Randomized Trial of a Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing Hematopoietic Stem Cell Transplantation (HCT)
Phase: NA
Conditions: Cancer
Sponsor: Massachusetts General Hospital

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing Hematopoietic 
Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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SECTION 1:
 Protocol Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SECTION 2:  BODY OF PROTOCOL 
Screening: 
• 
Caregiver ≥ 18 years of a patients undergoing 
hematopoietic stem cell transplantation (HCT). 
• 
Ability to read questions in English or willing to 
complete questionnaires with assistance of an 
interpreter. 
Patient Exclusion Criteria: 
• 
Major psychiatric or 
comorbid illness that 
prohibits ability to 
participate in study. 
Participants Enrollment 
 
• 
5-10 Caregivers approached at the time 
of HCT consent (2-4 weeks prior to HCT) 
• 
Baseline questionnaire and schedule 
intervention visits 
 
Psychological Intervention 
 
• 
Eight weekly sessions in-person or via 
telephone 
• 
Qualitative interviews and feedback from 
5-10 caregivers to refine the intervention.  
Refine the psychological 
intervention 
• 
Analyze qualitative interview data. 
• 
Refine the psychological intervention. 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing Hematopoietic 
Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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TABLE OF CONTENTS 
 
1 
Introduction ................................................................................................................................................................. 3 
1.1 
Overview ..................................................................................................................................................................... 3 
1.2 
Background and Significance ..................................................................................................................................... 3 
1.3 
Preliminary Studies ................................................................................................... Error! Bookmark not defined.5 
2 
Objectives ................................................................................................................................................................. 35 
3 
Research Subject Selection ....................................................................................................................................... 56 
3.1 
Study Subject Selection: ............................................................................................................................................ 56 
4 
Research Subject Entry ............................................................................................................................................... 6 
4.1 
Study Research Subject Entry ..................................................................................................................................... 6 
4.2 
Registrations and Procedures ................................................................................................................................... 67 
5 
Study Design and Methods ......................................................................................................................................... 7 
5.1 
Design/ Study Type .......................................................................................................................................... ………7 
5.2 
Selection of Study Instruments ........................................................................................................................ ………7 
5.3 
Description of Intervention ....................................................................................................................................... 98 
5.4 
Data Collection ......................................................................................................................................................... 98 
5.5 
Description of Study Process .................................................................................................................................... 98 
5.6 
Adverse Reactions and Their Management ............................................................................................................. 109 
6 
Ethical and Legal Issues ........................................................................................................................................... 10 
6.1 
Confidentiality ........................................................................................................................................................... 10 
7 
Statistical Analysis .................................................................................................................................................... 10 
7.1 
Study Endpoints: ....................................................................................................................................................... 10 
7.2 
Sample Size Calculation: .......................................................................................................................................... 10 
7.3 
Analysis Plan: ........................................................................................................................................................... 10 
8 
References ................................................................................................................................................................. 10 
9
 
Appendices..………………………………………………………………………………………………………..10
11 
 
 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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2 
Introduction 
2.1 
Overview 
This protocol proposes to begin Phase 1 of a two phase project to develop and test a multicomponent 
psychological intervention for caregivers of patients undergoing hematopoietic stem cell transplantation 
(HCT). During HCT, patients receive high-dose chemotherapy, which is associated with multiple toxicities 
and leads to burdensome physical symptoms and a prolonged hospitalization. Moreover, during the first 
100 days post-transplant while the patient continues to experience many challenging physical symptoms, 
both patients and their families attend multiple outpatient appointments, manage complex medication 
schedules, and cope with the uncertainty of the patient’s prognosis. Thus, the family and close friends (i.e. 
caregivers) of patients undergoing HCT are substantially impacted by the patient’s illness.  
Despite the immense physical and psychological burden experienced by caregivers of patients undergoing 
HCT, few interventions have been developed to address their needs during the transplant. Prior research 
on caregivers’ intervention has been challenging with many inconclusive or negative studies due to poorly 
defined interventions that are not specific to a particular population. Thus, there is a critical need to develop 
population-specific interventions with a sound methodological approach to address the specialized needs 
of caregivers and provide them with the necessary skills to care for and cope with their loved ones’ illness.  
We conducted a prospective longitudinal study of patients and caregivers during hospitalization for HCT, 
which clearly delineated the needs of caregivers during the transplant process. We utilized our data and a 
systematic review of the literature to develop a preliminary multicomponent psychological intervention to 
promote effective coping and caregiver well-being. In this proposed project, we will proceed in two phases 
that incorporate sequential mixed qualitative and quantitative methods. At this time, we are seeking IRB 
approval for phase 1 procedures only. During phase 1, we will obtain qualitative data from 5-10 caregivers 
who will participate in the psychological intervention during their loved ones’ HCT course to refine the 
intervention content and schedule to specifically meet the needs of caregivers.  
After finalizing the psychological intervention in Phase 1, we will then seek IRB approval to conduct Phase 
2 of the project. Phase 2 will only begin after Phase 1 is completed and an amendment has been filed and 
approved by the IRB.  During phase 2, we will conduct a pilot randomized controlled trial of the intervention 
versus usual care in 100 caregivers to assess the feasibility and preliminary efficacy of the intervention for 
improving caregiver QOL, mood, caregiving burden, and self-efficacy. The proposed project builds a strong 
foundation for the development of an innovative psychological intervention that will be tested in a future 
R01-funded trial. 
2.2 
Background and Significance 
Caregivers of patients undergoing HCT experience tremendous burden caring for their loved ones 
HCT is a commonly utilized treatment modality for patients with hematologic malignancies.1 During 
HCT, patients receive high-dose chemotherapy, which is associated with multiple toxicities and leads to 
both burdensome physical symptoms and a prolonged hospitalization.2-6 This phase of their illness often 
carries the highest degree of morbidity as patients cope with symptoms from both their underlying 
malignancy and from prior therapies.7 Moreover, during the first 100 days post-transplant while the patient 
continues to experience many challenging physical symptoms, both patients and their families attend 
multiple outpatient appointments, manage complex medication schedules, and cope with the uncertainty 
of the patients’ prognosis.8,9 Consequently, the family and close friends (i.e. caregivers) of patients 
undergoing HCT are substantially impacted by the patient’s illness. Watching a loved one struggle with the 
side effects during HCT can be emotionally challenging.7 Depending on the age and relationship of the 
caregiver, supporting a loved one through HCT may lead to significant disruptions in the caregiver’s 
personal life, including difficulties in maintaining responsibilities at home and work.10-12 Studies have shown 
that caregivers experience the highest distress immediately before and during their loves ones’ 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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hospitalization for HCT, with subsequent life disruptions seen in the first three months after transplant.7-9 
Hence, caregivers of patients undergoing HCT are a highly vulnerable population with substantial 
caregiving burden that results in significant physical and psychological distress. 
 
Addressing the needs of caregivers is necessary to improve both patients’ and caregivers’ 
outcomes 
 
Caregiving burden often leads to substantial negative effects on caregivers’ quality of life (QOL) 
and mood.13 In fact, more than a quarter of caregivers of HCT recipients experience significant depression 
and anxiety symptoms.7-9 Fatigue, sleep disturbances, and difficulty maintaining work are common 
challenges seen in this population.11,12,14-16 We have conducted a prospective longitudinal study of patients 
and caregivers during hospitalization for HCT (see preliminary studies), which demonstrates that 
caregivers experience a substantial decline in QOL and increase in depression symptoms during the HCT 
process.7  Hence, addressing the needs of caregivers has the potential to substantially impact their 
experience and overall QOL.7 Moreover, as caregivers provide the majority of care for patients undergoing 
HCT, attending to their needs is an essential step in ensuring the delivery of high-quality care for patients 
with hematologic malignancies.8,9,17  
Interventions to promote coping and reduce burden for caregivers of patients undergoing HCT are 
lacking 
Despite the significant physical and psychological burden experienced by caregivers of patients 
undergoing HCT, interventions to address their needs during the acute transplantation process are 
lacking.7,8,18 One study examined the effect of problem-solving intervention for caregivers after patients’ 
hospitalization for HCT.18 However, the intervention did not address the needs of caregivers immediately 
before and during the transplant hospitalization, when caregivers report the highest physical and 
psychological distress.7 No interventions have been developed to improve caregivers’ QOL and mood at 
their most challenging times during their loved ones’ hospitalization for HCT and in the first 100 days post-
HCT. 
Developing a population-specific psychological intervention for caregivers is critical to its success  
Based on a number of recent studies, researchers have demonstrated increasing interest in 
developing population-specific interventions to address the specialized needs of caregivers and provide 
them with the necessary skills to care for and cope with their loved ones’ illness.7,8,18-20 While the emerging 
data on caregivers’ interventions are encouraging, poorly defined interventions and outcome measures 
have hampered the field substantially.8,17,18 These methodological shortcomings have resulted in many 
inconclusive or negative studies, impeding the development of well-conceptualized and sufficiently 
powered randomized studies.17  
 
Research suggests that caregivers of HCT recipients may benefit from a multicomponent 
psychological intervention to promote effective coping and caregiver well-being.8,21 These components 
include 1) a psycho-educational component to enhance preparedness, manage expectations, and develop 
caregiving skills; 2) a psychosocial component to promote coping strategies and facilitating acceptance 
while living with uncertainty; and 3) a self-care component to enhance positive health behaviors and 
promote their well-being.8,21   
We propose to develop a multicomponent psychological intervention for caregivers during HCT 
Due to the immense caregiving needs during the first 100 days post-HCT, we propose a multi-
component psychological intervention for caregivers. We will utilize mixed qualitative and quantitative 
methods to refine the intervention and to assess its feasibility and preliminary efficacy in improving 
caregivers’ QOL, caregiving burden, mood, and self-efficacy. Our planned intervention is built upon a 
strong methodological foundation and the findings of a rigorous longitudinal study (see preliminary studies), 
which described comprehensively the experience patients undergoing HCT and their caregivers during the 
acute phase of transplantation.7,22  

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
5
Preliminary Studies: 
QOL and Mood of Patients and Caregivers During Hospitalization for HCT23: We conducted a prospective 
longitudinal study to investigate the impact of hospitalization for HCT on QOL and mood of patients and 
caregivers. We enrolled 95% (n =90) of potentially eligible patients undergoing HCT and 70% of their 
caregivers. We assessed longitudinal QOL and mood both weekly during the transplant hospitalization and 
at a follow up outpatient clinic visits, with a missing data rate of only 20%. We demonstrated that caregivers’ 
QOL declined over time, with significant decreases in both physical and mental health. Moreover, we 
showed that caregiver depression symptoms increased dramatically during the HCT hospitalization. This 
work demonstrates our research team’s success in conducting longitudinal studies in patients undergoing 
HCT and their caregivers. Additionally, the findings from this work were used to develop a palliative care 
intervention specifically addressing the needs of patients undergoing HCT. Our team utilized the data from 
this study to develop the psychological intervention targeting the specific needs of this population that we 
hope to further refine and test in this project. 
Inpatient palliative care integrated with transplant care improves patient-reported outcomes24: Based upon 
on our prior study describing QOL and mood in patients undergoing HCT,25-27 we developed a palliative 
care intervention targeting the specific needs of this population.  We enrolled 160 of 186 (86%) eligible 
patients in 16 months, with only one participant withdrawing from the study. Compared to transplant care, 
the palliative care intervention led to a rapid and dramatic improvement in patients’ QOL, depression, 
anxiety, and symptom burden. This work highlights our research team’s experience conducting supportive 
care interventions targeted to the specific needs of the population, and our ability to successfully recruit 
and enroll patients with hematologic malignancies for intervention studies. 
3 
Objectives 
The objective for Phase 1 of the study is described below.  
 
Objective 1: To refine a multicomponent psychological intervention to promote effective coping and reduce 
caregiving burden of FC of patients undergoing HCT. 
4 
Research Subject Selection 
4.1 
Study Subject Selection: 
During phase 1, we will use qualitative data to refine the multicomponent psychological intervention 
specifically targeting the needs of caregivers during their loved ones’ hospitalization for HCT and in the 
first 100 days post-HCT. We will recruit 5-10 adult caregivers of patients undergoing HCT at MGH to 
participate in phase 1 of this project. Caregivers will be recruited during the patient transplant consent 
visit, which typically occurs 2-4 weeks prior to admission for HCT.  Caregivers are required to attend the 
HCT consent visit with the patient.  
 
Caregivers Eligibility Criteria: 
1) Adult caregivers (≥18 years) of patients undergoing HCT at MGH. 
2) A relative or a friend who either lives with the patient or has in-person contact with him or her at least 
twice per week and is identified as the primary caregiver for transplant 
3) Ability to speak English or able to complete questionnaires with minimum assistance of an 
interpreter. 
 
Caregivers Exclusion Criteria: 
1) Significant uncontrolled psychiatric disorder (psychotic disorder, bipolar disorder, major depression) or 
other co-morbid disease (dementia, cognitive impairment), which the treating clinician believes 
prohibits the ability to participate in study procedures. 

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Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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5 
Research Subject Entry 
5.1 
Study Research Subject Entry 
A total of 5-10 caregivers of patients undergoing HCT will particpiate in phase 1 of this study. The 
research team will review the transplant clinic schedule to identify potentially eligible caregivers for study 
participation. We will approach caregivers to participate in phase 1 during the outpatient clinic visit when 
their loved ones’ consent for HCT, which typically occurs 2-4 weeks prior to HCT. Patients are required 
to be accompanied by a caregiver for the consent visit. The research team will contact eligible 
participants’ oncology clinicians to inform them that we plan to approach the caregiver and inquire about 
any concerns regarding their participation. If the clinician objects to the caregivers’ participation, we will 
document the reason and not approach those individuals. 
 
If the oncologist has no concerns regarding the caregivers’ participation, the research staff will approach 
eligible caregivers immediately after the transplant consent clinic visit. The research assistant (RA) will 
review the consent form with potential participants, which will clearly detail the nature of the study 
procedures and the time requirement. The RA will obtain written informed consent from participants and 
provide them with a copy of the signed consent form.  
 
Enrolled caregivers will complete a baseline self-report questionnaire (Appendix A) at the time of 
obtaining informed consent for the study or within the 72-hour window from study enrollment. Caregivers 
who provide informed consent and complete the baseline questionnaire will then be registered with ODQ 
and scheduled for their first study intervention visit either in-person or via telephone. The RA will be 
responsible for contacting ODQ. The ODQ will require a copy of the caregivers’ informed consent and 
eligibility checklist. 
5.2 
REGISTRATION PROCEDURES 
5.2.1 Registration process for DF/HCC and DF/PCC Institutions Registrations 
After completion of baseline questionnaires, caregivers will be registered centrally with the DF/HCC 
Office of Data Quality (ODQ) central registration system. Registration Process for DF/HCC Institutions 
DF/HCC Standard Operation Procedures for Human Subject Research Titled Subject Protocol 
Registration (SOP# REGIST-101) must be followed. For each study participant, we will complete the 
following registration procedures: 
• 
We will obtain written informed consent from the participant prior to the performance of any 
protocol specific procedures or assessments. 
• 
We will complete the ODQ protocol-specific eligibility checklist using the eligibility assessment 
documented in the research chart. Only eligible participants will be registered. To be eligible for 
registration to the protocol, the participant must meet all including and exclusion criterion as 
described in this protocol and reflected on our eligibility checklist. 
• 
We will fax the eligibility checklist(s) and all pages of the consent form(s) to the ODQ at 617-632-
2295. 
• 
The ODQ Registrar will a) review the eligibility checklist, b) register the participant on the 
protocol, and c) randomize the participant when applicable. 
• 
An email confirmation of the registration will be sent to the Overall PI, study coordinator(s), 
treating investigator, and registering person immediately following the registration. 
We are requesting a a HIPAA Waiver of Alteration to Use or Disclose of Protected Health Information 
from the IRB. This waiver is being requested to identify potential participants from a minimal chart review. 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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In accordance with the DF/HCC policy, this Waiver: (1) is being sought solely to review Protected Health 
Information as necessary to prepare a research protocol, (2) will not include removing Protected Health 
Information from the Covered Entity by the researcher, and (3) the Protected Health Information for 
which we are requesting access is necessary for the research purposes. 
5.2.2 Registration Process for Other Investigative Sites: Not applicable 
5 
Study Design and Methods  
5.1 
Design/ Study Type 
During phase 1, we will use qualitative data to refine a multicomponent psychological intervention 
specifically targeting the needs of caregivers’ during their loved ones’ hospitalization for HCT and in the 
first 100 days after transplant. 
 
Phase 1 Intervention Refinement: We utilized the findings from our longitudinal study and a thorough 
review of the literature to identify the necessary components of our planned caregiver intervention, as 
depicted in Table 1.7,8,21 The preliminary content includes three essential components: 1) a 
psychoeducational component to address preparedness, manage expectations, and develop caregiving 
skills; 2) a psychosocial component focusing on coping strategies, mindfulness, and facilitating acceptance 
while living with uncertainty; and 3) a self-care component to promote caregiver health and well-being. We 
anticipate that the psychological intervention will consist of eight individual sessions (30-45 minutes each) 
starting prior to admission for HCT and continuing until day + 70 after HCT, which will provide sufficient 
dose to promote effective coping and reduce caregiving burden. We will coordinate sessions with hospital 
and clinic visits or conduct them via phone to minimize participant burden and facilitate adherence. Dr. 
Jacobs (a behavioral psychologist and researcher) will deliver the intervention. Dr. Jacobs has extensive 
experience as a therapist on NIH-funded trials. During phase 1, we will refine the intervention based on 
qualitative interviews and feedback from 5-10 caregivers who will attend the psychological intervention 
sessions. We will then finalize the study intervention manual, which will be used in phase 2. 
 
Table 1 Potential Intervention Topics Based on Preliminary Conceptual Model 
Session 
Behavioral 
Target 
Skill Area 
Topics 
1 
Introduction 
Psychoeducation 
➢ 
Introduce intervention purpose and goals 
➢ 
Explore how FC cope with the HCT process 
➢ 
Manage expectations for HCT, acknowledge and normalize 
fears  
2,3 
Coping & 
managing 
emotions 
Psychosocial 
➢ 
Explore strategies for balancing acceptance and change-
oriented coping approaches. 
➢ 
Introduce mindfulness to observe the HCT experience 
(thoughts, feelings, loved ones’ symptoms) in an objective, 
nonjudgmental fashion 
➢ 
Explore the use of mindfulness to cope with HCT-related 
uncertainty 
➢ 
Identify ways to support loved ones during HCT hospitalization 
4,5 
Preparedness & 
caregiving skills 
Psychoeducation 
➢ 
Identify caregiving needs in the immediate post-HCT period 
➢ 
Help FC gain more confidence in responding to physical and 
psychosocial issues post-HCT 
➢ 
Elevate FC sense of self-efficacy 
➢ 
Enhance FC communication with the health care team 
6 
Healthy 
behaviors & 
self-care 
Self-care 
➢ 
Identify and explore FC needs 
➢ 
Introduce strategies for stress management, and promotion of 
self-care behaviors (sleep, healthy diet, exercise, and seeking 
support) 
7 
Interpersonal 
relationship 
Psychosocial 
➢ 
Identify attitudes and beliefs about FC relationship to the 
patient 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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➢ 
Identify differences between assertive, passive, aggressive 
behaviors 
➢ 
Introduce strategies to encourage relationship-enhancing 
behaviors 
8 
Program 
overview 
All 
➢ 
Summarize and review main content of the intervention 
➢ 
Address additional challenges and problems 
➢ 
Brainstorm strategies to maintaining use of skills over time. 
 
Utilizing data from phase 1 to refine the intervention: We will utilize the qualitative data obtained from 
phase 1 and clinicians’ experience to finalize the multicomponent psychological intervention. Specifically, 
we will refine the following aspects of the intervention: 
• 
Intervention content: We will use caregivers’ feedback to confirm the relevance of the intervention 
content, and to revise content as needed. For instance, if caregiver report that they would have liked 
to focus on more active coping strategies, we will increase the balance between change- and 
acceptance-oriented (e.g., mindfulness) approaches. To further enhance the intervention, we also 
may integrate caregivers’ real-life concerns as examples throughout the protocol when introducing 
the use of coping skills and strategies.  
• 
Program structure and schedule: We anticipate that caregivers will have different needs during 
their loved ones’ hospitalization for HCT vs. the immediate post-transplant period. However, we will 
use caregivers’ feedback to guide the order and timing of the eight intervention sessions during these 
two periods. Additionally, we may revise session number (8 sessions) or length (30-45 min per 
session) based on caregivers’ feedback about participation burden and utility. 
• 
Program modality: We will use exit interview data to determine whether the delivery of the 
intervention visit in-person or over the phone was acceptable to participants. 
• 
Additional areas of concern: We will identify any additional areas of concern from caregivers that 
were not addressed specifically in the intervention and integrate them in a revised intervention 
manual. 
 
5.2 
Selection of study instruments 
Baseline questionnaire: During the baseline questionnaire, we will obtain demographic data including 
age, gender, race, ethnicity, religion, relationship status, relationship of the caregiver to the patient, 
education level, and annual household income [Appendix A]. 
 
Qualitative interview guide: We will use a semi-structured interview guide that will explore 1) caregiver 
perception of the acceptability and content of the intervention; and 2) caregiver perceptions of the 
benefits of receiving the intervention. Facilitators will use probes to obtain comprehensive understanding 
of the caregivers’ perspectives. The semi-structured interview guide is detailed in Appendix B.  The 
interview will last approximately 30 minutes. The participants will not be required to complete any 
additional study instruments. The qualitative interview will be conducted in-person or over the telephone 
(Appendix C). 
 
Training of research coordinator to conduct qualitative interviews: We will utilize the MGH Cancer 
Outcomes Research Group (CORe) extensive experience training research assistants to conduct semi-
structured qualitative interviews with the use of the interview guide.  The research assistant will first 
complete an initial training with Dr. Elyse Park, a psychologist with extensive experience conducting 
qualitative interviews. They will then conduct mock practice interviews with the presence of both Dr. El-
Jawahri (PI) as well as Dr. Park (co-investigator).  They will be provided direct feedback regarding their 
qualitative interview technique.  Lastly, the research assistant will be supervised by Dr. El-Jawahri, Dr. 
Jacobs (a psychologist and co-investigator) or Dr. Park during their first two qualitative interviews with 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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study participants to ensure appropriate interview techniques.  Of note, the research assistant will utilize 
a semi-structured interview guide (Appendix C) for all interviews. 
5.3 
Description of Intervention 
The multicomponent psychological intervention is described in detail in section 5.1. It entails eight 
individual sessions (30-45 minutes each) starting prior to admission for HCT and continuing until day + 
70 after HCT, which will provide sufficient dose to promote effective coping and reduce caregiving 
burden. We will coordinate sessions with hospital and clinic visits or conduct them via phone to minimize 
participant burden and facilitate adherence. Dr. Jacobs (a behavioral psychologist and researcher) will 
deliver the intervention. Dr. Jacobs has extensive experience as a therapist on NIH-funded trials. 
 
5.4 
Data Collection 
We will audio-record all qualitative exit interviews and save them on HIPPA-compliant electronic storage. 
We will transcribe the interviews and we will save the text documents on HIPPA-compliant electronic 
storage for qualitative analysis. All additional data will be stored in locked cabinets at MGH as well as 
password-protected computer files, accessible only to trained study staff. Participants’ data will be 
identified by an ID number only, and a link between names and ID numbers will be kept in a separate file 
under lock and key. 
 
5.5 
Description of Study Process 
 
5.5.1 Study Instrument Administration 
After signing consent, we will schedule caregivers for their intervention visits with Dr. Jacobs. Upon 
completion of the intervention visits around day +90 (+/- 15 days) post-HCT, the trained research 
assistant or the principal investigator will conduct the qualitative exit interviews with study participants 
using a semi-structured interview guide (Appendix B). The interview will last approximately 30 minutes. 
Participants will be asked to be frank and will be reminded that there is no right or wrong answer to any 
question. Participants will also be reminded that they may refuse to answer any question that they 
choose. Drs. Areej El-Jawahri (Principal investigator), and Jamie Jacobs (clinical psychologist and co-
investigator) will be available to provide support and supervise the qualitative interview process. 
 
5.5.2 Intervention Administration 
Please see sections 5.1 and 5.3 as discussed previously regarding the intervention visits. 
 
5.5.3 Special Concerns 
We do not anticipate any complications with this study. If a participant expresses distress during the 
psychological intervention visits or exit interviews, they will be reassured by the psychologist and the 
research staff that they can stop the intervention and they need not to answer any of the interview 
questions which they find upsetting. They will also be reminded that study participation is voluntary. If 
participants remain distressed, both the Principal Investigator and the oncologist will be notified. 
Additionally, we will offer participants who remain distressed an opportunity to meet with either the 
principal investigator (Dr. Areej El-Jawahri) or a clinical psychologist (Dr. Jamie Jacobs, a co-
investigator) to help address their distress. 
 
5.5.4 Compensation: There will be no compensation for participating in this study. 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
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5.6 
Adverse Reactions and Their Management  
5.6.1 Reporting Adverse or Unanticipated Events  
We do not anticipate any harm with our study procedures. While some topics probed during the 
intervention are sensitive in nature, no adverse or unanticipated events occurred in previous studies of 
psychological interventions conducted by our research group. Additionally, our research team has 
extensive experience conducting psycho-behavioral interventions and qualitative interviews on sensitive 
topics without any adverse events. Should adverse or unanticipated events occur during the course of 
the study, a trained study staff member will report the events to the IRB as soon as they are discovered. 
5.6.2 Anticipated Reactions  
If a participant expresses distress during the psychological intervention visits or exit interviews, they will 
be reassured by the psychologist and the research staff that they can stop the intervention and they 
need not to answer any of the interview questions which they find upsetting. They will also be reminded 
that study participation is voluntary. If participants remain distressed, both the Principal Investigator and 
the oncologist will be notified. Additionally, we will offer participants who remain distressed an opportunity 
to meet with either the principal investigator (Dr. Areej El-Jawahri) or a clinical psychologist (Dr. Jamie 
Jacobs, a co-investigator) to help address their distress. 
5.6.3 Reaction Management  
Should caregivers experience distress during the intervention or the qualitative exit interview, Drs. Areej 
El-Jawahri (oncologist) and Jamie Jacobs (clinical psychologist) will be available to address their acute 
needs. Should participants require further support, we will offer them an opportunity to meet with the 
outpatient social worker for additional follow-up. 
6 
Ethical and Legal Issues  
6.1 
Confidentiality  
All patient information will remain confidential and stored on Partners computers.  Identifiers such as 
name will only be used during the initial data retrieval process and can be destroyed once all data 
records have been obtained and data analysis completed. 
7 
Statistical Analysis  
7.1 
Study Endpoints: 
7.1.1 Primary Endpoint:   
The primary endpoint of Phase 1 is developing a finalized version of the psychological intervention for 
caregivers of patients undergoing HCT based on the findings from the qualitative data analysis.  
7.2 
Sample Size Calculation:  
We will recruit and consent 5-10 caregivers for Phase 1. Based on our team’s prior qualitative research 
experience, we believe that this sample size will be sufficient to achieve thematic saturation.  
7.3 
Analysis Plan: 
Phase 1 Data Analysis and Interpretation: We will use descriptive statistics to summarize the 
demographic and clinical characteristics of the caregivers enrolled in the study. Our planned sample size 
(n = 5-10) will allow us to collect comprehensive feedback about the intervention and ensure that we 
have sufficient number of participants to achieve thematic saturation. The qualitative component of the 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
Protocol version 1/ 10-3-2016 
 
 
11
exit interviews will 1) explore caregiver perception of the acceptability and content of the intervention; 
and 2) explore caregiver perceptions of the benefits of receiving the intervention. We will also evaluate 
the acceptability of the intervention by exit interview responses. We will analyze the qualitative data from 
the exit interview according to the NIH-Best Practices for Mixed Methods research in Health Sciences for 
applicability, preferences, clinical relevance, intervention length/timing, and challenges.28 Study staff will 
independently review the qualitative interview transcripts to create a thematic framework for 
interpretation. Two independent coders (Drs. Jacobs and El-Jawahri) will independently code the data to 
enhance validity and credibility, until high reliability is achieved (Kappa >0.080). Discrepancies will be 
resolved by comparison to raw data and reviews by Drs. Temel, Jacobs, El-Jawahri, and Park.  
We will utilize the qualitative data obtained from phase 1 and clinicians’ experience to finalize the 
multicomponent psychological intervention. Specifically, we will refine the following aspects of the 
intervention: 
• 
Intervention content: We will use caregivers’ feedback to confirm the relevance of the intervention 
content, and to revise content as needed. For instance, if caregiver report that they would have liked 
to focus on more active coping strategies, we will increase the balance between change- and 
acceptance-oriented (e.g., mindfulness) approaches. To further enhance the intervention, we also 
may integrate caregivers’ real-life concerns as examples throughout the protocol when introducing 
the use of coping skills and strategies.  
• 
Program structure and schedule: We anticipate that caregivers will have different needs during 
their loved ones’ hospitalization for HCT vs. the immediate post-transplant period. However, we will 
use caregivers’ feedback to guide the order and timing of the eight intervention sessions during these 
two periods. Additionally, we may revise session number (8 sessions) or length (30-45 min per 
session) based on caregivers’ feedback about participation burden and utility. 
• 
Program modality: We will use exit interview data to determine whether the delivery of the 
intervention visit in-person or over the phone was acceptable to participants. 
• 
Additional areas of concern: We will identify any additional areas of concern from caregivers that 
were not addressed specifically in the intervention and integrate them in a revised intervention 
manual. 
8 
References 
 
1. 
Braamse AM, Gerrits MM, van Meijel B, et al: Predictors of health-related quality of life 
in patients treated with auto- and allo-SCT for hematological malignancies. Bone Marrow Transplant, 
2011 
 
2. 
Curtis RE, Rowlings PA, Deeg HJ, et al: Solid cancers after bone marrow transplantation. 
N Engl J Med 336:897-904, 1997 
 
3. 
Duell T, van Lint MT, Ljungman P, et al: Health and functional status of long-term 
survivors of bone marrow transplantation. EBMT Working Party on Late Effects and EULEP Study 
Group on Late Effects. European Group for Blood and Marrow Transplantation. Ann Intern Med 
126:184-92, 1997 
 
4. 
Gratwohl A, Baldomero H, Frauendorfer K, et al: EBMT activity survey 2004 and changes 
in disease indication over the past 15 years. Bone Marrow Transplant 37:1069-85, 2006 
 
5. 
Lee SJ, Joffe S, Kim HT, et al: Physicians' attitudes about quality-of-life issues in 
hematopoietic stem cell transplantation. Blood 104:2194-200, 2004 
 
6. 
Prieto JM, Atala J, Blanch J, et al: Patient-rated emotional and physical functioning among 
hematologic cancer patients during hospitalization for stem-cell transplantation. Bone Marrow Transplant 
35:307-14, 2005 

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Hematopoietic Stem Cell Transplantation (HCT) 
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7. 
El-Jawahri AR, Traeger LN, Kuzmuk K, et al: Quality of life and mood of patients and 
family caregivers during hospitalization for hematopoietic stem cell transplantation. Cancer 121:951-9, 
2015 
 
8. 
Gemmill R, Cooke L, Williams AC, et al: Informal caregivers of hematopoietic cell 
transplant patients: a review and recommendations for interventions and research. Cancer Nurs 34:E13-
21, 2011 
 
9. 
Beattie S, Lebel S: The experience of caregivers of hematological cancer patients 
undergoing a hematopoietic stem cell transplant: a comprehensive literature review. Psychooncology 
20:1137-50, 2011 
 
10. 
Fife BL, Monahan PO, Abonour R, et al: Adaptation of family caregivers during the acute 
phase of adult BMT. Bone Marrow Transplant 43:959-66, 2009 
 
11. 
Siston AK, List MA, Daugherty CK, et al: Psychosocial adjustment of patients and 
caregivers prior to allogeneic bone marrow transplantation. Bone Marrow Transplant 27:1181-8, 2001 
 
12. 
Foxall MJ, Gaston-Johansson F: Burden and health outcomes of family caregivers of 
hospitalized bone marrow transplant patients. J Adv Nurs 24:915-23, 1996 
 
13. 
Northouse L, Williams AL, Given B, et al: Psychosocial care for family caregivers of 
patients with cancer. J Clin Oncol 30:1227-34, 2012 
 
14. 
Langer S, Abrams J, Syrjala K: Caregiver and patient marital satisfaction and affect 
following hematopoietic stem cell transplantation: a prospective, longitudinal investigation. 
Psychooncology 12:239-53, 2003 
 
15. 
Gaston-Johansson F, Lachica EM, Fall-Dickson JM, et al: Psychological distress, fatigue, 
burden of care, and quality of life in primary caregivers of patients with breast cancer undergoing 
autologous bone marrow transplantation. Oncol Nurs Forum 31:1161-9, 2004 
 
16. 
Bishop MM, Beaumont JL, Hahn EA, et al: Late effects of cancer and hematopoietic stem-
cell transplantation on spouses or partners compared with survivors and survivor-matched controls. J Clin 
Oncol 25:1403-11, 2007 
 
17. 
Griffin JM, Meis LA, MacDonald R, et al: Effectiveness of family and caregiver 
interventions on patient outcomes in adults with cancer: a systematic review. J Gen Intern Med 29:1274-
82, 2014 
 
18. 
Bevans M, Wehrlen L, Castro K, et al: A problem-solving education intervention in 
caregivers and patients during allogeneic hematopoietic stem cell transplantation. J Health Psychol 
19:602-17, 2014 
 
19. 
Lambert SD, McElduff P, Girgis A, et al: A pilot, multisite, randomized controlled trial of 
a self-directed coping skills training intervention for couples facing prostate cancer: accrual, retention, 
and data collection issues. Support Care Cancer 24:711-22, 2016 
 
20. 
Shaw JM, Young JM, Butow PN, et al: Improving psychosocial outcomes for caregivers of 
people with poor prognosis gastrointestinal cancers: a randomized controlled trial (Family Connect). 
Support Care Cancer 24:585-95, 2016 
 
21. 
Sorensen S, Pinquart M, Duberstein P: How effective are interventions with caregivers? 
An updated meta-analysis. Gerontologist 42:356-72, 2002 
 
22. 
El-Jawahri A, Traeger, L., Kuzmuk K., et al: Prognostic understanding, quality of life, and 
mood in patients undergoing hematopoietic stem cell transplantation. Abstract Presented at ASCO 2014 
Palliative Care Symposium 2014 
 
23. 
El-Jawahri A, Traeger, L., Kuzmuk K., et al: Qualit yof life and mood of patients and 
family caregivers during hospitalization for hematopoietic stem cell transplantation. Cancer in press, 2014 

Psychological Intervention to Promote Coping for Caregivers of Patients Undergoing 
Hematopoietic Stem Cell Transplantation (HCT) 
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24. 
El-Jawahri AL, T. Vandusen, H. Traeger, L. Greer, J.A. Pirl, W.F. Jackson, V.A. Telles, J. 
Rhodes, A. Spitzer, T.R., McAfee, S. Chen, Y. Lee, SJ. Temel, J.S.: Randomized trial of inpatient 
palliative care for patients hospitalized for hematopoietic stem cell transplantation (HCT). Americal 
Society of Clinical Oncology (ASCO) 2016: oral presentation, 2016 
 
25. 
El-Jawahri A, Traeger L, Kuzmuk K, et al: Prognostic understanding, quality of life and 
mood in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant, 2015 
 
26. 
El-Jawahri AR, Traeger LN, Kuzmuk K, et al: Quality of life and mood of patients and 
family caregivers during hospitalization for hematopoietic stem cell transplantation. Cancer, 2014 
 
27. 
El-Jawahri AR, Vandusen HB, Traeger LN, et al: Quality of life and mood predict 
posttraumatic stress disorder after hematopoietic stem cell transplantation. Cancer, 2015 
 
28. 
Miles M HA: Qualitative data analysis: a sourcebook of new methods. Beverly Hills, CA, 
Sage Publications, 1984  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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9 
Appendices 
Appendix A: Baseline Questionnaire 
 
Caregiver Demographics 
Please check the appropriate box or boxes. 
 
1. Date of birth (mm/dd/yyyy) ___________ 
 
2. Gender 
 Man  
 Woman 
 Other 
 
3. Relationship to patient 
 Married or living as if married 
 Non-cohabiting relationship 
 Divorced/Separate 
 Child (daughter or son) 
 Parent (mother or father) 
 Sibling (brother or sister) 
 Friend 
 Other family 
 
4. Ethnicity 
 Hispanic or Latino 
 Not Hispanic or Latino 
 
5. Race (please check all that apply) 
 American Indian or Alaskan native 
 Asian 
 African American or Black 
 Native Hawaiian or other Pacific Islander 
 White 
 Other (please specify) ______________ 
 
6. Religion 
 Catholic Christian 
 Other Christian (such as Protestant, Orthodox, etc.) 
 Jewish 
 Muslim 
 Atheist 
 None 
 Other (please specify)_______________ 

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7. Please indicate your highest or current education level 
 11th grade or less 
 High school graduate or GED 
 2 years of college/AA degree/Technical school training 
 College graduate (BA or BS) 
 Masters degree 
 Doctorate/Medical degree/Law degree 
 
 
 
 
 
 
 
8. Current employment status 
(please check all that apply): 
 Employed (full-time or part-time) 
 Caring for home or family (not currently employed and not looking for paid work) 
 Unemployed and looking for work 
 Unable to work due to illness or disability 
 Retired 
 Student 
 Other (please specify) ________________ 
 
9. Please indicate how long you have known the patient: _________ years 
 
10. Do you live in the same residence as the patient? 
 Yes 
 No 
 
Your name: ____________________________ 
 
 
Please enter your email address 
(will only be used if necessary):  
______________________________________ 
 
 
What is the best phone number to use if we needed to reach you?  
 
_______________________________ 
 
 
 
 
 
 
 
 
 
Appendix B: Qualitative Interview Guide  

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INTRODUCTION 
 
You recently took part in a study that was designed to help caregivers of patients undergoing 
hematopoietic stem cell transplantation (HCT) cope most effectively with their loved ones’ illness. We 
are now interested to know about your satisfaction with different aspects of this research study so that we 
continue to shape how to provide it to patients. There is no right or wrong answer. Your answers will be 
kept confidential and will not affect your participation in future research studies or your access to medical 
care. 
 
First, I am going to ask you some questions about the timing of the sessions you had and how they were 
delivered. 
 
1. This study was scheduled to start 1-2 weeks prior to HCT. How do you feel about the timing of the 
program? 
 
A. Right time 
Additional Comments: 
B. 
Too soon before transplant 
C. 
Too close to time of 
transplant 
 
 
2. This study was scheduled to continue through day +70 after HCT. How do you feel about the timing 
of the program? 
 
A. Right time 
Additional Comments: 
B. 
Too short after HCT 
C. 
Too long after HCT 
 
 
3. The research study was designed so that sessions were scheduled along with your other medical 
appointments whenever possible. How do you feel about the convenience of attending the sessions?  
 
A. 
Convenient 
Additional Comments: 
B. 
Not convenient 
C. 
Not sure 
 
 
 

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4. What prevented you from attending the intervention sessions? What would help you attend more of 
these sessions? 
 
 
5. The research study was designed so that sessions can be scheduled over the phone when in-person 
visits were not possible. How do you feel about the phone sessions?  
 
A. 
Great 
Additional Comments: 
B. 
In-person was better 
C. 
Not sure 
 
Additional Probe: Would you have preferred all sessions to be delivered over the telephone for 
convenience? 
 
6. How do you feel about the total number of visits included in this research study (eight visits total)?  
 
A. 
Right amount 
Additional Comments: 
B. 
Too few 
C. 
Too many 
 
7. How do you feel about the amount of time each visit lasted?  
 
A. 
Right amount 
Additional Comments: 
B. 
Too short 
C. 
Too long 
 
Now I am going to ask you some questions about the material covered in your visits. 
 
8. During these sessions, you may have learned about strategies to help you cope most effectively with 
your loved ones’ illness.  How helpful did you find these strategies? 
 
A. 
Helpful 
Additional Comments: 
B. 
Not helpful 
C. 
Not sure 
 
Additional Probe: The interviewer can remind the caregiver about specific strategies such as 
acceptance, mindfulness, problem-solving, self-care, communication techniques, etc. Also ask which 
of these strategies was the most helpful 

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9. Since going to the study visits, how often have you used any of these strategies on your own? 
 
A. 
Daily 
Additional Comments: 
B. 
Few times/ week 
C. 
Once or twice 
D. 
Never 
 
10. During these sessions, you may have learned about skills or strategies that would help you gain more 
confidence in your ability to care for your loved one. How helpful was it to learn about these skills or 
strategies?  
 
A. 
Helpful 
Additional Comments: 
B. 
Not helpful 
C. 
Not sure 
 
Additional probe: Which of these strategies was the most helpful? 
 
11. Since going to the study visits, how often have you used any of the skills or strategies on your own?  
 
A. 
Daily 
Additional Comments: 
B. 
Few times/ week 
C. 
Once or twice 
D. 
Never 
 
12. During these sessions, you may have learned about skills or strategies that would help take better care 
of yourself during your loved ones’ illness. How helpful was it to learn about these skills or 
strategies?  
 
A. 
Helpful 
Additional Comments: 
B. 
Not helpful 
C. 
Not sure 
 
Additional probe: Which of these strategies was the most helpful? 
 
 
 

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13. Since going to the study visits, how often have you used any of the skills or strategies on your own?  
 
A. 
Daily 
Additional Comments: 
B. 
Few times/ week 
C. 
Once or twice 
D. 
Never 
 
14. During these sessions, you may have learned about skills or strategies that would help communicate 
more effectively with your loved one. How helpful was it to learn about these skills or strategies?  
 
A. 
Helpful 
Additional Comments: 
B. 
Not helpful 
C. 
Not sure 
 
 
 
 
Additional probe: Which of these strategies was the most helpful? 
 
15. Since going to the study visits, how often have you used any of the skills or strategies on your own?  
 
A. 
Daily 
Additional Comments: 
B. 
Few times/ week 
C. 
Once or twice 
D. 
Never 
 
 
16. Is there anything else that you found helpful about this program?  
 
 
 
 
17. Is there anything else that you found not helpful about this program?  
 
 
 
 
18. What other kinds of programs focusing on improving your well-being (if any) would have been 
helpful prior to your loved ones’ stem cell transplantation?  

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19. What other kinds of programs focusing on improving your well-being (if any) would have been 
helpful immediately after your loved ones’ stem cell transplantation?  
 
 
 
 
 
 
20. What other kinds of programs focusing on improving your well-being (if any) would be helpful to you 
now?  
 
 
 
 
21. People learn information in different ways. What would you prefer in terms of how the intervention is 
administered? 
 
A. 
One-on-one visit with a clinician 
Additional Comments: 
B. 
Reading information from a pamphlet 
C. 
Watching an informational video 
D. 
Telephone contact with a clinician 
 
 
 
F. 
Getting information from a mobile app 
 
 
G. 
Video (skype-like) sessions 
 
H. 
Group-based sessions with other 
caregivers 
 
 
 
22. Is there anything else that you would like to add that we have not discussed? 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix C: Qualitative Interview Phone Script  
 
Hello—is [name of caregiver] there? Hi, my name is [research coordinator’s name] I work 
at the MGH Cancer Center, and I am calling about the quality of life research study in 
which you are participating. Is now a good time to talk briefly? 
 
If yes→ Move on to next section.  
 
If no→  “Is there a better time at which I could call back? “ 
 
As a final part of the study procedures, we would like to ask you to complete an exit 
interview over the phone. As we discussed previously, we will audio-record our 
conversation to help improve the intervention for future research studies. Do you have 
about 30 minutes to complete it with me now? 
 
If yes→“Great, thank you.”  
Proceed to administering the qualitative interview (Appendix B). 
 
If no→  “Is there a better time at which I we could complete the interview?”