A Single-Site, Parallel-Group, Randomized-Controlled Pilot Trial Comparing BRIGHT With Active Control in Reducing Body Image Disturbance Among Head and Neck Cancer Survivors (BRIGHT 2.0)
Phase: NA
Conditions: Head and Neck Cancer
Sponsor: Medical University of South Carolina

BRIGHT 2.0 
 
Version 4.0  
Protocol #103191 
 
1 October 2021 
 
 
a
A Single-Site, Parallel-Group, Randomized-Controlled 
Pilot Trial Comparing BRIGHT with Active Control in 
Reducing Body Image Disturbance Among Head and 
Neck Cancer Survivors (BRIGHT 2.0) 
 
 
Protocol Number: 103191 
 
National Clinical Trial (NCT) Identified Number:  NCT03831100 
 
Principal Investigator: Evan Graboyes, M.D., M.P.H., FACS 
 
Sponsor: Hollings Cancer Center 
 
Grant Title: A Novel Treatment Strategy for Body Image Disturbance in Head and 
Neck Cancer Survivors 
 
Grant Number: R21CA245941 
 
Funded by: NCI 
 
Version Number:  v.4.0 (1 October, 2021) 
 

BRIGHT 2.0 
 
Version 4.0 
Protocol #103191 
 
1 October 2021 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
2 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 
 

BRIGHT 2.0 
 
Version 4.0 
Protocol #103191 
 
1 October 2021 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
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PROTOCOL VERSION HISTORY 
 
Section 5.2 Exclusion Criteria: Removed “exclusion criteria” of (1) recurrent/new primary cancer 
following trial registration and (2) major surgery following trial registration. These criteria were 
incorrectly listed as exclusion criteria even though their determination occurred after a patient was 
enrolled (and thus they cannot, by definition, be exclusion criteria). 
 
Section 5.5 Strategies for Recruitment and Retention: Changed target accrual from 48 to 52 patients to 
reflect a higher than anticipated rate of patients discontinuing the study due to recurrent or second 
primary cancers (Section 7.2). The evaluable sample size remains unchanged (N=44). 
 
Section 7.2 Participant Discontinuation/Withdrawal from the Study: Refined criteria for study 
discontinuation to clarify the difference between an exclusion criterion (which is determined at the time 
of study accrual) and criteria for study discontinuation (which are determined after a patient accrues to 
the study). The criteria (recurrence or second primary cancer; major head and neck surgery) and 
rationale (these events/.medical conditions are such that continued f/u of the patient in the study is not 
in the participant’s best interest and would confound interpretation of the study) remain the same but 
are now appropriately described as criteria for discontinuation instead of exclusion criteria. 
 
Section 9.2 Sample Size Determination: Changed target accrual from 48 to 52 patients to reflect a 
higher than anticipated rate of patients discontinuing the study due to recurrent or second primary 
cancers (Section 7.2). The evaluable sample size remains unchanged (N=44). 
 
Section 9.3 Population for Analyses: Amended to reflect updates to eligible vs evaluable population as 
described in Sections 5.2 and 7.2 
 
Section 10.4 Protocol Amendment History: Updated to reflect protocol revisions noted herein. 
 
 

BRIGHT 2.0 
 
Version 4.0 
Protocol #103191 
 
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TABLE OF CONTENTS 
Table of Contents 
CONFIDENTIALITY STATEMENT ........................................................................................................................................ 2 
PROTOCOL VERSION HISTORY.......................................................................................................................................... 3 
TABLE OF CONTENTS ........................................................................................................................................................ 4 
STATEMENT OF COMPLIANCE .......................................................................................................................................... 7 
INVESTIGATOR’S SIGNATURE ........................................................................................................................................... 8 
1 
PROTOCOL SUMMARY ......................................................................................................................................... 9 
1.1 
Synopsis..................................................................................................................................................... 9 
1.2 
Schema .................................................................................................................................................... 12 
1.3 
Schedule of Activities.............................................................................................................................. 13 
2 
INTRODUCTION .................................................................................................................................................. 15 
2.1 
Study Rationale ....................................................................................................................................... 15 
2.2 
Background ............................................................................................................................................. 15 
2.2.1 
Pyschosocial Morbidity in Head and Neck Cancer Survivors ............................................. 15 
2.2.2 
Prior Interventions to Treat BID in HNC Survivors ............................................................. 16 
2.2.3 
Time-Limited CBT for the Treatment of BID in Non-HNC Population ............................... 16 
2.2.4 
Content of BRIGHT .............................................................................................................. 16 
2.2.5 
Telemedicine Delivery Platform ......................................................................................... 16 
2.2.6 
Feasibility and Acceptability of BRIGHT ............................................................................. 17 
2.2.7 
Preliminary Clinical Impact of BRIGHT on BID.................................................................... 17 
2.2.8 
Preliminary Clinical Impact of BRIGHT on HNC-Related Quality of Life ............................ 18 
2.3 
Risk/Benefit Assessment ........................................................................................................................ 19 
2.3.1 
Known Potential Risks ........................................................................................................ 19 
2.3.2 
Known Potential Benefits ................................................................................................... 19 
2.3.3 
Assessment of Potential Risks and Benefits ....................................................................... 19 
3 
OBJECTIVES AND ENDPOINTS ............................................................................................................................ 21 
4 
STUDY DESIGN ................................................................................................................................................... 23 
4.1 
Overall Design ......................................................................................................................................... 23 
4.2 
Scientific Rationale for Study Design...................................................................................................... 24 
4.3 
Justification for Intervention .................................................................................................................. 24 
4.3.1 
Justification for the Mode of Delivery ................................................................................ 24 
4.3.2 
Justification for the Nubmber, Frequency, and Timing of Intervention Contacts ............ 24 
4.4 
End-of-Study Definition .......................................................................................................................... 25 
5 
STUDY POPULATION .......................................................................................................................................... 25 
5.1 
Inclusion Criteria ..................................................................................................................................... 25 
5.2 
Exclusion Criteria .................................................................................................................................... 26 
5.3 
Lifestyle Considerations .......................................................................................................................... 26 
5.4 
Screen Failures ........................................................................................................................................ 26 
5.5 
Strategies for Recruitment and Retention ............................................................................................. 26 
5.5.1 
Anticipated Screening and Accrual Targets ....................................................................... 26 
5.5.2 
Anticipated Accrual Rate and Accrual Feasibility ............................................................... 27 
5.5.3 
Planned Screening and Recruitment Strategies................................................................. 28 
5.5.4 
Strategies to Enhnace Retention ........................................................................................ 28 
5.5.5 
Retention Feasibility ........................................................................................................... 29 
5.5.6 
Participant Compensation .................................................................................................. 29 

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6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ................................................................... 29 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration .............................................. 30 
6.1.1 
Study Intervention Description .......................................................................................... 30 
6.1.2 
Administration and/or Dosing ............................................................................................ 31 
6.2 
Fidelity ..................................................................................................................................................... 32 
6.2.1 
Interventionist Training and Tracking ................................................................................ 32 
6.3 
Measures to Minimize Bias: Randomization and Blinding .................................................................... 32 
6.4 
Study Intervention Adherence ............................................................................................................... 32 
6.4.1 
BRIGHT 32 
6.4.2 
AC 
33 
6.5 
Concomitant Therapy ............................................................................................................................. 33 
6.5.1 
Rescue Therapy ................................................................................................................... 33 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL ............. 33 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation .................................................... 33 
7.2 
Participant Discontinuation/Withdrawal from the Study ..................................................................... 34 
7.3 
Lost to Follow-Up .................................................................................................................................... 34 
8 
STUDY ASSESSMENTS AND PROCEDURES ......................................................................................................... 35 
8.1 
Endpoint and Other Non-Safety Assessments ....................................................................................... 35 
8.2 
Safety Assessments................................................................................................................................. 38 
8.3 
Adverse Events and Serious Adverse Events ......................................................................................... 38 
8.3.1 
Definition of Adverse Events .............................................................................................. 38 
8.3.2 
Definition of Serious Adverse Events ................................................................................. 38 
8.3.3 
Classification of an Adverse Event...................................................................................... 39 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up................................... 39 
8.3.5 
Adverse Event Reporting .................................................................................................... 39 
8.3.6 
Serious Adverse Event Reporting ....................................................................................... 40 
8.3.7 
Reporting Events to Participants ........................................................................................ 40 
8.3.8 
Events of Special Interest ................................................................................................... 40 
8.3.9 
Reporting of Pregnancy ...................................................................................................... 40 
8.4 
Unanticipated Problems ......................................................................................................................... 40 
8.4.1 
Definition of Unanticipated Problems................................................................................ 40 
8.4.2 
Unanticipated Problems Reporting .................................................................................... 40 
8.4.3 
Reporting Unanticipated Problems to Participants ........................................................... 41 
9 
STATISTICAL CONSIDERATIONS ......................................................................................................................... 41 
9.1 
Statistical Hypotheses............................................................................................................................. 41 
9.2 
Sample Size Determination .................................................................................................................... 41 
9.3 
Populations for Analyses ........................................................................................................................ 43 
9.4 
Statistical Analyses.................................................................................................................................. 44 
9.4.1 
General Approach ............................................................................................................... 44 
9.4.2 
Analysis of the Primary Endpoint(s) ................................................................................... 44 
9.4.3 
Analysis of the Secondary Endpoint(s) ............................................................................... 44 
9.4.4 
Safety Analyses ................................................................................................................... 45 
9.4.5 
Baseline Descriptive Statistics ............................................................................................ 45 
9.4.6 
Planned Interim Analyses ................................................................................................... 46 
9.4.7 
Sub-Group Analyses ............................................................................................................ 46 
9.4.8 
Tabulation of Individual Participant Data .......................................................................... 46 

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9.4.9 
Exploratory Analyses .......................................................................................................... 46 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ....................................................... 46 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ..................................................................... 46 
10.1.1 
Informed Consent Process.................................................................................................. 46 
10.1.2 
Study Discontinuation and Closure .................................................................................... 47 
10.1.3 
Confidentiality and Privacy ................................................................................................. 47 
10.1.4 
Future Use of Stored Specimens and Data ........................................................................ 48 
10.1.5 
Key Roles and Study Governance ....................................................................................... 48 
10.1.6 
Safety Oversight .................................................................................................................. 49 
10.1.7 
Clinical Monitoring.............................................................................................................. 49 
10.1.8 
Quality Assurance and Quality Control .............................................................................. 49 
10.1.9 
Data Handling and Record Keeping .................................................................................... 49 
10.1.10 
Protocol Deviations............................................................................................................. 50 
10.1.11 
Publication and Data Sharing Policy ................................................................................... 50 
10.1.12 
Conflict of Interest Policy.................................................................................................... 51 
10.2 
Additional Considerations ...................................................................................................................... 51 
10.3 
Abbreviations and Special Terms ........................................................................................................... 51 
10.4 
Protocol Amendment History................................................................................................................. 53 
11 
REFERENCES ....................................................................................................................................................... 54 
 
 
 

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STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with International Council on Harmonisation Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the National 
Cancer Institute (NCI) Terms and Conditions of Award. The Principal Investigator (PI) will assure that no 
deviation from, or changes to the protocol will take place without prior agreement from the funding 
agency and documented approval from the Institutional Review Board (IRB), and the Investigational New 
Drug (IND) or Investigational Device Exemption (IDE) sponsor, if applicable, except where necessary to 
eliminate an immediate hazard(s) to the trial participants. All personnel involved in the conduct of this 
study have completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) must 
be obtained before any participant is consented. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the consent form(s) 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 

BRIGHT 2.0 
 
Version 4.0 
Protocol #103191 
 
1 October 2021 
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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator or Clinical Site Investigator: 
 
Signed: 
 
 
Date: 
 
3/10/20 
 
 
Name: Evan Graboyes 
Title: A Single-Site, Parallel-Group, Randomized-Controlled Pilot Trial Comparing BRIGHT 
with Active Control in Reducing Body Image Disturbance Among Head and Neck Cancer 
Survivors (BRIGHT 2.0) 
 
Investigator Contact Information 
Affiliation: Medical University of South Carolina 
Address: 135 Rutledge Avenue, MSC 550, Charleston, SC 29425 
Telephone: (843)-792-0719 
Email: graboyes@musc.edu 
 
CO-INVESTIGATORS: 
Stacey Maurer, PhD 
Wendy Balliet, PhD 
Hong Li, PhD 
Ken Ruggiero, PhD 
Katherine Sterba, PhD, MPH 
 

BRIGHT 2.0 
 
Version 4.0 
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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
 
Title: 
A Single-Site, Parallel-Group, Randomized-Controlled Pilot Trial 
Comparing BRIGHT with Active Control in Reducing Body Image 
Disturbance Among Head and Neck Cancer Survivors (BRIGHT 2.0) 
 
Grant Number: 
R21CA245941 
 
Study Description: 
In this pilot randomized controlled trial, we will evaluate the preliminary 
clinical impact and underlying behavioral mechanism of BRIGHT 
(Building a Renewed ImaGe after Head & neck cancer Treatment), a 
novel 5-session, manualized cognitive behavioral therapy (CBT) 
intervention to treat body image disturbance (BID) in head and neck 
cancer (HNC) survivors. We hypothesize that BRIGHT will decrease BID 
relative to active control (AC; patient-centered videos about HNC 
survivorship care) through improvements in body image coping 
behavior. 
 
Objectives: 
Primary Objective: 
To assess the clinical efficacy of BRIGHT compared with AC on BID in 
HNC survivors as determined by change in Body Image Scale (BIS) scores 
at 1-month post-intervention relative to baseline. 
 
Select Secondary Objectives:  
1. To assess the clinical efficacy of BRIGHT compared with AC on BID in 
HNC survivors as determined by change in IMAGE-HN scores at 1-month 
post-intervention relative to baseline 
 
2. To explore the behavioral mechanism of action of BRIGHT on changes 
in BID in HNC survivors as measured by the change in Body Image 
Coping Strategies Inventory (BICSI) scores at 1-week post-intervention 
relative to baseline. 
 
3. To provide preliminary estimates of the clinical effect of AC on BID in 
HNC survivors as determined by change in BIS scores at 1-month post-
intervention. 
 
4. To estimate the activity of BRIGHT compared with AC on BID in HNC 
survivors in terms of clinical response as measured by improvement in 
BIS scores at 1-month post-intervention relative to baseline. 
 
5. To assess the clinical efficacy of BRIGHT compared with AC on BID in 
HNC survivors as determined by change in BIS scores at 3-months post-
intervention relative to baseline. 
 

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Endpoints: 
6. To evaluate the preliminary clinical efficacy of BRIGHT compared with 
AC on changes in psychological, emotional, and social well-being in HNC 
survivors at post-treatment and 1- and 3-months post-intervention 
relative to baseline 
 
7. To evaluate the feasibility of BRIGHT, delivered via a tablet-based 
telemedicine, as a strategy to treat BID in HNC survivors 
 
8. To evaluate the acceptability of BRIGHT to as a strategy to treat BID in 
HNC survivors 
 
9. To determine the association of demographic variables with 
therapeutic alliance between the study participant and psychologist 
 
Primary Endpoint: 
Change in BIS score from baseline to 1-month post-intervention  
 
Select Secondary Endpoints: 
1. Change in IMAGE-HN score from baseline to 1-month post-
intervention. 
 
2. Change in BICSI scores from baseline to 1-week post-intervention 
 
3. Clinical response (BIS score at 1-month post-intervention that is less 
than the BIS score at baseline) 
 
4. Change in BIS score from baseline to 3-months post-intervention 
 
5. Change in Shame and Stigma Scores from baseline to 1- and 3-
months post-intervention 
 
6. Change in PROMIS SF v1.0-Depression 8a scores from baseline to 1-
month post-intervention and baseline to 3-months post-intervention 
 
7. Change in PROMIS SF v1.0-Anxiety 8a scores from baseline to 1-
month post-intervention and baseline to 3-months post-intervention. 
 
8. Change in PROMIS SF v2.0-Social Isolation 8a scores from baseline to 
1-month post-intervention and baseline to 3-months post-intervention 
 
9. Change in PROMIS SF v2.0-Satisfaction with Social Roles and Activities 
8a scores from baseline to 1-month post-intervention and baseline to 3-
months post-intervention 
 
Study Population: 
The study population will consist of head and neck cancer survivors with 
no evidence of disease, 18 years of age or older, of all races and sexes, 
with BID following treatment of HNC 
Phase or Stage: 
N/A 
  

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Description of 
Sites/Facilities Enrolling 
Participants: 
The study will be conducted, and participants enrolled, at a single site, 
the Medical University of South Carolina (MUSC) Hollings Cancer Center 
(HCC) Head and Neck Tumor Center. The Head and Neck Tumor Center is 
a high-volume, multidisciplinary center designed for unsurpassed clinical 
care and optimized for integration of research activities. The Head and 
Neck Tumor Center is a regional center of excellence for HNSCC clinical 
care. 
 
Description of Study 
Intervention/Experimental 
Manipulation: 
BRIGHT is 5 sessions of weekly, 60-minute, tablet-based, manualized 
individual tele-CBT targeting the behavioral and attitudinal components 
of HNC-related BID.  
 
Study Duration: 
24 months 
Participant Duration: 
4 months 
 
 

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1.2 
SCHEMA   
 
 
Fig. 1. Study Schema. Following completion of baseline questionnaires, participants will be randomized to 5 
weeks of BRIGHT or AC, then complete validated measures of BID, body image coping behavior and 
psychological, social, and emotional well-being at 1-week, 1-month, and 3-months post-intervention to assess 
the impact of BRIGHT on changes in BID and the role of body image coping behavior as a mediator of changes in 
BID. 

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1.3 
SCHEDULE OF ACTIVITIES  
 
Table 1. Schedule of Activities for BRIGHT and Active Control (5 weeks) and follow up (3 months) 
 
Pre Screen  
(-60 to 1) 
Visit 1 
Day 1a 
Visit 2 
Day 8 ±14 
Visit 3 
Day 15 ±7 
Visit 4 
Day 22 ±7 
Visit 5 
Day 29 ±7 
Visit 6 
Day 36 ±7 
Visit 7 
Day 43 ±14 
Visit 8 
Day 64 ±14 
Visit 9 
Day 124±14 
For Details, 
see section 
Informed Consent 
Review Study 
Eligibilityb 
X 
 
 
 
 
 
 
 
 
 
 
5 
Informed Consentc 
X 
 
 
 
 
 
 
 
 
 
 
10.1.1 
Study Procedures 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
6.3 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
8.1 
Clinical and 
Oncologic History 
 
X 
 
 
 
 
 
 
 
 
 
8.1 
ASI-R 
 
X 
 
 
 
 
 
 
 
 
 
8.1 
Monitoring 
AS/SAE 
Assessment 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
8.3 
Medication 
Assessment 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
8.3 
Intervention Administration 
BRIGHT or AC 
 
 
X 
X 
X 
X 
X 
 
 
 
 
6.1 
Efficacy Evaluation 
Body Image Scaled 
X 
 
 
 
 
 
 
X 
X 
X 
 
8.1 
IMAGE-HNd 
 
X 
 
 
 
 
 
X 
X 
X 
 
8.1 
PROM Assessments 
BICSId 
 
X 
 
 
 
 
 
X 
X 
X 
 
8.1 
Shame and Stigma 
Scaled 
 
X 
 
 
 
 
 
 
X 
X 
 
8.1 
PROMIS SF v1.0-
Depression 8ad 
 
X 
 
 
 
 
 
 
X 
X 
 
8.1 
PROMIS SF v1.0-
Anxiety 8ad 
 
X 
 
 
 
 
 
 
X 
X 
 
8.1 
PROMIS SF v2.0-
Social Isolation 8ad 
 
X 
 
 
 
 
 
 
X 
X 
 
8.1 
PROMIS SF v2.0- 
Social Roles 8ad 
 
X 
 
 
 
 
 
 
X 
X 
 
8.1 
EORTC QLQ-HN35d 
 
X 
 
 
 
 
 
 
X 
X 
 
8.1 
Other Evaluations 

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Intervention 
Fidelity 
 
 
X 
X 
X 
X 
X 
 
 
 
 
6.2 
Patient Adherence 
 
 
X 
X 
X 
X 
X 
 
 
 
 
6.4 
Program 
Evaluation 
 
 
 
 
 
 
 
X 
 
 
 
8.1 
WAI-SR 
 
 
 
X 
 
 
X 
 
 
 
 
8.1 
a: Every effort should be made to minimize the time between randomization and starting treatment 
b: Eligibility assessed using information in the electronic medical record as well as a screening Body Image Scale 
c: Written informed consent and HIPAA must be obtained prior to performing and protocol-specific procedures, 
including baseline evaluations. To optimize participant and researcher safety during the COVID-19 pandemic, 
informed consent may be obtained in person using a paper informed consent document or electronically using the 
eConsent. 
d: Sites are encouraged to administer PROMs using a site-based electronic device. If that is not feasible, 
administration of PROMs using a paper-based format is also acceptable. Sites are encouraged to align PROM 
assessments with clinic visits to facilitate in-person collection. In situations in which in-person collection is not 
feasible, PROMs may be collected via mail or email at the study coordinator’s discretion. When possible. PROMs 
should be completed prior to any other study procedures (following informed consent) and before clinic visits in 
which clinical information will be discussed to avoid biasing the patient’s responses to the questions. 
Acronyms:  AC, Active Control; AE, Adverse Event; ASI-R, Appearance Schemas Inventory-Revised; BICSI, Body Image 
Coping Strategies Inventory; BRIGHT, Building a Renewed ImaGe after Head & neck cancer Treatment; IMAGE-HN; 
Inventory to Measure and Assess imaGe disturbancE-Head & Neck; SAE, Serious Adverse Event; WAI-SR, Working 
Alliance Inventory-Short Revised 

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2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
Head and neck cancer (HNC) arises in cosmetically and functionally critical areas, resulting in substantial 
life-altering morbidity related to disfigurement, difficulty swallowing, and challenges speaking1,2. As a 
result, 75% of HNC survivors express body image concerns3,4. When severe, these concerns result in body 
image disturbance (BID), a multidimensional construct characterized by a displeasing self-perceived 
change in appearance and/or function4-6. Although BID is a source of significant morbidity and associated 
with stigmatization, social isolation, and decreased quality of life (QOL)7,8, effective therapies for BID in 
HNC survivors are lacking8. It is therefore critically important to develop and test novel interventions to 
minimize psychosocial morbidity and improve QOL in this population7,8. 
 
We have developed and pilot-tested BRIGHT (Building a Renewed ImaGe after Head & neck cancer 
Treatment), a novel 5-session, manualized cognitive behavioral therapy (CBT) intervention to treat BID in 
HNC survivors. BRIGHT targets the behavioral and attitudinal components of BID and can be delivered 
face to face or using a tablet-based telemedicine format. In our single-arm pilot study of BRIGHT, 
participants were given the option to select their delivery platform and overwhelmingly enrolled into 
tablet-based BRIGHT (n=10) instead of face to face BRIGHT (n=1). This pilot study showed that tablet-
based BRIGHT (n=10) is feasible (100% of sessions completed), is acceptable to patients (89% highly likely 
to recommend it), has the potential to decrease BID (mean decrease of 4.56 in BIS scores from baseline 
to 1-month post intervention (95% CI 1.55, 7.56), and may mediate a reduction in BID by improving body 
image coping behavior. 
 
In this proposal, we extend our initial research with a pilot randomized controlled trial (RCT) to examine 
the clinical impact and behavioral mechanistic underpinnings of BRIGHT on BID in HNC survivors. This 
proposed project will evaluate the preliminary clinical impact and behavioral mechanism of a novel 
psychobehavioral intervention delivered via a scalable, tablet-based telemedicine platform, thereby 
advancing our conceptual understanding of BID and establishing new treatment paradigms to directly 
address the lack of effective treatment for BID in HNC survivor. HNC survivors with BID will be randomized 
to 5-weeks of tablet-based BRIGHT or tablet-based active control (AC) (patient-centered videos about 
HNC survivorship care. Participants will complete the Body Image Scale (a validated measure of BID9; 
primary endpoint), the Body Image Coping Strategies Inventory (a validated measure of body image 
coping behavior10; behavioral mediator) and measures of psychological, social, and emotional well-being 
(secondary endpoints) at baseline, 1-week, and 1-month and 3-month post-intervention. 
 
2.2 
BACKGROUND 
2.2.1 PYSCHOSOCIAL MORBIDITY IN HEAD AND NECK CANCER SURVIVORS 
HNC, which arises in cosmetically and functionally critical areas (tongue, mandible, larynx, and neck) is 
diagnosed in 65,000 patients in the US annually11. HNC results in life-altering morbidity related to 
disfigurement, difficulty swallowing, impaired smiling, and challenges speaking12. Because changes occur 
in highly visible, socially significant parts of the body that are integral to self-conception, communication, 
and interpersonal relationships7,8,13, 75% of HNC survivors express body image concerns3,4. When severe, 
these concerns result in BID, a multidimensional construct characterized by a displeasing self-perceived 

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change in appearance and/or function6,7. Morbidity from BID includes social isolation14, stigmatization7, 
depression13,15, decreased intimacy16, and worse QOL7,8. Due to this psychosocial morbidity, survivors of 
HNC are 2-times more likely to die from suicide than survivors of any other cancer17. 
 
2.2.2 PRIOR INTERVENTIONS TO TREAT BID IN HNC SURVIVORS 
Managing BID is a key component of HNC survivorship care12. Unfortunately, no effective therapies for 
BID in HNC survivors have been described8. Researchers have evaluated the effect of cosmetic 
rehabilitation18 and skin camouflaging19 on BID in HNC survivors; neither intervention was effective at 
treating BID. As a result, treatment of BID in HNC survivors represents a significant unmet survivorship 
need20. It is thus critically important to address the lack of treatments for BID in HNC survivors to prevent 
continued psychosocial morbidity and decreased QOL8. 
 
2.2.3 TIME-LIMITED CBT FOR THE TREATMENT OF BID IN NON-HNC POPULATION 
Stand-alone, time-limited CBT produces durable reductions in the severity of BID in non-disfigured 
patients with eating or body dysmorphic disorders21-23, in part by improving body image coping 
behavior24. However, because HNC survivors have highly visible and socially significant impairments and 
disfigurement, they face a different set of body image concerns than patients with eating or body 
dysmorphic disorders5. No studies have demonstrated the efficacy or mechanism of action of CBT for 
BID in HNC survivors8,25. 
2.2.4 CONTENT OF BRIGHT 
BRIGHT was developed using an intervention mapping approach26. Our qualitative work with HNC 
survivors identified key domains of HNC-related BID which BRIGHT targets: personal dissatisfaction with 
appearance, other-oriented appearance concerns, appearance concealment, distress with functional 
impairments, and social avoidance27. 
 
2.2.5 TELEMEDICINE DELIVERY PLATFORM 
Cancer survivors face unique access-to-care barriers for face to face psychosupportive care28. For HNC 
patients, travel burden (due to the regionalization of HNC care29,30) is a critical barrier to psychosupportive 
care and contributes to excess morbidity and mortality31,32. HNC survivors also face physical access 
barriers that prevent face to face CBT including fatigue and treatment toxicity. As a result, innovative 
approaches to deliver psychobehavioral interventions to HNC survivors are needed33,34. Telemedicine is a 
promising solution because it decreases travel burden35, increases access to care36, and provides effective 
behavioral health interventions37 (including CBT28,38). 
 
We assessed the feasibility of delivering BRIGHT via patient-owned technology. Although a majority of our 
population owned a video-enabled device (smart phone=83%, tablet=36%, computer=64%, none=6%) and 
had home internet access (88%), we elected to provide each participant with the same video platform 
(tablet) and internet connection (cellular-enabled Wi-Fi) to enhance the standardization and rigor of our 
approach. 
 

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Our pilot data suggest that telemedicine is the preferred strategy to deliver CBT interventions to HNC 
survivors with BID. When patients chose the delivery method of BRIGHT (face to face or tablet-based) in 
our single-arm trial, tablet-based BRIGHT was overwhelmingly preferred (100% of patients traveling >25 
miles (8/8); 67% (2/3) of patients traveling < 25 miles) because of travel considerations, convenience, and 
flexibility. 
 
2.2.6 FEASIBILITY AND ACCEPTABILITY OF BRIGHT 
Feasibility and acceptability of BRIGHT was evaluated in a single-arm clinical trial (NCT03518671). 
BRIGHT was found to be highly feasible and acceptable to patients in terms of the timing, method of 
delivery, duration, and content of the intervention (Table 2). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.2.7 PRELIMINARY CLINICAL IMPACT OF BRIGHT ON BID 
BRIGHT demonstrated high levels of clinical activity in this population of HNC survivors with BID in our 
single-arm pilot trial39. Eighty-nine percent of participants (8/9) experienced improvement in their BID at 
1-month post-BRIGHT relative to baseline, pre-treatment levels. The clinical effect of BRIGHT on BID was 
large (Fig. 2); BRIGHT was associated with a mean decrease of 4.56 in BIS scores from baseline to 1-
month post intervention (95% CI 1.55, 7.56). This clinical effect on BID persisted at 3 months post-
BRIGHT relative to baseline (mean of the difference of BIS scores from baseline to 3-months post = 3.56; 
95% CI 1.15 to 5.96). 
 
 
Table 2. BRIGHT Feasibility and Acceptability 
Feasibility 
 
BRIGHT session length (median; IQR), minutes 
54; 5  
BRIGHT session completion, n (%) 
45, 100 
Major technical issues during BRIGHT sessions, n (%) 
0 (0) 
Minor technical issues during BRIGHT sessions, n (%) 
5 (11.1) 
Tablet returned to study team after BRIGHT, n (%) 
10 (100) 
Study dropout, n (%) 
1 (10) 
 
Acceptability to Patients (Program Evaluation) 
Mean (SD) 
How well did the timing of the program work for you? 
4.44 (0.73) 
How well did the method of program delivery work?  
4.67 (0.5) 
How well did the number of sessions work for you? 
4.56 (0.53) 
How relevant was the content of each session? 
4.56 (0.30) 
Session 1 
4.11 (1.27) 
Session 2 
4.44 (0.73) 
Session 3 
4.56 (0.53) 
Session 4 
4.89 (0.33) 
Session 5 
4.78 (0.44) 
How likely are you to recommend BRIGHT? 
4.89 (0.33) 
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2.2.8 PRELIMINARY CLINICAL IMPACT OF BRIGHT ON HNC-RELATED QUALITY OF LIFE 
BRIGHT was associated with improvements in psychosocial aspects of HNC-related QOL in our single-arm 
pilot trial of BRIGHT39. Specifically, BRIGHT was associated with improvements in the trouble with social 
eating at 1- and 3-months post BRIGHT as measured by the trouble with social eating subdomain of the 
EORTC QLQHN35 (median trouble with social eating scores = 66.67, 45.83, and 25, at baseline, 1-, and 3- 
months post-BRIGHT respectively; Fig. 3). BRIGHT was also associated with an improvement in the trouble 
with social contact at 1- and 3-months post BRIGHT as measured by the trouble with social contact 
subdomain of the EORTC QLQHN35 (median trouble with social contact scores = 40, 26.67, and 16.67 at 
baseline, 1-, and 3- months post-BRIGHT respectively). BRIGHT was not associated with improvements in 
depression, anxiety, or shame and stigma post-treatment relative to baseline. 
 
 
 
 
 
 
 
Fig. 2. A) Decrease in the severity of body image disturbance (as determined by Body Image Scale scores) 
at 1-month post-BRIGHT relative to baseline; B) Decrease in the severity of body image disturbance (as 
determined by Body Image Scale scores) at 3-months post-BRIGHT relative to baseline. 
Fig. 3. A) Decrease in difficulty with social eating (as determined by EORTC QLQ-H&N35 Trouble with 
Social Eating Subscale scores) at 1- and 3-months post-BRIGHT relative to baseline; B) Decrease in 
difficulty with social contact (as determined by EORTC QLQ-H&N35 Trouble with Social Contact Subscale 
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2.3 
RISK/BENEFIT ASSESSMENT  
2.3.1 KNOWN POTENTIAL RISKS  
Overall, this research study poses no more than minimal risks to participants. The single-arm pilot study 
of BRIGHT was a minimal risk study that was approved by the MUSC IRB under an expedited review 
(45CFR46.110). No formal DSMB was required, although a Data and Safety Monitoring Plan (DSMP) with 
PI and IRB-based oversight was created. The main study procedures include completion of questionnaires, 
which are generally considered minimal risk. There are no physical, financial, legal, social, or cultural, risks 
to the study participants by joining this study. The primary risks of the study are 1) 
psychological/emotional distress and 2) breach of privacy/confidentiality. 
 
Psychological/emotional distress: Subjects may experience adverse psychological reactions such as 
anxiety, depression, stress, or distress as a result of discussing issues related to cancer, body image, 
stigmatization, isolation, coping strategies, or social support. These issues may occur during the 
completion of study questionnaires (baseline or post-treatment) or during the intervention (BRIGHT or 
AC). However, based on our prior and ongoing research, we expect that low rates of participant distress 
and believe that this risk is minimal. Nevertheless, we do have a specific protocol should a participant 
become distressed as a result of participation in this study. The project coordinator and Dr. Maurer, the 
study psycho-oncologist both have extensive experience dealing with this patient population and 
appropriate safeguards have been put in place during our pilot work to mitigate against this risk in either 
situation. 
 
Breach of privacy/confidentiality: There is also a slight risk that confidential information about the 
participant may be accidentally disclosed as study participants may be asked to provide information 
considered confidential or private during study interviews. The likelihood of this risk is low as all the 
investigators have been involved in similar research in the past and have not experienced this problem 
before due to adequate safeguards. 
 
2.3.2 KNOWN POTENTIAL BENEFITS 
Based on our pilot data about the clinical impact of BRIGHT on BID, we hypothesize that participants in 
the BRIGHT arm of the study will have a reduction in the severity of their BID as well as improvement in 
their psychological, social, and emotional well-being). However, although we hypothesize a direct benefit 
to participants in the BRIGHT arm (in terms of BID, psychological, social, and emotional well-being), it is 
unknown whether patients will experience a direct benefit. Data generated from this proposal are 
expected to provide benefits to society by enhancing our theoretical models of how cognitive-behavioral 
interventions may help treat BID in cancer survivors. The study is also expected to have broad significance 
and therapeutic implications beyond BID through development of a novel platform to deliver a variety of 
psychobehavioral interventions to cancer survivors. 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
The decision to participate in this research will be voluntary and individuals may refuse to take part or 
choose to stop taking part at any time. Participants will also be encouraged to take their time when 
answering questions and may decline to answer any question at any time. If patients become upset talking 

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about their cancer and the barriers that they faced, they will be offered a referral to the HCC Behavioral 
Medicine program (which is covered by most health insurance programs) or the HCC Social Worker who 
will offer links to other HCC and community resources 
 
Measures to protect against psychological and emotional distress are described below. Participants will 
be reminded that the decision to initiate and/or continue participating in this research is voluntary. 
Participants will be informed from the outset that they are free to terminate the assessments, procedures, 
or therapy sessions at any time and/or refrain from answering any questions that make them 
uncomfortable. The interviewers are trained researchers who are experienced in the conduct of 
interviews related to psychosocial aspects of cancer. Our past experience using these study measures 
suggest that data collection using these instruments can be conducted without undue psychological 
distress or exacerbation of symptoms among this population (HNC survivors with body image concerns). 
The study participant will be encouraged to take time when answering questions and may refuse to 
answer any question at any time during the study. 
 
If at any point during the assessment, treatment, or follow-up period, subjects are in need of medical 
management, psychiatric consultation, or psychiatric hospitalization, they will be evaluated, and referral 
or treatment will be provided as indicated. If a subject becomes suicidal, emergency psychiatric 
assessment will be arranged. The subject will be closely monitored clinically until he/she is no longer 
suicidal, or an appropriate care plan is in place. 
 
If a participant has a psychological adverse event filling out a questionnaire, the program coordinator will 
immediately contact Dr. Maurer, a licensed clinical psychologist and the designated study psycho-
oncologist, to immediately asses the subject and determine the appropriate course of action. In the event 
that Dr. Maurer is not available, a fellow licensed psychologist who works in the HCC Behavioral Medicine 
program will be contacted. Immediate backup and support will be available. In situations in which suicidal 
ideation (or other psychiatric emergency) is endorsed during completion of study instruments and Dr. 
Maurer or immediate backup is not available, patients will be referred to the emergency room for 
immediate psychiatric assessment. 
 
Standard safeguards are also in place in case an adverse psychological reaction occurs during a BRIGHT 
(or AC) telemedicine session. These include determination of the appropriateness of the participant for 
home-based telemental health care, determination of the adequacy of infrastructure and technology, site 
assessments and procedures (obtaining patient’s address and local 9-1-1/Emergency medical service 
provider; local provider contact information, alternate patient and emergency contact information), and 
monitoring of risk during treatment (symptom levels, self-harm ideation, intention to harm others, 
changes in setting/patient situation) as described in the DSMP. 
 
All cases of possible psychological distress noted by study personnel will be reported to the PI. In situations 
in which a participant has psychological distress from participation in the study of which the study team 
is not aware, participants will be encouraged to notify the PI directly. These adverse events will be 
reported directly to the IRB per protocol. If project staff believe that a subject is distressed by participation 
in the study, the PI will be notified and will contact the subject to assess distress and assure subject safety. 
 
To help ensure and protect privacy of participants and confidentiality of research data for the study, we 
will assign a unique study ID number to each subject’s information in place of his/her name and will label 
data collection forms with the ID number. All hard copy and electronic files will be stored appropriately 
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to study records. Participant data will be collected and recorded on either a password-protected 
electronic data capture format (REDCap) or paper-based forms depending upon patient preference. For 
the paper collection data method, the data collection form will be labeled only with the participant's 
unique study ID number, and then stored within locked drawers in a locked office. The information on 
these paper forms will be transferred to a password-protected REDCap database. Any exported data for 
analysis will be de-identified with all privately identifiable information automatically removed. The key 
linking subject ID number to an individual will be stored in the password protected REDCap database. The 
audio recordings from the qualitative interviews will be labeled only with the patient’s unique study ID 
and stored using password-protected files only accessible by the study team through password-protected 
servers. Once data have been collected, only de-identified data will be exported for analysis. All study 
personnel will participate in training on protecting the privacy of study participants and personal 
information will not be disclosed to anyone outside of the research team. Only the principal investigator 
and study staff participating in data collection or analysis will have access to the data. We have no plan to 
use laptops, jump drives, CDs/DVDs to transport data. 
 
On the whole, given the minimal risks to the study participants and the potential benefit of the research 
to participants and society, we believe that the potential reward to participants and society substantially 
outweighs the risks to the participants. 
 
3 
OBJECTIVES AND ENDPOINTS  
 
Table 3. Study Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
Primary 
 
To assess the clinical efficacy of 
BRIGHT compared with AC on BID in 
HNC survivors as determined by 
change in BIS scores at 1-month 
post-intervention relative to 
baseline 
Change in BIS score from baseline to 1-month post-intervention 
Secondary 
To assess the clinical efficacy of 
BRIGHT compared with AC on BID in 
HNC survivors as determined by 
change in IMAGE-HN scores at 1-
month post-intervention relative to 
baseline and 3-months post-
intervention relative to baseline 
Change in IMAGE HN Scores from baseline to 1-month post-
intervention and from baseline to 3-months post-intervention 
To explore the behavioral 
mechanism of action of BRIGHT on 
changes in BID in HNC survivors as 
measured by the change in BICSI 
scores at 1-week post-intervention 
relative to baseline. 
Change in BICSI scores from baseline to 1-week post-
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Table 3. Study Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
To provide preliminary estimates of 
the clinical effect of AC on BID in 
HNC survivors as determined by 
change in BIS scores at 1-month 
post-intervention relative to 
baseline 
Change in BIS score from baseline to 1-month post-intervention 
To estimate the activity of BRIGHT 
compared with AC on BID in HNC 
survivors in terms of clinical 
response as measured by 
improvement in BIS scores at 1-
month post-intervention relative to 
baseline 
Clinical response (BIS score at 1-month post-intervention that is 
less than the BIS score at baseline) 
To assess the clinical efficacy of 
BRIGHT compared with AC on BID in 
HNC survivors as determined by 
change in BIS scores at 3-months 
post-intervention relative to 
baseline 
Change in BIS score from baseline to 3-months post-
intervention 
To evaluate the preliminary clinical 
efficacy of BRIGHT compared with 
AC on changes in psychological, 
emotional, and social well-being in 
HNC survivors as determined by 
change in respective PROM scores 
at 1- and 3-months post-
intervention relative to baseline 
Change in Shame and Stigma Scores from baseline to 1- and 3-
months post-intervention 
Change in PROMIS SF v1.0-Depression 8a scores from baseline 
to 1-month post-intervention and baseline to 3-months post-
intervention 
Change in PROMIS SF v1.0-Anxiety 8a scores from baseline to 1-
month post-intervention and baseline to 3-months post-
intervention. 
Change in PROMIS SF v2.0-Social Isolation 8a scores from 
baseline to 1-month post-intervention and baseline to 3-
months post-intervention 
Change in PROMIS SF v2.0-Satisfaction with Social Roles and 
Activities 8a scores from baseline to 1-month post-intervention 
and baseline to 3-months post-intervention 
Change in EORTC QLQ-HN35 scores from baseline to 1-month 
post-intervention and baseline to 3-months post intervention 
Feasibility 
To evaluate the feasibility of 
BRIGHT, delivered via a tablet-based 
telemedicine, as a strategy to treat 
BID in HNC survivors 
Intervention session duration (minutes) 
Intervention session completion rate 
Number of technical issues with tablet platform 
Return of study-issued tablet 
Study dropout 
Acceptability 
To evaluate the acceptability of 
BRIGHT to as a strategy to treat BID 
in HNC survivors 
Timing of Intervention (0-5 Likert scale) 
Method of Intervention delivery (0-5 Likert scale) 
# of Intervention sessions (0-5 Likert scale) 

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Table 3. Study Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
Intervention content relevance (0-5 Likert scale) 
Overall satisfaction with the Intervention (0-5 Likert scale) 
Likelihood of recommending the Intervention (0-5 Likert scale) 
To determine the association of 
demographic variables with 
therapeutic alliance between the 
study participant and psychologist 
Age, race, sex, Working Alliance Inventory- Short Revised score 
Acronyms: AC, Active Control; ASI-R, Appearance Schemas Inventory-Revised; BICSI, Body Image Coping 
Strategies Inventory; BID, Body Image Disturbance; BIS, Body Image Scale; BRIGHT, Building a Renewed 
ImaGe after Head & neck cancer Treatment; HNC; Head and Neck Cancer, IMAGE-HN; Inventory to 
Measure and Assess imaGe disturbancE-Head & Neck; WAI-SR, Working Alliance Inventory-Short 
Revised 
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
We will conduct a single-site, non-blinded, parallel-group, RCT of BRIGHT versus AC for the management 
of BID in surgically-managed HNC survivors. The study is designed to test the following hypotheses: 1) 
BRIGHT will result in a less severe BID relative to AC (primary objective) and 2) Improvements in body 
image coping behavior from baseline to 1-week post intervention will partially mediate a decrease in BID 
from baseline to 1-month post intervention. 
 
In this pilot RCT, participants will be allocated to the two study arms (BRIGHT or AC) as follows. Upon 
enrollment and completion of the baseline assessments, patients will be randomized 1:1 to BRIGHT or AC 
using a permuted block randomization method, with randomly selected block sizes of 2 or 4. 
Randomization will occur at the individual patient level. Given the impossibility of delivering BRIGHT in a 
non-blinded fashion, allocation concealment will be non-blinded. The study statistician will generate and 
implement the randomization schema and randomization list. The study coordinator will implement the 
randomization. Randomization errors will be handled as per the intention-to-treat population for the 
efficacy analysis. 
 
BRIGHT is 5 sessions of weekly, 60-minute, tablet-based, manualized individual tele-CBT targeting the 
behavioral and attitudinal components of HNC-related BID. BRIGHT focuses on adjustment to 
disfigurement, teaches coping and problem-solving skills, and addresses the behavioral implications of 
BID. 
 
In this RCT, BRIGHT will be compared with AC. AC is educational information about HNC survivorship 
developed (with permission) using resources from the NCI, American Head & Neck Society, Thyroid Head 
and Neck Cancer Foundation (THANC), and MUSC. AC consists of 5 weekly 30-minute sessions and is 
delivered one-on-one via a tablet-based telemedicine platform. AC replicates the number of sessions (5), 
frequency (weekly), and delivery method of BRIGHT (tablet-based telemedicine platform) but differs in 
content to isolate the ‘active’ ingredient in BRIGHT. AC was originally matched to BRIGHT for session 
duration (60 minutes) but was decreased to 30 minutes/session based on feedback during pilot testing 
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4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
We considered alternative study designs such as a single-arm pilot study with comparison to local and 
national historical control data. However, we consider the RCT a superior approach to a single-arm trial 
comparing to historical control40 because the RCT will allow us to demonstrate and precisely measure the 
control group, thereby avoiding sample error and case-mix differences between the single-arm and 
historical control41. As a result, the RCT design will provide us with more precise estimates of the effect 
size and sample size of the BRIGHT intervention relative to AC in preparation for the definitive phase III 
RCT42. 
 
An alternative approach is to compare BRIGHT to UC instead of AC. UC for HNC survivors with BID is 
educational material provided by HNC providers during routine survivorship visits7. Comparison to AC is a 
strength of our approach because AC is matched by duration, frequency, number, and delivery method 
and delivered using the same tablet platform as BRIGHT. The matching of dose and delivery format 
between BRIGHT and AC allows us to isolate the role of BRIGHT content in treating BID as opposed to 
other factors that might confound an association between BRIGHT and improvements in BID were BRIGHT 
compared with UC (e.g. receipt of the tablet, additional contact with the HNC team). 
 
4.3 
JUSTIFICATION FOR INTERVENTION 
4.3.1 JUSTIFICATION FOR THE MODE OF DELIVERY 
Cancer survivors face unique access-to-care barriers for face to face psychosupportive care28. For HNC 
patients, travel burden (due to the regionalization of HNC care29,30) is a critical barrier to psychosupportive 
care and contributes to excess morbidity and mortality31,32. HNC survivors also face physical access 
barriers that prevent face to face CBT including fatigue and treatment toxicity. As a result, innovative 
approaches to deliver psychobehavioral interventions to HNC survivors are needed33,34. Telemedicine is a 
promising solution because it decreases travel burden35, increases access to care36, and provides effective 
behavioral health interventions37 (including CBT28,38). 
 
We assessed the feasibility of delivering BRIGHT via patient-owned technology. Although a majority of our 
population owned a video-enabled device (smart phone=83%, tablet=36%, computer=64%, none=6%) and 
had home internet access (88%), we elected to provide each participant with the same video platform 
(tablet) and internet connection (cellular-enabled Wi-Fi) to enhance the standardization and rigor of our 
approach. 
 
Our pilot data suggest that telemedicine is the preferred strategy to deliver CBT interventions to HNC 
survivors with BID. When patients chose the delivery method of BRIGHT (face to face or tablet-based) in 
our single-arm trial, tablet-based BRIGHT was overwhelmingly preferred (100% of patients traveling >25 
miles (8/8); 67% (2/3) of patients traveling < 25 miles) because of travel considerations, convenience, and 
flexibility. 
 
4.3.2 JUSTIFICATION FOR THE NUBMBER, FREQUENCY, AND TIMING OF INTERVENTION 
CONTACTS 

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A needs assessment conducted within our prospective cohort study of BID in HNC survivors43 informed 
the timing (immediately after HNC treatment), setting (one-one psychotherapy), and delivery method 
(telemedicine or face to face) of BRIGHT. These facets of BRIGHT delivery were subsequently confirmed 
in our single-arm pilot trial of BRIGHT (Table 4) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.4 
END-OF-STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed the baseline 
assessment, and the 1-week, 1-month and 3-month follow-up assessments. The end of the study is 
defined as completion of the 3-month follow-up assessment shown in the SoA, Section 1.3. The end-of-
study definition will permit sufficient follow-up to capture the primary endpoint, change in BIS scores at 
1-month post-intervention relative to baseline, as well as secondary endpoints assessed at 3-months post-
intervention. 
 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Age > 18 years at the time of screening 
2. History of pathologically confirmed invasive SCC (or histologic variant) of the upper 
aerodigestive tract (oral cavity, pharynx, larynx, nose/paranasal sinuses), carcinoma of a major 
or minor salivary gland, or cutaneous malignancy of the face or neck 
3. History of curative intent surgery with or without adjuvant therapy, with or without 
reconstruction 
Table 4. Acceptability of Timing, Frequency, Duration, and Content of BRIGHT 
from the Single-Arm Pilot Trial (n=9) 
Acceptability to Patients 
Mean (SD) 
How well did the timing of the program work for you? 
4.44 (0.73) 
How well did the method of program delivery work?  
4.67 (0.5) 
How well did the number of sessions work for you? 
4.56 (0.53) 
How relevant was the content of each session? 
4.56 (0.30) 
Session 1 
4.11 (1.27) 
Session 2 
4.44 (0.73) 
Session 3 
4.56 (0.53) 
Session 4 
4.89 (0.33) 
Session 5 
4.78 (0.44) 
How likely are you to recommend BRIGHT? 
4.89 (0.33) 
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4. American Joint Committee on Cancer (AJCC) 8th Edition pathologic stage grouping I-IV 
5. Completion of oncologic treatment within 12 months of study enrollment (but no sooner than 6 
weeks post-treatment completion) 
6. No planned significant HNC ablative or reconstructive surgery (defined by a postoperative 
inpatient stay of at least three days) during the study intervention or follow-up period as 
determined by the HNC oncologic surgeon at the time of study accrual 
7. Willingness to be randomized to either BRIGHT or AC 
8. BIS score > 10 
 
5.2 
EXCLUSION CRITERIA 
Participants who meet any of the following criteria are not eligible to participate in the study: 
1. Inability to speak or write English 
2. Pre-existing, ongoing CBT services for other disorders and the participant is not willing to 
discontinue the prior therapy for the duration of the proposed trial. 
3. Initiation or adjustment (< 3 months of baseline) of psychotropic medication. 
4. Severe psychiatric comorbidity (e.g. suicidal ideation, psychosis) 
o The rationale for excluding these patients is that the study protocol may be 
therapeutically insufficient. 
 
5.3 
LIFESTYLE CONSIDERATIONS 
N/A 
 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in this study but are not 
subsequently assigned to the study intervention or entered in the study. Individuals who do not meet the 
criteria for participation in this trial (screen failure) because of meeting one or more exclusion criteria will 
not be rescreened. 
 
 
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
5.5.1 ANTICIPATED SCREENING AND ACCRUAL TARGETS 
We propose to enroll 52 patients over 19 months to have 44 analytic subjects complete the study. The 
planned accrual stratified by gender, race, and ethnicity is shown in Table 5. Individuals across the lifespan 
will be included with the following exception: children (i.e., individuals under age 18) will be excluded. 
Children are not eligible to participate in the study for the following scientific reasons: 1) HNC is a rare 
pediatric malignancy 2) the experiences of children with BID are different from those of adults. There is 
no maximum age to participate in the study. The investigative team has expertise working with adult HNC 
survivors across a large age range (19-89 years) in prior research. The Head and Neck Tumor Center, where 
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in the included age range. Age will be collected, and data will be disaggregated by age to allow for 
examination of age as a biological variable during data analysis. The age distribution included in the study 
(all ages > 18) will allow us to evaluate the impact of age on the feasibility, acceptability, and clinical impact 
of our study intervention. 
 
The planned distribution of subjects by sex in the clinical trial is 50% female and 50% male. The sex 
distribution for patients is expected to reflect the demographics of our target population (HNC survivors 
with BID following surgery at the Medical University of South Carolina [MUSC]) based on our pilot data. 
There are no specific outreach programs for recruiting based on sex. Subjects will not be excluded from 
this study based on sex. Sex will be collected, and data will be disaggregated by sex to allow for 
examination of sex as a biological variable during data analysis. 
 
Patients of all races and ethnicities will be recruited for the study in proportion to their existence in the 
study population (HNC survivors with BID following surgery at MUSC). The planned distribution of subjects 
by self-identified race in the trial is 78% white, 19% African American and 3% other. The rationale for the 
selection of racial proportions in the study is that race is not a known risk factor for BID. The planned 
distribution of subjects by self-identified ethnicity in the trial is 97% non-Hispanic and 3% Hispanic. The 
rationale for the selection of ethnic proportions in the study is that ethnicity is not a known risk factor for 
BID. Race will be collected, and data will be disaggregated by race to allow for examination of race as a 
biological variable during data analysis. 
 
Table 5. Planned Recruitment by Race, Ethnicity, and Gender 
 
Ethnic Categories 
Racial 
Categories 
Not Hispanic or Latino 
Hispanic or Latino 
Total 
Female 
Male 
Female 
Male 
White 
17 
18 
1 
1 
37 
African 
American 
3 
3 
0 
0 
6 
Asian 
1 
 
 
 
1 
Other 
 
 
 
 
 
Total 
21 
21 
1 
1 
44 
 
5.5.2 ANTICIPATED ACCRUAL RATE AND ACCRUAL FEASIBILITY 
The anticipated accrual rate over the course of the study is 52 accrued patients over 19 months to have 
44 analytic subjects complete the study. This accrual rate includes a 20% attrition due to study 
withdrawal or development of a clinical event that makes the patient non-evaluable. These estimates 
are based on pilot data from our single-arm pilot trial of BRIGHT. There are no specific accrual targets 
based on patient characteristics (sex, age, racial/ethnic group). For the proposed study, we predict an 
accrual rate of 2.3 subjects/month. We expect a slightly higher rate of accrual for the proposed trial 
because we have refined and optimized our recruitment strategies and SOP based on valuable lessons 
related to logistics, timing, and methods of screening that we learned while recruiting for the single-arm 
trial of BRIGHT. Although we would expect an even higher rate of accrual (e.g. 2.5 subjects/month) 
simply based on improvements that we have made while optimizing the SOP for recruitment, our 
proposed accrual rate is tempered slightly by the more stringent inclusion criteria that we will be using 
for the proposed trial. Although our single-arm pilot study included patients with a Body Image Scale 

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score >1, we refined our inclusion criteria for the proposed study to use a Body Image Scale score of > 
10 (a clinically relevant threshold), to allow us to target our intervention  more precisely and enhance 
our ability to evaluate mediation. The revised inclusion criterion is expected to impact recruitment 
minimally; 91% of patients who accrued to BRIGHT in our pilot study would have been eligible with the 
new criterion. Accrual for the single-arm pilot averaged 2.2 subjects/month. For the proposed study, we 
predict an accrual rate of 2.3 subjects/month based on the fact that although we improved our accrual 
strategy based on our pilot work, we will exclude 10% of previously eligible subjects because of more 
stringent inclusion criteria. Accruing 2.3 subjects/month, we would reach our goal (n=44) in 19 months 
5.5.3 PLANNED SCREENING AND RECRUITMENT STRATEGIES 
We will screen for potential participants using the electronic medical record (EMR) for the Head and Neck 
Tumor Center clinical schedule in collaboration with the HNC clinical team. To screen for study eligibility, 
the research staff will use the EMR to review clinic schedules for new or returning patients with an 
appointment who are potentially eligible for the study. These appointments will include both in-person 
clinic visits to the MUSC Head and Neck Tumor Center or a telemedicine visit with a head and neck 
oncology provider. Clinic rosters will be reviewed at a minimum of once per week, or more frequently if 
indicated by changes to the clinic schedule. As such, screening will generally be performed within 7 days 
of enrollment. After a patient who is potentially eligible for the study is identified, the patient will be 
contacted during the previously identified in-person clinic visit within the MUSC Head and Neck Tumor 
Center or the telemedicine visit with the head and neck oncology provider to discuss participation in the 
trial. If it becomes clear that further information is needed to determine study eligibility, the patient will 
be re-screened pending evaluation of the additional information.  
 
We will recruit participants for the single-site, pilot RCT comparing BRIGHT with AC using a “clinic”-based 
approach, recognizing that in the era of COVID-19, “clinic” now consists of a combination of in-person and 
telemedicine visits. In-person recruitment will occur at the Head and Neck Tumor Center of the MUSC 
NCI-designated Hollings Cancer Center and telemedicine-based recruitment will occur electronically 
during the telemedicine visit with the head and neck oncology provider that is happening in lieu of the in-
person visit. Recruitment for the study will occur using the tested, structured standard operating 
procedures (SOPs) developed and optimized during our single-arm pilot study of BRIGHT that have been 
adapted to reflect the addition of telemedicine-based recruitment. This protocol was initially based on 
structured recruitment protocols from the PI (Evan Graboyes, MD, MPH, FACS) and co-investigator 
(Katherine Sterba, PhD, MPH) that were previously successfully employed for clinic-based recruitment of 
HNC survivors into psychobehavioral studies. The original recruitment SOPs have been optimized based 
on our experiences in the pilot study of BRIGHT to address logistical issues related to coordination of clinic-
based screening, enrollment, and distribution of the tablet-based platform for BRIGHT delivery. Our 
experience recruiting for the single-arm study of BRIGHT also demonstrated that the active clinical 
practice of the PI and his clinical relationship with all members of the multidisciplinary HNC team is a key 
factor in maximizing recruitment. The study participants may include patients of the PI’s, but will not be 
exclusively patients of the PI. Other than the notification of the study by the attending physician for 
potential trial participants, the research team will not ask other HNC clinicians to be directly involved in 
recruitment. All of the recruitment will be handled by the study coordinator and study team. 
 
5.5.4 STRATEGIES TO ENHNACE RETENTION 

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We expect to continue the high rate of retention that we demonstrated in our single-arm pilot study 
through the following four well-established strategies. First, we maintain active communication with 
participants during the study including prior to and between visits via each patient’s preferred mode of 
contact (e.g. text message, phone call, e-mail). In addition, our pilot study showed us that having the 
program coordinator contact participants with a reminder message 1-day prior to a scheduled BRIGHT 
session helped ensure low rates of missed sessions and high rates of retention. Second, BRIGHT was 
designed using a patient-centered needs assessment approach to ensure that the timing (immediately 
after HNC treatment), format (one-one psychotherapy), and delivery method (telemedicine) would 
ensure design of a feasible and acceptable intervention. While the content of BRIGHT will not be active to 
the patients in the AC arm, the timing and delivery method are the same in both arms of the trial and will 
thus likely facilitate retention in the AC as well as the BRIGHT arm. Third, we have accounted for the 
burden of questionnaires while patients are recovering from treatment to ensure that the expected time 
survey-related time commitment is reasonable. Collection of questionnaires has been optimized in our 
pilot study to ensure that it is convenient for participants in terms of timing and method of completion. 
Fourth, participant retention is maximized through up-front careful screening and a thorough informed 
consent process to ensure that participants capable of, and interested in, participating in a clinical trial 
enroll. 
 
5.5.5 RETENTION FEASIBILITY 
Our pilot single-arm clinical trial of BRIGHT showed that retention for our study is highly feasible (90%; 
9/10 participants). The only participant who dropped out was the first participant enrolled in the study. 
This participant had multiply recurrent HNC and decided, after the first session of BRIGHT, that she had 
more significant, concurrent competing demands and thus the BRIGHT program was not applicable to her 
most pressing concerns. Although challenges with retention for cancer studies due to mortality (overall 
and disease-specific) and treatment toxicity are potentially problematic, our pilot data have shown that 
these hypothetical factors not significantly impacted retention feasibility. We have also developed 
exclusion criteria to minimize potential dropout. These include excluding potential participants with: 
1. High likelihood of requiring significant HNC surgery during the study period 
2. Pre-existing, ongoing CBT services for other disorders 
3. Current suicidal or homicidal ideation 
These strategies will ensure that retention is feasible, thus ensuring that given our feasible enrollment 
targets, the study remains appropriately powered. 
 
5.5.6 PARTICIPANT COMPENSATION 
We strive to reinforce participants appropriately for attending visits and completing study procedures. 
Remuneration also occurs on a schedule that provides significantly more compensation at the end of the 
study time period. In the proposed study, participants will receive up to $125: $25 for enrolling, $50 for 
the intervention, and $50 for the follow-up questionnaires.  Participants will be compensated by check. 
This level of compensation is viewed as appropriate for the time of the patient and not unduly coercive. 
 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 

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6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
6.1.1.1 BRIGHT 
 BRIGHT is 5 sessions of weekly, 60-minute, tablet-based, manualized individual tele-CBT targeting the 
behavioral, attitudinal, and cognitive components of HNC-related BID. The therapy manual and 
accompanying patient workbook include agendas for each session, the theoretical and clinical rationale 
supporting the content, homework, 
and policies for tardiness, attrition, 
and homework noncompliance. 
BRIGHT focuses on adjustment to 
disfigurement, teaches coping and 
problem-solving skills, and addresses 
the behavioral implications of BID. 
BRIGHT addresses the key conceptual 
domains of HNC-related BID (Table 
6)27.  BRIGHT session topics are shown in Table 7.  
 
6.1.1.2 AC 
AC is educational information about HNC survivorship developed (with permission) using resources from 
the NCI, American Head & Neck Society, Thyroid Head and Neck Cancer Foundation (THANC), and MUSC. 
AC consists of 5 weekly 30-minute sessions and is delivered one-on-one via a tablet-based telemedicine 
platform. The 5 sessions include of AC are shown in Table 8. AC was pilot tested with HNC survivors and 
refined based on their feedback to ensure its feasibility, appropriateness, and relevance. 
 
 
Table 6. Domains of HNC-Related BID Targeted by BRIGHT27 
Domains 
Personal dissatisfaction with appearance 
Other-oriented appearance concerns 
Appearance concealment 
Distress with functional impairments 
Social avoidance 
Table 7. BRIGHT Session Topics 
Session #   Content 
1 
Introduction to BRIGHT and setting goals for treatment 
2 
Cognitive behavioral model for body image disturbance 
3 
Cognitive restructuring – “talking back” to thoughts 
4 
Avoidance behaviors, safety behaviors, and social support 
5 
Identifying personal values and thinking ahead 
Table 8. AC Session Topics 
Session #   Content 
1 
HNC survivorship 
2 
HNC physical late and long-term treatment toxicity 
3 
HNC psychosocial late and long-term treatment toxicity 
4 
Health maintenance 
5 
Financial toxicity and return-to-work after HNC 

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6.1.2 ADMINISTRATION AND/OR DOSING 
Both BRIGHT and AC will be delivered using the same tablet-based telemedicine delivery platform. Upon 
enrollment, subjects in each arm receive, and are trained to use, a study-issued, Wi-Fi and 4GLTE cellular-
enabled iPads (32 Gb, 9.7-inch screen with LED retina display, 1.2 MP front-facing camera with 780 p 
video-resolution). Each iPad is locked to prevent downloading of additional applications and pre-loaded 
with a SIM Card to enable cellular communication. Cellular service is provided by Verizon (99.86% 
coverage of South Carolina). The iPad is preloaded with Vidyo, a HIPAA-compliant, video teleconference 
platform. Vidyo allows face to face communication, but also includes a within-video text feature for 
aphonic (due to surgical removal of their larynx) or severely dysarthric (due to surgical removal of their 
tongue) HNC patients. Subjects receive a hands-on tutorial about how to use Vidyo upon enrollment and 
a supplemental pictorial instructional booklet for reference at home. To log into a session, the subject 
clicks on the Vidyo application to enter the pre-assigned teleconference room and connect to the study 
psychologist (BRIGHT) or electronic information (AC). No user names, logins, or URLs are necessary. At the 
conclusion of the 5-week intervention, subjects return the iPads to the study team in pre-addressed, 
stamped, padded mailers. 
 
6.1.2.1 BRIGHT 
BRIGHT will be delivered in one-on-one, face-to-face sessions between the study psychologist and 
participant using a tablet-based telemedicine platform. The BRIGHT intervention consists of five sessions 
of weekly, 60-minute, tablet-based, manualized individual tele-CBT (see Section 1.3, Schedule of 
Activities). BRIGHT will be delivered by two licensed clinical psychologists at the MUSC Hollings Cancer 
Center (Stacey Maurer, PhD and Wendy Balliet, PhD). The use of two psychologists to deliver BRIGHT will 
enhance rigor and external validity and minimize confounding between the experimental intervention 
and interventionist. Based upon our pilot work, a full-dose of the intervention consists of five sessions 
within a six-week span with a mean session-length of 45 minutes. The relevant parameters when 
considering the delivery of BRIGHT include the number, frequency, and duration of tablet-based sessions. 
Participants in the trial are permitted to interact with other participants after randomization, regardless 
of treatment allocation. Such encounters may occur in waiting rooms before or after clinic appointments 
given the single-site design of the trial. Such encounters may also occur in the virtual and social network 
space through patient support forums and online communities of HNC survivors. 
6.1.2.2 AC 
AC consists of 5 weekly 30-minute sessions and is delivered one-on-one via a tablet-based telemedicine 
platform. AC replicates the number of sessions (5), frequency (weekly), and delivery method of BRIGHT 
(tablet-based telemedicine platform) but differs in content to isolate the ‘active’ ingredient in BRIGHT (see 
Section 1.3, Schedule of Activities). The relevant parameters when considering the delivery of AC include 
the number, frequency, and duration of tablet-based sessions to ensure that it is appropriately matched 
to BRIGHT. The AC matches (and replicates) the duration and frequency of BRIGHT. AC was originally 
matched to BRIGHT for session duration (60 minutes) but was decreased to 30 minutes/session based on 
feedback during pilot testing from HNC survivors. Session topics include: 1) HNC survivorship overview; 2) 
physical long-term HNC treatment toxicity; 3) psychosocial long-term HNC treatment toxicity, 4) health 
maintenance, and 5) financial toxicity and return-to-work. AC was pilot tested with HNC survivors and 
refined based on their feedback to ensure its feasibility, appropriateness, and relevance. The videos are 
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initiate and close the telemedicine session as described in the AC SOP, thereby enhancing participant 
adherence to AC. A full dose of AC is not known. Participants in the trial are permitted to interact with 
other participants after randomization, regardless of treatment allocation. Such encounters may occur in 
waiting rooms before or after clinic appointments given the single-site design of the trial. Such encounters 
may also occur in the virtual and social network space through patient support forums and online 
communities of HNC survivors. 
 
6.2 
FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
6.2.1.1 BRIGHT 
Standardization of intervention administration is critical to ensure scientific rigor, validity, reproducibility, 
and achievement of study objectives. The specific duties necessary to ensure consistent and optimal 
administration of BRIGHT are detailed in the BRIGHT manual and AC standard operating procedures (SOP). 
All sessions of BRIGHT and AC will be audio-recorded and randomly selected sessions (20%) will be 
reviewed by a co-investigator to ensure fidelity of BRIGHT and AC in a manner that is consistent with SOP. 
If insufficient adherence to the manual is identified, appropriate remediation will occur. For BRIGHT and 
AC, the study coordinator will keep a tracking log capturing session duration, content delivered, and 
technical problems with the tablet-based delivery system. Because Dr. Maurer, the study psychologist 
helped develop BRIGHT, delivered BRIGHT in our single-arm pilot trial, and has experience managing 
pyscho-oncologic concerns in HNC patients, no additional specific training is planned prior to the delivery 
of BRIGHT for this trial. 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
Bias will be minimized through the randomized permuted block design. Randomization will occur at the 
individual patient level. Patients will be randomized 1:1 to BRIGHT or AC using a permuted block 
randomization method, with randomly selected block sizes of 2 or 4. Given the impossibility of delivering 
BRIGHT in a non-blinded fashion, allocation concealment will be non-blinded. The study statistician (Hong 
Li, PhD) will generate and implement the randomization schema and randomization list. The study 
coordinator will implement the randomization using the REDCap randomization module. Randomization 
errors will be handled as per the modified intention-to-treat population for the efficacy analysis. 
 
 
 
6.4 
STUDY INTERVENTION ADHERENCE 
6.4.1 BRIGHT 
Adherence of subjects to BRIGHT study procedures are key to ensure scientific rigor, validity, 
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measures: 1) attendance at intervention visits; 2) duration of study visits; 3) homework completion, 4) 
psychologist rating of patient engagement and material comprehension. Attendance at all study visits are 
mandatory to remain an active participant. Adherence information will be ascertained from the BRIGHT 
visit note authored by the study psychologist in a patient-adherence tracking log in the EMR after each 
study visit and documented in the eCase Report Form (eCRF) after each study visit by the study 
coordinator. 
 
6.4.2 AC 
Adherence of subjects to AC study procedures are key to ensure matching of the delivery format, 
frequency, duration, and schedule of the control, and thus scientific rigor, validity, reproducibility, and 
achievement of study objectives. Adherence to AC will be assessed with the following measures: 1) 
attendance at intervention visits; 2) duration of study visits; and 3) homework completion. Attendance at 
all study visits are mandatory to remain an active participant. Adherence information will be ascertained 
by the study coordinator after each study visit and documented in the eCRF. 
 
6.5 
CONCOMITANT THERAPY 
For this protocol, participants may use antidepressants and anxiolytics at the discretion of their treating 
providers. Medication usage will be assessed at each study visit and documented in the eCRF.  
 
6.5.1 RESCUE THERAPY 
N/A 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
At subject, PI, or study team member request. 
 
When a subject discontinues from BRIGHT or AC but not from the study, remaining study procedures 
will be completed as indicated by the study protocol.  If a clinically significant finding is identified 
(including, but not limited to changes from baseline) after enrollment, the investigator or qualified 
designee will determine if any change in participant management is needed. Any new clinically relevant 
finding will be reported as an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
The reason(s) for discontinuing the participant from the intervention, and methods for 
determining the need to discontinue 
• 
If the participant is due to complete assessments within 2 weeks of being discontinued from the 
study intervention, those assessments will be administered at the time of discontinuation; if the next 
scheduled assessments are more than 2 weeks from the discontinuation date, the discontinued 

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participant will wait for the next scheduled assessment. Thereafter, the participant will be included in all 
future scheduled assessments, even though not participating in the intervention. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. The 
investigators will seek to minimize participant discontinuation/withdrawal from the study (see Section 
7.3, Lost to Follow-Up) except for safety reasons. 
 
An investigator or the IRB may discontinue a participant from the study for the following reasons: 
• 
Significant study intervention non-compliance  
• 
Lost-to-follow up; unable to contact subject (see Section 7.3, Lost to Follow-Up) 
• 
Any event or medical condition or situation occurs such that continued collection of follow-up  
study data would not be in the best interest of the participant or might require an additional 
treatment that would confound the interpretation of the study 
o Subjects who are enrolled into the study and undergo a significant HNC ablative or 
reconstructive surgery (defined by a postoperative inpatient stay of at least three days) 
during the study intervention or follow-up period 
o Subjects who are enrolled in the study and develop a recurrence of their index HNC (local, 
regional or distant recurrence, radiologic or biopsy-proven) or metachronous second 
primary cancer (radiologic or biopsy-proven) during the study intervention or follow-up 
period 
 
The rationale for having these patients discontinue the study is that a significant HN-related surgery, 
development of a HNC recurrence, or development of a second primary cancer may introduce new body 
image concerns, confounding the association between BRIGHT (or AC) and changes in BID. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the CRF. 
Subjects who sign the informed consent form and are randomized, regardless of whether or not they 
received the intervention, will not be replaced.  
 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for two scheduled visits and 
study staff are unable to contact the participant after at least 3 attempts.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant, reschedule the missed visit within 2 weeks, 
counsel the participant on the importance of maintaining the assigned visit schedule and ascertain 
if the participant wishes to and/or should continue in the study 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts will be documented in the participant’s medical record or study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 

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8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
To screen for study eligibility, the research staff will use the EMR to review clinic schedules for new or 
returning patients with a physical appointment in the MUSC Head and Neck Tumor Center or telemedicine 
visit with a head and neck oncology provider who are potentially eligible for the study. Clinic rosters will 
be reviewed at a minimum of once per week, or more frequently if indicated by changes to the clinic 
schedule. As such, screening will generally be performed within 7 days of enrollment. After a patient who 
is potentially eligible for the study is identified, the patient will be contacted at the previously identified 
clinic visit (either physically within the MUSC Head and Neck Tumor Center or during the telemedicine 
visit) to discuss participation in the study as described below. The study coordinator who is screening the 
clinic schedule weekly will determine whether or not the potential trial participant has consented in EPIC 
to participate in research studies. For patients who have consented in EPIC to participate in research 
studies, the study coordinator will recruit using existing protocols for face-face clinic-based recruitment 
and study-specific documents to describe the study. For patients who have not consented in EPIC to 
participate in research studies, the  head and neck oncology provider for the patient will notify the patient 
of the study and introduce the study to the potential participant. Following this introduction, if the 
potential participant is interested in learning additional information about the trial, the study coordinator 
will recruit using existing standard operating procedures for clinic-based or telemedicine-based 
recruitment. Patients who meet demographic and oncologic inclusion criteria will complete a screening 
BIS questionnaire; those with scores > 10 will be eligible for the study. Those with scores < 10 will not be 
eligible for the study, their BIS questionnaire will be shredded, and no personal information about the 
patient will be saved. 
 
Primary Endpoint 
Change in BIS scores. The BIS is a validated, 10-item patient-reported outcome measure (PROM) that 
assesses the affective, cognitive, and emotional aspects of body image due to cancer or its treatment over 
the prior 7 days9. Responses include ‘not at all’, ‘a little’, ‘quite a bit’, and ‘very much’, and are scored from 
0-3, respectively. Total BIS scores can range from 0-30, with higher scores indicating greater body image 
dissatisfaction. The BIS is a reliable PROM validated in oncology patients and has been widely used to 
study BID in patients with HNC44. 
 
Secondary Endpoints 
Behavioral Mediator 
Change in Body Image Coping Strategies Inventory (BICSI) scores. The BICSI is a 29-item validated measure 
of the cognitive and behavioral responses to manage threats to body image10.  BICSI contains three sub-
domains; 1) appearance fixing (altering appearance by covering, camouflaging, or correcting the perceived 
defect), 2) avoidance (an attempt to escape or avert stressful body-image situations), and 3) positive 
rational acceptance (acceptance of the challenging event and positive self-care or rational self-talk about 
one’s appearance). Items are scored on a 4-point Likert scale from ‘definitely not like me’ to ‘definitely 
like me’ (0-3). The scores for each subscale are calculated by summing the values for the individual 
questions and thus range as follows: 1) appearance fixing (0-30), 2) avoidance (0-24), 3) positive rational 
acceptance (0-33). For each subscale, higher scores indicate greater quantities of each conceptual domain 
(appearance fixing, avoidance, and positive rational acceptance). Avoidance and appearance fixing are 
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distress, and poorer psychosocial functioning. Positive rational acceptance is a positive means of coping 
that is associated with lower levels of BID and distress. 
 
Clinical Activity 
Change in IMAGE-HN scores: The IMAGE-HN is a psychometrically sound, 24-item, multi-domain PROM 
consisting of 4 sub-scales and a global scale that can be used to measure key aspects of HNC-related BID 
due to HNC or its treatment45. Responses include ‘Never’, ‘Rarely’, ‘Sometimes’, ‘Often’, ‘Always’, 
corresponding to a Likert scale of 0-4, respectively. Total IMAGE-HN scores on the global domain (21 
questions) range from 0-84, with higher scores indicated greater HNC-related body image dissatisfaction. 
Raw scores for each sub-scale as well as the global scale can be converted to scaled scores for each, which 
range from 0-100 with higher scores representing greater HNC-related BID. 
 
Response. Response is defined as a BIS score at 1-month post-intervention that is lower than the BIS score 
at baseline. 
 
Secondary Measures of Psychosocial Wellbeing 
Change in Shame and Stigma Scale scores. The Shame and Stigma Scale is a 20-item, validated, 
unidimensional PROM that measures four domains (shame with appearance, stigma, regret, and 
social/speech concerns) in patients with HNC over the prior 7 days46. Responses include ‘never’, ‘seldom’, 
‘sometimes’, ‘often’, and ‘all the time’ and are scored 0-4, respectively. The total score is calculated by 
summing the individual responses (except for 4 questions which are reverse scored) and thus ranges from 
0-80. Higher scores reflect greater shame and stigma from HNC. 
 
Change in PROMIS SF v1.0-Depression 8a scores. PROMIS SF v1.0-Depression 8a is a validated, 8-item 
measure developed by the NIH to assess self-reported negative mood, views of self, and decreased 
positive affect and engagement47. Items are scored using a 5-point Likert scale from ‘never’ to ‘always’ (1-
5). The total score is calculated by summing the individual responses and thus ranges from 8-40. Higher 
scores reflect more severe depressive symptoms. 
 
Change in PROMIS SF v1.0-Anxiety 8a scores. The PROMIS SF v1.0-Anxiety 8a is a validated, 8-item 
measure developed by the NIH to assess self-reported fear, worry, and hyperarousal47. Items are scored 
using a 5-point Likert scale from ‘never’ to ‘always’ (1-5). The total score is calculated by summing the 
individual responses and thus ranges from 8-40. Higher scores reflect more severe anxiety. 
 
Change in PROMIS SF v2.0-Satisfaction with Social Roles and Activities 8a scores. PROMIS SF v2.0-
Satisfaction with Social Roles and Activities 8a is a validated, 8-item, measure developed by the NIH to 
assess self-reported satisfaction with performing one’s usual social roles and activities48. Items are scored 
using a 5-point Likert scale from ‘not at all’ to ‘very much’ (1-5). The total score is calculated by summing 
the individual responses and thus ranges from 8-40. Higher scores reflect more severe anxiety. 
 
Change in PROMIS SF v2.0-Social Isolation 8a scores. PROMIS SF v2.0-Social Isolation 8a is a validated, 8-
item, measure developed by the NIH to assess self-reported perceptions of being avoided, excluded or 
unknown by others48.  Items are scored using a 5-point Likert scale from ‘never’ to ‘always’ (1-5). The total 
score is calculated by summing the individual responses and thus ranges from 8-40. Higher scores reflect 
more severe social isolation. 
 
Feasibility 
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Intervention session completion is the number of intervention sessions completed by each participant 
 
Technical issues during tablet-based telemedicine sessions. Technical issues include inability to connect 
to the internet, video conference session, lack of video, lack of audio, insufficient tablet battery power, or 
any other technology related issues that prevents the session from otherwise functioning in a smooth and 
timely fashion. 
 
Tablet return is defined as the receipt of the study-issued tablet by the study team within three months 
of the completion of the five sessions of the intervention.  
 
Study dropout is defined as a participant voluntarily withdrawing from the study for whatever reason  
 
Acceptability 
Timing of Intervention will be assessed using a study-specific Likert scale measuring satisfaction with the 
timing of the intervention relative to the completion of treatment. Scores range from 0-5 with higher 
scores representing greater satisfaction with the timing of the intervention. 
 
Method of Delivery of the Intervention will be assessed using a study-specific Likert scale measuring 
satisfaction with the method of delivery of the intervention. Scores range from 0-5 with higher scores 
representing greater satisfaction with the method of delivering the intervention. 
 
Number of Intervention Sessions will be assessed using a study-specific Likert scale measuring satisfaction 
with the number of sessions of the intervention. Scores range from 0-5 with higher scores representing 
greater satisfaction with the number of intervention sessions. 
 
Session content relevance will be assessed using a study-specific Likert scale measuring satisfaction with 
the content relevance of each session. Scores range from 0-5 with higher scores representing greater 
satisfaction with the content of the intervention. 
 
Overall satisfaction will be assessed using a study-specific Likert scale measuring overall satisfaction with 
the intervention. Scores range from 0-5 with higher scores representing greater satisfaction with the 
intervention. 
 
Likelihood of Recommending the Intervention will be assessed using a study-specific Likert scale 
measuring likelihood of recommending the intervention. Scores range from 1-5 with higher scores 
representing greater likelihood of recommending the intervention. 
 
Working Alliance Inventory-Short Revised (WAI-SR) score. The WAI-SR is 12-item measure of working 
alliance consisting of three subscales assessing: 1) how closely client and therapist agree on and are 
mutually engaged in the goals of treatment (goals), 2) how closely client and therapist agree on the 
therapeutic tasks necessary to reach the treatment goals (tasks), and 3) the degree of mutual trust, 
acceptance, and confidence between client and therapist (bond). Patients score on a 5-point Likert scale 
ranging from rarely to always (1-5). Subscales scores for each of the subscales (goals, tasks, bond) range 
from 4-20. Total scores range from 12 to 60 with higher scores representing a stronger working alliance 
between the therapist and participant. 
 
Covariates 

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Appearance Schemas Inventory-Revised (ASI-R) Score. The ASI-R is a psychometrically sound, 20-item 
measure of image investment49. The ASI-R consists of two subdomains: Self-Evaluative Salience (of 
Appearance) and Motivational Salience (of Appearance). Items are scored using a 5-point Likert scale from 
‘strongly disagree’ ‘strongly agree’ (1-5). Items 1, 4, 5, 9, 11, 12 are reverse scored. The composite ASI-R 
score is calculated as the mean of the 20 items, and thus composite ASI-R scores range from 1-5. The score 
for each subscale is also calculated as the mean of its included items. Higher scores reflect greater levels 
of image investment. 
  
The individual’s medical chart will be used to collect information performed as part of an individual’s 
regular medical care are going to be used as a part of collection of trial data. As such, Health Insurance 
Portability and Accountability Act (HIPAA) rules, other relevant federal or state laws, and local institutional 
requirements will be followed, as applicable. The following information is to be obtained through review 
of existing data: 
 
Demographics. Demographic characteristics include age, race, ethnicity, sex, marital status, living 
situation, insurance. 
 
Clinical and Oncologic Characteristics. Clinical characteristics will include body mass index (BMI), comorbid 
medical conditions, and cancer history. Oncologic characteristics will include HNC tumor subsite, HNC 
tumor histology, American Joint Committee on Cancer TNM Class and overall stage grouping, type of 
ablative surgical, type of reconstruction, adjuvant radiation dose, adjuvant chemotherapy dose and agent, 
and time since completion of treatment. 
 
8.2 
SAFETY ASSESSMENTS 
N/A 
 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
This trial is considered to carry a low risk to subjects (i.e. has a “no more than minimal risk” designation). 
As such, this protocol defines an adverse event (AE) as any undesirable sign, symptom, medical, 
psychological, social, or emotional reaction that is definitely, probably, or possibly related to the study 
intervention.  
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
A serious adverse event (SAE) will be defined as any undesirable sign, symptom, or medical condition 
which is fatal, is life-threatening, requires or prolongs inpatient hospitalization, results in persistent or 
significant disability/incapacity, is medically significant and which the investigator regards as serious 
based on appropriate medical judgment that is directly due to a study intervention. An important medical 
event is any AE that may not result in death, be life-threatening, or require hospitalization but may be 
considered an SAE when, based upon appropriate medical judgment, it may jeopardize the patient and 
may require medical or surgical intervention to prevent one of the outcomes listed in the definitions of 
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8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”. 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
All AEs will have their relationship to study procedures, including the intervention, assessed by the PI 
based on temporal relationship and his clinical judgment. The degree of certainty about causality will be 
graded using the categories below.  
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study procedures administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study procedures should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a 
reasonable time after administration of the study procedures, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal.  
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of study procedures). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
Recording/reporting of AEs will begin after the subject signs informed consent and end after the subject 
completes the intervention and follow up period as defined in the protocol. 
 
8.3.5 ADVERSE EVENT REPORTING  

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All AEs, as defined above, will be collected and reported. Data collection will occur via electronic 
spreadsheet. The information will be saved in REDCap and managed by the study team. In consultation 
with the PI, a trained member of the study team will be responsible for conducting an evaluation of a 
SAE and shall report the results of such evaluation to the NIH and the reviewing Institutional Review 
Board (IRB) as soon as possible and in accordance with the reviewing IRB policy 
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
In consultation with the PI, a trained member of the study team will be responsible for conducting an 
evaluation of a SAE and shall report the results of such evaluation to the NIH and the reviewing IRB as 
soon as possible and in accordance with the reviewing IRB policy. 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
N/A 
 
8.3.8 EVENTS OF SPECIAL INTEREST  
N/A 
 
8.3.9 REPORTING OF PREGNANCY  
N/A 
 
8.4 
UNANTICIPATED PROBLEMS 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
This protocol uses the definition of Unanticipated Problems (Ups) as defined by the Office for Human 
Research Protections (OHRP). OHRP considers unanticipated problems involving risks to participants or 
others to include, in general, any incident, experience, or outcome that meets all of the following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the IRB-approved research protocol and 
informed consent document; and (b) the characteristics of the participant population being 
studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
8.4.2  UNANTICIPATED PROBLEMS REPORTING  
The investigator will report UPs to the reviewing IRB and to the lead PI. The UP report will include the 
following information: 
 

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• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number 
• 
A detailed description of the event, incident, experience, or outcome  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:  
• 
Ups will be reported to the IRB and to the NCI in accordance with policy regarding timeliness of 
reporting 
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the OHRP in 
accordance with policy regarding timeliness 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
N/A 
 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
• 
Primary Endpoint: 
We hypothesize that, compared with patients who receive the AC, patients who receive BRIGHT will 
have reduced BID as measured by change in BIS scores at 1-month post-intervention relative to 
baseline. Alternatively, our null hypothesis is that there will be no difference between BRIGHT and AC 
in terms of improving BID, as measured by change in BIS scores at 1-month post-intervention relative 
to baseline. 
 
 
• 
Secondary Endpoint(s): 
We hypothesize that improvements in body image coping behavior (improvement in BICSI scores from 
baseline to 1-week post intervention) will partially mediate a decrease in BID (reduction in BIS scores from 
baseline to 1-month post intervention) and this relationship will be maintained at 3-months. 
 
We hypothesize that BRIGHT will improve psychological (larger decrease in Shame and Stigma scores), 
emotional (larger decrease in PROMIS depression and anxiety scores), and social well-being (larger 
decrease in PROMIS social roles and social isolation scores) relative to AC at 1- and 3-months post-
intervention. 
 
9.2 
SAMPLE SIZE DETERMINATION 

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Our primary objective is to compare change in BIS scores from baseline to 1-month intervention between 
the BRIGHT and AC arms. The primary endpoint is ∆ in Body Image Scale scores from baseline to 1-month 
post-intervention. We hypothesize that, compared with patients who receive the AC, patients who receive 
BRIGHT will have reduced BID as measured by change in BIS scores at 1-month post-intervention relative 
to baseline. Alternatively, our null hypothesis is that there will be no difference between BRIGHT and AC 
in terms of improving BID, as measured by change in BIS scores at 1-month post-intervention relative to 
baseline. All power and sample size calculations were performed using PASS 2008 version 08.0.13. Based 
on data from our prospective cohort study50 and single-arm pilot of BRIGHT, we estimate the mean ∆ in 
Body Image Scale scores ± SD from baseline to 1-month post are 0.2 ± 5.9 and 4.6 ± 3.9 for control and 
BRIGHT, respectively. This effect size is clinically significant and realistic given results of other 
psychobehavioral interventions in breast cancer patients with BID51,52. For n=22/arm (proposed sample 
size), power exceeds 80% for mean difference in change in Body Image Scale scores of at least 3.1 (with 
SD as large as 4) or mean difference of at least 5.5 (with SD as large as 7) based on two-sided t-test with 
α=0.1 (Fig. 4A). Group sample size of n=22 (AC, BRIGHT) achieved 80.2% power to detect the 
standardized effect (mean difference in ∆ Body Image Scale score from baseline to 1-month divided by 
the pooled SD=5.62) of 0.78 based on the two-sample t-test with two-sided α=0.1 (Fig 4B). We will have 
greater than 90% power for a standardized effect size of 0.93 and greater than 80% power for a 
standardized effect size of 0.78. These are both considered moderate effect sizes and are feasible for 
continuous outcomes in the context of variables that are expected to be modulated by the cancer 
experience. Our power estimate is conservative given our proposed analysis plan using LME regression, 
which borrows strength over time and is generally more efficient than a t-test. As such we anticipate that 
smaller effect sizes than described above will be detectable. Our selection of relaxed significance (α = 0.1) 
with maintained power (1 – β = 0.8) is based on the desire to emphasize power over type I error at this 
early stage of development (single-site pilot RCT) to ensure follow-up on promising interventions to guide 
and power a subsequent larger RCT to fully evaluate the efficacy of BRIGHT as a treatment of BID in HNC 
survivors (i.e. test BRIGHT with significance level of 0.05). We therefore consider our RCT to be 
appropriately and rigorously designed to detect a clinically meaningful reduction in BID. 
 
Fig. 4. Power Calculations for (A) Mean difference in ∆ in Body Image Scale scores between baseline and 1-
month post intervention, comparing BRIGHT and AC; (B) standardized effect, comparing ∆ in Body Image 
Scale scores between BRIGHT and AC from baseline to 1-month post intervention 

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In order to have 44 patients eligible for the efficacy analysis in the modified ITT population (see Section 
9.3, Population for Analyses), we plan to enroll 52 patients. Our sample size is inflated by 20% based on 
interim accrual data. This inflation account for study dropout and the predictable subset of patients would 
be enrolled in the study, be randomized to BRIGHT or AC, receive a portion or all of the intervention and 
then subsequently are withdrawn from the study and non-evaluable due to a major HNC surgery or 
recurrent or second primary cancer. 
 
Every effort will be made to minimize missing data and lost-to-follow-up participants. Participants will 
complete assessments at baseline, 1-week post-intervention, 1-month post-intervention, and 3-months 
post intervention using an iPad-based REDCap collection method. The program coordinator will attempt 
to contact patients at least three times using a variety of methods of communication (e.g. text message, 
phone call, email, mail, etc.) to complete outcome measures. This method resulted in 100% instrument 
completion in our single arm pilot study. In the event that missing data do occur, we will address them via 
standard multiple imputation procedures53,54. As participants will be randomized to treatment, it is 
unlikely that missing data will produce biased estimates of treatment effect, as observed and unobserved 
covariates should theoretically be balanced across treatment groups. In general, less than 10% missing 
data has little impact on study power and does not induce bias regardless of the missing data 
mechanism55. If missing data is greater than 10%, it will be imputed using propensity score54,56 or Markov 
Chain Monte Carlo (MCMC) methods57. When covariate information is associated with whether the 
imputed variable values are missing, we will use the propensity score method, which calculates the 
propensity score from modeling the distribution of the missing indicator variable based on the observed 
data and then applies an approximate Bayesian bootstrap imputation to each group identified by the 
propensity score. Otherwise, we will use the MCMC method. The data augmentation will be applied to 
Bayesian inference with missing data by repeating imputation step (i.e., simulating the missing values 
based on the observation) and step for exploring the posterior distribution based on the complete sample 
estimates obtained from the imputation step. 
 
9.3 
POPULATIONS FOR ANALYSES 
Participants will be defined as evaluable for the primary endpoint (change in BIS from baseline to 1-month 
post-treatment) and thus included in the efficacy analytic population if they are enrolled in the study and 
randomized. However, there are two subsets of patients (7.2, Participant Discontinuation/Withdrawal) 
for whom the investigator may discontinue participation due to an event or medical condition or situation 
occurs such that continued collection of follow-up  study data would not be in the best interest of the 
participant or might require an additional treatment that would confound the interpretation of the study. 
Specifically,  
1. Subjects who are enrolled into the study and undergo a significant HNC ablative or reconstructive 
surgery (defined by a postoperative inpatient stay of at least three days) during the study 
intervention or follow-up period. 
2. Subjects who are enrolled in the study and develop a recurrence of their index HNC (local, regional 
or distant recurrence, radiologic or biopsy-proven) or metachronous second primary cancer 
(radiologic or biopsy-proven) during the study intervention or follow-up period. 
 
We will also perform an efficacy analysis on the per-protocol analytic dataset, a subset of the ITT 
population who completed all 5 intervention (BRIGHT and AC) sessions. These patients are judged to have 
complied with the protocol sufficiently to ensure that these data would be likely to represent the effects 
of BRIGHT according to the underlying scientific model. 

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9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
Graphical displays such as scatterplots and boxplots will be constructed to demonstrate patterns of 
individual continuous measures and differences between baseline, 1-week, 1- and 3-months post 
intervention. Summary descriptive statistics (e.g. frequencies and percent for categorical variables, and 
mean, median, standard deviation, and range for continuous variables) will be reported. For inferential 
tests, we will use a p-value of 0.05, two-sided, and 95% confidence intervals (CIs) to assess statistical 
significance (Type I error). Covariates will be pre-specified as described below. Normality of the data will 
be assessed before underlying statistical procedures will be performed. We will evaluate variable 
transformations as needed to satisfy assumptions and consider transformations of variables to induce 
approximate normality and stabilize variance as needed. Nonparametric tests will be applied when 
appropriate. 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
Longitudinally measured BIS scores will be modeled using linear mixed effects (LME) regression with the 
measures at each time point relative to baseline (denoted by ∆) as the response variable and fixed effects 
for experimental conditions (BRIGHT, AC), time (1-week, 1-month, and 3-months post intervention) and 
their interaction. Models will include subject-specific random effects to account for correlation among 
measures obtained from the same subject over time. We will use qq-plots and histograms to investigate 
the assumption of approximate normality and consider transformations (e.g., log) as needed. We will 
assess the functional form of time to account for any non-linear temporal trends and consider 
transformations as needed. Comparisons of the change from baseline to each time point between 
conditions will be performed using model-based linear contrasts. Data will be disaggregated by age, sex, 
and race to allow for analysis of each as biological variables. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
For secondary endpoints related to psychological, emotional, and social well-being, graphical displays 
such as scatterplots and boxplots will be constructed to demonstrate patterns of individual continuous 
measures and differences between baseline, 1-week, 1- and 3-months post intervention. Summary 
descriptive statistics (statistics (e.g. frequencies and percent for categorical variables, and mean, median, 
standard deviation, and range for continuous variables) will be reported. Longitudinal measures of 
psychological, social, and emotional well-being will be modeled using LME regression with the measures 
at each time point relative to baseline (denoted by ∆) as the response variable and fixed effects for 
experimental conditions (BRIGHT, AC), time (1-week, 1-month, and 3-months post intervention) and their 
interaction. Models will include subject-specific random effects to account for correlation among 
measures obtained from the same subject over time. We will use qq-plots and histograms to investigate 
the assumption of approximate normality and consider transformations (e.g., log) as needed. We will 
assess the functional form of time to account for any non-linear temporal trends and consider 
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conditions will be performed using model-based linear contrasts. Data will be disaggregated by age, sex, 
and race to allow for analysis of each as biological variables. 
 
To evaluate whether the effect of 
BRIGHT on change in BID at 1-month 
post-intervention is partially mediated 
by changes in body image coping 
behavior at 1-week post intervention, 
we will perform exploratory mediation 
analysis.  The total effect of the 
intervention (path c) will be partitioned 
into direct (path c’) and indirect effects, 
which we will test for statistical 
signiﬁcance (Fig. 5). We will examine the 
direct effect of the intervention on 
change in BID (∆ in Body Image Scale 
score) the mediating effect of change in 
body image coping behavior (∆ in Body 
Image Coping Strategies Inventory 
score) on change in BID, and the effect of the intervention on the mediator (∆ in Body Image Coping 
Strategies Inventory score). If paths a, b, and c are statistically significant and c’ (the direct effect) is 
reduced compared with c (the total effect), then partial mediation criteria are satisfied. The significance 
of the mediating effect will be tested using robust bootstrapping. Bootstrapping is considered superior to 
other methods of analyzing indirect effects because bootstrapping provides confidence intervals based 
on the bootstrap distribution instead of simply p values. In situations with smaller samples and non-
normal distributions, the bootstrapping method is more likely to achieve an unbiased estimate of the 
indirect effect than other methods. The confidence interval for the mediating effect will be provided from 
the bootstrap analysis with the ‘robmed’ R package. This analysis will be repeated for change in BID at 3-
months post and change in image coping behavior at 1-month post-intervention. Plots of mediated effect 
will be made to investigate the distribution of data and improve understanding of the relations among 
the variables. LME regression will be considered to assess the three-way interaction (moderator-
intervention-time) for age, sex and race.  
 
For secondary endpoints related to the feasibility and acceptability objectives, simple frequencies will 
characterize participant satisfaction with the following aspects of the intervention: timing, method of 
delivery, number of sessions, content relevance, homework utility, attentiveness of the study 
psychologist, overall satisfaction, and likelihood to recommend BRIGHT. Descriptive statistics will be 
presented. Our interdisciplinary team will meet after completion of study data analyses to interpret the 
implications of these findings for how to refine BRIGHT based on these data in preparation for our future 
large-scale trial. 
 
9.4.4 SAFETY ANALYSES 
N/A 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Fig. 5. Exploratory mediator analysis. Changes in body image 
coping behavior (Mediator [M1]) are hypothesized to mediate 
the effect of the intervention (independent variable [IV]) on 
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Baseline characteristics (e.g., demographics, oncologic details, behavioral characteristics) for the BRIGHT 
and AC arms will be compared and descriptive statistics calculated. Baseline differences between the two 
groups will be compared using t-tests and chi-square tests, or Wilcoxon rank sum and Fisher’s exact tests 
as appropriate. 
 
9.4.6 PLANNED INTERIM ANALYSES  
N/A 
 
9.4.7 SUB-GROUP ANALYSES 
Planned sub-group analyses of the primary endpoint will occur based on age, race, and sex to evaluate 
the impact of inclusion across the lifespan, race, and sex as biologic variables. 
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Individual participant data will not be listed by measure and time point. 
 
9.4.9 EXPLORATORY ANALYSES 
N/A 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED 
TO 
PARTICIPANTS 
 
 
Consent forms describing in detail the study intervention, study procedures, and risks will be provided to 
the participant (either on paper or electronically as an eConsent) and documentation of informed consent 
will be completed prior to starting the study intervention.  
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
We will obtain full written (either via paper-based or electronic signature) informed consent from patients 
enrolling in the study. Informed consent will occur via face-face discussion in clinic or via telemedicine 
between one of the study team members designated to perform informed consent and the potential 
study participant. The study member will explain the elements of the informed consent form including 
purpose, methods, extent of the study, risks, benefits, and alternatives to potential participants. 
Participants will be asked to read the consent form, given appropriate time to read the document on their 
own, and allowed to ask any questions prior to signing it. Consents will be written in simple, easy-to-
understand language and obtained on the day of enrollment by one of the study team members 
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study and participants will be asked to sign the consent and HIPAA forms. All participants will sign 
informed consent forms before the interview (either via paper-based informed consent or electronic 
signature of the REDCap-based electronic informed consent).  All participants will receive a copy of their 
informed consent and HIPAA forms for their records (either a paper copy or an emailed copy). The 
informed consent process will take place in a private room in the Rutledge Tower Head and Neck Cancer 
Clinic, in a private room in the HCC, or the location that the patient is conducting the telemedicine clinic 
visit in cases of electronic informed consent. Only the study participant will provide informed consent. 
Subjects will be allowed up to one week to decide whether to participate in the study. Participants will 
also complete a HIPAA form at the same time using the same procedures as described above. All 
participants will receive a copy of their informed consent and HIPAA forms (either paper or emailed) for 
their records. Separate copies of the documents will be stored in the study binder under each patient’s 
section. 
 
 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study participants, investigator, funding agency, and regulatory 
authorities. If the study is prematurely terminated or suspended, the PI will promptly inform study 
participants, the IRB, and sponsor/funding agency and will provide the reason(s) for the termination or 
suspension. Study participants will be contacted, as applicable, and be informed of changes to study visit 
schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Insufficient compliance of study staff to the protocol (e.g. significant protocol violations) 
• 
Data that are not sufficiently complete and/or evaluable 
 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the funding agency, sponsor, IRB, Food and Drug Administration (FDA), or other relevant 
regulatory or oversight bodies (OHRP, DSMB). 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, 
the safety and oversight monitor(s), and the sponsor(s) and funding agency. This confidentiality is 
extended to the data being collected as part of this study. Data that could be used to identify a specific 
study participant will be held in strict confidence within the research team. No personally identifiable 
information from the study will be released to any unauthorized third party without prior written approval 
of the sponsor/funding agency. To help protect participant confidentiality, we will assign a unique study 
ID number to each subject’s information in place of his/her name and will label data collection forms only 
with the ID number. All hard copy and electronic files will be stored appropriately using double-locked 
methods and password-protection. Only the study team member will have access to study records. 
Participant data will be collected and recorded on either a password-protected electronic data capture 
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preference. For the paper collection data method, the data collection form will be labeled only with the 
participant's unique study ID number, and then stored within locked drawers in a locked office. The 
information on these paper forms will be transferred to a password-protected REDCap database such that 
all data will be stored in the password-protected REDCap Database. Only members of the study team will 
have access to the data. We have no plan to use laptops, jump drives, CDs/DVDs to transport data. 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor or funding agency, representatives of 
the IRB, regulatory agencies or representatives from companies or organizations supplying the product, 
may inspect all documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, Institutional policies, or sponsor/funding agency 
requirements. 
 
It is NIH policy that the results and accomplishments of the activities that it funds should be made available 
to the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all mechanisms used to 
share data will include proper plans and safeguards for the protection of privacy, confidentiality, and 
security for data dissemination and reuse (e.g., all data will be thoroughly de-identified and will not be 
traceable to a specific study participant). Plans for archiving and long-term preservation of the data will 
be implemented, as appropriate.  
 
To further protect the privacy of study participants, the Secretary, Health and Human Services (HHS), has 
issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, behavioral, clinical 
or other human subjects research funded wholly or in part by the federal government.  Recipients of NIH 
funding for human subjects research are required to protect identifiable research information from forced 
disclosure per the terms of the NIH Policy (see https://humansubjects.nih.gov/coc/index). As set forth 
in 45 CFR Part 75.303(a) and NIHGPS Chapter 8.3, recipients conducting NIH-supported research covered 
by this Policy are required to establish and maintain effective internal controls (e.g., policies and 
procedures) that provide reasonable assurance that the award is managed in compliance with Federal 
statutes, regulations, and the terms and conditions of award. It is the NIH policy that investigators and 
others who have access to research records will not disclose identifying information except when the 
participant consents or in certain instances when federal, state, or local law or regulation requires 
disclosure. NIH expects investigators to inform research participants of the protections and the limits to 
protections provided by a Certificate issued by this Policy. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
Data collected for this study will be analyzed and stored with the study team. After the study is completed, 
the de-identified, archived data will be transmitted to and stored with the study team, for use by other 
researchers including those outside of the study. 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator 

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Evan Graboyes, MD, MPH, FACS 
Medical University of South Carolina  
135 Rutledge Ave, MSC 550 
Charleston, SC 29425 
843-792-0719 
graboyes@musc.edu 
 
10.1.6 SAFETY OVERSIGHT 
Safety oversight will be under the direction of a PI. Aggregate reviews will occur by the PI for all AEs, UPs, 
protocol violations, audit results, early withdrawals, whether the study accrual pattern warrants 
continuation/action, and endpoint data. Aggregate reviews will occur monthly. 
 
10.1.7 CLINICAL MONITORING 
N/A 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data and biological specimen 
collection, documentation and completion. 
 
Quality control (QC) procedures will be implemented as follows: 
 
Informed consent --- Study staff will review both the documentation of the consenting process as well as 
a percentage of the completed consent documents.  This review will evaluate compliance with GCP, 
accuracy, and completeness.  Feedback will be provided to the study team to ensure proper consenting 
procedures are followed.  
 
Source documents and the electronic data --- Data will be initially captured on source documents (see 
Section 10.1.9, Data Handling and Record Keeping) and will ultimately be entered into the study 
database.  To ensure accuracy site staff will compare a representative sample of source data against the 
database, targeting key data points in that review. 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in 
Section 6.2.1, Interventionist Training and Tracking.  
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related 
sites, source data/documents, and reports for the purpose of monitoring and auditing by the 
sponsor/funding agency, and inspection by local and regulatory authorities. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  

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Data collection will be the responsibility of the clinical trial staff at the site under the supervision of the 
site investigator. The investigator will be responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported. All source documents will be completed in a neat, legible manner to 
ensure accurate interpretation of data.  
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant consented/enrolled in the study.  Data recorded in the electronic case 
report form (eCRF) derived from source documents will be consistent with the data recorded on the 
source documents.  
 
Clinical data will be entered into REDCap. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, incomplete, or 
inaccurate. Clinical data will be entered directly from the source documents. 
 
10.1.9.2 STUDY RECORDS RETENTION  
In accordance with Health and Human Services regulation at 45 CFR 46.115(b), we will retain IRB records 
for at least three years. At the end of three years, records will be boxed, labeled, and sent to central 
storage for another three years. Research records will be retained for six years to allow evaluation and 
repetition by others of the results and to investigate an allegation of research misconduct. 
 
10.1.10 
PROTOCOL DEVIATIONS   
A protocol deviation is any variance from the protocol involving a subject or subjects that is not approved 
by the IRB prior to its initiation or implementation, and occurs when a member of the study team departs 
from the IRB-approved protocol in any way without the investigator first obtaining IRB approval (See 
MUSC IRB Policy HRPP 4.14). 
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY  
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed 
journals.  Data from this study may be requested from other researchers 2 years after the completion of 
the primary endpoint by contacting Evan Graboyes, MD, MPH, FACS.  Considerations for ensuring 
confidentiality of these shared data are described in Section 10.1.3. 
 

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10.1.12 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest 
will be required to have such conflicts managed in a way that is appropriate to their participation in the 
design and conduct of this trial. The study leadership in conjunction with the NCI has established policies 
and procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 
 
10.2 ADDITIONAL CONSIDERATIONS 
N/A 
 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
Table 9. Abbreviations and Special Terms 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Council on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 

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MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
THANC 
Thyroid Head and Neck Cancer 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
 
Table 10. Protocol Amendment History 
Version 
Date 
Description of Change  
Brief Rationale 
2.0 
3/10/2020 
Title 
SoA 
Endpoints: added IMAGE-HN, EORTC 
Inclusion Criteria: added cutaneous 
and salivary gland 
Sample Size: up to 48 
Grammar 
Harmonize w/ eCRF 
Novel measures 
Inclusively target population 
 
Revised effect size of AC 
3.0 
8/9/20 
Investigator signature page 
 
Screening, recruitment, and 
informed consent 
Change of study team 
 
COVID-19 related changes to 
clinic workflow necessitating 
telemedicine recruitment and 
electronic informed consent 
4.0 
10/1/21 
Sample size to 52 
 
 
 
clarify certain exclusion criteria 
should have been described as 
criteria for study discontinuation 
Larger than expected 
proportion of patients meeting 
criteria for study 
discontinuation due to cancer 
recurrence/2nd cancers 
 
Recognition that 
inclusion/exclusion criteria are 
determined at the time of 
accrual 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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