A Proof-of-Concept Trial of a Positive Psychology Intervention for Allogeneic Stem Cell Transplant Patients
Phase: NA
Conditions: Hematologic Malignancy, Hematopoietic/Lymphoid Cancer, Blood Cancer
Sponsor: Brigham and Women's Hospital

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
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DF/HCC NON-CLINICAL PROTOCOL 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROTOCOL TITLE: 
Development of a positive psychology intervention to improve mood and health related 
quality of life in patients post hematopoietic stem cell transplantation- Proof of 
Concept Trial 
 
PRINCIPAL INVESTIGATOR: 
Hermioni Lokko, MD, MPP 
Department of Psychosocial Oncology and Palliative Care 
Telephone Number: 617-732-4241 
Email Address: Hermioni_lokko@dfci.harvard.edu 
 
VERSION NUMBER:6 
DATE: 8/9/2019 
Date of Submission: 8/9/2019 
 
 
NCT03654404 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
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Table of Contents 
1.0 
Objectives* .............................................................................................................. 3 
2.0 
Background* ............................................................................................................ 3 
2.3 
Relevant Preliminary Studies. .................................................................................. 5 
3.0 
Inclusion and Exclusion Criteria* ............................................................................ 6 
4.0 
Study-Wide Number of Subjects* ........................................................................... 7 
5.0 
Study-Wide Recruitment Methods* ........................................................................ 7 
6.0 
Multi-Site Research* .............................................. Error! Bookmark not defined. 
7.0 
Study Timelines* ..................................................................................................... 7 
8.0 
Study Endpoints* ..................................................................................................... 8 
9.0 
Procedures Involved* ............................................................................................... 8 
10.0 Data and Specimen Banking* ................................................................................ 14 
11.0 Data Management* and Confidentiality ................................................................ 14 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* ................. Error! 
Bookmark not defined. 
13.0 Withdrawal of Subjects* ........................................................................................ 16 
14.0 Risks to Subjects* .................................................................................................. 16 
15.0 Potential Benefits to Subjects* .............................................................................. 17 
16.0 Vulnerable Populations* ......................................... Error! Bookmark not defined. 
17.0 Community-Based Participatory Research* ........... Error! Bookmark not defined. 
18.0 Sharing of Results with Subjects* ......................................................................... 18 
19.0 Setting .................................................................................................................... 18 
20.0 Resources Available ............................................................................................... 18 
21.0 Prior Approvals ...................................................................................................... 20 
22.0 Recruitment Methods ............................................................................................. 20 
23.0 Local Number of Subjects ..................................................................................... 20 
24.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 20 
25.0 Compensation for Research-Related Injury ........................................................... 21 
26.0 Economic Burden to Subjects ................................................................................ 21 
27.0 Consent Process ..................................................................................................... 21 
28.0 Process to Document Consent in Writing .............................................................. 22 
29.0 Drugs or Devices ..................................................... Error! Bookmark not defined. 
 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 3 of 22 
 
1.0 
Objectives* 
1.1 Purpose 
The purpose of this study is to perform a proof-of-concept trial for a novel phone-
based positive psychology intervention for hematopoietic stem cell transplant (HSCT) 
patients to assess feasibility and acceptability of the intervention prior to a larger pilot 
study. 
1.2 Specific Aims/Objectives 
Specific Aim #1 (Feasibility and Acceptability; primary aim): To assess 
whether the novel positive psychology intervention is feasible (participants will 
complete 5 out of 8 phone sessions) and acceptable in HSCT patients. 
 
Specific Aim #2 (Effects on psychological outcomes): To assess whether this 
preliminary intervention appears to result in improvement in positive affect and 
other psychological well-being factors as measured by dispositional optimism, 
anxiety, and depression. 
 
Specific Aim #3 (Effects on other outcomes): To examine the impact of the 
intervention on overall function and health-related quality of life.  
 
1.3 Hypothesis 
Hypothesis #1: The PP exercises will be feasible (i.e., 5 of the 8 phone sessions 
will be completed by a majority of patients) and acceptable (mean score of at least 
6 out of 10 on ratings of ease of completion and subjective utility of the 
exercises). Furthermore, we will obtain complete objective follow-up data in at 
least 80% of enrolled participants at the end of the intervention. 
Hypothesis #2: The intervention will lead to improvements in positive affect and 
other psychological well-being factors as measured by dispositional optimism, 
anxiety, and depression at completion compared to baseline. 
Hypothesis #3: The intervention will lead to improvements in health-related 
quality of life and functional outcomes at completion compared to baseline. 
 
2.0 
Background* 
2.1 
Scientific or scholarly background 
and Significance. 
Hematopoietic stem cell transplantation (HSCT) is the transplantation of stem cells 
(either from the patient themselves [autologous], or a donor [allogeneic]) derived from 
bone marrow or from peripheral or cord blood for the treatment of blood or bone marrow 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 4 of 22 
 
malignancies including leukemias, lymphomas, mylodysplastic syndromes and 
myelomas. About 22,000 HSCTs take place annually in the United States.  
Adherence to frequent clinic visits, active medication management and health 
behaviors such as healthy diet and regular physical activity is essential for a successful 
routine follow-up care after HSCT. Additionally, HSCT patients and their caregivers are 
required to constantly monitor for risks and symptoms of infections, graft vs. host 
disease, or relapse, and such vigilance requires high psychological well-being and 
motivation.2  
Most HSCT patients are not clinically depressed. However, many experience deficits 
in psychological well-being (e.g., optimism or positive affect). Low levels of positive 
states and constructs contribute to fatigue and reduced physical functioning, which 
inevitably can negatively impact the successful adherence to the intensive follow-up care 
required after HSCT, health-related quality of life and overall long-term recovery. 
Importantly, positive states and depression are not simply mirror images of each other 
(and are only modestly inversely correlated), and the beneficial effects of positive states 
on outcomes in medical illnesses persist even after accounting for depression/negative 
affect. This suggests that it is not simply an absence of depression that confers the benefit 
associated with positive emotions. Indeed, in a wide variety of chronic medical 
conditions, positive psychological interventions (including exercises to cultivate 
gratitude, acts of kindness, recall positive life events, and express optimism) completed in 
a systematic deliberate manner have been prospectively linked to improved well-being, 
reduced distress/depression, improved medication adherence, and more physical activity.  
Although PP states have been shown to positively impact the adherence to health 
behaviors in patients with chronic medical illnesses, it has not been studied in HSCT 
patients. Also, there is minimal understanding and report of the deficits in positive 
emotional states (e.g., optimism or positive affect) in HSCT patients. Additionally, 
interventions that help boost PP states in HSCT patients have been minimally studied 
despite their well-documented overall efficacy in other medical populations. We have 
completed a systematic review of the literature on PP constructs and interventions in 
HSCT; our review did not yield any preexisting studies that have used PP interventions in 
any HSCT population. 
A PP intervention, consisting of simple, enjoyable exercises that can be delivered via 
phone by clinicians with a wide range of training, may provide substantial benefit. PP 
states have been prospectively linked with superior long-term health outcomes and 
survival in medically ill persons, independent of medical or socio-demographic variables. 
Additionally, the prospective association between positive states and mortality 
demonstrated in patients with chronic medical conditions is usually independent of 
negative emotional states and relevant medical factors. Although PP interventions are 
easy to deliver and could boost mood and health-related quality of life (HRQoL) in many 
HSCT patients, they have never been tested in this population.  
2.2 Prior Experience and gaps in current knowledge. 
      Prior to this work with HSCT patients, Dr. Lokko has been the site principal 
investigator for observational and intervention studies as well as randomized control 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
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trials focusing on positive psychological states and PP interventions in acute coronary 
syndrome patients to improve cardiac health behaviors. 
 
Dr. Lokko has also just completed qualitative research (Protocol # 17-154) 
in HSCT patients at the DFCI to learn more about the psychological experiences 
(both positive and negative) of patients who have hematologic malignancies who 
have received HSCT. Dr. Lokko successfully enrolled 25 patients for 30-60 
minute interviews at two time points. Hence she has experience recruiting this 
patient population, administering validated questionnaires and instruments in 
addition to working with these patients clinically on the inpatient psychiatry 
consult service. Dr. Lokko attends the weekly HSCT team meetings, interfaces 
with the various clinicians who care for this patient population and has gained 
familiarity with the patient population, their hospital course after transplant and 
some of the challenges associated with the immediate recovery phase. 
 
Dr. Lokko is currently working on a systematic review on the association 
of positive psychological constructs on various psychological and medical 
outcomes in HSCT- to her knowledge there are no current systematic reviews 
looking at the association between positive psychological constructs in HSCT. 
 
As mentioned in an earlier section, although PP interventions have been 
shown to positively impact different psychological and functional outcomes in 
other chronic medical populations, it has not been studied in HSCT. We hope to 
address this gap in knowledge by testing the feasibility and impact of a novel PP-
based intervention that has been adapted for HSCT patients. It is our hope that 
this PP intervention will provide a breadth of significant health benefits for HSCT 
patients and their well-being. 
2.3 
Relevant Preliminary Studies. 
In the first phase of the treatment development (Protocol # 17-154), we aimed to 
explore and understand the deficits in positive psychological states in this population to 
inform the creation of our novel PP intervention for HSCT patients. We have successfully 
performed qualitative interviews (N=25) in approximately the first 30 to 100 days post 
HSCT to learn about: a) the emotional states (both positive and negative), health 
behaviors, quality of life and function, b) the sources of emotional states, c) potential 
links between positive emotional deficits and quality of life and function and d) the utility 
of potential PP exercise in HSCT patients.  
Some of the lessons from the preliminary analysis of the first phase of the study are 
outlined as follows: 1) Patients embraced the opportunities to share about their 
experiences with HSCT; 2) Patients experience both positive and negative emotions as 
part of the HSCT recovery and these emotions impact patient’s overall function and 
quality of life; 3) Patients are interested in increasing positive emotions during HSCT 
recovery; and 4) The burden of side effects and complications in the first 60 days post 
HSCT varies significantly among patients and may be challenging for patients to actively 
participate in an intervention. With the information from our qualitative research phase 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 6 of 22 
 
and existing literature, we have developed a customized, PP health intervention for HSCT 
patients.  
 
In the current phase of the treatment development (Phase 2: Refining the 
intervention), we will perform a proof-of-concept trail (N=25) to ensure our 
intervention’s initial feasibility and to refine the intervention for a larger pilot study. 
 
Essentially, for this phase of the project we hope to do the following: 
1. Test an 8-week, telephone-delivered PP intervention in a brief, non-randomized, 
proof-of-concept trial (N=25). 
2. Determine whether this initial intervention is feasible and acceptable in this 
cohort of HSCT patients. 
3. Explore potential benefits of the intervention on outcomes of interest (e.g., 
optimism, positive affect). 
 
3.0 
Inclusion and Exclusion Criteria* 
Study participants will be adult (age ≥18) English speaking patients with hematologic 
malignancies recruited from the Dana Farber Cancer Institute (DFCI) HSCT Program 
who have access to a phone. Eligible study participants will be identified during the 
weekly HSCT program meeting, where all transplant attending physicians, physician 
assistants, nurse practitioners, and infectious disease clinicians review all the upcoming 
scheduled admissions and discharges as well as the hospital course of admitted patients. 
Patients who have been approved for the study by their transplant attending physicians at 
the DFCI weekly transplant meeting who are clinically stable during their HSCT 
hospitalization will be approached by principal investigator. Willing patients will be told 
the details of the study and inclusion/exclusion criteria will be assessed. Eligible study 
participants will then be consented and screened for the study. 
The DFCI will register eligible participants in the Clinical Trials Management System 
(CTMS) OnCore as required by DF/HCC SOP REGIST-101. When required by 
REGIST-101, registration must occur prior to the initiation of protocol-specific 
procedures or assessments. 
Inclusion Criteria: 
• Adult patients with hematologic malignancies hospitalized for allogeneic 
HSCT at the DFCI inpatient units who are medically stable and 
appropriate for study approach.  
• Ability to speak, read and write English  
• Access to a telephone 
 
Exclusion Criteria: 
• Current major depressive episode, bipolar disorder, psychosis or active 
substance use disorder diagnosed via the Mini International 
Neuropsychiatric Interview (MINI) given that they require more intensive 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 7 of 22 
 
psychological and psychiatric care. We will however enroll patients with 
moderate mood and anxiety symptoms as they are likely to benefit from a 
PP intervention and incorporating their experiences will be useful. 
• Cognitive deficits impeding a study participant’s ability to provide 
informed consent or participate adequately in the study assessed via a 
commonly used 6-item cognitive assessment with the Brief Interview for 
Mental Status (BIMS) screening tool that is sensitive and specific for 
screening for cognitive impairment in research subjects. 
• Medical conditions precluding interviews. 
 
Special Populations 
• Individuals who are unable to consent or are not yet adults (including 
infants, children, teenagers), pregnant women or prisoners will be 
excluded from the study 
 
4.0 
Study-Wide Number of Subjects* 
We are recruiting 25 patients from only one site. This is not a multisite 
study. 
 
5.0 
Study-Wide Recruitment Methods 
This is not a multicenter study and all subjects will be recruited from one local 
site. 
 
6.0 
Multi-Site Research 
This study is located to one study site which is the DFCI main campus in 
Longwood. 
 
7.0 
Study Timelines* 
7.1 Subject Participation in the study 
The planned duration of total participant participation in the 
intervention is 24 weeks, broken down as follows: at weeks four, eight 
and twelve following consent and eligibility determination, 
participants will receive check-in/psychosocial support phone calls 
about their recovery, then week 14 is for self-assessment 
questionnaires prior to the 8-session weekly positive psychology 
treatment, and the last week will be used for a repeat of self-report 
measures obtained at baseline. Patients will also be given the option to 
complete self-reported measures via mail vs. phone. 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 8 of 22 
 
Based on prior recent experience with recruitment from this patient 
population, we anticipate about 6-months for the total number of 
patients for the study. 
We are estimating the study will be completed in June 2019. 
 
 
 
 
 
 
Enrollment 
Check-
In/Psychoso
cial support 
phone calls 
(weeks, 4, 8, 
12) 
Pre-
Interven
tion 
Visit 
Week 1 
of PP-
intervent
ion 
Week 2 
of PP-
intervent
ion 
Week 3 
of PP-
intervent
ion 
Week 4 
of PP-
intervent
ion 
Week 5 
of PP-
intervent
ion 
Week 6 
of PP-
interventi
on 
Week 7 
of PP-
intervent
ion 
Week 8 
of PP-
intervent
ion 
 
Follow-Up 
Session 
HSCT team meeting review to 
confirm eligibility 
X 
 
 
 
 
 
 
 
 
 
 
 
Assessment of inclusion criteria  
X 
 
 
 
 
 
 
 
 
 
 
 
Obtain Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
10-min phone call 
 
X 
 
 
 
 
 
 
 
 
 
 
PP exercise 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Follow-up session 
 
 
 
 
 
 
 
 
 
 
 
X 
Self-report measures 
(LOT-R, PANAS, HADS, 
PROMIS-PF-20, PROMIS-
Fatigue-8a, FACT-BMT) 
X 
 
X 
 
 
 
 
 
 
 
 
X 
 
8.0 
Study Endpoints* 
Primary Endpoint: Establishing the positive psychology intervention 
feasibility and acceptability in HSCT patients will be the primary 
endpoint.  
Secondary Endpoint: Assessing the immediate impact of the PP 
intervention on participants’ positive psychological state and 
psychological well-being (as measured by dispositional optimism, positive 
affect, anxiety and depression, adherence and functional outcomes) will be 
the secondary endpoint. 
 
There are currently no anticipated primary or secondary safety endpoints. 
 
9.0 
Procedures Involved* 
9.1 Study Design 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 9 of 22 
 
The goals of this study are to assess the feasibility, acceptability and 
preliminary impact of this novel 8-session weekly PP-based intervention 
for HSCT patients. 
Patients will be approached close to their discharge from the hospital after 
their HSCT for eligibility determination and to obtain consent. After 
consent is obtained, eligibility will be determined with the mini 
international neuropsychiatric interview (MINI) and a brief cognitive 
assessment (with the BIMS) to exclude patients who need more intensive 
psychological or psychiatric care or have cognitive deficits.  Upon 
agreement and consent to participate in the study, participants will receive 
check-in/psychosocial support phone calls at weeks four, eight and twelve 
to provide support and check-in on how their recovery is going since 
discharge, develop rapport and prepare them for the positive psychology 
treatment portion of the intervention which will start between Day 90-120 
post HSCT. Between the 90-120-day point, when patients return to the 
clinic for their routine 100-day post HSCT follow-up, the 
interventionist/principal investigator will meet briefly with the patients in 
clinic to complete self-assessment questionnaires to measure positive 
affect, optimism, anxiety, depression, HSCT-specific health related quality 
of life, adherence and overall function. For the rare situations when 
participants cannot complete these self-assessment questionnaires in 
person, patients will be given the option to complete self-assessment 
questionnaires by phone or mail. 
After completion of the questionnaires, participants will be provided with a 
treatment manual, with weekly PP exercises for 8-sessions. All participants will 
be asked to complete 8 weekly PP exercises and will be asked to speak with the 
study interventionist, in this case the principal investigator, weekly. Immediately 
after the completion of the exercises, the participants will rate the ease of exercise 
completion, overall utility of the exercise, and their current levels of positive 
affect. For the last week of the intervention, baseline self-assessment 
questionnaires will be reviewed. At study completion, we will inquire about 
participants’ potential interest in being contacted about our future studies. We will 
adhere to any and all participant requests regarding contact. 
 
 
9.2 Research Procedures 
Psychosocial Support/Check-In phone calls: Study participants will 
receive monthly phone calls from the study interventionist/principal 
investigator at weeks four, eight and twelve following their enrollment. 
The goal of the psychosocial support/check-in phone calls is to provide 
study participants an avenue to talk about their adjustment and transition 
to the outpatient care from inpatient, quality of life and coping during 
recovery, adherence to treatment, etc…which will be beneficial to patients 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 10 of 22 
 
and help with rapport building with the interventionist prior to the positive 
psychology intervention.  
Pre-intervention visit: The first physical contact with the patient since 
consent and enrollment during the HSCT hospitalization will be at the 
routine 100-day follow-up visit (around Day 90-120) in clinic. The visit 
will happen in a private room at in the DFCI outpatient clinic. Patients will 
complete the following self-assessment scales: Positive and Negative 
Affective Scale (PANAS) to measure positive affect, Life Orientation 
Test-Revised [LOT-R] to measure optimism and the Hospital Anxiety and 
Depression Scale [HADS] to measure anxiety and depression. We will 
also assess HSCT-specific HRQoL with the Functional Assessment of 
Cancer Therapy-Bone Marrow Transplantation [FACT-BMT] scale), 
overall function (PROMIS-PF-20), and fatigue (PROMIS-Fatigue-8a). 
Data about medical and oncologic history, treatment course and 
medications will be obtained from the electronic medical record. – A 
waiver of HIPAA authorization would be requested for this and will only 
be clarified with patients if there are inconsistencies in the medical 
records. This in person session should take about 30 minutes. Patients will 
also be given the option to complete this visit over phone if in person visit 
cannot be coordinated with other routine 100-day follow-up care. 
After completion of the questionnaires, participants will be provided with a 
treatment manual, with weekly PP exercises.  Participants will be assigned the 
first exercise (gratitude for positive events) in preparation for their first phone 
session.  
 
 
Weekly phone sessions for positive psychology intervention: All participants will 
be asked to complete 8 weekly PP exercises and to speak with the interventionist 
weekly. Weekly phone sessions will last approximately 30 minutes. Prior to 
completing each phone session, participants will be asked to rate their current 
level of happiness and optimism, using a 10-point Likert scale. Immediately after 
completing the exercise and phone session, participants will rate the ease of 
exercise/session completion, overall utility of the exercise/phone session, and 
their current levels of happiness and optimism, all using 10-point Likert scales. 
These calls will be recorded so that a percentage (10%) of these recordings can be 
reviewed by research mentor, Dr. Huffman to ensure that the PP intervention is 
being delivered as described in the protocol. 
 
Follow-up session: The last week of the study will be used for a repeat of the self-
assessment questionnaires obtained at the beginning of the study. This will be 
done either via phone or mail depending on patient preference. 
 
Positive Psychology Program Content. All phone sessions will include (a) a 
review of the ease and utility of the week’s PP exercise (b) a discussion of the 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 11 of 22 
 
rationale of the next week’s PP exercise through a guided review of the PP 
manual, and (c) assignment of the next week’s PP exercise. During the calls, the 
interventionist and participant will also review the next section of the treatment 
manual and prepare for the upcoming week’s exercise. 
 
Positive Psychology Exercises. The PP exercises used in this study were selected 
based on the qualitative study results from the first phase of this study (IRB: 17-
154), their superior performance in our pre-pilot research and others’ work with 
medical populations. They will be grouped into three modules focusing on a 
different psychological state: 
 
Module 1: Gratitude-based activities 
Week 1: Gratitude for positive events.  
Participants recall three events, small or large, in the preceding week that were 
associated with satisfaction, happiness, pride, or other positive states. 
 
Week 2: Expressing gratitude.  
Participants write a letter of gratitude thanking a person for an act of kindness; 
participants may, at their discretion, share the letter with the other person. 
 
 
Module 2: Strength-based activities 
 
Week 3: Remembering a past success.  
Participants recall a prior event in which they experienced success. They write 
about the event, their contribution to the success, and the positive feelings evoked 
by recalling it. Finally, they consider how they might use the experience to be 
successful in the future. 
 
Week 4: Using personal strengths.  
Participants choose a personal strength that is important to them and then find a 
new way to use that strength over the following week. 
 
Week 5: Using Perseverance 
Participants work to learn the skills of sticking with something when things get 
though especially as it pertains to their recovery from the transplant. 
 
Module 3: Meaning-based activities 
Week 6: Enjoyable and meaningful activities.  
Participants complete a series of self-selected activities that vary between those 
that bring immediate boosts in mood and those that are more deeply meaningful.  
 
 
 
Week 7: The Good Life 
Participants work to articulate what their values are and what their perception of a 
good life will look like especially as it pertains to their health and recovery. 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 12 of 22 
 
 
Week 8: Planning for the Future. 
Participants work to perform enjoyable and meaningful acts for themselves and 
others in daily life. Trainers help participants create a plan for using these skills 
on their own in the near future. 
 
 
Follow-Up Session 
At the last week of the study, a member of the study staff will call participants to 
repeat the self-report questionnaires that were administered at baseline. Positive and 
Negative Affective Scale (PANAS) to measure positive affect, Life Orientation Test-
Revised [LOT-R] to measure optimism and the Hospital Anxiety and Depression 
Scale [HADS] to measure anxiety and depression. We will also assess HSCT-specific 
HRQoL with the Functional Assessment of Cancer Therapy-Bone Marrow 
Transplantation [FACT-BMT] scale), fatigue (PROMIS-Fatigue-8a) and overall 
function (PROMIS-PF-20).  Finally, patients will be asked about their experience in 
the study, including any aspects of the intervention or study procedures that could be 
improved. In sum, these scales should take approximately 30-40 minutes to complete. 
If participants would rather complete the follow-up questionnaires in written form 
rather than over the phone, we will send them a paper packet at the time of the 
follow-up. 
 
Given the results of our prior PP studies in medical populations yielding a 64-85% 
completion rate of the exercises, and given that this is a feasibility study (i.e., we want to 
assess participants’ willingness to complete the phone sessions), we will expect 
participants to complete at least 5 PP exercises. In other words, if a participant completes 
at least 5 sessions, missed sessions will not be considered a deviation from the protocol. 
 
Training. The PP exercises for this trial have been identified via published literature, or 
directly from researchers, and modified appropriately for this population based on results 
from first phase of the study that the IRB approved (17-154). Additional text outlining 
the rationale and instructions for each exercise are in the written packets for each exercise 
that are provided to participants. Dr. Lokko will engage in several training exercises prior 
to study initiation. Dr. Lokko’s research mentor, Dr. Jeff Huffman, and his research 
group have had substantial experience in explaining and delivering PP exercises from 
their studies in cardiac and psychiatric patients, which will inform Dr. Lokko’s training. 
Together with Dr. Huffman, Dr. Lokko will review the treatment manual and the team’s 
prior training manuals related to these exercises. They then will complete all exercises 
together to gain experience performing and reviewing each exercise.  
9.3 Procedures performed to lessen the probability or magnitude of 
risks. 
Confidentiality. As with any study, there is the risk of a breach of confidentiality; 
these risks will be minimized by using participant identification numbers rather than 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 13 of 22 
 
identifying personal data on study documents, and by using locked cabinets/offices and 
password-protected databases to store personal information. Only study staff (the PI, the 
research assistant entering data) will have any access to personally identifiable 
information about participants, and such access will be limited only to information 
necessary to complete study tasks. We will ensure that contact with participants is 
confidential by using only the phone numbers and other contact information that are 
specifically allowed by the participants and not leaving study-related messages for 
participants unless expressly allowed by participants. Upon enrollment, we ask all 
participants if it is acceptable to leave voice messages on their phones, as well as the 
appropriate times to call them. We adhere to any and all patient requests regarding 
contact.  
Digital recordings of the sessions will be completed using portable recorders. If a study 
participant were to refuse audio recordings, they can either remove themselves from the 
study or work with the study investigator to choose an alternative to audio recording such 
as transcription. The principal investigator and the senior research mentor will randomly-
select recorded phone sessions to review for competence and adherence to the protocol. 
All recordings will be downloaded immediately from the recorders and the electronic 
files will be kept within the firewalled, password-protected file on a Partners server. 
Recordings will contain no personally identifiable information (and principal investigator 
will not use names or other identifying information on the recordings) and will be erased 
following review.  
 
Informed consent process. Regarding the consent process, we will 
approach/recruit participants in the hospital only after their clinicians in the HSCT 
transplant team have approved for them to be approached. When discussing the study, we 
will emphasize the study’s optional nature and participants’ ability to opt out/un-enroll at 
any time, for any reason.  
 
Medical & psychiatric emergencies. If patients report acute medical symptoms, 
they will be directed to emergency medical care, and their primary medical physicians 
may be contacted as needed. If study staff have questions regarding medical symptoms 
and their urgency, patients’ primary oncologist and their HSCT clinicians and the PI will 
be available to consult (and call patient) as needed. We will ask participants to report 
adverse events related to study participation they may have experienced at any time 
throughout the study. 
We will obtain data using different measures as listed below. We will also check 
the patient electronic medical records to confirm baseline demographic 
information. The measures we will use are as follows: 
• Optimism: LOT-R  
• Positive affect: Positive Items on the PANAS 
• Anxiety/depression: HADS 
• HSCT-related QoL: FACT-BMT 

PROTOCOL TITLE: Development of a positive psychology intervention to improve 
mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
Page 14 of 22 
 
• Overall function: PROMIS-PF-20 
• Fatigue: PROMIS-Fatigue-8a 
 
 
9.4 Long-term follow-up. 
This study does not have long-term follow-up as part of the protocol. As 
aforementioned, the last week of the program entails obtaining some 
feedback about patient’s perception of the intervention, as well as a repeat 
of the baseline questionnaires. 
10.0 Data and Specimen Banking 
We will not be collecting any data or specimen that will need banking for this 
study. 
 
11.0 Data Management* and Confidentiality 
11.1 Data analysis plan, including any statistical procedures. 
Data will be downloaded from REDCap into the Stata statistical 
package. For Aims 1 and 2 (feasibility, acceptability, and immediate 
impact), descriptive statistics will be used to report proportion of 
phone session completion and mean scores on exercise ratings.  
To compare mean scores on outcome variables for Aim 3, paired t 
tests will be used to explore mean differences between baseline and 
follow-up values. All statistical tests will be two-tailed and p<.05 
considered significant, though this study will not be powered to 
detect statistically significant differences between baseline and 
follow-up points. Given the sample size and potential for drop-out, 
we will also consider alternatives to a t-test such as non-parametric 
tests, effect size calculations to support feasibility of study 
assessment procedures. 
11.2 Power analysis. 
This exploratory proof-of-concept study with 25 patients (anticipated 
10 patients to complete the study), as noted, will not be powered to 
detect statistically significant differences between baseline and 
follow-up points, and is designed to assess feasibility of methods. 
11.3 Data Security Plan. 
All source data (e.g., chart review data and participant self-report) 
will be entered into the REDCap database. The PI (Dr. Lokko) will 
review this data to ensure that it is being entered correctly and will 
perform ‘test downloads’ of the data to ensure that it can be captured 
in the statistical package to be used in this study. We will also use 

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mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
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locked cabinets/offices and password-protected databases to store 
personal information. Only study staff (currently just the PI) will 
have any access to personally identifiable information about 
participants, and such access will be limited only to information 
necessary to complete study tasks.  
We will ensure that contact with participants is confidential by using 
only the phone numbers and other contact information that are 
specifically allowed by the participants and not leaving study-related 
messages for participants unless expressly allowed by participants. 
Upon enrollment, we ask all participants if it is acceptable to leave 
voice messages on their phones, as well as the appropriate times to 
call them. We adhere to all patient requests regarding contact. 
11.4 Quality Control. 
Safety monitoring will be performed by Dr. Lokko (PI), who will 
ensure that the study team is adequately identifying, reviewing, and 
reporting adverse events and unanticipated problems to the 
Institutional Review Board (IRB). A more detailed description of 
monitoring mechanisms, intervals, and the information monitored is 
outlined below. 
 
Monitoring mechanism: Dr. Lokko (PI) will take primary 
responsibility for the data safety monitoring. However, this study 
will have a formal data safety monitoring board (DSMB), which will 
be chaired by Dr. Jeff Huffman (psychiatry, primary mentor), and 
populated by Dr. Chris Celano (psychiatry, peer-mentor), and Dr. 
Rachel Millstein (psychologist, external to study).  
Monitoring intervals: Monitoring of adverse events will occur on an 
ongoing basis with notification of Dr. Lokko with any adverse study-
related events. More systematic weekly meetings for review of 
feasibility/acceptability information and minor IRB deviations will 
be held between Dr. Lokko and Dr. Huffman. Dr. Lokko will then 
discuss any potential issues regarding data safety or protocol 
deviations with Dr. Huffman during weekly supervision meetings. 
This allows the team to review this information and adjust 
procedures as required. Furthermore, monthly journal clubs are held 
with the study team; these include discussions of related projects 
(e.g., studies of physical activity in cardiac patients, studies of 
positive psychological interventions). Finally, the formal DSMB will 
meet every four months to monitor patient safety outcomes. These 
ongoing, weekly, and intermittent reviews ensure that the study 
procedures minimize research-related risk by reviewing specific 

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mood and health related quality of life in patients post hematopoietic stem cell 
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outcomes linked to the project and by reviewing relevant literature to 
ensure that interventions are best practice.  
Information to be monitored: Information to be monitored will 
include: (a) an evaluation of the progress of the research study, 
including assessments of data quality and timeliness and participant 
recruitment, accrual and retention consistent with plans for diversity 
and generalizability, (b) a review of study safety data—adverse 
event (and minor deviation) information—to determine whether the 
study should continue as originally designed, be changed, or be 
stopped, (c) review of procedures to maintain participant 
confidentiality (e.g., storage of identifiable information in locked 
cabinets, ensuring study databases have no personal identifying 
information, use of study participant numbers on communications 
about the study), and (d) an assessment of external factors or 
relevant information (e.g., developments in the literature, results of 
related studies, etc.) that may have an impact on the safety of 
participants or on the ethics of the research study, such as through 
the journal club listed above. 
 
12.0 Provision to Monitor the Data to Ensure the Safety of Subjects 
This research does not require or involve more than minimal risk to subjects. 
 
13.0 Withdrawal of Subjects* 
We do not anticipate any circumstances under which the subjects will be 
withdrawn from the research without their consent. We do not anticipate 
any termination of patients. When informed consent is being obtained 
from patients, we will emphasize to patients that they can withdraw from 
the study at any time for any discomforts. Subjects who withdraw from the 
study will still have their data potentially analyzed depending on when in 
the study they withdraw and patients will be informed of this as well. We 
will ensure that contact with participants is confidential by using only the 
phone numbers and other contact information that are specifically allowed 
by the participants and not leaving study-related messages for participants 
unless expressly allowed by participants. Upon enrollment, we ask all 
participants if it is acceptable to leave voice messages on their phones, as 
well as the appropriate times to call them. We adhere to any and all patient 
requests regarding contact. 
 
 
14.0 Risks to Subjects* 

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mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
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The risks to participating in this study should be relatively limited. We anticipate no 
physical risks to participating in this study. Study participants may experience discomfort 
from discussing psychological experiences and could experience the evaluation as 
intrusive.  Study participants who do not find any benefit from participation may find this 
upsetting. Activities to obtain data through the follow-up assessment may also provide 
some inconvenience to study participants. We will take all measures to ensure patient 
comfort and will postpone or end interviews at study participants’ requests. We will also 
ensure that the PI or other psychiatry study staff is available to intervene if needed (due to 
patient discomfort or to answer specific questions about the study), during baseline and 
phone assessments. We have used the briefest methods necessary to assess emotional 
states and other outcomes to reduce patient discomfort.  
 
As with any study, there is the risk of a breach of confidentiality of data collected. To 
minimize the potential loss of confidentiality, we will employ multiple safeguards and 
measures. Interviews will be administered by trained interviewwes. Study participants 
will be assigned a unique study identification number which will be stored separately 
from personal identification information. All data, including telephone recordings and 
transcripts will be securely stored in locked file drawers. All project file cabinets and 
computer databases will be secured in locked offices. We will ensure to not provide any 
data to third particies. Data will be aggregated and summary reports will be generated 
without any personal identification information. 
 
15.0 Potential Benefits to Subjects* 
Patients may not benefit from participating in this study. However, as part of the 
intervention, patients may obtain benefit from sharing their experiences especially as they 
explore and notice their positive experiences more than baseline. Contact with study 
interventionist and principal investigator may also provide support and social connection 
for study participants during the high risk post-discharge period of HSCT recovery.  
Patients will be given the opportunity to identify positive emotions and consider ways to 
enhance their own positive emotions. Description of the PP exercises may enlighten them 
as to potential means of improving their own emotional states. Furthermore, they will 
have the opportunity to consider possible barriers to adherence to health-related 
behaviors. Patients who are identified as suffering from depression on the HADS scale 
will be offered opportunities to get treatment for such symptoms.  
Optimism and other positive affective states are prospectively associated with increased 
participation in healthy behaviors in other medically ill populations and HSCT patients 
may benefit from this as well.  This study therefore has the potential to identify key 
factors related to overall function, quality of life and adherence to health behaviors in 
HSCT patients. The creation of a PP-based intervention—based on this qualitative 
research phase—targeted at improving positive emotional states in HSCT patients could 
lead to a novel approach to enhancing adherence, overall function and quality of life in 
this population, which in turn might result in decreased morbidity and mortality in this 
population. Future studies could investigate the feasibility of implementing this 

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mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
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intervention in a similar population and examine the impact on psychological outcomes. 
If the PP intervention in these studies prove to be feasible, well-accepted, and associated 
with improvements in physical activity and other key outcomes, it may well be possible 
to utilize these easily-delivered and completed exercises as part of a clinical care package 
for HSCT patients. Thus participation in this study may result in substantial benefit to 
future patients. 
 
16.0 Vulnerable Populations 
This project does not involve vulnerable populations including pregnant women, 
prisoners, adults who cannot consent, children or patients with cognitive 
difficulties.  
 
17.0 Community-Based Participatory Research 
This research does not involve community-based participatory research 
 
18.0 Sharing of Results with Subjects* 
We do not anticipate sharing individual subject results with third parties. 
We hope to publish the results from the study in peer review journal 
articles but data will be de-identified. Patients will be made aware of the 
fact that the results will be published. 
19.0 Setting 
Study participants will be adult (age ≥18) English speaking patients with hematologic 
malignancies recruited from the Brigham and Women’s Hospital (BWH) and Dana 
Farber Cancer Institute (DFCI) HSCT Program in Brookline, MA. Eligible study 
participants will be identified during the weekly HSCT program meeting, which 
reviews all the upcoming scheduled admissions and discharges. Patients will be 
approached when clinically stable during their HSCT hospitalization in their private 
hospital rooms at BWH for eligibility determination and to obtain consent. Upon 
agreement to participate in the study, contact will be maintained with patients from 
discharge date to day 90-120 post-HSCT via three phone calls at weeks 4, 8, and 12 
to check in with patients, cultivate a relationship, and to remind them of study launch. 
At the 100-day oncology visit at the DFCI Yawkey Building in Brookline, MA, self-
assessment questionnaires will be obtained after consent is reaffirmed. The 
intervention will be delivered via phone and patients will be called on a private phone 
they designate. 
There will be no involvement from a community advisory board and no research will 
be conducted outside the DFCI or its affiliates. 
 
20.0 Resources Available 

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mood and health related quality of life in patients post hematopoietic stem cell 
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The principal investigator has experience recruiting from this patient population 
and most recently with the successful recruitment of patients for study (IRB 17-
154). The PP exercises for this trial have been identified via published literature, 
or directly from researchers, and modified appropriately for this population based 
on results from first phase of the IRB approved (17-154). Dr. Lokko will engage 
in several training exercises prior to study initiation. Dr. Lokko’s research mentor, 
Dr. Jeff Huffman, and his research group have had substantial experience in 
explaining and delivering PP exercises from their studies in cardiac and 
psychiatric patients, which will inform Dr. Lokko’s training. Together with Dr. 
Huffman, Dr. Lokko will review the treatment manual and the team’s prior 
training manuals related to these exercises. They then will complete all exercises 
together to gain experience performing and reviewing each exercise.  
 
We have decided to recruit 25 patients for this feasibility study based on 
experience from other studies in medical populations involving positive 
psychology exercises. In the first phase of the study, we recruited 25 
patients, a month earlier than our recruitment timeline, an indication that 
recruiting 25 patients for the feasibility study is reasonable. The DFCI 
HSCT sees approximately 550 patients annually for a transplant so we are 
targeting only 1.8% of the patients that come through the HSCT program. 
 
We will also have research assistants who will help with different aspects 
of the study including organizing materials for the intervention, managing 
databases, coding qualitative interviews, performing data analysis and 
organizing documentation for the study. 
 
I will be devoting 40-50% of my productivity time to this research. 
 
Patients will be seen for consent in their private BWH inpatient rooms. 
They will be seen for baseline data collection in a private outpatient 
consulting room at the DFCI. All phone communications will be done 
using DFCI phones. 
 
If patients report acute medical symptoms, they will be directed to emergency 
medical care, and their primary medical and transplant oncologists may be 
contacted as needed. If the patient is at imminent risk to self-harm, the study 
psychiatrist will take all needed steps to ensure emergent psychiatric evaluation, 
which may include ensuring evaluation in the nearest emergency room. 
Participants will be informed of these measures to ensure confidentiality—and the 
limits of confidentiality, such as arranging for emergent medical or psychiatric 
care if safety is at imminent risk—as part of the informed consent process. 
However, given that this is a medical rather than a psychiatric population we 
anticipate the rate of suicidality in this population will be low.  

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mood and health related quality of life in patients post hematopoietic stem cell 
transplantation- Proof of Concept Trial 
 
 
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All study staff for the project will meet weekly to discuss progress of the 
study and to review any changes in the protocol. Currently, the PI is the 
only study staff but as research assistants come on board to enter and 
manage databases such as RedCap, the IRB will be notified, they will be 
oriented to the details of the study protocol, as well as their individual 
roles in data collection and management. 
21.0 Prior Approvals 
This research does not involve any prior approvals for subjects. 
 
22.0 Recruitment Methods 
Hospital (BWH) and Dana Farber Cancer Institute (DFCI) HSCT Program 
in Brookline, MA as was approved for protocol 17-154. Eligible study 
participants will be identified during the aforementioned weekly HSCT 
program meeting of HSCT attendings, which reviews all the upcoming 
scheduled admissions and discharges. Patients will be approached when 
they are medically stable after HSCT in their private hospital rooms at 
BWH for eligibility determination and to obtain consent. Upon agreement 
to participate in the study, contact will be maintained with patients from 
discharge date to day 90-120 of HSCT via three monthly phone calls to 
check in and to remind them study initiation. At the routine 100-day 
oncology visit at the DFCI Yawkey Building in Brookline, MA, self-
assessment questionnaires will be obtained. Patients will also be given the 
option to complete self-assessment questionnaires via phone or mail. 
DFCI HSCT program will be the source of the subjects for this study. 
Eligible study participants will be identified during the weekly HSCT 
program meeting, which reviews all the upcoming scheduled admissions 
and discharges. 
Patients will be approached based on approval by the HSCT oncologists at 
the transplant team meeting. Hence there aren’t specific materials or 
advertisements to recruit patients. 
Patients will not receive payments for participating in the study. 
 
23.0 Local Number of Subjects 
The plan is to accrue 25 subjects locally. We are expecting to enroll about 
25 patients with an anticipated number of completers to be 10. 
24.0 Provisions to Protect the Privacy Interests of Subjects 
In the consent process, it will be emphasized to the patient that at any time 
during the research, they are free to say they will not participate in the 

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mood and health related quality of life in patients post hematopoietic stem cell 
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study. Their decision to participate in any part of the study will not in any 
way interfere with their care at the DFCI. We will also emphasize that 
only study staff will have access to the data. 
It will be emphasized throughout the study that participants should not feel 
obligated to answer any questions that is asked of them that causes 
uneasiness.  
Informed consent will be obtained from patient before any information is 
accessed in their medical records. Only study staff identified with the 
study will handle patient data. Participants’ information will not be shared 
with third parties or study members who are not directly part of the study. 
 
25.0 Compensation for Research-Related Injury 
We do not anticipate any research-related injury to participants. 
26.0 Economic Burden to Subjects 
We do not anticipate any costs to the subjects because of participation in 
the research. 
 
27.0 Consent Process 
Informed consent will be obtained for the study. Patients identified at 
the HSCT weekly meeting based on the inclusion and exclusion 
criteria will be approached by the principal investigator. After a 
verbal discussion of the study in detail, patients will be given 
adequate time to read a written IRB-approved consent form and to 
ask questions. If they desire, study participants will have at least 24 
hours to consider enrollment. To ensure that study participants 
have the capacity to provide informed consent, we will ask them to 
describe their understanding of the study’s purpose and their role 
(e.g., that they understand the timing of intervention and its 
purpose, audiotaping of some of the intervention sessions and the 
purpose for the audiotaping, confidentiality and its limits, our 
focused review of medical records, and their ability to end 
participation in the study at any time for any reason). Patients will 
also be informed of the lag time between consent and study 
initiation within which they can change their mind about 
participating in the study during contact with study staff. Before 
baselines are obtained from patients for study initiation, consent 
will be reviewed with patients for a final decision. 

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mood and health related quality of life in patients post hematopoietic stem cell 
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The informed consent document will cover study purpose, alternative 
options, study logistics as well as risks and benefits of study 
participation. The consent will provide contact numbers for questions 
regarding the study. The consent document will be signed by the study 
participant and the investigator to the document that the consent took 
place. The original consent document will be kept in the study’s 
research file and a copy will be provided to the study participant. We 
plan to follow SOP: Informed Consent Process (CON-100). 
28.0 Process to Document Consent in Writing 
We plan to follow SOP: Informed Consent Process (CON-100) and 
the consent document is part of this application. 
Our research presents no more than minimal risk of harm to subjects 
and involves no procedures for which written documentation of 
consent is normally required outside of the research context. 
29.0 Drugs or Devices 
This study does not involve any drugs or devices.