A Multisite RWCT Comparing the Effectiveness of a Goals of Care Video and Navigator Intervention, the VIDEO-PEDS Experience, Versus Usual Care in Pediatric Cancer
Phase: NA
Conditions: Pediatric Cancer
Sponsor: Massachusetts General Hospital

 
Version 1, 2024.05.1 
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Institutional Review Board 
Intervention/Interaction Detailed Protocol 
 
 
Principal Investigator: 
Joanne Wolfe, MD MPH  
 
Project Title: 
Video Images about Decisions for Ethical Outcomes in Pediatrics (VIDEO-PEDS) 
 
Version Date: 
May 1, 2024 
 
 
Version Name/Number: 
1.0 
 
 
 
 

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Table of Contents  
Table of Contents ......................................................................................................................................... 2 
1. Summary .................................................................................................................................................. 2 
2. 
Background and Significance ................................................................................................................ 6 
2.1 
Background ................................................................................................................................. 6 
2.2 
Preliminary work ......................................................................................................................... 9 
2.2.1 
Preliminary Studies in Cancer ............................................................................................. 9 
2.2.2 
Using Video Decision Aids  ............................................................................................... 10 
2.2.3 
Using NLP for obtaining GOC Outcomes .......................................................................... 11 
2.2.3 
Minority Sampling ............................................................................................................ 12 
2.4 
Summary ................................................................................................................................... 12 
3 
General Study Design ......................................................................................................................... 13 
4 
Specific Aims and Objectives .............................................................................................................. 14 
4.1  
Timelines ................................................................................................................................... 12 
4.2  
Parent Focus Groups ................................................................................................................. 12 
4.3  
Refilming the Video Decision Aid .............................................................................................. 12 
4.4  
Parent Advisory Board .............................................................................................................. 12 
4.5  
Pilot Intervention Components ................................................................................................. 12 
4.5.1 
The Navigator ................................................................................................................... 16 
4.5.2 
Video Decision Aid ............................................................................................................ 18 
4.6 
Randomized Waitlist-Controlled Trial ....................................................................................... 20 
4.6.1 
Schema ............................................................................................................................. 21 
5. 
Subject Selection ................................................................................................................................ 21 
5.1 
Inclusion/Exclusion Criteria ....................................................................................................... 24 
5.2 
Screening Procedures ............................................................................................................... 25 
5.3 
Consent Procedures .................................................................................................................. 26 
5.4 
Retention Strategies ................................................................................................................. 27 
6. 
Data Study Procedures ....................................................................................................................... 28 
6.1 
Data Variables and Collection Methods .................................................................................... 28 
6.1.1 
NPL ................................................................................................................................... 28 
6.1.2        Primary and Secondary Outcomes ...................................................................................... 31 
6.2 
Ensuring Study and Intervention Fidelity .................................................................................. 31 
6.3 
Alternative Treatments and End of Study Procedures .............................................................. 34 
6.4 
Study Incentives ........................................................................................................................ 34 

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7. 
Statistical Analysis .............................................................................................................................. 43 
7.1 
Data analysis plan for quantitative outcomes .......................................................................... 37 
7.2 
Data analysis plan for qualitative outcomes ................................ Error! Bookmark not defined. 
7.3 
Power analysis .......................................................................................................................... 38 
8. 
Risks and Discomforts ........................................................................................................................ 36 
8.1. 
Potential Risks ........................................................................................................................... 36 
8.2 
Protections to Minimize Risks ................................................................................................... 37 
9. 
Benefits .............................................................................................................................................. 37 
10. Data Management Plan ...................................................................................................................... 42 
10.1 
Monitoring and Quality Assurance ........................................................................................... 42 
10.1.1 
Adverse event criteria and Reporting Procedures ........................................................... 43 
10.1.2 
Data and Safety Monitoring Plan ..................................................................................... 44 
11. Return of Results ................................................................................................................................ 45 
12. Long Term Data Storage ..................................................................................................................... 45 
13. ClinicalTrials.gov ................................................................................................................................. 45 
14. References .......................................................................................................................................... 47 
APPENDIX A ................................................................................................................................................ 56 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1. Summary 
Background: Cancer remains the leading cause of death in children.1 Parents of children with 
cancer often face complicated decision making throughout their child’s illness. The National 
Academies of Sciences, Engineering and Medicine have called for the development of 
interventions to increase effective goals-of-care (GOC) communication.2 GOC interventions help 
patients, their families, and clinicians communicate and discuss preferences for treatments 
together to ensure medical care is "consistent with the family’s values, goals, and informed 
preferences."3,4 To date, most GOC interventions have focused on adults and adolescents 
resulting in a critical disparity of available tools for children with advanced cancer. While most 
studies show better family outcomes when parents are prepared for the child’s end of life,5-7 GOC 
conversations are grossly inadequate. Specifically, GOC conversations between parents, who 
serve as primary decision makers for children, and clinicians often rely on verbal or written 
information about possible medical interventions, such as cardiopulmonary resuscitation (CPR) 
or placement on a respirator, during crises of clinical decline.4 However, this approach is often 
inadequate as it is presently conducted, leaving families ill-prepared in times of distress.8  
The majority of children with cancer and their families prefer to die at home, yet most children 
with cancer die in the hospital, and this disproportionately affects African American, Hispanic, and 
rural patients.9-13 Novel interventions are needed to ensure GOC conversations happen earlier to 
ensure goal-concordant care.14 The lack of GOC discussions may be due to clinician reliance on 
ad hoc verbal descriptions of goals and possible treatment options. Treatment options (e.g., CPR) 
are difficult for parents to envision. Moreover, the information provided is often variable, and 
verbal explanations of medical interventions are less effectual given literacy and language 
barriers.15-17 To address these shortcomings, we have developed theory-based GOC video 
decision aids in English and Spanish for patients with cancer.18-32 We have shown the efficacy of 
similar decision aids in adults using Natural Language Processing (NLP), a form of computer-
assisted abstraction, in pragmatic trials; but have not examined the impact of these videos in 
children with cancer and their parents.  
 
Aims: The overall objective of this UG3/UH3 study is to build the infrastructure for and conduct 
a large randomized pragmatic trial in three diverse health care systems (Dana-Farber Cancer 
Institute, Children's Healthcare of Atlanta, and the University of Alabama).  
  
UG3 Aims (Establish a trial infrastructure in three health care systems) 
Aim 1: Guided by patient and clinician input, refine and finalize the GOC Video Intervention. 
Aim 2: Finalize clinics and workflows to implement the intervention. 
Aim 3: Validate and fully define clinically meaningful NLP outcome measures. 
Aim 4: Pilot-test the intervention and outcomes in 9 patients with cancer at each site to ensure 
feasibility. 
  
UH3 Aims (Conduct a large pragmatic randomized waitlist-controlled trial)  
Aim 1: To compare GOC documentation in 504 patients aged 0-12 with cancer randomly 
assigned to our GOC Video Intervention vs. Waitlist-Control. Hypothesis (H) 1a: Intervention 
patients will be more likely to have GOC documentation compared to Waitlist-Controls during 
the intervention period. H1b: Intervention effects will be greater in African American, Hispanic, 
and rural patients as compared to non-Hispanic, non-rural Whites.  
Aim 2: To characterize detailed patient- and parent-centered outcomes. H2: Patients and 
parents in the intervention phase (vs. control) will have improved outcomes.  

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Aim 3: Using the RE-AIM QuEST mixed-methods framework, we will assess dimensions critical 
for consistent use, implementation, and adoption of the program in clinical settings using mixed 
methods. 
 
Methods: The study will be conducted in phases. 1) Recruitment for focus groups to inform 
development of the video decision aid. 2) Refilming of video decision aid, training navigators. 3) 
Pilot-test the intervention and surveys in 9 children with cancer and their parents at each site: 
This will involve 9 parents per site (one per child) from 3 enrolling sites (27 total), who will all 
receive the intervention. Our goal will be to ensure that the intervention is appropriate as well as 
useful to parents and the clinical staff before we conduct the larger pragmatic trial. 
 
Randomized, waitlist-controlled trial (RWCT): Following the finalization of the video decision 
aid, we will conduct a large, pragmatic, randomized, waitlist-controlled trial (RWCT) including 
504 parents of children with cancer aged 0-12 years. This trial will target parents of 76 African 
American, 76 Hispanic, and 76 rural children with cancer (45% of total enrollment) by design. 
Parent participants will be randomized to Waitlist-Control or the GOC Video Intervention in 
which the video decision aid will be shared with their parents along with in-person and telehealth 
sessions conducted by Navigators to elucidate GOC preferences. After the intervention period 
(detailed below), the waitlist will open and all parents (i.e., Waitlist-Controls) will receive the 
intervention. Using NLP to detect outcomes (e.g., GOC documentation), we hypothesize that 
children of parents that receive the intervention, as compared to controls, will have more GOC 
documentation (primary outcome).  
 
Timeline and random assignment: We will conduct three cycles of the nine-month RWCT 
design as shown in Figure 5. Thus, over the course of 27 months, three cycles of unique 
participants will be randomized (9 months per cycle x 3 cycles = 27 months). The recruitment 
period is 36 months to account for the last nine months of intervention for Waitlist-Controls in the 
last cycle. We will examine data on a total of 504 children with cancer and their parents over the 
course of the four years of the UH3 Phase. At the start of each our three cycles, we will ask each 
health system to curate and finalize a list of all eligible patients. For each cycle, one-third of the 
total 504 participants (i.e., N=168) will be randomized in 1:1 assignment, stratified by health 
system and demographic characteristic (African American, Hispanic, and rural) to Waitlist-Control 
or GOC Video Intervention. For each cycle, there will be pre-specified subgroups targeting 
parents of 25 African American (15%), 25 Hispanic (15%), and 25 rural children (15%). (Please 
note that 76 per subgroup over the course of three years ÷ three cycles ≈25 patients per subgroup 
per cycle, a very reasonable goal).  
Race/ethnicity variables are based on the commonly used methods of self-identification within 
the EHR, and our three health care systems are within national guidelines for reliable race and 
ethnicity data.162 Race/ethnicity will be of the child; thus, parents may be a different race. Rural 
will be defined using the U.S. Census method.163 Within the rural subgroup, we will aim to include 
by design 15% (N=11) African American rural children and 15% (N=11) Hispanic rural children. 
In 2021, 24% (105 children) of rural children were African American and 18% (75 children) of rural 
children were Hispanic, making the proposed recruitment numbers for rural African American and 
rural Hispanic children high feasible. At the start of each of our three cycles, a new list of eligible 
children with cancer will be curated since this will change over time (i.e., every nine months). 
 
Outcomes: In the development and pilot phase (UG3), outcomes of acceptability and usefulness 
will be defined by parent and clinician feedback gathered in the focus groups and survey data.  

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NLP outcome measures: For the proposed trial, we will use NLP, a form of computer-assisted 
abstraction, to detect primary and secondary outcomes (e.g., GOC documentation). Our research 
group has published the original studies using NLP in GOC research, as we have already 
successfully applied this methodology in other large-scale trials and have already validated the 
NLP for the pediatric cancer care context.21,22,25-29,32,48,87,88,94,106-109,146 Below, we detail the software 
program we developed and annotator training. The ability to use NLP to rapidly abstract outcomes 
from a large number of EHR records lays the groundwork for the VIDEO-PEDS Proposal. A rule-
based software equipped with text annotation capabilities will be used to assess outcomes for the 
study. This software, ClinicalRegex,147 was developed by our research team. The software has 
been used to assess process-based quality measures in multiple studies across clinical 
settings.110,112,148-160 ClincalRegex identifies all pre-specified keywords and phrases within a 
corpus of text (i.e., clinical notes). Human annotators then use ClinicalRegex’s user interface and 
pre-specified annotation guidelines to interpret the documentation and to indicate whether the 
keywords and phrases identified by the software are in the appropriate context.  
2. Background and Significance 
2.1 Background 
Mounting evidence suggests that children with cancer and their parents rarely participate in GOC 
discussions and receive intensive care at the end of life: Increasingly, adults and adolescents with 
cancer have access to interventions aimed at facilitating GOC discussions.33,34 However, children 
and parents, their natural decision makers, typically experience ad hoc GOC discussions, driven 
primarily by individual clinicians and often too late during clinical crises.5 As a likely result, young 
patients with cancer often receive intensive medical services at the end of life.10 Specifically, 
children experience high rates of hospital deaths, intensive care unit admissions, and intubation 
and CPR.3 Compared with adults, children are also more likely to receive cancer-directed therapy 
at the end of life.2 Parents of children with cancer experience high levels of psychological 
distress35 and when not well-supported in decision making, experience high levels of regret.36 
Parental grief is prolonged, intense, and is highly associated with the child’s end-of-life 
experience. Importantly, our clinical experience and the literature suggest that parents of young 
children with cancer hold multiple, blended GOC, including hoping for life extension and child 
comfort. For example, parents may opt for continued cancer-directed therapy, yet wish to forgo 
care in the ICU. High-quality GOC discussions are required to delineate nuanced goals for 
medical care2; however, we are not aware of any formal GOC interventions for parents of young 
children with cancer. Notably, early GOC communication facilitates less intensive medical care 
among adults, including fewer high-intensity interventions, fewer terminal hospitalizations, earlier 
palliative care use, more hospice use, and better family bereavement outcomes.2,37 GOC 
interventions are urgently needed among pediatric patients with cancer to ensure medical care is 
"consistent with the family’s values, goals, and informed preferences."3,4 
Ethical framework for decision making in pediatric patients vs. adults: In adults, substituted 
judgment (what decision would the patient have made if they were able to make decisions) is 
the common standard used for patients without capacity.38,39 In pediatric patients aged 0-12, 
this is an uncommon standard for decision making. Rather, clinicians and parents are expected 
to consider the child’s “best interests”5 in decision-making. Best interests determinations, 
however, are complicated by variable clinician and parent values and priorities.40 Parents are 
generally better situated than others to understand the unique needs of their children and to 
make appropriate, caring decisions regarding their children’s healthcare.38,39,41 As some have 
noted, this is not an absolute legal right because clinicians have an interest in protecting the 

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child from harm and can challenge parental authority in situations in which a minor is put at 
significant risk of harm.38,39,41 Parental decision making is primarily understood as parents’ 
responsibility to support the interests of the child and to preserve family relationships, rather 
than being focused on their rights to express their own autonomous choices.41  Clinicians must 
balance the need to work collaboratively with parents, respecting their cultures, religions, and 
the importance of family autonomy with the need to protect the child from harm. 41 Informed 
GOC conversations facilitate better outcomes. However, as practiced today, most pediatric 
patients with cancer do not have GOC discussions documented in their medical records 
suggesting that shared decision making and parents’ preferences, which are based on 
understanding the unique needs of their children, may be overlooked and lead to poor quality 
end-of-life care.14 
African Americans, Hispanics, and people with low health literacy experience poor quality end-
of-life care: African American and Hispanic children are disproportionately affected by poor end-
of-life outcomes. Specifically, compared to white patients they are more likely to experience 
death in the hospital and hospice use is highly varied.10,42 Substantial communication 
disparities exist; for example, pediatric oncologists often underestimate the information needs of 
minority parents43 and are inaccurate in predicting decisional preferences.44 Language barriers 
also negatively impact the quality of informed decision making in pediatric cancer care.45 
Unfortunately, low health literacy and low English proficiency serve as significant 
communication barriers impeding high-quality GOC discussions. 46 Approximately 90 million 
U.S. adults have low health literacy and the prevalence of low health literacy is higher among 
minorities and people with low educational attainment.47 People with low health literacy are 
much more likely to misunderstand key facets of GOC discussions.30,48 Similarly, people with 
low health literacy and/or low English proficiency are less likely to have GOC discussions, an 
advance directive, health care proxy, or to have discussed their medical wishes with their family 
members.17,49-56 In addition, people with low health literacy are more likely to want intensive end-
of-life care as their initial approach to care; however, we have shown that brief, balanced, video 
decision aids significantly improve knowledge, decisional certainty, and better align preferences 
for care with individual values among people with low health literacy.30,57 Addressing the needs 
of these communities has the potential to improve the delivery of medical care. 
GOC research in rural populations is urgently needed and has been understudied: The majority 
of GOC research has been conducted in metropolitan settings and populations. 3,58-60 This rural-
urban divide in GOC studies is a glaring gap in the literature given the dearth of palliative care 
specialists in rural areas.61 In many health care contexts, it has been well-documented that 
rural populations have a heightened risk for poor quality of care.61-64 Research focused on GOC 
in rural populations is urgently needed and offers the potential to improve the decision making 
and health care experience of Americans living in rural areas. 
Video decision aids improve GOC discussions and health care delivery by surmounting health 
literacy and communication barriers: The traditional approach to GOC discussions, which 
primarily relies on ad hoc verbal descriptions of hypothetical clinical situations and treatment 
choices, is limited because complex scenarios are difficult to envision, provider information is 
inconsistent, and verbal explanations are hampered by literacy, emotional and language 
barriers. 2,65-67 This is particularly true for parents who are making decisions for ventilatory 
support or other life-prolonging interventions for their child. 68,69 Parents’ heightened emotional 
state may interfere with cognitive processing and this reaction may be exacerbated when 
clinicians insufficiently attend to this affect and emotion. 70-74 For the GOC process to lead to 
optimal decisions, parents require accurate and comprehensible information about their options, 
and a care setting where communication needs are addressed early in the illness trajectory.75-78  

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Over the past few years, investigators have recognized the shortcomings of prior efforts and 
have developed new interventions to better facilitate GOC discussions and the delivery of 
better-aligned medical care with individual values. 2,79-84 The theory-based video decision aids 
proposed for this study focus not only on GOC-related decisions such as resuscitation 
preferences, but also provide education about palliative care and hospice services earlier in the 
course of serious illness. The videos attempt to overcome language and literacy barriers and to 
present potential scenarios with a sense of reality lacking in verbal descriptions.28-30 These 
videos have been proven effective in adult patients in increasing GOC conversations, GOC 
documentation, and hospice utilization.18-20,22,24,27,48,85,86 Increase in hospice utilization avoids 
unwanted burdensome interventions, better aligns patient preferences with care delivery, leads 
to improved caregiver bereavement, and results in more cost-effective care. 18-20,22,24,27-30,48,87. 
The VIDEO-PEDS study proposed is based on strong evidence that communication barriers can 
be overcome with high-quality GOC discussions using video decision aids. 
Optimizing GOC discussions with video decision aids and navigators: Navigators will be used to 
help parents of children with cancer use their knowledge of their child and family along with 
information obtained from video decision aids to contemplate GOC and future decision making. 
Navigators will be trained in VitalTalk, which is the most widely disseminated evidence-based 
teaching method that focuses on patient-centered communication skills training. 88-90 Prior work, 
including several RCTs, supports the efficacy of the GOC videos with navigators. 86,91-93 The 
VitalTalk model is built upon the premise that effective learning of communication skills requires 
observation of exemplar behaviors and observed practice with targeted feedback and includes 
training in skills related to GOC conversations and responding to emotion. The curriculum is 
delivered in an online format combining both synchronous and asynchronous components and 
continuing to apply state of the art learning principles. In earlier studies, VitalTalk demonstrated 
that trained participants acquired a mean of 5.4 new skills in delivering bad news (P < 0.001) 
and 4.4 new skills in GOC (P < 0.001).94 VitalTalk has over 500 faculty, has trained over 
14,000 clinicians, runs courses around the world, and is in high demand by health care systems. 
A pragmatic, randomized waitlist-controlled trial (RWCT) is well-suited to evaluate the 
implementation of the GOC Video Intervention: Pragmatic trials are increasingly used in health 
services research, and there are several notable advantages of this design for testing 
communication interventions.95 A significant barrier to large trials is the challenge of individual 
enrollment. With the RWCT design, all patients will eventually receive the intervention and 
individual written consent procedures are waived, consistent with the low-risk nature of the 
intervention. The large number of patients also allows for robust subgroup analyses (i.e., African 
American, Hispanic, and rural patients). The RWCT design is ideally suited to evaluate 
implementation of communication interventions and conduct subgroup analyses. 
Pragmatic trials evaluate GOC interventions under real-world clinical settings: To date, most 
randomized GOC trials evaluated the effects of interventions under ideal circumstances (i.e., 
explanatory trials).96-99 Explanatory trials are often plagued by poor enrollment and 
predominantly white populations.96-100 Based on the Pragmatic–Explanatory Continuum Indicator 
Summary Tool, the rationale for the proposed pragmatic trial is compelling. 101-105 Further 
evidence for the feasibility of this pragmatic trial include clinics and hospitals chosen that have 
efficient and established infrastructures for new program implementation as well as integrated 
electronic health records (EHRs), providing an easily accessible data source for patient 
phenotype characterization, intervention implementation, and outcomes measurement. Thus, 

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the proposed pragmatic trial is a logical next step towards understanding the real-world 
application of the intervention. 
Natural Language Processing (NLP) allows for trials of this size: For the proposed trial, we will 
use NLP, a form of computer-assisted abstraction, to detect the primary outcome (GOC 
documentation). Our research group has published seminal studies using NLP as we have 
already successfully applied this methodology in other large-scale trials. 22,25,86,91,92,94,106-112 The 
ability to use NLP to rapidly and more efficiently abstract outcomes from a large number of EHR 
records lays the groundwork for a trial of this magnitude and complexity.  
2.2 Preliminary work 
Preliminary Studies: Over the last decade, the research team has focused on improving decision 
making for persons with serious illness, with a particular focus on cancer and pediatrics, by 
creating and studying innovative decision aids. The work cited below demonstrates the research 
team's experience, commitment, and ability to effectively use a wide array of clinical research 
methods to design, administer, and complete projects focused on the care of patients with 
advanced illness and poor prognosis. The research team has also led some of the critical research 
work in pediatric cancer care. The studies below represent a systematic series of investigations 
that set the stage for this proposal. 
1. 
 
2.2.1 Preliminary studies in cancer: The first 
video our team produced was a 5-minute decision 
aid depicting the GOC for adults with cancer.27 In an 
RCT, 
patients 
with 
advanced 
cancer 
were 
randomized to either listen to a verbal description of 
the GOC (N=27) or view the video decision aid 
(N=27), and then asked the level of care they would 
want. The three levels of care included: life-
prolonging care (hospitalization, intensive care unit); 
limited/selective care (hospitalization but no ICU); or 
comfort care (symptom relief only). We also 
assessed uncertainty regarding decision making 
using the Decisional Conflict Scale with scores 
ranging from 3 (high uncertainty) to 15 (no 
uncertainty). End points were the selected GOC, 
uncertainty in decision making, and comfort viewing 
the video. Patients in the video arm (vs. control) were more likely to opt for comfort, were more 
informed, and more certain of their decision. Among patients receiving the verbal narrative, 26% 
desired life-prolonging care, 52% chose limited/selective care, and 22% preferred comfort care 
(see Figure 2). In the video group, none desired life-prolonging care, 4% chose limited/selective 
care, 92% preferred comfort care, and 4% were uncertain (P < 0.001). Participants in the video 
group had less uncertainty (mean uncertainty score, 13.7; [95% CI, 12.8 to 14.6]; P = 0.002) 
compared to participants randomized to the verbal group (mean uncertainty score, 11.5; [95% CI, 
10.5 to 12.6]). Of the patients randomized to the video group, 82% felt “very comfortable” watching 
the video, and 82% would “definitely recommend” the video to other patients.  
2. 
 
Figure 2 

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Based on this work, the research team completed a larger NCI-funded trial in adult patients that 
was published in the Journal of Clinical Oncology and presented as an oral abstract at the annual 
meeting of the American Society for Clinical Oncology.22 In this multi-center randomized trial of a 
video decision aid exploring CPR, 150 participants were randomly assigned to either a verbal 
description of CPR (N=80) vs. the video decision aid (N=70) explaining the risks and benefits of 
CPR (see Figure 3). Health literacy was also measured using the Rapid Estimate of Adult Literacy 
in Medicine (REALM) tool. In the verbal arm, 48% of participants wanted CPR vs. 20% in the 
video arm (P < 0.001). Furthermore, patients watching the video were more knowledgeable (score 
range 0-4, mean video score, 3.3 ± 1.0; mean verbal 
score, 2.6 ± 1.3; P < 0.001). Of the patients who viewed 
the video, 77% would "definitely recommend" the video, 
and 20% would "probably recommend" the video. In a 
multivariate logistic regression model, random assignment 
to the video (adjusted OR [aOR], 4.7; 95% CI, 2.1 to 10.7) 
and higher health literacy level (7th-8th grade vs. < 6th 
grade: aOR, 3.6; 95%CI, 1.1 to 12.0; > 9th grade vs. < 6th 
grade: 
aOR, 
3.8;95%CI, 
1.3 
to 
10.8) 
remained 
independently associated with a preference for more 
comfort-oriented 
care 
and 
to 
forgo 
high-intensity 
interventions. These findings suggest that patients with 
low health literacy may particularly benefit from the use of 
tailored decision aids to explain GOC.  
 
Using the above preliminary work in adult patients with 
cancer, the research team based out of Massachusetts 
General Hospital and Dana-Farber Cancer Institute is 
leading a large pragmatic trial of the video decision aids in 
more than 20,000 patients with cancer at 39 oncology clinics (UG3/UH3 AG060626-01).92  
3. 
 
 
2.2.2 Using video decision aids in patients with cancer quadruples hospice utilization: We 
recently completed a randomized trial assessing the impact of a video decision aid on hospice 
utilization in patients with advanced cancer.85 Patients receiving the video were more likely to 
utilize hospice (85.2% vs. 63.6%; P = 0.01) and had longer hospice length-of-stay (median 12 vs. 
3 days; P < 0.001) compared to those receiving usual care. Patients in the video group also 
reported greater knowledge about hospice and more favorable perceptions of hospice care. 
Caregivers of patients assigned to the video were also more likely to prefer hospice for their loved 
ones (94.4% vs. 65.4%, P = 0.03), reported greater knowledge about hospice, and were more 
likely to have favorable perceptions of hospice care. Our intervention promotes education in the 
different GOC and leads to increased hospice utilization for those with advanced cancer. 
4. 
 
Using video decision aids in adolescents and young adults with cancer: The research team 
recently completed an NCI-funded (1R21CA234708) pilot randomized trial assessing the impact 
of a video decision aid on GOC knowledge in adolescents and young adults with cancer. Fifty 
patients with cancer aged 18-39 were randomized 1:1 to the video or usual care. Patient-centered 
and clinically meaningful outcomes including GOC knowledge, readiness to discuss GOC, and 
decisional conflict for future care were obtained pre- and post- intervention and compared 
between groups. Patients in the video arm showed greater change in mean knowledge (0.6 vs. 
0.3), readiness scores (1.2 vs. 0.6), and improved decisional conflict (0.7 vs. 0.1) compared to 
controls. The video was highly rated by patients: 95% found the video helpful, 95% were 
comfortable viewing the video, and 91% indicated they would recommend the video to other 
Figure 3: CPR Preferences 

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patients facing similar decisions.122 A video-based GOC tool was well-liked by patients, resulted 
in increased GOC knowledge, less decisional conflict, and more GOC readiness. 
 
Significant work in young children with cancer and documenting the need for improvement 
in pediatric GOC communication: Our research team has been at the forefront of conducting 
clinical trials involving young children with cancer and their parents. We successfully completed 
a multi-centered RCT evaluating whether providing e-PROMs feedback (symptom and HRQoL 
[Health Related Quality of Life] summary scores via a paper report) to families and clinicians of children 
with cancer, improved child’s HRQoL and symptom burden. In the intervention arm, all scores changed 
in the expected directions but changes were small, not reaching statistical significance. In post-hoc 
subgroup analyses looking at older children and those who survived 20 weeks, larger improvements in 
almost all scores were observed in the intervention group, especially in emotional PedsQL scores.124 
This study was among the first palliative care trials in children with cancer successfully demontrating 
feasibility.125 Notably, enrolled parents reported highly valuing palliative care studies and that their 
primary reason for enrollment was helping other cancer patients and their families. We have also just 
completed accrual for a follow-up trial pairing e-PROM symptom and HRQoL feedback with intervention 
by a specialty palliative care service in four large pediatric cancer centers. Our research group has also 
shown that pediatric clinicians identify numerous barriers to holding GOC discussions with families of 
seriously ill children and believe parents are not ready for such discussions.126 We also demonstrated 
the unintended consequences of limited GOC discussions in seriously ill children and their families.5 
Specifically, without GOC discussions parents are less likely to be prepared for their child’s last days 
and are less able to plan their child’s location of death and quality of life. In contrast, when discussions 
involve specific assessment of family goals, the child is less likely to experience suffering at the end of 
life (adjusted odds ratio 0.23; 95% CI 0.02-0.87). As such, there is a critical need for interventions that 
educate and prepare parents for GOC discussions. 
 
2.2.3 Using NLP for obtaining GOC outcomes in pediatric patients with cancer: To rigorously 
assess outcomes in a trial of this scale, we will use rule-based NLP to query large volumes of 
EHR data. In a paper presently under review, we used NLP to identify GOC conversations 
documented in physician notes during hospital admissions. The NLP algorithm was developed 
and validated on a dataset consisting of 641 notes (containing 895,328 tokens) from 402 patients. 
For detecting GOC documentation at the note level, the algorithm had a sensitivity of 93.5% (95% 
CI, 90.0%-98.0%), and a specificity of 91.0% (95% CI, 86.4%-95.3%). Based on this and other 
work, we further refined the NLP-assisted and human-confirmed approach. In our ongoing U-
grant pragmatic trial (UG3/UH3 AG060626-01), we validated our NLP approach compared to 
human coders. Specifically, we compared the ability of two coders who manually reviewed 981 
EHR notes for 30 patients compared to the results of our NLP-assisted and human-confirmed 
approach.127 There were no reviewer-identified outcomes that were not identified by NLP (i.e., 
100% sensitivity). Every false positive was excluded by human review (resulting in a specificity of 
100%) or included as a true outcome, representing events missed by manual chart review. In this 
study, manual abstraction of GOC outcomes took the chart reviewer approximately 30-120 
minutes per patient. In contrast, NLP analysis of each patient’s compiled clinical notes took 1-5 
minutes. Our research team is also the first to study the use of NLP in pediatric oncology. In a 
manuscript presently under review, we validated the rule-based NLP in the pediatric cancer 
setting. We conducted a single center cohort study of children aged 0-25 years who died of cancer 
between January 1, 2014, and December 31, 2022, while receiving care at Yale New Haven 
Children’s Hospital/Smilow Cancer Hospital, a National Cancer Institute-designated cancer 
center. Our study cohort consisted of 101 childhood cancer decedents with 29,934 notes from the 
last six months of life. First, we randomly selected a 10% sample of decedents and conducted a 
manual chart review of all clinical notes in the last six months of life in the EHR. These randomly 

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selected 10 decedents accumulated 5,076 notes in the last six months of life. We then ran the 
NLP software on the same set of notes. We validated the NLP software by comparing 
performance of the NLP to manual chart review in identifying documentation of GOC process 
measures in clinical notes. The manual chart review was considered the gold standard corpus in 
this comparison. We utilized a second random sample of notes from 10% of decedents to 
complete this process. We evaluated true positives, or NLP identification of a process measure 
that has also been identified in the gold standard corpus; false positives, or NLP identification of 
a process measure when absent in the gold standard corpus; false negatives, or when a process 
measure is present in the gold standard corpus but not identified by NLP; and true negatives, or 
when a process measure is uniformly absent in both the gold standard corpus and the NLP 
software. Performance statistics, including precision, recall, and F1 score, were then computed. 
Precision, or positive predictive value, is defined as true positives / true + false positives. Recall, 
or sensitivity, is defined as the true positives / true positives + false negatives. The F1 score is 
the harmonic mean of these values, calculated as 2* [(precision*recall)/(precision+recall)]. During 
the validation process, we continued to iteratively revise the keyword library to improve 
performance statistics. We aimed to achieve precision > 90% and an F1 score as close to 1 as 
possible, optimizing accuracy of the NLP pipeline. For our study cohort consisting of 101 
childhood cancer decedents with 29,934 notes from the last six months of life, the validation data 
set assessed the performance of our refined keyword library ultimately achieving robust 
performance statistics (F1 score = 1.0 across all process measures). Compared to manual chart 
review, our NLP-assisted and human-confirmed approach is highly accurate and completed in a 
tiny fraction of the time.  
2.2.4. Minority Sampling: Our research team has extensive experience with large pragmatic 
trials, implementation science, and recruiting African American, Hispanic, and rural patients and 
over the last decade has been a key member of the NIH Pragmatic Trials Collaboratory.128,129 
We are conducting three large pragmatic trials; all using video decision aids. The first is using 
video decision aids with navigators in the skilled nursing home setting using a cluster-
randomized study design of 432 skilled nursing facilities. Of note, we recruited 1,692 African 
American patients for this study of older patients (UG3/UH3 AG049619-03).130 The second is 
using video decision aids and navigators in a non-randomized pragmatic trial of over 15,000 
older patients in ambulatory practices. Of note, we recruited 2,248 patients who identified as 
either African American or Hispanic (3UH3 AG060626-03S1).86 Our third trial is implementing 
video decision aids and communication skills training in oncology practices in a large pragmatic 
trial of over 20,000 adult patients with cancer (UG3/UH3 AG060626-01; race/ethnicity data 
analyses pending).92 We also have experience with recruiting patients in rural settings. Our 
research team was the first to study video decision aids in a rural population,26 exhibiting similar 
patient-centered outcomes (improved GOC knowledge and improved communication with the 
health care team) as those found in our studies of urban populations. Further, our research 
team has extensive experience recruiting under-represented minorities in pediatric oncology 
studies through community partnerships and culturally adapted materials. We have conducted 
bereaved interviews to establish quality measures for children with cancer in both California and 
Alabama; in both sites we successfully sampled to have 50% represented minorities.11 The 
research team has the depth and breadth of experience with large pragmatic trials, 
implementation science, and a highly successful track record of recruiting African American, 
Hispanic, and rural populations to successfully accomplish the aims of this study. 
2.3 Summary 
Our preliminary work shows that: 1. There is both a need and opportunity to improve the care of 
pediatric patients with cancer and their parents through better GOC discussions; 2. 

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Interventions to improve GOC discussions uniformly suggest that patients using the videos are 
more knowledgeable, more certain about their decisions, and more likely to have GOC 
conversations that lead to care delivery aligned with medical preferences; 3. Videos surmount 
barriers posed by language and limited health literacy; 4. Videos are a practical approach to 
improve GOC discussions that have been shown to be efficacious and can be implemented in 
health care systems; 5. Using navigators who have been trained in communication skills and 
using videos is a practical approach to improve GOC discussions that has been shown to be 
efficacious in several RCTs; 6. The research team has deep experience with NLP, pragmatic 
trials, and recruiting African American, Hispanic, and rural patients; and, 7. The investigators 
have experience conducting trials in young children with cancer. 
3.General Study Design 
The overall objective of this UG3/UH3 study entitled Video Inspired Discussions for Ethical 
Outcomes in Pediatrics (VIDEO-PEDS) is to build the infrastructure for and conduct a large 
randomized pragmatic trial of a GOC video decision aid in three diverse health care systems 
(Dana-Farber Cancer Institute, Children’s Healthcare of Atlanta, and the University of Alabama). 
During the UG3 Phase (first two years), we will refine the GOC video decision aid, finalize clinics 
and workflows, train annotators on the NLP process, and pilot-test the intervention. During the 
UH3 Phase (subsequent four years), we will conduct a large, pragmatic, randomized, waitlist-
controlled trial (RWCT) including 504 parents of children with cancer aged 0-12 years. This trial 
will include 76 African American, 76 Hispanic, and 76 rural children with cancer (45% of total 
enrollment) by design. Children will be randomized to Waitlist-Control or the GOC Video 
Intervention in which the video decision aid will be shared with their parents along with in-person 
and telehealth sessions conducted by navigators to elucidate GOC preferences. After the 
intervention period, the waitlist will open and all parents (i.e., Waitlist-Controls) will receive the 
intervention. Using NLP to detect outcomes (e.g., GOC documentation), we hypothesize that 
intervention children, as compared to controls, will have more GOC documentation (primary 
outcome).  
4.Specific Aims and Objectives 
 
Objectives for this proposal will be achieved via the following Specific Aims: 
Phase UG3 Aims (Establish a trial infrastructure in three health care systems) 
Aim 1: Guided by patient and clinician input, refine and finalize the GOC Video Intervention. 
Aim 2: Finalize clinics and workflows to implement the intervention. 
Aim 3: Train annotators on the NLP process using EHR notes. 
Aim 4: Pilot-test the intervention and outcomes in 9 patients with cancer at each site to ensure 
feasibility. 
 
Phase UH3 Aims (Conduct a large pragmatic randomized waitlist-controlled trial)  
1. 
 
Aim 1: To compare GOC documentation in 504 children with cancer aged 0-12 years 
randomly assigned to our Video Intervention vs. Waitlist-Control. Hypothesis (H) 1a: Children 
whose parents have been assigned to the intervention arm will be more likely to have GOC 
documentation compared to Waitlist-Controls during the intervention period. H1b: Intervention 
effects will be greater in African American, Hispanic, and rural children as compared with non-
Hispanic, non-rural Whites.  

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Aim 2: To characterize detailed patient- and parent-centered outcomes. H2: Patients and 
parents in the intervention phase (vs. control) will have improved patient- and parent-centered 
outcomes.  
Aim 3: Using the RE-AIM QuEST mixed-methods framework, we will assess dimensions 
critical for consistent use, implementation, and adoption of the program in clinical settings 
using a mixed-methods framework. 
 
1.1 Timelines 
The study will take place over a 6 year period. The initial phases of development and 
piloting will happen in the first 2 years, while the RWCT will take place over years 3-6 (as 
shown in Table 1 below).  
 
Table 1. Various Recruitment Aims of Phases UG3 and UH3 are outlined by 
the year of the grant  
Phase Year 
Tasks 
UG3 
Year 1-
2 
Focus Groups, N=12 (Parents)  
Pilot Study, N= 13, 9 Parents and 4 Providers (Exit Interviews) 
UH3 
Year 3-
5 
RWCT, N=252 (EHR Data-Patient, Intervention-Parent, 3 cycles x 9 months each) 
Consent Recording, N=13 (fidelity of verbal consent) 
Random Survey, N=68 (survey at start and stop of each cycle, 1:1 both arms) 
Stakeholder Interviews, N=4 Parents, N=4 Clinicians, N=2 Clinical Leaders. (end of 
Year 6) 
Year 6 
As above 
*Accrual goals here are specific to DFCI, and site goals are variable for UH3.  
 
Table 2. Development and Pilot PHASE (UG3): Timelines for various aims are 
outlined  
Milestone 
           
 
Table 2: 24 Months of UG3 Phase 
Infrastructure 
0-2 
4 
6 
8 
10 
12 
14 
16 
18 
20 
22 
24 
Biweekly & Monthly Meetings  
 
 
 
 
 
 
 
 
 
 
 
sIRB & Reliance Agremts. 
 
 
 
 
 
 
 
 
 
 
 
 
DSMB 
 
 
 
 
 
  
 
 
 
 
 
Finalize UH3 Milestones 
 
 
 
 
 
 
 
 
 
 
 
 
Pilot-Testing 
 
 
 
 
 
 
 
 
 
 
 
 
Focus Groups 
 
 
 
 
 
  
 
 
 
 
 
Refilm & Finalize Video 
 
 
 
 
 
  
 
 
 
 
 
Train Navigator 
 
 
 
 
 
  
 
 
 
 
 
Finalize Clinics  
 
 
 
 
 
 
 
 
 
 
 
 
Define Workflows 
 
 
 
 
 
  
 
 
 
 
 
Train Annotators 
 
 
 
 
 
 
 
 
 
 
 
 
Pilot Intervention 
 
 
 
 
 
 
 
 
 
 
  

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Finalize GOC Intervention  
 
 
 
 
 
 
 
 
 
 
 
 
Finalize Workflows 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.2 Study design of parent focus groups: 3 focus groups of 3-5 parents will be held. (Screening 
and Consenting procedures are detailed in section 5.2 and 5.3 below). One of these will be in 
Spanish, and populations will represent that intended for the eventual RCT (so we will target to 
include15% African American, 15% Hispanic, and 15% rural, based on feasibility of sampling. Of 
note, rural participants may be recruited for the English or Spanish focus group.) Parents will join 
a 1-2-hour virtual focus group discussion via Zoom. The moderators, Drs. Snaman and Eche, will 
use a semi-structured interview guide in order to ask a series of questions designed to better 
understand the GOC informational needs of parents, but will also allow the flexibility to ask 
additional questions to probe on topics as they come up.131 We will begin by asking about their 
GOC informational needs in general, purposively open-ended to uncover a wide range of 
responses, and then delve deeper into more specific questions about additional decision-making 
needs they might have, the perceived barriers to effective GOC discussions, how clinicians can 
understand those barriers, and interest in learning about the different GOC medical decisions. 
We will explore the potential role of navigators, the comfort level of broadly discussing GOC with 
navigators, the topics preferred to be discussed with clinicians vs. non-clinicians (i.e., navigators), 
and the frequency with which interacting with navigators would be of value. The group will also 
view a GOC video decision aid that discusses GOC broadly focusing on values (e.g., quality of 
life and quantity of life), including spiritual and religious values, and specific interventions (e.g., 
CPR, intubation). One Spanish-language focus group will be held remotely at each site by Drs. 
Dussel and Volandes as they have done in prior work.87,132,133 The Spanish focus groups will follow 
a similar format as the English focus groups.  
 
After viewing the video, parents will be asked to rate on a Likert scale how much this video met 
their decision-making needs, was understandable, and if they would recommend it to others in 
their position; we will then ask them open-ended questions to further discuss their ratings. Please 
see the Parent Focus Group Semi-Structured Guide.  
 
Focus groups will be audio recorded on Zoom Business accounts and stored on secure password 
protected encrypted devices as further detailed below in the data management section. All 
transcription of audio will be done in MAXQDA, for qualitative analysis of major themes.  
 
4.3 Refilming of video decision aid: As we have done in prior work,135,136 Drs. Volandes, Davis, 
Paasche-Orlow, Eche, and Dussel will refilm the video decision aid in English and Spanish based 
on the analyses as described above. Consistent with our prior refinement of videos, we expect 
changes in GOC themes covered, images used, and new content added. Our research team has 
considerable experience in refilming videos and incorporating focus group feedback. After a 
preliminary refilmed video is created, we will have an additional abbreviated (1 hour) focus group 
for an iterative process of comments and editing. (Only Part B of the same Parent Focus Group 
Semi-Structured Guide will be used and is approximated to take less than an hour.) A subset of 
the 36 parents (12 per site) will be invited in order to include 12 (3-5 parents per site). A link to 
the improved version of the video will be emailed to these participants if they are unable to see 
the video over the Zoom call. HIPAA compliant Video cards can also be pre-arranged if there are 
barriers to internet or devices identified. It is assumed only a subset of these parents will reply to 
the initial follow-up focus group invitation. A reminder will be sent if there is no response after a 
week.  
 

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4.4 Parent Advisory Board: Parents of children aged 0-12 with cancer will play an essential role 
in all aspects of this trial. The perspective of parents, who have had or have a child with cancer, 
will be and has been a key part of the development of this proposal and a major impetus to 
conduct this study. Three parents from each health care system, who have had or have a child 
with cancer in the last three years, will be identified by each of our three site-PIs (Drs. Snaman, 
Johnston, and Brock). Diversity in race, ethnicity, and gender will be prioritized. Dr. Eche, who 
has expertise in community engagement, will ensure best practices for community engagement 
to ensure all voices are heard. Furthermore, the Pediatric Patient and Family Advisory Councils 
(PPFAC) at Dana-Farber Cancer Institute and Massachusetts General Hospital (Mass General 
for Children) will facilitate the active participation of the Parent Advisory Board during the UG3 
and UH3 Phases. The Parent Advisory Board will play an important role in ensuring that all 
aspects of the trial remain patient-centered and clinically significant by meeting annually.  
 
4.5 Pilot Intervention Components 
We will pilot-test the GOC Video Intervention at each of our three clinics at each site (i.e., 9 
parents total at each site with all parents receiving the intervention). GOC conversations with the 
Navigator (explained further in 4.5.1) will be audio recorded for quality assurance and training 
(with parental verbal consent). They will experience an abbreviated 3 month study duration in 
which the Navigator will communicate with them (versus the 9 month RWCT). These 9 parents 
will be asked to complete exit interviews. Their primary providers will also be invited to do so (with 
a goal of hearing from 4/9). Audio recording may be done via a pre-tested handheld device (to be 
stored in a locked file cabinet in a locked office on site) if completed by phone or in-person. Others 
will be recorded by Zoom audio if the participant prefers to meet via video-conferencing. 
 
We will also pilot our brief survey, which should take parents approximately 5 minutes to complete.  
• 
Parent Feeling Heard and Understood: We will ask five validated items regarding “feeling 
heard and understood” (e.g., I felt heard and understood by the oncology team. I felt my 
child was heard and understood. I felt the team put my child’s best interests first. I felt the 
team saw my child as a person. I felt the team understood what was important to my 
child).161 Each statement is rated on a five-point Likert scale. 
• 
Parent Satisfaction with Healthcare: We will use two items from the Survey about Caring 
for Children with Cancer (SCCC) to assess satisfaction with healthcare.35 The first 
assesses the care team’s sensitivity to the child’s needs (response options: a great deal, 
a lot, somewhat, a little, not at all). The second assesses quality of care delivered by the 
care team (response options: excellent, very good, good, fair, poor).  
 
Our GOC Video Intervention is a combination of a video decision aid and navigator.  
 
4.5.1 The Navigator 
A member of the research team at each site will serve as a Navigator. They will go through 
standardized training in VitalTalk, delivery of procedures through comprehensive Standard 
Operating Procedures (being developed with the PI and PM) and receive ≥ 8 hours of witnessed 
training including role-playing to demonstrate mastery of materials. Using lay coaches as 
navigators is a major strength towards scalability if the trial results show promise. 
For parents piloting or randomized to the intervention, they will meet at an in-person clinic visit 
or via Zoom (on an institutional / business account that is HIPAA compliant). The navigator will 
then have structured, iterative, and longitudinal GOC conversations to support parents’ 
understanding and encourage deliberation regarding GOC decision making in a manner that is 
sensitive to and respectful of cultural diversity regarding GOC decision making. To this end, the 
navigator will begin by asking if the parent has any questions about GOC in general. The navigator 

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will then use a structured framework, which we have used in our prior trials (1R01AG072911 and 
3UH3AG060626) and also studied by others,170-173 to facilitate the GOC conversation, but 
discussion will not be limited to pre-determined topics. The navigator will determine within the first 
few minutes of the encounter the timing of showing the video decision aid to explore general GOC 
values and to explore level of care and specific interventions. As in our other trials, videos are 
shown early during the encounter to spark a discussion and reflection. Navigators will show the 
video on a tablet or iPad if in person.  
 
The navigator will then engage the parent in the following topics (As outlined in the submitted 
Navigator GOC Conversation Guide) since they are critical to providing medical care that is 
aligned with individual preferences: 1) What do you feel is most important for your child? What 
makes your child happy or gives them joy?; 2) What do you worry about regarding your child 
getting sicker and needing more medical care? What symptoms concern you the most?; 3) Are 
there any medical interventions that you feel strongly about, that you may or may not want for 
your child? Are there any that might be too much?; and 4) In times of difficulty, where do you find 
your strength? Do you have any religious, spiritual, or cultural beliefs that might guide choices 
about your child’s medical care? In addition, the navigator will explore the video viewing 
experience. In general, the GOC conversation will explore initial feelings about GOC and then 
transition towards the video viewing experience (e.g., How did watching the video make you feel? 
What thoughts did the video provoke?). This will help gauge how interested the parent is in 
discussing their preferences further or if they would rather defer decisions until they consult with 
others (e.g., family, religious advisor, primary clinical team). If the parent is comfortable with 
further discussion, the conversation will be guided by the following topics, which may be covered 
in future interactions: 1) whether the parent perceived that having a GOC conversation is 
important at this point in their child’s medical care; 2) reviewing the value-based questions 
presented in the video to help the parent focus their decision making; 3) further explaining the 
GOC; and, 4) if appropriate, eliciting the parent’s GOC preferences. Exploring these topics with 
the parent may lead to a conversation about the importance of completing an advance 
directive/POLST with the primary clinical team. The navigator will encourage the parent to make 
their wishes known to their primary clinical team. Parents will have access to the video decision 
aid after the visit as described below. 
 
The role of the navigator is to engage parents in a general GOC discussion that focuses on 
values. The navigator (who is not a clinician) is not positioned to accept or reject a parent’s choice 
but instead positioned to start a discussion by introducing the general GOC themes. The navigator 
will then communicate with the primary clinical team the summary content of the discussion 
surrounding GOC. It is up to the primary clinical team to further discuss the GOC and whether 
they align with the actual needs of the patient. 
 
The navigator will check-in with the parent as needed via email, telehealth, or in-person after 
the in-person visit, but at least once, at minimum, over the course of the intervention (nine months, 
or three in the case of the Pilot phase). The cadence of check-ins will not be pre-determined 
(reflecting actual clinical care and maximally pragmatic) and may change over time as GOC needs 
of the child change over time (e.g., change in functional status or acute illness). All three of our 
health care systems use EHRs that include two key native EHR functions: (1) An updated panel 
of children with scheduled calls and reminders, and (2) Automatic notifications of health status 
change of any child on their panel (e.g., hospitalization, urgent care visit, critical data). Thus, 
navigators will leverage the native functions of each health care system’s EHR to follow their 
panel of children. Number and length of all in-person or telehealth (audio or visual) interactions 
will be documented in REDCap, allowing for additional analyses based on “dose” of the 
intervention (e.g., how many contacts the navigator had with the parent). Navigators will have 
flexibility to address the needs of any individual parent (e.g., frequency of calls, topics addressed, 
etc.) but will follow the above GOC iterative framework over the course of the intervention that 

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was used in our prior work. Parents will have the contact information of the navigator should they 
wish to schedule additional telehealth or in-person visits. 
 
Telehealth is widely used at our three health systems in response to the pandemic and 
includes telephonic and audio-visual telecommunication. As an accepted part of patient-clinician 
interactions, telehealth has remained a permanent fixture for our three health systems. All 
navigators will undergo training in telehealth best practices by Dr. Michael Paasche-Orlow, a 
national expert on telehealth and video decision aids. Each of our health care systems report over 
99% of patients have telehealth (audio or audio-video) capabilities. In the rare case that a parent 
does not have access to audio (i.e., telephone), the navigator will provide an inexpensive 
disposable phone with pre-paid card for follow-up visits.  
 
At the initial visit, navigators will assess how a video will be shared with the parent for home 
use. The video can be shared through telehealth, and when telephonic, a link to the video can be 
texted via smartphone or emailed to patients or provided through the EHR portal. This means of 
disseminating videos was widely used in our prior studies with great success. For parents who do 
not have access to a smartphone, internet, or other means to watch a video, the video will be 
given to parents using a disposable videocard player that will be provided by the navigator at the 
in-person visit. Videocards are inexpensive, similar in size to a standard tablet screen, allow for 
the videos to be uploaded, allow tracking of use, and have a 10-hour battery life (that is 
rechargeable). Thus, all patients will have access to the video decision aid; digital access and 
literacy will not be a barrier to the GOC Video Intervention.  
 
The navigator will engage the parent(s) in GOC discussions and provide educational support 
using the video. Navigators will be staff members of their respective health systems and will help 
coordinate GOC decision making and medical care with the child’s primary medical team. They 
will prompt the primary clinical team in engaging with the parent regarding GOC that reflect the 
parent’s wishes. Independent of the work and function of the navigator, all clinicians will be able 
to place requests for palliative care consultation. A key part of this pragmatic trial is the integrated 
role of the navigator.  
For the Pilot portion of the study, the follow-up duration will be 3 months versus the full 9 months 
anticipated for the larger trial.  
1. 
 
 
4.5.2 Video decision aid 
The video decision aid that will be discussed in the focus groups is available in both English and 
Spanish. (Note that Spanish materials for this study will be provided to the IRB in a subsequent 
amendment.) The decision aid followed a systematic approach, using an iterative process of 
reviews by oncologists, palliative care physicians, pediatric specialists, intensivists, and decision-
making experts, regarding the design, content, and structure of the video. The decision aid was 
designed using the internationally recognized decision aid criteria to which our team was a 
contributor (International Patient Decision Aid Standards134 [IPDAS], http://ipdas.ohri.ca/). Our 
research team members have been pioneers in the creation of video decision aids, and we have 
published widely on the use of videos to inform patients and families in an unbiased fashion.135,136 
The decision aid was developed with content that is intended to be objective and balanced. It is 
scripted at a fourth-grade level of health literacy in both English and Spanish and has closed 
captioning. The Spanish script was also back-translated into English to ensure cultural 
appropriateness and accuracy. A Certificate of Accuracy will be provided in our IRB submission. 
The decision aid first discusses GOC broadly focusing on values (quality of life and quantity 
of life), including spiritual and religious values. The video, which is narrated by a physician, 
presents a general understanding of the GOC process, the questions that parents of children with 
cancer should reflect upon to elicit values and beliefs, and specific questions to ponder. The video 
begins by establishing the importance of the parent’s personal values and perspective by asking 
the viewer four questions: 1) What do you feel is most important for your child? What makes your 

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child happy or gives them joy?; 2) What do you fear about your child getting sicker and needing 
more medical care? What symptoms concern you the most?; 3) Are there any medical 
interventions that you feel strongly about, that you may or may not want for your child? Are there 
any that might be too much?; and 4) Do you have any religious, spiritual, or cultural beliefs that 
might guide choices about your child’s medical care? The images accompanying the questions 
reflect the questions asked and the potential scenarios. 
The second part of the video explores the three GOC with a focus on interventions associated 
with each of the three goals. The physician-narrator introduces the three general GOC (life-
prolonging care, limited/selective medical care, and comfort-focused care). The subsequent 
narration and visual images characterize these three goals. The visual images illustrating life-
prolonging care include interventions that are available in a modern-day hospital such as CPR, 
intubation, mechanical ventilation, and treatment in the ICU. The second option, limited/selective 
medical care, is described as providing medical treatments that may be life-prolonging but do not 
subject the child to intensive care. This may include hospitalization, intravenous medications, and 
antibiotics, but not CPR or ICU care. Visual images include a seriously ill child getting medicine 
via a peripheral venous catheter, scenes from a typical medical ward, and a child wearing a nasal 
cannula and receiving breathing treatments. The third option, comfort-focused care, is described 
as aiming to maximize comfort and to relieve pain. Only measures that provide comfort are 
performed, and it includes a review of hospice care. Comfort care is compatible with oxygen and 
analgesics, but not with hospitalization unless necessary to provide comfort or based on an 
identified family preference. Visual images include a child on hospice care at home receiving pain 
medications, and a child with a respiratory face mask receiving oxygen at home. All three 
sequences of video images accompanying the narration attempt to help the viewer imagine the 
experience and likely outcomes of the three general GOC. The video was filmed and edited by 
the research team without the use of prompts or stage directions to convey a candid realism in 
the style known as cinema verite.136  
A major strength of the VIDEO-PEDS study is that the video decision aid is available in both 
English and Spanish. The process of culturally tailoring GOC video decision aids to the Spanish 
language and culture is a major innovation of this study. Over the last decade, our team has 
developed a transcreation process to translate and then create tailored video decision aids for 
Spanish-speakers. The transcreation process is based on user-centered design137 in which the 
team uses a mixture of investigative methods and tools (e.g., surveys, interviews, focus groups) 
and generative ones (e.g., brainstorming) to develop an understanding of user needs.136,137 Our 
interdisciplinary team includes cultural anthropologists, ethnographers, film-makers, medical 
interpreters and translators, among others. The first phase of transcreation includes a scoping 
review of published materials on medical decision making and GOC, followed by focus-groups 
and transcriptions of interviews with patients, caregivers, clinicians, cultural experts (e.g., religious 
leaders, etc.) regarding GOC and the explanatory framework138 that Spanish-Speakers use for 
illness. We then take the original English script and based on a cross-cultural adaptation process 
developed by Beaton et al.,139,140 we perform the following: (i) Independent translation of the 
original by two bilingual native speakers; (ii) Synthesis of the two translations into a first consensus 
language version; (iii) Back-translation into English; (iv) Expert committee’s assessment based 
on investigative methods, analyses and results; and finally, (v) Qualitative assessment by focus 
groups. Once a finalized script is crafted, filming begins including narrators, patients, families, and 
clinicians living in the U.S. that are native to the culture and language. The choice of scenes and 
camera angles have been described in detail by our research team and are the national standard 
that others have used.135,136 The preliminary video is then reviewed and edited by parents, the 
Parent Advisory Board, and then by clinicians.  
 
 

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Our goal will be to ensure that the intervention is appropriate as well as useful to parents and the 
clinical staff before we conduct the larger pragmatic trial. During this pilot, we will also make sure 
that we have optimized our ability to identify and curate a list of eligible patients and to obtain 
oncologists’ approval for parent participation with minimal staff burden. We will refine all workflows 
relating to the initial visit with navigators, and also assess whether showing videos at the in-person 
first visit was successful or if giving links to the videos is more appropriate. We will also ensure 
that videocards are available and are successful in surmounting issues relating to digital literacy 
and internet access.  
 
4.6 Randomized Waitlist-Controlled Trial (PHASE UH4) 
The overall goal of the VIDEO-PEDS proposal is to conduct a large, pragmatic, randomized, 
waitlist-controlled trial (RWCT) of 504 parents of children aged 0-12 with cancer. Participants will 
be randomized 1:1 to Waitlist-Control or the GOC Video Intervention in which a video decision 
aid will be shared with parents along with in-person and telehealth sessions conducted by trained 
navigators to help elucidate GOC preferences. 
 
We will use the RWCT study design in which eligible parents are randomized to either Waitlist-
Control or to the GOC Video Intervention for nine months (See Figure below for schema). After 
nine months of the intervention period, the intervention ceases for Intervention parents, and the 
Waitlist-Control parents come off the “waitlist” and receive the intervention for nine months.  
 
Random assignment: We will conduct three cycles of the nine-month RWCT. Thus, over the 
course of 27 months, three cycles of unique patients will be randomized (9 months per cycle x 3 
cycles = 27 months). The recruitment period is 36 months to account for the last nine months of 
intervention for Waitlist-Controls in the last cycle. We will examine data on a total of 504 children 
with cancer and their parents over the course of the four years of the UH3 Phase. At the start of 
each our three cycles, we will ask each health system to curate and finalize a list of all eligible 
patients. Each cycle, one-third of the total 504 children (i.e., N=168) will be randomized in 1:1 
assignment, stratified by health system and demographic characteristic (African American, 
Hispanic, and rural) to Waitlist-Control or GOC Video Intervention. For each cycle, there will be 
pre-specified subgroups of 25 African American (15%), 25 Hispanic (15%), and 25 rural children 
(15%). (Please note that 76 per subgroup over the course of three years ÷ three cycles ≈25 
patients per subgroup per cycle, a very reasonable goal).  
Race/ethnicity variables are based on the commonly used methods of self-identification within 
the EHR, and our three health care systems are within national guidelines for reliable race and 
ethnicity data.162 Race/ethnicity will be of the child; thus, parents may be a different race. Rural 
will be defined using the U.S. Census method.163 Within the rural subgroup, we will include by 
design 15% (N=11) African American rural children and 15% (N=11) Hispanic rural children. In 
2021, 24% (105 children) of rural children were African American and 18% (75 children) of rural 
children were Hispanic, making the proposed recruitment numbers for rural African American and 
rural Hispanic children high feasible. At the start of each of our three cycles, a new list of eligible 
children with cancer will be curated since this will change over time (i.e., every nine months). 
 
Waitlist-Controls: Participants randomized to Waitlist-Control will use existing procedures in place 
at their health care setting (i.e., usual care). Presently, there are no system-wide GOC initiatives 
at our three health care systems. We recognize that over the course of the trial, our three health 
systems might use other programs or initiatives intended to improve GOC discussions. However, 
this is what “usual” care reflects in a pragmatic trial. Navigators (in the capacity of that role) will 
not interact with any Waitlist-Controls during the intervention phase. The navigators will not 
actively monitor the waitlist-control patients during the control period. Thus, lack of GOC 

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discussions and documentation may affect care in the waitlist-controls during the control period; 
however, this is the standard of care.  
 
4.6.1 RWCT Schema 
 
5. Subject Selection 
There are three types of subjects who will participate in this study:  
 
Eligible Patients, N=504
(76 AA, 76 Hispanic, 76 Rural)
Intervention
N=252
Waitlist-Controls
N=252
Videos + 
Navigator 
Interactions
Usual Care
Waitlist-Controls
Receive Intervention
Nine Months
Nine Months
Videos + 
Navigator 
Interactions
Figure 5 

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(1) Patients (via EHR only; N=504) - Patients aged 0-12 years diagnosed with cancer in one of 
the ambulatory cancer clinics involved in this study at Dana-Farber Cancer Institute/Boston 
Children’s Hospital (N=252), Children’s Hospital of Atlanta/Aflac Cancer Center (N=126), and 
the University of Alabama in Birmingham (N=126). From within the pool of these 504 
participants, randomly half of the participants in each stratum (See Table 1) will start the 
intervention at the beginning of one of the three nine-month cycles, and the other half will be on 
the waitlist. After nine months, the waitlist is opened and all patients (i.e., their parents) will 
receive the intervention until the end of the subsequent nine months of participation. Data from 
electronic medical records will be used to ascertain: (a) GOC documentation; (b) medical orders 
for resuscitation preferences; (c) health care utilization; and (d) palliative care and hospice use. 
These participants do not interact with navigators nor do they watch any video decision aids. 
We will only interact with the children’s parents.  
 
(2) Parents of children with cancer – We will interact with parents of children with cancer in 
different ways throughout the UG3 and UH3 Phases. See section 2 Tables 1 and 2 below. 
 
2a. Focus Groups (N=36) (UG3): Parents of children with cancer will participate in focus 
groups in which they will describe their informational needs for their children with cancer 
regarding goals of care. They will also view GOC videos that are designed to empower 
parents. We will recruit 12 parents from each of our three recruiting sites.  
 
2b. Pilot Study (N=27) (UG3): Parents of children with cancer will participate in a pilot 
during the end of the second year of the UG3 Phase. Nine parents from each site will be 
recruited to undergo the GOC Video Intervention including viewing the video and 
speaking with a navigator. They will be invited to participate in exit interviews.  
 
2c. Randomized-Waitlist Controlled Trial (N=504) (UH3): Parents of children with cancer 
will participate in the main trial of the UH3 Phase in which 504 parents will be randomly 
assigned to Intervention or Waitlist-Control over the course of three cycles lasting nine 
months each. At the end of each nine months, the waitlist will be lifted and Waitlist-
Controls will also receive the Intervention. There will only be interactions with the 
parents; there is no interaction with the children. We will recruit 252 participants from our 
larger site (Dana-Farber Cancer Institute) and 126 participants from each of our two 
smaller sites (Children’s Hospital of Atlanta/Aflac Cancer Center and the University of 
Alabama in Birmingham). 
 
2d. Surveys (N=136) (UH3): A random sample of 136 parents of children with cancer will 
participate in a short survey during the UH3 Phase. The 136 parents will be evenly 
divided between the two arms of the study and the three study sites. They will receive 
the self-administered survey via email/mailing at the beginning of their nine-month period 
and again at the end of their nine-month period. We will recruit 68 participants from our 
larger site (Dana-Farber Cancer Institute) and 34 participants from each of our two 
smaller sites. These parents are already included in 2c. 
 
2e. Stakeholder Interviews (N=12) (UH3): Parents of children with cancer will participate 
in stakeholder interviews at the end of the UH3 Phase. We will recruit 4 parents from 
each of our three sites. The stakeholder interviews will assess the acceptability of our 
intervention. We will ask parents to comment on perceived usefulness of the 
intervention, whether anything was learned, and how communication may have changed 

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with their clinician since the intervention. Prospective verbal informed consent will be 
obtained from parents. These parents are already included in 2c. 
 
2f. Parents (via audio-recordings with navigators; N=25) (UH3): From within the pool of 
504 parents, we will audio-record with verbal consent 5% of all interactions for 
intervention fidelity purposes (N=25). The recordings will be used by site PIs at each site 
for supervision, feedback, and learning purposes. In addition, a subset of recordings will 
be transcribed and analyzed. Some of these interactions will take place in languages 
other than English (i.e., Spanish). The consent process for these will be conducted with 
approved language appropriate methods and the resulting transcripts will be translated. 
Prospective verbal informed consent will be obtained from parents.  
 
(3) Stakeholders (Qualitative Interviews; UG3 N=12, UH3 N=30) – We will invite the 9 primary 
providers we engage with for the UG3 pilot families at each site to participate in exit interviews. 
We anticipate completion of 4 interviews based prior response rates of similar trials, so 12 total 
interviews from the pilot intervention primary providers across sites. For the larger UH3 RWCT 
phase, we will target 30 stakeholder interviews (10 per site with 4 parents (already described in 
2e), 4 clinicians, and 2 clinical leaders). Participants will be from ambulatory clinics involved in 
this study at our three health care systems to assess the acceptability of our intervention. We 
will ask parents to comment on perceived usefulness of the intervention, whether anything was 
learned, and how communication may have changed with their clinician since the intervention. 
We will ask clinicians and leaders about barriers and facilitators to the integration of the 
intervention into clinical workflow and to identify strategies for eventual dissemination. *These 
comprehensive Appendix Materials will be provided in an amendment after the development 
phase of the study.  
 
Accrual Summary: 
Site  
Accrual 
Total Accrual 
DFCI 
Parents: 12 focus group, 
9 pilot, 252 RWCT (x2 
for affiliated patient/ 
child)  
Providers: 4 pilot, 6 
RWCT stakeholders 
556 
UAB 
Parents: 12 focus group, 
9 pilot, 126 RWCT 
(x2 for affiliated patient/ 
child) 
Providers: 4 pilot, 6 
RWCT stakeholders 
304 
CHOA 
Parents: 12 focus group, 
9 pilot, 126 RWCT 
(x2 for affiliated patient/ 
child) 
Providers: 4 pilot, 6 
RWCT stakeholders 
304 
All sites 
 
 
1164 
 
 
Table 1. UH3 Child and Parent Strata Assignment to be Randomized to Intervention vs. Waitlist-Control 
(N=1008; 504 children and 504 parents) 
 
 
 
 
DFCI 
(n=504) 
Atlanta 
(n=252) 
Birmingham 
(n=252) 
Non-Hispanic 
African 
American 
Child 
Rural 
Male 
0 
2 
2 
Female 
0 
2 
2 
Non-rural 
Male 
19 
3 
3 
Female 
19 
13 
11 
Parent 
Rural 
Male 
0 
2 
2 

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Female 
0 
2 
2 
Non-rural 
Male 
9 
3 
3 
Female 
29 
11 
13 
Hispanic 
Child 
Rural 
Male 
0 
2 
2 
Female 
0 
2 
2 
Non-rural 
Male 
19 
8 
7 
Female 
19 
8 
7 
Parent 
Rural 
Male 
0 
2 
2 
Female 
0 
2 
2 
Non-rural 
Male 
9 
3 
3 
Female 
29 
11 
13 
Non-Hispanic 
White/Other 
Child 
Rural 
Male 
9 
15 
15 
Female 
9 
14 
14 
Non-rural 
Male 
79 
30 
30 
Female 
79 
29 
29 
Parent 
Rural 
Male 
5 
8 
8 
Female 
13 
21 
21 
Non-rural 
Male 
39 
15 
15 
Female 
119 
44 
44 
 
 
 
Table 2. Parent Strata for Focus Groups/Pilot (N=63) and Stakeholder Interviews with Clinicians and Leaders 
(N=18)  
 
 
 
 
DFCI  
(n=27) 
Atlanta 
(n=27) 
Birmingham 
(n=27) 
Non-Hispanic 
African 
American 
Child 
Rural 
Male 
0 
0 
0 
Female 
0 
0 
0 
Non-rural 
Male 
0 
0 
0 
Female 
0 
0 
0 
Parent 
Rural 
Male 
0 
0 
0 
Female 
0 
0 
0 
Non-rural 
Male 
2 
2 
2 
Female 
3 
3 
3 
Hispanic 
Child 
Rural 
Male 
0 
0 
0 
Female 
0 
0 
0 
Non-rural 
Male 
0 
0 
0 
Female 
0 
0 
0 
Parent 
Rural 
Male 
0 
0 
0 
Female 
0 
0 
0 
Non-rural 
Male 
2 
2 
2 
Female 
3 
3 
3 
Non-Hispanic 
White/Other 
Child 
Rural 
Male 
0 
0 
0 
Female 
0 
0 
0 
Non-rural 
Male 
0 
0 
0 
Female 
o 
0 
0 
Parent 
Rural 
Male 
2 
2 
2 
Female 
3 
2 
3 
Non-rural 
Male 
6 
6 
6 
Female 
6 
6 
6 
 

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5.1 Inclusion/Exclusion Criteria 
Eligibility for parent participation will be based on eligibility of their child; however, the parent will 
be the individual participating in focus groups and study activities during the UG3 and UH3 
Phases. 
 
Eligibility criteria for children with cancer and their parents will be the same for UG3 and 
UH3 Phases. Of note, for the pragmatic trial and for our primary outcome (GOC documentation), 
one or both parents (if present) will be involved in the GOC Video Intervention as this is the case 
in clinical care (and unlike our focus groups in which only one parent will participate). For the 
subgroup of 136 parents who complete surveys, only one parent per child will participate. 
 
4. 
 
Eligibility criteria for children with cancer: Children must meet all inclusion criteria: 1. Age 
0-12 years (in our three states, parents are considered surrogate decision makers for children; 
after 12 years of age, children begin to develop agency to partake in decision making); and 2. 
Any child diagnosed with cancer. Our eligibility criteria are a considerable strength given that they 
are maximally pragmatic (all stages and types of cancer) and clinically relevant (i.e., GOC 
conversations are relevant for all patients with cancer). Exclusion criteria include: 1. Any patient 
who is not receiving their medical care primarily from the cancer clinic (i.e., no second-opinion 
consultations); 2. Patients under the care of family members or foster parents who do not have legal 
guardianship; and, 3. Any child already referred to the palliative care team who had a full initial consult 
and was followed by the team, since a majority will already have documentation of GOC as a result of 
palliative care engagement; and 4. Life expectancy less  than 2 months since the study aims to 
changes in GOC documentation over time, but estimations of prognosis are poor beyond such a 
short period (eligibility will be confirmed by PI.) 
5. 
 
 
Eligibility criteria for parents: We will recruit parents of pediatric patients with cancer for the 
focus groups (N=36; 12 parents from each of our three sites). Parents (or guardians) meeting all 
of the following inclusion criteria are eligible: 1. The decision maker for their child; 2. Biological 
parent, step-parent, or legal guardian (e.g., adoptive parent); 3. Grandparent’s medical consent 
form (e.g., grandparent authorized to make medical decisions); 4. Has a child that meets the 
above child inclusion criteria; and, 5. Able to communicate in English or Spanish (the languages 
of our video decision aids). Exclusion criteria include: 1. Visually impaired beyond 20/200 
corrected and not able to view the video (note, hearing impaired is not an exclusion as the videos 
are closed captioned); 2. Psychological state not appropriate for GOC discussions as determined 
by the primary oncologist. If there are two parents that are eligible for a single child, only one 
parent will be able to participate; and 3. Participants who do not speak English or Spanish are 
excluded because these are the two languages of our video decision aids and the intervention is 
not yet validated in other languages 
 
Eligibility Checklist for Child 
Inclusion Criteria (All criteria must be met): 
o 
Age 0-12 years 
o 
Diagnosed with any type or stage of cancer  

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o 
Receiving cancer directed treatment 
Note: Eligibility is maximally pragmatic and clinically relevant as GOC conversations 
are appropriate for all pediatric cancer patients. 
Exclusion Criteria (Any one criterion excludes participation): 
o 
Not receiving primary medical care from the cancer clinic (e.g., second-opinion consultations 
only) 
o 
Under the care of family members or foster parents without legal guardianship 
o 
Already referred to and fully consulted by the palliative care team 
o 
Prognosis of less than 2 month life expectancy 
Eligibility Checklist for Parents 
Inclusion Criteria (All criteria must be met): 
o 
Decision maker for the child. 
o 
Biological parent, step-parent, or legal guardian (e.g., adoptive parent), grandparent with 
medical consent authority. 
o 
Has a child meeting the child inclusion criteria listed above. 
o 
Able to communicate in English or Spanish (the languages of the video decision aids). 
Exclusion Criteria (Any one criterion excludes participation): 
o 
Visually impaired beyond 20/200 corrected and unable to view the video (note: hearing 
impaired is not an exclusion as the videos are closed captioned). 
o 
Psychological state not appropriate for GOC discussions, as determined by the primary 
oncologist per the opt-out. 
o 
Participants who do not speak English or Spanish are excluded because these are the two 
languages of our video decision aids and the intervention is not yet validated in other 
languages 
 
5.2 Screening Procedures 
We seek verbal consent and request a waiver of written consent documentation. 
For focus groups:  
Potential participants will be identified by key informants: parents of children who meet the 
eligibility criteria detailed in section 5.1 will be identified by providers from the neuro-oncology, 
hematological malignancy and solid tumor teams. We will draw a purposeful sample to 
maximize variation and include critical cases in each of our three health care systems. 

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Potentially eligible patients will be entered into an excel “pool list.” This screening strategy is 
equivalent to running a census of the base population and as such minimizes bias in 
identification of potential subjects and ensures that the pool of participants invited to participate 
is representative of the base population. RAs will screen medical records of children entered 
into the pool list to identify whether the child belongs to the base population. Children identified 
as potentially eligible will be assigned a study ID and entered into the VIDEO-PEDS REDCap 
screening and tracking database, adapted from our prior PQ-Response study to complete 
screening. (Of note, this REDCap will be built during the Development and Pilot UG3 phase of 
the study. Initial screening will progress in Excel during this preparation, for feasibility and so as 
not to delay the research.) The RA will complete an Eligibility Checklist of each criteria via a 
REDCap form that will then be emailed to the PI for confirmation. The response will generate a 
“Validation” email from the PI (serving the regulatory need for a screening Source Document). 
(Of note, this process can also be done manually via email until the REDCap is built.) We will 
email the disease program leader to request a blanket approval and authorization to contact 
providers’ patients and ask that the providers specify any patients whose parent/guardian 
should not be approached. We provide clinicians with the opportunity to opt-out. If no opt out 
notice is received within 3 days (72 hours), families will be considered approachable for 
recruitment. If an out of office reply is received, we will contact a second clinician (such as a 
nurse or fellow on the patient’s care team rather than waiting on their attending). In the case of 
participants referred by their  primary provider, we will use an abbreviated process bypassing 
the optout process. 
 
Children with cancer will be identified using their electronic medical record as described above. 
To conduct this screening procedure, parent participants will sign a separate HIPAA authorization. 
We will use ICD-10 codes and review the medical record.  
 
5.3 Consent Procedures 
We seek verbal consent and request a waiver of written documentation of consent. 
We will enroll one parent per child, as designated by the family, and will suggest it be the parent 
who is formally or informally the primary caregiver. The consent process will include the 
following steps: 
• 
During the first video or in-person meeting, the research assistant (RA) will introduce the 
study. The bilingual information sheets will assist the consent process. The RC will be 
trained in presenting the study using sensitive language without coercion or undue 
influence and allowing parents enough time to field questions. Potential participants will 
be encouraged to seek clarification regarding study procedures and efforts will be made 
to ascertain parent’s understanding before inquiring about willingness to participate. The 
elements of consent will be addressed during this conversation.  
• 
If a parent manifests interest in participating with their child, the RA will seek verbal 
permission for parental involvement, which will include medical record abstraction from 
the child and their own participation: 
o secure verbal parental permission for data collection (from medical record). 
We will not be able to seek assent or consent from participating children  

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o separately ask for verbal parent consent for their participation in the study 
involving data collection (from surveys, interview, and medical record abstraction)  
• 
The information sheet documents will contain all the required elements of an informed 
consent including a disclosure statement containing study details, information regarding 
the data that will be collected, when they will be collected, by whom, and how. The 
disclosure statement will also describe the child and parent’s potential risks and benefits 
of participation. 
• 
The study will recruit Spanish speaking participants. We will use language adapted 
study materials, as mentioned in section 4.2. and will integrate interpreters into the 
consent conversation of these parents. Interpreters will be called for in-person/phone 
services throughout the study through BCH interpreter services. Certified Spanish 
speaking members of the BCH study team will take point with the Spanish speaking 
families. 
• 
Risks for coercion or undue influence will be minimized by: i) thorough training of 
RAs in using appropriate and sensitive language to explain the study goals and 
procedures and transmit that the decision to enroll is voluntary and will not affect regular 
care; ii) research staff that is unrelated to the primary clinical teams; and, iii) inclusion of 
email and virtual enrollment procedures, which in our experience have allowed for 
greater decision autonomy (unpublished). 
• 
Parents who decline participation and those who do not answer the initial surveys, and 
are therefore not randomized, will be sent the non-participation survey. 
• 
We request a waiver of written documentation of consent for child and parent 
participation based on the following considerations: (i) participating in the study, which 
involves answering surveys and one semi-structured interview, and in the case of 
participants assigned to the intervention constitutes “no more than minimal risk”; (ii) the 
rights and welfare of the subjects will not be adversely affected: study staff will present 
all the elements of informed consent during the consent process; (iii) increased study 
feasibility: most consent processes will occur virtually to accommodate better to parent’s 
schedules. The need to sign and send a paper document will incur in unnecessary 
burden for parents. We have successfully used this consent method in our prior 
PediQUEST Response trial. The verbal consent (including permission to contact in the 
future) will be registered by the RA in REDCap. 
• 
Consent to contact at 6 months post-study: As the post-study measurement point will 
only be done in a subgroup of participants (the first 12 enrolled), we propose to, rather 
than adding this evaluation to the study information sheet, re-consent this group of 
subjects during their exit interview, i.e. ask permission to contact them again at 6 months 
post-study to have them answer two surveys and a brief interview. Consent procedures 
for this portion of the study will mimic what was explained above including providing 
them with a specific information sheet that describes the procedures of this evaluation 
and the request of a waiver of written documentation of consent. Verbal consent will also 
be registered in our REDCap database. 

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For the RWCT, we request a waiver of written documentation of consent, except as otherwise 
delineated (if of the subset of the cohort also asked for audio recording).  
(1) Parents for focus groups: Parents will be providing verbal consent but we request a waiver of 
documentation of consent given that this is conduct remotely and presents added burden to 
parents in a minimal risk study.  
 
 
(2) Parents for pilot: Parents will undergo the video intervention with navigators during the 
second year of the UG3 year to pilot the intervention.  
 
(3) Parents (Audio-recordings): For parents who will be subjects in this research for audio-
recordings, individual verbal informed consent using an IRB approved script will be obtained. 
(This applies both to the 5% of Navigator conversations that will be recorded, as detailed further 
below, and the parent interviews and focus groups.) 
 
(4) Stakeholders (Qualitative Interviews): Primary oncology providers will be informed through 
study staff about the purpose and procedures of the study using forums such as meetings, 
posters, or internal newsletters. With regards to the subset of providers who are invited to 
participate in the exit interviews, the elements of informed consent will be provided on the 
invitation email (see template submitted), including a statement about how information will be 
handled and stored and a section detailing our privacy and confidentiality safeguards.  
We request a waiver of documentation of consent for primary providers participating in 
the stakeholder interviews based on the following considerations: (i) participating in the study, 
by either interacting with the Navigator as part of the intervention and/or participating in an 
interview to reflect on their experience with study patients and procedures, constitutes “no more 
than minimal risk”; (ii) the rights and welfare of the subjects will not be adversely affected: study 
staff will present to providers all the elements of informed consent during training and through 
exit interview’s invitation email; (iii) increased study feasibility: we would like to reduce the 
burden of participating for providers.  Further, in the case of provider interviews, confidentiality is 
unlikely to be breached given that tapes and transcripts will be coded, securely stored, and de-
identified (as detailed in sections below on Data Management and Confidentiality). 
 
(5) Parents (randomized waitlist-controlled trial): As described above, we will secure verbal 
parental permission for child or adult child participation, involving data collection (from medical 
record) and being followed by the PPC team if assigned to the intervention. We will not be able 
to seek assent or consent from participating children because of their cognitive impairments, so 
rely on surrogate consent from the parent. Separately we will ask for verbal parent consent for 
their participation in the study involving data collection (from surveys, interview, and medical 
record abstraction) and meeting with the PPC team if assigned to the intervention. In 
accordance with the pragmatic trial of a minimal risk intervention that is being implemented as 
the standard of care for parents of children with cancer randomized to the intervention, and then 
applied to Waitlist-Controls after the intervention period is over. The data for our primary 
outcome and some of our secondary outcomes are derived from the EHR. Thus, for this aspect 
of our proposal, we will seek a waiver of individual informed consent and parent participants will 
sign a separate HIPAA authorization. The research involves no more than minimal risk to the 
subjects as described above. We do not believe the waiver will adversely affect the rights and 
welfare of the subjects. As a pragmatic trial of outpatients, this research could not practicably be 

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carried out without the waiver nor without access to and use of patients’ PHI. Finally, we have 
developed a plan to protect identifiers from improper use and disclosure.  
 
Parent participants will sign a separate HIPAA authorization.This will be needed to identify 
potential patient participants. It is our assessment that this study meets the regulatory 
requirements for the preparatory for research provisions of the HIPAA privacy rule (45 CFR 
164.512) and will work with each institutional IRB and Privacy Officer to establish that this does 
meet the standards for the security of protected health information. In accordance with this 
provision, only researchers and staff who are a part of the “covered entity” will use the 
preparatory research provision to curate the list and then randomly assign children with cancer 
and their parents to their study trial arm. No identifiable PHI will leave any covered entity without 
consent and an approved procedure.  
5.4 Retention Strategies 
Strategies to enhance recruitment and retention will be implemented. Offering a variety of 
flexible options for participation helps with inclusion and recruitment success. RA support to 
facilitate study completion where requested or needed is key. Contact information will be provided 
to reach a member of the research team or the PI directly. We have highly motivated site-PIs, 
which is a key factor in ensuring access to this population of patients. We will also utilize the 
qualitative interviews with parents and clinicians to assess recruitment and retention facilitators 
and barriers and discuss how they can be addressed. We aim to reduce gate-keeping effects by 
educating oncologists about high family satisfaction with GOC discussions and the improvement 
in child-centered care delivery. Similarly, we anticipate more referrals by having broad eligibility 
criteria and having more educated clinicians about the study. Retention should be high because 
of the relatively short follow-up (or cross sectional timepoints in the case of focus groups) and 
having highly experienced navigators on the study. We similarly expect adherence to study 
procedures to be high.  
6. Data Study Procedures 
6.1 Data Variables and Data Collection Methods 
Enrolled participants will be registered to Oncore, as Applicable DF/HCC policy (REGIST-101) 
must be followed. 
 
Research material for this study includes screening/enrollment data collected for tracking 
purposes by the RA (including the inclusion and exclusion criteria, screening date and source, 
and some demographics as noted above), secondary screening and SOP documentation in 
REDCap (Eligibility Checklist, PI Validation, Provider Opt-Out, Approach, End of Study Checklist, 
etc.), survey responses in REDCap and response rates, and audio-recorded parent and clinician 
perspectives. RAs will receive 8 hours of training in study procedures to ensure high quality data 
collection. (Navigators will receive additional training as described above, including VitalTalk.)  
 
6.1.1 NPL Outcome Measures 
For the proposed trial, we will use NLP, a form of computer-assisted abstraction, to detect primary 
and secondary outcomes (e.g., GOC documentation). A rule-based software equipped with text 
annotation capabilities will be used to assess outcomes for the study. This software, 

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ClinicalRegex,147 was developed by our research team. The software has been used to assess 
process-based quality measures in multiple studies across clinical settings.110,112,148-160 
ClincalRegex identifies all pre-specified keywords and phrases within a corpus of text (i.e., clinical 
notes). Human annotators then use ClinicalRegex’s user interface and pre-specified annotation 
guidelines to interpret the documentation and to indicate whether the keywords and phrases 
identified by the software are in the appropriate context.  
6. 
 
Identification of Keywords and Phrases in Clinical Notes: A keyword library has been 
developed to identify keywords and phrases relating to the outcomes of interest (NLP domains) 
within the clinical notes and has already been validated in the pediatric cancer setting (See § 4.3 
Data Analyses, Supplementary Table 1 and Table 2). Each NLP domain’s keywords were defined 
a priori by clinical experts tasked with the question, “how would you spontaneously write about 
this topic in the pediatric cancer clinic?” Abstraction guidelines (i.e., guidelines used to determine 
whether a term from the keyword library that appears in a clinical note appears in the context 
pertinent to the study outcome(s)) with abstraction criteria and inclusive/exclusive examples, were 
then developed. For patients for whom the presence of the outcome is flagged as present using 
the NLP search, the annotator (i.e., RA, study staff) will review the flagged section of text to 
confirm that the documentation reflects GOC. Once these variables have been abstracted from 
the health care system's EHR, the data will be collected for each patient. The primary outcome of 
the trial will be ascertained through NLP-identified instances of GOC: GOC conversations, code 
status limitations, palliative care, hospice, and time-limited trials. Secondary outcomes for this trial 
will characterize care preferences, including documentation of preferences for resuscitation and 
intubation, enteral feeding, and dialysis. We will also use NLP to abstract additional secondary 
patient-centered outcomes such as use of palliative care and hospice. We will also look at the 
number and timing of high-intensity, burdensome treatment utilization from the EHR (CPR, 
intubation, etc.), as well as emergency department visits and location of death, when applicable. 
 
Domain 
Outcome 
Definition 
Annotation Criteria 
Goals-of-Care 
Discussion 
Primary 
Conversations with patients or support 
persons regarding the patient’s goals, 
values, or priorities for treatment and 
outcomes. As well as the evidence that 
elements of advance care planning were 
discussed, reviewed, or completed.  
 
0 = No discussion  
1 = Discussion 
 
Code Status 
Limitations 
Primary 
Limitations to cardiopulmonary 
resuscitation and intubation. 
 
0 = No limitation 
1 = Limitation 
 
Palliative Care 
Primary 
Mention of a visit with a specialty 
palliative care clinician, mention of 
specialist palliative care discussion, or 
patient preferences regarding seeing a 
palliative care clinician. 
0 = No discussion  
1 = Discussion 
 
Hospice 
Primary 
Statements mentioning a discussion of 
hospice, prior enrollment in hospice, 
patient preferences regarding hospice, or 
assessments of hospice eligibility. 
 
0 = No discussion  
1 = Discussion 
 
Time-Limited Trial 
Primary 
Conversations with patients or family 
members about the use of a treatment or 
0 = No discussion  
1 = Discussion 

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procedure for a set amount of time with a 
pre-defined goal and plan related to the 
outcome at the end of the trial. 
 
 
Resuscitation and 
Intubation Preferences 
Secondary 
Preferences for, or limitations to, 
cardiopulmonary resuscitation and/or 
intubation. 
0 = No documentation 
1 = DNR/DNI 
2 = No limitation  
3 = DNR [Intubation is 
okay] 
4 = DNI [Resuscitation is 
okay] 
 
Enteral Feeding 
Secondary 
Mention of conversation with patient or 
family regarding preferences for, or 
limitations to feeding tubes. 
0 = No discussion 
1 = Limitation  
2 = No limitation 
 
Dialysis 
Secondary 
Mention of conversation with patient or 
family regarding about preferences for, or 
limitations to dialysis. 
0 = No discussion 
1 = Limitation  
2 = No limitation  
 
 
Domains 
Keywords 
Goals-of-Care Discussion 
GOC, goals of care, family meeting, family discussion, patient goals, patient 
values, quality of life, prognostic discussions, illness understanding, serious 
illness conversation, serious illness discussion, advance care planning, 
advanced care planning, ACP, end of life, end-of-life, what matters most, poor 
prognosis, limited prognosis, prognosis, prognostic, dying, die, death, 
incurable, not curable, not curative, non-curable, non-curable, non-curative, 
non-curative, no cure, isn’t a cure, is no cure, not reversible, non-reversible, 
treatments are palliative, treatment is palliative, palliation, extend life, 
extending life, life-extending, life extending, lengthening life, life-lengthening, 
life lengthening, life limiting, life-limiting, does not wish to know, does not want 
to know, hours to days, days to weeks, weeks to months, months to years, 
month left, months left, years left, year left, weeks left, week left, unfortunate, 
regrettably, I am afraid, frank discussion, frank conversation, honest 
discussion, honest conversation, difficult conversation, difficult discussion, out 
of options, no remaining options, no more therapy, no further treatment, end 
of life care, limit invasive procedures, natural death, molst, polst, advance 
care, advanced directive, advanced directives, advance directive, advance 
directives, life support, life prolonging, prolong life  
 
Code Status Limitations 
Intubation, resuscitation, vent, CPR, no intubation, no resuscitation, no CPR, 
declines CPR, do not intubate, do not resuscitate, DNR/DNI, DNR, DNI, 
DNRDNI, DNH, declines cardiopulmonary resuscitation, no cardiopulmonary 
resuscitation, declines intubation, no chest compressions, no compressions, 
no defibrillation, no mechanical intubation, refuses intubation, refuses CPR, 
DNAR, do not attempt resuscitation, no bipap, no NIPPV, comfort care, 
comfort approach, CMO, comfort directed care, prioritize comfort, comfort 
measures, code status, DNR OK to intubate, DNR/DNI/+LLST 
 
Hospice 
Hospice, bridge to hospice, home hospice, inpatient hospice, hospice house, 
hospice at home, GIP 

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Palliative Care 
Palliative medicine, Palliative care, pall care, pal care, pallcare, palcare, PC, 
supportive care, pediatric palliative care (PPC) 
 
Time Limited Trial 
Time limited trial, limited trial, TLT 
 
Resuscitation and 
Intubation Preferences 
Full code, FC, full intubation, full resuscitation, Intubation, resuscitation, CPR, 
no intubation, no resuscitation, no CPR, declines CPR, do not intubate, do not 
resuscitate, DNR/DNI, DNR, DNI, declines intubation, declines 
cardiopulmonary resuscitation, no chest compressions, no compressions, no 
defibrillation,      mechanical intubation, refuses intubation, refuses CPR, code 
status discussion, discussed code status, life support, DNAR, do not attempt 
resuscitation, allow natural death, code status 
 
Enteral Feeding 
Artificial nutrition, feeding tube, supplemental nutrition, nutrition support, PEG, 
dobhoff, G tube, gtube, g tube, J tube, jtube, j tube, GJ tube, gj tube, no 
artificial feeding, no feeding tube, declines feeding tube, refuses feeding tube, 
enteral feeding, gastrostomy tube, NG tube, nasogastric tube, OG tube, 
orogastric 
 
Dialysis 
Renal replacement therapy, hemodialysis, HD, iHD, CVVH, AVVH, 
hemodialysis not within goals, RRT, conservative management, medical 
management without dialysis, no dialysis, dialysis, peritoneal dialysis, PD 
 
Support for NLP will also come from Yale University, a subcontract site in the grant though they 
will be IRB exempt since no human subjects research or identifiable data sharing will occur. The 
PI, Dr. Prasanna Ananth, will assist with validating keyword libraries for domains of interest 
(e.g., goals of care) across multiple study sites. She will also oversee natural language 
processing methods to evaluate the key study outcomes in clinical notes extracted from the 
electronic health record. 
6.1.2 Primary and Secondary Outcomes 
Child- and Parent-level data: Demographic: We will obtain key baseline patient demographic 
information from each health system’s EHR. This will include: age, gender identity, race/ethnicity 
identity, primary language, religion. We will also use the Social Deprivation Index (SDI), which 
is a composite measure of seven demographic characteristics collected in the American 
Community Survey (ACS): percent living in poverty, percent with less than 12 years of education, 
percent single-parent households, the percentage living in rented housing units, the percentage 
living in the overcrowded housing unit, percent of households without a car, and percentage 
nonemployed adults under 65 years of age.178 The SDI measure was calculated at four 
geographic areas: county, census tract, aggregated Zip Code Tabulation Area (ZCTA), and 
Primary Care Service Area (PCSA). SDI scores are available for all counties, census tracts, 
ZCTA’s, and PCSA’s.178 Diagnoses: The EHR will provide baseline information about diagnoses 
for children. 
 
TABLE 4: Data Element 
Purpose 
EHR 
Survey 
Video Link 
Demographic 
Covariate (moderator) 
X 
 
 
Disease type 
Target 
sub-population 
identification, 
covariate 
X 
 
 
GOC documentation 
1o outcome 
X 
 
 

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GOC documentation (Primary Outcome): We will obtain the presence and content of GOC 
documentation from the EHR as assessed by documentation of GOC in the patient’s notes using 
the NLP-assisted and human-confirmed program used in our prior work.  
 
Preferences (Secondary Outcome): We will follow resuscitation preferences such as Full code, 
Do-not-resuscitate (DNR), Do-not-intubate (DNI), Do-not-hospitalize (DNH), and preferences 
around nutrition and hydration, and dialysis from the EHR. We will obtain the number and timing 
of palliative care visits and hospice use.  
 
Additional pragmatic outcomes: Health services utilization: We will obtain the use, timing, 
and extent (instances or days of service) of ICU, CPR, ventilation, and hospice use, as well as 
burdensome interventions (CPR, intubation, tracheostomies and dialysis). Intervention 
implementation: We will obtain data about the use of the videos through the video links and 
video cards by monitoring video use by the navigators as well as remote viewings by parents. 
 
Parent surveys: A subgroup of 136 randomly chosen parents in the intervention and control 
periods will have surveys assigned to them via REDCap. (This can be done via REDCap to assure 
random selection.) We will oversample parents of African American, Hispanic, and rural children 
as we have done for the larger trial. Given that African American, Hispanic, and rural children are 
at higher risk for dying in the hospital, we will over-sample our patients to include 45% (N=228) 
from under-represented communities. Parents will receive the survey at the time of randomization 
(i.e., initial visit), and then again after nine months (i.e., end of intervention or control period/cycle). 
We will contact parents by telephone after a week if the nine-month survey is not completed. 
 
Parental Health Literacy Activities Test (PHLAT): We will use the PHLAT survey tool to measure 
health literacy during the baseline interview.179 The PHLAT is a well-validated tool to assess 
parental health literacy and numeracy skills and has also been validated in Spanish-speaking 
parents (PHLAT Spanish).179,180 Assessment of health literacy will occur at the baseline visit. 
 
 
Parent Feeling Heard and Understood: We will ask 5 validated items regarding “feeling heard and 
understood” by the oncology team (e.g., I felt heard and understood by the oncology team. I felt 
my child was heard and understood. I felt the oncology team put my child’s best interests first. I 
felt the oncology team saw my child as a person. I felt the oncology team understood what was 
important to my child).161 Each statement is rated on a five-point Likert scale. 
 
Parent Satisfaction with Healthcare: We will use two items from the Survey about Caring for 
Children with Cancer (SCCC) to assess satisfaction with healthcare.35 The first assesses the care 
team’s sensitivity to the child’s needs (response options: a great deal, a lot, somewhat, a little, 
not at all). The second assesses quality of care delivered by the care team (response options: 
excellent, very good, good, fair, poor). Both surveys are available and validated in Spanish. 
 
This survey for UH3 will be provided in a subsequent amendment following any UG3 phase 
refinements.  
6.2 Ensuring Study and Intervention Fidelity 
Ensuring Study and Intervention Fidelity: A fully pragmatic trial aims to maximize the “real 
world” character of the intervention implementation. It is also desirable to evaluate implementation 
Preferences (CPR, etc.) 
2o outcome 
X 
 
 
Health Services Utilization 
2o outcome 
X 
 
 
Parent Surveys 
2o outcome 
 
X 
 
Intervention/Video use 
Monitoring fidelity 
 
 
X 
Navigator activity 
Monitoring fidelity 
 
X 
 

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fidelity. Accordingly, we will monitor aspects of the intervention (Table 3) including number of 
interactions with parents over the course of the nine months of the intervention per cycle. This will 
include: length of each interaction, presence of additional family members, and, telephonic vs. 
televisual (each is automatically documented in the EHR with telehealth visits). Navigators will 
also use REDCap forms that template each aspect of the intervention. Accordingly, we will derive 
a measure of navigator implementation fidelity through REDCap based on a survey tool developed 
by Ang and colleagues specifically to assess fidelity of GOC interventions.73 Navigator use of these 
forms will yield: length of contact; content addressed (GOC, code status, video use, other); contact 
with family and type (e.g., number of parents/family, friend); and, strategy used to assess patient 
comprehension.74 
 
We will employ rigorous training procedures with in-person and remote training for navigators 
delivering the intervention. There will be continuous quality assurance by the investigative team 
and bi-weekly supervision calls with the Navigators. Bi-weekly supervision calls will include Drs. 
Volandes and Paasche-Orlow, who have trained over 1,000 clinicians in the GOC Video 
Intervention, and/or the PIs. This will involve review of challenging cases and role-playing. In 
addition to the bi-weekly individual calls, there will also be monthly group calls that will be 
supervised by Drs. Wolfe and Snaman covering GOC topics and case discussions. A key aspect 
of intervention fidelity will be review of audio-recorded calls. We will audio-record (with verbal 
parent consent) 5% of calls from each navigator over the course of the RWCT to enable us to 
assess the content of clinical encounters. The local site-PIs and overall site PI/Co-I/PM at MGH 
will review these audio-recorded interactions to provide feedback to navigators. This will be done 
with each navigator once during each of the three randomization cycles. In addition, themes from 
these feedback sessions will be brought anonymously to monthly group case-based navigator 
discussion sessions. 
 
Table 3: Fidelity 
Steps Taken to Ensure Fidelity 
Fidelity Assessment 
 
Navigator 
Training 
- Use of a standard intervention training for 
navigators 
- Bi-weekly check-ins run by Drs. Volandes 
and Paasche-Orlow 
- Monthly remote Case-study sessions (PI led) 
- Retraining seminars via video conferencing 
with all navigators delivering the intervention 
- Complete review of intervention guide 
- Completion of VitalTalk training session 
- Ongoing participation in Case-Study 
sessions 
- Assess pre- and post-knowledge that 
navigators acquired during retraining 
 
Intervention 
Delivery 
- Measure extent of exposure to the GOC 
video 
- Evaluation of REDCap documentation of 
content addressed during encounters 
 
- Measure video exposure, document date 
of video viewing & playthrough rate 
- Site-PIs will review REDCap forms and 
audio-recorded visits (5%) to ensure 
adherence to content 
 
 
Data Collection based on RE-AIM QuEST Framework: The RE-AIM framework is used to 
systematically assess key dimensions of intervention implementation to enable future 
dissemination in real-world clinical settings. RE-AIM developers emphasize the importance of 
collecting qualitative data to complement quantitative measures to comprehensively understand 
the contextual determinants of intervention implementation.174-177 Throughout the project period, 
we will hold monthly video conferences with navigators and create a log describing the barriers 
and facilitators for implementation and adoption. Drs. Volandes and Eche are nationally 
recognized leaders in implementation science and qualitative data analysis. They will then use 
this feedback to further develop the semi-structured interview guides for the qualitative interviews 
with key informants. We will conduct qualitative interviews stratified by participating site. For each 
key informant group, we will interview 30 individuals (i.e., ten at each site). Specifically, we will 
conduct interviews with 1) 4 parents ; 2) 6 clinicians (4 primary oncology providers and two clinic 
leaders) at each site for a total of 30 key informants to identify facilitators and barriers to the 

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adoption, implementation, and maintenance of the GOC Video Intervention. We will collect the 
following data:  
Reach: We will assess: 1) the number of eligible parents who were approached with the 
intervention; 2) number engaged, and characteristics of refusers and enrollees; and 3) reason for 
refusal to engage. We will also utilize the qualitative interviews with parents and clinicians to 
assess recruitment and retention facilitators and barriers and discuss how they can be addressed.  
Effectiveness: We will evaluate effectiveness based on the comparative effectiveness of the 
video program to usual care on parent-reported outcomes. Additionally, we will analyze qualitative 
interviews of parents and clinicians about perceived effective features of the intervention.  
Adoption: To examine adoption, we will assess parent participation rates (i.e., % of eligible 
parents viewing videos and telehealth sessions). We will also quantitatively summarize proportion 
of navigators completing the REDCap surveys for telehealth visits. We will solicit feedback during 
our qualitative interviews with navigators, clinicians, as well as clinic leaders related to 
implementation logistics and barriers to integration of these care models into clinical practice. In 
qualitative interviews with parents, we will focus on individual factors that may have affected their 
participation and their desire to engage with the intervention and whether it addressed their needs.  
Implementation: We will assess implementation based on fidelity to the protocol and intervention 
delivery. We will review and quantitatively summarize data on documentation of GOC domains 
addressed during navigator encounters using the EHR. We will also review the REDCap surveys 
from navigators longitudinally to assess changes in the patterns of GOC domains addressed 
throughout the project period. In qualitative interviews with parents and clinicians, we will assess 
overall satisfaction with the intervention and focus on ideas for intervention modification and 
adaptation to maximize implementation into practice.  
Maintenance: We will assess the comparative effectiveness of the intervention vs. usual care on 
care delivery to assess maintenance of intervention effects. During qualitative interviews with 
parents, we will explore whether modification to the intervention is needed. With clinicians, as well 
as clinic leaders, we will explore barriers and facilitators to the intervention maintenance and 
integration into standard practice. The team will continually review processes and surmount 
barriers to successful implementation of the intervention. 
6.3 Alternative Treatments and End of Study Procedures 
The alternative to participation in the pilot and development UG3 phase is not participating. 
Compared to standard care, involvement in the RCT (UH3) will involve answering surveys and 
participating in a semistructured interview. Additionally, those assigned to the intervention will be 
followed-up by the Navigator. Similarly to UG3, the alternative is not to participate. At end of study, 
control participants will be offered the Video component of the intervention also. No other ancillary 
care needs are expected. People who decline participation will continue to receive standard care 
without participation in the proposed research. 
6.4 Study Incentives 
UG3: Parent or provider participants will be offered a $50 gift card (for either focus group or 
interview participation). 
UH3: Parents will be offered $20 for participation in the intervention, $20 for surveys (for the 
subset assigned this additional ask), and $50 for exit interviews. Providers (primary oncologists 
or clinic leaders) will be offered $50 for exit interviews.  
 
Parent Advisors (N=3) will receive $100 gift card for their collaboration.  
 
We believe the amount is a symbolic thank you for their time that will not be an undue influence 
on the decision to participate. Gift cards will be delivered by email or in-person. 

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7. Statistical Analysis 
 
Given the randomized nature of the planned study, we will report our results according to 
CONSORT guidelines. We will record subject attrition and note all adverse events. We will 
employ the intent-to-treat principle in our comparative analyses between the intervention group 
and the control group. Our pre-specified hypothesis tests limited to three in number (2 from Aim 
1 and 1 from Aim 2) and each will employ its own nominal significance level.  Any post hoc 
analyses will employ adjustments for multiple hypothesis testing via a Bonferroni correction. In 
univariate analyses, we will examine the distribution of outcome variables, as well as the 
distributional characteristics of all other salient study variables. We will generate descriptive 
statistics (means, standard deviations, quantiles for continuous variables; counts and 
percentages for categorical variables) and schematic plots (box-and-whisker, quantile-quantile 
plots). We will compare the study groups in descriptive analyses to examine the balance in 
distributions on covariates achieved through randomization. We will compare the outcomes 
between study groups using chi-square tests for categorical outcomes and two-sample t tests 
for continuous outcomes. In addition, we will use multiple logistic or linear regression models to 
include randomization stratifying variables (site) and predictors of outcomes to increase the 
precision of effect estimates. These additional variables will be better defined in an amendment 
prior to the UH3 phase after year 2 involving randomization. SAS version 9.4 will be employed 
for all statistical analyses. 
In addition to comparing the Intervention to Waitlist-Control arms, we will perform “dose-
response” analyses within the intervention arm using the rate per month per patient of the 
number of telephone contacts made by the navigator as the measure of the level of treatment. 
We will first examine the distributional characteristics of this variable both overall and within 
each subgroup of interest (e.g., race/ethnic groups, rural/not rural) in order to determine the 
form of the variable that will produce the most valid and clinically relevant estimate of 
association with outcomes. This represents a quantitative assessment of fidelity. In addition, we 
will have a qualitative assessment of fidelity (described below).  
Reporting dropout and missing data. Whenever a participant drops out of the study, we will 
document the specific reason for dropout, who decided that the participant would drop out, and 
whether the dropout involved intervention participation. If a participant withdraws from the 
intervention only, we will continue to collect data on all outcome measures. As noted above, all 
participants included will be accounted for in a CONSORT diagram. All post-randomization 
exclusions will be documented and accompanied by a rationale for exclusion. 
9.1 Data analysis plan for quantitative outcomes 
For UG3 acceptability, we will use proportions, means and SD, medians and IQR, or raw 
numbers as appropriate. We will report race/ethnicity and language profile of enrolled, refusals, 
and dropouts as well as reasons for refusals and dropout to assess the risk for selection bias 
and incorporate this information into our trial design. 
For UH3,  we will compare GOC documentation in 504 patients aged 0-12 with cancer randomly 
assigned to our GOC Video Intervention vs. Waitlist-Control.  
9.2 Data analysis plan for qualitative outcomes 
We will use a focused classic thematic analysis approach using grounded theory as the 
conceptual framework. Starting with a set of predefined codes (deductive coding) we will use 
inductive coding with further iterations to fit the data until saturation is reached.109  Data coding 
will be performed by at least two people. Differences will be solved by team reflective discussion. 

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Analyses will be done using MaxQDA software.110 Given their expertise in qualitative methods, 
Drs. Wolfe,and Snaman (site PI at DFCI) will oversee all aspects of focus group and exit interview 
analyses.   
 
9.3 Power analysis  
Statistical power and sample size. Our estimates for GOC documentation rate for Waitlist-
Controls and Intervention for overall and each mutually exclusive subgroup are summarized in 
the table below. The study is planned for testing the interaction for H1b; therefore, it has more 
than sufficient power for H1a.  
 
 Table 1 
Total 
N 
Waitlist-
Controls 
Intervention 
Power 
MDD* 
Overall 
504 
4.8% 
27.3% 
99% 
7.2% 
Non-Hispanic, non-rural White 
276 
6.5% 
20.1% 
80% 
13.6% 
Minority 
228 
2.6% 
36.0% 
  
10.3% 
Non-Hispanic African American 
76 
2.6% 
36.8% 
91% 
28.0% 
Hispanic 
76 
2.6% 
36.8% 
91% 
28.0% 
Rural 
76 
2.6% 
34.2% 
86% 
28.0% 
 * minimally detectable difference with 80% power assuming alpha=0.05 for the overall group 
and alpha=0.0125 for the four mutually exclusive subgroups.  
 
H1a Overall. We expect 4.8% documentation in the waitlist-control arm and 27.3% in the 
intervention arm. This is similar to our prior trials showing similar effects.2,3 We will have 99% 
power to detect the difference of 22.5% which well exceeded the minimal detectable difference 
of 7.2% with 80% power and a two-sided alpha of 0.05.  
H1a Subgroup-specific differences. We also examine power for subgroup-specific differences in 
GOC documentation at an alpha level of 0.0125 to account for multiple comparisons hypothesis 
testing. As shown in the Table, all 4 subgroups will have 80% or higher power for the 
comparison between the two study arms.  
H1b Heterogeneity-of-treatment effects. We expect the intervention effect to be a 13.6% 
increase (from 6.5% to 20.1%) in GOC documentation among non-Hispanic, non-rural Whites 
compared to a 33.3% increase (from 2.6% to 36%) among all other groups combined. This is 
similar to our prior trials showing greater effect in subgroups.2-4 The study will have 80% or 
higher power to detect the difference-in-differences with a two-sided alpha of 0.1.   
In summary, we expect that we will have sufficient statistical power to detect clinically 
meaningful effects of the GOC intervention for our primary outcome and in subgroup-specific 
analyses. 
8. Risks and Discomforts 
8.1 Potential Risks  
There are no known risks for any subjects participating in this study beyond the emotional 
reaction that some questions might cause and the erroneous sharing of protected health 
information. There is potential benefit to subjects participating in some aspects of this study. 

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The experience of the intervention could serve to improve parents’ understanding of medical 
care for their children and improve communication for GOC and self-determination. 
 
With the randomized waitlist-controlled trial we can curate the list of people who will be assigned 
to get the intervention at the start of each of our three nine-month cycles to either Intervention or 
Waitlist-Controls. We have pre-specified the target gender, racial and ethnic distribution of 
children in each health system who will be in this trial, that is: 50% Women, 15% Hispanic, 15% 
Non-Hispanic Black, 15% non-Hispanic rural, and 55% Non-Hispanic White (see Planned 
Enrollment Table). The randomized waitlist trial method enables these prespecified design 
choices. Further, we will strive for the 5% audiotaped sample of navigator interactions with 
parents will reflect the demographic distribution of the study population.  
 
We do not foresee a significant challenge with ensuring follow-up as all study activities are 
completed either passively by patients (i.e., via EHR), through consent in a single recorded 
episode (i.e., the interaction between the navigator and the parent), or through consent in a 
single qualitative interview. For the subgroup of parents that will be surveyed, we expect 5% of 
parents not to complete the surveys and we have chosen an appropriate number of parents to 
survey to have the appropriate powered analyses. 
  
To date, most randomized trials conducted with children with cancer and their parents were 
evaluated under ideal circumstances (i.e., explanatory trials). Pragmatic trials, which intend to 
determine the effects of interventions under usual conditions, are a next critical step in research 
involving children with cancer and their parents. Based on the Pragmatic–Explanatory 
Continuum Indicator Summary Tool, the rationale for the proposed pragmatic trial is compelling 
and we will abide by the extended CONSORT recommendations for pragmatic trials.63-65 Our 
three participating health care systems will engage parents of children with cancer in goals of 
care as a standard of care. Thus, the proposed trial is designed in a manner that fits the ethical 
and clinical parameters of outpatient-based palliative care and will provide data to understand 
the impact of our proposed intervention.  
While many large-scale pragmatic trials are implemented with a stepped-wedge design, this trial 
is designed as a pragmatic randomized waitlist-controlled trial. We can do the randomized 
waitlist-controlled trial design as our intervention model and clinical context allow for this 
approach, which has several notable advantages over the stepped-wedge design. This design 
is practical for the circumstances of the current proposal and provides the full research rigor of 
an RCT that is randomized at the patient level. This is far superior to randomization at a group 
level (e.g., provider, clinic). The stepped-wedge design is much more susceptible to the 
influence of secular trends and would require a much larger patient sample size to evaluate the 
same outcomes. Similarly, in the context of a stepped-wedge design pre-specified subgroup 
designation for oversampling is not feasible. Accordingly, the waitlist design is more efficient, 
more rigorous, and more amenable to research regarding demographic subgroups than a 
stepped-wedge design. Both study designs share the benefit of being able to eventually provide 
the intervention to all people in the target population; this is a trial design feature that was 
preferred by our clinical partners. 
 
One of the principal risks of participating in this research is the possibility of loss of confidentiality. 
The likelihood of these risks is very low. The questions that could cause emotional responses are 
clearly within the scope of normal clinical care. In the unexpected event of significant 
psychological distress due to participation, 1) Participants will be reminded that participation is 
voluntary and that they may stop participating at any time for any reason. 2) If a participant 

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experiences distress, additional psychological support will be offered to the participant at that 
time. Each pediatric cancer center has a system of psychosocial support for patients and family 
members, and participants will be referred to these existing supports should they experience 
distress and require additional support. 3) The site-PI will also be notified of any participant who 
experiences distress and be responsible for coordinating psychosocial referrals and ensuring 
follow-up. The MPIs will be notified within one business day from the time the site-PI is notified 
Given the extensive safeguards in place to protect subject’s confidentiality, the risk of serious 
breaches is extremely low. 
8.2 Protections to Minimize Risks 
Overall, this study presents no more than minimal risk. None of the risks are expected to be 
significant. The following safeguards to minimize such risks will be in place:  
Subjects will be informed that they can refuse to answer any question and may choose to stop 
participating at any time. In addition, if at any time participants report feeling distressed because 
of study participation, a referral to a psychosocial clinician will be offered. Should a participant 
become distressed because of completing study they can stop at any time. The RA will offer to 
phone them back the next day to see how they are managing. If deemed necessary, the RA may 
suggest to the parent that they contact their primary healthcare provider. In the event the parent 
does not have a primary healthcare provider, the RA will offer the parent a list of appropriate 
referral sources if they wish. We will schedule all interviews at the convenience of parents and 
will administer them using their preferred method when possible (phone, video conference, in-
person). Notably, we have used similar procedures during prior trials and have not had anyone 
ask for or require added psychosocial support. 
Protections against risk from participation 
Subjects in the usual care arm will receive routine care and as such if a child presents with 
persistent distress, they will be cared for through typical mechanisms. During the consent process 
all participants will be counseled to follow-up with their usual providers if they are concerned about 
distress. For subjects in the intervention, GOC communication will be funneled to the primary 
oncology provider as appropriate and the pediatric palliative care (PPC) team may be referred 
when needed.  
Confidentiality safeguards  
Confidentiality safeguards include the use of unique study alpha-numeric code identifiers for all 
subjects. In addition to what was described in section previously, the REDCap system validates 
the identity of trusted partners using digital certificates and keep a full audit trail of all transactions.  
Management of PHI: PHI data will be collected directly through the pool list and REDCap. Most 
identifiers (names, emails, addresses) will be stored in separate protected tables accessible only 
to the local study team, system managers, and the PM. Once the database is locked, these 
identifiers will be destroyed (only those identifiers needed for analysis will remain in the final 
database). For subjects deemed ineligible (pool list and REDCap data), all PHI obtained for 
screening purposes will be destroyed as soon as possible. No study information will be released 
to any other party except to MGB or site IRBs and local regulatory authorities, if requested. 
Any breach of confidentiality will be subject to a root cause analysis and preventive measures 
taken as appropriate. All these procedures are likely to be effective based on our prior research 
experience. 

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Privacy and Confidentiality 
☒ Study procedures will be conducted in a private setting 
☒ Only data and/or specimens necessary for the conduct of the study will be collected 
☒ Data collected (paper and/or electronic) will be maintained in a secure location with appropriate 
protections such as password protection, encryption, physical security measures (locked 
files/areas) 
☒ Specimens collected will be maintained in a secure location with appropriate protections (e.g. 
locked storage spaces, laboratory areas) 
☒ Data and specimens will only be shared with individuals who are members of the IRB-approved 
research team or approved for sharing as described in this IRB protocol 
☒  Data and/or specimens requiring transportation from one location or electronic space to 
another will be transported only in a secure manner (e.g. encrypted files, password protection, 
using chain-of-custody procedures, etc.) 
☒   All electronic communication with participants will comply with Mass General Brigham secure 
communication policies 
☒ Identifiers will be coded or removed as soon as feasible and access to files linking identifiers 
with coded data or specimens will be limited to the minimal necessary members of the research 
team required to conduct the research 
☒ All staff are trained on and will follow the Mass General Brigham policies and procedures for 
maintaining appropriate confidentiality of research data and specimens 
☒ The PI will ensure that all staff implement and follow any Research Information Service Office 
(RISO) requirements for this research 
☒ Additional privacy and/or confidentiality protections 
 
 

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Each site will maintain and adhere to the process and procedures for the protection of human 
subjects and protected health information (PHI) for their covered entities. All data collected by 
the RAs will be stored in protected files on servers behind institution firewalls. Participant 
identifiers will be kept in separate password protected files and a third linking file will be 
maintained. The linking file will also be password protected, access will be minimized, and a 
logging feature will be used to identify each user and instance of use. Only the minimum amount 
of PHI necessary will be collected from study participants. Data from each of the clinical sites 
will be transmitted via secure, institutionally approved methods to MGH for data management 
and qualitative analyses. The MGH Research team, under the direction of Dr. Wolfe, will 
produce written transcripts of the videos and may also assist in coding the transcripts and 
grouping/summarizing the codes into themes for analysis using MAXQDA software.  
 
All information in the REDCAP database will be indexed by subject identifier, so that even if the 
database server is compromised subjects cannot be identified, thus maintaining the privacy of 
their information. Also, assurance of confidentiality of information will be made to all subjects. 
Data will be handled with the same confidentiality accorded to patients’ medical records. 
Specific procedures protecting subject confidentiality will be as follows:  
1. ID number only will be placed on electronic (or paper) study forms or records on which data 
are collected and/or stored.  
2. Access to data files will be secured with a password-filing system (that logs entry) and is 
restricted to authorized staff only.  
3. Necessary hard-copy records containing study data of any type will be kept in locked files.  
4. Master lists linking subject information with ID number will be numbered consecutively and 
prepared before data collection (to ensure accurate accounting). These lists will be kept locked, 
in duplicate, with access only by the PIs and the other investigators.  
5. All project staff will sign an oath of confidentiality to ensure their understanding of the terms of 
confidentiality required. They will be trained in specific procedures to ensure confidentiality.  
6. Sign-out procedures for all access to data files will be strictly enforced.  
7. All reports and publications will preserve participants anonymity. 
 
We will use of Dropbox for Business (DBFB) as the central repository for storing all of the fixed 
and NLP data that the sites send to us which will allow our data team to store data, 
documentation about data and code used to analyze the data in a platform that best 
compliments their workflow. DBFB is HIPAA compliant, approved for use by all sites, and will 
only be accessed by study staff.  
 
To carry out the study it will be necessary to collect and store some personal health information 
(PHI) including: 
• Contact information (names, addresses, email addresses, and phone numbers) necessary 
to identify subjects initially and ask for consent, send the mail surveys throughout the study. 
Medical record numbers needed to verify eligibility and abstract medical information.  
• Patient’s / Parent’s dates of birth, to calculate their age. 
 
These data will be collected during the recruitment process in the pool list and REDCap. All 
research staff collecting PHI will have HIPAA Certification and the training mandated by the 
Institutional Review Board. Confidentiality safeguards have been thoroughly described in 
sections 10 (Data Management Plan) and 8.2 (Protection against risks). 
 
Additional security features of the REDCap include: 

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• 
secure user authentication, password encryption in both front and back ends, and role-
based access controls that prevents users from accessing data that they are not 
authorized to see (e.g. patients cannot see other patients’ data and local RAs, Project 
Manager, or PIs cannot see other sites information; only authorized technical personnel 
who provide support can have access to each of the system’s back end data).  
• 
validation of the identity of trusted partners using digital certificates and full audit trail of 
all transactions.  
All study desktops and hand-held computers will be within the sites firewall. All participating 
centers’ information technology groups adhere to policies and practices under the HIPAA 
regulations creating a very tight computing environment, which makes it difficult for individuals 
external to the study to access the databases.  
Because of the safeguards in place, we believe that subjects’ confidentiality will not be affected, 
and the risk of serious breaches is extremely low.  
9. Benefits 
Potential benefits of the research to research subjects and others: The risks to subjects are 
reasonable in relation to anticipated benefits and in relation to the importance of the knowledge 
expected to result from the clinical trial. The research team has hypothesized a greater 
proportion of intervention participants will have documentation of GOC discussions (primary 
outcome) in the electronic health record. However, there may be no benefits to subjects from 
participation in the proposed research. Society, medical science and the health care system 
may benefit from the information obtained in the research on improving care for patients with 
advanced illnesses and limited prognosis.  
Data collected as part of the study will be made available to investigators who are part of the 
proposed study team or who join the study team. In addition, data will be shared with other 
investigators via the Open Science Framework repository (or other venue as directed by NCI) in 
accordance with NCI policy. This sharing and additional analyses promise to allow exploration 
of additional scientific questions.  
 
Why the risks to subjects are reasonable in relation to the anticipated benefits to subjects and 
others: Anticipated benefits exist for individual subjects as the intervention may improve care for 
patients. Specifically, there is a potential benefit to children to receive medical care that is 
concordant with their (parents’) goals and wishes. 
 
Importance of the knowledge to be gained as a result of the proposed research and why the 
risks are reasonable in relation to the importance of the knowledge that reasonably may be 
expected to result: Determining the use of video decision support tools for more informed 
decision-making for parents and children with cancer is an important area of research where 
there are currently very few data. The minor risk for the subjects in this study may be 
considered to be counterbalanced by the knowledge gained. The results gleaned from the study 
are intended to identify factors that promote medical care for cancer that are consistent with the 
individual preferences of parents. The use of video can be applied to design future interventions 
aimed at improving communication between clinicians and parents. The risks to subjects in this 
study are reasonable in relation to the importance of the knowledge that is expected to result. 
Thus, the risk/benefit balance for this study appears favorable. 

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10. Data Management Plan 
Data management will occur at all sites and data collected will flow to the lead site, MGB, for 
analysis and monitoring. As the Study Data Center (SDC), this will be covered by subcontract 
and data use agreements necessary. MGB will be responsible together with the study Data and 
Safety Monitoring Board (DSMB) for providing a specific data collection and monitoring system, 
including the design of the Data Management Plan, Standard Operating Procedures (SOPs), 
Data Validation Plan, study data collection and completion guidelines for investigators, 
supervising data collection procedures, assuring maintenance of high quality databases, and 
arranging an efficient and safe transfer of non-electronic study data, in compliance with Good 
Clinical Practices (GCPs). RAs and site PIs will be responsible for the local data centers (LDC) 
and will communicate with the SDC on a routine basis. RAs will be trained in data management 
procedures, GCPs, and human subjects protection before starting enrollment. All sites adhere to 
policies and practices under the HIPAA regulations creating a very secure computing 
environment. 
 
Each subject (child and parent) will be assigned a unique study identification number. Hard copy 
surveys will be stored in locked file cabinets and labeled with study ID rather than patient 
identifiers. Survey data will be entered into REDCap. Most data collection will be done using 
password protected Excel and REDCap systems on protected servers. (Minimally identified 
datasets from these sources will be shared with MGH through Dropbox Business as described.) 
All other source documents, audio files and transcripts, and survey data, will be created as or 
converted to electronic format and stored on HIPAA compliant cloud servers, accessible only 
through use of a unique password. In the case of audio recordings, participants’ names will not 
be directly linked in any way with the recordings and all personal references will be removed 
when the tapes are transcribed. Excel files are stored in RA’s computers or site’s network and 
accessible only to the study team. RAs will generate de-identified reports that will be shared 
with the lead site. Data user and confidentiality agreements between sites are in place allowing 
data to flow to MGH. Data will be sent by secure file transfer as allowable per site regulations 
and meeting GCP and HIPAA compliance standards (see Section 7.2.3. Confidentiality, for 
more details).  
 
We will track enrollment, retention, and data completion. Whenever an inconsistency is 
detected, it will be solved by the site RA and validated in the database by the PM at the SDC. 
The PM will audit inclusion, recruitment, and medical record abstraction processes by 
comparing inclusion/eligibility forms, and data abstracted from charts against medical records 
on a random sample of 10% of all screened subjects.  
 
Access to the data will be limited to the PI and designated study personnel at the above 
mentioned sites on a “need to know” basis and covered by Data User Agreements (DUA). The 
datasets may contain some identifiers such as dates of birth or death, zip code, or diagnosis 
needed for analysis (specified in the corresponding DUA) and will be shared through HIPAA 
compliant cloud servers (Dropbox Business). The SDC will oversee intra-study data sharing 
processes, with input from the DSMB. While on study, local PIs will have access to their site 
data and to summary reports of trial progress.  
 
At the end of the study, and after a comprehensive quality check and assurance, the final data 
validation will be run. If there are no inconsistencies, a pre-lock checklist will be used and 
completion of all data management activities will be confirmed. Once the approval for locking is 
obtained from all key project stakeholders, including the study statistician, the database will be 

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locked and clean data will be extracted for statistical analysis. The database will not be changed 
in any manner after locking. Once the database is consolidated, all investigators that are 
interested in leading a particular analysis, will be given access to the final password-protected 
de-identified (or minimally identified) data sets. Out of study investigators may be allowed 
access to the datasets after a formal analysis proposal is approved by the steering committee. 
This protocol operates under the single IRB model and as such, all sites will cede the review to 
the lead site and rely upon the DFCI IRB, as the MGH IRB of record. The study team will 
prepare and submit a "requested to rely" form for the DFCI IRB to serve as the IRB of record for 
this project. Ancillary reviews may still be completed by local IRBs as required.  
10.1 Monitoring and Quality Assurance 
10.1.1 Adverse event criteria and Reporting Procedures 
Any adverse events related to study procedures will be initially monitored by the study team 
(using the standard site study adverse event form / log), reviewed in site team meetings, and 
escalated as required. (The project manager, co-Investigators, MPIs and statistician will review 
aggregate data regarding adverse events in a blinded manner when at all possible.) 
Safety monitoring for the study will be overseen by the Safety Monitoring Committee (SDC) and 
the Data Safety Monitoring Board (DSMB). Information on all potential types of adverse events 
will be collected at all assessment points and recorded on standard forms (major violation or minor 
deviation logs). In preparation for their quarterly feedback, the DSMB will analyze the rates of 
adverse events and evaluate the possibility that the intervention is causing harm. If at any point 
there is a severe adverse event (such as a death, suicide or serious consideration of suicide, or 
a change in mental health requiring hospitalization, that is felt to be related to the study), we will 
suspend study activities and try to determine if there is any link between study procedures and 
the adverse event and determine if any modification is advised or if the study should be stopped. 
If an adverse event is detected, the PI will be responsible for promptly reporting it consistent with 
Mass General Brigham, local sites, and funding agency policies.  
The MPIs and the DSMB are responsible for monitoring the proposed clinical trial as supervised 
by their respective IRBs. The DSMB will further monitor the study to review any breaches in 
protocol or confidentiality or other adverse events. To evaluate safety in the randomized trial 
and to review any potential breaches in protocol or confidentiality, and other adverse effects, the 
DSMB will have planned meetings every six months and additional meetings if needed. 
Additional meetings will be arranged if required based on a need to review information about 
events or issues that may arise, such as an unexpected number or severity of adverse events. 
For safety monitoring, discussion will take place on whether or not reported incidents are 
unanticipated and/or place subjects or others at greater risk of harm and if protocols or consent 
processes need to be modified. Unanticipated incidents will be reported to the IRB and/or 
funding agency promptly.  
We will follow guidelines set forth by each site’s IRB regarding “unanticipated problems” and 
“adverse events.” Unanticipated problems are defined at MGH/Dana-Farber as events that are 
1) unanticipated, 2) related to the research, and 3) a new risk or serious event (e.g., death, life 
threatening, hospitalization, disability, birth defect, or requires medical or surgical intervention to 
prevent any of those from happening). Unanticipated problems will be reported within two days 
of the investigator learning of the incident as well as to the IRB. The report will explain why the 

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incident is considered an unanticipated problem and how the protocol will be modified in 
accordance with a corrective action plan. Incidents that do not meet all three of the criteria noted 
above will be considered adverse events or serious adverse events but not unanticipated 
problems. In these cases, they will be reported to the IRB at the time of the annual progress 
report. The report will provide information on cumulative incidents, and if in total the events 
suggest that subjects or others are at greater risk than initially determined, then the 
investigators will address whether or not the consent form needs to be changed.  
10.1.2 Data and Safety Monitoring Plan 
As the sIRB hub of this project, Dana-Farber Cancer Institute IRB will serve as the hub for all 
ethical and regulatory processes for the protection of human subjects and privacy protections.  
A study scientific Data Safety and Monitoring Board (DSMB) consisting of scientists who are not 
affiliated with any of the study sites will be convened at the beginning of the study, via several 
conference calls / videoconferencing, 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. They will also provide input and feedback every six months, via 
e-mail and conference calls, related to study recruitment, study eligibility determination issues, 
consent processes, data completion rates, and adverse events. Well-respected scientists with 
clinical trial research experience in decision making or related areas with children with cancer 
and are familiar with all of the areas noted above will be selected.  
We have created a list of DSMB Advisors with expertise in pediatric cancer care, palliative care, 
pragmatic trials, implementation science, and biostatistics. DSMB Advisors include: Pamela S. 
Hinds, RN, PhD, Executive Director of the Department of Nursing Science, Professional 
Practice, and Quality, the William and Joanne Conway Endowed Chair in Nursing Research, 
and the Research Integrity Officer at Children's National Health System in Washington, D.C., 
and a Professor of Pediatrics at the George Washington University, School of Medicine and 
Health Sciences in Washington, D.C. Dr. Hinds is an international leader in pediatric cancer 
care, GOC discussions, palliative care, and quality improvement; Dr. Tammy I Kang, MD, 
MDCE, Professor of Pediatrics, Palliative Care, Baylor College of Medicine and inaugural 
Division Chief of Palliative Care at Texas Children’s Hospital and board member with the 
American Academy of Hospice and Palliative Medicine. Dr. Kang is an international leader in 
pediatric palliative care program development, implementation, and evaluation; Rachel 
Thienprayoon, MD, MSCS Associate Professor of Anesthesia, University of Cincinnati, Medical 
Director of StarShine Hospice and Palliative Care. Dr. Thienprayoon is an expert in pediatric 
palliative care quality improvement and a member of the board of directors of the Palliative Care 
Quality Collaborative and the Chair of the Pediatric Palliative Care Taskforce of the National 
Coalition of Hospice and Palliative Care; Liliana Orellana, PhD, Professor of Biostatistics, 
Deakin University. Dr. Orellana has served as the lead biostatistician on the PediQUEST Trials, 
evaluating primary and specialty palliative care interventions in children with cancer. 
In preparation for their feedback, the DSMB will compile the rates of adverse events and 
evaluate the possibility that the intervention is causing harm. Project staff will provide data to the 
DSMB. The DSMB will be free to determine the need to stop the protocol due to harm or early 
proven benefit (or futility) - based on examination of adverse events or a proven statistically 
significant difference between intervention and control as determined by a blinded between arm 
analysis done at predefined intervals. The DSMB will independently confirm all parameters of 

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early stopping rules as well as all other procedures as part of initiating their DSMB Charter. At 
minimum, in each report it will be recommended that the DSMB will examine rates of adverse 
events and evaluate a preset stopping rule for a statistically significant (one sided P<0.05) 
higher count of adverse events (i.e., emotional distress) in the intervention group. The study 
team will be blinded to the results. Further, the study team, including the project manager, 
statistician, co-Investigators and research assistants, led by the study MPIs, will report to the 
DSMB regarding the progress of the research, including periodic assessments of data quality, 
subject recruitment, accrual, and factors external to the study when interpreting the data, such 
as scientific developments or the new availability of proven clinical services that could have an 
impact on the safety of the subjects, the performance of the study or the ethics of the study.  
Meetings of the DSMB will have open-session and closed-session periods. The MPIs and the 
co-Investigators will attend the open portion of these meetings but will not vote and will not 
participate in the closed portion of the meetings. Blinded reports will be generated for these 
sessions. The study statistician, Dr. Yuchiao Chang will be designated to remain at the start of 
the closed session if unblinding will be requested. Dr. Chang has no contact with study subjects 
and is well versed in the ethical requirements of working with and between a study team and a 
DSMB. Following each meeting, the DSMB will make recommendations on continuation, 
modification, or termination of the studies. Within three months of the start of funding we will 
constitute the DSMB, name the members and establish its charter. We have had success with 
these DSMB methods in pervious trials.  
Risk assessment  
Participation in the proposed research is “minimal risk” which is defined as “the probability and 
magnitude of harm or discomfort anticipated in the research are not greater in and of 
themselves from those ordinarily encountered in daily life or during the performance of routine 
physical or psychological examinations or tests,” (from 45 CFR 46.102(i)), with the exception of 
the risk of loss of confidentiality. This risk (as well as the other risks) is addressed above. The 
risk of breach of confidentiality is best addressed by appropriate study procedures; however, the 
MPIs will be responsible for assuring that study procedures are adhered to regarding data 
security, transfer, and communications in tracking subjects by meeting regularly with study staff, 
reviewing procedures and performing quality control reviews of study forms. Our assessment 
that the proposed project be regarded as minimal risk is based on over a decade of research 
experience relating to decision making and has been affirmed by 16 different institutional review 
boards that have been involved with various previous and current multi-site trials. If the 
institutional review board for the current proposal arrives at a different assessment, we would 
certainly adapt our approach accordingly.  
Data Management and Security to Protect Privacy  
The Data Management Plan (DMP) employed in this clinical trial has been developed in other 
studies and assures high quality forms, monitors data quality, and tracks and links the multiple 
data sources. Data are linked and entered using multiple checks. The DMP develops data 
collection forms, designs the database management system for data entered and for subject 
tracking, implements procedures for quality control, and provides statistical programming and 
collaborates in report writing and presentation of study results.  
Databases are located on secure, password-protected servers, behind the MGH/Dana-Farber  
firewalls. The web and database servers use Secure Socket Layering (SSL) to ensure data 

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security and confidentiality. Servers incorporate RAID hard drives for data redundancy. A 
separate web server dedicated for Cold Fusion applications is also available. Specifically, the 
policies for computer systems security implemented at MGH/Dana-Farber are as follows:  
o Provide physical security of data. The server resides in the same building as the Medical 
Center Office of Information Technology (OIT) servers. The lobby of the building in which the 
systems reside is under the security purview of the General Services Security Office and is 
under surveillance. All central systems are physically secured behind two card-access doors 
with access to the primary door restricted to key personnel in the OIT. Access through the 
primary door is also protected by a keypad alarm system that is tied directly into the on-site 
central emergency response security control center. Written policies exist for contingencies to 
provide access to the room to those not explicitly authorized.  
o Provide virtual security via connectivity. Internal access to all systems is done via Microsoft 
Challenge Handshake Authentication Protocol. With the exception of internet provider-based 
services, external client access must first gain access to the internal network before connecting 
to the systems. This connection is initiated via a Virtual Private Network connection using Point-
to-Point Tunneling Protocol or through the University's modem pool which require Kerberos 
authentication. All web-based mail is encrypted with high-encryption domestic SSL.  
All data are protected with disaster recovery via several methods:  
o Hardware redundancy: Several stages of redundancy exist at the hardware level to minimize 
failure: Dual-redundant power supplies exist on each disk array; hot-spare disk is configured to 
automatically self-heal in the event of a disk failure in the array; emergency power generators 
ensure a 100% electrical uptime; and uninterrupted power supplies present the systems with 
conditioned steady-state power.  
o Data backup: Backups are completed daily over the network using both on-site and off-site 
disk-based backup devices.  
o Data Security: All data are stored on servers that are password protected. To protect against 
security breaches, data will be electronically encrypted so that only the intended recipient can 
decode.  
Data collection forms. The DMP will support the research team in designing, piloting, and 
implementing data collection forms by ensuring that the data fields are unambiguous, and the 
systems for recording information function smoothly.  
Data Management Manual of Operations. The DMP includes a Manual of Operations to 
document all data collection and management procedures for the study.  
Quality control procedures for data collection and data entry. Quality control measures are 
essential in any research effort. The quality control measures implemented by the data 
management team and described in the manual of operations include detailed and 
unambiguous specifications for completion of each of the data collection forms, including rules 
for coding skipped questions, missing data, etc., and interim incremental data reviews to assess 
for variation in the data. Throughout the conduct of the study, the data management team will 

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be available to the research personnel by email, tele- and web-conference to clarify questions 
regarding the data collection.  
Quality control (QC). The Project Manager will monitor the quality of the data throughout the 
study, maintaining vigilance for outliers and other "blips" in precision, and, when found, exert 
prompt corrective action. QC measures will be: Detailed and unambiguous specifications for 
completion of study data; check for out-of-range codes and internal inconsistencies; data 
quality; interim analyses comparing data collectors to determine variations.  
Creation of analytic datasets for statistical programming. For qualitative data, Drs. Snaman and 
Eche will be responsible for supervising the coding, analyses, any consensus processes 
needed, and maintaining the data. Dr. Lindvall’s data teams will be responsible for cleaning the 
quantitative datasets, construction of the analytical variables, and writing the computer code to 
format and label each variable in the datasets. Documentation will be developed that will include 
data dictionaries defining the field names, location, and formats of all variables, the data 
collection forms, coding manuals, and documentation for computed variables and scale 
construction. Data will be cleaned in “batches” and cleaned batches appended to the master 
database. Statistical summaries will be provided.  
11. Return of Results 
Analysis of the trial results will include the full sample, unless scientifically justified. The Steering 
Committee will make recommendations regarding when and what material should be submitted 
for publication. Each paper will be reviewed and approved by the SC members prior to 
submission. The SC will work to reduce the interval between end of data collection and release 
of the study results. Publications will take place after each phase of the study. We expect to take 
about 4 to 6 months to compile and submit the main papers. Study results will be released to the 
participating physicians and referring physicians through publications in peer-reviewed journals, 
congress abstracts, and oral presentations. We will design lay summary materials to disseminate 
results among study participants (through the email addresses provided for the study) and the 
general public. 
Participants in the research can opt in to being contacted later with the eventual findings and 
publications of the study. This will be documented at the time of participation (where consent is 
waived) or consent. 
12. Long-term Data Storage 
Data stored on the DFCI server will reside there only for the periods they are required to be there for 
study usage. After analysis is complete we will keep our datasets stored for the required seven 
years and de-identified data indefinitely, which will reside at MGH in long-serve storage.  
13. ClinicalTrials.gov Requirement 
This application includes an applicable clinical trial that requires registration (e.g., at 
ClinicalTrials.gov) as the FDA Amendments Act (FDAAA) mandates registration and results 
reporting. Registration will be completed prior to enrolling the first participant in the clinical trial. 
The MPIs will be responsible for registration. As the trial has not yet been funded, it has not yet 
been registered and as such an NCT number is not available.  

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14 . References 
 
1.  McGuire DO, Tian LH, Yeargin-Allsopp M, Dowling NF, Christensen DL. Prevalence of cerebral 
palsy, intellectual disability, hearing loss, and blindness, National Health Interview Survey, 2009-
2016. Disabil Health J. 2019 Jul;12(3):443–451. PMCID: PMC7605150 
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APPENDIX A 
 
Data Monitoring Committee / Data and Safety Monitoring Board 
Appendix 
 
 
A Data Monitoring Committee (DMC) or Data and Safety Monitoring Board (DSMB) will be convened for 
safety monitoring of this research study. The following characteristics describe the DMC/DSMB 
convened for this study (Check all that apply): 
 
☒ The DMC/DSMB is independent from the study team and study sponsor. 
 
☒ A process has been implemented to ensure absence of conflicts of interest by DMC/DSMB 
members. 
 
☒ The DMC/DSMB has the authority to intervene on study progress in the event of safety 
concerns, e.g., to suspend or terminate a study if new safety concerns have been identified or 
need to be investigated.  
 
☒ Describe number and types of (i.e., qualifications of) members: 
See section 10.2 
 
☒  Describe planned frequency of meetings: 
See section 10.2 
 
☒ DMC/DSMB reports with no findings (i.e., “continue without modifications”) will be submitted 
to the IRB at the time of Continuing Review. 
 
☒ DMC/DSMB reports with findings/modifications required will be submitted promptly (within 5 
business days/7 calendar days of becoming aware) to the IRB as an Other Event.