return to work of cancer patients after a multidisciplinary intervention 
including occupational counselling and physical exercise in cancer patients: a prospective study 
in the Netherlands. BMJ Open, 2017. 7(6): p. e014746. 
60. 
Feuerstein, M., et al., Work productivity in brain tumor survivors. J Occup Environ Med, 2007. 
49(7): p. 803-11. 
61. 
Kennedy, M., et al., Prevalence and predictors of reduced work productivity in patients with 
psoriatic arthritis. Clin Exp Rheumatol, 2014. 32(3): p. 342-8. 
62. 
Lyons, K.D., et al., Goal Attainment and Goal Adjustment of Older Adults During Person-Directed 
Cancer Rehabilitation. American Journal of Occupational Therapy, 2018. 72(2): p. 
7202205110p1-7202205110p8. 
63. 
Fillion, L., et al., Validation of the Shortened COPE for use with Breast Cancer Patients 
Undergoing Radiation Therapy. Current Psychology, 2002. 21(1): p. 17-34. 
64. 
Thompson, E.H., A.L. Stanton, and J.E. Bower, Situational and dispositional goal adjustment in 
the context of metastatic cancer. Journal of Personality, 2013. 81(5): p. 441-451. 
65. 
Szanton, S.L., et al., Effect of a Biobehavioral Environmental Approach on Disability Among Low-
Income Older Adults: A Randomized Clinical TrialEffect of a Biobehavioral Environmental 
Approach on Disability Among Older AdultsEffect of a Biobehavioral Environmental Approach on 
Disability Among Older Adults. JAMA Internal Medicine, 2019. 179(2): p. 204-211. 
66. 
Carver, C.S. and M.F. Scheier, On the self-regulation of behavior, ed. Anonymous. 1998, New 
York, NY, US: Cambridge University Press. xx. 
67. 
Carver, C.S., et al., Quality of life among long-term survivors of breast cancer: different types of 
antecedents predict different classes of outcomes. Psycho-Oncology, 2006. 15(9): p. 749-758. 
68. 
Carver, C.S., et al., How coping mediates the effect of optimism on distress: A study of women 
with early stage breast cancer. Journal of Personality and Social Psychology, 1993. 65(2): p. 375-
390. 
69. 
Hull, J., Modeling the Structure of Self-Knowledge and the Dynamics of Self-Regulation, in Self 
and Motivation: Emerging Psychological Perspectives, A. Tesser, D.A. Stapel, and J.V. Wood, 
Editors. 2002, American Psychological Association: Washington, DC. p. 173-206. 
70. 
Wrosch, C. and C.M. Sabiston, Goal adjustment, physical and sedentary activity, and well-being 
and health among breast cancer survivors. Psycho-Oncology, 2013. 22(3): p. 581-589. 
71. 
Hopko, D.R., et al., Contemporary behavioral activation treatments for depression: Procedures, 
principles, and progress. Clinical Psychology Review, 2003. 23(5): p. 699-717. 
72. 
Cuijpers, P., A. van Straten, and L. Warmerdam, Behavioral activation treatments of depression: 
A meta-analysis. Clinical Psychology Review, 2007. 27(3): p. 318-326. 
73. 
Cuijpers, P., A. van Straten, and L. Warmerdam, Problem solving therapies for depression: A 
meta-analysis. Eur Psychiatry, 2007. 22(1): p. 9-15. 
74. 
Hegel, M.T. and P.A. Arean, Problem-solving treatment for primary care: A treatment manual for 
depression, Project IMPACT. 2003, Hanover, NH: Dartmouth College. 

Mass General Brigham Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
Version 2021.06.10 
 
Page 27 of 28 
75. 
Baum, C.M. and C.H. Christiansen, Person-environment-occupation-performance: An occupation-
based framework for practice, in Occupational therapy: Performance, participation, and well-
being, C.H. Christiansen, C.M. Baum, and J. Bass-Haugen, Editors. 2005, SLACK, Inc: Thorofare, 
NJ. p. 243-266. 
76. 
Law, M., et al., Canadian Occupational Performance Measure. 5th ed. 2014, Toronto: Canadian 
Association of Occupational Therapists. 
77. 
Rovner, B.W., et al., Low vision depression prevention trial in age-related macular degeneration: 
A randomized clinical trial. Ophthalmology, 2014. 121(11): p. 2204-2211. 
78. 
Arean, P., et al., Effectiveness of Problem-Solving Therapy for older, primary care patients with 
depression: Results from the IMPACT Project. The Gerontologist, 2008. 48(3): p. 311-323. 
79. 
Prochaska, J.O., C.A. Redding, and K.E. Evers, The Transtheoretical Model and Stages of Change, 
in Health Behavior: Theory, Research and Practice, K. Glanz, B.K. Rimer, and K. Viswanath, 
Editors. 2015, Jossey-Bass: San Francisco. p. 125-148. 
80. 
Popp, L. and S. Schneider, Attention placebo control in randomized controlled trials of 
psychosocial interventions: theory and practice. Trials, 2015. 16: p. 150. 
81. 
Brown, H. and R. Prescott, Applied Mixed Models in Medicine, 3rd Ed. 2015, Chichester, England: 
Wiley. 
82. 
van Buuren, S., Flexible imputation of missing data. Chapman & Hall/CRC interdisciplinary 
statistics series. 2012, Boca Raton, FL: CRC Press. 
83. 
van Buuren, S. and K. Groothuis-Oudshoorn, mice: Multivariate Imputation by Chained 
Equations in R. Journal of Statistical Software, 2011. 1(3). 
84. 
Molenberghs, G. and M. Kenward, Missing Data in Clinical Studies. 2007, Hoboken: Wiley. 
85. 
Benjamini, Y. and Y. Hochberg, Controlling the false discovery rate: A practical and powerful 
approach to multiple testing. Journal of the Royal Statistical Society. Series B (Methodological), 
1995. 57(1): p. 289-300. 
86. 
Strobl, C., J. Malley, and G. Tutz, An introduction to recursive partitioning: rationale, application, 
and characteristics of classification and regression trees, bagging, and random forests. Psychol 
Methods, 2009. 14(4): p. 323-48. 
87. 
Hothorn, T., K. Hornik, and A. Zeileis, Unbiased recursive partitioning: A conditional inference 
framework. Journal of Computational and Graphical Statistics, 2006. 15(3): p. 651-674. 
 
 
APPENDIX A 
 
Data Monitoring Committee / Data and Safety Monitoring Board 
Appendix 
 
 
 
• 
To be completed for studies monitored by Data Monitoring Committee (DMC) or Data and Safety 
Monitoring Board (DSMB) if a full DMC/DSMB charter is not available at the time of initial IRB 
review. 
• 
DMC/DSMB Charter and/or Roster can be submitted to the IRB later via Amendment, though these 
are not required.  
 

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A Data Monitoring Committee (DMC) or Data and Safety Monitoring Board (DSMB) will be convened for 
safety monitoring of this research study.  The following characteristics describe the DMC/DSMB 
convened for this study (Check all that apply): 
 
☒ The DMC/DSMB is independent from the study team and study sponsor. 
 
☒ A process has been implemented to ensure absence of conflicts of interest by DMC/DSMB 
members. 
 
☒ The DMC/DSMB has the authority to intervene on study progress in the event of safety 
concerns, e.g., to suspend or terminate a study if new safety concerns have been identified or 
need to be investigated.   
 
☒ Describe number and types of (i.e., qualifications of) members: 
There are 8 standing members of the DSMAC, representing different disciplines and 
laboratories. 
 
☒  Describe planned frequency of meetings: 
Data is submitted and reviewed annually 
 
☒ DMC/DSMB reports with no findings (i.e., “continue without modifications”) will be submitted 
to the IRB at the time of Continuing Review. 
 
☒ DMC/DSMB reports with findings/modifications required will be submitted promptly (within 5 
business days/7 calendar days of becoming aware) to the IRB as an Other Event.