The Promoting Resilience in Stress Management (PRISM) Intervention: a Multi-site Randomized Controlled Trial for Adolescents and Young Adults With Advanced Cancer
Phase: NA
Conditions: Cancer, Quality of Life, Anxiety, Depression, Hope, Coping Skills, Communication
Sponsor: Dana-Farber Cancer Institute

Site Principal Investigator: Joyce Yi-Frazier, PhD
Protocol Version Number: 16
Protocol Version Date: 4/17/2023
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PROTOCOL TITLE:
The Promoting Resilience in Stress Management (PRISM) Intervention: a multi-site randomized 
controlled trial for Adolescents and Young Adults with advanced cancer
SPONSOR: Dana-Farber Cancer Institute
STUDY PRINCIPAL INVESTIGATOR: Abby Rosenberg, MD, MS, MA
SITE PRINCIPAL INVESTIGATOR:
Joyce Yi-Frazier, PhD
Seattle Children’s Research Institute
1920 Terry Ave Cure 4
Seattle, WA 98101
206-884-1456
joyce.yi-frazier@seattlechildrens.org
Enrolling Sites: Seattle Children’s Research Institute (coordinating site), Children’s Hospital of Los 
Angeles, Texas Children’s Hospital, University of Pittsburgh Medical Center Children’s Hospital
Dr. Yi-Frazier assumes responsibility for the conduct of the study at Seattle Children’s.
ClinicalTrials.gov Identifier: NCT03668223

Site Principal Investigator: Joyce Yi-Frazier, PhD
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Table of Contents
1.0
Objectives...........................................................................................................................5
2.0
Background ........................................................................................................................8
3.0
Inclusion and Exclusion Criteria .......................................................................................13
4.0
Study-Wide Number of Subjects ......................................................................................16
5.0
Study-Wide Recruitment Methods....................................................................................17
6.0
Multi-Site Research ..........................................................................................................17
7.0
Study Timelines ................................................................................................................18
8.0
Study Endpoints ...............................................................................................................18
9.0
Procedures Involved.........................................................................................................19
10.0
Data and Specimen Banking ............................................................................................29
11.0
Data Analysis/Management..............................................................................................29
12.0
Confidentiality ...................................................................................................................33
13.0
Provisions to Monitor the Data to Ensure the Safety of Subjects .....................................33
14.0
Withdrawal of Subjects .....................................................................................................37
15.0
Risks to Subjects ..............................................................................................................38
16.0
Potential Benefits to Subjects...........................................................................................39
17.0
Vulnerable Populations.....................................................................................................39
18.0
Community-Based Participatory Research.......................................................................40
19.0
Sharing of Results with Subjects ......................................................................................40
20.0
Setting ..............................................................................................................................40
21.0
Resources Available.........................................................................................................40
22.0
Prior Approvals .................................................................................................................40
23.0
Participant Incentives .......................................................................................................41
24.0
Use of Social Media..........................................................................................................41
25.0    Local Number of Subjects……   ……………………………………………………….…   ...41
26.0
Provisions to Protect the Privacy Interests of Subjects ....................................................41
27.0
Compensation for Research-Related Injury .....................................................................41
28.0
Economic Burden to Subjects ..........................................................................................41
29.0
Consent Process ..............................................................................................................42
30.0
Process to Document Consent in Writing.........................................................................46
31.0
Drugs or Devices ..............................................................................................................46
32.0
Good Clinical Practice ......................................................................................................46
33.0    References…………………………………………………………………………………....….47

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ABBREVIATIONS AND DEFINITIONS OF TERMS
AYA
Adolescent and Young Adult
CRA
Clinical Research Associate
DFCI
Dana-Farber Cancer Institute
HRV
Heart Rate Variability
HRQOL
Health-Related Quality of Life
PRISM
Promoting Resilience in Stress Management
PRISM-AC
PRISM for Patients with Advanced Cancer
RCT
Randomized Controlled Trial
RPCA
Resilience in Pediatric Cancer Assessment
SCH
Seattle Children’s Hospital
1. Objectives

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1.1 Overview. Among patients with cancer and their families, early integration of palliative care may 
improve quality of life. This is particularly important for Adolescents and Young Adults (AYAs) 
because their distinct developmental challenges related to identity, relationships, and vocation 
may add to the burden of cancer.1-5 Among AYAs with advanced cancer, most understand that 
they may die and report that discussing end-of-life preferences, goals, and fears would be 
helpful; however, only 53% engage in such conversations.6-8  While national guidelines call for 
integrated palliative care in AYA oncology,9-11 developmentally targeted, evidence-based 
interventions designed to meet psychosocial and communication needs are lacking. 
A potential barrier to improving the experiences of AYAs with advanced cancer may be their 
limited opportunities to develop “resilience resources” such as stress-management, goal-
setting, positive reframing, and meaning-making skills.12  These resources may mitigate 
negative outcomes, facilitate engagement in goals of care discussions, and improve quality of 
life.13-15  Furthermore, promoting these resources among AYAs may give them the tools to 
more successfully navigate the challenges of the cancer experience.  
Our research program is built on the central hypothesis that promoting resilience resources will 
improve psychosocial well-being.  Over a series of studies, we developed a conceptual 
framework of resilience in pediatric cancer,12,16 affirmed associations between resilience 
resources and outcomes,17 and developed a novel resilience resources intervention (Promoting 
Resilience in Stress Management, PRISM).18  PRISM is a manualized, skills-based training 
program comprised of four 30-60 minute, in-person, one-on-one sessions plus a facilitated 
parent/caregiver/spouse/significant other family-meeting. 
We recently completed a pilot Randomized Controlled Trial (RCT) to test the efficacy of PRISM 
among 100 AYAs, 6-months following their diagnosis of new (n=73) or recurrent (n=27) cancer 
(manuscript under review).  Final results suggest PRISM is feasible, highly acceptable, and 
associated with increased patient-reported resilience as well as key clinically significant patient-
centered outcomes such as quality of life and psychological distress.  Subgroup analyses 
comparing patients with advanced cancer to those with new cancer suggested differentially 
stronger positive effects in the advanced cancer group, raising a hypothesis to be tested in 
dedicated trials.  However, qualitative feedback from patients with advanced cancer suggested 
refinements targeting hopes, worries, and contextual meaning-making might strengthen 
PRISM’s usefulness.  
The overall objective of this project is to refine PRISM to meet the distinct needs of 
AYAs with Advanced Cancer.  We will first adapt and iteratively test the existing PRISM 
based on established guidelines for intervention development.19  Then, we will conduct a 
multi-site randomized controlled trial to test the efficacy of a new PRISM for Advanced 
Cancer (PRISM-AC). Exploratory outcomes will assess a biomedical variable associated 
with psychological distress called heart rate variability (HRV).  We hypothesize that 
AYAs with advanced cancer who receive PRISM will report fewer mixed affective 
symptoms and show improved biomedical outcomes. Findings will inform the 
development of larger dissemination studies and standards of AYA end-of-life and 
palliative care.  Ultimately, this research has the potential to reduce the burden of cancer 
in a highly vulnerable population.

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1.2 Purpose of the Study Protocol
1.2.1 The protocol is intended to be used by all study staff as the approved procedures for 
conduct of the study.  
1.2.2 Primary Aim:  Evaluate the effect of PRISM-AC compared to usual care on Health-
Related Quality of Life (HRQOL) among AYAs with advanced cancer or 
recurrent/progressive tumors.
1.2.2.1 Primary Outcome Measure: AYA-reported Pediatric Quality of Life Inventory 4.0 
(PedsQL)20,21 scores 3-months post-enrollment.  
1.2.2.2 Primary Hypothesis: PRISM will be associated with higher patient-reported 
HRQOL compared to usual care.
1.2.3 Secondary Aims
1.2.3.1 Create PRISM-AC by refining the existing PRISM for patients with 
advanced cancer.
1.2.3.1.1 Deliverable: Refined manual of PRISM with targeted elements to meet 
the needs of patients with advanced cancer.  
1.2.3.1.2 Anticipated Findings: PRISM-AC will target the same 4 resilience 
resources and have additional module and practice opportunities for 
meaning-making and advance care planning.
1.2.3.2 Assess the feasibility and acceptability of PRISM-AC.  
1.2.3.2.1 Deliverable: feasibility will be defined as >70% enrollment and >70% 
completion of at least 4 sessions.  Acceptability will be evaluated 
qualitatively.  
1.2.3.2.2 Anticipated Findings: PRISM-AC will be feasible and acceptable.
1.2.3.3 Determine if PRISM-AC improves other key patient-reported outcomes
1.2.3.3.1 Outcome Measures: Anxiety and Depression (measured with Hospital 
Anxiety and Depression Scale, HADS)22, symptom burden (Memorial 
Symptom Assessment Scale, MSAS)23,24, hopeful patterns of thought 
(Hope Scale)25, Cancer-Specific Quality of Life (PedsQL 3.0 Cancer 
Module)21, and Resilience (Connor Davidson Resilience Scale, CDRISC-2) 
3-months post-enrollment.  
1.2.3.3.2 Hypotheses: PRISM recipients will report lower anxiety and depression, 
lower symptom distress, higher hope, and higher resilience compared to 
controls.  
1.2.3.4 Evaluate the impact of PRISM-AC on parent distress.

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1.2.3.4.1 Outcome Measures: parent anxiety (Generalized Anxiety Disorder 
Screener, GAD-7),26 depression  (PHQ-8),27,28 and HRQOL (SF-36),29  3-
months post-enrollment. 
1.2.3.4.2 Hypothesis: Parents of PRISM-AYAs will report lower anxiety and 
depression, and better HRQOL compared to parents of AYAs in usual 
care. 
1.2.3.4.3 Exploratory Outcome: Family Experience (selected items from Hospital 
Consumer Assessment of Healthcare Providers and Systems [HCAHPS] 
survey).30
1.2.3.5 Evaluate the impact of PRISM-AC on family “palliative care activation.”
1.2.3.5.1 Outcome measures: (a) AYA- and parent- perceptions of AYA 
involvement in Decision-Making, measured with the Decision-Making 
Involvement Scale31; (b) medical record documented goals of care 
conversations; and, (c) medical record documented AYA utilization of 
formal palliative care and other psychosocial services, hospice, limitation 
of intervention orders, and other advance care plans. 
1.2.3.5.2 Hypothesis: PRISM families will demonstrate higher levels of activation 
compared to usual care.
1.2.3.6 Explore longitudinal impact of PRISM-AC on above outcomes at 6-, 9-, and 12- 
months following enrollment.  
1.2.4  Exploratory Aims
1.2.4.1 Prospectively describe associations between PRISM, patient reported anxiety 
and depression, and stress biomarkers.
1.2.4.1.1 Outcome measures: heart rate variability (HRV) as measured by the 
standard deviation of normal to normal beats (SDNN).
1.2.4.1.2 Hypothesis: PRISM recipients will demonstrate larger improvements in 
HRV compared to controls. 
1.3 Rationale for the Selection of Outcome Measures
Palliative Care interventions aim to alleviate suffering and improve HRQOL.32,33  Hence, we 
selected HRQOL as our primary outcome, with additional clinically relevant patient-centered 
outcomes including symptom burden and psychological symptoms as our secondary outcomes.
Patient outcomes are not the only ones of import in pediatric, adolescent, and young adult 
populations.  Indeed, patient and parent outcomes are inextricably linked. Parent psychological 
distress is highly prevalent among children with advanced cancer, and it is associated with 
perceived child suffering and quality of family communication.34  Hence, we elected to determine 
if a patient-centered intervention could also improve parent outcomes.

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Regarding palliative care utilization, traditional measures focus on the circumstances of death 
(e.g., chemotherapy within the last 30 days, advance care planning documentation).  These 
metrics are less relevant in pediatric and AYA populations.35 AYA advanced cancer may last 
years.36  Content and AYA participation in goals of care discussions evolve.35,37   Low-intensity 
palliative chemotherapy may improve quality of life.38  And, AYAs defer to their parents for 
medical decision-making, suggesting formal advance care planning documents incompletely 
represent AYA perspectives.35 For these reasons, pediatric palliative care research has shifted 
towards outcomes of patient/family engagement and activation.35 Activation is defined as the 
extension of self-efficacy into self-management.  It implies knowledge and confidence to take 
action, actively change behaviors, and maintain changes over time.39 It may be more 
representative of evolving pediatric and AYA palliative care involvement.  Importantly, higher 
activation is associated with improved psychological wellbeing and HRQOL among adults with 
chronic illness,40,41 and with medication-adherence and clinical outcomes in pediatric settings.42-
44  Hence, we selected global activation as a measure of palliative care utilization in this study.
Emerging data indicate anxiety and depression can impact cancer-related outcomes through 
immune-mediated processes, with sympathetic nervous system activation as a central 
mechanism.45  HRV is a commonly used, noninvasive indicator of autonomic nervous system 
activity with published normative values.46
Finally, few palliative care studies include longitudinal outcomes assessments.33,47  In order to 
explore the durable impacts of PRISM-AC, as well as capture cohort data to describe ongoing 
patient-reported and parent-reported outcomes, we will continue to survey patients and families 
quarterly for a year following their enrollment.
2.0 Background
2.1 Prior Literature and Previous Studies
2.1.1 Background & Rationale
Adolescents and Young Adults (AYAs) with cancer are at high risk of poor 
psychosocial outcomes, perhaps because cancer disrupts normal developmental 
experiences like establishment and identification of personal, social, and sexual 
identity, and pursuit of educational and vocational goals.1-5 Unmet needs (e.g., 
inadequate psychosocial support and lack of information about disease management) 
may further contribute to poor outcomes, including poor health-related quality of life 
(HRQOL).48-51 
AYAs may have not yet developed the skills to navigate the adversities of cancer.  In 
this regard, positive psychological resources are important because they may mitigate 
negative outcomes.52,53 “Resilience” implies an ability to bounce back from adversity, 
and is evidenced by emotional and physical well-being after significant stress.54  The 
study of resilience in cancer has lacked consensus of either definitions or outcomes 
indicative of resilience.54,55  However, several personal resources are consistently 
associated with resilience among AYAs and older adults,12,53,56 and parents of children 
with cancer.16,17  These include skills in stress-management, problem-solving, goal-
setting, benefit-finding, and meaning-making.  Bio-behavioral models suggest these 
resources relate to HRQOL, health behaviors, self-advocacy, and immune function.13  

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We term these variables “resilience resources,” and believe they represent an 
additional unmet need. 
Practical challenges limit the success of traditional behavioral interventions.  Time-
commitments of cognitive behavioral therapy (CBT) may be prohibitive for AYAs.  The 
average refusal rate in adolescent chronic disease settings is 37%; subsequent 
attrition is up to 32%.57  Shorter skills-based interventions may be more successful.58 
AYAs learn and communicate differently than younger and older patients, 
necessitating age-appropriate language and educational methods.59  Also, CBT is 
designed for patients with maladaptive coping, whereas AYAs may avoid maladaptive 
behaviors through brief preventive learning.     
Stress and coping theory (Figure 1)14 provides an excellent platform for intervention-
development.  Few interventions have obtained positive outcomes for AYAs, and 
fewer still have suggested mechanisms to build resilience resources.53,60,61  Stress and 
coping theory suggests three categories of resilience resources: (1) dispositional 
factors (e.g., optimism); (2) situational factors (e.g., stress-management); and, (3) 
coping processes to create positive meaning (e.g., cognitive reframing).  Among older 
adults with cancer, stress-management interventions show promise at the beginning,62 
middle,63 and end of therapy,64 and meaning-making improves HRQOL.65 Among well 
AYAs, goal-seeking skills promote psychosocial well-being.66  Among AYAs with 
chronic disease, positive re-appraisal of stressors reduces distress and improves 
adherence66 and HRQOL.67,68  Additionally, biobehavioral models suggest that 
resilience resources relate to long-term quality of life, health behaviors, immune 
function, and overall health and well-being.13 
Communication support is another unmet AYA need.  AYAs with advanced cancer 
face added challenges with prognostic uncertainty and missed goals.69  They 
understand death may be a consequence of their disease.  Most report it would be 

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helpful, if not imperative, to discuss wishes, worries, and information to be shared with 
friends and family.6-8  Only half engage in these discussions, however, and when they 
occur, discussions may be held too late for AYAs to accomplish their goals.8,70  
Indeed, despite guidelines for palliative care integration to facilitate psychosocial 
support and communication,9-11 barriers remain.  These include misconceptions of 
“palliative care,” leading to late referrals,36,71 and a lack of evidence-based, AYA-
specific interventions.72  Existing interventions are limited for 2 important reasons: (1) 
Although they show promise in promoting AYA-parent agreement about later, 
hypothetical decisions, they have only been tested in AYAs with early stage cancer.73 
(2) They tend to target advance care planning in the transition from cure-to-comfort 
directed care.74 However, the experience of AYA advanced cancer may last years, 
and families’ prognostic understanding (and corresponding advance care planning) is 
often delayed.36,75  As a result, AYAs with already advanced cancer miss early, 
ongoing opportunities to explore their hopes and worries.37   
AYA cancer has broad family- and public health-level implications.  For AYAs with 
advanced cancer, missed opportunities to identify and articulate hopes, worries, and 
corresponding treatment decisions contribute to patient suffering, parent distress, and 
decisional regret.73,76-78 Further, parent-child HRQOL is reciprocal.78-80 Parent 
perceptions of patient wellbeing are associated with parent sleep disturbances, 
impaired physical health, and financial hardship.81  Parents of AYAs with advanced 
cancer are at risk for serious psychological distress,82 family dysfunction, and poor 
health behaviors,17 which may affect them for decades.83 Importantly, short-term 
parental distress and perceived quality of oncology care are related to long-term 
parental adjustment, whatever the outcome of the child’s illness.84-86  These data 
underscore the need to understand associations between patient-directed 
interventions and parent outcomes.87  
The Promoting Resilience in Stress Management (PRISM) Intervention has the 
potential to meet these needs and improve outcomes.  As described below, PRISM 
was developed based on stress and coping theory to be a brief, skills-based 
intervention targeting AYA resilience resources.  Results from a phase II randomized 
controlled trial (RCT) suggest it is associated with increased AYA patient-reported 
resilience and HRQOL.  It also provides opportunities for AYAs to articulate goals and 
meaning from their cancer experience, thereby facilitating communication and patient-
activation.  
2.1.2 The Promoting Resilience in Stress Management (PRISM) intervention
Our central hypothesis is that promoting resilience resources will improve outcomes for 
AYAs with advanced cancer and their families.  We followed a stepwise approach to 
testing this hypothesis.  
2.1.2.2 Concept and survey development. First, we conducted a cross-sectional, mixed-
methods study to explore the construct of resilience in pediatric and AYA 
oncology.  Qualitative findings directed the development a conceptual 
framework16 and a survey comprised of validated instruments to measure 
corresponding patient-centered outcomes [the “Resilience in Pediatric Cancer 

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Assessment” (RPCA)].16,17,88 Quantitative findings confirmed associations 
between lower resilience resources and higher distress, lower social function, 
and poorer health behaviors.17
2.1.2.3 Prospective study of AYA perceptions of resilience.  Second, in the “Resilience in 
Adolescents and Young Adults with Cancer” study, we collected survey data and 
conducted consecutive 1:1 semi-structured interviews with AYA patients at the 
time of their diagnosis, 3-6 and 12-18 months later.12,89,90 Several participants 
had advanced cancer at the time of the study.  Thematic analyses suggested that 
AYAs endorse the need for strong resilience resources, but that they lack the 
skills.  Specifically, AYAs stated stress-management, goal-setting skills, “staying 
positive,” and “making meaning” from adversity were essential to their well-
being.12  
2.1.2.4 Intervention Development.  These studies provided rationale for the design of a 
novel intervention to promote resilience resources, the “Promoting Resilience in 
Stress Management” (PRISM, Table 1).18 PRISM is based on stress and coping 
theory (Figure 1),14 our prior research, and successful interventions described in 
other populations.  It is manualized (i.e., it has been standardized via 
comprehensive protocols).  The initial design was refined with expert opinion 
and interviews with patients, psychologists, and social workers.  Details are 
described below. Briefly, PRISM’s overall objective is to increase resilience 
resources at times of high stress, thereby alleviating distress and improving 
quality of life.  
2.1.2.5 Feasibility and Acceptability study of PRISM Intervention.  We completed a 
formative study of PRISM among 24 AYAs to determine the optimal content and 
timing of PRISM sessions.  We found it to be feasible and highly valuable to AYA 
patients and parents.18 Eighty percent of AYA participants completed the 
intervention and feedback was universally positive: “This was so helpful, I wish 
we had done this sooner,” or “I think it’s good techniques to use, definitely.  I am 
teaching my little sister.  I’m sure it can help her, too.”
2.1.2.6 PRISM Phase II RCT (clinicaltrials.gov NCT 02340884).  Next, in a phase II RCT 
testing PRISM efficacy among AYAs with new or recurrent cancer, we refined 
processes of enrollment, randomization, implementation, and data collection.  
We completed our target enrollment of 100 AYAs with either new or newly 
Table 1. Original PRISM intervention content 
Topic
Details
Format
1.
Managing Stress
Mindfulness techniques, relaxation strategies, obtaining social support
2.
Goal-setting
Setting specific, realistic, desirable goals, planning for roadblocks
3.
Positive Reframing
Recognizing negative self-talk, replacing with positive, realistic, manageable 
ones
4.
Meaning Making
Identifying benefits, purpose, meaning, or legacy from cancer experience 
One-on-One
5.
Coming Together
Discussion about what was learned, what helped, what they can do to help 
Family meeting
6.
Boosters
In-person/digital/video conference modules to practice, further develop, and 
track skills. 
One-on-One
7.
Practice 
Opportunities
Paper-pencil and app-based modules to practice and further develop skills
Digital or 
Paper
Note: Sessions delivered approximately every 1-2 weeks, arranged in advance in conjunction with clinic and hospital visits.  

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recurrent cancer 2-months ahead of schedule.  At the time of enrollment, 27 
patients had recurrent cancer. Enrollment rates were 78% and similar among 
patients with new versus recurrent cancer.  Thirteen experienced progressive 
disease during the study observation period, and 18 died of disease or treatment-
related mortality prior to the 6-month end-point, including 5 of the 27 who 
enrolled with recurrent cancer.  Attrition among surviving participants was similar 
on the PRISM (25%) and usual care (14%) arms, and primarily due to medical 
complications.  Of 49 AYAs assigned to PRISM, 48 completed ≥1, and 43 
completed all scheduled sessions.  Only 2 PRISM and 6 usual care patients 
declined continued participation due to the burden of intervention sessions or 
surveys.
The primary objective of the phase II RCT was to assess patient-reported 
resilience 6 months following enrollment. Secondary outcomes included 
psychological distress and HRQOL at the same time-point.  Final pilot results 
(n=92 with intention-to-treat analyses) suggest the intervention was associated 
with improved patient-reported resilience, distress, and quality of life scores with 
moderate effect sizes (Table 2).91  Exploratory analyses suggested a stronger 
intervention effect among AYAs who enrolled with advanced cancer (Figure 2).  
Taken together, these findings are promising because: (a) meta-analyses 
suggest even small effect sizes of positive psychology interventions are 
associated with clinically meaningful patient-centered outcomes;92 (b) we 
demonstrated feasibility among the sickest patients with advanced cancer; and, 
(c) the intervention may be even more impactful in this high risk group of 
patients.
2.1.2.7 Adaptation of PRISM for patients with advanced cancer.  The phase II RCT 
included embedded requests for feedback regarding PRISM’s usefulness and 
potential for improvement.   Thematic comments from patients who entered the 
Table 2. Results from completed pilot RCT among AYAs with new or newly recurrent cancer (n=74)
Usual Care (mean, SD)
PRISM (mean, SD)
Effect Size (Cohens’ d, 95% CI)
Instrument
Baseline
6-months
Change
Baseline
6-months
Change
For change 
For 6-month
CDRISC (Resilience)
28 (6)
28 (6)
-1 (3)
29 (6)
30 (5)
+2 (5)
0.6 (0.1, 1)
0.4 (0, 0.9)
K6 (Psychological 
distress)
8 (5)
7 (5)
0 (5)
6 (5)
5 (3)
-1 (5)
-0.2 (-0.6, 0.3)
-0.5 (-1, 0)
PedsQL (generic HRQOL)
59 (21)
60 (19)
0 (20)
62 (16)
67 (15)
+6 (21)
0.3 (-0.2, 0.7)
0.4 (-0.1, 0.8)
PedsQL (cancer-specific)
65 (17)
64 (20)
-2 (13)
66 (16)
72 (11)
+ 8 (16)
0.7 (0.2, 1.2)
0.5 (0.1, 1.0)
Figure 2. Mean 
cancer-specific 
HRQOL scores 
at baseline (BL) 
and 6-months), 
by advanced 
cancer status 
(red = PRISM; 
black = usual 
care)

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study with advanced cancer and those who experienced progressive disease 
during the study period suggested PRISM should remain essentially the same, 
but that individual modules could include language relevant to the advanced 
cancer experience.  For example, the goal-setting session could include 
opportunities to explore holistic hopes and how they could translate to actionable 
goals, the positive reframing exercises could include language about how 
negative self-talk can help identify worries about the future, and the meaning-
making sessions could focus on what AYAs identify as important.  All of these 
minor changes were thought to have potential to facilitate later conversations 
about AYA wishes, worries, and priorities. A more significant suggestion was to 
add an additional module to formally begin the process of advance care planning, 
in particular to focus explicitly on AYA values and perceptions of quality of life.  
Hence, we expanded the intervention script to reflect minor suggestions while 
adding a new session to introduce simple, evidence-based, and age-appropriate 
advance care planning exercises (select excerpts from Voicing my Choices)74.
2.1.3
Rationale for this Study
Taken together, the background literature and our prior experiences underscore three 
critical knowledge gaps: (1) Although PRISM is feasible, our pilot RCT was not powered 
to test its impact specifically among AYAs with advanced cancer. (2) Although AYA and 
parent well-being are related, associations between AYA-PRISM and parent outcomes are 
unknown. And, (3) although PRISM enables AYAs to identify stressors and goals, how it 
translates to patient activation and subsequent engagement is unclear.  Additionally, we 
will explore whether PRISM is associated with measurable biomarkers of stress and 
resilience. We propose to address these gaps in the current proposal.
3.0 Inclusion and Exclusion Criteria
3.1 Recruitment and Screening:
We will recruit AYAs and their primary caregivers from outpatient Clinics and inpatient wards of 
Seattle Children’s Hospital, Texas Children's Hospital (Baylor), Children’s Hospital Los Angeles 
(CHLA), and University of Pittsburgh Medical Center Children’s Hospital. Research Associates 
(RAs) at each site will screen patients via review of the new diagnoses lists, tumor board 
rosters, attendance at weekly team rounds, clinic rosters and sign-outs, communication with 
clinicians, and/or overnight call lists, followed by a medical chart review to verify eligibility. Staff 
will verify the patient’s diagnosis with a trained oncology provider. 
Recruitment will occur either in person (inpatient hospital rooms and/or outpatient clinic) or by 
phone/video call/text (i.e., direct contact by study staff). Patients will either be approached 
inpatient/in clinic (including initial approach by the patient’s nurse or other known member of clinic 
team) or will be mailed a letter or e-mail introducing them to the study and giving them the 
opportunity to “opt out” of future contacts if desired. If potentially eligible patients who receive the 
letter or email do not opt-out of being approached about the study, we may call them to assess 
their interest and arrange to discuss the study by phone/video or meet them in-person at an 
upcoming clinic visit. Study staff will reach out to potential participants (by phone/video, email, 

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text, or in clinic) to try and gauge interest in the study for a maximum of six attempts (with a 
maximum of 3 attempts wherein direct communication is achieved, such as leaving a voicemail 
message or having a conversation with the potential participant). Text communication will occur 
only after initial contact is made with a family via a non-text method. 
Regarding privacy, hospital inpatient rooms and clinic rooms are all private. When by 
phone/video, patients and parents will be asked if they have time to talk and if there is a quiet 
space to discuss the study.  
There will be a flyer posted in inpatient units and clinic areas. The flyer may also be handed out 
to potential participants before or during the consent conference if it occurs in person.
The RA will approach families and ask if they are interested in learning about a research study. 
Study personnel may contact patients and their parents to discuss the project, and answer 
questions by phone (and in advance of their clinic visit) or while at a regularly scheduled 
outpatient visit or inpatient. Should families prefer to continue to discuss the study in person, we 
will arrange a follow-up conversation regarding the study at the time of their clinic visit or 
inpatient admission, or while they plan to be at the hospital. If it is not feasible to conduct the 
consent conference in person, consent discussions will occur by phone call or video conference 
call (WebEx, Zoom, or Skype). Consent conferences will not be recorded. Study staff will use a 
phone guide for consent discussions over the phone/video. All consent methods will be used, in 
order to accommodate all patients, as well as to maximize recruitment to achieve study goals. 
Some patients come to clinic once every few months. The rationale for conducting the consent 
conference over the phone/video includes that in-person consenting may pose an infection risk 
to this subject population, e.g. COVID-19. In addition, in-person consenting may cause 
unnecessary subject burden, while obtaining consent by phone/video would achieve the same 
purpose without reducing subject informedness. Consenting by phone/video also allows 
potential subjects more time to consider participation. Furthermore, when speaking to potential 
subjects in person, providers may interrupt the consent conference to provide important clinical 
care, clinic or inpatient staff may advise us that the day is not “good” for the family to be 
approached, or illness status may preclude the patient from being cognitively able to provide 
consent/assent that day. When recruitment is done in person, the CRA will explain informed 
consent in a private area (e.g., clinic room, inpatient room). 
Patients and families will be given an addendum to the consent form to participate in the 
optional heart rate variability component of the study.  We will emphasize there will be no 
penalties if patients or families opt out of the HRV portion of the study. This optional procedure 
will be presented at the time of the consent conference. All patients fitting the eligible criteria 
3.2.1.1-3.2.1.4 and 3.2.1.6-3.2.1.8 will be eligible for the HRV component of the study. In other 
words, patients will only be eligible for the HRV component at the Seattle Children’s site. 
Parents do not take part in the HRV component. In cases where it is necessary to minimize in-
person contact with participants to minimize exposure risk (i.e. during COVID-19 pandemic), the 
HRV component will not be offered.
We recognize potential risks for adolescents involved in recruitment; there could be 
embarrassment or discomfort for adolescents if asked to participate. Adolescents may feel 
coercion to be part of the study. To mitigate these risks, we will emphasize the voluntary nature 
of the study to adolescents and parents and that the study will in no way impact or influence 

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clinical care. We will let adolescents know that their information will be kept confidential and that 
audio transcripts will be de-identified and audio recordings destroyed after transcribing. We will 
let adolescents know that they can change their mind about participating and may decide to 
withdraw from the study at any time.
Each of the participating sites has significant experience with clinic recruitment for studies and 
has developed processes to ensure best practices with study recruitment. These procedures 
and scripts also emphasize that any potential coercion on the part of parents should not take 
place, and that adolescents’ decision for or against participation in the study does not affect the 
clinical care they receive. 
The investigators and staff will be available to answer any questions from potential participants 
and participants via phone or email throughout the study. Any issues or concerns raised during 
enrollment processes will be reviewed by the PI and/or Co-Investigators and resolved within a 
timely fashion.  We will emphasize that the decision of whether or not to be part of this study 
does not affect patients’ ongoing care at their respective institutions.
3.2 Eligibility Criteria:
3.2.1
Inclusion Criteria FOR AYA PATIENTS (RCT & Run in)
3.2.1.1 Age 12-24 years
3.2.1.2 Patient aged 12-17 years: has signed informed assent and their 
parent/legal guardian has signed informed consent for study participation.
3.2.1.3 Patient aged 18-24 years: has signed informed consent for study 
participation.
3.2.1.4 Diagnosed with advanced cancer (progressive, recurrent, refractory 
disease, or any diagnosis associated with <50% survival), or any other 
progressive/recurrent brain or solid tumor, at least 2 weeks prior to 
enrollment.
3.2.1.5 Receiving care at Seattle Children’s Hospital (SCH), Texas Children’s 
Hospital/Baylor College of Medicine (BCM), Children’s Hospital Los 
Angeles (CHLA), or University of Pittsburgh Medical Center Children’s 
Hospital (UPMC)
3.2.1.6 Able to speak English language (for PRISM sessions)
3.2.1.7 Able to read English or Spanish language (for completion of surveys)
3.2.1.8 Cognitively able to participate in interactive interviews, PRISM sessions, 
and survey completion, as deemed by medical staff.
*Note: Concurrent parent participation is not required for AYA patient 
participation
3.2.2
Exclusion Criteria FOR AYA PATIENTS:

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3.2.2.1 Patient refusal to participate (any age), or parental refusal to participate for 
patients less than 18 years of age
3.2.2.2 Cognitively or physically unable to participate in interactive interview
3.2.2.3 Patient unable to read in the English or Spanish language
3.2.2.4 Patient does not have a diagnosis of advanced cancer or any other 
progressive/recurrent brain or solid tumor as defined in inclusion criteria. 
3.2.3
Inclusion Criteria FOR PARENTS or GUARDIANS OF AYA PATIENT 
PARTICIPANTS to participate in SURVEY-COMPLETION (RCT phase only)
3.2.3.1 AYA Child of parent or guardian agrees to participate in study.
3.2.3.2 AYA child participant provides verbal assent or verbal consent if 18 or over 
for parent or guardian to complete surveys.
3.2.3.3 One parent per patient parent dyad.
3.2.3.4 Parent/guardian is cognitively and physically able to participate.
3.2.3.5 Parent/guardian is able to speak and read English or Spanish language.
3.2.3.6 Parent/guardian participant has signed informed consent for study 
participation
*Note: Parent survey-completion occurs ONLY in the RCT phase of the protocol 
(not in the run-in phase).  Parent survey completion is not required for AYA 
patient participation. 
**Note: Only one parent may complete surveys. 
3.2.4
Inclusion Criteria FOR PARENTS, CAREGIVERS, GUARDIANS, SPOUSES, 
OR SIGNIFICANT OTHERS to participate in PRISM SESSION 6, “Coming 
Together” (where eligible) (RCT phase & Run in)
3.2.4.1 AYA meets above criteria listed in sections 3.2.1, AND
3.2.4.2 AYA participant randomized to PRISM intervention arm of study in RCT 
phase of study, AND
3.2.4.3 AYA participant provides verbal assent or verbal consent if 18 or over for 
parent, guardian, spouse, and/or significant other to be present during this 
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3.2.4.4 Parent/Caregiver/Spouse/Significant other is cognitively and physically able 
to participate
3.2.4.5 Parent/Caregiver/Spouse/Significant other is able to speak and read in 
English or Spanish
3.2.4.6 Parent/Caregiver/Spouse/Significant other has signed informed consent for 
study participation
3.2.5
Exclusion Criteria for PARENTS or GUARDIANS of AYA PATIENT 
PARTICIPANTS
3.2.5.1 AYA refusal to participate
3.3
Special populations: Please see section 17 for details about special populations including 
adults unable to consent, minors (individuals who are not yet adults), wards of the state, 
pregnant women, and prisoners.
4.0 Study-Wide Number of Subjects
4.1 Number of subjects: 
Run-In PRISM-AC development, feasibility, and acceptability testing: We will enroll up to 
30 AYAs on a “run-in” pilot trial to refine process measures in conducting the newly added 
5th session that is part of PRISM-AC.  This phase of the study will be conducted ONLY at 
Seattle Children’s Hospital.  Briefly, this “run-in” is designed as a cohort study to be 
conducted prior to launching the RCT phase of the study at Seattle Children’s and is 
expected to last approximately 6-12 months.  
Parent/Caregivers/spouses/significant others may participate in PRISM session 6 (family 
meeting called “coming together”) but are otherwise not active study participants in this 
phase of investigation.
RCT phase: The target sample size is N=144 AYA participants (72/arm).  Based on our 
prior work and characteristics of AYAs at participating centers (Table 3), we estimate 
identifying a total of 120 eligible AYAs/12-months (300 over the 30 months of enrollment).  
Assuming a conservative enrollment rate of 65% (versus 78% in phase II RCT), we expect 
to enroll and randomize 78 AYAs/12-months (target enrollment n=195 over the 30-months 
of recruitment).  With a conservative attrition rate of 26% (due to medical complications as 
seen in pilot), we expect complete data collection on 144 AYAs (72/arm).  This sample 
size achieves 80% power to detect an increase of 8.1 in mean Total PedsQL score, the 
main study outcome.  Parent/Caregivers will also be invited to participate in this RCT 
phase of investigation as additional study subjects to complete surveys and participate in 
the PRISM session 6. Parents will complete surveys at the same time points as the AYAs.  
In our prior studies including AYA-parent dyads, >90% of caregivers participated.  Hence, 
we expect complete data from a minimum of 128 caregivers (64/arm). Only one caregiver 
will be invited to complete questionnaires, and will be designated at enrollment.

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This is a 6-year study, including a 6-12 month run in, and a 5-year RCT of PRISM-AC 
compared to usual care among AYAs with advanced cancer or a progressive/recurrent 
tumor and their caregivers (6-mo preparation, 30-mo rolling recruitment, 12-mo follow-up, 
12-mo data analyses and manuscript preparation).  Study-wide, we intend to enroll a total 
of 174 AYAs (30 for run-in and 144 for RCT).  Only SCH-based patients will enroll in the 
run-in.  The RCT will be conducted at a 4 sites: Seattle Children’s Hospital (SCH), Texas 
Children’s Hospital/Baylor College of Medicine (BCM), University of Pittsburgh Medical 
Center Children’s Hospital (UPMC), and Children’s Hospital, Los Angeles (CHLA).  
5.0 Study-Wide Recruitment Methods
All recruitment methods will be conducted and overseen by local sites per local practices.  There are 
no study-wide recruitment methods (e.g., no call centers or national advertisements); however, the 
trial will be listed at clinicaltrials.gov and therefore identifiable by national search engines. Please 
see section 3.1 for more information about recruitment methods and screening. 
6.0 Multi-Site Research
6.1 Enrolling sites. We will recruit consecutive AYAs and their primary caregivers from outpatient 
clinics and inpatient wards at the 4 participating sites (SCH, BCM, UPMC, and CHLA) 
6.2 Coordinating site responsibilities. The Seattle lead CRA will ensure the following:
6.2.1 All required approvals have been obtained at each site (including approval by the 
IRB of record or any other contingencies and rules required by the NIH).
6.2.2 All sites have the most current version of the protocol, consent documents, and 
HIPAA authorization. 
6.2.3 All modifications have been communicated to sites, and approved (including 
approval by the IRB of record and/or any other regulatory requirements) before the 
modification is implemented.
6.2.4 All engaged participating sites will safeguard data as required by local information 
security policies.
6.2.5 All local site investigators conduct the study appropriately.
Table 3. Annual number of AYAs with advanced cancer (12-25 yrs-old) who are eligible, enrolled, 
and evaluable at 3 months for RCT
Site
Total
Eligible
Enrolled
Evaluable
Seattle Children’s
45
35
23
17
Texas Children’s
55
35
21
16
Children’s Hospital, Los Angeles
55
30
21
16
Children’s Hospital, University 
Pittsburgh Medical Center
35
20
13
9
Total/12-months
190
120
78
58
Total for 30-month recruitment period:
195
144

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6.2.6 All non-compliance with the study protocol or applicable requirements will be 
reported in accordance with local policy.
6.3 Study oversight. 
Overall study oversite remains the responsibility of Dr. Abby Rosenberg at the Dana-Farber Cancer 
Institute. Due to her new engagement at Dana-Farber, she will have frequent check-ins with the 
coorninating center, Seattle Children’s, to monitor progress on enrollment, intervention delivery, data 
completion, and protocol adherence. She will also be involved in monthly multisite calls to maintain up 
to date on study progress.
 
Seattle Children’s will remain the coordinating center and maintain the following responsibilities on Dr. 
Rosenberg’s behalf. The SCH lead CRA will have at minimum monthly meetings with each site to 
review and troubleshoot trial conduct and questions, including (but not limited to) regulatory oversight, 
recruitment, data collection, intervention delivery, clinical concerns and/or other concerns.  The lead 
CRA will review current documents and any changes that are upcoming or approved. The lead CRA will 
review any interim results or necessary information the sites should have as well as all study 
procedures, including modifications, updates, study closure, etc. The DFCI lead interventionist 
(Junkins) will have at minimum twice monthly meetings with interventionist(s) to administer re-training 
as needed and review intervention delivery and fidelity. A lead SCH study team member will conduct 
yearly on-site or remote monitoring of participating sites for review of study documents and databases. 
 This will include verification of consent/assent forms, documentation of eligibility, completeness of 
Case Report Forms (CRFs), and regulatory submissions and approval.  
7.0 Study Timelines
Study activities include start-up, conduction and oversight, followed by dissemination of results.  
Projected activities and deliverables are described in Table 4.
Table 4. Anticipated timeline of research activities 
Year 1
Year 2
Year 3
Year 4
Year 5
Year 6
Activities
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Run-In Feasibility and Acceptability 
IRB Protocol Submission
PRISM-AC development
Recruitment
Analysis
RCT Implementation Activities
IRB Protocol Modification
Design of Case Report Forms and RedCap database
Conduct of PRISM RCT for AYAs with cancer
Recruitment
Follow-up
Monitoring and Analyses
Monitoring of PRISM intervention fidelity
Interim data analysis (design, program, and run)
Full data analysis (design, program, and run)
Manuscript submission and dissemination

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8.0 Study Endpoints
8.1.1
Primary Endpoint: 3-month follow-up of last AYA participant including 
patient-reported outcome survey completion. 
8.1.2
Secondary Endpoints:
8.1.2.1 3-month follow-up of last parent participant including parent-reported 
outcome survey completion.  
8.1.2.2 3-month data collection of “palliative care activation” measures, including 
surveys, medical record data extraction. 
8.1.2.3 12-month follow-up of last participant for exploratory cohort.
9.0 Procedures Involved
9.1 Enrollment 
9.1.1 Once consent documents are signed and all questions addressed, the consenting RA or 
study staff will register the patient in the REDCap system. For the RCT (all participating 
sites), randomization will not occur until after baseline Resilience in Pediatric Cancer 
Assessment (RPCA) surveys are collected (see below).  Site RAs will maintain original 
copies of all consent forms when possible.  Consent forms completed electronically will be 
saved and stored on a restricted research drive.
9.2 Randomization (RCT only) 
9.2.1  As a quality control measure, a randomization log will be maintained at SCH to track the 
participant ID, stratum, randomized assignment, and date of randomization.  Patients will be 
randomized only after completion of baseline surveys and in a 1:1 ratio to receive usual, 
non-directive, supportive care without PRISM (“control” arm) or with PRISM (“experimental” 
arm). Randomization will be stratified by age (patients ages 12-17 versus ages 18-25) and 
site. Biostatisticians who will conduct data analysis will be blinded from the treatment group 
allocations.
9.2.2  Throughout the screening period until allocation of the control or PRISM, participants will 
be assigned a screening number, according to the chronological order of screening. Once 
enrolled, the participant will be assigned a study ID. 
9.3  Scheduling of study procedures with participants  
9.3.1 Run in
Upon enrollment, study staff will return to all participants to deliver the baseline RPCA 
survey and create a study calendar outlining survey due-dates and PRISM sessions. Staff 
will query participants about preferred survey completion; all patients will be offered 
electronic surveys in their preferred language. If English, the survey will first be offered by 
email via REDCap or via REDCap on a study team iPad. Spanish instruments will be 
available in paper-pencil form only.  To compare survey data to our prior historical cohort 
studies, surveys in the run-in group will be collected at baseline, week 6 and week 12 

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(Figure 3A). Parent proxy report (as an option in cases where patients cannot fill out 
surveys) will not be offered in the Run-in. 
9.3.2 RCT participants: 
9.3.2.1 Baseline Survey Completion. Upon enrollment, study staff will deliver the baseline 
survey in participant’s preferred language (English or Spanish). The study will first be 
offered by email via REDCap or via REDCap on a study team iPad. Upon request, staff 
will offer paper-pencil versions and/or interview-based versions.
9.3.2.2  Randomization.  Patients will be randomized following completion of baseline 
RPCA surveys.  Staff will aim for the RPCA surveys to be completed immediately 
following enrollment.  Baseline surveys will be collected within the two weeks.  If 
surveys are not completed within this time-frame, staff will return to the participant to 
confirm interest and offer a digital (or, when requested paper-pencil or interview-based) 
survey to be completed. If participants do not complete the survey at that time, they will 
be removed from the study.  For those who do complete the survey, following 
completion, staff at each site will register participants and receive their randomization 
allocation.  They will then return to patients and families to relay this information and 
create a study calendar outlining survey due-dates and, where relevant, PRISM 
sessions. Where relevant, PRISM-sessions will be scheduled approximately every 
other week, beginning within the first week of enrollment following survey completion.
 
9.4 Overview and Session Details of Intervention Arm.  
The original Promoting Resilience in Stress Management (PRISM) intervention consists of four, 
30-50 minute, one-on-one, in-person sessions approximately 1-2 weeks apart, plus a session 
for AYA and caregivers, together (Table 1).  Supplemental materials (e.g., media-links to 
resources, worksheets, text-based reminders, and a digital app to track and practice skills) are 
provided between sessions. The digital app is an interactive platform to practice the same 
PRISM exercises that are taught in the PRISM intervention script. Please note that the app’s 
visual content is “fixed”/does not move. As such, all VISUAL components of the app are 
available in the PRISM App Screenshots document. All AUDIO content of the app is available in 
the PRISM App script appendix. The app is not being evaluated for safety and/or efficacy. Data 

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about the app will not be submitted to or held for inspection by the FDA. All digital data collected 
by the app is de-identified; we cannot connect data to individual users. We only know by 
population how often a given ‘page’ of the application is opened. 
To increase translation and wider application of PRISM in the future, a trained non-clinical 
research associate administers it, as described in previous models and our pilot studies.18,93  
The 1st session occurs within 2 weeks of enrollment.  Other sessions are scheduled around 
patient clinic and/or hospital visits (depending on concurrent illness and medical needs).  
Following the “Coming Together” session, intervention participants will be offered every other 
week “booster” contacts until they reach the 3 month point from enrollment. Although in person 
visits are preferred for all of the PRISM sessions, if a patient explicitly requests or if scheduling 
barriers preclude in-person visits, sessions may be done via phone or other web based 
communication (Zoom, WebEx, or Skype).
Details of the sessions are listed in Table 1.  Briefly, session 1 (“Stress-management”) focuses 
on mindfulness skills including deep breathing and relaxation techniques, and building 
awareness and acceptance of stressors.  Session 2 (“Goal setting”) teaches simple goal-setting 
skills (e.g., identifying realistic, concrete and actionable goals, planning steps towards their 
achievement, preparing for roadblocks and identifying alternative pathways).  Session 3 
(“Cognitive Restructuring”) trains patients to recognize negative emotions and demoralizing self-
talk and helps them develop skills to reframe these in a positive light.  Session 4 (“Benefit 
Finding”) focuses on finding meaning and/or benefit from difficult situations (including cancer).  
For this study and the development of PRISM-AC, we will add a 5th main session focused on 
early advance care planning, using the age-validated and widely used Voicing My Choices: A 
Planning Guide for Adolescents and Young Adults (VMC, see full copy in appendix)74. Briefly, 
VMC was designed in partnership with AYA patients, parents, and Aging with Dignity 
(agingwithdignity.org) to mimic legal advance directives available for older adults.  The 
document has been tested for feasibility and acceptability among AYAs with cancer and other 
life-limiting illness, and is the established standard of care for advance care planning in this age 
group. The instrument is designed to be introduced by trained staff (including research staff and 
non-medical personnel), and completed by AYAs either with such staff present, with family, or 
independently, depending on AYA preferences.  For the purposes of the present study, we 
consulted with VMC creators regarding a recommended approach and ideal VMC content to be 
included in PRISM-AC.  
Because PRISM sessions 1-4 build skills to identify goals and values, VMC is an appropriate 
culmination of skills and offers concrete examples of how to utilize them.  For this reason, 
PRISM-AC will introduce specific VMC pages (see appendix) as examples of how such skills 
might be helpful in cases of advanced cancer and progressive/recurrent tumors, and then offer 
opportunities to practice them in real time. Interventionists will only complete up to four specific 
pages with AYAs: page 4 “My Comfort”, page 5 “My support”, page 8 “My Friends and Family to 
Know”, and page 9 “My Spiritual Thoughts”. If AYAs express a desire to do any of the other 
pages, we will redirect them to their medical team, social work, and/or their parents. Specifically, 
we will introduce the VMC booklet and then highlight the pages and allow participants to choose 
the one(s) that resonate with them “a la carte” (see appendix). Although advance care planning 
includes sensitive topics like end-of-life planning, this booklet was selected specifically because 
they are more generic and applicable to all AYAs with illness.  If an AYA has no specific 
preferences, the interventionist will direct the patient to the page about “my comfort” (VMC page 
4) and complete that page during the session.  

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Introductory scripts were approved by VMC developers and are provided in the Voicing My 
Choices Session appendix document. Following the completion of VMC pages during the 
PRISM-AC session 5, AYAs will keep their booklet and have opportunities to continue exercises 
on their own, with family, with study staff during return visits (see “boosters” below), or with 
medical staff, as appropriate and/or desired. Again, interventionists will only do the four selected 
pages with the AYA and will redirect as appropriate if the AYA wishes to complete other pages. 
Finally, at the close of the fifth session, AYAs will be given a checklist of all the skills and topics 
covered throughout PRISM-AC, including VMC content. Staff will ask what they would like to 
share with their parent(s), spouses, significant others, or guardians during the final session (see 
“coming together” below) such that the interventionists can prepare to facilitate the final session. 
The final session (“Coming together”) allows patients to reflect on the skills they have learned, 
to identify those that resonate and work for them, and to share their thoughts with parents, 
family-members, and loved ones. During this last session, parents, spouses, caregivers, and/or 
significant others are explicitly asked to join and listen to the discussion.  Study personnel will 
review and share with attendees the explicit skills endorsed by patients on the aforementioned 
checklist and encourage shared conversation about how parents/patients can support one 
another. As above, for families where parents prefer Spanish or another non-English language, 
this final session will be conducted with a trained interpreter of the native language of the 
parent. In the phase II RCT, the majority of the PRISM arm opted into the fifth session even 
though it was an optional study procedure in that study (n = 38 out of 40 who completed all four 
PRISM sessions). Because advance care planning requires parent participation and an aim of 
this study is to determine if the additional PRISM session #5 will enable those discussions, we 
have opted to include the coming together as a standard in this and all future projects.  
However, patients may still opt out of the coming together session if they request to do so 
explicitly.  We will continue to follow them and offer an optional booster session with the 
interventionist in lieu of the family meeting in these cases. Additionally, the coming together 
session may not be feasible if parents/caregivers/guardian/spouse/significant others have not 
agreed to be a part of the study. In such cases, we will re-offer participation in real time.  If 
parents/caregivers/guardians/spouses/significant others still decline, then we will skip the family 
meeting.  
Sessions may be combined (maximum 2 modules/session) based on patient preference/ 
research discretion for reasons including (but not limited to): illness severity/progression or 
patient availability.
All of the sessions of the PRISM will be audio-recorded as possible, barring issues with the 
recorder or refusal of the patient to be recorded. Sessions will not be recorded through WebEx, 
Zoom, or Skype platforms. Administrators of PRISM will explain that the sessions will be taped 
and reviewed by the study team with the goal of assessing adherence to the protocol, inclusion 
of required elements, and presence/absence of additional information with the exception of the 
feedback questions. As possible, the PI or supervising team member will review the first 6 
sessions for each interventionist, and score them for fidelity using a standardized tool (see 
appendix). After the first 6 sessions are reviewed for each interventionist, approx. one in every 5 
sessions will be randomly selected to be monitored for fidelity, with feedback and re-training 
regarding adherence to protocol and approach to be refined if needed.    
Participants on the intervention arm will also receive once every other week “booster” contacts 
until they reach the 3 month point from enrollment, for both the run in and the RCT. These will 
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based communication (Zoom, WebEx, or Skype) or by email and will consist of opportunities to 
practice specific skills (at the patient’s discretion).  Study staff will contact patients to coordinate 
such visits and will prompt them by asking: “Would you like to review or practice any of the 
resilience skills?” [If needed, staff will remind patients of all 5 sessions.  If patients are willing, 
study staff will ask,] “Which one?”
Finally, in order to practice skills between sessions, all participants with smart phones assigned 
to the PRISM will be invited to download the PRISM app. This platform is available in both the 
iTunes Store as well as the Google Play Store, however, the content within the app is only 
accessible with a password that will be provided by the PRISM team. App passwords are a 
short code specific to site and group arm (i.e. PRISMAC_SCH_Control) that participants are 
prompted to enter immediately upon opening the PRISM app. The app includes digital content 
of all paper-pencil “cheat sheets” and worksheets (see manual in appendix for paper versions 
and screen-shots of app).  Participants will be given access to both types of materials.  Use of 
the app is optional for study participation. Where relevant (i.e., for participants without a 
smartphone), we will provide iPads to be used in hospital settings.  Note these participants may 
need to establish email account for such purposes if they do not already have one. 
Each site’s interventionist(s) will be responsible for delivering PRISM to their site’s participants 
in the majority of cases. In rare circumstances (e.g., interim coverage for unexpected lapses in 
staffing), trained interventionists from SCH or DFCI may deliver sessions to other sites’ 
participants pending approval from the site’s IRB. In these instances, the site coordinator will be 
responsible for scheduling the session and setting up a videoconference using the site’s own 
HIPAA compliant software (i.e., Zoom, WebEx) for session delivery. Thus, no contact would 
occur between SCH or DFCI interventionists and site participants outside of session delivery. At 
the start of the session, the site coordinator will briefly join the video call in order introduce to the 
patient and SCH or DFCI interventionist using first names only. Any correspondence between 
site coordinators and SCH or DFCI interventionists regarding session scheduling will use study 
ID numbers only. All interventionists will have a Bachelor’s degree or higher and will be trained 
according to Section 21.1.  
9.5  Data collection schedule for study staff.
9.5.1 For the AYA and caregiver survey schedules for both the run in and RCT, please see 
Figures 3A and 3B.Medical record data will be collected at baseline and monthly until the 3-
month mark in both the run in and RCT. Additional medical record abstraction will occur for 
the RCT at 6-, 9, and 12-months. The caregiver to complete the surveys will be designated 
at enrollment.  RA’s at each site will prospectively abstract information from the medical 
record using a study-specific case report form (CRF) adapted from prior studies.94  This will 
include: (1) AYA participation in goals of care conversations: dates of documented 
conversations with medical team regarding prognosis, treatment decisions, and/or goals of 
care, whether or not AYA was present, and if there is documented active AYA participation.  
(2) Benchmarks of Palliative Care Utilization: number and frequency of documented 
psychosocial and palliative care referrals and meetings, hospice referrals, limitation-of-
resuscitation orders, completion of advance care planning documents, and end of life 
details (i.e. location of death, clinical involvement and family support (sibling & financial 
assessments)).  (3)  Clinical covariates: the AYA’s diagnosis, cancer/tumor-directed 
treatments, and intensity in the past month,38 number of and reason for hospital days 

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(anticipated and unanticipated), prescription psychiatric and/or mood altering medications, 
prescription opioids and other pain medications, and number of documented palliative 
care/psychosocial encounters. These variables were selected based on prior evidence that 
child well-being and family psychosocial needs affect immediate psychosocial outcome 
metrics (e.g., psychological distress and quality of life).38,95  
9.6 Resilience in Pediatric Cancer Assessment (RPCA) Survey (all participants, including 
AYAs of run-in cohort):
Patient (and parent)-reported outcomes (PROs) will be measured with the Resilience in 
Pediatric Cancer Assessment (RPCA), a comprehensive survey comprised of age-
appropriate validated instruments (Table 5).  The RPCA was designed with AYA and parent 
stakeholders to capture patient-reported outcomes associated with resilience resources.16 
We have successfully used it in several of our prior studies.16,17,88-90,96 The survey includes 
embedded validated instruments as well as standard demographics (age, sex, and 
race/ethnicity, education, income, number of children in the home).  For the present study, 
we added an ad-hoc checklist querying the number and duration of discussions the family 
has had with health-care, psychosocial, or palliative care teams regarding concepts of 
prognosis, treatment goals, AYA hopes, worries, or concerns, and to what degree AYAs 
were involved in such discussions.
The full RPCA survey will be administered at baseline and week 12 in the RCT. (Figure 3).  
In order to optimize engagement, patients in both arms of the study will be asked to 
complete the abbreviated Resilience in Pediatric Cancer Assessment (aRPCA) during the 
Table 5. Resilience in Pediatric Cancer Assessment (RPCA) Instruments 
Objective
Concept
Instrument(s) 
Source
HRQOL (Primary 
Outcome)
PedsQL Generic Core and Cancer Modules (PedsQL)20,21†‡ 
Anxiety/ Depression
Hospital Anxiety and Depression Scale (HADS)22†‡
Symptom Burden
Memorial Symptom Assessment Scale (MSAS)24†‡
Hope
Hope Scale25†
2-item Connor-Davidson Resilience Scale97
Aim 1 (AYA 
Outcomes)
Resilience
10-item Connor-Davidson Resilience Scale94†
AYAs
Anxiety
Generalize Anxiety Disorder Screener (GAD-7)26
Depression
Patient Health Questionnaire (PHQ-8)27
HRQOL
Medical Outcomes Study Rand Short-Form 3629‡
Aim 2 
(Parent 
Outcomes)
Family Experience
Family Experience Survey (HCAHPS)30
Caregivers
Decision Making Involvement Scale31‡
Survey of Caring for Children with Cancer (SCCC) †‡
 Patient Activation Measure (PAM-13)120 †
Aim 3 
(Activation)
Activation
Benefit Finding121 †
AYAs and 
Caregivers
Demographic 
Questionnaire
Demographic information †
AYAs and 
Caregivers
COVID-19 Impact
The COVID-19 Impact Questionnaire ‡
AYAs and 
Caregivers
Quality of Care 
Checklist 
Quality of Care Checklist †
AYAs
† Included in RPCA for “run-in” 
‡ Included in abbreviated RPCA surveys

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prospective longitudinal follow-up period (months 6, 9, and 12).  The aRPCA will assess 
only selected outcomes (patient outcomes of HRQOL & symptoms, parent outcomes of 
HRQOL, and family activation variables), as described below.  For those on the non-
intervention arm of the study, staff will schedule a “study check-in” visit to coordinate the 
aRPCA completion and thank families for their continued participation.
In both arms of the study, if any participant declines to complete the full RPCA survey 
and/or if participants or family members report participants are unable to complete the 
survey due to illness complications, staff will offer in the following order: (a) an in-person 
(English-speaking, interview based) survey session, and (b) abbreviated versions of the 
questionnaire for patients to complete.  Only at follow-up timepoints and in cases where 
participants are too ill to provide self report in writing or interviews, staff will offer 
abbreviated versions of the survey for parents to complete as proxy respondents.  These 
options will be offered in an effort to collect full data for primary endpoint assessment, 
including the aRPCA or even a survey containing only the primary outcome of HRQOL.   
Participants in both arms of the study will be scheduled for their surveys at the time of 
enrollment and then reminded prior to each survey due-date.  Participants will be contacted 
by phone, email or mail to receive their RPCA survey. If we have not received a response 
within a day of initial contact, participants will receive up to 4 follow-up phone calls, texts, 
and/or emails (approximately once weekly) within a 28 day window before and after surveys 
are due.  Participants will remain eligible for subsequent survey completion and follow-up 
even if surveys are missing and the same procedures will be conducted for each survey 
due-date until the 12-month follow-up point.  
9.6.1 RPCA item details
9.6.1.1 AYA Version (not included in parent surveys):
9.6.1.1.1 Pediatric Quality of Life (PedsQL) Generic and Cancer Module Teen 
Reports. The PedsQL 4.0 Generic and 3.0 Cancer Module include 50 items 
evaluating HRQOL of AYAs with cancer.  Queries assess physical, emotional, 
social, and school well-being, plus cancer-related pain and hurt, nausea, 
procedural anxiety, treatment anxiety, worry, cognitive problems, perceived 
physical appearance, and communication.  Scales are available for teens and 
young adults,20,21 and have been used successfully with low rates of refusal and 
minimal missing data.98 Items are rated on a 5-point Likert scale and total scores 
transformed to a 0-100 scale with higher scores representing better HRQOL. 
Internal consistency ranges from 0.75 to 0.92.21  These instruments are included 
in all surveys, including the full surveys for the run-in Cohort and RCT, and the 
abbreviated survey for the RCT.
9.6.1.1.2 Hospital Anxiety and Depression Scale (HADS).  The HADS assesses 
mixed affective symptoms in patients with serious illness.22  It has been validated 
in AYAs with chronic illness99 as well as AYA cancer survivors.100  The scale has 
excellent reliability (α=0.83-0.82).22  It consists of 7 questions for anxiety and 7 for 
depression.  Each is scored from 0-3, for a total range of 0-21 points per 
subscale.  “Caseness” of anxiety and depression is defined as ≥8 points, with 
sensitivity/specificity of 0.8/0.9 for anxiety and 0.8/0.8 for depression.22  This 

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instrument will be included only in PARTICIPANT surveys.  It will be included in 
both full and abbreviated surveys (RPCA and aRPCA) in order to optimize 
primary outcome data collection in the event of illness complications or death.  
9.6.1.1.3 Memorial Symptom Assessment Scale (MSAS). The MSAS measures the 
presence, severity, frequency, and extent of bother from symptoms with high 
consistency (α>0.8).23,24  For the run-in, we will use the Pediatric-validated MSAS 
instrument (32-items) and for the RCT, we will use a version of the MSAS that has 
been previously developed for and used among children with advanced cancer 
(26-items Likert scales assess physical (pain, fatigue, drowsiness, nausea, 
anorexia, cough, diarrhea, vomiting, itching, skin issues, constipation, dysphagia, 
dry mouth, numbness, sweating, dyspnea, and dysuria), and psychological 
(irritability, sleep disturbance, nervousness, sadness, worrying, difficulty 
concentrating, and image issues) symptoms.  Total- and sub-scores are 
calculated as an average, with higher scores representing higher symptom 
burden.  This instrument is included in all surveys, including the full surveys for 
the run-in Cohort and RCT, and the abbreviated survey for the RCT
9.6.1.1.4 Hope Scale. The Snyder “Hope” Scale contains 8 hope items plus 4 “filler” 
questions, and measures “the overall perception that one’s goals can be met.”25  
The instrument was named based on patterns of hopeful thought and assesses 
patient-reported efficacy by assessing  the ability to generate a route to one’s 
goals (termed “pathway” thoughts) and the ability to initiate and maintain the 
actions necessary to reach a goal (termed “agency” thoughts).  Prior studies 
performed among AYA cancer patients have shown that high-hope individuals 
have improved psychosocial outcomes.  The instrument has been validated in 
both adult and pediatric settings and is scored on an 8-point Likert scale.  Higher 
scores imply greater levels of hopeful thought patterns.  Cronbach’s alphas for the 
whole scale range from .74 to 0.84. This instrument is included in the full (not 
abbreviated) surveys for both the run-in cohort and the RCT.
9.6.1.1.5 Connor-Davidson Resilience Scale. The Connor-Davidson Resilience 
Scale is a reliable and widely used instrument to measure inherent 
resiliency.97  Questions revolve around personal problem-solving and 
approaches to adversity.  The 10-item instrument has high internal 
consistency (Cronbach’s alpha = 0.85), and has been used in diverse 
populations including adolescents, parents and cancer patients.97,101  
Correlative studies have evaluated the scale with other psychosocial 
measures such as psychological distress,102 PTSD,103 and social 
support.104  It also has been used in pharmacologic and other intervention 
studies to model modifiable outcomes  Each item consists of a 5-point 
Likert scale (scored from zero to four) for total of 40 points.  The mean 
score among well US adults is 31.8, with higher scores reflecting greater 
resilience.  This instrument is included in the full (not abbreviated) surveys 
for both the run-in cohort and the RCT.
9.6.1.1.6 Patient Activation Measure. The 13-item PAM includes 3 domains to 
measure AYA or parent knowledge, confidence, and willingness to act regarding 
the AYA’s health.39,105,106  It is well-validated among chronically ill and healthy 

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adult populations, and studied among AYAs and parents of children with 
cancer.106 Both patient and parent versions have acceptable internal consistency 
and reliability (α=0.86 and 0.85, respectively).  Items are scored on a 4 point 
Likert scale; responses are summed and transformed to 0-100.107  Higher scores 
suggest higher activation and thresholds distinguish 4 categories: (1) staying the 
course; (2) taking action; (3) confidence and knowledge to take action; and (4) 
believes active role important. This survey is only included in the run in.39
9.6.1.1.7 Benefit/Burden Scale for Children: The Benefit/Burden Scale for Children 
(BBSC) was adapted by pediatric psychosocial clinicians from the Benefit Finding 
Scale for Children.108 BBSC measures benefit finding, illness-perceived burdens 
and psychological functioning in children. Factor analysis revealed a two-factor 
solution and each subscale had strong internal validity; benefit finding (α = .852; 
10 items) and illness-related burden (α = .804; 10 items). All items are answered 
on a 5-point Likert scale ranging from “not at all” to “very much.” This survey is 
only included in the run in.
9.6.1.1.8 Quality of Care. The run in will include a check list asking AYAs about quality 
of care from their care team. 
9.6.1.2 Parent version (not included in AYA surveys)
9.6.1.2.1 Generalized Anxiety Disorder Screener (GAD-7). This 7-item survey is 
commonly used to identify cases of generalized anxiety disorder and to assess 
symptom severity.26,109  Participants are asked how often during the last two 
weeks they have been bothered by each of the 7 core symptoms of generalized 
anxiety disorder. Response options include “not at all,” “several days.” “more than 
have the days,” and “nearly every day,” scored as 0, 1, 2, and 3, respectively. 
Therefore, GAD-7 score range from 0 to 21, with scores of ≥5, ≥10, and ≥15 
representing mild, moderate, and severe anxiety symptoms levels, respectively. 
Internal consistency was acceptable (α=0.89). Inter-correlations ranged from r = 
0.45 to r = 0.65.This instrument is included in the full (not abbreviated) surveys for 
the RCT.
9.6.1.2.2 Patient Health Questionnaire (PHQ-8). This 8-item survey is widely used 
among general populations, patients with chronic illness, and in parents of 
children with cancer.27,28,110-113  It is identical to the also widely used PHQ-9, with 
the exception that PHQ-8 deletes a question about suicidal ideation.  Research 
indicates that the deletion of this question has a minimal effect because self-harm 
thoughts are relatively rare and this item is the least commonly endorsed item on 
the 9-item survey.  Furthermore, the original validation studies of the two 
instruments demonstrate similar psychometrics and identical thresholds for 
depression severity.  The instruments have excellent psychometric properties 
(α=0.86-0.89).  Each item is scored on a 4-point Likert scale and the sum (0- 27) 
indicates the degree of depression, with scores of ≥5, ≥10, and ≥15 representing 
mild, moderate, and severe depression.  Scores correlate with functional status 
and are sensitive to behavioral interventions.113,114  This instrument is included in 
the full (not abbreviated) surveys for the RCT.

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9.6.1.2.3 Medical Outcomes Study Rand 36-item Health Survey (SF-36). The SF-36 
is the most widely used generic measure of HRQOL among U.S. Adults.115  It 
incorporates 8 concepts: physical functioning, body pain, limitations due to 
physical health problems, role limitations due to personal or emotional problems 
as well as emotional well-being and social functioning, energy, fatigue and 
general health perceptions.  It includes a single item regarding perceived change 
in health.29  Internal reliability ranges from α=0.78-0.93.  This instrument is 
included in both the full and abbreviated surveys for the RCT.
9.6.1.2.4 Hospital Consumer Assessment of Healthcare Providers and Systems 
(HCAHPS). This survey is a widely used and standardized tool to measure patient 
and family perspectives on hospital care.30  It has been endorsed by the National 
Quality Forum (NQF) in order to allow for cross-hospital comparisons.   The 
survey includes a core set of questions that can also be combined with 
customized project- or site-specific items.   For this study, we have included 
domains regarding care for teenaged patients, communication and child-centered 
care, and overall hospital ratings.  All items are scored on a Likert Scale (for 
example, to the question “During this hospital stay, how often did providers 
involve your child in discussions about his or her health care?” response options 
include “Never,” “Sometimes,” “Usually,” and “Always.”    This instrument is 
included in the full (not abbreviated) surveys for the RCT.
9.6.1.3 Both AYAs and Parents 
9.6.1.3.1 The Decision-Making Involvement Scale (DMIS). The 30-item DMIS was 
developed to assess child and adolescent involvement in decisions having to do 
with illness management.31  Specifically, items assess child- and parent-behaviors 
that reflect the way children are involved in decisions, regardless of who ultimately 
makes the decision.  Both AYAs and parents are asked to reflect on an important 
conversation from the past month and then respond to items based on a 4-point 
Likert Scale.  Although there is a potential total score, instrument authors suggest 
scoring based on subscales assessing specific dimensions of involvement, 
including “child seek,” “child express,” “parent seek,” “parent express,” and 
“joint/options.”  Range of scores for each subscale = 0-4 and Cronbach’s alpha = 
0.68-0.71.    This instrument is included in full and abbreviated surveys for the 
RCT.
9.6.1.3.2 The Survey about Caring for Children with Cancer (SCCC).  This 
questionnaire was developed from literature and focus groups of parents and 
medical providers to identify key domains relevant to caring for children with 
advanced cancer. Items were adapted from existing validated surveys116 and 
evidence-based guidelines.117  The survey has been extensively tested for 
content, wording, response burden, and cognitive validity.118 It has been used in 
multiple pediatric palliative care clinical trials, with several key analyses 
conducted by the PI.82,119,120   For this study, we included select items to assess 
parent-/patient- perceptions of prognosis, treatment goals, ability to express 
hopes and worries, as well as questions assessing satisfaction with overall care, 
and an ad-hoc checklist querying the number and duration of discussions the 
family has with health-care, psychosocial, or palliative care teams regarding 
prognosis, treatment goals, AYA hopes and worries, and to what degree AYAs 

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were involved in such discussions.75,121 This instrument is included in full and 
abbreviated surveys for the RCT and the run-in.
9.6.1.3.3 The COVID-19 Impact Questionnaire. (COVID-IQ)This 7-item, self-report 
questionnaire was developed for this study to assess perceived impact of the 
COVID-19 pandemic on AYAs and parents. Items assess worry/anxiety related to 
COVID-19, life events as a result of COVID-19 (e.g., loss of job, missed school), 
lifestyle changes (e.g., social distancing), and known COVID-19 
symptoms/diagnoses/treatments of self and family members. Respondents are 
invited to provide free text responses for two additional items: 1) “What is helping 
you through the COVID-19 pandemic” and 2) “Please tell us about other effects of 
COVID-19 on yourself, your child(ren) and/or your family, both negative and/or 
positive.” Lastly, respondents are asked to rate the extent to which their 
responses to other survey questionnaires were impacted by the COVID-19 
pandemic.  
9.7 Optional Heart Rate Variability Procedures
9.7.1 Data Collection 
HRV will be measured using the Actiheart 5 external device (CamnTech, Inc, UKFDA class 
2, 510(k) number K052489). The Actiheart 5 is an FDA-approved, lightweight, wireless 
electrocardiogram (ECG) monitor that attaches to a patient’s torso via two standard ECG 
electrodes. Patients who consent to the optional HRV measurement portion of the study will 
be given their Actiheart monitor at enrollment.  A study CRA or investigator will place the 
monitor on the patient and ensure adequate ECG signal acquisition, or a study CRA will 
instruct the patient on placing the monitor themselves.  The patients will wear the monitor 
for a 24h period, and then return the device to a study team member.  The devices will be 
collected at the next planned clinic appointment if outpatient, or the next day if inpatient. 
The HRV monitoring would not be expected to affect the subject’s usual clinical care.  
Subjects could undergo lab draws, clinic visits, receive chemotherapy, and maintain their 
usual level of activity without interference from the HRV monitor.  If a subject needed to 
undergo emergent imaging of the chest (where the HRV device may obstruct some of the 
visual field), or an emergent surgical procedure while wearing the monitor, it would simply 
be removed.  The study team would otherwise coordinate HRV monitor placement so that it 
does not overlap with planned chest imaging or surgical procedures. If a subject need to 
remove the monitor for any reason, we would not expect the subject to replace and wear 
the monitor again during that 24-hour recording period.  
9.7.2 Data Collection Schedule
HRV data will be collected at clinically relevant and study specific time intervals where 
possible (Table 6).  When not possible, HRV data collection will be scheduled at the 
patient’s convenience.

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10.0 Data and Specimen Banking
10.1 Data Storage and Confidentiality  
De-identified data (including medical record, RPCA survey data, and transcripts of recorded 
sessions and/or interviews) will be stored indefinitely within a database saved on a password 
protected server at Seattle Children’s Research Institute. Upon completion of data collection, 
SCH will transfer the limited dataset to DFCI per the Data Transfer Agreement.  Original surveys 
will be saved at SCH for 10 years or until final analyses are completed, whichever occurs last, in 
order to ensure data quality.  Only study staff with human subjects training will have access to 
the data, subject to approval by the SCH site PI, Dr. Yi-Frazier. De-identified study data will be 
banked indefinitely for future use by the group of investigators conducting the study and access 
will be controlled by the PI’s. PIs will verify that additional analyses have IRB approval. No data 
will be withdrawn from the study database. Results of initial analyses will be shared with 
participants if participants request on the consent form that they would like a summary of study 
results. 
10.2 Data and/or Sample Sharing
Data will not be shared outside the group of investigators conducting the study but will be fully 
shared during and after the study with investigators in the group.  When other investigators are 
interested in new analyses, the PIs will verify they have IRB approval to conduct additional 
analyses. De-identified study data will be banked indefinitely for future use by the group of 
investigators conducting the study and access will be controlled by the PI’s.  Future studies will 
formally test the intervention once its feasibility is confirmed.  Should the intervention be 
effective, it will be made publicly available for use by the broader medical communities caring 
for AYAs with serious illness.
11.0 Data Analysis/Management
11.1 Run-In Cohort: Data will be analyzed descriptively, including demographic and clinical 
characteristics of participants (i.e., age, sex, cancer or tumor-type, time since diagnosis, number 
of days in hospital during PRISM study).  Eligible AYAs who decline to participate will be asked 
to provide a reason for declining the study and the above characteristics will be obtained from 
the medical record; such that we can compare participants and non-participants to determine 
biases in enrollment preferences. 
11.2 “Feasibility” will be defined as: (1) at least 70% enrollment of approached and eligible 
patients; and (2) at least 70% completion of the 5 main PRISM sessions (not including “Coming 
Table 6. HRV data collection schedule
Time Point
T1
(Baseline)
T2
(PRISM session 
#1)
T3
1 month 
(survey timepoint)
T4
3 months 
(survey timepoint)
T5
6 months 
(survey timepoint)
Where?
In clinic/at home 
OR inpatient
In clinic/at home 
OR inpatient
In clinic/at home 
OR inpatient
In clinic/at home 
OR inpatient
In clinic/at home 
OR inpatient
How long?
24 hours
24 hours
24 hours
24 hours
24 hours

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Together,” as we have done for prior feasibility determinations) among enrolled patients.  
“Acceptability” will be assessed qualitatively, as we have done in all prior pilot studies of 
PRISM’s development.  Briefly, prior to each session (beginning with session #2), 
interventionists will solicit feedback regarding the usage and utility of the prior learned skill(s).  
Following the final session, we will solicit more detailed feedback regarding timing and value of 
the intervention and its content (see PRISM manual and Voicing My Choices session in 
appendices).  Because the additional session involving early advance care planning is new for 
this study, we have designed additional pointed questions to gather user feedback about these 
exercises, including their perceived value, format preferences, timing, and if/how the session 
compares to the other skills (See Voicing My Choices appendix document).   Finally, baseline 
and follow-up RPCA scores will be determined and these data will be entered into the secure 
database.  For this pilot study, we will describe pre-and post-intervention scores and score 
changes for each instrument, with effect sizes calculated accordingly.    
11.3 Randomized Controlled Trial (RCT): The primary statistical analyses will be intention-to-
treat to avoid confounding by non-random participant attrition.  Demographics, clinical 
characteristics, and items within the RPCA will all be summarized at each time-point using 
descriptive statistics: frequencies and proportions for categorical variables, means and standard 
deviations for continuous variables, or median and interquartile range if distribution is skewed.  
All analyses will be adjusted for patient age and site, as randomization is stratified by age and 
site, as well as baseline characteristics clearly imbalanced between groups.  Additional baseline 
characteristics we consider as potential confounders include sex, race, and primary language 
spoken at home.
11.3.1 Sample Size Determination and Power
11.3.1.1 Our focus for sample size estimation is the primary outcome: AYA PedsQL 
generic core scores at 3-month observation. Sample size is based on published data 
from the pediatric advanced cancer population, where baseline scores were normally 
distributed with mean 70.9 and standard deviation 17.2.122 Assuming 26% attrition, we 
will randomize 195 AYAs (98 per arm) to obtain an evaluable sample size of 144 AYA 
participants (72 per arm).  This sample size achieves 80% power to detect an 8.1 
point difference in the mean 3-month total PedsQL score (Table 6). 
11.3.1.2 Power calculations for select secondary AYA outcomes are listed in Table 6.
11.3.1.3 Parent Reported Outcomes: Assuming >90% caregiver participation (as in 
our prior studies), we anticipate a minimum sample size of 128 caregivers (64 per 
arm).  This caregiver sample size achieves ≥80% power to detect reasonable effects 
for parent outcomes, based on standard deviations and other parameters from our 
preliminary data and published literature (Table 7).

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11.4 Randomization
11.4.1 The randomization algorithm will be constructed by the study statistician using a 
permuted blocks scheme with varying block sizes; only the statistician will be aware 
of the block sizes until completion of the study. A statistician independent of the 
study will prepare the final randomization list, which will be administered by a 
clinical research associate independent of the study using the SCH/UW REDCap.   
Randomization will be stratified by age (patients ages 12-17 versus ages 18-25) 
and site. 
11.5 Analysis Plan
11.5.1 Overview. The primary statistical analyses will be intention-to-treat to avoid 
confounding by non-random participant attrition.  Demographics, clinical 
characteristics, and items within the RPCA will be summarized at each time-point 
using descriptive statistics: frequencies and proportions for categorical variables, 
means and standard deviations for continuous variables, or median and 
interquartile range if the distribution is markedly skewed.  All analyses will be 
adjusted for site and patient age, as randomization is stratified by these 2 
variables, as well as baseline characteristics clearly imbalanced between groups.
11.5.2 Primary Outcome. Our primary outcome is AYA reported HRQOL at 12 weeks.  
Because the amount of change depends strongly on the initial HRQOL at baseline 
we will control for baseline HRQOL as a covariate in the regression. Regression 
models will be used to estimate mean-level differences and 95% confidence 
Table 7. Detectable Differences in selected Mean Instrument Scores Between Groups Given 80% Power and 5% 
Type I Error Rate
Aim
Sample (N)
Outcome (Instrument)
Sample Mean 
(SD)
Source
MCID*
DD (SD)
Quality of Life – General 
(PedsQL 4.0)
70.9 (17.2)
Published 
Data122 
4.4
8.1 (17.2) 
AYA Quality of Life – 
Cancer (PedsQL 3.0 
Cancer)
65.3 (16.3)
Phase II RCT
(not published)
7.7 (16.3)
Anxiety (HADS-A)
5.9 (3.4)
Phase II RCT
1.3-1.8
1.6 (3.4)
Depression (HADS-D)
5.2 (3.6)
Phase II RCT
1.5
1.7 (3.6)
1
AYAs (144)
AYA Hope (Hope Scale)
Mean 50 (8.3)
Phase II RCT
(not published)
3.9 (8.3)
Anxiety (GAD-7)
2.95 (3.4)
Published 
Data26
(not published)
1.7 (3.4)
Depression (PHQ-8)
3.3 (3.7)
Published 
Data123
5
1.8 (3.7)
HRQOL-physical (SF-36 
PCS)
50.3 (6.9)
Published 
Data124
3-5
3.4 (6.9)
2
Parents 
(128)
HRQOL-mental (SF-36 
MCS)
42.9 (11.9)
Published 
Data124 
3-5
5.9 (11.9)
Legend: MCID: Minimal Clinically Important Difference (*reported when published); DD: Detectable Difference in Mean

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intervals comparing scores in the PRISM intervention to those in usual care. The 
mean total PedsQL generic core score will be the outcome, and the PRISM 
intervention the predictor, of interest. A generalization of the two-sample t-test 
based on a contrast of the regression model will examine if there is an increase in 
PedsQL scores from baseline for PRISM versus usual care at the primary time 
point of interest, 3 months following enrollment. The same analysis will be 
undertaken for the domain subscales of PedsQL (physical and psychosocial), the 
cancer-specific module, and secondary outcomes included in AYA surveys. 
Subgroup analyses will explore whether the effect of the intervention is modified by 
medical covariates, symptom distress, and/or concurrent parent distress. 
Response type (survey, interview, or parent proxy) will be included in sensitivity 
analyses and data reported separately if indicated.  The rationale for these 
subgroup analyses is grounded in prior findings suggesting symptoms and parent 
wellbeing are associated with patient HRQOL.83,122
11.5.3 Secondary Outcomes
11.5.3.1 The goal for parent outcomes is to evaluate the effect of the intervention 
on parent psychological distress and HRQOL.  Mean total scores from 
each parent instrument at 12 weeks will be the secondary outcomes of 
interest.  We will model distress and HRQOL separately and follow a 
similar approach to the analyses for continuous outcome measures in 
Aim 1.  As sex and baseline patient HRQOL may be predictors of these 
outcomes,78,125 each will be included if imbalanced between arms.
11.5.3.2 To compare patient and caregiver activation, we will measure patterns in 
multiple domains: AYA- and parent-reported Decision-Making 
Involvement Scores, AYA participation in goals of care conversations, 
and formal palliative care service utilization including documented 
referrals for hospice and charted decisions to limit resuscitative efforts.  
For all outcomes, results between trial groups will be compared using 
analysis of variance with trial group as the factor of interest. We will 
explore whether change in activation scores are correlated within families 
and/or modified by parent/child characteristics (sex, psychological 
distress scores, cancer/tumor-type, among others) using ordinal logistic 
regression models with cumulative logits, where change activation level is 
categorized as negative, null, or positive.  
11.5.3.3 Exploratory analyses will evaluate prospective and longitudinal survey 
and clinical data beyond month 3 (primary endpoint) at months 6, 9, and 12 
of the study.  Comparisons between groups will still use an intention to treat 
approach as described above.  Additionally, we will explore the relationship 
between biomedical variables and patient reported anxiety and depression 
through a combination of paired and unpaired t-tests, chi-squared (or 
Fisher’s exact) tests, and linear and logistics regression. HRV will be 
measured in 24-hour increments using both time and frequency domain 
parameters as established by the international Cardiology task force 

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guidelines.126 Means and standard deviations will be compared to published 
normative data in adolescents.46  
11.5.3.4 Additional analyses will include process evaluations that include: (a) 
intervention fidelity; (b) satisfaction queries; and (c) mediation analyses to 
evaluate relationships between PRISM, family activation, and outcomes.  
For example, the intervention effect on parent outcomes may be 
mediated by parent activation.  If we find a positive intervention effect on 
parent psychological distress, we will explore activation mediation using 
the counterfactual framework with indirect mediation effects computed 
through G-estimation and incorporating confounders of the mediator-
outcome association.127  Finally, we will conduct a planned interim 
analysis for data-safety monitoring purposes when half of AYA 
participants have reached the primary endpoint (see Human Subjects). 
11.5.3.5 Multiple comparisons. Multiple comparisons are a concern since we are 
collecting multiple measures from both patients and caregivers and are 
interested in several hypotheses.  We minimize this problem by specifying 
a limited number of main hypotheses for each aim.   False Discovery 
Rate criterion will be used to correct for multiple testing in analyses that 
are not pre-specified. Likewise, in manuscripts and presentations, we will 
report the number of tests performed and interpret results within this 
context.  
11.5.3.6 Considerations regarding missing data.  Effective data collection at 
scheduled times will be monitored and attrition minimized as described 
below. While our goal will be to minimize missing data, data may still be 
missing due to patients/families skipping individual items, omissions in 
medical records, lack of follow-up, medical complications, or death.  We 
will quantify the amount of missing data, evaluate the association of 
participant characteristics with missing data, and minimize bias and 
increase efficiency in the associations of interest by applying appropriate 
methods to account for missing data.128-130  For example, where missing at 
random (MAR) is a plausible assumption, we will use multiple imputation 
or inverse probability weighting, depending on the statistical model being 
considered. For missing not at random (MNAR), we will use sensitivity 
analyses.  In all cases, we will assess the robustness of estimates due to 
assumptions.
12.0 Confidentiality 
12.1 Data Storage. All information collected for research purposes will be de-identified.  
Identifying information (names, addresses and phone numbers) will be used initially only to 
identify potential patients to approach.   The only link between the participant identifiers and 
their study identifier will be kept on a password protected database and in a locked filing 
cabinet. There are no patient identifiers collected and retained for research purposes. 
Feasibility data will represent only frequencies and percentages.  

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12.2 Patient Identifiers within stored data.  No participant identifiers will be kept with or 
included in the study data.  All identifying patient information will be stored on a secure 
database, or in a locked filing cabinet with the study team.  This data will be stored and 
maintained for a minimum of ten years or until final analyses are completed, whichever 
occurs last, in order to ensure data quality. 
12.3 Study-wide data management.  Individual sites will be responsible for original source data 
(surveys, Case Report Forms) until study completion.  All such materials will be stored in a 
locked file cabinet or other office with access only to study staff.  Upon study completion (last 
data collection for last patient), all materials will be de-identified (labeled only with study ID) 
and faxed or scanned to the coordinating center for electronic storage.  As described above, 
monthly site data collection responsibilities will include monitoring of local data completeness 
and troubleshooting with the coordinating center for data completion, if necessary. Per the 
Data Transfer Agreement, a Limited Data Set will be transmitted by Seattle Children’s 
research staff to external collaborators using a secure, institutionally approved method. Any 
data provided from SCH to Dr. Rosenberg and DFCI for oversight purposes during active 
data completion will also be limited.
When Zoom is used, the following actions will be taken to protect confidentiality and privacy:
1.
The latest version of Zoom that is available will be used.
2.
The meeting room will be set to private.
3.
A password/passcode will be required for meeting entry.
4.
The private chat function will be disabled.
5.   The General chat function will be used. Examples of General chat use may include 
sharing approved resources and PRISM app passwords (as described in Section 
9.4), communicating if there are technical difficulties, and the accommodation of 
specific needs by participant’s request (e.g. if a patient has a medical reason that 
may impact verbal communication). 
13.0 Provisions to Monitor the Data to Ensure the Safety of Subjects
13.1 Data collection 
Data collection will occur at each of the 4 enrolling study sites: SCH, BCM, UPMC, and 
CHLA. Data collection will consist of self-report questionnaires and electronic ECG 
recordings from HRV monitors. Research material collected will be in the form of data from 
standardized questionnaires, digital ECG files, and also from medical record information 
extracted from the patient’s electronic medical record. Protected health information (PHI) is 
accessible only by site PIs and key study personnel.
13.2 Data Management
Research material collected will be in the form of data from the standardized questionnaires, 
digital ECG files and medical record information. Protected health information (PHI) is 
accessible only by the site PIs and key study personnel, and the on-site monitoring from the 
coordinating site (SCH). A variety of measures will be utilized to ensure participant privacy. 
Minimal paper records, such as consent forms, will be kept in a locked drawer in the site PIs’ 
research offices. No identifiable patient information will be labeled on the surveys or ECG 

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files; all will be identified with a study-specific identifier with assigned identifier kept on a 
password protected encrypted server. Data will be stored in an electronic database (REDCap 
-Research Electronic Data Capture) using the participant’s study identifier. REDCap data 
collection projects rely on a thorough study-specific data dictionary defined as an iterative 
self-documenting process by all members of the research team. We have conducted the 
iterative development and testing process previously, resulting in well-planned data 
collection. REDCap servers are housed in a data center and all web-based information 
transmission is encrypted. REDCap was developed specifically around HIPAA-Security 
guidelines and is recommended to researchers at various institutions by both Privacy Officers 
and Institutional Review Boards. REDCap has been disseminated for use locally and at other 
institutions and currently supports over 300 academic/non-profit consortium partners on six 
continents and over 20,000 research end-users (www.project-redcap.org). The REDCap data 
record may contain some identifying information. Subjects will be tracked using their study 
identifier. The identifiable data will be designated as “PHI” in the REDCap database which 
will allow us to exclude access to the identifiable information as necessary.
13.3 Survey Data
The study questionnaire (“Resilience in Pediatric Cancer Assessment”, RPCA) and the 
intervention (“Promoting Resilience in Stress Management”, PRISM) may address sensitive 
matters. Participants may be prompted to think about the threat to their life posed by their 
cancer/tumor, as well as other difficult topics such as psychological distress, grief, 
bereavement, and health behaviors. The topics to be covered may provoke sadness, anxiety, 
depression, fear or doubt. 
While surveys will be coded to protect anonymity and do not include instruments to directly 
measure suicidal ideation or other self-harming behaviors, they will be reviewed within 72 
hours by the site study team for (a) missingness (see 13.4.1 below); and (b) unanticipated 
immediate threats to participants’ or others’ safety. As part of their informed consent process, 
participants will be made aware of the survey-review timeline as well as the fact that 
confidentiality may be broken in the case that providers see an immediate threat to the 
patient’s or another’s safety. No physical risks are expected to arise from the study.
If indicated, referral for consultation will include a direct phone call (or in-person consultation) 
by PI or research team member to recommend further help. This would include alerting: a) 
current therapist (if they have one), and b) their oncology social worker. The participant will 
also be given the phone number to the Seattle Children’s, Baylor College of Medicine, or 
Children’s Hospital of Los Angeles outpatient psychiatric clinic. County-specific crisis line 
phone numbers will also be provided as needed. 
In the event of other concerns from interventionists and/or other study staff based on 
interactions with AYAs and families, as well as in other cases of concern for patient or others’ 
safety, the same processes will occur, including immediate referrals to the site PI, and the 
patients’ primary medical and social work teams for in-person evaluation or referral to the 
appropriate mental health professional if warranted. After hours, the site PI and on-call 
providers from the medical teams will be notified.  All study-related concerns for patient or 
other person’s safety will be reported as an adverse event (AE) to the IRB and Data Safety 
Monitoring Committee (DSMC, see “Data Safety Monitoring Plan”), within 1 week of study 
staff awareness.  In addition, the PI will review the potential risks and reported findings at least 
once monthly with study staff from all participating sites.  While this is not a pharmacologic 

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trial and we do not anticipate medical complications, sites will nevertheless notify the IRB and 
DSMC of all participant deaths at the time of study renewal (annually).  Unanticipated (non-
medical) participant deaths will be reported to the DSMC within 1 week with a determination if 
the event might be attributable to the study.  In such cases, the DSMC chair may convene the 
committee and/or suspend the study for additional review (see section 13.5 below).  
13.4 Heart Rate Variability Data
Following a 24-hour recording, a study team member will collect the Actiheart monitor from the 
patient (either in clinic or while in the hospital).  De-identified data from the device will be 
uploaded into the Actiheart software (CamnTech, Inc), which will be installed on one computer 
located in the locked office of the study PI.  Data will then be transferred to the above 
mentioned encrypted RedCap database.
13.5  Data Collection Procedures/ Internal Site Monitoring plan
The coordinating center will be responsible for systematic data collection, quality control, and 
data-management procedures including: (1) oversight of ongoing data collection; (2) rigorous 
training and ongoing monitoring of adherence to protocols; (3) regular review of questionnaire 
response rates and missing items to identify and correct problems; (4) verification of all data 
through computerized data entry systems restricting invalid/out-of-range responses; (5) at 
minimum monthly meetings and progress reports to provide feedback to study staff 
concerning difficulties and follow-up to ensure problems are resolved quickly; and, (6) yearly 
on-site monitoring of participating sites
13.5.1 Survey data. To optimize collection, all participant surveys will be available by paper 
or online via the REDCap system, a secure HIPAA-compliant, high-quality data 
collection tool. Surveys may also be completed in person with a study team member. 
The rationale for offering both paper-pencil and electronic versions is based on our 
prior experience where participants preferred the former,90 which in turn facilitated 
more complete data collection.  To ensure primary outcome data, we will offer an 
interview and/or abbreviated survey with only the PedsQL for those who do not 
complete all assessments or who request to drop out or who are too ill to complete 
the entire survey. To ensure data quality, a RA will review RPCA surveys within 72 
hours of their completion for missing fields and call participants sites to clarify and 
query/complete individual missing items verbally. 
13.5.2 Medical record data. RA’s will collect and upload CRF data monthly for both the run 
in and RCT 3 months post baseline. CRF data will also be collected at 6-, 9-, and 12-
monthsfor the RCT only. To ensure reliability and validity of abstracted medical 
record data, we will use our current methods for training and quality, including guided 
practice abstraction and independent abstraction with reconciliation by a trainer.  A 
10% random sample will be dual abstracted.  A RA assignment will monitor and 
reconcile case report forms with RedCap data once monthly.
13.5.3 Heart Rate Variability Monitors
Staff investigators and RA’s will be trained on recognizing adequate signal 
acquisition on the Actiheart monitors when the patient initially has the device placed.  
If there is suboptimal recording identified, the team member placing the device will 
be able to recognize in real time and make appropriate adjustments to the equipment 
based on Actiheart user manual suggestions.

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13.6 Safety and Compliance Monitoring 
This is a small multisite clinical trial of a supportive care intervention with no more than a 
minor increase over minimal risk and the prospect of direct benefit. As such, data monitoring 
will be primarily carried out by the Lead RA at the coordinating site (SCH) and a small, 
external Data Safety Monitoring Committee (DSMC). 
13.6.1 Data and Safety Monitoring Plan. Safety monitoring will be the responsibility of a 4-
member Data Safety and Monitoring Committee (DSMC) composed of professionals 
across the country representing different disciplines and expertise (see table below). 
All members are independent of the protocol.  The committee will be convened at the 
beginning of the study and then twice annually via conference calls, to provide input 
and guidance on the study evaluation and intervention protocols, including quality 
assurance and safety issues related to the protocols, as well as data handling 
activities. As above, in the event of an unanticipated patient death, the committee 
may convene an ad-hoc session and/or suspend the study to assess patient risk 
and/or necessary revisions to the protocol.
13.6.2 Data and Safety Monitoring Committee 
Member Name, Title
Discipline
Research Expertise
Leanne Embry, PhD (Associate 
Professor, Pediatrics University of 
Texas, San Antonio)
Pediatric Psychology
Behavioral Science, Adolescent and Young Adult 
Oncology 
Donna Johnston, MD (Professor, 
Pediatrics Children’s Hospital, Eastern 
Ontario)
Pediatric Oncology and 
Palliative Care
Pediatric Oncology and Palliative Care, Clinical Trial 
Design, Patient-Reported Outcomes  
Barbara Jones, PhD, MSW (Professor, 
Pediatrics University of Texas, Austin)
Pediatric Social Work
Psychosocial Oncology, Pediatric Palliative  Care, 
Adolescent and Young Adult Oncology
Kira Bona, MD, MPH (Assistant 
Professor, Pediatrics, Boston 
Children’s Hospital & Dana Farber 
Cancer Institute)
Pediatric Oncology
Pediatric Oncology and Palliative Care, Patient-
Reported Outcomes
13.6.3 Monitoring study safety.  DSMC members will provide input and feedback to the PI 
and Co-investigators, via e-mail and conference calls, related to (a) accrual rate, (b) 
study eligibility determination issues, (c) data completion rates including conformance 
with informed consent requirements, (d) intervention fidelity indicators, (e) adverse 
events, and (f) compliance with data management procedures. The lead statistician 
will oversee the summarization of online data to evaluate data completeness and 
protocol adherence. The Lead RA will also send monthly reports summarizing 
recruitment and other site specific data (such as indicators of intervention delivery, 
occurrence of adverse events, and conformance with IRB requirements). 
The committee will also receive information on questionnaire data, presented for the 
participants overall rather than by study group. This study will not have pre-set 
stopping rules, but the DSMC will have the option of requesting the data be unblinded 
and considering altering the study or stopping the study early.  Although the full 
committee will meet twice-yearly, the chair will be free to assemble the full committee 

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at any time if the chair believes it is important. Because committee members may be 
located at various sites, the committee meetings may be conducted by phone. 
Data safety monitoring for the intervention will focus on assuring that subjects are not 
experiencing any significant or unexpected distress and that they are satisfied with the 
intervention components; we will monitor all complaints about the study.  We do not 
anticipate stopping the study early for efficacy or harm, but the DSMC will have the 
option to consider such action in the event of a highly unexpected result. The DSMC 
will review the draft questionnaires to be sent to subjects and review any complaints 
that may be received from patients, family members, clinicians, or others.  We do not 
anticipate any external factors such as findings from ongoing trials that will affect the 
safety of participants or the ethics of this research study.
13.6.4 Identification, review and report of adverse events and unanticipated problem. 
Adverse events information will be collected at all assessment points and recorded on 
standard forms. We will collect information on all potential types of adverse events. 
Consistent with NIH and the sites IRBs policies, adverse events will be promptly 
reported in writing to the NIH, individual IRBs, and the DSMC chair. The DSMC will 
modify or stop the study if any such complaints represent a legitimate concern about the 
study procedures or methods.  
13.6.5 Compliance with monitoring requirements. Compliance with the monitoring plan 
will be ensured through the Lead RA’s close supervision. The Lead RA will hold no less 
than monthly calls with the sites to monitor recruitment and protocol adherence. Site 
RAs will gather required information on an ongoing basis and send monthly written 
reports to Lead RA. The Lead RA will schedule yearly on-site monitoring visits as the 
coordinating site for data completeness and accuracy. Site RAs will assist in providing 
on-site monitors with appropriate access to all study related charts and databases 
during the visit.
13.6.6 Assessment of relevant external factors. Given the characteristics of the 
intervention, it is unlikely that a breakthrough result from another study will change the 
course of this study. 
13.6.7 Interim analysis plan.  A primary endpoint interim analysis to assess for safety and 
missingness will be led by the study statistician after half of the targeted sample size of 
participants have reached the primary endpoint. The DSMC will determine a priori 
stopping occurrence of serious events, including (but not limited to) stopping the study 
for efficacy if interim analysis is significant. For efficacy endpoint, if an effect were 
found, the DSMC will be presented with unblinded results (i.e. they will be able to 
ascertain which results correspond to the intervention arm). Based on these results, the 
DSMC will present recommendations to the study team regarding early stopping or 
continuation of the trial. There are no pre-planned stopping rules for adverse events 
since these are not anticipated.
14.0 Withdrawal of Subjects
14.1 Plan for Non-Responders

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Response to the intervention will be determined upon study completion (not in “real-
time,”).  All participants, including those on the intervention arm, will continue to receive 
usual care, including as-needed referrals for professional psychology services. 
14.2 Early Withdrawal of Subjects
All participants may choose to withdraw from the study at any time.  We will track date of 
discontinuation and request a brief reason to be recorded for tracking purposes.  In the 
event of serious medical complications (or death) precluding participation, participants will 
be censored after 2 months of missing data. In all other cases, staff will continue to 
request surveys until 2 months following the study endpoint (12 months for RCT, 3 months 
for Run-In), as described above. 
14.3 When and How to Withdraw Subjects
In this intention-to-treat analysis plan, all participants who fill out a baseline survey will be 
included in analyses.  As above, withdrawal will be determined by study staff only in the 
event of medical complications or death.  
14.4 Data Collection and Follow-up for Withdrawn Subjects 
Unless explicitly indicated by participants who withdraw their consent, baseline data for all 
eligible patients will be maintained and utilized in analyses.  
15.0 Risks to Subjects
The intervention (“Promoting Resilience in Stress Management”, PRISM) and our surveys may 
address sensitive matters in that it they patients to identify stressors and negative thoughts.  
Adolescent and young adult participants may be prompted to think about the threat to their life 
posed by their cancer/tumor. During the coming together session and/or while completing surveys, 
parents may be prompted to think about the threat to their child’s life by their cancer/tumor. The 
topics to be covered may provoke sadness, anxiety, depression, fear or doubt for AYAs and/or 
their parents.  Any spouse, caregiver, significant other, caregiver, etc. who participates in the 
coming together session may be also prompted to think about the threat to the AYA's life posed by 
their cancer/tumor and these topics may provoke sadness, anxiety, depression, fear or doubt for 
AYAs and/or their parents. 
Administrators of the intervention will be trained to inform the patient’s primary social work and/or 
medical teams if the patient and/or parents/guardians/spouses/significant others endorses 
thoughts of self-harm or harm to others. As part of their informed consent process, participants will 
be made aware of this policy, as well as the fact that confidentiality may be broken in the case that 
providers see an immediate threat to the patient’s or another’s safety.  Patients who participate in 
the optional HRV measurement component of the study may experience some mild physical 
discomfort or skin irritation associated with wearing the ECG monitor.  The risk is minimal, as this 
process is identical to standard ECG measurements obtained for clinical purposes, of which all 
participants will have undergone. No significant physical risks are expected to arise from the study. 
The primary risk to participants will be concerns about confidentiality, and stress of discussing the 
topic of their or their child’s cancer/tumor experience. While the potential risks to participants are 
low, we will take steps to ensure that all potential risks are handled appropriately as described 

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below. Due to the nature of the PRISM intervention, all staff and participants will be unblinded from 
the time of randomization. 
We recognize the unique risks of data collection for an AYA population. The major risk is 
compromise of personal data. Thus, confidentiality procedures for all data will be a priority for this 
study.  All data will be maintained on secure computers or in locked offices at Seattle Children’s 
Research Institute (data collection center).  The study results will be kept for at least ten years or 
until final analyses are completed, whichever occurs last, in order to ensure data quality.  The 
subject’s consent to use or share PHI does not expire.  Access to the building where the study data 
will be kept at Seattle Children’s Research Institute is limited to authorized personnel. The Lead 
RA and other researchers involved in this project have years of experience and has received 
ongoing training at Seattle Children’s Research Institute on confidentiality as well as HIPAA 
confidentiality standards. Our and other previous trials have kept their data at Seattle Children’s 
Research Institute in the recent past, and the security and confidentiality of the data have never 
been compromised.
15.1 Alternatives:  Patients may opt not to participate in the research.  Their care will not be 
affected in any way should they decline participation. 
16.0 Potential Benefits to Subjects
We hypothesize that patients who receive the intervention will have diminished psychological 
distress and greater quality of life.  We also hypothesize that parents/caregivers/significant 
others/spouses will benefit similarly from their child’s/partner’s participation because prior 
experience in pediatric cancer studies suggests it is personally important for some patients and 
caregivers to share their perspectives, challenges and growth experienced during their cancer.  
However, there may be no direct benefit for participating in this study if our hypotheses are wrong. 
More broadly, information gained from this study may heighten the understanding of the AYA 
cancer and progressive/recurrent tumor experience and elucidate strategies that foster resilience 
and promote better quality of life in this group of high risk patients. These strategies could be 
extended to the care of other AYA patients facing non-cancer or tumor-related life-threatening 
illness. This research has the potential to contribute to the research base concerning the promotion 
of optimal quality of life and mental wellness for all AYA patients.   
17.0 Vulnerable Populations
17.1 This study includes the following vulnerable populations:
A. Individuals who are not yet adults (children, teenagers): Pediatric patients with serious 
illness are at risk for poor outcomes and may benefit from resilience-enhancing 
interventions in the future. We justify the inclusion of children in this project because the 
implementation of those interventions requires feasibility information and patient feedback. 
This study will provide those crucial data.  Patients enrolling in this study may, in fact, 
benefit from the intervention; however, at the time of consent, we will ensure that all 
patients and families understand the objective of this study are to test the feasibility of this 
intervention such that it may be used prospectively in the future (see risks/benefits above). 
B. Pregnant women: There is a chance that a parent or spouse/significant other of a 
patient participant is pregnant and therefore could participate in the survey and/or ‘coming 
together’ portion of this study.  This study does not involve interventions/invasive 
procedures to the woman or fetus and does not involve fetuses or neonates as subjects.

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17.2  This study will not include:
17.2.1 Prisoners 
17.2.2 Cognitively impaired adults
17.2.3 Wards of state
18.0 Community-Based Participatory Research
N/A
19.0 Sharing of Results with Subjects
19.1 Following completion of the study, a written summary of the main results will be provided 
to all interested participants.
20.0 Setting
20.1 Patients will be identified and recruited at their home institution (SCH, BCM, UPMC, 
CHLA). See section 23 for specifics. 
20.2 Study visits may be done in person at the hospital/clinic, in the inpatient room or in the 
outpatient clinical research center. PRISM sessions may also be conducted by phone or 
other web based communication (Zoom, WebEx, or Skype).
20.3 There will not be an involvement of any community advisory board.  
20.4 All local research will be conducted via patients’ home institution (i.e., in Seattle, research 
activities will occur within Seattle Children’s Hospital and Clinics; however as above, 
patients/families may be at home and participate remotely via video call.)
21.0 Resources Available
21.1 Interventionist Training and Fidelity.  PRISM has been standardized through the 
creation of comprehensive protocols for those who implement it.  Session-by-Session 
details are provided in the PRISM manual and in the Voicing My Choices Session 
Appendix document; on outline of each main section is listed in Table 1.  All 
interventionists undergo at least 4 hours of training including role-playing and progressive 
mastery of intervention materials.  The fidelity of all sessions will be systematically 
assessed via audio-recording.  As possible, the PI or supervising team member will review 
the first 6 sessions for each interventionist, and score them for fidelity using a 
standardized tool (see appendix.)  Interveners will receive feedback regarding adherence 
to protocol and approach will be refined with additional training, if needed.   
21.2 Refer to Table 3 for annual numbers of AYAs.  We will consecutively enroll patients at 
SCH, BCM, UPMC, and CHLA.  
21.3 Refer to ‘Table 4’ for the Timeline of conducting and completing the research. 
21.4 The local research teams will work closely with the Hematology/Oncology medical and 
social work teams if outside resources or needs arise. 
22.0 Prior Approvals

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22.1 NIH R01 CA222486-01A1 was reviewed by the relevant study section. The final notice of 
award was received 8/1/13.  
23.0 Participant Incentives 
For the Run-In, participants will be receive $20 for each survey (total $60 for 3 surveys) following 
the completion of each survey  No parent incentives or compensation will be offered as parents are 
not participants in the run in study.
For the RCT, all active patient participants will receive $50 in total, in multiple installments. The 
total amount of $50 will either be administered in two installment payments in the form of a $25 gift 
card or five installment payments in the form of a $10 gift card during the 12-month duration of the 
study. For example, for participants who are very ill or for whom survival is unlikely, we would 
provide the payment installments at earlier time points (e.g., baseline survey, 3-month survey). Per 
HRP-316: a) credit for payment will accrue as the study progresses as all participants will be paid 
in separate installments in conjunction with completion of a survey, b) payment will not be 
contingent on completing study procedures as the first payment installment would occur prior to the 
final study component (12-month survey). C) The amount of payment and the proposed method 
and timing of disbursement is neither coercive nor presented undue influence.
Participants will also receive small, non-monetary items, such as pens, lanyards, or tote bags 
throughout the study. Parents and guardians will also be offered non-monetary items such as 
pens, bags, stress balls, mugs, etc. Patients will receive payment regardless of if they complete the 
full RPCA, aRPCA, or the primary outcome measure only. Patients will not be paid more for 
participation in the optional HRV procedures.
Patient participants who complete both the baseline and 6-month surveys will also be entered in a 
raffle to win an iPad. At each site, raffles will take place once per year or after 10 participants have 
completed all study procedures, whichever occurs first. Each participant in the raffle will therefore 
have 10% or greater chance of winning an iPad.
24.0 Use of Social Media
We will not use social media for this study. 
25.0 Local Number of Subjects
See section 4.1. 
26.0 Provisions to Protect the Privacy Interests of Subjects
When recruitment is done in person, the study team will use a private room to discuss potential 
participation and the use of an intermediary (as needed) if the subject does not know the 
researcher. When recruitment is done via phone/video call, patients and parents will be asked if 
they have time to talk and if there is a quiet space to discuss the study. Emphasis will be made to 
ensure that subjects know that not participating will not impact patient care.

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When possible, texting participants will occur on a secure, HIPAA-compliant platform. If a HIPAA-
compliant platform is not available or allowable per specific site restrictions, research staff will not 
include PHI in texting communications with participants and families. Depending on the texting 
platform used, subjects may be able to send text messages back to the study team. Any texting 
platform used (depending on local site requirements) that allows research staff to receive text 
messages from subjects will be HIPAA compliant and will protect all information received from 
subjects.  
The study team will warn the participant of the possibility of sensitive subject matter before the 
session. The study team will be sure to emphasize to the participant that this study is completely 
optional and the participant has the right to not answer any questions that they feel uncomfortable 
with, that they can withdraw their participation at any time, and that their refusal to participate in 
this research will not impact their care.
The study team will have access to any patient/participant information that could pertain to study 
participation or that has an influence on how a participant participates.
27.0 Compensation for Research-Related Injury
There is no compensation for research-related injury. 
28.0 Economic Burden to Subjects
28.1 We strive to complete these visits with patients while they are already at the hospital. As 
above, intervention sessions may be conducted via phone or other web-based 
communication (e.g., Zoom, WebEx, or Skype) or via phone.  
Study visits will be scheduled in conjunction with other medical visits as much as possible 
to minimize additional hospital/clinic visits or burdens to families.  Prior experience 
suggests some families prefer to come back to the hospital/clinic for these visits, even 
when they require additional time.  No additional incentives or financial support will be 
provided in such cases (e.g., gas-cards or transportation), unless requested by families 
and considered on a case-by-case basis by study staff.  
Patients and families will be asked if they would like to receive text messages from the 
study team for study participation coordination (e.g., enrollment, survey reminders, 
intervention session scheduling, payment). Standard text messaging rates from mobile 
phone providers may be incurred. The study team will inform patients and families of 
potential charges in the consent conference and give them an opportunity to opt out to 
avoid potential charges. 
29.0 Consent Process
We will request a waiver of consent for screening purposes for this study and a waiver of 
documentation of consent for study enrollment in cases where in-person consent 
conferences are not feasible. This will be done so that CRAs may identify potential and 

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eligible patients prior to their scheduled clinic visits and to ensure that recruitment is 
possible whilst protecting participant safety.  
Consent Conferences. The consent meeting between the CRA and eligible participants 
(with parents if applicable) will include an explanation of the study in developmentally 
appropriate lay-language.  All AYA participants will provide either written informed 
consent (if aged 18 years or more (or assent (if <18 years-old). Parents of teens (<18 
years-old) will provide written informed consent. As described in the inclusion/exclusion 
criteria above (Section 3), participants must speak English fluently; however, they are 
eligible if English is not their primary language spoken at home (or if it is not their first 
language). In cases where parent consent is required and parents do not speak English 
fluently (or prefer another language), all conferences will be had in the presence of a 
trained medical interpreter either in person or via phone interpreter.  All participants and 
parents will be provided an opportunity to read the consent/assent form in their preferred 
language (English or Spanish), to ask questions about the study and have those 
questions answered by the research team member before deciding about study 
participation and signing the consent/assent form.  Parental permission for study 
participation will be obtained first if the patient is under 18, then patient assent will be 
obtained for all patients 12-17 years of age.  If a patient indicates that they do not want 
to participate in the study that non-assent will override the parent’s permission and the 
patient will be recorded as a refusal.  The research team member will redirect any parent 
who attempts to convince their child to participate in the study and remind them of their 
child’s right as a potential research participant to refuse participation without coercion.  
Consent to study participation will be obtained from patients 18 years of age and above. 
The CRA will emphasize to all patients and parents in developmentally appropriate lay-
language that being in the study is their choice, and that they may choose not to 
participate or may change their mind at any time and it will not affect how their nurses or 
doctors care for them. 
When conducting the consent conference in person, those who agree to participate will 
sign a paper consent form. When the consent conference is conducted over the 
phone/video, those who agree to participate will complete an electronic consent form via 
the REDCap database using the REDCap e-consent framework. Study staff may also 
email a copy of the consent form to subjects if requested. The body of the consent form 
will be identical, whether on paper or in REDCap. A link to the electronic consent form 
will be e-mailed to participants prior to the phone/video consent conference. Study staff 
will answer any questions about the study, and those who agree to participate will 
provide an electronic signature, date, and time on the REDCap form to indicate their 
consent.  The REDCap e-consent framework allows participants to create an electronic 
signature using their cursor and provides a timestamp. This framework also 
automatically generates an extra certification page for participants to confirm the 
correctness of their responses before submitting; stores a static copy of their responses 
as a PDF in the study’s file repository. Subjects will also be prompted to download a 
copy of their signed consent form from REDCap, or study staff can e-mail the signed 
form. 
After conducting the consent conference either in person or by phone/video, RAs will 
create a consent process note for REDCap and the EMR. Included in this note will be 
the date of the consent conference, the names of the patient and parent (if applicable), 

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the name of the person obtaining consent, the fact that the subject agreed to participate 
and that all risks and opportunities of the study were explained, and that the subject had 
adequate opportunity to have their questions answered. If an interpreter is used, the 
name of the interpreter will be documented.
The rationale for separate consents from parents is as follows: 
parents/caregivers/spouse/significant other will provide an addendum to the AYA 
consent/assent to acknowledge that they may participate in the ‘Coming Together’ 
portion of the study.  Parent/guardian separate consent will be obtained because parents 
will be completing their own study questionnaires and will be disclosing their own 
financial and quality of life information in surveys.  Parents/guardians may still be 
involved in the ‘Coming Together’ portion of the study and not want to sign consent to 
complete questionnaires and vice versa, they may want to complete questionnaires and 
not participate in the ‘Coming Together’ portion of the study either by their or the 
patient’s choice or patient may be on control arm and will not have the option of the 
‘Coming Together’ visit. 
There will be an addendum to the consent form for the optional HRV measurement 
component of the study.  Patients and families will be presented this consent form during 
their consent conference.
For eligible patients who are visually impaired, the font size on consent forms and other 
documents will be enlarged according to patient preferences. If eligible patients with 
visual impairment cannot read large print text, the consent materials will be explained to 
the subject in the presence of an impartial witness who observes the entire consent 
process. In that case, sufficient time will be allowed for questions to be asked and 
answered, to ensure that the subject comprehends the consent information. The 
presence of the witness will be documented in the chart note and on the consent form. 
29.1.1 Non-English Speaking Subject:
29.1.1.1 Patients who speak English but have non-English speaking 
parents/guardians/caregivers/ spouses/significant others will be eligible 
to participate.  Procedures for screening, approach, and enrollment of 
these families will be similar to above, except as follows:
29.1.2 For Spanish Speaking Parents:
29.1.2.1 For patients < 18 years-old: Spanish-English translations of the 
consent and assent forms will be provided for parents during 
discussions of the study and consent conferences and all discussions 
will occur with trained medical interpreters.  
29.1.3 For patients 18 years and older: 
29.1.3.1 Spanish-English translations of the consent will be provided for 
parents during discussions of the study and consent conferences at 
patients’ requests.  Likewise, if patients wish their parents/guardians/ 
caregivers/spouses/significant others to participate in session 6, 
“coming together,” they will be invited to sign a Spanish version of the 
coming together addendum.  All discussions involving Spanish (non-

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English) speaking participants will occur with trained medical 
interpreters.  
29.1.4 For all patients: 
29.1.4.1 Session 6 (“Coming together”) will be offered in the presence of an 
interpreter in the parents'/guardians/ caregivers/spouse/significant 
other's first language.  All other 1:1 sessions will still be conducted in 
English with English-speaking, trained interventionists.  
29.1.5 For Other Non-English Speaking Parents, on a case-by-case basis:
29.1.5.1 Discussions of study will occur with interpreters in the appropriate 
language.  If families and patients are interested in participation, 
informed consent forms would be translated into the native language of 
the parent.
29.1.5.2 Everything pertaining to Spanish speaking parents would be the 
same for other non-English speaking parents except that discussions, 
conferences, and Session 6 would be in the native language of the 
parent, spouse, caregiver, significant other, etc. 
29.2 If a patient is still active on study, however is no longer coming to clinic on a 
regular basis and turns 18 years old or needs to re-consent due to a modification with 
the protocol (or other cause), study staff will mail or email the consent to the participant 
and will call the participant (and parents if applicable) and go over study changes. When 
sent via mail, the consent mailing will include a pre-paid return mailing envelope so the 
participant can sign and return to return to study staff. The study staff will make note of 
the date of the re-consent conference.  When the participant/parent-signed form is 
returned, the researcher will then sign and date it with the current date.  The researcher 
will add a notation that the actual consent conference took place on the date noted via 
telephone.  Similarly, if participants move away from a study center, staff will query their 
continued interest in study participation and offer all study activities remotely via phone 
or other web based communication (skype, Blue Jeans, go to meetings, WhatsApp, etc.) 
to encourage continued participation. Additionally, staff will ask that participants provide 
a contact number or email of their new clinical team such that issues of safety can be 
communicated. Per the Certificate of Confidentiality, patients do not need to sign a 
Release of Information for us to contact their provider in issues of safety to themselves 
or others.
29.3 Waiver or Alteration of Consent Process (consent/parental permission will not be 
obtained, required information will not be disclosed, or the research involves 
deception); Waiver or Alteration of HIPAA
29.3.1 We will request a Waiver of HIPAA Authorization for recruitment and 
Alteration of HIPAA Authorization: The research involves no more than 
minimal risk to the subjects.
29.3.1.1 The waiver of HIPAA is being requested for preliminary screening 
purposes. Preliminary screening procedures are minimal risk; they 
include a basic review of the patient’s medical records to identify 
whether or not the patient meet basic eligibility requirements. No study 

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activities occur prior to the documentation of informed consent by 
patient and/or parent participants. In addition, an alteration is being 
requested for cases in which it is necessary to conduct consent 
remotely (via phone or video-conference) because we cannot 
approach eligible patients in person due to patient safety concerns 
(e.g. during COVID-19 pandemic). Many of our participants are 
immunocompromised, and there will be many cases unrelated to or 
after the COVID-19 pandemic in which it would be much safer to 
approach patients remotely (e.g., when staff are ill, when participants 
are receiving immunosuppressing treatment, when participants are 
very ill). In these cases, we will follow remote consent procedures 
outlined above, and patients/parents will indicate their willingness to 
participate both verbally and via digital signature on the REDCap 
forms. In-person approaches and consent conferences will be 
prioritized when they are possible, and in those cases written 
signatures will be obtained. Research coordinators will collaborate with 
the site PIs to determine when remote consenting is necessary. Site 
PIs will make the final determination as to when remote consenting is 
needed. 
29.3.1.2 The waiver or alteration will NOT adversely affect the rights and 
welfare of the subjects. Provide protocol specific findings justifying this 
determination: The confirmation of eligibility relies in part upon the 
expertise of clinicians and by the patient’s medical record. This is 
information that the patient’s clinicians would have as a part of the 
patient’s clinical care. The information collected is narrow in scope and 
will not affect a potential participant’s insurance, employability, or lead 
to stigmatization. Screened patient information will be stored in a 
database and will be used for demographic tracking purposes and for 
preventing re-approach. All publication or presentation of research 
results will be done in a manner that would not reveal an individual’s 
identity. In remotely conducted consent conferences, we will explain 
the study in as much detail as we would in person and ask questions 
throughout the discussion to ensure participant comprehension. 
Therefore, conducting consent conferences remotely will not be 
significantly different from in-person consenting or have significant 
adverse impacts.
29.3.1.3 The research could NOT practicably be carried out without the waiver 
or alteration. Provide protocol specific findings justifying this 
determination:  We need to have the waiver in order to determine 
potentially eligible participants for this study. If we did not confirm 
eligibility with the clinicians giving care, confirmation of eligibility would 
be dependent upon the patient and parents.  It is likely that they would 
be able to confirm the eligibility criteria but there is the possibility that 
some may not be able to do so for all of the study criteria. It is also 
possible that they may be uncomfortable being asked to confirm the 
eligibility criteria or wonder why it is that they are being asked to do so. 

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We also need this alteration to be able to consent participants in cases 
where in-person consent conferences may pose risk to the patients, 
particularly within this immunosuppressed, high-risk population. The 
advanced cancer and progressive/recurrent tumor patients we are 
attempting to enroll are often highly immunocompromised, with a much 
higher risk for infection by a multitude of transmissible illnesses, and 
these patients are susceptible to substantially worse symptoms and 
outcomes from such illnesses than a person of average health. For 
example, as of Spring 2020, the COVID-19 pandemic has significantly 
impacted our ability to approach patients and conduct consent 
conferences in person; therefore, this has led us to revisit our previous 
practices for in-person consenting, and determine that, in order to 
protect patient safety while still giving all eligible patients the 
opportunity to participate in this potentially beneficial research, we 
need the option to enroll patients remotely.
In addition, both of our previous procedures for remote consent 
conferences are no longer feasible in this circumstance, as follows: 1) 
When a remote consent conference was requested by patients or 
families, we had previously mailed consent forms prior to a phone 
consent conference and requested that families sign the forms and 
return via mail. However, during this unique time, families of individuals 
in our target population are likely exercising extreme caution to protect 
their at-risk child’s health, meaning many may prefer to avoid sharing 
of physical documents via mail. Furthermore, requiring families to 
return documents via mail may pose additional risk and burden as they 
will need to leave their homes to locate mailboxes or visit the post 
office. 2) We had also previously e-mailed consent forms to families 
and requested that they print, sign, scan and return to us via email. 
However, we have found that this option is very often not doable for 
families in this population as it requires them to have access to a 
printer and scanner, which the majority do not (e.g., families not living 
at home, when the AYA in inpatient, etc.) Therefore, in order to 
continue to recruit for this study whilst ensuring patient safety and 
minimizing any burden or stress on families, providing an electronic 
means for families to review consent forms and indicate willingness to 
participate (via digital signature) is necessary.
29.3.1.4 Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation. Provide protocol specific 
findings justifying this determination: Study participants will be provided 
with any additional information that may become known during the 
course of the study which may influence their decision to be in the 
study.
29.3.2 Waivers for participants who turn 18: 

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29.3.2.1 We will re-approach and consent participants if they turn 18 while 
they are still actively participating in the study.  However, we request 
the waiver of consent & HIPAA for patients that turn 18 if no further 
data collection and study related activities are occurring, as their data 
is limited to the continued use of existing data. 
29.4 Subjects who are not yet adults (infants, children, teenagers)
29.4.1 Consent/assent will be obtained for all patients 12 years-old and older 
(written assent for those ages 12-17, and written consent for those 18 
years and older).  These consent conferences will be documented in the 
patient’s medical record.  If patients indicate that they do not want to 
participate in the study, that non-assent will override the parent’s permission 
and the parent will be recorded as a refusal.  The research team member will 
redirect any parent who attempts to convince their child to participate in the 
study and remind them of their child’s right as a potential research participant 
to refuse participation without coercion.  The CRA or PI will emphasize to all 
patients and parents in developmentally appropriate lay-language that being in 
the study is their choice that they may choose not to participate or may 
change their mind at any time and it will not affect how their nurses or doctors 
care for them.                                                                             
29.4.2 Since this is a minimal risk study, consent will be obtained by one parent 
even if the other parent is alive, known, competent, reasonably available, 
and shares legal responsibility for the care and custody of the child.
29.4.3 We will re-approach and consent the children of participants if they turn 
18 while they are still actively participating on study.  However, we 
request the waiver of consent & HIPAA for patients that turn 18 if no further 
data collection and study related activities are occurring, their data is limited to 
the continued use of existing data, which entails minimal risk to the subjects.  
Subjects will have assented to participate in the study as minors and provided 
assent on the consent form, so the rights of subjects who turn 18 while the 
study is ongoing will not be affected by continuing to use the data after contact 
has ceased.  Given that active participation in the research would be 
complete, it would not be practicable to seek consent because of the potential 
difficulty locating subjects, or it may be inappropriate to re-approach the 
subjects due to their health status. 
29.5 Cognitively Impaired Adults
29.5.1 NA
29.6 Adults Unable to Consent
29.6.1 NA 
29.7 Consent for use of HUD
29.7.1 NA 

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30.0 Process to Document Consent in Writing
Consent documents are attached in the appropriate section of the Click smart form, including the 
identical REDCap consent forms for remote consenting. We are following the SOP as written with 
the exception that we will ask 12 & 13 year old patients to co-sign the consent form with their 
parents. As described in Section 29.0, we will also enlarge the print on consent forms and other 
study documents if we have an eligible patient who is visually impaired. 
We will obtain written assent/consent from participants whenever possible, as a wet ink of 
signature. When this is not possible, we will obtain a digital signature to indicate willingness to 
participate.  Upon enrollment and randomization, the PI or Co-I’s will place a research note in the 
medical record to document the discussion and participants.  Additionally, we will ask for a waiver 
of documentation of consent for providing updated information about text messaging approved with 
MOD00009623.
31.0 Drugs or Devices
N/A
32.0 Good Clinical Practice
We are committed to conduct the described study per International Center for Harmonization of 
Good Clinical Practice (ICH-GCP).

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Zebrack BJ. Psychological, social, and behavioral issues for young adults with cancer. Cancer 2011;117:2289-94.
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Jacobs S, Perez J, Cheng YI, Sill A, Wang J, Lyon ME. Adolescent end of life preferences and congruence with their 
parents' preferences: results of a survey of adolescents with cancer. Pediatr Blood Cancer 2015;62:710-4.
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Washington, DC2014.
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NCCN Guidelines: Adolescent and Young Adult (AYA) Oncology. 2016. (Accessed 10/31/2016, 
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American Academy of Pediatrics. Committee on Bioethics and Committee on Hospital Care. Palliative care for 
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Rosenberg AR, Yi-Frazier JP, Wharton C, Gordon K, Jones B. Contributors and Inhibitors of Resilience Among 
Adolescents and Young Adults with Cancer. J Adolesc Young Adult Oncol 2014;3:185-93.
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Andersen BL, Thornton LM, Shapiro CL, et al. Biobehavioral, immune, and health benefits following recurrence for 
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Folkman S, Greer S. Promoting psychological well-being in the face of serious illness: when theory, research and 
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Rosenberg AR, Baker KS, Syrjala KL, Back AL, Wolfe J. Promoting resilience among parents and caregivers of 
children with cancer. J Palliat Med 2013;16:645-52.
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Rosenberg AR, Wolfe J, Bradford MC, et al. Resilience and psychosocial outcomes in parents of children with 
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Rosenberg AR, Yi-Frazier JP, Eaton L, et al. Promoting Resilience in Stress Management: A Pilot Study of a Novel 
Resilience-Promoting Intervention for Adolescents and Young Adults With Serious Illness. Journal of pediatric psychology 
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Czajkowski SM, Powell LH, Adler N, et al. From ideas to efficacy: The ORBIT model for developing behavioral 
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Varni JW, Burwinkle TM, Katz ER, Meeske K, Dickinson P. The PedsQL in pediatric cancer: reliability and validity of 
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general population. Gen Hosp Psychiatry 2006;28:71-7.

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