Building Adaptive Coping and Knowledge to Improve Daily Life (Back2Life): A Pilot Feasibility Clinical Trial for Youth With Chronic Sickle Cell Pain
Phase: NA
Conditions: Sickle Cell Disease
Sponsor: Emory University

Study Protocol 
 
Title: Building Adaptive Coping and Knowledge to Improve Daily Life 
(Back2Life): A Pilot Feasibility Clinical Trial for Youth With Chronic Sickle 
Cell Pain 
 
NCT Number: NCT04602728 
 
Protocol date: August 17, 2021 

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PROTOCOL TITLE:   Building Adaptive Coping and Knowledge to Improve Daily Life (Back2Life): 
A Pilot Feasibility Clinical Trial for Youth with Chronic Sickle Cell Pain.
PRINCIPAL INVESTIGATOR:
Soumitri Sil, Ph.D.
Assistant Professor of Pediatrics
Aflac Cancer and Blood Disorders Center
Co-Investigators
Carlton Dampier, M.D.
Professor of Pediatrics
Aflac Cancer and Blood Disorders Center
 
Lindsey Cohen, Ph.D.
Professor of Psychology
Georgia State University
Professional Staff Psychologist
Children’s Healthcare of Atlanta
 
Vivien Sheehan, M.D., Ph.D.
Associate Professor of Pediatrics
Aflac Cancer and Blood Disorders Center
 
Study Interventionists
Kerri Woodward, Ph.D.
Psychology Postdoctoral Fellow
Aflac Cancer and Blood Disorders Center
Yelena Johnson, Ph.D.
Psychology Postdoctoral Fellow
Aflac Cancer and Blood Disorders Center
 
EXTERNAL (NON-EMORY) COLLABORATORS N/A ☐:                                                                   N/A 
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FUNDING SOURCE: National Heart Lung and Blood Institute 1K23HL133457-01A1

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REVISION HISTORY
Revision #
Version 
Date
Summary of Changes
V. 2
5-11-20
Misc. details for IRB submission
V. 3
6-9-20
Clarification regarding the use of verbal consenting,  
clarification regarding subject recruitment, changes to 
participant compensation, updated version and date, 
added study team info
V.4
8-17-21
Addition of opt-in portion of the study involving blood 
sample to coincide with assessment time points

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Table of Contents
1.0
Study Summary....................................................................................................................5
2.0
Objectives* ..........................................................................................................................5
3.0
Background*........................................................................................................................5
4.0
Study Endpoints*.................................................................................................................5
5.0
Study Intervention / Design.................................................................................................6
6.0
Procedures Involved* ..........................................................................................................6
7.0
Data and Specimen Banking* ..............................................................................................6
8.0
Sharing of Results with Participants* ..................................................................................7
9.0
Study Timelines*..................................................................................................................7
10.0
Subject Population*.............................................................................................................7
11.0
Vulnerable Populations* .....................................................................................................8
12.0
Local Number of Participants ..............................................................................................8
13.0
Recruitment Methods..........................................................................................................8
14.0
Withdrawal of Participants*................................................................................................9
15.0
Risks to Participants*...........................................................................................................9
16.0
Potential Benefits to Participants*......................................................................................9
17.0
Data Analysis, Management* and Confidentiality.............................................................10
18.0
Provisions to Monitor the Data to Ensure the Safety of Participants*..............................10
19.0
Provisions to Protect the Privacy Interests of Participants and Confidentiality of 
Participants’ identifiable data.......................................................................................................11
20.0
Compensation for Research-Related Injury.......................................................................11
21.0
Economic Burden to Participants ......................................................................................11
22.0
Consent Process.................................................................................................................12
23.0
Process to Document Consent in Writing..........................................................................15
24.0
Setting................................................................................................................................15
25.0
Resources Available...........................................................................................................16
26.0
Multi-Site Research*  ....................................................................................................16
27.0
References.........................................................................................................................17

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1.0
Study Summary
Study Title
Building Adaptive Coping and Knowledge to Improve 
Daily Life (Back2Life): A Pilot Feasibility Clinical Trial 
for Youth with Chronic Sickle Cell Pain 
Study Design
Single-Arm, Uncontrolled Behavioral Clinical Trial 
Primary Objective
Conduct a pilot proof-of-concept clinical trial to 
evaluate the feasibility, acceptability, and preliminary 
efficacy of Back2Life with youth with chronic SCD pain 
and their parents
Secondary Objective(s)
Refine intervention content and delivery based on 
participant qualitative feedback; Evaluate a biological 
response to intervention 
Research 
Intervention(s)/Interactions
The treatment program includes 6-sessions of 
standard cognitive-behavioral therapy (CBT) 
treatment (delivered to all participants) and 1-4 
tailored sessions to address common co-morbidities 
associated with chronic pain (sessions assigned based 
on results of baseline assessment). The treatment 
manual leverages existing evidence-based 
interventions into a treatment package that will be 
tailored to individual patient and family needs.  
Study Population
Children with sickle cell disease (SCD) aged 10-18 
years old and their parent(s)
Sample Size
25 parent-child dyads
Study Duration for 
individual participants
8 months
Study Specific 
Abbreviations/ Definitions 
Back2Life: Building Adaptive Coping and Knowledge 
To improve daily Life
CBT: cognitive-behavioral therapy 
Funding Source (if any)
NHLBI
2.0
Objectives*
2.1
Primary Aim: Conduct a pilot proof-of-concept clinical trial to evaluate 
the feasibility, acceptability, and preliminary efficacy of Back2Life with youth 
with chronic SCD pain and their parents (n=25). We will use an adaptive 
treatment approach with 6-10 module-based treatment sessions selected on the 

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basis of baseline assessment (rather than a fixed treatment approach) to allow 
flexibility in tailoring treatment components to meet individual family needs.
2.2
Hypothesis 1: It is expected that the Back2Life treatment program will be 
feasible and acceptable as demonstrated by high levels of treatment 
engagement (≥80% attendance of treatment sessions) and high ratings of 
treatment satisfaction. 
2.3
Hypothesis 2: Participants who complete the Back2Life treatment 
program will report reductions in pain interference and pain symptoms (intensity 
and frequency) at post-treatment and 6-month follow-up. Preliminary efficacy 
will be defined as clinically significant (≥30%) reductions in pain interference and 
pain.
2.4
Exploratory hypothesis 1: We will explore reductions in secondary 
outcomes related to healthcare use for pain (inpatient hospitalizations, ED visits, 
and opioid use) at 6-month follow-up.  
2.5
Exploratory hypothesis 2: The Back2Life treatment program will result in 
measurable reductions in inflammatory biomarkers from baseline to 3-month 
and 6-month follow-up.
3.0
Background*
3.1
Pediatric sickle cell disease (SCD) is a genetic disorder of the hemoglobin 
in which the course of acute pain from vaso-occlusion and its sequelae vary 
widely across genotypes and individual patients. SCD pain often begins during 
childhood and can progress to chronic pain for approximately 23% of children 
and adolescents1. Youth with chronic SCD pain, that is pain that is present on 
most days per month and persists for at least 6 months2, report high levels of 
functional disability, elevated depressive and anxiety symptoms, and reduced 
quality of life relative to youth with SCD without chronic pain1. The complex, 
multifactorial nature of chronic SCD pain can also contribute to increased 
healthcare utilization for pain1,3-5. The most effective management and 
treatment of chronic SCD pain likely requires individualized, multimodal, 
multidisciplinary treatments that go beyond pharmacological management 
alone6. A range of evidence-based non-pharmacological treatments, such as 
behavioral health, complementary, and integrative health approaches, are 
recommended for chronic pain management and are gaining greater awareness 
and integration into comprehensive chronic pain care6,7)
3.2
Behavioral health treatment, such as cognitive-behavioral therapy (CBT) 
for pain, focuses on improved daily functioning and coping through several core 
treatment components such as psychoeducation about how the body processes 
pain, relaxation skills training, and cognitive strategies8. CBT is effective for 
youth with a variety of chronic pain conditions, including chronic headache, 
recurrent abdominal pain, fibromyalgia, and recurrent sickle cell pain, in reducing 
pain intensity immediately following treatment and reducing pain-related 

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disability post-treatment and up to 12 months later9. CBT has been shown to 
reduce proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), C-
reactive protein (CRP), interleukin-1β (IL-1 β), and interleukin-6 (IL-6), in adult 
patients with stroke, cardiovascular disease, cancer, depression, and anxiety. 
Interventions that reduce inflammation are especially needed for youth with SCD, 
for whom the propagation of inflammatory activity is a central mechanism that 
triggers vaso-occlusive episodes and long-term disease complications, such as 
organ damage. The few existing randomized clinical trials (RCTs) of CBT for acute 
or recurrent SCD pain in pediatrics are primarily limited by small sample sizes, 
poor treatment engagement, and inadequate randomization, stratification, or 
blinding; further, no clinical trials have yet to specifically target chronic SCD 
pain10.  
3.3
Youth with chronic SCD pain need an evidence-based, culturally informed, 
adaptive treatment. Behavioral treatments that are tailored to patient and 
family needs are beneficial when patients may require different levels of care11. 
Tailored or adaptive treatments align with a stepped care model that moves 
from lower (screening) to higher (intervention) levels of care in a cost-effective 
manner12. Adaptive treatments have been successful for a variety of pediatric 
chronic conditions, such as asthma13, depression14, anxiety15, and adults with 
chronic pain and co-morbid psychological disorders16-18. Adaptive designs are 
more effective in improving health outcomes, satisfaction with treatment, and 
reducing healthcare use than standard protocols where patients receive a fixed 
“one size fits all” treatment that is not personalized to their needs; adaptive 
designs are also recommended for tailoring evidence-based interventions with 
culturally diverse populations19-21. Adaptive treatments can integrate evidence-
based strategies to address common co-morbid problems associated with chronic 
pain, such as elevated anxiety or depressive symptoms or sleep 
disturbance14,16,22,23 . Teaching parents problem-solving skills can reduce 
caregiver stress among families managing chronic pain and illness13,24,25. 
3.4
We will utilize an adaptive behavioral treatment to target psychosocial 
risk factors for youth with chronic SCD pain as a first step towards developing a 
stepped care model for SCD pain. The proposed treatment, called Back2Life, is 
innovative because it is culturally informed by families’ and patients’ feedback 
regarding their treatment preferences and targets psychological co-morbidities 
that are often excluded in clinical trials. The overarching hypothesis driving the 
proposed intervention is that disrupting the complex interacting psychosocial 
factors that can exacerbate chronic SCD pain will prevent and/or reduce poor 
health outcomes in children and adolescents with SCD. 
4.0
Study Endpoints*
4.1
Primary study endpoints include markers of treatment feasibility,  
acceptability, and preliminary efficacy related to pain interference, pain 
characteristics (burden, intensity, frequency), and pain coping efficacy. Secondary 

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outcomes will include healthcare use for pain (admissions, ED visits, opioid use) 
and inflammatory biomarkers (e.g., proinflammatory cytokines).
5.0
Study Intervention / Design 
A proof-of-concept trial is a cost-effective method to determine if the 
treatment package can achieve a clinically significant improvement in 
outcome in a small, select sample26. As a single-arm trial, a proof-of-
concept determines whether the treatment merits rigorous and costly 
testing using an RCT or requires further optimization, thereby minimizing 
waste of resources and first ensuring clinically significant improvements can 
be achieved under optimum conditions. 
A manualized treatment protocol, including intervention content, delivery 
style, and materials were adapted for optimization based on analyses of 
qualitative feedback from qualitative interviews and theater testing (i.e., 
pre-testing the intervention with the target audience to examine attitudes 
towards the format, content, etc). The treatment program includes 6-
sessions of standard treatment (delivered to all participants) and 1-4 
tailored sessions to address common co-morbidities associated with chronic 
pain (sessions assigned based on results of baseline assessment). The 
treatment manual leverages existing evidence-based interventions into a 
treatment package that will be tailored to individual patient and family 
needs.  
6.0
Procedures Involved*
6.1
Patients and parents who provide consent/assent will participate for 8 
months (between 12-17 study visits).  The study involves a combination of 1) 
assessments (4 study visits), 2) treatment sessions (6-10 study visits), 3) booster 
sessions (1 study visit), and 4) a qualitative interview (combined with a post-
treatment assessment).  
6.2
Baseline Assessment: Parents and teens will complete an assessment of 
surveys at a baseline study visit. We will ask parents and teens to complete brief 
questionnaires about the teen’s pain, sleep, mood, physical functioning, and 
interest in participating in the program (see Measures below). Parents will also 
complete a brief questionnaire about stress related to parenting. Teens will 
complete a 1-week daily diary to record pain ratings, school attendance, sleep 
quality, and medication use. 
6.3
Treatment Program: All teens will receive the standard 6-session pain 
coping skills training program (learning ways to cope with and manage chronic 
sickle cell pain). The standard program includes topics that were identified by 
teens with chronic sickle cell pain and their parents as important skills for all 
teens with chronic pain and sickle cell disease. Research staff will use the 
information from the baseline assessment to tailor the treatment program to the 
needs of each teen and family. In addition to the standard 6-session program, 

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teens may receive an additional 1 to 4 sessions that may help with specific 
problems and/or co-morbidities related to pain. For example, additional sessions 
may include topics such as difficulty sleeping, bad moods, or parenting stress. 
Patients and parents who do not screen into the additional tailored sessions 
based on their baseline assessment scores will still have the option to participate 
in any of the additional sessions. Please see Appendix A for Back2Life Treatment 
Session Overview. 
6.4
Treatment Sessions: The treatment sessions will be conducted in-person 
at a CHOA hospital campus or via telehealth using HIPPA-compliant platform 
(e.g., Zoom). An in-person study visit for the first treatment session is strongly 
encouraged to promote optimal therapeutic rapport, and all remaining 
treatment sessions may be conducted in-person or via telehealth, based on 
patient/family preference. Treatment sessions will begin 1 week following the 
completion of baseline assessment. Each session will last about 1 hour, once a 
week. A treatment session window of +/- 14 days will allow flexibility to support 
adherence.  Each session will focus on teaching a new skill or strategy to improve 
chronic pain management. Sessions will be led by a psychology provider (PhD 
student, post-doctoral fellow, psychologist). Teens will be asked to practice the 
coping skills at home between sessions and keep a brief diary of their practice, 
pain symptoms, school attendance, and medication use. At least one parent or 
guardian is required to attend with their teen. However, all interested family 
members (parents, grandparents, siblings) are encouraged to attend sessions 
with their teen. Parents will also receive education and training in the skills their 
teen will be learning along with behavior management strategies to support 
teen’s use of skills at home. One booster session will be offered 2 months after 
completing the program. The booster session will focus on problem-solving any 
difficulties teens or parents may have had with using the skills at home or school. 
The booster session will be conducted either in-person, telehealth, or by phone, 
depending on family preference. Intervention content will be sensitive to 
developmental differences. For example, parents of school-aged children will be 
guided to coach their children’s use of coping strategies. Parents of adolescents 
will be guided to provide monitoring and oversight of adolescent self-
management and communication with providers to promote independence. 
Sessions may be audio recorded and will only be reviewed by research staff to 
make sure that the content of the training program is being provided accurately 
and thoroughly to all participants. Between sessions, follow-up by phone or 
during inpatient admissions will allow for opportunities to problem-solve 
integration of strategies. Make-up sessions will be built into the treatment 
session timeline to allow flexibility and treatment adherence.
6.5
Follow-Up Assessments: All teens and parents will complete the same 
assessment of surveys after completing the standard 6-session program (post-
treatment evaluation). Parents will also report on any changes to their teen’s 
medical treatment plan since the last assessment. All teens and parents will 

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complete the assessments at 3-months and 6-months follow-up from baseline. All 
assessments can be completed in-person, at home using online or paper-and-
pencil questionnaires, or by telehealth (video or phone) depending on teen and 
parent preference. An assessment window of +/- 2 weeks will allow flexibility to 
support recruitment and adherence. 
6.6
Blood Sample Collection: As an optional component of the study, all teens 
will have the option to consent to blood sample collection at three assessment 
visits: baseline, 3-month follow, and 6-month follow-up. Blood sample collection 
will occur at or close to each time point allowing at least 2 weeks following an 
acute care visit for pain to ensure steady disease state collection. To enhance 
clinical implementation and acceptability, efforts will be made to coordinate 
blood sample collection during routine medical visits to minimize blood draws. 
Each sample will be about 4 teaspoons (about 20 milliliters) of blood, which will 
be drawn in the clinic or hospital, and will only take a few seconds. Collected 
blood samples will be immediately transported to Dr. Sheehan’s laboratory for 
labeling, processing, storage, and analysis. 
6.7
Qualitative Interview: At the end of the treatment program, parents and 
teens will be asked for feedback in a one-on-one interview lasting about 30 
minutes. Feedback may include how they liked the program, what they thought 
about the content of the program, and any suggestions or changes to the 
materials or format. Information from these interviews will be used to refine and 
modify the Back2Life program. Interviews can be conducted in-person or by 
telehealth (video and/or phone). Interviews will be audio recorded as digital files 
and transcribed for analysis by advanced psychology PhD students or trained 
study members. Audio recordings will be saved for up to 6 years following 
completion of the study and saved via password-protected computer that is only 
accessible to the PI to ensure security. No audio recordings will be used for 
educational or presentation purposes. The research design does not require 
subjects to be deceived. 
6.8
Intervention fidelity. Written intervention manuals will promote quality 
assurance and include materials for training, supervision, and fidelity monitoring. 
All sessions may be audio recorded; a random sampling of 25% of sessions from 
each family will be reviewed with mentors to monitor protocol adherence. 
Fidelity checklists will be completed independently by 2 reviewers (PhD students). 
Participant homework completion will be routinely assessed. 
6.9
Measures
Study measures are described below. Based on PedIMMPACT guidelines29, the 
primary treatment outcomes will be pain interference, pain characteristics 
(burden, intensity, frequency), and pain coping efficacy. Secondary outcomes will 
include healthcare use for pain (admissions, ED visits, opioid use). Questionnaires 
will be completed online using REDCap or paper-and-pen, depending on 

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participant preference. Children and their parents will complete their 
questionnaires separately. The total time for the full battery of child and parent 
questionnaires is approximately 20 minutes. We will monitor changes in medical 
or psychiatric treatment during the study through medical chart review. 
6.10
Treatment Feasibility
1) Study recruitment and enrollment statistics
2) Treatment adherence as demonstrated by drop-out rate, session completion, 
missed/rescheduled treatment sessions, therapist ratings of participants’ 
homework completion
3) Completion of study assessments 
4) Participant ratings on whether they thought the Back2Life program is a 
reasonable approach for chronic pain management, if the program was helpful, 
could be integrated into their lifestyle, and description of barriers in 
implementing the program. 
6.11
Treatment Acceptability
Treatment Evaluation Inventory, Short Form will be completed at immediate 
post-treatment. It includes 9 items adapted to be specific to pediatric pain. Items 
are rated on a 5-point Likert scale ranging from 1 to 5. Total scores range from 9-
45. Scores ≥ 27 indicate “moderate” treatment acceptability30. 
6.12
Primary Treatment Outcomes
1) PROMIS Pediatric Short Form-Pain Interference, Self- and Parent-Proxy Report 
is an 8-item self-report measure that will assess functional interference due to 
pain in the past 7 days. PROMIS Pediatric measures have been well validated 
among youth with SCD and chronic pain in inpatient and outpatient settings31-
34. (2-3 mins)
2) Sickle Cell Pain Burden Interview for Youth, Self--Proxy Report is a brief, 
validated measure of pain burden in 7-21 year olds. It demonstrated strong 
reliability and validity among youth with SCD from inpatient and outpatient 
settings35. Patient self-report and parent-proxy report of total pain days in the 
past month and duration of chronic pain will also quantify pain frequency1,35. 
(2-3 min)
3) PROMIS Pediatric Short Form-Pain Behaviors, Parent-Proxy Report is an 8-item 
measure completed by parents that assesses pain behaviors displayed by their 
child in the past 7 days. PROMIS Pediatric measures have been well validated 
among youth with SCD in inpatient and outpatient settings (2-3 min)

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4) Child Self-Efficacy Scale, Self- and Parent-Proxy Report is a well-established, 7-
item measure of self-efficacy for functioning despite pain for 8-19 year olds36. It 
demonstrated good internal consistency and validity among youth with a variety 
of pain problems37. (2-3 min)
6.13
Secondary Treatment Outcomes 
1) Healthcare utilization will be extracted from the medical record to document 
the total number of emergency department (ED) visits and admissions for pain 
for 6-months and 12-months pre- and post-treatment.  
2) Opioid use will be calculated based on participant completion of daily diaries 
for 1-week at each assessment visit. Participants will record opioid use daily 
(presence/absence). Opioid use also will be documented on daily diaries 
throughout the course of treatment. 
3) Inflammatory biomarkers, including but not limited to, proinflammatory 
cytokines and markers, such as interleukin -1β (IL-1β), interleukin – 6 (IL-6), 
interleukin – 8 (IL-8), tumor necrosis factor – alpha (TNF-α), c-reactive protein 
(CRP), brain-derived neurotrophic factor (BDNP), and interferon gamma (INF-y) 
will be analyzed. Plasma concentrations for each biomarker will be determined 
by a custom multiplex kit (e.g., FirePlex-384 Multiplex Assay by abcam), an 
immunoassay panel detected by flow cytometry used for simultaneous 
quantitative measurement in a single sample with high sensitivity and high 
throughput capacity. All samples will be analyzed in triplicate.  
6.14
Psychosocial Measures - Tailoring Variables and Predictors of Treatment 
Success 
Based on baseline assessment of the following measures, additional sessions will 
be tailored to each family’s needs. 
1) Pediatric Inventory for Parents, Parent Report is a 42-item parent-reported 
measure of caregiver stress related to child chronic illness. It has shown high 
internal consistencies among caregivers of youth with SCD38,39. Total scores 
that are ≥ 1 SD above the mean will be eligible for tailored sessions on caregiver 
stress.  (5-7 mins)
2) Adolescent Sleep Wake Scale (ASWS), Adolescent Report is a 28-item patient-
reported describing the occurrence and frequency of various behavioral sleep 
characteristics over the past month. It is a commonly used measure of sleep in 
pediatric pain with good psychometric reliability and validity40,41. Total scores 
that are ≥ 1 SD above the mean will be eligible for tailored sessions on behavioral 
sleep strategies.  (3-5 mins)

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3) PROMIS Pediatric Short Form - Depressive Symptoms, Self- and Parent-Proxy 
Report. An 8-item measure designed for youth to assess self-reported symptoms 
of depression, and has been utilized among a wide array of pediatric chronic 
illness, including chronic pain and SCD32,42. Teens reporting T-Score ≥ 65 will be 
eligible for tailored sessions focused on managing depressive symptoms.  (1-2 
mins)
4) Pain Catastrophizing Scale-Child and Parent Report is a 13-item well-validated 
self-report and parent-report measure of worried thoughts about pain. It is 
widely used in chronic pain and demonstrated strong internal consistency in 
SCD28,43. Total scores ≥26 by parent or child report will be eligible for tailored 
sessions focused on managing anxiety and fear of pain. (2-3 mins)
5) Pain Stages of Change Questionnaire- Adolescent and Parent Report is a 30-
item measure designed to evaluate parent and adolescent perceptions of 
readiness to adopt a self-management approach to pain44,45. (5 mins)  
6.15
Compensation
Parents and teens will be compensated for their time and participation for each 
completed study visit. Participants who do not finish the study will be paid for the 
visits they have completed. Parents and teens will each receive between $435 to 
$595 total, if they complete all study visits. Reimbursements are detailed below.
Baseline and Follow-up Surveys: Parents and teens will each receive $25 for 
completing the baseline study visit, $30 for end of treatment assessment, $35 for 
3-month assessment, and 40 for 6-month assessment. 
Treatment and Booster Sessions: To reimburse transportation costs for attending 
each treatment session or to offset the costs for cellular data or WiFi usage for 
telehealth sessions, parents and teens will each receive $40 for every attended 
session (between 7-11 sessions). 
Qualitative Interview:  Parents and teens will also each receive $50 for 
completing the qualitative interview at the end of the program.
Blood Sample Collections: Teens will receive $30 for completing each blood 
sample collection at the baseline study visit, 3-month assessment, and 6-month 
assessment.
7.0
Data and Specimen Banking*
7.1
N/A
8.0
Sharing of Results with Participants*
8.1
As a clinical service to participants, patients and parents may elect to 
receive aggregate data on the study findings at the completion of the study. 

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9.0
Study Timelines*
9.1
Patients and parents who provide consent/assent will participate for 8 
months (between 12-17 study visits).  The study involves a combination of 1) 
assessments (4 study visits), 2) treatment sessions (6-10 study visits), 3) booster 
sessions (1 study visit), and 4) a qualitative interview (combined with a post-
treatment assessment).  
10.0 Subject Population*
10.1
Inclusion Criteria:  Youth will be eligible for inclusion if they are (a) 10-18 
years old, (b) diagnosed with SCD (any genotype), (c) report chronic pain, (d) 
speak and read English, and (e) have not initiated new disease modifying-
treatments (e.g, hydroxyurea, Endari, voxeletor, crizanlizumab, chronic 
transfusions) or significantly increased dosages (mg/kg) of any disease-modifying 
treatments in the past 3 months. As in our prior work1,28, chronic pain 
classification will be based on pain frequency and persistence: 1) patient reports 
≥ 12 pain days per month, and 2) pain frequency persisted for ≥ 3 months. 
Parents or caregivers will be eligible if they speak and read English.  
10.2
Exclusion Criteria:  Youth will be excluded if they (a) have comorbid 
medical conditions typically associated with pain but unrelated to SCD (e.g., 
rheumatologic disorders or inflammatory bowel disease); (b) are receiving 
chronic transfusion indicated for central nervous system risks and/or 
complications, previous overt strokes, or significant cognitive or developmental 
limitations, as per their healthcare provider or parent, that would impair 
completion of self-report measures or engagement in treatment sessions; and 
(d) received ≥ 3 sessions of outpatient psychological therapy for pain 
management in the 6 months prior to screening to ensure inclusion of patients 
and families who are naïve to CBT for pain. Parents or caregivers will be excluded 
if they have significant cognitive limitations or severe psychiatric conditions, as 
per the child’s healthcare team or history, that would impair completion of self-
report measures or engagement in treatment sessions.
10.3
25 child-parent dyads will be recruited from CHOA SCD clinics. 
Participants will include parents and children with SCD aged 10-18, which 
represents the developmental period when chronic pain is prevalent among 
youth27. Patients who are 18 years old may participate without a parent or 
caregiver, although parent participation is preferred. 
10.4
Community Participation (if applicable)
• N/A
11.0 Vulnerable Populations*
11.1 The research involves children under 21 who have not attained the legal 
age for consent to treatments or procedures involved in research. This study 
involves no greater than minimal risk to children. It presents the prospect of 

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anticipated direct benefit to individual participants by teaching coping skills 
that may help improve pain management. Parental permission of one 
parent will be obtained and assent will be obtained from children to ensure 
voluntary participation. Parental permission, parental consent, and child 
assent will be documented.   
12.0 Local Number of Participants
12.1 25 parent-child dyads
13.0 Recruitment Methods
13.1
Eligible patients will be identified for the study from new or existing SCD 
patients being seen through the CHOA Comprehensive Sickle Cell Program. We 
will use multiple recruitment strategies used in past studies. Describe the source 
of participants.
13.2
Participants in our research database who have agreed to be contacted 
for future studies will be contacted with a letter describing the study in a “who, 
what, where, and why” format and/or a personal phone call to the family to 
describe the study in further detail and determine interest and eligibility. Patients 
and parents expressing interest in the study will be provided the option to 
complete web-based or paper baseline measures at home, during their next 
scheduled outpatient clinic appointment, or during/following their inpatient 
admission. Verbal consent with the parent will be completed over the phone for 
participants from the existing study cohort.  The research team will call 
participants to follow-up about baseline survey completion.
13.3
Second, all eligible patients will be approached and screened during their 
routine outpatient SCD appointment or inpatient admission. Parents or legal 
guardians of patients must provide written consent for their child to be eligible 
for inclusion, and youth will provide written assent.  Parents will be invited to 
participate as well and must provide written consent for their own participation.  
How will eligibility be determined? Provide a detailed description of any eligibility 
screening done prior to enrolling subject (including whether any identifiers will be 
recorded – note that IP address is an identifier)
13.4
Third, parents and youth with SCD who meet the inclusion criteria and did 
not attend their scheduled outpatient appointment will be contacted by a letter 
describing the study.  Approximately one week after the letter is mailed, a 
member of the research team will call the family, describe the study in further 
detail, and ask if they are interested in participating. Families who express an 
interest or agree to participate will complete verbal consent and assent over the 
phone and will be mailed a packet of questionnaires or a link to complete 
questionnaires online via a secure CHOA REDCap site, based on their preference 
and access to internet.  The progress of the study in terms of recruitment will be 
monitored via a data tracking system that will allow the PI to review subject 
enrollment by age, gender and race.  

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14.0 Withdrawal of Participants*
14.1 Participants have the right to leave the study at any time without penalty. 
If participants choose to go off the study treatment or leave the study 
before the final planned study visit, participants may be asked to have 
some final study procedures completed including but not limited to follow-
up surveys at the planned end of the program, and follow-up surveys at 3-
months and 6-months after the program. 
14.2 Study personnel may stop participant involvement in the study without 
participant consent for any reason to maintain the best interest of the 
participant or if participants object to any future changes that may be 
made in the study plan. 
15.0 Risks to Participants*
15.1
Assessments:  The risks for participation in the study are minimal. Study 
questionnaires contain potentially sensitive questions concerning pain, 
psychosocial functioning, and sickle cell disease, which may elicit emotional 
discomfort.  Completion of questionnaire assessments may produce fatigue in 
some participants and burden related to length of assessments will be kept at a 
minimum. 
15.2
Treatment Sessions: The potential risk to participants is minimal.  
Potential risks for participants include feelings of emotional discomfort when 
discussing their/their child’s experiences with sickle cell disease and pain 
management and loss of confidentiality. Some participants enjoy talking about 
their symptoms and functioning and learning about self-management 
approaches. Participants may obtain more information about their pain 
condition and gain confidence in their ability function despite pain. Procedures 
to protect against these risks are detailed in the Protections Against Risk section 
below. Overall, the focus group discussions do not significantly increase the 
participants’ risk of harm beyond those risks that are inherent in ordinary daily 
living.
15.3
Blood Draws: Children and adolescents have the option to consent to 
blood sample collection. Participation in the assessments and treatment sessions 
will not require consent for blood sample collection. If they consent to this opt-in 
portion of the study, teens will have a needle stick to get the required blood. 
This may cause pain, bruising, bleeding, or infection at the site of the needle 
stick. There should be minimal discomfort related to blood draws. 
16.0 Potential Benefits to Participants*
16.1
General: To help reduce any uneasiness or discomfort about answering 
questions about their health, the research protocol includes standardized 
measures that have been widely used in other research of youth in this age 
range with SCD without adverse effects. Participants will be allowed to skip any 

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questions that they do not feel comfortable answering, will be allowed the 
freedom to leave during treatment sessions or the qualitative interview at any 
time, and will have opportunities for breaks to minimize fatigue.  Participants will 
be informed of their right to terminate their participation in any part of data 
collection at any time and will be given phone numbers of the PI as well as the 
Emory IRB if they would like to issue a complaint or desire any additional 
information regarding the study. Participants will receive financial compensation 
for the time commitment necessary for their study participation.  Participant 
compensation will be provided in the form of Visa cash cards. To ease the travel 
burden associated with transportation, participants also will be provided with 
gas cards.  
16.2
Blood draws:  To help minimize discomfort from blood draws, every 
effort will be made to coordinate study visits with clinic visits to minimize 
repeated blood draws and reduce the amount of time needed for additional 
sample collection. Well-trained phlebotomists at CHOA are experienced in 
conducting blood draws with minimal risk. Child life specialists are available to 
offer coping support to children and adolescents, if needed. 
16.3
Depression Screening: In the event that one of the procedures reveals 
indicators of significant depressive symptoms or suicidal ideation, a standard 
suicide-risk plan will be implemented.  Dr. Sil and her research staff are already 
trained in a standard risk assessment protocol that has been successfully 
implemented in Dr. Sil’s prior studies. Research staff will already be reviewing 
baseline assessment measure to determine the need for tailored sessions. The 
treatment program will be delivered by highly trained psychology postdoctoral 
fellows supervised by the PI. In the event that a participant endorses clinically 
significant depressive symptoms, suicidal ideation, or reveals a history of abuse 
on questionnaires or during treatment sessions, a risk assessment will be 
conducted by the psychology fellows under Dr. Sil’s supervision. Dr. Sil is a 
licensed clinical psychologist and will be available 24 hours a day to be called via 
cell phone to address crisis questions. Psychiatric or other life crises that are high 
risk and imminent will be acted upon immediately with staff linking participants 
to appropriate crisis services (e.g., a referral to the ED (if necessary), community 
agencies for ongoing care). These are reviewed immediately with the clinically 
responsible PI and/or primary co-mentor (Dr. Cohen), who is also a licensed 
clinical psychologist. Lower risk and less imminent crises will result in an attempt 
to help the participant devise a plan for treatment and/or safety.  For example, 
major stresses, availability of social supports, access to treatment, and plans for 
safety will be discussed in detail with the participant, and appropriate referrals 
for treatment will be provided. These cases will be reviewed within 24 hours by 
the clinically responsible PI and mentors. All actions taken will be documented 
on a case report form. Based on our prior experience in similar psychosocial pain 
research in SCD, we anticipate this risk to be very low. 

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16.4
Benefits to participant or future benefits. Participation in the clinical trial 
may or may not directly benefit participants. This study is designed to learn more 
about how teens with chronic sickle cell pain respond to the program and if it 
helps them manage their chronic pain. Although we do not know for certain 
whether the treatment will reduce pain, the study results will allow us to 
develop better treatment programs which might be used to help others in the 
future. This will provide critical knowledge for the further intervention 
refinement and testing in a controlled trial in a future study. The potential risks 
of participation to participants are considered to be minimal in relation to the 
potential gain. 
17.0 Data Analysis, Management* and Confidentiality
17.1
Data Management.  All data will be entered into REDCap (supported by 
both Emory and CHOA), a secure web-based application for managing surveys 
and databases online, and exported into SPSS. The first step will be to compute 
descriptive statistics for all measures (means, standard deviations, range and 
skewness). This process will allow us to determine if there are any extreme 
outliers and whether the variables are normally distributed. If a variable is not 
normally distributed, log transformations will be used in all further analyses.  
Bivariate correlations among demographic variables and variables of interest will 
be examined to identify any meaningful covariates that will need to be 
controlled in further analyses.  Missing data will be handled by using Multiple 
Imputation or Maximum Likelihood methods of handling missing data.
17.2
Treatment Feasibility. Feasibility will be assessed using 4 metrics:
1) Study recruitment and enrollment statistics, such as proportion of eligible 
participants approached for the study who consent to participant 
2) Treatment adherence as demonstrated by drop out rate, session completion, 
missed/rescheduled treatment sessions, therapist ratings of participants’ 
homework completion, including the proportion of participants who attend at 
least 80% of sessions
3) Proportion of participants who complete study assessments 
4) Participant ratings on whether they thought the Back2Life program is a 
reasonable approach for chronic pain management, if the program was helpful, 
could be integrated into their lifestyle, and description of barriers in 
implementing the program. 
17.3
Treatment Acceptability. Acceptability of the intervention will be 
assessed through the Treatment Evaluation Inventory Short Form as well as 
qualitative interviews that will elicit perceptions about treatment content 
(utility, appropriateness) and format (convenience, number and length of 
sessions). See Appendix B for Interview Guide. Audio recordings of qualitative 
interviews will be transcribed for analysis. A coding system for thematic domains 

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and a coding scheme will be developed. Qualitative data will be analyzed using 
MAXQDA. Interview data will be coded by two independent reviewers to 
enhance confirmability and dependability of conceptual domains. Describe the 
steps that will be taken to secure the data (e.g., training, authorization of access, 
password protection, encryption, physical controls, certificates of confidentiality, 
and separation of identifiers and data) during storage, use, and transmission.
17.4
Preliminary efficacy will be examined by calculating standard effect sizes 
and 95% confidence intervals on primary outcomes (pain interference, pain, 
coping) at post-treatment and 3- and 6-month follow-up. Changes in primary 
outcomes over time will be assessed using repeated measures ANOVA. 
Comparisons between time points will be made using paired tests or Wilcoxon 
tests. In an adjusted analysis, potential control covariates (e.g., child age, 
number of sessions, changes in treatment) will be examined as appropriate. 
Based on past CBT pain trials, pain reductions typically occur from baseline to 
follow-up and independent of changes in pain interference9. To account for 
potential non-significant changes in pain intensity, we will examine individual 
clinically significant (≥30%) reductions in pain and interference.
17.5
Power Analysis: We are not attempting to fully power this proof-of-
concept study and will only examine preliminary efficacy using exploratory 
analyses. Preliminary power analyses were based on meta-analysis of CBT for 
pediatric chronic pain. We estimate an effect size of d=.55 for pain reduction at 
follow-up (30% pain reduction)9. A sample size of n=25 would achieve power 
estimates of approximately 80%. 
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants*
This project is a pilot feasibility study of the Back2Life intervention. Because it 
involves a behavioral intervention, we recognize the need to provide a plan to 
ensure the scientific integrity and safeguard the well-being of study participants. 
The study team is highly qualified to lead the cognitive-behavioral intervention.  
All study staff will be trained to conduct the interventions using a manualized 
protocol and will monitor the comfort and safety of participants at each session.  
The PI and study therapists will have regular monthly meetings to monitor the 
progress of the study, the integrity of the treatment and safety monitoring 
including a review of any adverse events. The PI will report any significant study-
related or unanticipated adverse events to the Institutional Review Board based 
upon institutional guidelines. Given that this is a feasibility study, it is felt that 
monitoring at the level of the PI and research team, with oversight from the IRB 
is sufficient.
The research team will utilize a variety of safeguards to protect the study from 
loss of data. Data will be collected using electronic or hard-copy versions of 
measures and will only be identified with the participant ID number. The codes 
that link the name of the participant to the study ID will be kept confidential in a 
secured cabinet. Collected forms will be electronically transferred or hard copies 

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will be transported to the Clinical Research Office. Data will be entered in the 
computer independently by two trained data entry staff, and discrepancies will 
be corrected by the PI based on source documents. The quality of the data will 
be monitored once per month. Data quality will be monitored by random 
inspection of the completed forms by the research staff and any problems 
detected will be discussed with the PI. Transcripts of qualitative interviews will 
be reviewed by an independent transcriber. Qualitative data will be coded by 
two independent reviewers and any discrepancies will be discussed to reach 
consensus during research team meetings. Research staff will receive 
standardized training on administration of assessments. Dr. Sheehan will oversee 
blood sample analysis, entry, management, quality assurance, and storage of 
quantified values in a de-identified database.
19.0 Provisions to Protect the Privacy Interests of Participants and 
Confidentiality of Participants’ identifiable data
19.1
This study will have several protections in place to minimize risk to loss of 
participant confidentiality. The participant’s identity, research records, and 
personal health information will be safeguarded using secure password-
protected services. Primary sources of data from questionnaires and digital 
audio files will be stored on a secure password-protected database that is 
protected by the highest standards for electronic data safety. The Aflac Clinical 
Research Office (CRO) will be responsible for the entry, management, quality 
assurance, and storage of the data. The CRO and research staff will utilize a 
variety of safeguards to protect the study from loss of data. The staff will 
perform routine backup of all study files, including main study database, digital 
audio files, transcriptions, files created for analyses, and programs used to 
process and analyze data. All files will be archived on a daily basis. All data will be 
coded with participant ID and no personal identifiers will be associated with 
these data. Only the study PI and other members of the research team will be 
able to access participant data. The list of identifying information linking subjects 
to their ID numbers will be kept in a restricted electronic file. A hard copy of the 
list will be kept in a locked file cabinet in my office away from research 
databases. 
19.2
Every effort will be made to assure that the data from the recorded 
treatment sessions and qualitative interviews are kept confidential. At the onset 
of each session and interview, participants will be reminded of audio recording 
and will be asked to refrain from revealing personal information that could result 
in identifying them to protect anonymity and confidentiality. The audio 
recordings produced from the sessions and interviews will be used only for the 
purposes of the study. The audio files will be stored in a password-protected 
computer folder accessible only to the study team. Each participant will be 
assigned an anonymous study code number in the transcript of the audiotape. 
Once transcribed, the computer data files will be password-protected, and these 

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data files will have no personal identifiers and contain no information linking an 
individual participant with their study code. These protections will be explained 
in the consent form. 
20.0 Compensation for Research-Related Injury
20.1 N/A.
21.0 Economic Burden to Participants
21.1 N/A
22.0 Consent Process
22.1
Written or verbal informed parental consent and child assent (as 
participants will be ages 10-18 years old) will be obtained prior to the initiation 
of any study procedures.  Participants will be explicitly told that their care at 
CHOA will not be affected whether they choose to participate in the study or 
decline participation.  Copies of parental consent and assent forms will be given 
to participants at the study visit.
22.2
For patients and families who are recruited via mailed letters or phone 
contact, verbal consent and assent will be obtained over the phone.  Following 
verbal consent, participants will be provided with a web link to complete the 
web-based questionnaires or paper-pencil forms will be mailed (based on family 
preference and internet access).   
23.0 Process to Document Consent in Writing
23.1 Procedures in accordance with Emory IRB Policy (HRP-091) will be followed 
to document written consent for participants recruited in-person during 
routine clinic visits. For participants who are recruited and consent by 
phone, verbal consent will be obtained. 
24.0 Setting
24.1
Patients and parents will have the option to complete assessments (either 
web-based measures or paper-and-pencil measures) during a routine outpatient 
sickle cell clinic visit at CHOA or at home.  Participants will be provided the option 
to take home packets of paper-pencil questionnaires or have packets mailed 
home to them if time prohibits their participation in clinic or internet access is not 
available in the home. Participants across all three CHOA sites will be eligible. 
Treatment sessions will occur at a CHOA campus location. Describe the sites or 
locations where your research team will conduct the research.
25.0 Resources Available
25.1 Children’s Healthcare of Atlanta is home to the nation’s largest pediatric 
sickle cell disease program with over 2000 active patients followed 
annually. Approximately 1000 patients are aged 10-18 years old. Based on 

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prior work in chronic SCD pain, approximately 20% of age-eligible patients 
are expected to meet diagnostic criteria for chronic pain in SCD. Study 
funding further supports 75% of the PI’s effort to direct towards research 
activities. The PI (Dr. Sil) has well-developed plans and resources to support 
psychological and behavioral human research (see Protections Against Risk 
for additional information). 
25.2
 Research coordinators and assistants will complete and maintain CITI 
certification and undergo training to use REDCap for data collection and 
management.  The PI will train research personnel in the process of screening 
eligible participants, recruitment, and the consenting process.  Research 
personnel also will receive standardized training on the administration and 
scoring of measures using REDCap as well as paper-pencil measures.  The 
research staff also will be trained in a specific procedural plan for identifying 
potential suicidal ideation and contacting a psychologist (Dr. Sil and/or Aflac 
Psychology team) to conduct a risk assessment at the site of data collection.  
Psychology postdoctoral fellows and/or Ph.D. students will be trained in 
transcription and coding of qualitative data under the supervision of the PI and 
qualitative methods expert. Psychology postdoctoral fellows also will undergo 
intensive training in the treatment manual led by the PI. 
26.0 Multi-Site Research*  
•
N/A
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