Culturally Adapted Mobile Treatment of Chronic Pain in Adolescent Survivors of Pediatric Bone Sarcoma
Phase: NA
Conditions: Bone Sarcoma, Childhood Cancer
Sponsor: St. Jude Children's Research Hospital

Amendment 5.0, dated 03-06-2024
 
Protocol document date: 03-06-2024
St. Jude
ADAPTED
Initial version, dated:  08-25-2022, (IRB Approved: 00-00-00)
Amendment 1.0:  Dated 10-20-22 (IRB Approved: 11-14-23) Activated: 02-09-23
Amendment 2.0:  Dated 04-20-23, (IRB Approved:  06-01-23) Activated: 06-13-23
Amendment 3.0:  Dated 08-01-23, (IRB Approved:  08-24-23) Activated: 09-06-23
Amendment 4.0: Dated 11-20-23, (IRB Approved:  12-15-23) Activated: 12-20-23
Unnumbered Revision: Dated 02-21-24, (IRB Approved: 00-00-00) Activated: 00-00-00
Amendment 5.0: Dated 03-06-24, (IRB Approved: 00-00-00) Activated 00-00-00
CULTURALLY ADAPTED MOBILE TREATMENT OF CHRONIC PAIN IN 
ADOLESCENT SURVIVORS OF PEDIATRIC CANCER
Principal Investigator
Tara Brinkman, PhD
Department of Psychology and Biobehavioral Sciences
Department of Epidemiology & Cancer Control
Co-Investigators
Dylan Graetz, MD1
Michael Bishop, MD2
I-Chan Huang, PhD3
Nicholas Phillips, MD3
Deo Kumar Srivastava, PhD4
Kevin Krull, PhD5
Kirsten Ness, PhD3
Jerlym Porter, PhD5
Chiara Papini, PhD5
Global Pediatric Medicine1, Oncology2, Epidemiology and Cancer Control3, Biostatistics4, 
Psychology and Biobehavioral Sciences5 
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, Tennessee 38105-3678
Telephone: (901) 595-3300
Contents of this document may not be extracted without permission from the Principal Investigator.
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NCT05746429

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List of Collaborating Investigators/Institutions
Contact Information 
Dr. Tonya Palermo
Professor of Anesthesiology and Pain Management
 University of Washington/Seattle Children’s Hospital (SCH)
2001 8th Ave, CW8-6 Child Health, Behavior and Development
Seattle, WA 98121
206-884-7591
tonya.palermo@seattlechildrens.org
Dr. Eric Chow
Associate Professor of Pediatrics
University of Washington/Seattle Children’s Hospital (SCH)
4800 Sand Point Way NE
M.B. 8.501
Seattle, WA 98105
206-987-2106
ericchow@u.washington.edu
Dr. Karen Effinger
Assistant Professor in the Department of Pediatrics 
Emory University School of Medicine/Children’s Healthcare of Atlanta (CHOA)
5461 Meridian Mark Road, Suite 400
Atlanta, GA 30342
404-785-1112
karen.effinger@emory.edu
Dr. Lisa Wang
Associate Professor 
Baylor College of Medicine/Texas Children’s Hospital (TCH)
6621 Fannin St, Houston, TX 77030
832-824-4822
LLWANG@texaschildrens.org 
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Protocol Summary
MNEMONIC and Title: ADAPTED - CULTURALLY ADAPTED MOBILE 
TREATMENT OF CHRONIC PAIN IN ADOLESCENT SURVIVORS OF 
PEDIATRIC CANCER
Principal Investigator: Tara Brinkman, PhD
IND Holder: Not applicable
Brief Overview: This study will include (1) cultural adaptation of an evidence-based 
mobile cognitive behavioral therapy (CBT) program for chronic pain and procedures for 
transcranial direct current stimulation (tDCS) and (2) a feasibility study of adapted mobile 
CBT paired with tDCS. Participants will be recruited from four large pediatric cancer 
centers: St. Jude Children’s Research Hospital (SJCRH), Children’s Healthcare of Atlanta 
(CHOA), Texas Children’s Hospital (TCH), and Seattle Children’s Hospital (SCH). 
CHOA, TCH, and SCH will provide the study brochure, and if willing, participants will 
complete a Consent to Contact form.  SJCRH will screen, consent, and conduct all study 
procedures for all eligible participants for the study. 
Intervention: We will conduct a series of focus groups with non-Hispanic Black and 
Hispanic childhood cancer survivors to obtain their input on culturally adapting a mobile 
CBT program for chronic pain and tDCS procedures. Once this adaptation process is 
completed, we will conduct a feasibility trial with non-Hispanic Black, Hispanic and non-
Hispanic White childhood cancer survivors with chronic pain.
Study Design: Prospective study employing focus groups to culturally adapt CBT and 
tDCS procedures which will then be used for the second phase, a feasibility study. The 
feasibility study will assign eligible participants to either culturally adapted mobile CBT + 
active tDCS to the dorsolateral prefrontal cortex or culturally adapted mobile CBT + sham 
tDCS. 
Sample Size: We anticipate approximately 60 participants for the focus groups and 
approximately 30 participants for the feasibility study for a total of about 90 participants.
Data Management: The Study Team at SJCRH will design forms for data collection 
within the electronic database. Statistical analysis will be provided locally by the 
Biostatistics Department at St. Jude Children’s Research Hospital.
Human Subjects: The risks of participating in the study are low. This time commitment 
could be seen as a burden and some of the questions may make the participant 
uncomfortable. There may be some stress or anxiety based on the questions we will be 
asking. There is a risk of privacy loss, but we have taken measures to mitigate the risk, as 
will be detailed later in the protocol. There is low risk to participants related to active 
tDCS. Potential side effects include redness and slight tingling at the site of stimulation, 
and all side effects are transient. Recent meta-analyses show side effects to occur no more 
frequently than placebo conditions. 
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TABLE OF CONTENTS
1.0
OBJECTIVES....................................................................................................................1
1.1 Primary Objective ................................................................................................................1
2.0
BACKGROUND AND RATIONALE .............................................................................1
2.1 Background ..........................................................................................................................1
2.2 Rationale...............................................................................................................................7
3.0
PARTICIPANT ELIGIBILITY CRITERIA AND STUDY ENROLLMENT............8
3.1 Inclusion Criteria for focus groups.......................................................................................8
3.2 Exclusion Criteria for focus groups .....................................................................................9
3.3 Inclusion Criteria for feasibility study .................................................................................9
3.4 Exclusion Criteria for feasibility study ................................................................................9
3.5 Research Participant Recruitment and Screening ................................................................9
3.6 Enrollment on Study at St. Jude...........................................................................................9
3.7 Procedures for Identifying and Screening Participants......................................................10
4.0 DESIGN AND METHODS...................................................................................................10
4.1 Design and Study Overview...............................................................................................10
4.2 Study Procedures................................................................................................................17
4.3 Study Measures/Observations............................................................................................19
4.4 Sites....................................................................................................................................22
5.0 REQUIRED EVALUATIONS, TESTS, AND OBSERVATIONS....................................23
5.1 Pre-Study and Study Activities ..........................................................................................23
6.0 CRITERIA FOR REMOVAL FROM PROTOCOL.........................................................23
6.1 Off Study Criteria...............................................................................................................23
7.0 SAFETY AND ADVERSE EVENT REPORTING REQUIREMENTS..........................24
7.1 Adverse Events (AEs)........................................................................................................24
7.2 Definitions..........................................................................................................................24
7.3 Handling of Adverse Events (AEs) and Deaths.................................................................24
7.4 Process for Communicating Study-Wide Adverse Events.................................................26
8.0 DATA COLLECTION, STUDY MONITORING, AND CONFIDENTIALITY............27
8.1 Data Collection...................................................................................................................26
8.2 Data Collection Instructions for Collaborating Sites .........................................................26
8.3 Study Monitoring- Non-Therapeutic Risk Categories .......................................................26
8.4 Confidentiality....................................................................................................................27
9.0 STATISTICAL CONSIDERATIONS.................................................................................27
9.1 Anticipated Completion Dates (elements required by CT.gov).........................................29
10.0 OBTAINING INFORMED CONSENT ............................................................................29
10.1 Informed Consent Prior to Research Interventions..........................................................29
10.2  Consent at Age of Majority.............................................................................................29
10.3 Consent When English is Not the Primary Language......................................................30
11.0 REFERENCES…………………………………………………………………….…...31
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1.0 OBJECTIVES
  
1.1 Primary Objective
1.1.1. To leverage stakeholder input to culturally adapt an evidence-based 
mobile cognitive behavioral therapy (CBT) intervention for comorbid chronic 
pain in non-Hispanic Black and Hispanic adolescent survivors, and to obtain 
input on transcranial direct current stimulation (tDCS) implementation. 
Hypothesis: Stakeholder feedback will enable the cultural adaptation of 
intervention content and delivery for non-Hispanic Black and Hispanic 
adolescents through identification of tailoring variables and implementation 
strategies to maximize engagement.
1.1.2. To assess the feasibility of applying a culturally adapted mobile CBT 
and remote tDCS to a racially/ethnically and geographically diverse sample 
of non-Hispanic White, non-Hispanic Black, and Hispanic adolescent 
survivors of pediatric cancer with chronic pain (n=30).
 
Hypothesis: >60% of survivors will complete >75% of the mobile/remote 
intervention procedures.
2.0 BACKGROUND AND RATIONALE
2.1 Background
Survivors of pediatric cancer are a growing population with a high burden of 
morbidity: Advances in treatment and supportive care have improved 5-year 
overall survival for pediatric cancer to over 85%.1 However, the intensive 
treatments required to achieve cure often result in a high burden of physical health 
morbidity for survivors.2 It is estimated that 80% of adult survivors of childhood 
cancer will have at least one severe or life-threatening treatment-related chronic 
health condition by 45 years of age.3 Specific to survivors of bone sarcomas, 
survival has increased from less than 20% to 65-75% for localized disease over the 
past five decades.4, 5 Five-year survival for soft tissue sarcomas has improved from 
30% to 70%, although with variability by risk status.6, 7 Multimodal therapy for 
pediatric sarcomas often includes high-dose chemotherapy as well as primary 
tumor local control with aggressive surgery and/or high-dose radiation.8 This 
aggressive therapy places survivors at risk for long-term morbidity, including 
chronic pain, reduced physical function, and chronic health conditions. By 35 
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years of age, pediatric Ewing sarcoma and osteosarcoma survivors have an 
average of 3.5 and 4 severe and life-threatening chronic health conditions, 
respectively, compared to 0.9 in community controls.9 Long-term survivors of soft 
tissue sarcomas are at-risk for endocrinopathies and diseases of the nervous 
system, digestive organs, and urinary system.6 Racial/ethnic differences exist in 
the incidence of bone sarcomas as Blacks and Hispanics have higher rates of 
osteosarcoma compared to Whites.10 Similarly, soft tissue sarcoma incidence in 
children and young adults is higher among blacks compared to Whites.10 
Unfortunately, survivors who are members of racial or ethnic groups that have 
historically been underserved, mistreated, or marginalized by the biomedical 
community face disproportionately poor outcomes. For example, mortality is 
notably higher among Black and Hispanic compared to White pediatric sarcoma 
patients, and survival disparities by race and ethnicity in this population have 
grown over the past four decades.11 Importantly, disparities in pediatric cancer 
incidence and survival are not limited to sarcoma patients. For example, Hispanic 
individuals experience increased incidence of ALL compared to non-Hispanic 
Whites.10 Moreover, non-Hispanic Black and Hispanic patients with childhood 
cancer have worse survival for all pediatric cancers combined (leukemias and 
lymphomas, brain tumors, and solid tumors) compared to non-Hispanic Whites.12
Chronic pain is prevalent among survivors of childhood cancer: Chronic pain, 
defined as pain that lasts or recurs for 3 or more months,13 has a significant 
economic impact in the United States (U.S.), with an estimated yearly cost of over 
$19.5 billion for adolescents alone.14 A recent review of chronic post-surgical pain 
in children reported a prevalence of 20% (IQR, 15% to 38%) 12-months post-
surgery. Because pediatric bone sarcomas often require invasive local control 
(amputation or limb-sparing surgery), it is not surprising that pain is prevalent in 
these survivors. A recent report indicated that among pediatric patients with 
osteosarcoma, 34.5% met criteria for chronic post-surgical pain.15 We recently 
reported that long-term survivors of bone sarcoma were nearly 4 times as likely to 
experience moderate to severe pain that interfered with daily functioning than non-
cancer controls while survivors of soft tissue sarcomas were 9 times more likely to 
report such pain.16 However, data from the St. Jude Lifetime Cohort Study 
indicates that all childhood cancer survivors are at-risk for developing moderate 
to severe pain with daily interference compared to non-cancer community controls 
(e.g., Hodgkin Lymphoma OR: 3.38, 95% CI, 2.06-5.55; Non-Hodgkin 
Lymphoma OR: 4.13, 95% CI, 2.40-7.10; ALL OR: 3.10, 95% CI, 1.95-4.92).17 
Therefore, the experience of chronic pain is not limited to survivors of pediatric 
sarcoma, despite a higher prevalence in these survivors. Racial/ethnic disparities 
consistent with those observed in the general population also exist among 
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Political and Socioeconomic Context
Cultural and Societal Values
Socioeconomic
Position
Parent Education
Parent Employment
Household Income
Gender
Race
Ethnicity
Biological Factors
Comorbid health
conditions
Behavioral Factors
Physical activity
Substance use
Psychosocial Factors
Depression
Anxiety
Sleep
Fatigue
Peer relations
Parentaffectivefactors
Material Conditions
Access to recreational
spaces
Neighborhood SES
Health Care System
Health care access
Pain management
Cancer Diagnosis &
Treatment
Physiologic/
Psychological
Effects of Cancer
Treatment
Bone/tissue damage
Cancer-related worry
Health and
Well-Being
Differences in chronic
pain
Intermediate Determinants
of Health
Structural Determinants
of Inequality
survivors across all diagnoses as Hispanic and Black survivors are more likely to 
report pain than white survivors.18
Risk 
factors 
and 
comorbidities 
associated 
with 
chronic pain: Our 
discussion 
of 
potential risk factors 
and 
comorbidities 
associated 
with 
chronic 
pain 
is 
structured within the 
World 
Health 
Organization’s 
Commission on the 
Social Determinants 
of Health (CSDH) 
Framework.19 
Like 
other 
similar 
frameworks, 
including the framework developed by the National Institute on Minority Health 
and Health Disparities,20 CSDH asserts that health and well-being vary across 
domains and levels of influence. However, CSHD reorganizes the levels of 
influence into two broad categories: structural, which exert more distal influences 
on health outcomes and intermediate which have more proximal influences on 
outcomes. An additional benefit of CSHD is its description of how different 
categories of risk factors influence each other; this allows greater conceptual 
clarity than frameworks that simply present a list of categories. 
Structural determinants of inequality: The political and socioeconomic context 
(left side of Figure 1) of the U.S. is not the focus of this application. Nevertheless, 
we acknowledge that cultural and societal values, our economic system, and 
historical and persistent racism are key to setting the stage for health inequities. 
There is significant evidence from non-cancer populations that chronic pain is 
related to variables that shape an individual’s socioeconomic position. For children 
and adolescents, socioeconomic position is almost entirely dependent upon the 
position of their parents (e.g., parental education, income). Not surprisingly, 
socioeconomic risk factors for chronic pain in youth are similar to those of adults 
and include both female sex and lower household income.21, 22 Among adolescent 
survivors of childhood cancer, knowledge of how socioeconomic position 
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influences chronic pain is limited, but data from adult survivors reflect similar 
trends as observed in the general population with risk factors including female sex, 
lower educational attainment, unemployment, household income <$20,000, and 
Black and Hispanic race/ethnicity.18, 23 Importantly, childhood cancer and its 
treatment can have a substantial negative impact on parental socioeconomic 
situation. A recent systematic review revealed a high level of disruption in parental 
employment, income loss, and increased perceived financial burden following a 
child’s cancer diagnosis.24 In addition, >30% of families reported experiencing 
household material hardship at least 1 year-off therapy.25 These potential threats to 
parental socioeconomic position likely influence the experience of chronic pain 
and its management for adolescent survivors of childhood cancer.
Intermediary determinants of health: In addition to variables that shape 
socioeconomic position, intermediary determinants (middle part of Figure 1) 
including behavioral and psychosocial factors, material conditions, and healthcare 
systems may also be associated with chronic pain in childhood cancer survivors. In 
terms of behavioral factors, sedentary behavior and low cardiorespiratory fitness 
have been associated with increased risk of pain among children.26 A recent study 
revealed that drinking to intoxication was associated with a 3-fold increased 
likelihood of persistent pain among survivors of childhood cancer.27 Related to 
psychosocial factors, adolescents with chronic pain often experience mental health 
comorbidities28, including anxiety29 and depression.30 Fatigue and sleep 
disturbance are common among adolescents with chronic pain.31 Sleep is a 
potential mechanism underlying the transition from acute to chronic pain in 
youth,32 and fatigue has been shown to mediate the relationship between pain 
intensity and pain-related disability in youth with chronic pain.33 Parental affective 
factors, including anxiety have been associated with increased child pain intensity 
and analgesic use.34 As adolescent development is characterized by greater 
autonomy from parents and increased emphasis on peer relations, it is not 
surprising that peer relationship quality moderates associations between parent and 
adolescent cognitive and behavioral pain responses.35 
Studies on how material conditions, particularly neighborhood SES and built 
environment, contribute to pain are also relevant. In pediatric patients with upper 
extremity fractures, children living in areas with the greatest social deprivation 
reported worse function, mobility, pain interference, and peer relations compared 
to children with the least social deprivation.36 Another study among children with 
chronic pain demonstrated that patients from more socially deprived areas were 
less likely to be referred to a chronic pain service and less likely to attend 
appointments.37 In a sample of youth considered to be at-risk for chronic pain, high 
risk status was associated with living in neighborhoods with less walkability and 
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further proximity to parks.38 These studies demonstrate the importance of 
considering material conditions in interventions targeting chronic pain in 
adolescents.
Even though childhood cancer survivors are at increased risk for chronic pain 
when compared to peers, a recent study indicated that only half of adolescent 
survivors of childhood cancer received follow-up healthcare after treatment 
completion.39 It is likely that socioeconomic inequalities impact not only access to 
healthcare, but also access to treatment or interventions for chronic pain 
management in cancer survivors. Children with chronic pain whose parents are 
from a higher occupation level are more likely to travel a greater distance to access 
specialized treatment than are those from lower occupation levels,40 and 
individuals from underserved populations, particularly Blacks, are less likely to 
receive opioids for the management of acute and chronic pain. This is despite the 
fact that Blacks are less likely to misuse opioids than Whites.41 Nonetheless, 
overreliance on opioids has resulted in a national health crisis, with adolescents 
and young adults experiencing a significant increase in opioid overdose 
mortality.42 This is relevant for childhood cancer survivors as they are 1.5 to 4 
times more likely than age-, sex-, and region-matched peers to fill opioid 
prescriptions,43 and bone tumor survivors are significantly more likely than 
survivors of hematologic cancers to use opioids and experience potential misuse in 
the first year post-therapy.44 Among survivors, pain is associated with a more than 
2-fold increased risk of opioid use cross-sectionally,45, 46 with persistent and 
increasing pain over a 4-year interval resulting in a nearly 8-fold increased risk of 
opioid use.47 In the general population, adolescents with chronic pain are more 
likely to misuse opioids as adults,48 where treatment of chronic pain with opioids 
is often ineffective and may result in opioid-induced hyperalgesia49 as well as 
misuse and abuse.50 These data support the need for alternative, non-
pharmacologic approaches for chronic pain.
Cancer diagnosis & treatment exposures: Most bone sarcoma patients with 
extremity tumors are candidates for limb sparing surgery, which usually involves 
en bloc removal of the tumor and involved bone, and reconstruction with 
endoprosthesis or allograft. This invasive surgery may result in chronic 
neuropathic or musculoskeletal pain.51 In fact, data from our institution indicate 
that more than one-third of pediatric osteosarcoma patients treated with limb-
sparing surgery report significant chronic pain.15 We also found that among adult 
survivors, those who underwent limb-sparing surgery during childhood were twice 
as likely to report pain with daily interference than survivors who did not.16 These 
data suggest a high prevalence of chronic pain among adolescent survivors of bone 
sarcomas that appears to persist into adulthood and, coupled with high opioid use, 
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indicate a clear need for non-pharmacologic pain interventions in this population. 
Cancer survivors are at-risk for developing cancer-related worry or fear of 
recurrence. A recent report indicated that 43% of adolescent and young adults 
survivors reported fear of cancer recurrence.52 Given that many sarcoma patients 
identify pain as an early presenting symptom of their cancer diagnosis, survivors 
may be more hypervigilant to pain and interpret it as an indicator of cancer 
recurrence. This likely contributes to an ongoing pain and fear cycle, with each 
serving to maintain or exacerbate the other. Because pain is associated with 
increased risk of worry about relapse in long-term survivors,53 cancer-related 
worry is an important outcome to consider in interventions targeting pain in cancer 
survivors. 
Non-pharmacologic interventions for chronic pain: Data indicate that pain is 
significantly undertreated among children with cancer. This may stem, in part, to 
historical overreliance on opioids as well as stigma related to psychological 
interventions. For children with osteosarcoma, the duration of pain is significantly 
longer in patients who are resistant to psychological interventions.15 Importantly, 
non-pharmacological approaches to pain management in adolescents with chronic 
pain are highly effective. Cognitive behavioral therapy (CBT), the gold standard 
and predominant psychological treatment for chronic pain in pediatric 
populations,54 is designed to reduce negative thoughts about pain and modify 
maladaptive behavioral patterns in response to pain.55 A recent meta-analysis of 24 
randomized controlled trials for multiple chronic pain conditions in adolescents 
showed that CBT has a moderate effect on pain intensity reduction after treatment, 
and a modest effect on disability reduction after treatment and at follow-up.54 
Improvements in anxiety post-treatment are also reported. 
Despite its efficacy, traditionally delivered CBT (i.e., face-to-face psychotherapy) 
is often underutilized due to limited availability and access to trained 
professionals, costs, stigma associated with professional psychological support, 
geographical distance from treatment centers, and long waiting lists.56 These 
barriers are even more salient in underserved populations. To reduce access 
barriers and promote participation in CBT (i.e., treatment uptake), alternative 
delivery models have been developed. One approach is technology-delivered CBT 
(computer and mobile applications). A recent meta-analysis of 4 internet-delivered 
CBT programs for pediatric chronic pain found it produced medium to large effect 
sizes for reducing pain intensity.57 The mobile CBT program for the proposed 
study, WebMAP, reduced activity limitations at 6 and 12 months post-intervention 
in 11-17 year old adolescents with multiple different sources of chronic pain.58, 59 
While mobile CBT can reduce barriers to access care, it’s reach, utility, and uptake 
remain limited to the extent that it is sensitive and responsive to cultural 
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differences. Culture impacts both the content and process of psychotherapy.60, 61 
Cultural adaptation, or the “systematic modification of an evidence-based 
treatment or intervention protocol to consider language, culture, and context in 
such a way that is it compatible with the client’s cultural patterns, meanings and 
values”(p.362)62 increases treatment engagement and effectiveness. A meta-
analysis reviewed 76 studies that employed culturally adapted mental health 
treatments and reported that interventions targeted to specific ethnic groups 
produced 4 times stronger effects than those provided to diverse ethnic groups.63 
To our knowledge, mobile CBT interventions for chronic pain have not been 
adapted to incorporate cultural differences and preferences for Black and Hispanic 
youth, who disproportionately experience chronic pain and barriers to its 
treatment. Although mobile CBT is attractive because it is portable and likely 
amenable to cultural adaptation, data indicate that it is not as effective as CBT 
delivered in-person.64 The effectiveness of mobile CBT may be enhanced by a 
companion intervention that augments cognitive and affective processing of pain.
Transcranial direct current stimulation (tDCS) is a non-invasive method of brain 
stimulation and an emerging treatment for chronic pain.65, 66 Excitatory (anodal) 
stimulation over the dorsolateral prefrontal cortex (DLPFC) is a common tDCS 
regimen for treating pain. Transcranial direct current stimulation differs from 
conventional interventions in that it directly stimulates specific brain regions 
responsible for cognitive and affective processing similar to those activated during 
CBT for chronic pain.67 Transcranial direct current stimulation involves 
modulation of cerebral cortex excitability by direct application of low-level 
electric current to an anode electrode site, the current travels to a cathode electrode 
site stimulating brain regions that lie in the path of current flow. Studies have 
shown analgesic effects on reported pain intensity and improvements in quality of 
life after treatment,65 as a result of local and connectivity effects within the pain 
processing brain network.68, 69 Anodal tDCS of the DLPFC modulates both 
sensory and cognitive-affective networks70 and reduces pain by inhibiting the 
maladaptive allocation of cognitive and attentional resources and, influencing 
emotional and motivational aspects of pain.69 A recent integrated review and meta-
analysis reported that anodal tDCS to the DLPFC produced an effect size of -0.54 
(95% CI, -0.91 to -0.16).71 A recent trial of home-based tDCS to the DLPFC 
demonstrated a 46% reduction in pain scores after 20 sessions.72 Due to its 
dependency on brain state,73, 74 tDCS appears to be more efficacious at augmenting 
effects of a simultaneous/combined treatment rather than inducing de-novo 
changes.75 For example, larger benefits of CBT on psychological outcomes (e.g., 
depression) have been observed when administered with tDCS,76, 77 although this 
treatment combination has not yet been examined in a sample with chronic pain.78 
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2.2 Rationale
Survivors of pediatric cancers are at high risk for developing chronic pain. 
Unfortunately, because of the limited availability of and access to evidence-based 
interventions, these survivors are disproportionally using prescription opioids to 
manage their pain. Racial and ethnic disparities exist, both with respect to the 
prevalence of chronic pain and its management, and these are strongly influenced 
by social determinants of health (SDOH). Non-pharmacological interventions are 
efficacious in treating chronic pain, but their uptake and efficacy is limited across 
diverse cultural groups. In addition, while mobile CBT has promise to transcend 
historical access barriers to psychological care, its impact on improving chronic 
pain does not appear to be as robust as traditionally delivered CBT. Therefore, we 
propose to pair culturally adapted mobile CBT with remotely delivered tDCS to 
enhance the effectiveness of CBT for improving comorbid chronic pain in 
adolescent survivors of pediatric cancer. The mobile CBT program does not need 
to be adapted specifically to cancer survivors as it has demonstrated effectiveness 
in adolescents with multiple pain conditions.
3.0 PARTICIPANT ELIGIBILITY CRITERIA AND STUDY 
ENROLLMENT 
We will enroll Hispanic and non-Hispanic Black parents of childhood cancer 
survivors and adult childhood cancer survivors as well as 10–17-year-old 
adolescent survivors for the first part of the study aiming to adapt a mobile 
cognitive behavioral therapy intervention for chronic pain with input on tDCS 
implementation.  The second part of the study will be an intervention enrolling 
non-Hispanic Black, Hispanic and non-Hispanic White adolescents with pediatric 
cancer who have chronic pain These participants will use the adapted mobile 
cognitive behavioral therapy with tDCS. 
According to institutional and NIH policy, the study will accession research 
participants regardless of gender and ethnic background.  Institutional experience 
confirms broad representation in this regard.
3.1 Inclusion Criteria for focus groups
3.1.1 Adults
3.1.1.1. Hispanic or non-Hispanic Black childhood cancer survivor or 
parent of Hispanic or non-Hispanic Black childhood cancer survivor 
3.1.1.2 18 years or older
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3.1.2 Adolescents
3.1.2.1 10-17 year-old survivors of childhood cancer
3.1.2.2 At least one-year post treatment completion
3.1.2.3 Hispanic or non-Hispanic Black
3.1.2.4 Phase 4 only: History of chronic pain
3.1.2.4.1 Pain that was present for more than 3 months
3.2 Exclusion Criteria for focus groups
3.2.1 Adults/Adolescents
3.2.1.1 Inability or unwillingness of research participant or legal 
guardian/representative to give written informed consent.
3.3 Inclusion Criteria for feasibility study
3.3.1 Hispanic, non-Hispanic Black, and non-Hispanic White 10–17-year-old 
survivors of pediatric cancer
3.3.2 At least one-year post treatment completion
3.3.3. Pain present over the past 3 months and pain at least once per week
3.3.4. Pain interfering with at least one area of daily functioning
3.4 Exclusion Criteria for feasibility study
3.4.1. Limb amputation
3.4.2. History of seizure disorder or other neurological disorders
3.4.3. Presence of metallic intracranial implants (neurostimulator, Ommaya 
reservoir, CSF shunt, or aneurysm clip), and metallic and non-metallic 
cranial, excluding the bones of the face and jaw, prosthesis 
(implants/plates).
3.4.4. Serious comorbid psychiatric condition
3.4.5. Current substance abuse
3.4.6. History of development delay or significant cognitive impairment
3.4.7. History of brain tumor diagnosis
3.5 Research Participant Recruitment and Screening
Four institutions will collaborate in the proposed protocol:  St. Jude Children's 
Research Hospital (SJCRH); Children’s Healthcare of Atlanta (CHOA), Texas 
Children’s Hospital (TCH); and Seattle Children’s Hospital (SCH). The three 
sites will provide contact information only for potential participants. SJCRH will 
screen, recruit, and consent all eligible participants for the study. 
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3.6 Enrollment on Study at St. Jude
A member of the study team will confirm potential participant eligibility as 
defined in Sections 3.1-3.2 and complete the ‘Participant Eligibility Checklist’ in 
OnCore if required by the study team.  Eligibility will be reviewed, and a research 
participant-specific consent form and assent document (where applicable) will be 
generated. The entire signed consent/assent form(s) must be scanned into the 
Electronic Health Record (EHR) by the study team designee.
3.7 Procedures for Identifying and Screening Participants 
Prior to initiating the study, a workshop will be held by SJCRH with team 
members from all sites participating. The background to the study, study 
procedures, consent processes, data transfer, and plans to monitor intervention 
integrity and data quality will be the content for that workshop. 
Following the workshop and preparation of sites for identifying potentially 
eligible research participants will begin.  Eligibility of newly admitted research 
participants will be confirmed during daily discussions between the study 
investigators, research assistants, and attending physician for both the Solid 
Tumor and Leukemia teams.
4.0 DESIGN AND METHODS
4.1 Design and Study Overview
This study will include the (1) cultural adaptation of an evidence-based mobile 
CBT program for chronic pain and procedures for tDCS and (2) a feasibility study 
of adapted mobile CBT paired with tDCS. Participants will be recruited from four 
large pediatric cancer centers: St. Jude Children’s Research Hospital (SJCRH), 
Children’s Healthcare of Atlanta (CHOA), Texas Children’s Hospital (TCH), and 
Seattle Children’s Hospital (SCH). Collaborating sites will provide SJCRH with 
potential participant contact information and SJCRH will consent and enroll 
participants 
on 
the 
study 
at 
SJCRH. 
Mobile 
cognitive 
behavioral 
therapy for chronic pain: The 
mobile CBT program we propose 
to utilize, WebMAP mobile,79 was 
created by Dr. Palermo (Co-I). 
The program is available on 
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Android and iOS operating systems and is an interactive, self-guided intervention 
with six core treatment modules. These modules focus on 1) pain education, 2) 
stress, emotions, and thoughts (e.g., pleasant activity scheduling, thought 
stopping), 3) relaxation and imagery, 4) lifestyle and school interventions, 5) 
staying active, and 6) maintenance and relapse prevention. Within the app, 
participants complete screening questions to set up a profile and evaluate the need 
for two supplementary treatment modules focused on comorbidities of negative 
mood and sleep. There are several functional components to the app, including 
places and lessons (each place has 3-5 lessons that provide education and teach 
pain management skills), library (information on skills presented through audio 
clips, videos), check-in (allowing participants to track their pain, activity, mood, 
and sleep), and skills tracker (participants record practicing specific skills such as 
sleep relaxation). Screen shots from the app are shown in Figure 2. Content is 
metered according to a time schedule, requiring youth to spend 5 days on skills 
practice before an assignment can be completed. Components of the program can 
be used daily (e.g., check in, skills practice). Total treatment duration is 
approximately 20 min per week over 6 to 8 weeks depending on the number of 
supplementary modules assigned. The app uses daily reminder notifications to 
encourage users to log in and complete assigned tasks. If needed, participants will 
be provided with a mobile device to access the intervention.
Cultural adaption of mobile CBT: A recent 
systematic review of cultural adaption of internet- 
and 
mobile-based 
interventions 
for 
mental 
disorders identified specific components necessary 
for cultural adaptation that fall under 3 key 
domains: content, methodological, and procedural 
(see Table 1).80 For the current proposal we will 
culturally adapt mobile CBT, separately for Black 
and Hispanic survivors of childhood cancer, guided 
by key domains in Table 1 and identify tailoring 
variables that will be used to assign adapted 
intervention content. This will avoid the assumption of complete homogeneity 
within any one culture. The objective of cultural adaptation is to improve the 
ecological and external validity of an intervention for a culture group different 
than the group it was originally intended for. Nonetheless, it is important to retain 
core components of the program to maintain effectiveness in the target 
population.81
Table 1. Key domains and 
components of cultural adaption 
of mobile-based interventions for 
mental disorder80
Content 
Illustrations 
Language 
Mental health concepts
Methodological 
Structure of the intervention
Functionality 
Design and Aesthetics
Procedural
Methods used to obtain 
information
Persons involved
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Our cultural adaptation will include five phases: (1) expert consultation, (2) 
stakeholder feedback, (3) preliminary content adaptation, (4) iterative content 
adaptation with stakeholder feedback, and (5) finalized adaptation. 
All cultural adaptation processes will occur separately, but in parallel, for 
non-Hispanic Black and Hispanic participants. We will use self-
identification/report 
to 
determine 
race/ethnicity. 
For 
Phase 
1 
(expert 
consultation), experts will include Dr. Palermo (CBT, chronic pain, WebMAP 
creator), Dr. Brinkman (tDCS, cancer survivorship), Dr. Graetz (culture and 
communicatio
n, 
SDOH), 
and at least 
one 
non-
Hispanic 
Black and one 
Hispanic 
parent of an 
adolescent 
childhood 
cancer 
survivor from 
the Children’s 
Oncology 
Group Patient 
Advocate 
Committee 
and St. Jude 
Children’s 
Research 
Hospital Patient and Family Advisory Council, and at least one Black and one 
Hispanic young adult childhood cancer survivor (lived experience participants). 
We will solicit feedback from stakeholders and lived experience participants 
related to the study design and conduct.
Phase 1 will involve a minimum of two 1-hour meetings to identify possible 
adaptations including surface (e.g., characters, activities, language), conceptual 
(e.g., treatment goals, values, mental health concepts) and mobile specific 
considerations (e.g., amount of human guidance). Preliminary identification of 
tailoring variables will also be discussed. Non-Hispanic Black and Hispanic 
participants will meet separately.
 
Cultural Adaptation Phases 
Phase 1 (Expert Panel) consultation to 
identify potential adaptations to mobile CBT 
program and preliminary identification of 
tailoring variables.
Virtual meetings with non-Hispanic 
Black & Hispanic parents & young 
adult childhood cancer survivors.
(2-3) 1-hour meetings 
Phase 2 (Stakeholder Consultation) identify 
adaptations of intervention content and 
review preliminary tailoring variables.
Virtual focus groups with non-
Hispanic Black & Hispanic adolescent 
childhood cancer survivors.
(2-4) 45-minute sessions
Phase 3 (Preliminary Content 
Adaptations) based on qualitative analysis 
based of stakeholder feedback.
Co-investigators make preliminary 
intervention content adaptations.
Phase 4 (Iterative Content Adaptation) with 
ongoing stakeholder feedback. Adaptations 
shared with survivors and additional feedback 
solicited.
Virtual focus groups with non-
Hispanic Black & Hispanic adolescent 
childhood cancer survivors with 
chronic pain. Ongoing program 
content adaptation based on 
qualitative analysis.
(2-4) 45-minute sessions
Phase 5 (Finalized Adaptation) with ongoing 
stakeholder feedback. Finalized adaptions 
and tailoring variables shared with survivors.
Virtual focus groups with non-
Hispanic Black & Hispanic adolescent 
childhood cancer survivors who 
participated in previous sessions. Final 
program content adaptation based on 
qualitative analysis.
(2-3) 45-minute sessions 
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Phase 2 (stakeholder consultation), we will recruit 8 to 12 Black and 8 to 12 
Hispanic adolescent (10-17 years of age) survivors of childhood cancer who are 
at least one-year post-treatment completion to serve as initial stakeholders and 
participate in virtual focus groups. All focus groups will be conducted via an 
online HIPAA compliant platform, audio-recorded, and transcribed verbatim. 
Our team has experience conducting focus groups virtually in multiple cultures 
and languages.82, 83 We will engage in purposive sampling to include 
representation by sex and neighborhood disadvantage as this is an important 
SDOH related to treatment uptake and engagement. To avoid potential 
saturation of our sample for the intervention phase, we will not restrict 
participation in the adaptation phase to bone sarcoma survivors. Focus groups 
will be conducted by two facilitators who will use a guide/probe structured 
around the 3 key domains of cultural adaptation, to solicit specific feedback 
about potential adaptation of the images, concepts, personal stories, daily life 
examples and preliminary tailoring variables identified during the expert 
consultation phase. If Hispanic participants indicate that they would prefer a 
Spanish translation of the entire program or specific components (e.g., videos) 
this be incorporated into the adaption process. Dr. Graetz is fluent in Spanish 
and has research assistants who are native Spanish speakers trained to conduct 
focus groups; therefore, we will be able to provide focus groups in Spanish or 
with staff who are bilingual, if preferred by stakeholders. We plan to hold 
approximately three 45-minute sessions over a at least a 3-week period to allow 
for sufficient time to review all program material. We will hold separate focus 
groups for non-Hispanic Black youth and for Hispanic youth.
 
Phase 3 We will make preliminary content adaptations based on results of our 
qualitative analysis of stakeholder feedback (see analytic description below) and 
create mock- ups to demonstrate these adaptations. We will show how identified 
culturally relevant tailoring variables (e.g., family involvement, spirituality, 
values, amount of guidance) can assign adapted intervention content (e.g., 
tailored vignettes) or functionality. For example, if religiosity is deemed an 
important tailoring variable, character stories will be tailored to incorporate 
prayer and religious social support. Any proposed changes to app functionality 
(e.g., amount of human guidance) will be considered at this phase.
Phase 4 This will be an iterative adaptation process where we demonstrate our 
proposed adaptations to stakeholders. We will refine the adaptations by eliciting 
rapid iterative feedback from youth in three cycles, with 5-7 Black and 5-7 
Hispanic adolescent survivors of childhood cancer who have a history of 
chronic pain participating per cycle (n=15-21 total). This will allow us to be 
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informed by survivors with lived experience of chronic pain. We will again 
engage in purposive sampling to include representation by sex and 
neighborhood disadvantage. We plan to hold approximately three sessions 
(about 45-minutes each) with adequate time in between to work with our 
programming team to make modifications to app mock-ups. Importantly, because 
this group of stakeholders will have chronic pain, these focus groups will 
specifically emphasize the acceptability of adapted vignettes and pain 
management practice skills. This phase also will allow for refinement of 
tailoring variables.
 
Phase 5 will involve approximately two meetings with 5-7 non-Hispanic Black 
and 5-7 Hispanic adolescent survivors of childhood cancer who participated in 
earlier phases to present the adapted interventions from the results of focus 
groups and rapid feedback cycles. Feedback will be collected and analyzed to 
inform any further changes.
Transcranial 
direct 
current 
stimulation 
(tDCS) – Mobile System: For remotely 
supervised tDCS stimulation, we will employ a 
procedure consistent with recently published 
professional guidelines84 and with those 
utilized in our ongoing NEUROSTIM and 
ALLSUP studies. The mobile tDCS system is manufactured by Soterix Medical 
and consists of a rechargeable lithium battery pack, handheld control unit and a 
self-positioning headband with electrodes (Figure 3). This device is specifically 
designed for remote studies. It has an easy set-up and allows for precise 
reproduction of electrode positioning. This system allows for double-blind 
application of the intervention or sham treatments through the use of single-use 
passcodes. An anodal electrode will be placed over the dorsolateral prefrontal 
cortex (equivalent to F3 and F4 electrode sites) on the side of the body reported 
to experience the most pain, with a cathode reference electrode placed at the 
supraorbital region ipsilateral to the side of the body reported to experience the 
most pain. The electrodes are single-use and snap into pre-configured fixed 
locations of a flexible headband that is individualized for each participant. 
Participants will complete training via a telehealth platform that includes 
instruction on how to connect the electrodes, place the headband, and operate the 
device. As part of this training, participants will complete a single session of 
tDCS treatment.
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During active sessions participants will receive 1mA direct current flow for 20 
minutes. Sham sessions provide a ramp up to 1mA direct flow over a 5 second 
interval and return to no current flow for the remainder of the session. The tDCS 
unit requires a unique code for each stimulation session. Each remote session will 
be monitored for adherence and tDCS device connection quality. If needed, 
participants will be supplied with a device (iPad, laptop) to allow for video 
monitoring of the sessions. This methodology is consistent with the approach 
successfully utilized in our pilot study and ongoing studies. Cultural 
considerations: While the extent of cultural adaptation that can be applied to 
tDCS is, unfortunately, limited, we will utilize the above-described focus groups 
to discuss tDCS. We will conduct a 4th focus group during each phase dedicated 
exclusively to tDCS procedures. We will solicit feedback from stakeholders on 
acceptable language to describe tDCS and obtain feedback on study materials 
(e.g., handouts, images, instructions) and procedures (e.g., family involvement). In 
our ongoing study, NEUROSTIM, we have made adaptations to tDCS head straps 
to accommodate different hairstyles and will solicit feedback on the 
appropriateness of this and other adaptations across cultures.
Feasibility Study: Eligible participants will be assigned to either culturally 
adapted mobile CBT + active tDCS to the DLPFC or culturally adapted mobile 
CBT + sham. For the pilot phase, 10 participants will be enrolled from each racial 
and ethnic group (non-Hispanic Black, Hispanic, non-Hispanic White), and 5 
participants in each group will be allocated to receive active tDCS and 5 to sham 
tDCS. We will alternate assignment of tDCS location within each group as 
participants are enrolled using an ABAB design for treatment allocation, 
separately for each racial and ethnic group. Because this is a feasibility study, 
blocked randomization and blinding is not necessary, but will be employed in a 
later study.  Participants will complete two 20-minute stimulation sessions per 
week for 6 weeks. Each week, tDCS sessions will be paired with the mobile CBT 
program (e.g., core content, practice skills) at a time that is convenient to the 
participant. Two sessions will not occur within the same 24-hour period. As 
described above, participants will receive a unique activation code prior to each 
stimulation session. Each active session will be pre-programmed to deliver 1mA 
of direct current for 20-minutes; each sham session will be programed to provide 
a ramp up to 1mA over a 5 second interval and no current flow for the remainder 
of the session. tDCS parameters cannot be changed by participants. Adolescents 
will complete the outcomes measures listed below (e.g., pain intensity, functional 
disability) and parents will complete measures of SES, anxiety, depression, and 
their child’s medication use at baseline and post-intervention.
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Adverse event monitoring: Patient reports of AEs will be surveyed weekly, with 
symptoms reported for the prior tDCS sessions. Information will be collected by 
incident participant reporting and direct questioning using the patient report of 
incidence of side effects (PRISE).85 Side effects will be assessed during weekly 
sessions. The PRISE assesses the presence of side effects for several biological 
systems. For each system (skin, nervous, eyes/ears, sleep, other), participants 
indicate the presence of a side effect, and if present, the tolerability of the side 
effect (tolerable or distressing). The PRISE includes commonly reported side 
effects of tDCS: tingling, itching sensation, burning sensation, pain, headache, 
fatigue, difficulty concentrating, and nervousness.86 Participants will also be 
asked to report any other symptoms experienced during the tDCS session.
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Figure 4a. Study Schema – Virtual Focus Groups
Consent
Stakeholder Feedback
Non-Hispanic Blackstakeholder focusgroups
to review program content – adolescent survivors
Stakeholder Feedback
Hispanic stakeholder focusgroupsto review 
program content – adolescent survivors
Preliminary Content Adaptations
Co-investigators will make preliminary content 
adaptationsbasedon results of qualitative analysis 
of non-Hispanic Black stakeholder feedback
Iterative Content Adaptations
Non-Hispanic Blackstakeholder focusgroups
to review content adaptations and suggest 
additional modifications– adolescent survivors 
with chronic pain
Preliminary Content Adaptations
Co-investigators will make preliminary 
content adaptationsbasedon results of
qualitative analysis of Hispanic stakeholder 
Iterative Content Adaptations
Hispanic stakeholder focusgroups to review 
content adaptations and suggest additional 
modifications– adolescent survivors with chronic 
pain
Finalized Adaptations
Non-Hispanic Blackstakeholder focusgroups
to review content adaptations and suggest 
final modifications
Finalized Adaptations
Hispanic stakeholder focusgroupsto review 
content adaptations and suggest final 
modifications
Expert Panel
Hispanicparentsand youngadult childhood
cancer survivors & key study investigators for
Expert Panel
Non-Hispanic Blackparentsand youngadult 
childhood cancer survivors & key study 
investigators 
Focus Groups
Online Virtual Platform
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Treatment 
Assignment
Baseline/Eligibility 
Assessment
Adapted 
CBT
+ 
Active 
tDCS
Post- Intervention 
Assessment
6-8 Week 
Intervention
Adapted 
CBT
+ 
Sham
tDCS
Figure 4b. Study Schema – Feasibility Pilot Study
4.2 Study Procedures: 
All cultural adaptation processes will occur separately, but in parallel, for non-
Hispanic Black and Hispanic participants. See detailed descriptions of procedures 
in 4.1 Design and Study Overview above.
Expert Panel via virtual meetings - 2 to 4 (1) hour virtual meetings with non-
Hispanic Black and Hispanic parents and young adult survivors of childhood 
cancer and key study investigators. Sessions will be audio-recorded and 
transcribed verbatim.
Stakeholder Focus Group via virtual focus groups - (2-4) 45-minute sessions 
with non-Hispanic Black and Hispanic adolescent survivors of childhood cancer. 
Sessions will be audio-recorded and transcribed verbatim. 
 
Preliminary Content Adaptations – based on results of qualitative analysis of 
stakeholder feedback. 
Iterative Adaptation Process via virtual focus groups - (2-4) 45-minute 
sessions where adaptations will be presented to lived experience stakeholders 
(non-Hispanic Black and Hispanic survivors of childhood cancer with chronic 
pain). Sessions will be audio-recorded and transcribed verbatim.
Feedback meetings via virtual focus groups – (2-3) with 5-7 non-Hispanic 
Black and 5-7 Hispanic adolescent survivors who participated in previous 
sessions to review final program adaptations. Sessions will be audio-recorded and 
transcribed verbatim.
Mobile Cognitive Behavioral Therapy (CBT) - for chronic pain: Participants in 
the stakeholder focus group and the feasibility study will use mobile CBT 
program, WebMAP. Available on Android and iOS operating systems, this 
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program is interactive, self-guided intervention with six core treatment modules. 
These modules focus on 1) pain education, 2) stress, emotions, and thoughts (e.g., 
pleasant activity scheduling, thought stopping), 3) relaxation and imagery, 4) 
lifestyle and school interventions, 5) staying active, and 6) maintenance and 
relapse prevention. Within the app, participants complete screening questions to 
set up a profile and evaluate the need for two supplementary treatment modules 
focused on comorbidities of negative mood and sleep. There are several 
functional components to the app, including places and lessons (each place has 3-
5 lessons that provide education and teach pain management skills), library 
(information on skills presented through audio clips, videos), check-in (allowing 
participants to track their pain, activity, mood, and sleep), and skills tracker 
(participants record practicing specific skills such as sleep relaxation).
 
Stakeholders in the focus groups will offer specific feedback about potential 
cultural adaptation of the images, concepts, personal stories, daily life examples 
and preliminary tailoring variables following proposed changes from the expert 
panel. 
During the feasibility study phase eligible adolescent participants with chronic 
pain will be asked to use the CBT program with tDCS 20 minutes a day, twice a 
week for 6 weeks.
 
Transcranial Direct Current Stimulation (tDCS) Eligible participants will be 
assigned to either culturally adapted mobile CBT + active tDCS to the DLPFC 
OR culturally adapted mobile CBT + sham. For the feasibility phase, 10 
participants will be enrolled from each racial and ethnic group (non-Hispanic 
Black, Hispanic, non-Hispanic White), and 5 participants in each group will be 
allocated to receive active tDCS and 5 to sham tDCS. We will alternate 
assignment of tDCS location within each group as participants are enrolled using 
an ABAB design for treatment allocation, separately for each racial and ethnic 
group. Because this is a feasibility study, blocked randomization and blinding is 
not necessary, but will be employed in the R33 phase. Participants will complete 
two 20-minute stimulation sessions per week for 6 weeks. Each week, tDCS 
sessions will be paired with the mobile CBT program (e.g., core content, practice 
skills) at a time that is convenient to the participant. Two sessions will not occur 
within the same 24-hour period. As described above, participants will receive a 
unique activation code prior to each stimulation session. Each active session will 
be pre-programmed to deliver 1mA of direct current for 20-minutes; each sham 
session will be programed to provide a ramp up to 1mA over a 5 second interval 
and no current flow for the remainder of the session. tDCS parameters cannot be 
changed by participants. Adolescents will complete the outcomes measures listed 
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below (e.g. pain intensity, functional disability) and parents will complete 
measures of SES, anxiety, depression, and their child’s medication use at baseline 
and post-intervention.
During the stakeholders focus groups, participants will be asked to give 
feedback to the extent cultural adaptation can be applied to tDCS.  During the 
feasibility study phase eligible adolescent participants with chronic pain will be 
asked to use the CBT program with tDCS 20 minutes a day, twice a week for 6 
weeks.
4.3 Study Measures/Observations
Participants in both the focus group and feasibility study will be asked to fill out 
screening questions as described in the paragraph below.
Demographics:  Participants will complete a consent to contact form and, if 
willing, will complete demographics questions during the screening process to 
obtain ethnicity, race, and other information needed to target recruitment to meet 
enrollment goals. If we are unable to confirm diagnosis or other screening 
information needed to confirm eligibility, study staff will ask the parent/guardian 
to sign a medical release form to obtain pertinent medical records.
Participants in the feasibility study will complete the outcomes measures listed 
below (e.g. pain intensity, functional disability) and parents will complete 
measures of SES, anxiety, depression, and their child’s perception of pain and 
medication use at baseline and post-intervention (Table 2)
Pain intensity and pain interference: The Brief Pain Inventory-Short Form 
(BPI) includes a 4-item pain severity scale.87 Participants rate their worst and 
least pain in the last week, average pain, and current pain.88 The BPI pain 
intensity has good internal consistency in survivors of childhood cancer 
(α=0.87).89 This measure includes a body diagram to allow participants to 
indicate where they experience the most pain. This will be used to inform 
placement of the anodal tDCS electrode (i.e., right vs. left DLPFC).90, 91
Pain catastrophizing: The Pain Catastrophizing Scale, Child version (PCS-C)92 
is a 13-item self-report measure of overly negative attitudes of pain and it consists 
of three scales of rumination, magnification, and helplessness. Higher scores 
indicate more pain catastrophizing.93 This measure has good reliability 
(Cronbach’s α=0.90) in a clinical sample of children and adolescents with chronic 
or recurrent pain.92  The Pain Catastrophizing Scale, Parent version (PCS-P) is a 
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modified version of the PCS-C based on parent report of their own 
catastrophizing related to their child’s pain. It assesses the same three factors of 
rumination, magnification, and helplessness.94, 95  
Depression: The PROMIS Pediatric Depressive Symptoms96 is an 8-item measure 
of self-reported symptoms of low mood in children and adolescents over the past 
7 days. Higher scores indicate greater symptoms.  The Patient Health 
Questionnaire-2 (PHQ-2) inquires about the frequency of depressed mood and 
anhedonia over the past 2 weeks. A score of 3 points is the preferred cut-off for 
identifying possible depression (if the score is 3 or greater, major depressive 
disorder is likely).97
Anxiety: The PROMIS Pediatric Anxiety96 is an 8-item measure of self-reported 
symptoms of anxiety symptoms in children and adolescents over the past 7 days. 
Higher scores indicate greater symptoms.  The Generalized Anxiety Disorder 2-
item (GAD-2) is a very brief and easy to perform initial screening tool for 
generalized anxiety disorder. A score of 3 points is the preferred cut-off for 
identifying possible cases and in which further diagnostic evaluation for 
generalized anxiety disorder is warranted. Using a cut-off of 3 the GAD-2 has a 
sensitivity of 86% and specificity of 83% for diagnosis of generalized anxiety 
disorder.98
Cancer-related worry: The Fear of Cancer Recurrence Inventory99 is a 9-item 
measure developed specifically for survivors of childhood cancer (8-18 years) to 
assess the presence of fear of recurrence and perceived risk recurrence. Higher 
scores indicate greater cancer-related worry. Internal consistency is good 
(ICC=0.88).
Physical functioning: The PROMIS Pediatric Mobility100 is an 8-item measure of 
self-reported ability at physical activities in children and adolescents in the past 7 
days with higher score indicating greater ability. It has excellent test-retest 
reliability (ICC=0.73) and adequate internal consistency (Cronbach’s α=0.73-
0.74).101 The PROMIS Pediatric Upper Extremity100 is an 8-item measure of self-
upper extremity function in the past 7 days with higher score indicating greater 
ability. It has excellent test-retest reliability (ICC=0.71) and adequate internal 
consistency (Cronbach’s α=0.62-0.63).101 Both measures are sensitive to change 
in youth with chronic pain.102  The PedsQL™ 4.0 Generic Core Scale is reliable 
and valid in children and adults with cancer and includes a physical functioning 
scale, an emotional functioning scale, a social functioning scale, a school 
functioning scale, a total summary score, and both physical and psychosocial 
health summary scores.  The instrument is available in young child, child, 
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adolescent, and adult versions (scales) if child/adolescent agrees and is able.  All 
versions of this instrument are scored on a 0-100 scale.103, 104
Peer relations: The PROMIS Pediatric Peer Relationship17 is an 8-item measure 
that assesses the quality of peer relationships. Higher score indicating higher 
quality. It has excellent test-retest reliability (ICC=0.81) and excellent internal 
consistency (Cronbach’s α=0.83-0.84).101
Fatigue: The PROMIS Pediatric Fatigue100 is a 10-item measure that assesses 
symptoms of fatigue in the past 7 days. Higher scores indicate more fatigue. It has 
excellent test-retest reliability (ICC=0.76) and internal consistency (Cronbach’s 
α=0.87).101
Sleep: The Adolescent Sleep Wake Scale (ASWS) short form105 is a 14-item 
measure of behavioral sleep patterns in adolescents. Internal consistency was 
good (α=0.74-0.84) in a pooled clinical sample of adolescents with mixed health 
conditions).105 Acceptable reliability was reported in a sample of ethnically 
diverse adolescents from an economically disadvantage community (α=0.70-
0.90).106 We also will use the PROMIS Sleep-Related Impairment107 8-item 
measure to allow for assessment of sleep quality during the night as well as the 
impact of sleepiness on daytime function. This measure is validated for children 
and adolescents and assess sleep-related impairment over the past 7 days.
Global acceptability and satisfaction with treatment: Acceptability and 
satisfaction with treatment will be assessed using a 5-point numerical rating scale 
(NRS) (strongly disagree to strongly agree). The NRS has been recommended for 
use in pediatric pain clinical trials.108 Two adapted questions from the modified 
treatment evaluation inventory will be utilized.108, 109 We will also assess patient 
global impression of change using a single question to assess perceived 
improvement in pain.110, 111
Opioid Use: At each timepoint participants and/or their parents will be asked to 
list the names of their medications, doses taken, and the frequency with which the 
medications were taken over the past 2 weeks.112 Medications will be classified as 
anti-inflammatory (e.g., nonsteroidal anti-inflammatory drugs); regular (daily) 
opioids, opioid medication as required (PRN), adjuvant pain medications (e.g., 
anticonvulsants). Opioid doses will be converted to morphine equivalent doses 
(MED) using an opioid equivalence table.113, 114
Parent anxiety and depression: Parental affective symptoms will be measured at 
each time point using the Patient Health Questionnaire 8-item (PHQ-8), a 
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measure of symptoms of major depressive disorder115 and the Generalized 
Anxiety Disorder 7-item (GAD-7), a measure of symptoms of generalized 
anxiety.116
Table 2.
Outcome Measure
Questionnaire
Brief Pain Inventory-Short Form 
(BPI)
Pain Catastrophizing Scale, Child 
version (PSC-C)
Pain 
Pain Catastrophizing Scale, Parent 
version (PSC-P)
PROMIS Pediatric Depressive 
Symptoms
Depression
Patient Health questionnaire-2 
(PHQ-2)
PROMIS Pediatric Anxiety
Anxiety
Generalized Anxiety Disorder-2 
(GAD-2)
Cancer-related worry
Fear of Cancer Recurrence 
Inventory
PROMIS Pediatric Mobility
PROMIS Pediatric Upper Extremity
Physical functioning
PedsQL (ages 8-12 &13-18)
Peer relations
PROMIS Pediatric Peer 
Relationship
Fatigue
PROMIS Pediatric Fatigue
Adolescent Sleep Wake Scale 
(ASWS) short form
Sleep
PROMIS Sleep-Related Impairment
Global acceptability & 
satisfaction with treatment
2 adapted questions using numerical 
rating scale
Medications Survey
Opioid Use
Patient Health questionnaire 8-item 
(PHQ-8)
Parent anxiety and 
depression
Generalized Anxiety Disorder 7-
item (GAD-7)
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4.4 Sites
All collaborating sites (Seattle Children’s Hospital, Children’s Healthcare of 
Atlanta, and Texas Children’s Hospital) will identify potentially eligible 
participants, provide the study brochure, and provide the consent to contact form 
for interested participants.  St. Jude will complete the remaining study activities.
5.0 REQUIRED EVALUATIONS, TESTS, AND OBSERVATIONS
5.1 Pre-Study and Study Activities
FOCUS GROUPS AND FEASIBILITY STUDY ACTIVITIES
STUDIES ACTIVITIES
Pre-
Study
Focus Group
Phase
Feasibility Study
Phase
Off 
Study
Screening
X
X
X
Consent
X
X
X
Expert Panel – virtual meetings 
with stakeholders & key 
investigators
X
X
Stakeholder Feedback – virtual 
focus groups
X
X
Preliminary Content Adaptation - 
co-investigators only
X
X
Iterative Content Adaptation – 
virtual focus groups
X
X
Finalized adaptation – virtual 
focus groups
X
X
Culturally Adapted CBT + active 
tDCS or Culturally Adapted CBT 
+ sham for 20 min sessions twice a 
week for 6 weeks
X
X
Completion of Questionnaires
X
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6.0 CRITERIA FOR REMOVAL FROM PROTOCOL
6.1 Off Study Criteria
Death
Lost to follow-up
Request of the Patient/Parent
Discretion of the Study PI, such as the following 

The researcher decides that continuing in the study would be harmful 

The participant misses so many appointments that the data cannot be 
used in the study

The participant’s condition gets worse

New information is learned that a better treatment is available, or that 
the study is not in the participant’s best interest

Study evaluations are complete
7.0 SAFETY AND ADVERSE EVENT REPORTING REQUIREMENTS
7.1 Adverse Events (AEs)
Adverse events will be monitored from the start of the study. Participants will 
be instructed to report all AEs during the study and will be assessed for the 
occurrence of AEs throughout the study. Weekly PRISE forms will be 
completed. 
7.2 Definitions
Adverse Event (AE): Any untoward medical occurrence associated in a study 
participant after the beginning of the study. Adverse Events will be graded by 
the NCI CTC AE version 5.0. Participants will be instructed to report all AEs 
during the study and will be assessed for the occurrence of AEs throughout the 
study. 
Serious Adverse Event (SAE):  Any adverse event temporally associated with 
the subject’s participation in research that meets any of the following criteria:

results in death;

is life-threatening (places the subject at immediate risk of death from 
the event as it occurred);

requires inpatient hospitalization or prolongation of existing    
hospitalization;

results in a persistent or significant disability/incapacity;

results in a congenital anomaly/birth defect; or

any other adverse event that, based upon appropriate medical judgment, 
may jeopardize the subject’s health and may require medical or surgical 
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intervention to prevent one of the other outcomes listed in this 
definition.
7.3 Handling of Adverse Events (AEs) and Deaths
Recording of Adverse Events and Serious Adverse Events:  Adverse 
events of all types will be recorded in the database. 
Reporting Adverse Events and Serious Adverse Events:  
Adverse events will be surveyed weekly. Event information will be collected 
using a modified version of patient report of incidence of side effects 
(PRISE: see description above)
The St. Jude PI, upon awareness of an event, will determine the seriousness 
of AEs and ensure that all UPs are entered into the electronic submission 
system (iris) within 10 days.  All (pertinent, as in recording above) AEs, 
serious or not, will be recorded in a log, spreadsheet, or report and 
submitted to the St. Jude IRB at the time of continuing review.  
Unanticipated Problems (UPs):  The St. Jude PI will refer to St. Jude 
Human Research Protection Program (HRPP) Policy 01.720 for definitions 
and specifics for reporting of unanticipated problems to the St. Jude IRB.  
The St. Jude IRB reports UPs to BIMO as per 21 CFR 56.  The UP policy 
link 
follows:    
https://home.stjude.org/hrpp/Policies/01720.pdf#search=unanticipated.
Collaborating sites:  
Report Serious Adverse Events as defined in section 7.2 internally per your 
IRB of record’s policy and to the St. Jude Principal Investigator as soon as 
possible.   
Report Unanticipated Problems to your IRB of record per policy and to the 
St. Jude Principal Investigator within 15 days.
Sharing of SAEs:  
The St. Jude PI will ensure that all unexpected, possibly related Serious 
Adverse Events on study are shared with all sites.  Collaborative sites will 
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share SAEs based on guidelines of CTA SOP 28 for more details.  Link:  
https://home.stjude.org/clinical-trials-administration/Pages/sop.aspx.
Deaths:  Deaths meeting reporting requirements are to be reported 
immediately to the St. Jude IRB, but in no event later than 48 hours after the 
investigator first learns of the death.
7.4 Process for Communicating Study-Wide Adverse Events 
The study PI will document their plan for obtaining adverse event information 
from a collaborator, and for disseminating study-wide adverse event 
information to the collaborators.
8.0 DATA COLLECTION, STUDY MONITORING, AND 
CONFIDENTIALITY
8.1 Data Collection 
Electronic case-report forms (e-CRFs) will be completed by the St. Jude 
Clinical Research Associates or the site Study Coordinator. Data from the 
participant’s record will be entered directly into a secure study-specific 
database.  Instructions for data entry are outlined in the database.
Data management will be supervised by the ADAPTED study team. Protocol-
specific data and adverse events will be recorded in the electronic database, 
ideally within 2 to 4 weeks of the study procedure. All questions will be 
directed to the Principal Investigator, Dr. Tara Brinkman, PhD., or designee 
and will be reviewed at regularly scheduled working meetings. 
Regular summaries of protocol events will be generated for the PI and the 
Department of Biostatistics to review.
8.2 Data Collection Instructions for Collaborating Sites 
Collaborating sites may collect data either by using Case Report Forms or by 
remote electronic data entry.  Timeframes for entry of study data or completion 
of case report forms will be outlined so that study data may be obtained in a 
timely and consistent manner.
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When CRFs are used, they will include the name and contact information of 
the person to whom the forms are to be sent.  
8.3 Study Monitoring- Non-Therapeutic Risk Categories
This study is considered low risk for monitoring purposes.  The Principal 
Investigator (PI) and study team are responsible for ensuring participant 
eligibility and protocol compliance. The study team will hold meetings as 
needed to review case histories or quality summaries on participants and will 
generate minutes which are signed by the PI.
CTO will review up to 10% of the study participants the first year for life 
status, status on study, and the appropriateness of the informed consent and 
eligibility processes. During this monitoring, the monitor will verify regulatory 
documentation pertinent to the study, all Serious Adverse Event reports, and 
Age of Majority consenting on all study participants. St. Jude affiliates and 
domestic collaborating study sites will be monitored remotely, in the same 
method as St. Jude, by the St. Jude Monitor. If there are no unresolved issues, 
no further monitoring will be performed.  The PI and study team will be 
responsible for ensuring protocol and regulatory compliance.  The Monitor will 
generate a follow-up letter which is shared with the Principal Investigator, 
study team, and the Internal Monitoring Committee (IMC).
Protocol continuing reviews by the Institutional Review Board (IRB) and 
Scientific Review Committee (CT-SRC) will occur at least annually.  In 
addition, Unanticipated Problems and/or Serious Adverse Event reports are 
reviewed by the IRB.
8.4 Confidentiality
Confidentiality will be maintained. Data forms will be kept in locked file 
cabinets, in locked office space, accessed only study staff on an “as needed” 
basis. Data files will be de-identified, linked by a participant identification 
number to a separate secure database. Data files downloaded for statistical 
analyses will not contain personal identifiers.
The medical records of study participants may be reviewed by the St. Jude 
IRB, FDA, clinical research monitors, etc.
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9.0 STATISTICAL CONSIDERATIONS
The primary objective Qualitative analysis plan for focus groups: We will 
develop a codebook using a priori codes based on key domains and 
components from the literature,80 as well as novel codes inductively derived 
through transcript review. Two coders will independently code focus group 
transcripts and meet regularly to resolve discrepancies and evaluate inter-
rater reliability. Thematic content analysis will focus on identifying culturally 
specific adaptations and will be used to modify intervention content. 
MAXQDA software will be used for data management and processing. Given 
the iterative nature of our approach and the need for timely adaptation of the 
intervention, a rapid qualitative analysis technique117 will be used to 
summarize and analyze transcript data. Rapid analysis is being increasingly 
utilized in implementation science research and has been demonstrated to 
yield results similar to in-depth qualitative analytic methods.118, 119 Our 
analysis will focus on the 3 key domains of content, methodology, and 
procedure with flexibility to include additional domains or components 
derived from transcript review. Two qualitative analysts will pilot, revise, 
and utilize transcript summary templates based on these domains to identify 
adaptations which will be used to modify content.
Intervention feasibility: We will assess feasibility using three primary 
criteria: 1) proportion of approached survivors who agree to participate in the 
intervention trial, 2) adherence to interventions parameters (module/session 
completion, reasons for dropouts), and 3) acceptability of intervention 
procedures. For the R61 feasibility trial we aim to enroll 30 participants (10 
from each racial/ethnic group: non-Hispanic White, non- Hispanic Black, 
Hispanic). In an ad hoc manner, if fewer than 50% of approach survivors 
agree to participate, the intervention will not be considered feasible (i.e., if 
we need to approach more than 60 survivors to enroll 30 for the feasibility 
trial). A participant will be considered a “completer” if he/she completes at 
least 75% of all the sessions (4/6 CBT and 9/12 tDCS sessions). The 
intervention will be considered feasible if at least 60% of the participants are 
completers. The feasibility will be assessed in the overall sample of 30 using 
exact 95% lower confidence bound (Clopper-Pearson method). Thus, the 
intervention will be considered feasible if 23 or more participants complete 
the intervention with 95% exact lower confidence bounds (0.61, 1.0). In 
addition, in an exploratory manner we will assess completion rates in each 
racial/ethnic group to see if differences are observed. We also will assess 
treatment acceptability. If >50% of participants report the intervention as 
‘unacceptable’ the intervention will not be considered feasible as designed. 
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Finally, we will estimate preliminary effectiveness of the intervention to 
inform potential changes to the proposed sample size needed for the larger 
R33 clinical trial. We will compare mean change scores for pain intensity and 
functional disability in survivors who received active tDCS vs. sham using a 
two-sample t-test. Although we will not be powered to detect a statistically 
significant difference between the groups, we will use the effect estimate to 
inform power calculations for the R33 clinical trial. If any of the feasibility 
parameters including 1) participation rate, 2) adherence, or 3) acceptability 
do not meet our a priori defined feasibility definitions, we will re-engage 
stakeholders and individuals with lived experiences for input and make 
adaptions to the interventions based their feedback as well as data we collect 
from participants related to reasons drop out and unfavorable acceptability. 
Transition to the R33 phase will be contingent on meeting milestones defined 
in the Study Timeline. These include: 1) adaptation and tailoring of 
intervention content, 2) completion of mobile CBT program modifications, 
and 3) completion of the 6-week feasibility trial of culturally adapted CBT + 
tDCS.
9.1 Anticipated Completion Dates (elements required by CT.gov)

Anticipated Primary Completion Date: October, 2024  

Anticipated Study Completion Date October, 2025  
10.0 OBTAINING INFORMED CONSENT
10.1 Informed Consent Prior to Research Interventions 
Participants will be informed that all study procedures are for research 
purposes only. Participants will be introduced to the study during the 
consent process by e-mail and phone. The consent conference for remote 
participation will be completed by phone.  A member of the study team will 
explain the study and review the potential risks and benefits.
If the participant expresses interest, they will be e-mailed, faxed, or 
mailed/FedExed a copy of the consent form if they agree to consent 
conference via phone; the consent conference will occur via phone and e-
mail, or e-signature will be used to document informed consent. Once the 
consent signature page is received the participant is enrolled on study as 
described in Section 3.6.
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10.2 Consent at Age of Majority
The age of majority in the state of Tennessee is 18 years old.  Research 
participants must be consented at the next clinic visit after their 18th birthday. 
Please refer to HRPP Policy 01.722 Legally Effective and Prospectively 
Obtained Informed Consent and Assent for Research and Documentation.  If 
an affiliate or collaborating site is located in a country or state where a 
different age of majority applies, that location must consent the participants 
according to their local laws. 
10.3 Consent When English is Not the Primary Language
When English is not the patient, parent, or legally authorized representative’s 
primary language, the Social Work department will determine the need for an 
interpreter.  This information documented in the participant’s medical record.  
Either a certified interpreter or the telephone interpreter’s service will be used 
to translate the consent information.  The process for obtaining an interpreter 
and for the appropriate use of an interpreter is outlined on the Interpreter 
Services, OHSP, and CTO websites.
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11.0 REFERENCES
1. Ehrhardt MJ, Krull KR, Bhakta N, et al. Improving quality and quantity of life for 
childhood cancer survivors globally in the twenty-first century. Nat Rev Clin Oncol. 2023;20: 
678-696.
2. Bhakta N, Liu Q, Ness KK, et al. The cumulative burden of surviving childhood cancer: an 
initial report from the St Jude Lifetime Cohort Study (SJLIFE). Lancet. 2017;390: 2569-2582.
3. Hudson MM, Ness KK, Gurney JG, et al. Clinical ascertainment of health outcomes among 
adults treated for childhood cancer. JAMA. 2013;309: 2371-2381.
4. Gaspar N, Hawkins DS, Dirksen U, et al. Ewing Sarcoma: Current Management and Future 
Approaches Through Collaboration. J Clin Oncol. 2015;33: 3036-3046.
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Collaborative Pathway to Success. J Clin Oncol. 2015;33: 3029-3035.
6. Norsker F, Boschini C, Rechnitzer C, et al. Risk of late health effects after soft-tissue 
sarcomas in childhood - a population-based cohort study within the Adult Life after 
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7. Oberoi S, Crane JN, Haduong JH, et al. Children's Oncology Group's 2023 blueprint for 
research: Soft tissue sarcomas2023.
8. Bishop MW, Janeway KA, Gorlick R. Future directions in the treatment of osteosarcoma. 
Curr Opin Pediatr. 2016;28: 26-33.
9. Bishop MW, Ness KK, Li C, et al. Cumulative Burden of Chronic Health Conditions in 
Adult Survivors of Osteosarcoma and Ewing Sarcoma: A Report from the St. Jude Lifetime 
Cohort Study. Cancer Epidemiol Biomarkers Prev. 2020;29: 1627-1638.
10. Marcotte EL, Domingues AM, Sample JM, Richardson MR, Spector LG. Racial and 
ethnic disparities in pediatric cancer incidence among children and young adults in the United 
States by single year of age. Cancer. 2021;127: 3651-3663.
11. Jacobs AJ, Lindholm EB, Levy CF, Fish JD, Glick RD. Racial and ethnic disparities in 
treatment and survival of pediatric sarcoma. J Surg Res. 2017;219: 43-49.
12. Zhao J, Han X, Zheng Z, et al. Racial/Ethnic Disparities in Childhood Cancer Survival in 
the United States. Cancer Epidemiol Biomarkers Prev. 2021;30: 2010-2017.
13. Treede RD, Rief W, Barke A, et al. Chronic pain as a symptom or a disease: the IASP 
Classification of Chronic Pain for the International Classification of Diseases (ICD-11). Pain. 
2019;160: 19-27.
14. Groenewald CB, Essner BS, Wright D, Fesinmeyer MD, Palermo TM. The economic 
costs of chronic pain among a cohort of treatment-seeking adolescents in the United States. J 
Pain. 2014;15: 925-933.
15. Allen JM, Niel K, Guo A, Su Y, Zhang H, Anghelescu DL. Psychosocial Factors and 
Psychological Interventions: Implications for Chronic Post-Surgical Pain in Pediatric Patients 
with Osteosarcoma. J Clin Psychol Med Settings. 2021;28: 468-476.
16. Tonning Olsson I, Alberts NM, Li C, et al. Pain and functional outcomes in adult 
survivors of childhood cancer: A report from the St. Jude Lifetime Cohort study. Cancer. 
2021;127: 1679-1689.
17. DeWalt DA, Thissen D, Stucky BD, et al. PROMIS Pediatric Peer Relationships Scale: 
development of a peer relationships item bank as part of social health measurement. Health 
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18. Lu Q, Krull KR, Leisenring W, et al. Pain in long-term adult survivors of childhood 
cancers and their siblings: a report from the Childhood Cancer Survivor Study. Pain. 
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19. Commission on Social Determinants of Health. Closing the gap in a generation: Health 
equity through action on the social determinants on health. Geneva, Switzerland: World 
Health Organization, 2008.
20. U.S. Department of Health and Human Services, National Institutes of Health, National 
Institute on Minority Health and Health Disparities. NIMHD Research Framework,. Available 
from URL: https://www.nimhd.nih.gov/about/overview/research-framework/nimhd-
framework.html 2022].
21. King S, Chambers CT, Huguet A, et al. The epidemiology of chronic pain in children and 
adolescents revisited: a systematic review. Pain. 2011;152: 2729-2738.
22. Tran ST, Koven ML, Castro AS, Goya Arce AB, Carter JS. Sociodemographic and 
Environmental Factors are Associated with Adolescents' Pain and Longitudinal Health 
Outcomes. J Pain. 2020;21: 170-181.
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