A Multi-Site, Parallel-Group, Randomized Clinical Trial Comparing a Brief Tele-Cognitive Behavioral Therapy Intervention (BRIGHT) With Attention Control for the Reduction of Body Image-Related Distress Among Head and Neck Cancer Survivors
Phase: NA
Conditions: Head and Neck Cancer, Body Image Disturbance, Body Image, Survivorship, Psychosocial Impairment, Mental Health Issue
Sponsor: Medical University of South Carolina

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
 
 
a
A Multi-Site, Parallel-Group, Randomized Clinical 
Trial Comparing a Brief Tele-Cognitive Behavioral 
Therapy Intervention (BRIGHT) with Attention 
Control for the Reduction of Body Image-Related 
Distress Among Head and Neck Cancer Survivors 
 
Protocol Number: 103733 
 
National Clinical Trial (NCT) Identified Number: NCT 05442957 
 
Principal Investigator: Evan Graboyes, M.D., M.P.H., FACS 
 
Sponsor: National Cancer Institute 
 
Grant Title: A Randomized Controlled Trial to Evaluate a Novel Treatment 
Strategy for Body Image-Related Distress Among Head and Neck Cancer 
Survivors 
 
Grant Number: R37 CA269385 
 
Funded by: NCI 
 
Version Number:  v.3.0 (8 February, 2023) 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
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recipient that no unpublished information contained herein will be published or disclosed without prior 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 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
3 
PROTOCOL VERSION HISTORY 
 
1.2 Schema: Updated to reflect changes to stratification variables for randomization (see 6.3 below) and 
more clearly illustrate study endpoints. 
 
1.3 Schedule of Activities: Corrected erroneous omission of intervention session 6 from Schedule of 
Activities in Protocol v2.0 (8 December 2022). Addressed downstream ramifications to other aspects of 
the Schedule of Activities created by adding a column for intervention session 6. 
 
5.4 Screen Failures: Clarified definition of screen failure and circumstances for re-screening. 
 
6.2 Fidelity: Changed from 20% of sessions to 17% of sessions to harmonize with prior change from 5 to 
6 intervention sessions. 
 
6.3 Measures to Minimize Bias: Randomization and Blinding: Added free flap reconstruction (yes/no) 
as stratification variable for randomization. Protocol harmonized in sections 1.2 (Schema), 4.1 (Overall 
Design) and 9.4.2 (Analysis of Primary Endpoint). Clarified blinding of investigators, patients, and 
outcome assessors. 
   
8.2 Baseline Assessments: Added baseline patient self-report assessment of history of medication or 
counseling for mental health disorders (Y/N). 
 
8.3 Endpoint and other Non-Safety Assessments: Added information about scoring all PROMIS 
measures using the T-distribution. Provided additional details about fidelity assessments. 
 
8.4 Adverse Events and Serious Adverse Events: Updated definition of adverse events to align with best 
practices for psychological clinical trials. Provided additional detail about methods of collecting adverse 
event data. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
4 
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 .................................................................................................................................................. 11 
1.3 
Schedule of Activities ............................................................................................................................ 12 
2 
INTRODUCTION ............................................................................................................................................... 14 
2.1 
Study Rationale ..................................................................................................................................... 14 
2.2 
Background ........................................................................................................................................... 14 
2.2.1 
Prevalence of BID Among HNC Survivors ......................................................................... 14 
2.2.2 
Consequences of BID Among HNC Survivors .................................................................... 15 
2.2.3 
Longitudinal Course of BID Among HNC Survivors ........................................................... 15 
2.2.4 
Prior Interventions to Manage BID Among HNC Survivors............................................... 16 
2.2.5 
Rationale for a CBT-Based Approach to Manage HNC-Related BID ................................. 16 
2.2.6 
Mechanism of Change Underlying CBT for BID ................................................................ 16 
2.2.7 
Rationale for Telemedicine Delivery Platform .................................................................. 17 
2.2.8 
Development of BRIGHT ................................................................................................... 17 
2.2.9 
Feasibility and Acceptability of BRIGHT ............................................................................ 18 
2.2.10 
Preliminary Effect of BRIGHT on BID ................................................................................ 19 
2.2.11 
Preliminary Effect of BRIGHT on Other Psychosocial Outcomes and QOL ....................... 20 
2.2.12 
Preliminary Mechanism of BRIGHT ................................................................................... 21 
2.3 
Risk/Benefit Assessment....................................................................................................................... 21 
2.3.1 
Known Potential Risks ....................................................................................................... 21 
2.3.2 
Known Potential Benefits ................................................................................................. 22 
2.3.3 
Assessment of Potential Risks and Benefits ..................................................................... 22 
3 
OBJECTIVES AND ENDPOINTS .......................................................................................................................... 26 
4 
STUDY DESIGN ................................................................................................................................................. 27 
4.1 
Overall Design ....................................................................................................................................... 27 
4.2 
Scientific Rationale for Study Design .................................................................................................... 27 
4.3 
Justification for Intervention ................................................................................................................ 27 
4.3.1 
Justification for the Mode of Delivery .............................................................................. 27 
4.3.2 
Justification for the Nubmber, Frequency, and Timing of Intervention Contacts............ 28 
4.4 
End-of-Study Definition ........................................................................................................................ 28 
5 
STUDY POPULATION ........................................................................................................................................ 28 
5.1 
Inclusion Criteria ................................................................................................................................... 28 
5.2 
Exclusion Criteria .................................................................................................................................. 29 
5.3 
Lifestyle Considerations ........................................................................................................................ 29 
5.4 
Screen Failures ...................................................................................................................................... 29 
5.5 
Strategies for Recruitment and Retention ........................................................................................... 29 
5.5.1 
Anticipated Screening and Accrual Targets ...................................................................... 29 
5.5.2 
Anticipated Accrual Rate and Accrual Feasibility ............................................................. 30 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
5 
5.5.3 
Planned Screening and Recruitment Strategies ............................................................... 30 
5.5.4 
Strategies to Enhnace Retention ...................................................................................... 31 
5.5.5 
Retention Feasibility ......................................................................................................... 32 
5.5.6 
Participant Compensation ................................................................................................ 32 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ................................................................. 32 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ............................................. 32 
6.1.1 
Study Intervention Description ......................................................................................... 32 
6.1.2 
Administration and/or Dosing .......................................................................................... 34 
6.2 
Fidelity................................................................................................................................................... 35 
6.2.1 
Interventionist Training .................................................................................................... 35 
6.2.2 
Intervention Fidelity .......................................................................................................... 35 
6.3 
Measures to Minimize Bias: Randomization and Blinding ................................................................... 35 
6.4 
Study Intervention Adherence ............................................................................................................. 36 
6.5 
Concomitant Therapy ........................................................................................................................... 36 
6.5.1 
Rescue Therapy ................................................................................................................. 36 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL ............. 36 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ................................................... 36 
7.2 
Participant Discontinuation/Withdrawal from the Study .................................................................... 37 
7.3 
Lost to Follow-Up .................................................................................................................................. 37 
8 
STUDY ASSESSMENTS AND PROCEDURES ....................................................................................................... 37 
8.1 
Screening Procedures ........................................................................................................................... 37 
8.2 
Baseline Assessments ........................................................................................................................... 38 
8.2.1 
Demographic ..................................................................................................................... 38 
8.2.2 
Clinical and Oncologic ....................................................................................................... 38 
8.3 
Endpoint and Other Non-Safety Assessments...................................................................................... 38 
8.3.1 
Efficacy………. ..................................................................................................................... 38 
8.3.2 
Mechanism ........................................................................................................................ 40 
8.3.3 
Intervention Fidelity .......................................................................................................... 40 
8.3.4 
Participant Adherence ...................................................................................................... 41 
8.4 
Adverse Events and Serious Adverse Events ........................................................................................ 41 
8.4.1 
Definition of Adverse Events............................................................................................. 41 
8.4.2 
Definition of Serious Adverse Events ................................................................................ 41 
8.4.3 
Classification of an Adverse Event .................................................................................... 41 
8.4.4 
Time Period and Frequency for Event Assessment and Follow-Up .................................. 42 
8.4.5 
Adverse Event Reporting .................................................................................................. 42 
8.4.6 
Serious Adverse Event Reporting...................................................................................... 42 
8.4.7 
Reporting Events to Participants ...................................................................................... 42 
8.4.8 
Events of Special Interest .................................................................................................. 43 
8.4.9 
Reporting of Pregnancy .................................................................................................... 43 
8.5 
Unanticipated Problems ....................................................................................................................... 43 
8.5.1 
Definition of Unanticipated Problems .............................................................................. 43 
8.5.2 
Unanticipated Problems Reporting .................................................................................. 43 
8.5.3 
Reporting Unanticipated Problems to Participants .......................................................... 43 
9 
STATISTICAL CONSIDERATIONS ....................................................................................................................... 43 
9.1 
Statistical Hypothesis ............................................................................................................................ 43 
9.2 
Sample Size Determination .................................................................................................................. 44 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
6 
9.3 
Populations for Analyses ...................................................................................................................... 44 
9.4 
Statistical Analyses................................................................................................................................ 45 
9.4.1 
Missing Data ...................................................................................................................... 45 
9.4.2 
Analysis of the Primary Endpoint ...................................................................................... 45 
9.4.3 
Analysis of Secondary Endpoints ...................................................................................... 46 
9.4.4 
Safety Analyses ................................................................................................................. 47 
9.4.5 
Planned Intermin Analyses ............................................................................................... 47 
9.4.6 
Sub-group Analyses ........................................................................................................... 47 
9.4.7 
Exploratory Analyses ......................................................................................................... 48 
9.5 
Regulatory, Ethical, and Study Oversight Considerations .................................................................... 48 
9.5.1 
Single IRB Coordination .................................................................................................... 48 
9.5.2 
Informed Consent Process ................................................................................................ 49 
9.5.3 
Study Discontinuation and Closure ................................................................................... 50 
9.5.4 
Confidentiality and Privacy ............................................................................................... 50 
9.5.5 
Future Use of Stored Specimens and Data ....................................................................... 51 
9.5.6 
Key Roles and Study Governance ..................................................................................... 51 
9.5.7 
Safety Oversight ................................................................................................................ 52 
9.5.8 
Clinical Monitoring ............................................................................................................ 52 
9.5.9 
Quality Assurance and Quality Control ............................................................................. 52 
9.5.10 
Data Handling and Record Keeping .................................................................................. 52 
9.5.11 
Protocol Deviations ........................................................................................................... 53 
9.5.12 
Publication and Data Sharing Policy ................................................................................. 53 
9.5.13 
Conflict of Interest Policy .................................................................................................. 53 
9.6 
Additional Considerations .................................................................................................................... 53 
9.7 
Abbreviations and Special Terms ......................................................................................................... 53 
9.8 
Protocol Amendment History ............................................................................................................... 56 
10 
REFERENCES ..................................................................................................................................................... 57 
 
 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
7 
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 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
8 
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: 
 
7/13/22 
 
 
Name: Evan Graboyes 
Title: A Multi-Site, Parallel-Group, Randomized Clinical Trial Comparing a Brief Tele-
Cognitive Behavioral Therapy Intervention (BRIGHT) with Attention Control for the 
Reduction of Body Image-Related Distress Among Head and Neck Cancer Survivors 
 
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: 
Elizabeth Hill, PhD 
Ken Ruggiero, PhD 
Katherine Sterba, PhD, MPH 
Sidharth Puram, MD, PhD 
Steven Chang, MD (site PI at Henry Ford) 
Patrik Pipkorn, MD, MSCI (site PI at Washington University in St. Louis) 
 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
9 
1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
 
Title: 
A Multi-Site, Parallel-Group, Randomized Clinical Trial Comparing a Brief 
Tele-Cognitive Behavioral Therapy Intervention (BRIGHT) with Attention 
Control for the Reduction of Body Image-Related Distress Among Head 
and Neck Cancer Survivors 
Grant Number: 
R37 CA269385 
Study Description: 
In this multi-site, parallel-group, randomized clinical trial, we will evaluate 
the efficacy of BRIGHT compared with attention control (AC) for managing 
body image distress (BID) among head and neck cancer survivors (HNC) 
survivors, examine BRIGHT’s underlying mechanisms, and characterize 
factors affecting the future adoption of BRIGHT into clinical care. 
 
Objectives: 
Primary Objective: 
To evaluate the efficacy of BRIGHT compared with AC on HNC-related BID 
as measured by change from baseline in the IMAGE-HN score. 
 
Secondary Objectives:  
1. To evaluate the clinical response rate of BRIGHT compared with AC on 
HNC-related BID as measured by proportion of patients with a clinically 
meaningful change from baseline in the IMAGE-HN score. 
 
2. To further evaluate the longer-term efficacy of BRIGHT compared with 
AC on HNC-related BID as measured by change from baseline in the 
IMAGE-HN score at 9-month follow-up (post-randomization). 
 
3. To evaluate the efficacy of BRIGHT compared with AC on psychological 
and social well-being as measured by change from baseline in Shame and 
Stigma Scale in HNC, PROMIS SF v1.0-Depression 8a, PROMIS SF v1.0-
Anxiety 8a, Beck Scale for Suicidal Ideation, and PROMIS SF v2.0-Ability to 
Participate in Social Activities-8a scores at 3-, 6-, and 9-month follow-up. 
 
4. To evaluate the efficacy of BRIGHT compared with AC on quality of life 
(QOL) as measured by change from baseline in the EORTC QLQ-HN35 
score at 3-, 6-, and 9-month follow-up. 
 
5. To examine the mechanism of change underlying BRIGHT for HNC-
related BID as measured by change from baseline in Body Image Coping 
Strategies Inventory subscale scores and the Automatic Thoughts 
Questionnaire score. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
10 
 
Endpoints: 
 
Primary Endpoint: 
Change in the IMAGE-HN score from baseline to 6-month follow-up 
 
Select Secondary Endpoints: 
1. Change in the IMAGE-HN score from baseline to 2-, 3- and 9-month 
follow-up 
 
2. Proportion of patients with a decrease in the IMAGE-HN score of > 9 
points from baseline at 3-, 6-, and 9-month follow-up 
 
3. Change in the Shame and Stigma Scale in HNC score from baseline to 3-, 
6-, and 9-month follow-up 
 
4. Change in the PROMIS SF v1.0-Depression 8a score from baseline to 3-, 
6-, and 9-month follow-up 
 
5. Change in the PROMIS SF v1.0-Anxiety 8a score from baseline to 3-, 6-, 
and 9-month follow-up 
 
6. Change in the Body Image Coping Strategies Inventory Avoidance, 
Positive Rational Acceptance, and Appearance Fixing subscale scores from 
baseline to 2, 3-, and 6-month follow-up  
 
Study Population: 
The study population will consist of adult HNC survivors with HNC-related 
BID 
Phase or Stage: 
N/A 
Description of 
Sites/Facilities Enrolling 
Participants: 
 
The study will be conducted, and participants enrolled, at three sites: (1) 
the Medical University of South Carolina (MUSC), (2) Henry Ford Health, 
and (3) Washington University in St. Louis 
Description of Study 
Intervention/Experimental 
Manipulation: 
BRIGHT is 6 sessions of weekly, 60-minute, manualized individual tele-
cognitive behavioral therapy based on a transactional coping model of 
HNC-related BID 
Study Duration: 
49 months 
Participant Duration: 
9 months 
 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
11 
1.2 
SCHEMA   
 
 
Fig 1. Schema. In this multisite RCT, HNC survivors with clinically significant HNC-related BID (N=180) from 
the Medical University of South Carolina (MUSC), Washington University School of Medicine (WUSM), and 
Henry Ford Health (HFH) will be randomized 1:1 to BRIGHT or AC with randomization stratified by site 
(MUSC, WUSM, HFH). Patients will complete measures of HNC-related BID (primary endpoint), 
psychological and social well-being, and mechanisms of change underlying CBT at 2, 3, 6, and 9-month 
follow-up (post-randomization) to assess the effect of BRIGHT on BID, psychological and social well-being 
and quality of life, and mechanism of change underlying BRIGHT. 
Eligibility
AC (n=90)
Primary Endpoint:  IMAGE-HN (6m)
Secondary Endpoints:
-Depression, Anxiety, Suicidal Ideation
-Social Isolation, Shame/Stigma, QOL
-Body Image Coping Strategies
• Hx of HNC (UADT, salivary, skin)
• Tx w/ surgery +/- adjuvant
• Completed tx 6 wks-12 mos
• English-speaking
• IMAGE-HN > 22
Follow-up (2, 3, 6, 9m)
tele-survivorship education
(1 hr/wk x 6 wks)
BRIGHT (n=90)
tele-CBT
(1 hr/wk x 6 wks)
RANDOMIZE 1:1*
* Stratified by trial site, recon

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
12 
1.3 
SCHEDULE OF ACTIVITIES  
Table 1. Schedule of Activities for BRIGHT and AC:  Screening, Treatment, and Follow-up 
Study Period 
Screening 
Allocation 
Treatment 
Follow-upb 
For Details 
Visit Label 
Session 
2 
m 
3 
m 
6 
m 
9 
m 
1 
2 
3 
4 
5 
6 
Visit # 
1a 
-- 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
Study Activity 
Enrollment Eligibility Screenc 
X 
 
 
 
 
 
 
 
 
 
 
 
5 
Informed Consentd 
X 
 
 
 
 
 
 
 
 
 
 
 
9.5.2 
Allocation 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Study 
Intervention 
BRIGHT 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
6.1.1 
AC 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
6.1.2 
Study Assessments 
Baseline 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
8.2 
Clinical and Oncologic 
X 
 
 
 
 
 
 
 
 
 
 
Safety 
Adverse Events 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
8.4 
Concomitant 
Meds 
Medication Assessment 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
6.5 
Efficacye 
IMAGE-HN 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
8.3.1 
Shame and Stigma Scale 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
PROMIS SF v1.0-
Depression 8a 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
PROMIS SF v1.0-Anxiety  
8a 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
Beck Scale for Suicidal 
Ideationf 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
PROMIS SF v2.0-Social 
Activitites-8a 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
EORTC QLQ-HN35 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
Mechanism BICSI 
X 
 
 
 
 
 
 
 
X 
X 
X 
 
8.3.2 
 
Automatic Thoughts 
Questionnaire 
X 
 
 
 
 
 
 
 
X 
X 
X 
 
Intervention 
Fidelity 
BRIGHT Fidelity and 
Competence Scale 
 
 
 
 
 
 
 
 
X 
 
 
 
8.3.3 
Interventionist self-report 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
Patient 
Adherence 
Attendance, Homework 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
8.3.4  
Common 
Factors 
WAI-SR-Therapist 
 
 
 
 
 
 
 
X 
 
 
 
 
8.3.3 
Therapist Empathy Scale 
 
 
 
 
 
 
 
X 
 
 
 
 
Credibility/Expectancy 
Questionnaire 
X 
 
 
 
 
 
 
X 
 
 
 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
13 
 
 
 
 
Table 1. Schedule of Activities for BRIGHT and AC:  Screening, Treatment, and Follow-up 
Study Period 
Screening 
Allocation 
Treatment 
Follow-upb 
For Details 
Visit Label 
Session 
2 
m 
3 
m 
6 
m 
9 
m 
1 
2 
3 
4 
5 
6 
Visit # 
1a 
-- 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
a: Every effort should be made to minimize the time between randomization and starting treatment 
b: Study assessments are determined based on time since randomization. Follow-up study assessments 
should be completed +/-1 week from the indicated timing. 
c: Eligibility assessed using information in the electronic health record as well as a screening IMAGE-HN 
d: Written informed consent and HIPAA must be obtained prior to performing and protocol-specific 
procedures, including baseline evaluations. 
e: 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, text message, 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. 
f: Beck suicidality scale requires the program coordinator to monitor responses for suicidality via REDCap-
based alert system and address accordingly as outlined in section 2.3.3. 
Abbreviations:  AC: Attention Control; AE: Adverse Event; BICSI: Body Image Coping Strategies Inventory; 
BRIGHT: Building a Renewed ImaGe after Head & neck cancer Treatment; EORTC: European Organisation 
for Research and Treatment of Cancer; IMAGE-HN: Inventory to Measure and Assess imaGe disturbancE-
Head & Neck; PROMIS: Patient-Reported Outcome Measurement Inventory System; WAI-SR: Working 
Alliance Inventory-Short Revised 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
14 
2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
Head and neck cancer (HNC) results in substantial life-altering morbidity related to disfigurement, 
difficulty swallowing, impaired smiling, and challenges speaking.1,2 As a result, 75% of HNC survivors 
express body image concerns3 and 28% meet criteria for body image-related distress (BID).4 BID is a 
source of devastating psychosocial morbidity and functional impairment for HNC survivors, contributing 
to a six-fold increase in depression, high rates of social isolation, and decreased quality of life (QOL).4-9 
Due in part to BID, HNC survivors have a 2-fold higher rate of suicide mortality relative to other cancer 
survivors and a 4-fold higher rate than the general population.10 Although it is critical that HNC survivors 
with BID have access to evidence-based care, a recent national survey found that management of BID 
was the single most commonly omitted component of HNC survivorship care.11 Among HNC survivors 
with BID, trials evaluating interventions to conceal disfigurement12,13 and improve self-compassion14 
showed that these strategies were ineffective. To date, theoretically grounded, evidence-based 
strategies to manage HNC-related BID are lacking.15 
 
To address this gap, we developed BRIGHT (Building a Renewed ImaGe after Head & neck cancer 
Treatment),16 a 6-session manualized tele-cognitive behavioral therapy (CBT) based on a transactional 
coping17 model of HNC-related BID. Findings from our single-arm16 and pilot randomized clinical trial 
(RCT) showed that BRIGHT was feasible, acceptable, and resulted in a statistically and clinically 
significant reduction in BID relative to dose- and delivery-matched attention controls (ACs) at 1- and 3-
month post-intervention follow-up. There is consensus that evidence-based psychotherapy should be 
supported by theory-based mechanisms of change;18,19 however, a gap remains in our understanding of 
mechanisms of change underlying CBT for BID.20-24 Preliminary data suggest that BRIGHT reduces HNC-
related BID by enhancing adaptive body image coping skills (reducing avoidance, increasing positive 
rational acceptance [i.e. rational appearance related self-talk]).16 These promising data support further 
evaluation of BRIGHT’s efficacy and mechanism in a large-scale RCT. Finally, recognizing the chronic 
evidence-to-practice gap that limits the delivery of psychosocial care to cancer survivors,25 it is 
imperative that we concurrently identify strategies to enhance the future adoption of BRIGHT into 
routine care. 
 
Herein we extend our initial research with a multisite, parallel-group, RCT we will evaluate the efficacy 
of BRIGHT compared with AC for managing BID among HNC survivors, examine BRIGHT’s underlying 
mechanisms, and characterize factors affecting the future adoption of BRIGHT into clinical care. HNC 
survivors with clinically significant HNC-related BID4 (N=180) will be randomized to BRIGHT or AC, a 
manualized tele-supportive care intervention that controls for professional attention, dose, delivery 
method, and common factors (alliance, empathy, expectations).26 HNC survivors will complete the 
Inventory to Measure and Assess imaGe disturbancE14-Head & Neck (IMAGE-HN; a valid measure of 
HNC-related BID27), measures of psychological and social well-being and QOL, and measures of theory-
derived mechanisms of change underlying BRIGHT at 2-, 3-, 6-, and 9-months post randomization. We 
will conduct semi-structured interviews and in-depth site visits to develop an implementation toolkit to 
enhance the adoption of BRIGHT into clinical care. 
2.2 
BACKGROUND 
2.2.1 PREVALENCE OF BID AMONG HNC SURVIVORS 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
15 
There are nearly 500,000 HNC survivors in the US28 and this population is growing exponentially.29 
Standard of care treatment involves combinations of surgery, radiation, and chemotherapy to 
cosmetically and functionally critical areas such as the face, lips, tongue, teeth, jaw, and throat. As a 
result, treatment results in substantial life-altering morbidity related to facial disfigurement, difficulty 
swallowing, impaired smiling, and challenges speaking.1 These treatment-related toxicities occur in 
highly visible, socially significant parts of the body and limit basic daily activities such as eating, engaging 
in conversation, being understood by others, and participating in social interactions.5-7 As a result of 
these impairments in communication, interpersonal relationships, and self-concept, 75% of HNC 
survivors express body image concerns3 and 20-28% have clinically significant BID.4,30 
2.2.2 CONSEQUENCES OF BID AMONG HNC SURVIVORS 
HNC survivors with BID suffer devastating psychosocial morbidity and reduced QOL.5-7 Relative to HNC 
survivors without BID, those with BID have a six-fold increase in moderate-severe depressive symptoms 
and an eight-fold increase in moderate-severe anxiety symptoms.4 HNC-related BID also drives 
impairments in social and relationship functioning by increasing social anxiety, social isolation, and 
feelings of stigmatization.31 In addition, HNC-related BID exacerbates financial toxicity, as HNC survivors 
with BID are more likely to discontinue employment and be unemployed or on disability.8,9 Finally, due 
in part to BID, HNC survivors have a 2-fold higher rate of suicide mortality relative to other cancer 
survivors and a 4-fold higher rate than the general population.10 BID among HNC survivors is common, 
causes significant psychosocial morbidity, and is a key contributor to decreased QOL; treatment for BID 
should be widely available to HNC survivors. 
2.2.3 LONGITUDINAL COURSE OF BID AMONG HNC SURVIVORS 
Most studies of BID among HNC survivors have either been cross-sectional6,32-36 or included only short-
term follow-up.37,38 In one prospective cohort study using a purposive sample of 68 patients with HNC, 
patients completed the Body Image Scale39 pretreatment and 1, 3, 6, 9, and 12-months post-treatment. 
Change in Body Image Scale score (higher score indicates worse BID) relative to pretreatment were 
analyzed with a linear mixed 
model. 43% of patients had 
persistently elevated Body 
Image Scale score 9-months 
after HNC treatment.40 In this 
subset of patients, the mean 
change in Body Image Scale 
score remained elevated at all 
timepoints for the first year 
post-treatment 
relative 
to 
baseline (Figure 2).40 These 
findings suggest that nearly 
four in ten HNC survivors 
experience BID that persists 
for at least 1 year post-
treatment 
without 
any 
spontaneous improvement.40 
 
Fig 2. Temporal Trajectory of BID Among HNC Survivors. Changes in 
the severity of BID (as determined by the mean change in Body Image 
Scale score at each post-treatment time point relative to baseline, 
stratified by those with or without persistent elevation of Body Image 
Scale scores at 9 months post-treatment. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
16 
2.2.4 PRIOR INTERVENTIONS TO MANAGE BID AMONG HNC SURVIVORS 
Evidence-based strategies to manage BID among HNC survivors are lacking.5 To date, three trials have 
evaluated different strategies to manage HNC-related BID. Huang et al. showed that a cosmetic 
rehabilitation intervention did not improve BID among HNC survivors relative to control (p>0.05).12 An 
RCT by Chen et al. evaluating a skin camouflage program among HNC survivors found no benefit relative 
to usual care (p=0.56).13 Finally, a single-arm pre-post study showed that MyChangedBody (MyCB), a 
web-based self-compassion expressive writing activity, failed to improve HNC-related BID (p=0.73).14 
The lack of efficacy of MyCB among HNC survivors with BID is important because MyCB improved BID 
among breast cancer survivors in a large RCT (N=304) relative to control (p=0.035).41 These trials (1) 
reinforce the need to develop effective strategies to improve BID among HNC survivors and (2) motivate 
shifting the paradigm away from concealing disfigurement and enhancing self-compassion in favor of a 
fundamentally different approach that addresses the causal mechanisms underlying BID among HNC 
survivors. 
2.2.5 RATIONALE FOR A CBT-BASED APPROACH TO MANAGE HNC-RELATED BID 
CBT is a promising approach to manage HNC-related BID. Multiple meta-analyses have demonstrated 
that CBT produces durable reductions in BID in patients without visible disfigurement (e.g., eating 
disorders, body dysmorphic disorder).42-45 However, the evidence base supporting CBT for BID in 
patients with visible disfigurement is much weaker.46-48 Whereas some studies have suggested that CBT 
may reduce BID among patients with disfigurement (e.g., facial burns, craniofacial disorders, breast 
cancer),49-52 two recent systematic reviews noted significant methodologic limitations in these studies 
including small sample size, non-randomized allocation, and comparison to waitlist control.53,54 These 
findings underscore the need for rigorous trials evaluating the efficacy of CBT as novel paradigm to 
manage BID for HNC survivors. 
 
Operating within David’s integrative cognitive psychology model of human feelings and behaviors,19 we 
conceptualize HNC-related BID according to Folkman’s transactional theory of stress and coping.17,24,46,55 
According to our model, when a HNC survivor is confronted with a body image stimulus that may result 
in distress such as being invited to eat dinner with a friend at a restaurant, she attends to the stimulus, 
appraises it via automatic thoughts related to body image self-evaluation, and generates body image-
related emotional, cognitive, and behavioral responses. When the body image response is negative, the 
HNC survivor utilizes a body image coping strategy to regulate the distress. Based on work by our team56 
and others,24,46 the underlying mechanisms causing HNC-related BID are (1) unhelpful automatic 
thoughts and (2) maladaptive body image coping skills. In our example, a HNC survivor with BID may 
have an unhelpful automatic thought that everyone at the restaurant will notice and react negatively to 
her asymmetric face and drooling (e.g., a cognitive distortion of fortune-telling). A HNC survivor may 
attempt to cope with this stressor using a maladaptive body image coping strategy of avoidance and 
stay at home instead of going to eat at the restaurant with her friend. Together unhelpful automatic 
thoughts and maladaptive body image coping strategies initiate and maintain HNC-related BID. HNC 
survivors are unique in their experience of disfigurement and function-related impairment that is 
noticed and reacted to negatively by others through actions such as staring.56,57 Thus for HNC survivors, 
the experience of distressing body image-related emotions is based in part in reality instead of being 
driven solely by unhelpful automatic thoughts, the dominant causal mechanism for patients with BID 
and no visible disfigurement.24 As a result, a CBT paradigm for HNC survivors with BID should target 
body image coping skills in addition to unhelpful automatic body image thoughts. 
2.2.6 MECHANISM OF CHANGE UNDERLYING CBT FOR BID 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
17 
The mechanisms of change underlying CBT for BID are poorly characterized. As interventions to manage 
HNC-related BID are developed, it is essential to evaluate the underlying theoretical mechanism of 
change to (1) avoid pseudoscientific interventions, (2) optimize the effectiveness of treatment, and (3) 
advance the science of CBT broadly by identifying psychological factors involved in pathology and health 
which the therapeutic package targets.18,19 Although CBT is effective at managing BID,42-45 very little is 
known about underlying theory-based mechanisms of change, particularly among patients with visible 
disfigurement.24 Many trials evaluating CBT for BID among patients with disfigurement have not been 
theory-driven and thus did not evaluate the mechanisms of change at all.49-52 Limited correlational and 
clinical trial data suggest that CBT for BID (1) enhances adaptive body image coping strategies such as 
positive rational acceptance (i.e., rational appearance related self-talk) and (2) decreases maladaptive 
body image coping strategies such as avoidant coping.46,48,58-61 However, these studies are limited by the 
absence of underlying theory, small sample size, unclear temporal precedence of the mediator, and lack 
of formal mediation analyses. Furthermore, they fail to evaluate mechanisms of change underlying 
various forms of CBT (e.g., automatic thoughts [cognitive therapy], unconditional self-acceptance 
[rational emotive behavioral therapy]).19,62 Collectively, these data show that our understanding of the 
role of body image coping strategies and theory-based mechanisms of change underlying CBT for BID 
remains extremely limited, and thus rigorous clinical trial theory18 testing is necessary. 
2.2.7 RATIONALE FOR TELEMEDICINE DELIVERY PLATFORM 
Cancer survivors face unique access-to-care barriers for face to face psychosocial care.63 For patients 
with HNC, travel burden (due to the regionalization of HNC care64,65) is a critical barrier to mental health 
care and contributes to excess morbidity and mortality.66,67 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 psychosocial interventions to HNC survivors are needed.68,69 Telemedicine is a 
promising solution because it decreases travel burden70, increases access to care71, and provides 
effective behavioral health interventions72 (including CBT63,73). 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.16 
2.2.8 DEVELOPMENT OF BRIGHT 
The lack of effective interventions to manage BID among HNC survivors12-14 and persistence of clinically 
significant BID40 confirm the need to develop novel strategies to manage BID. BRIGHT was developed 
using Intervention Mapping.74 We included extensive stakeholder engagement; N=22 HNC survivors 
completed semi-structured interviews to inform the content of BRIGHT.56 Patients in our cohort study37 
also completed a quantitative needs assessment to inform the delivery of BRIGHT. BRIGHT is situated 
within a cognitive psychology perspective19 of BID and conceptualizes HNC-related BID according to 
Folkman’s transactional theory of stress and coping.17,24,46,55 Our qualitative work identified key domains 
of HNC-related BID that informed the content of BRIGHT: personal dissatisfaction with appearance, 
other-oriented appearance concerns, distress with functional impairments, and social avoidance.56 
Stakeholder feedback from HNC survivors and clinicians helped define BRIGHT’s timing (early post-
treatment), setting (one-on-one therapy), duration (limited number of sessions), and delivery method 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
18 
(telemedicine). Our conceptual model of BRIGHT is shown in Figure 3. 
2.2.9 FEASIBILITY AND ACCEPTABILITY OF BRIGHT 
Feasibility and acceptability of 
BRIGHT was initially evaluated 
in our 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).16 
 
Feasibility and acceptability of 
BRIGHT were subsequently 
evaluated in our single-site 
pilot RCT (NCT03831100).  Of 
the 252 patients screened over 
a 17-month period, 24.6% 
(n=62) met eligibility criteria 
and 87% (n=54) of eligible 
patients accrued to the trial. 
Six percent of randomized 
patients (n=3) dropped out of 
the study and 13% (n=7) went 
off study per protocol after developing a recurrence or new primary cancer. The remaining 82% of 
patients (n=44) completed BRIGHT or AC as  allocated, of whom 96% (42/44) completed follow-up 
assessments as 1-week and 100% (44/44) completed assessments at 1-month and 3-months post-
intervention (0% lost to follow-up). 
 
 
Table 2. BRIGHT Feasibility and Acceptability: Single-arm pilot trial 
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) 
Tablet returned to study team after BRIGHT, n (%) 
10 (100) 
Study dropout, n (%) 
1 (10) 
Acceptability to Patients (Program Evaluation) 
Mean (SD)a 
How well did the timing of the program work for you? 
4.4 (0.7) 
How well did the method of program delivery work?  
4.7 (0.5) 
How well did the number of sessions work for you? 
4.6 (0.5) 
How relevant was the content of each session? 
4.6 (0.3) 
Session 1 
4.1 (1.3) 
Session 2 
4.4 (0.7) 
Session 3 
4.6 (0.5) 
Session 4 
4.9 (0.3) 
Session 5 
4.8 (0.4) 
How likely are you to recommend BRIGHT? 
4.9 (0.3) 
aScale 0-5; higher score indicates greater satisfaction. 
Fig 3. Conceptual Model of BRIGHT. BRIGHT is a cognitive therapy whose therapeutic package 
(cognitive restructuring of dysfunctional body image thoughts,  body image coping skills training [gray 
box]) targets the underlying theory-based mechanism of the disorder (unhelpful automatic thoughts 
related to body image, maladaptive body image coping strategies; mechanisms of change [white box]), 
thereby decreasing BID and downstream psychosocial morbidity (clinical outcomes [teal box]). 
BRIGHT
-Cognitive Restructuring
-Disfigurement
-Functional Impairment
-Body Image Coping
Skills Training
Mechanism of Change
Unhelpful Automatic 
Thoughts
Body Image Coping 
Skills 
Positive Rational
Acceptance
Avoidant Coping
Secondary: 
Depression
Anxiety
Shame/Stigma
Social Isolation
Suicidal Ideation 
Quality of Life
Primary:
Body Image
Related
Distress
Outcomes

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
19 
Patients in BRIGHT rated the timing 
of the intervention relative to HNC 
treatment, method of delivery, 
content, workbook, homework, and 
relevance of the material highly (all 
mean > 4/5/5) (Table 3). Overall, 
75% of patients (15/20) reported 
that they were highly likely to 
recommend BRIGHT to other HNC 
survivors with BID. 
 
 
 
 
 
 
 
2.2.10 PRELIMINARY EFFECT OF BRIGHT ON BID 
In our single-arm pilot trial, BRIGHT 
demonstrated high levels of clinical activity at 
reducing BID among HNC survivors.16 Eighty-nine 
percent of participants (8/9) experienced a 
decrease in their Body Image Scale score from 
baseline to 1-month post-BRIGHT.16 The clinical 
effect of BRIGHT on BID was large (Figure 4); 
BRIGHT was associated with a mean decrease of 
4.56 in the BIS score from baseline to 1-month 
post intervention (95% CI 1.55, 7.56).16 This 
clinical effect on BID persisted at 3 months post-
BRIGHT relative to baseline (mean of the 
difference of the BIS score from baseline to 3-
months post = 3.56; 95% CI 1.15 to 5.96).16 
 
In a subsequent single-site pilot RCT comparing 
BRIGHT with dose and delivery-matched AC 
(survivorship video educational materials), 
BRIGHT showed continued efficacy at improving 
BID among HNC survivors.75 At 1-month post-
intervention, the mean change from baseline in 
the IMAGE-HN score was significantly improved 
for patients in BRIGHT compared with patients in 
AC (mean model-based difference in change in 
the IMAGE-HN score = -7.9 [90% CI, -15.9 to 0.0] points; P = 0.10).75 At 3-months post-intervention, 
BRIGHT improved the IMAGE-HN score from baseline relative to AC (mean model-based difference in 
change in IMAGE-HN score = -17.1 [90% CI, -25.6 to -8.6] points; P = 0.002).75 At 3 months post-
intervention, the improvement from baseline in the IMAGE-HN score for BRIGHT relative to AC was 
Table 3. BRIGHT Acceptability: Single-Site Pilot RCT 
Measure 
Mean (SD)a 
The timing of the program worked well for me. 
4.5 (0.8) 
The method of program delivery (telemedicine) 
worked well for me. 
4.5 (0.9) 
The number of sessions (5) worked well for me. 
4.2 (1.2) 
The content of each session was helpful to me. 
4.7 (0.6) 
The BRIGHT Workbook was useful to me. 
4.5 (0.7) 
The BRIGHT Homework assignments were useful. 
4.5 (0.6) 
The in-session activities were useful. 
4.8 (0.4) 
The material was relevant to my concerns. 
4.7 (0.9) 
Overall, I was satisfied with the BRIGHT Program. 
4.7 (0.5) 
I am likely to recommend BRIGHT to a different 
head and neck cancer survivor. 
4.7 (0.6) 
a Scores range from 0-5; higher values representing greater 
satisfaction or stronger agreement. 
Fig 4.  Decrease in the severity of BID (as 
determined by Body Image Scale scores) at 1- 
and 3-months post-BRIGHT relative to baseline. 
The mean Body Image Scale scores at baseline, 1-
month post, and 3-month post are 13.22, 8.67, 
and 9.76, respectively. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
20 
clinically significant and corresponded to a large effect size (Cohen’s d = -0.9 [90% CI, -1.4 to -0.4]).75 The 
longitudinal change in HNC-related BID, as measured by change in the IMAGE-HN score from baseline, 
for patients allocated to BRIGHT and AC is shown in Figure 5A.  
 
BRIGHT was effective at reducing HNC-related BID for the majority of patients. The waterfall plot 
demonstrating each patient’s clinical response to BRIGHT or AC, as measured by change in IMAGE-HN 
scores from baseline to 3-months post-intervention, is shown in Figure 5B. At 3-months post-
intervention, patients in BRIGHT had a 6.6-fold increase in the odds of clinical response (proportion of 
patients with a clinically meaningful decrease in IMAGE-HN scores of > 9) relative to patients in AC 
(model-based odds ratio [OR] = 6.6 [90% CI, 2.0 to 21.8]; p = 0.09).75 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.2.11 PRELIMINARY EFFECT OF BRIGHT ON OTHER PSYCHOSOCIAL OUTCOMES AND QOL 
In our single-arm pilot trial, BRIGHT was associated with improvements in psychosocial aspects of HNC-
related QOL in our single-arm pilot trial of BRIGHT.16 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 European Organisation for Research and Treatment of 
Cancer (EORTC) QLQHN35 (median trouble with social eating scores = 66.67, 45.83, and 25, at baseline, 
1-, and 3- months post-BRIGHT respectively; Figure 6).16 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).16 
Mean Change from Baseline and Response of Head and Neck Cancer (HNC)-Related Body Image 
Distress for Patients in BRIGHT and Attention Control 
Fig 5. A. Line graph demonstrating the mean change from baseline in IMAGE-HN scores over time by 
intervention allocation. Error bars represent 1 SE above and below the mean. B. Waterfall plot showing 
response to BRIGHT and Attention control, as measured by absolute change from baseline in IMAGE-HN 
scores at 3 months postintervention. IMAGE-HN scores range from 0 to 84, with higher scores indicating 
worse HNC-related BID (and negative bars thus indicating improvement in HNC-related BID). The dashed 
horizontal line at +/- 9 indicates a clinically meaningful change in IMAGE-HN score. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
21 
 
 
 
2.2.12 PRELIMINARY MECHANISM OF BRIGHT 
Preliminary data from our single-arm and pilot 
RCT suggest that BRIGHT decreased BID by 
enhancing body image coping strategies. 
During semi-structured interviews, HNC 
survivors from our single-arm trial described 
how BRIGHT decreased HNC-related BID by 
improving body image coping skills (Table 4).16 
Preliminary analysis of pilot RCT data showed 
that the treatment effect of BRIGHT on BID 
was mediated by enhancing adaptive body 
image coping skills such as positive rational 
acceptance (indirect effect = -0.96; 95% CI -
4.79 to 1.24) and decreasing maladaptive body 
image coping skills such as avoidance (indirect 
effect 3.91; 95% CI -0.50 to 9.93). Although the 
quantitative analyses are exploratory and underpowered to detect a causal mediation relationship, 
these data suggest that (1) BRIGHT enhances adaptive body image coping skills and (2) these 
improvements in body image coping skills mediate improvements in HNC-related BID. In the pilot RCT, 
therapeutic alliance between the patient and BRIGHT therapist was not correlated with change in 
IMAGE-HN score from baseline to 3-months post-intervention (r= -0.06; p=0.77 for Working Alliance 
Inventory-Short Revised (WAI-SR) Client76).  
2.3 
RISK/BENEFIT ASSESSMENT  
2.3.1 KNOWN POTENTIAL RISKS  
Fig. 6. 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 scores) at 1- and 3-months post-BRIGHT relative to baseline 
Table 4. BRIGHT Enhances Adaptive Body Image
Coping Skills: Representative Quotations from Semi-
Structured Interviews16
“I used the tools I learned during BRIGHT to get the
courage to take a trip to visit my son…and held it together
when others stared at me.” (ID 2)
“BRIGHT brought attention to thinking about myself rather
than just feeling sorry for myself.” (ID 3)
“BRIGHT gave me new tools to help cope with things that I
didn’t know how to think about…being grounded with
image issues when I have to go out in public to have the
courage to do it and know how to cope with it.” (ID 4)
“BRIGHT helped me handle uncomfortable situations to get
back to activities.” (ID 8)
“BRIGHT gave me a lot of smart idea, thoughts, techniques
for how to deal with things and what to think about my body
and the surgery.” (ID 9)

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
22 
Overall, this research study poses no more than minimal risks to participants. The single-arm pilot study 
of BRIGHT and single-site pilot RCT comparing BRIGHT with AC were minimal risk studies that were 
approved by the Medical University of South Carolina (MUSC) Institutional Review Board (IRB) under an 
expedited review (45CFR46.110). The proposed study will use a single IRB structure with MUSC serving 
as the IRB of record. No formal Data and Safety Monitoring Board was required in the prior studies of 
BRIGHT, although a Data and Safety Monitoring Plan (DSMP) with principal investigator (PI) and IRB-
based oversight was created. The main study procedures include (1) either BRIGHT (CBT) or AC (a 
manualized tele-supportive care intervention that controls for professional attention, dose, delivery 
method, and common factors) and (2) completion of study questionnaires. These are generally 
considered minimal risk activities, although one of the questionnaires inquires about suicidal ideation. 
There are no physical, financial, legal, social, or cultural, risks to the study participants by joining this 
study. The primary risks of the study associated with the intervention or study assessments include 
psychological/emotional distress and breach of privacy/confidentiality. 
 
Psychological/emotional distress: Subjects may experience adverse psychological reactions such as 
anxiety, depression, stress, distress, or suicidal ideation 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 experience with prior similar trials, we expect only minimal risk to 
participants. Nevertheless, we have a specific protocol to address situations in which a patient becomes 
distressed as a result of either the study intervention or study assessments. The project coordinator and 
all of the study interventionists have extensive experience dealing with this patient population and 
appropriate safeguards have been put in place to mitigate against this risk in either situation. There is a 
licensed clinical psychologist at each site that is trained in assessing and intervening upon distress. 
 
Breach of privacy/confidentiality: There is also a risk that confidential information about the participant 
may be accidentally disclosed to non-study personnel, resulting in loss of privacy and potential risk to 
reputation. The risk is estimated to be extremely 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. 
However, records which identify subjects such as the signed informed consent document may be 
inspected by the NIH/NCI and the MUSC IRB. In addition, if it were learned that the patient is a danger to 
her/himself or others, then appropriate authorities would be notified, as required by law. Because of the 
need to release information to these parties, absolute confidentiality cannot be guaranteed, but the risk 
of accidental breach of confidentiality is extremely low. 
2.3.2 KNOWN POTENTIAL BENEFITS 
Based on our pilot data about the clinical impact of BRIGHT on BID16, we hypothesize that participants in 
the BRIGHT arm will have a clinically significant reduction in the severity of their BID as well as 
improvement in their psychological and social well-being and QOL. However, although we hypothesize a 
direct benefit to participants in the BRIGHT arm (in terms of BID, psychological, and social well-being 
and QOL), 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 CBT 
interventions may help treat BID in cancer survivors. 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
The adequacy of protection against potential risks and assessment of potential risks and benefits is 
described below. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
23 
Informed Consent. We will obtain full written informed consent from patients prior to enrolling in the 
study. Informed consent will occur via face-face discussion between one of the study team members 
designated to perform informed consent and the potential study participant. The study team member 
will explain to potential participants the elements of the informed consent form including the study 
purpose, methods, extent, risks, benefits, and alternatives. 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 designated to perform informed 
consent. A study team member will answer any questions about the study and participants will be asked 
to sign the informed consent. All participants will receive a copy of their informed consent and HIPAA 
forms for their records. The informed consent process will take place in a private room in the Head and 
Neck Cancer Clinic at each participating site. Only the study participant will provide informed consent. 
Subjects will be allowed up to one week to decide whether to participate in the study. The signed copy 
of the informed consent document will be stored in the study binder in each patient’s section. 
 
Confidentiality. Protecting the confidentiality of data is essential in any research endeavor but is 
particularly important in a study that gathers information about sensitive topics. Measures that will be 
taken to maximize confidentiality and anonymity include the following: (1) all data will be referred to by 
identification numbers only and (2) data in digital files will be identified by code numbers only. 
Additionally, digital audio recordings of the interviews will be coded and maintained in password-
protected locations on our secure server. The likelihood that these methods will effectively protect the 
confidentiality of participants is considered to be extremely high. Based on our experience conducting 
prior similar studies, it is believed that these procedures will be effective in protecting confidentiality of 
subjects and minimizing any potential risk from participation. Emphasis on confidentiality will be 
stressed in all aspects of the study. No information about participation in the study will be divulged 
without specific and written consent to release this information. The only exception would be mandated 
reporting of allegations of child or elder abuse or disclosures of intent to harm self or others. These 
confidentiality limits will be documented in the written consent form and verbally explained to all 
participants. 
 
Data Management. Data will be compiled using codes in lieu of personal identifiers. Prior to and during 
the study, development of – and security oversight for – the electronic database for this study will be 
performed by study personnel using REDCap, a secure, web-based, MUSC Information Technology and 
Institutional Review Board-approved application to support data capture. The application will provide: 
(1) an intuitive interface for data entry (with data validation); (2) audit trails for tracking data 
manipulation and export procedures; (3) automated export procedures for seamless data downloads to 
common statistical packages; (4) procedures for importing data from external sources; and (5) advanced 
features, such as branching logic and calculated fields. Finally, only de-identified information will be 
entered into the REDCap electronic database. Thus, no protected health information (PHI) will be 
entered into the database. The data entry management system will be accessed and housed at MUSC. 
Although no PHI will be entered into the database, data system security will be ensured by 
implementing multiple layered firewalls and a network intrusion prevention system for identifying and 
blocking malicious network activity in real time. An electronic study log linking patient names with study 
ID numbers will be kept on a secure service at MUSC and access to this log will be limited to only key 
study personnel. 
 
Responding to Suicidal Ideation Endorsed During Study Interventions. One situation in which study 
personnel might have to evaluate whether they have a legal or ethical responsibility to break 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
24 
confidentiality is when there is the potential of danger of the participant to her/himself or to another 
person. For participants enrolled in the BRIGHT arm, the study interventions will be delivered by a 
licensed clinical psychologist at each site. Each psychologist is familiar with standard of care and best 
practices for the assessment and management of suicidal ideation during tele-CBT, which are described 
in detail in the BRIGHT Therapy Manual. During each BRIGHT session, the psychologist will establish the 
patient’s physical location, nearest emergency medical service provider, and emergency contact 
information to ensure that the team can intervene if needed. A determination about the 
appropriateness of the participant for home-based tele-mental health care will be made including the 
adequacy of infrastructure and technology. Participants will be instructed of legal requirement break 
confidentiality to notify emergency services for a welfare check should there be concern for the 
participant or others safety and the participant cannot be properly evaluated by the clinical psychology 
team (e.g., lost contact with patient and patient cannot be reached again). During sessions, monitoring 
of risk will occur during treatment (symptom levels, self-harm ideation, intention to harm others, 
changes in setting/patient situation) as described in the DSMP. If suicidality is endorsed, staff will assess 
risk, including frequency, lethal means, intent, behavior, and plans. If risk is moderate to low (e.g., no 
intent or plan), the psychologist and patient will establish a safety plan, including identifying warning 
signs and internal coping strategies, having the patient or others remove lethal means (e.g., firearms, 
medication), activating social support, and accessing professional services. Each site will follow its own 
procedures for sharing regional, and/or national hotlines (e.g., National Suicide Prevention Lifeline = call 
or text 988). MUSC and Henry Ford also provide local call options (MUSC = 843-792-212, Henry Ford = 
314-916-2600 at Henry Ford), while Washington University only uses national hotlines. If risk is deemed 
to be imminent, the psychologist will call emergency services for immediate psychiatric assessment. 
 
Similar procedures will be followed for the AC arm with modifications for the delivery of AC by the 
licensed clinical interventionist (e.g., nurse, advanced practice provider) instead of a psychologist. The 
clinical interventionist will receive standard training in best practices for the assessment and 
management of suicidal ideation during tele-medicine visits, which are described in detail in the SOP for 
AC. During each AC session, the clinical interventionist will establish the patient’s physical location, 
nearest emergency medical service provider, and emergency contact information to ensure that the 
team can intervene if needed. A determination about the appropriateness of the participant for home-
based tele-mental health care will be made including the adequacy of infrastructure and technology. 
Participants will be instructed of legal requirement break confidentiality to notify emergency services for 
a welfare check should there be concern for the participant or others safety and the participant cannot 
be properly evaluated by the clinical psychology team (e.g., lost contact with patient and patient cannot 
be reached again). During sessions, monitoring of risk will occur during treatment (symptom levels, self-
harm ideation, intention to harm others, changes in setting/patient situation) as described in the DSMP. 
If suicidality is endorsed, the clinical interventionists will assess risk, including frequency, lethal means, 
intent, behavior, and plans. Then, the clinical interventionist will immediately engage the study 
psychologist at each site to assess risk. If that psychologist is not available, the clinical interventionist 
will contact the on-call psychologist at each site (who is available 24 hours a day). If risk is moderate to 
low (e.g., no intent or plan), the psychologist and patient will establish a safety plan, including 
identifying warning signs and internal coping strategies, having the patient or others remove lethal 
means (e.g., firearms, medication), activating social support, and accessing professional services. Local, 
regional, and/or national hotlines will be shared, as is done in standard practice at each site (e.g., 
National Suicide Prevention Lifeline = call or text 988). MUSC and Henry Ford also provide local call 
options (MUSC = 843-792-212, Henry Ford = 314-916-2600 at Henry Ford), while Washington University 
only uses national hotlines. If risk is deemed to be imminent, the licensed clinical interventionist will call 
emergency services for immediate psychiatric assessment. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
25 
 
Responding to Suicidal Ideation Endorsed During Study Assessments. One of the study assessments, the 
Beck Scale for Suicidal Ideation, specifically assesses suicidal ideation. Therefore, we have developed a 
detailed protocol, outlined below, to address endorsements of this item. We have established 
procedures to automate a “red flag” process within REDCap anytime (in real time) a participant 
endorses positive values for these questions. This red flag indicator will be checked daily and met with 
appropriate response from our clinical team. This approach has been utilized in multiple IRB approved 
trials led by our team and other close collaborators at MUSC. The psychologist at each site will conduct a 
follow up risk assessment, safety planning, and initiation of emergency services consistent with the 
procedures described above. For example, with low- to moderate-risk participants, we will establish a 
collaborative safety plan and provide local, regional, and/or national hotlines with follow-up scheduled 
as needed; and for participants at imminent risk, the supervisor will call emergency services and remain 
on the phone with the participant until emergency services arrives, and the study team will follow up 
with the participant within 72 hours to ensure their continued safety. In the event that a member of our 
clinical team contacts the participant, the participant expresses an imminent likelihood of harming 
oneself, and the connection is lost, the psychologist will contact emergency services and will provide 
emergency services with the participant’s contact information and physical location. In the event that 
the participant is not in imminent danger, the psychologists will provide referrals for local mental health 
resources and/or instruction to go to a local Emergency Department or call 9-1-1 should suicidal 
ideation worsen. We will suggest that the participant seek treatment and then will follow up with the 
participant by phone one week later. 
 
Responding to Physical/Emotional Distress. Measures to protect against study-related psychological and 
emotional distress (without suicidal/homicidal ideation) during the study intervention or follow up 
assessments 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 BID). 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. 
 
Participants in either study condition who do NOT have current suicidal or homicidal ideation but 
nevertheless appear to be experiencing a high level of distress during the study will be asked if they 
would like to talk to one of site-Pis or associated licensed clinical psychologists. In these instances, the 
site PI or one of the study psychologists will contact the participant within 24 hours to assess the nature 
and urgency of the distress, determine the need for clinical intervention beyond any treatment that they 
may already be receiving, and arrange appropriate mental health referral. In the event that one of the 
clinical psychologists participating in the trial is not available, a licensed psychologist who works at the 
relevant site (MUSC, Washington University School of Medicine [WUSM], or Henry Ford Health [HFH]) 
will be contacted instead. Immediate backup and support will be available. As part of our initial training 
of the program coordinator at each site, we will work closely with the HFH and WUSM teams to identify 
local mental health and crisis intervention resources that can be used by Drs. Chang or Pipkorn for 
referrals should a patient express significant distress in the context of the post-baseline assessment. In 
rare cases where a mental health referral is needed, the investigator will re-contact the participant 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
26 
within one week of the referral to determine whether additional resources are needed or if assistance is 
needed in navigating the referral. 
 
Overall assessment of risks and benefits. 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. Results from the RCT may 
provide rigorous evidence supporting BRIGHT as the first evidence-based strategy to manage BID among 
HNC survivors. Such a result would represent a paradigm shift in management of the disorder, help 
develop new standards of clinical care, and improve psychosocial morbidity and QOL for HNC survivors. 
Theory-driven mechanism of change data may also help identify specific therapeutic elements to 
optimize the effectiveness of CBT for BID as well as advance our understanding of the underlying theory 
of CBT. Furthermore, data from this study will inform the development of a type I hybrid effectiveness-
implementation trial evaluating BRIGHT as a new standard of clinical care in a national sample of HNC 
survivors with BID from diverse cancer care settings. 
3 
OBJECTIVES AND ENDPOINTS  
Table 5. Study Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
Primary 
 
To evaluate the efficacy of BRIGHT compared 
with AC on HNC-related BID as measured by 
change from baseline in the IMAGE-HN score. 
Change in the IMAGE-HN score from baseline to 6-
months follow-upa 
Secondary 
To evaluate the clinical response rate of 
BRIGHT compared with AC on HNC-related 
BID as measured by proportion of patients 
with a clinically meaningful change from 
baseline in the IMAGE-HN score. 
Proportion of patients with a decrease in the IMAGE-
HN score of > 9 points from baseline 
To further evaluate the short and longer-
term efficacy of BRIGHT compared with AC 
on HNC-related BID as measured by change 
from baseline in the IMAGE-HN score. 
Change in the IMAGE-HN score from baseline to 2-, 3-, 
and 9-month follow-up 
To evaluate the efficacy of BRIGHT compared 
with AC on psychological and social well-
being as measured by change from baseline 
in the Shame and Stigma Scale in HNC, 
PROMIS SF v1.0-Depression 8a, PROMIS SF 
v1.0-Anxiety 8a, Beck Scale for Suicidal 
Ideation, and PROMIS SF v2.0-Ability to 
Participate in Social Activities-8a scores. 
Change in the Shame and Stigma in HNC score from 
baseline to 3-, 6-, and 9-month follow-up 
Change in the PROMIS SF v1.0-Depression 8a score 
from baseline to 3-, 6-, and 9-month follow-up 
Change in the PROMIS SF v1.0-Anxiety 8a score from 
baseline to 3-, 6-, and 9-month follow-up 
Change in the Beck Scale for Suicidal Ideation score 
from baseline to 3-, 6-, and 9-month follow-up 
Change in the PROMIS SF v2.0-Ability to Participate in 
Social Activities 8a score from baseline to 3-, 6-, and 9-
month follow-up  
To evaluate the efficacy of BRIGHT compared 
with AC on QOL as measured by change from 
baseline in the EORTC QLQ-HN35 score. 
Change in the EORTC QLQ-HN35 Trouble with Social 
Eating and Trouble with Social Contract subscale 
scores from baseline to 3-, 6-, and 9-month follow-up  

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
27 
Table 5. Study Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
To examine the mechanism of change 
underlying BRIGHT for HNC-related BID as 
measured by change from baseline in the 
Body Image Coping Strategies Inventory 
(BICSI) subscale scores and Automatic 
Thoughts Questionnaire scores. 
Change in the BICSI Avoidance subscale score from 
baseline to 2-, 3-, and 6-month follow-up 
Change in the BICSI Positive Rational Acceptance 
subscale score from baseline to 2-, 3-, and 6-month 
follow-up 
Change in the BICSI Appearance Fixing subscale score 
from baseline to 2-, 3-, and 6-month follow-up  
Change in the Automatic Thoughts Questionnaire 
score from baseline to 2-, 3-, and 6-month follow-up 
a: All follow-up assessments are measured as time since randomization 
Abbreviations:  AC: Attention Control; AE: Adverse Event; BICSI: Body Image Coping Strategies 
Inventory; BRIGHT: Building a Renewed ImaGe after Head & neck cancer Treatment; EORTC: European 
Organisation for Research and Treatment of Cancer; IMAGE-HN: Inventory to Measure and Assess 
imaGe disturbancE-Head & Neck; PROMIS: Patient-Reported Outcome Measurement Inventory 
System; WAI-SR: Working Alliance Inventory-Short Revised 
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
We will perform a multisite RCT comparing BRIGHT with AC to test our hypothesis that BRIGHT reduces 
BID among HNC survivors as measured by change from baseline in IMAGE-HN score (primary objective). 
In this multisite, parallel-group RCT, patients from MUSC, WUSM, and HFH 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 stratified permuted block randomization design 
with randomly selected block sizes of 4 or 6. Randomization will be stratified by site (MUSC, HFH, 
WUSM) and free flap reconstruction (yes/no) to minimize variability in practices or patient 
characteristics between sites. Randomization will occur at the individual patient level. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
We considered alternative study designs such as comparison with usual care. Usual care for HNC 
survivors with BID is educational material provided by HNC providers during routine survivorship visits.7 
Comparison with AC is a strength of our approach because AC controls for professional attention (i.e., 
ensures that findings are not driven by simply interacting with an empathic interventionist), common 
factors,26 dose, and delivery method while not providing the active, behavior change mechanism in 
BRIGHT. 
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 psychosocial care.63 For patients 
with HNC, travel burden (due to the regionalization of HNC care64,65) is a critical barrier to mental health 
care and contributes to excess morbidity and mortality.66,67 HNC survivors also face physical access 
barriers that prevent face to face CBT including fatigue and treatment toxicity. As a result, innovative 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
28 
approaches to deliver psychosocial interventions to HNC survivors are needed.68,69 Telemedicine is a 
promising solution because it decreases travel burden70, increases access to care71, and provides 
effective behavioral health interventions72 (including CBT63,73). 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.16 
4.3.2 JUSTIFICATION FOR THE NUBMBER, FREQUENCY, AND TIMING OF INTERVENTION 
CONTACTS 
The number, frequency, and timing of BRIGHT sessions was justified based on our formative work. 
Stakeholder feedback from HNC survivors and clinicians helped define BRIGHT’s timing (early post-
treatment), setting (one-on-one therapy), duration (limited number of sessions), and delivery method. 
The number, frequency, and timing of BRIGHT sessions was then evaluated in our single-arm clinical trial 
(NCT03518671) (Table 2)16 and single-site pilot RCT (NCT03831100). Patients in BRIGHT rated the timing 
of the intervention relative to HNC treatment highly (all mean > 4/5/5) (Table 3). 
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-, 3-, and 6-month post-treatment assessments. The end of the study is 
defined as completion of the 6-month post-treatment assessment shown in the SoA, Section 1.2. 
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 on the day of informed consent 
2. History of pathologically confirmed squamous cell carcinoma (or histologic variant) of the 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 
4. Completion of oncologic treatment within 12 months of study enrollment (but no sooner than 6 
weeks post-treatment completion) 
a. Patients who complete definitive HNC-directed therapy (e.g., surgery or radiation 
therapy) but are on an adjuvant immunotherapy trial are considered eligible 
5. Cancer-free at the time of accrual 
a. Patients with known indolent malignancies (e.g., non-melanoma skin cancer, low risk 
thyroid cancer, untreated prostate cancer, etc.) would not exclude a patient from the 
study 
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. IMAGE-HN score > 22 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
29 
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 read English 
2. Pre-existing, ongoing psychotherapy services for any disorder 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 mental illness that would prevent trial participation 
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 randomized or entered in the study due to not meeting 1 or more eligibility criteria. 
Individuals who do not meet the criteria for participation in this trial (screen failure) because of meeting 
one or more exclusion criteria may be rescreened if the investigator believes that there has been a 
change in eligibility status. Patients who re-screen must re-consent. 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
5.5.1 ANTICIPATED SCREENING AND ACCRUAL TARGETS 
To achieve our target sample of N = 180 evaluable patients with an expected attrition rate of 20%, we 
plan to enroll 226 patients. Patients will be accrued from three sites: MUSC, WUSM, and HFH. The 
planned accrual stratified by gender, race, and ethnicity is shown in Table 6. We will recruit by age and 
sex in proportion to the population; this approach resulted in a diverse sample in our pilot RCT. 
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 and (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 in this patient 
population. The study sites 
where clinic-based recruitment 
and enrollment will occur 
(MUSC, WUSM, HFHS) all have appropriate facilities to accommodate individuals in the included age 
range. 
 
There are no inclusion or exclusion criteria based on sex. The planned distribution of subjects by sex in 
the clinical trial is 50% female and 50% male. The distribution is expected to reflect the demographics of 
our target population (HNC survivors with BID following surgery) based on our prior studies at each of 
Table 6. Planned Recruitment by Race, Ethnicity, and Gender 
Racial 
Categories 
Ethnic Categories 
Not Hispanic or Latino 
Hispanic or Latino 
Total 
Female 
Male 
Female 
Male 
Asian 
3 
3 
0 
0 
3 
Black 
22 
23 
0 
0 
45 
White 
60 
60 
5 
4 
129 
> 1 Race 
0 
0 
0 
0 
0 
Total 
85 
86 
5 
4 
180 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
30 
the three sites. None of the three sites have experienced any difficulty in achieving equality in 
representation by sex in prior studies in this patient population. 
 
Patients of all races and ethnicities will be recruited for the study. The population distribution of 
subjects by self-identified race in the catchment areas for the three sites is 77% white, 16% Black and 7% 
other. However, significant Black/White racial disparities in outcomes exist in HNC; it is thus critical that 
we enroll a racially diverse population to ensure the external validity of trial findings. Therefore, we will 
stratify accrual by race (Black vs White/other) and oversample Black patients (25%) relative to their 
frequency in our population (16%). The PI and research team will leverage their experience and strong 
track record of recruiting and engaging underserved and racial minorities in their HNC research. The 
planned distribution of subjects by self-identified ethnicity in the trial is 95% non-Hispanic and 5% 
Hispanic. The rationale for the selection of ethnic proportions in the proposed trial is that prior studies 
have demonstrated no association between ethnicity and BID among HNC survivors. 
5.5.2 ANTICIPATED ACCRUAL RATE AND ACCRUAL FEASIBILITY 
Targeting an attrition rate = 20%, we propose to enroll 226 patients to achieve a final sample size of N = 
180 evaluable patients. In the pilot RCT of BRIGHT at 
MUSC, we accrued 54 eligible patients in 17 months (3.2 
patients/month); 87% (54/62) of eligible patients 
accrued to the study. Below we outline our assumptions 
to demonstrate the feasibility of recruitment and 
retention for the proposed multisite RCT (Figure 7). 
Clinical volumes are similar at MUSC, HFH, and WUSM 
and thus we present the data in its aggregate across all 
three sites. 
 
We estimate n = 16 HNC survivors returning to 
clinic/month based on (1) registry data from each cancer 
center and (2) recruitment for HNC survivors with BID at 
prior studies at MUSC, HFH, and WUSM. We estimate 
the prevalence of BID among HNC survivors at 28% 
based on (1) our prior cohort studies of HNC survivors at 
MUSC, HFH, and WUSM4 and (2) screening for our pilot 
RCT of BRIGHT at MUSC. We target an accrual rate of 
50% for the proposed multisite RCT. This is a highly 
conservative estimate since we accrued 87% of eligible HNC survivors with BID to the pilot RCT of 
BRIGHT. At the targeted conservative accrual rate of 5.5 patients/month, we would accrue N = 226 
patients in 41 months. We estimate an attrition rate of 20%  based on our pilot RCT of BRIGHT and other 
trials we have conducted among HNC survivors. 
5.5.3 PLANNED SCREENING AND RECRUITMENT STRATEGIES 
The multidisciplinary HNC team (surgical, radiation, and medical oncologists, and advanced practice 
providers for each specialty) actively participated in the recruitment and retention of HNC survivors with 
BID in prior studies. The HNC team at each site is thus already aware of our ongoing studies and clinical 
trials in this area. As we prepare to recruit for the proposed RCT, the site-PI will introduce the new 
clinical trial concept to the HNC team at their weekly multidisciplinary HNC tumor board. The site-PI will 
also conduct in-person staff trainings about recruitment protocols during the initial planning period and 
Fig. 8. Anticipated accrual rate and 
accrual feasibility 
All Sites
HNC Survivors returning to clinic 
6 weeks to 1-year post-treatment
16 patients/month
HNC Survivors with BID who
Accrue to the RCT
5.5 patients/month
Eligible HNC Survivors with BID
3.9 patients/month
28% prevalence 
of BID
50% Accrual 
Rate*
Evaluable Patients
4.4 patients/month 
20% Attrition 
Rate
N=180 Evaluable Patients
41 Months of 
Accrual

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
31 
review sessions as needed throughout the enrollment process. We have developed project recruitment 
milestones and metrics. We will review progress and troubleshoot recruitment issues if they arise during 
weekly team-wide study meetings. It is expected that each site-PI, as a clinically active HNC surgeon, will 
help engage other members of the multidisciplinary HNC team in the recruitment planning efforts. 
 
The program coordinator at each site (MUSC, HFH, WUSM) will screen for potential participants using 
the electronic health record (EHR) to preview the weekly HNC clinic schedule. EHR-based screening will 
be supplemented by in-person discussion with the HNC clinical team at each site to optimize 
identification of potentially eligible patients. Research staff will review clinical documentation for all 
HNC survivors with an appointment in the HNC clinic to identify patients who meet clinical study 
inclusion criteria and are scheduled for an appointment. 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 treating physician will approach 
the potential participant to introduce the research study directly to the patient at the clinic visit. Study 
information provided by the clinician will not include any language or information that may be perceived 
as unduly influencing or coercive, or imply that medical care could be influenced by choice to participate 
or not. If the patient is interested in the research study, then he/she will contact the research team for 
more information. 
 
If the patient is interested in participating in the research study, the program coordinator will discuss 
participation in the trial at that clinical encounter. Because IMAGE-HN is not used in clinic as standard of 
care at each site, a waiver of documentation of the informed consent process will be utilized to allow for 
IMAGE-HN to be used as a screening tool for the trial. The potential participant will complete the 
IMAGE-HN to determine trial eligibility; those with an IMAGE-HN score <22 do not have clinically 
significant HNC-related BID and thus are not eligible. At this in-person clinic visit the program 
coordinator will confirm the rest of the inclusion/exclusion criteria that could not be obtained in the 
EHR. 
 
Each site (MUSC, HFH, WUSM) will use a clinic-based screening and recruitment approach that we 
optimized in our prior studies.4,16,27,40 Recruitment for the study will occur using the standard operating 
procedures (SOPs) that we optimized during our single-arm and pilot RCTs of BRIGHT at MUSC. These 
SOPs will be adapted and optimized for clinic workflow at HFH and WUSM. The recruitment protocols 
have been optimized based on our experiences in prior studies to address logistical issues related to 
coordination of clinic-based screening and enrollment. Our experience recruiting for BRIGHT also 
demonstrated that the active clinical practice of the site-PI and his clinical relationship with all members 
of the multidisciplinary HNC team are key factors in maximizing recruitment. Recruitment at each site 
will be handled by the project coordinator and study team at that site. 
5.5.4 STRATEGIES TO ENHNACE RETENTION 
We expect to continue the high rate of retention that we demonstrated in our single-arm and pilot RCT 
through the following five 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/AC session helped ensure low rates of missed sessions and high rates of retention. Second, 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
32 
BRIGHT was designed using a patient-centered 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 and AC differ, the timing 
and delivery method are the same in both arms of the trial and will thus likely facilitate retention in the 
AC arm 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 studies 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. 
Fifth, we strive to compensate 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 assessments. 
5.5.5 RETENTION FEASIBILITY 
Our prior studies demonstrate our strong track record of retention. In our pilot RCT of BRIGHT, 20% of 
accrued patients (11/54) went off study: n = 7 (13%) went off study per protocol due to the 
development of HNC recurrence or second non-HNC malignancy; n = 3 (7%) withdrew due to 
intercurrent physical demands, and n = 1 (2%) was enrolled erroneously. We are encouraged by the very 
low rate of withdrawal (7%) and the finding that no evaluable patients were lost to follow-up. The rate 
of recurrence or second primary non-HNC malignancy was significantly higher than expected based on 
population data and is likely an aberrant finding in a small sample. We do not expect the rate of patients 
going off protocol due to recurrent HNC or second non-HNC primary malignancies to stay this high in the 
larger sample for the proposed multisite RCT. In our single-arm study of BRIGHT, retention was 90% 
(9/10 participants).16 The 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. 
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) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION DESCRIPTION 
6.1.1.1 BRIGHT 
BRIGHT is a manualized theory-based tele-CBT intervention consisting of 6 weekly 60-minute sessions. 
BRIGHT will be delivered one-on-one by a licensed clinical psychologist at each site (MUSC, HFH, WUSM) 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
33 
via standard video tele-CBT platform. BRIGHT is situated within a cognitive psychology perspective19 of 
BID and conceptualizes HNC-related BID according to Folkman’s transactional theory of stress and 
coping.17,24,46,55 Table 7 shows the psychotherapeutic techniques utilized in BRIGHT to address key 
theorized targets. 
Psychologists deliver BRIGHT 
according to the BRIGHT 
Manual, which outlines the 
underlying theoretical basis of 
BRIGHT as well as the topics, 
objectives, psychotherapeutic 
techniques, and content for 
each session. Patients receive 
the BRIGHT Patient Workbook, 
which contains objectives, 
educational materials, 
exercises, and homework for 
each week. The BRIGHT 
materials were developed 
with engagement from HNC 
survivors to ensure that the content was language and literacy-level appropriate and refined with HNC 
survivors from our single-arm trial and pilot RCT to optimize relevance, clarity, and readability.  
 
Psychologists at each site (MUSC, HFH, WUSM) have experience delivering video tele-mental health care 
to patients with HNC. The HIPAA-compliant and institutionally-approved video telemedicine platform at 
each site uses face to face communication and includes a within-video text feature for patients with 
challenges speaking due to surgical removal of the voice box or tongue. Although the COVID-19 
pandemic rapidly accelerated the uptake of telemedicine for HNC survivorship care77,78 and CBT,79,80 the 
potential for a digital divide remains.81 To enhance equity and minimize the digital divide, we will 
provide patients with a study-issued, cellular-enabled iPad if needed, show patients how to use the iPad 
and telemedicine platform, and provide patients with a pictorial instructional booklet for home 
reference. Each iPad is locked to prevent downloading of additional applications, pre-loaded with a 
HIPAA-compliant video teleconference platform, and has cellular service with > 97% coverage for each 
state.82 Patients receive a pre-addressed, stamped, padded mailer to return the iPad. We successfully 
delivered BRIGHT using this approach in our single-arm trial16 and pilot RCT. 
6.1.1.2 AC 
Following best practices for choosing control groups within behavior change RCTs,83,84 we designed AC 
to control for professional attention (i.e., ensuring that findings are not driven by simply interacting with 
an empathic interventionist), common factors,26 dose, and delivery method while not providing the 
active, behavior change mechanism in BRIGHT. AC is a manualized tele-supportive care intervention 
delivered by licensed HNC clinical staff (e.g., advanced practice provider) at each site (MUSC, HFH, 
WUSM) that addresses non-body image aspects of HNC survivorship. The AC manual provides 
educational content (Table 8) and directs the interventionist to provide empathic comments but 
contains no psychotherapeutic techniques. The manual also outlines the hypothesized behavior change 
mechanisms in BRIGHT that should not be addressed by AC and provides strategies for the 
interventionist to re-direct the conversation if BID arises. Identical to BRIGHT, AC consists of 6 weekly 
60-minute sessions delivered by a trained empathic interventionist via standard video-telemedicine 
Table 7. BRIGHT Psychotherapeutic Techniques and Objectives
Technique
Session Objectives
Psycho-
education
-Understand the cognitive model of body image and how 
HNC survivors are affected by BID
Self-
Monitoring
-Learn how thoughts, feelings, and behaviors about body 
image are related
-Begin to self-monitor situations that contribute to BID
Cognitive 
Restructuring
-Identify unhelpful automatic HNC body image schemas
-Challenge unhelpful automatic HNC body image thoughts 
and substitute more balanced thoughts
Body Image 
Coping 
Strategies
-Identify body image avoidance behaviors and recognize 
how they increase long-term BID
-Develop an action plan for situations that are being avoided
Relapse 
Prevention
-Reflect on progress made during BRIGHT
-Set goals aligned with personal values to prevent relapse

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
34 
(with iPad provision if 
necessary). AC is an 
adaptation of the control 
intervention used in our pilot 
RCT that we modified for 
manualized delivery by an 
interventionist. We pre-
tested the interventionist- 
delivered AC with HNC 
survivors and then refined it 
based on their feedback to 
optimize its feasibility, 
credibility, and relevance.  
6.1.2 ADMINISTRATION AND/OR DOSING 
BRIGHT and AC will be delivered using the same telemedicine delivery platform at each site (MUSC, HFH, 
WUSM). The Health Insurance Portability and Accountability Act (HIPAA)-compliant and institutionally-
approved video telemedicine platform at each site uses face to face communication and includes a 
within-video text feature for patients with challenges speaking due to surgical removal of the voice box 
or tongue. Although the COVID-19 pandemic rapidly accelerated the uptake of telemedicine for HNC 
survivorship care77,78 and CBT,79,80 the potential for a digital divide remains.81 To enhance equity and 
minimize the digital divide, we will provide patients with a study-issued, cellular-enabled iPad if needed, 
show patients how to use the iPad and telemedicine platform, and provide patients with a pictorial 
instructional booklet for home reference. Each iPad is locked to prevent downloading of additional 
applications, pre-loaded with a HIPAA-compliant and institutionally-approved video teleconference 
platform, and has cellular service with > 97% coverage for each state.82 Patients receive a pre-addressed, 
stamped, padded mailer to return the iPad. We successfully delivered BRIGHT using this approach in our 
single-arm trial16 and pilot RCT. 
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 standard of care video telemedicine platform. The BRIGHT intervention consists of 6 
sessions of weekly, 60-minute, tablet-based, manualized individual video tele-CBT (see Section 1.3, 
Schedule of Activities). BRIGHT will be delivered by licensed clinical psychologists at each site with 
experience delivering manualized CBT and working with cancer survivors. The use of multiple 
psychologists to deliver BRIGHT will enhance rigor and external validity and minimize confounding 
between the experimental intervention and interventionist. The relevant parameters when considering 
the delivery of BRIGHT include the number, frequency, and duration of telemedicine 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 will be delivered in one-on-one, face-to-face sessions between the clinical provider and participant 
using a standard of care video telemedicine platform (see Section 1.3, Schedule of Activities). The 
relevant parameters when considering the delivery of AC include the number, frequency, and duration 
Table 8. Attention Control Topics and Objectives
# Topic
Objectives
1 Survivorship Intro
Understand the new normal of HNC survivorship
2 HNC Physical 
Treatment Toxicity
Learn ways to manage physical changes including 
radiation side effects, dysphagia, and lymphedema
3 Psychosocial 
Effects of HNC 
Normalize post-treatment psychosocial changes 
including anxiety and depression
4 Health 
Maintenance
Develop strategies for a healthy diet and exercise; 
address nutritional challenges for HNC survivors
5 Financial Toxicity 
& Return-to-Work 
Discuss strategies to get back to work and manage 
finances following HNC treatment
6 Fear of Cancer 
Recurrence
Learn ways to manage fear of cancer recurrence

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
35 
of video telemedicine sessions to ensure that it is appropriately matched to BRIGHT. AC controls for 
professional attention (i.e., ensuring that findings are not driven by simply interacting with an empathic 
interventionist), common factors,26 dose, and delivery method while not providing the active, behavior 
change mechanism in BRIGHT. 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 
6.2.1.1 BRIGHT 
BRIGHT will be delivered by licensed clinical psychologists at each site (MUSC, HFH, WUSM) with 
experience delivering manualized CBT and working with cancer survivors. Dr. Maurer, the psychologist 
who helped develop BRIGHT with Dr. Graboyes, will train the psychologists at each site. BRIGHT training 
will occur virtually for 12 hours over 3 days. Training will include (1) background readings and a guided 
discussion about HNC-related BID, (2) comprehensive and interactive orientation to the BRIGHT Therapy 
Manual and Patient Workbook, (3) review of previously recorded BRIGHT sessions, (4) simulated BRIGHT 
delivery via roleplay with mock participants, and (5) discussion of study protocol and standard operating 
procedures (SOPs). Following training, Dr. Maurer will meet with the interventionists virtually 
once/month to discuss challenges delivering BRIGHT. 
6.2.1.2 AC 
AC will be delivered by licensed HNC clinical staff at each site (MUSC, HFH, WUSM) with experience 
working with HNC survivors. A HNC survivorship Physician Assistant at MUSC will work with Dr. Graboyes 
to train the AC Interventionists to deliver AC using the methods described above (but adapted for AC). 
6.2.2 INTERVENTION FIDELITY 
We will ensure the consistent delivery of study interventions (BRIGHT, AC) via the following 
mechanisms. First, tele-sessions in both groups will be recorded. The trained PC will review randomly 
selected sessions (17%) to monitor for therapeutic drift85 and assess fidelity quantitatively using a 
modified version of the BRIGHT Fidelity and Competence Scale.86 Second, at the conclusion of each 
session, the interventionist will complete the electronic case report form (eCRF) for fidelity monitoring 
which assesses session completion, duration, content delivered, and delivery mode. For AC, fidelity 
monitoring will also include assessments of negative fidelity to ensure that BID is not discussed. The 
accuracy of fidelity self-reporting for the video-recorded sessions is enhanced through the bogus 
pipeline.87 Third, the specific duties necessary to ensure consistent and optimal delivery of the 
interventions (BRIGHT, AC) are detailed in the respective manuals, thereby minimizing therapeutic 
drift.85 If insufficient fidelity to the manual is identified, the interventionist will be remediated until 
competency is demonstrated. 
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. Following provision of written informed consent and completion of baseline 
study assessments, patients will be randomized 1:1 to BRIGHT or AC using a stratified permuted block 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
36 
randomization design with randomly selected block sizes of 4 or 6 to avoid deterministic treatment 
allocation. Randomization will be stratified by site (MUSC, HFH, WUSM) and free flap reconstruction 
(yes/no) to minimize variability in practices or patient characteristics between sites. The random 
allocation sequence will be generated by the lead study biostatistician using a computer-generated 
algorithm. The program coordinator will implement the random allocation sequence using the REDCap 
randomization feature to conceal the sequence until intervention assignment. Randomization errors will 
be handled as per ITT analyses for the efficacy population. 
 
Study investigators will be blinded to allocation. Outcome assessors are not blinded to allocation, but all 
study assessments are patient-reported outcomes and thus unlikely to be biased by outcome assessors 
knowing study allocation. Staff delivering BRIGHT/AC cannot be blinded due to face-to-face intervention 
delivery. Patients are not blinded but they also are not instructed whether BRIGHT or AC is the active 
intervention. 
6.4 
STUDY INTERVENTION ADHERENCE 
Adherence of subjects to BRIGHT/AC study procedures are key to ensure scientific rigor, validity, 
reproducibility, and achievement of study objectives. Adherence will be assessed with the following 
measures: (1) attendance at intervention visits; (2) duration of study visits; (3) homework completion 
(for BRIGHT); (4) interventionist rating of patient engagement and material comprehension. Attendance 
at all study visits is mandatory to remain an active participant. Adherence information will be assessed 
by the interventionist and documented in the eCRF after each study visit. 
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.  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 
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. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
37 
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 
 
The date and reason for participant discontinuation or withdrawal from the study will be recorded in the 
eCRF. 
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 5 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 using a variety of contact modalities (e.g., telephone 
call, email, text message, communication through the EHR). 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. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Each site (MUSC, HFH, WUSM) will be responsible for collecting study assessment data as described 
below and entering it into the REDCap eCRFs. There will be a single central REDCap developed and 
maintained at MUSC. 
8.1 
SCREENING PROCEDURES 
The program coordinator at each site (MUSC, HFH, WUSM) will screen for potential participants using 
the EHR to preview the weekly head and neck oncology clinic schedule at each site. EHR-based screening 
will be supplemented by in-person collaboration with the head and neck clinical team at each site. 
Research staff will review clinical documentation for all new or returning patients with an appointment 
in the head and neck clinic to identify patients who meet clinical study inclusion criteria and are 
scheduled for an appointment. 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 within the head and neck clinic to discuss 
participation in the trial.  All screening information and criteria necessary to establish trial eligibility 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
38 
other than the IMAGE-HN score are available in the HER but will be confirmed with the patient and 
treating clinician 
 
After a patient who is potentially eligible for the study is identified, the patient will be contacted at the 
previously identified clinic visit to discuss participation in the study as described below. The head and 
neck oncology clinician 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 program 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 the IMAGE-HN as a screening assessment to identify patients 
with clinically significant HNC-related BID; those with score > 22 will be eligible for the study. 
 
Once a subject has signed the informed consent form (ICF), an identification number will be assigned to 
him/her and the study related screening procedures will start. A subject will be randomized into the 
study after he/she has signed the ICF and all eligibility criteria have been met. 
8.2 
BASELINE ASSESSMENTS 
8.2.1 DEMOGRAPHIC 
Demographic information is gathered as patient self-report in the eCRF. Demographic characteristics 
include sex, age, race, ethnicity, marital status, insurance, educational attainment, employment, and 
history of medication or counseling for mental health disorders. 
8.2.2 CLINICAL AND ONCOLOGIC  
Clinical and oncologic characteristics are assessed using clinical documentation within the EHR unless 
otherwise indicated. 
 
Baseline oncologic characteristics include history of mental health diagnoses, concomitant 
antidepressant or anxiolytic usage, head and neck tumor subsite, tumor histology, p16/human 
papillomavirus (HPV) tumor status, date of treatment completion, head and neck cancer treatment 
modalities, type of ablative surgery, type of surgical reconstruction, American Joint Committee on 
Cancer (AJCC) 8th edition pathologic TNM Class, AJCC 8th edition overall pathologic stage grouping. 
8.3 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
Sites are encouraged to administer patient-reported outcome measures (PROMs) using an electronic 
device/tablet. If that is not feasible, administration of PROMs using a paper-based format is also 
acceptable. Sites are encouraged to align PROS 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, 
text message, or email at the program 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. 
8.3.1 EFFICACY 
IMAGE-HN. The IMAGE-HN is a 24-item, validated, PROM of HNC-related BID.27 Items are rated on a 5-
point Likert scale from ‘Never’ (0) to ‘Always’ (4). The total global score is calculated by summing item 
responses across 21 items (all items except 3, 4, and 19). The total IMAGE-HN score on the global 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
39 
domain (21 questions) ranges from 0-84; higher scores indicate worse HNC-related BID. An IMAGE-HN 
score of > 224 indicates clinically-significant HNC-related BID and a change in IMAGE-HN score of > 9 
points is clinically meaningful.88 
 
Shame and Stigma Scale in HNC. The Shame and Stigma Scale in HNC 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 days.31 Items are rated on a 5-point Likert 
scale from ‘Never’ (0) to ‘All the time’ (4). The total score is calculated by summing the individual 
responses (except for 4 questions which are reverse scored). Shame and Stigma Scale in HNC scores 
range from 0-80; higher scores reflect worse HNC-related shame and stigma. 
 
PROMIS SF v1.0- Depression 8a. The PROMIS SF v1.0-Depression 8a is an 8-item validated measure 
developed by the NIH to assess patient-reported negative mood, views of self, and decreased positive 
affect and engagement.89 Responses rate the strength of agreement with statements about depressive 
symptoms using a scale that ranges from 1-5. The total raw score is calculated by summing the 
individual responses. The PROMIS SF v1.0-Depression 8a raw score ranges from 8-40; a higher score 
reflects more severe depressive symptoms. The PROMIS SF v1.0-Depression 8a total raw score is 
translated into a T-score for each participant according to the PROMIS Scoring manual. The T-score 
provides a standardized score with a mean of 50 and a standard deviation of 10. 
 
PROMIS SF v1.0-Anxiety 8a. The PROMIS SF v1.0-Anxiety 8a is an 8-item, validated, developed by the 
NIH to assess patient-reported fear, worry, and hyperarousal.89 Responses rate the strength of 
agreement with statements about anxiety symptoms using a scale that ranges from 1-5. The total raw 
score is calculated by summing the individual responses. The PROMIS SF v1.0-Anxiety 8a raw score 
ranges from 8-40; a higher score reflects more severe anxiety symptoms. The PROMIS SF v1.0-Anxiety 8a 
total raw score is translated into a T-score for each participant according to the PROMIS Scoring manual. 
The T-score provides a standardized score with a mean of 50 and a standard deviation of 10. 
 
Beck Scale for Suicidal Ideation. The Beck Scale for Suicidal Ideation is a 21-item, validated, patient-self 
report rating scale to rate the severity of a patient's suicidal thoughts and plans.90 Each item consists of 
three options graded according to suicidal intensity from 0 to 2. The ratings for the first 19 items are 
summed to yield a total score, which ranges from 0 to 38. Higher scores represent more severe suicidal 
ideation.91 A cutoff score of > 2 is optimal to indicate high/low risk of suicidal ideation.92 
 
PROMIS SF v2.0-Ability to Participate in Social Activities 8a. PROMIS SF v2.0-Ability to Participate in 
Social Activities 8a is an 8-item, validated, unidimensional measure of patient-reported perceptions of 
participation in social activities.93,94 Items are scored using a 5-point Likert scale from 'Never' (1) to 
'Always' (5). The total raw score is calculated by summing the individual responses. The total raw score 
ranges from 8-40; a higher score reflects more severe inability to participate in social activities. The total 
raw score is translated into a T-score for each participant according to the PROMIS Scoring manual. The 
T-score provides a standardized score with a mean of 50 and a standard deviation of 10. 
 
EORTC QLQ-HN35 Trouble with Social Eating Subscale. The EORTC QLQ-HN35 Trouble with Social Eating 
Subscale is a 4-item, validated measure of trouble with social eating for patients with HNC.95 The 
subscale is composed of QLQ-H&N35 items 19-22. Items are scored using a 4-point Likert scale from 'not 
at all' (0) to 'very much' (3). The total score is calculated by summing the individual responses. Total 
subscale scores range from 0-12; higher scores reflect more trouble with social eating. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
40 
EORTC QLQ-HN35 Trouble with Social Contact Subscale. The EORTC QLQ-HN35 Trouble with Social 
Contact Subscale is a 5-item, validated measure of trouble with social contact for patients with HNC.95  
The subscale is composed of QLQ-H&N35 items 18, 25-28. Items are scored using a 4-point Likert scale 
from 'not at all' (0) to 'very much' (3). The total score is calculated by summing the individual responses.  
Total subscale scores range from 0-15; higher scores reflect more trouble with social contact. 
8.3.2 MECHANISM 
Body Image Coping Strategies Inventory. The BICSI is a 29-item, validated measure of the cognitive and 
behavioral responses to manage threats to body image.55 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’ (0) to ‘Definitely like 
me’ (3). The score for each subscale is calculated by summing the values for the individual questions and 
thus ranges as follows: Appearance fixing (0-30), Avoidance (0-24), and Positive rational acceptance (0-
33). For each subscale, higher scores indicate greater reliance on that type of body image coping 
strategy. 
 
Automatic Thoughts Questionnaire. The Automatic Thoughts Questionnaire is a 15-item, validated, 
patient-reported measure of negative automatic thoughts.96 Items are scored using a 5-point Likert scale 
(1-5). The total score is calculated by summing the individual responses. Total scores range from 15-75; 
higher scores reflect more negative automatic thoughts. 
 
Working Alliance Inventory-Short Revised-Therapist. The Working Alliance Inventory Short Revised-
Therapist Version is a 10-item, validated, assessment of the strength of alliance (bond, goals, task) 
between the therapist and client, as rated by the therapist.76 Items are scored using a 5-point Likert 
scale from 'Seldom' (1) to 'Always' (5). The total score is calculated by summing the individual responses. 
The total score ranges from 10-50; higher scores reflect stronger alliance (bond, goal, task) between the 
therapist and the client as rated by the therapist. 
 
Therapist Empathy Scale. The Therapist Empathy Scale is a 9-item validated measure of therapist 
empathy as rated by a 3rd party observer.97 Items are scored using a 7-point Likert scale from 1-7. The 
total score is calculated by summing the individual responses and thus ranges from 9-63. Higher scores 
reflect more frequent empathy by the therapist. 
 
Credibility/Expectancy Questionnaire-Expectancy Subscale. The Credibility/Expectancy Questionnaire- 
Expectancy Subscale is a 3-item, validated assessment of the patient's expectations for improvement 
with the intervention.98 Items are scored using a 9-point Likert scale from 1-9. The total score is 
calculated by summing the individual responses and thus ranges from 3-27. Higher scores reflect greater 
expectation of improvement from the intervention. 
8.3.3 INTERVENTION FIDELITY 
BRIGHT Fidelity and Competence Scale. The BRIGHT Fidelity and Competence Scale is a system for rating 
the fidelity and skill level of therapists delivering BRIGHT that consists of 11 items grouped in 3 
subscales: Assessment (1 item), General (4 items), and BRIGHT (6 items). All of the items use a common 
Likert-type scale from 1-7. For each item, two dimensions are rated using this Likert scale. The first 
dimension, ‘Frequency and Extensiveness’, is a ‘quantity’ or ‘fidelity’ rating that taps the degree to which 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
41 
the intervention was present in that session (e.g., whether it occurred and with what intensity). The 
second dimension, ‘Skill Level’, is a ‘quality’ or ‘competence’ rating that indicates skill with which the 
therapist delivered the intervention (and is rated only if the intervention occurred within the rated 
session). ‘Frequency and Extensiveness’ is rated on a Likert scale of 1-7 (not at all to extensively) with 
higher scores reflecting greater frequency and extensiveness of the item. ‘Skill level’ is rated from 1-7 
(very poor to excellent) with higher scores reflecting greater skill on each item. The BRIGHT Fidelity and 
Competence Scale is modeled from the Yale Adherence and Competence Scale (YACS), a validated scale 
for rating therapist adherence and competence in delivering behavioral treatments for substance use 
disorders.86 Details for scoring and interpreting the BRIGHT Fidelity and Competence Scale are provided 
in its accompanying Rater Manual. 
 
Interventionist Self-Report. The Interventionist Self-Report is a self-report checklist (yes/no) mapped to 
agenda content for each of the 6 sessions for BRIGHT or AC. 
8.3.4 PARTICIPANT ADHERENCE 
Adherence will be assessed with the following measures: (1) attendance at intervention visits; (2) 
duration of study visits; (3) homework completion (for BRIGHT); (4) interventionist rating of patient 
engagement and material comprehension.  
 
8.4 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.4.1 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 sustained undesirable psychological, social, 
or emotional reaction that is definitely, probably, or possibly related to the study intervention. AEs 
include suicide attempt, sustained emotional distress, sustained depression, or other sustained mental 
health deterioration. This definition of an adverse event follows best practices for recording adverse 
events during psychological treatments. 99 
8.4.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
A serious adverse event (SAE) will be defined as any sustained undesirable psychological or mental 
health 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 SAEs. 
8.4.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.4.3.1 SEVERITY OF EVENT 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
42 
• 
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”. 
8.4.3.2 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. 
8.4.4 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. AEs may be reported by the 
patient via self-report, noted in the electronic medical record, or reported directly by study personnel.  
8.4.5 ADVERSE EVENT REPORTING  
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 at each site. 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 
8.4.6 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. 
8.4.7 REPORTING EVENTS TO PARTICIPANTS  
N/A 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
43 
8.4.8 EVENTS OF SPECIAL INTEREST  
N/A 
8.4.9 REPORTING OF PREGNANCY  
N/A 
8.5 
UNANTICIPATED PROBLEMS 
8.5.1 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. 
8.5.2  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: 
• 
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 National Cancer Institute (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 
8.5.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
N/A 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESIS 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
44 
We hypothesize that, compared with patients randomized to AC, patients randomized to the BRIGHT 
intervention will have reduced BID as measured by change in the IMAGE-HN score of > 9 from baseline 
to 6-months follow-up. Alternatively, our null hypothesis is that BRIGHT will not improve BID relative to 
AC, as measured by change in the IMAGE-HN score of < 9 from baseline to 6-months follow-up. 
9.2 
SAMPLE SIZE DETERMINATION 
The primary endpoint for the proposed RCT is the change in the IMAGE-HN score from baseline to 6-
month follow-up. Our primary objective is to test the hypothesis that BRIGHT decreases HNC-related BID 
from baseline to 6-month follow-up (as measured by clinically significant reduction in the IMAGE-HN 
score) relative to AC. We target a mean difference in IMAGE-HN score reduction of 9 between BRIGHT 
and AC at 6 months. This targeted difference is (1) clinically important using widely accepted 
distribution-based methods of patient reported outcome measure interpretation88 and (2) 
commensurate with clinically meaningful differences in BID among cancer survivors from other 
appropriately powered trials.14,41,100 In our pilot RCT, at 3-months post-intervention (a timepoint similar 
to 6 month follow-up), BRIGHT improved IMAGE-HN scores from baseline relative to AC (mean model-
based difference in change in IMAGE-HN score = -17.1 [90% CI, -25.6 to -8.6] points; P = 0.002). The 
targeted clinically important difference in IMAGE-HN score reduction of 9 thus appears highly feasible. 
Determining the sample size for the proposed RCT requires adjusting for the clustering of trial 
participants within psychologist (BRIGHT arm) or HN clinical staff member (AC arm). We expect the 
number of clusters in each arm to be 9 with an average of 10 trial participants per cluster. We further 
estimate an intra-class correlation coefficient (ICC) = 0.05101,102 and standard deviation = 16 based on 
similar studies.41,100 Given these assumptions, a sample size of N = 180 (n = 90/arm) yields 83.7% power 
to detect the targeted 9-point average reduction in IMAGE-HN scores between the BRIGHT and AC arms 
with two-sided α = 0.05 (PASS v 08.0.13, Inequality Tests for Two Means in a Cluster-Randomized Design 
module). 
 
Targeting an attrition rate = 20%, we plan to enroll 226 HNC survivors with BID to achieve our target 
sample size of N = 180 evaluable patients for the modified intention-to-treat (ITT) analyses of the 
efficacy population. In our pilot RCT, 20% (11/54) of eligible patients who accrued to the RCT were not 
evaluable for the primary endpoint: n = 7 (13%) went off study per protocol due to the development of 
recurrent HNC or a second non-HNC malignancy; and n = 3 (7%) withdrew due to intercurrent physical 
demands. No patients were lost to follow-up. 
9.3 
POPULATIONS FOR ANALYSES 
The safety analysis set (SAS) is composed of all patients enrolled who receive any part of either the 
BRIGHT or AC intervention. The SAS will be used to conduct all safety analyses. Patients will be analyzed 
based on the intervention received regardless of the assignment at randomization. 
 
The 6-month IMAGE-HN evaluable set is composed of all patients enrolled in the trial who have 
completed the baseline and 6-month follow-up IMAGE-HN survey instrument. Analysis will be 
performed based on assignment at randomization regardless of the intervention received (modified 
intent to treat). This analysis set will be used for analysis of the primary endpoint. 
 
Analysis sets for secondary endpoints specific to PROMs at a given follow-up timepoint will be defined 
as the set of trial participants who have completed both the baseline and the follow-up survey at the 
specified timepoint. Analysis will be performed based on assignment at randomization regardless of the 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
45 
intervention received (modified intent to treat). These analysis sets will be used for analysis of the 
secondary endpoints (Table 5). 
 
The full analysis set (FAS) is the set of all trial participants who enroll and are eligible for the study. 
Patients who enroll but subsequently drop out prior to receiving any of the assigned intervention will be 
replaced. This analysis set will be used for secondary analyses of both the primary endpoint and 
secondary endpoints. 
 
Per protocol set is composed of all patients enrolled in the trial who have completed 6-weeks of the 
BRIGHT/AC interventions as described in the protocol. This analysis set will be used for secondary 
analyses of both the primary endpoint and secondary endpoints. 
 
Details about the analytic plan for each population are described in detail in Section 9.4. 
 
9.4 
STATISTICAL ANALYSES 
A statistical analysis plan (SAP) will be developed prior to database lock. The SAP will detail all planned 
analyses and analytic methods. 
 
All statistical analyses will be performed using SAS or R packages. Graphical displays (e.g., bar charts, 
boxplots) and summary statistics (e.g., mean, median, standard deviation, interquartile range) will be 
used to characterize the data. Two sample t-tests or non-parametric Wilcoxon rank-sum tests will be 
used to compare continuous measures. Normality and variance homogeneity assumptions will be 
assessed, with appropriate data transformations as needed. The chi-square test will be used to evaluate 
associations between discrete variables. 
 
9.4.1 MISSING DATA 
The analytic method for the primary endpoint will be generalized estimating equations (GEEs), which 
requires missing data to be missing completely at random for valid inference. We expect the rate of 
missing data to small and anticipate GEE analysis to be appropriate. However, if the rate of missing data 
is significant, we will use linear mixed effect regression (LMER) as our primary analytic approach and 
GEEs as a secondary approach. A review of the data will be performed prior to database lock to establish 
overall rates of missingness for the primary endpoint and the SAP updated if needed to reflect any 
changes in planned analyses. 
 
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT 
We will use a model-based approach to analyze change in IMAGE-HN score from baseline to 6-month 
follow-up. Specifically, change in IMAGE-HN score will be modeled using a regression model with a 
factor for trial arm, covariates for the randomization stratification variable of site and free flap 
reconstruction, and pre-specified baseline covariates known to be prognostic for the primary endpoint 
including baseline IMAGE-HN score, gender, education, employment, tumor location, and adjuvant 
therapy.8,75 The selection of pre-specified baseline covariates known to be prognostic follows best 
practices for randomized clinical trials.103 Additionally, adjusting for the baseline score in a change-score 
analysis is discussed at length by Frank Harrell and James Slaughter.104 The GEE regression model was 
selected to account for the clustering of patients within psychologist (BRIGHT arm) or HN clinical staff 
member (AC arm). Our preferred model-based approach is a marginal model using GEEs because 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
46 
subsequent inference best aligns with the trial’s stated primary objective. Furthermore, GEEs are robust 
to variance misspecification. We will use GEEs with an identity link and an exchangeable working 
correlation structure. Final inference will be based on the robust sandwich estimator.  
 
The primary analysis will use the 6-month IMAGE-HN evaluable set, which eliminates unit non-response, 
that is, patient data where the baseline or 6-month survey is not completed. However, the potential for 
survey item non-response exists. There are three types of item non-response to consider: (1) the item is 
missing at baseline and at follow-up; (2) the item is missing at baseline but not missing at follow-up; and 
(3) the item is not missing at baseline but is missing at follow-up. We expect the rate of item non-
response at baseline to be 0% given training of study coordinators and our experience with the pilot 
study. In the event of item non-response at the 6-month follow-up, we adopt a conservative imputation 
approach to avoid inflation of treatment effect. Accordingly, we will impute the baseline value for the 
given item to reflect no change. As a sensitivity analysis, we will also impute the item’s value from the 
most recent follow-up time prior to 6-months. Finally, depending on the extent of missing data, we may 
additionally perform sensitivity analyses using multiple imputation or treating survey total scores as 
interval censored. 
 
To evaluate the inferential impact of our modeling choice (GEE) and cross-sectional (as opposed to 
longitudinal) data analyses, the following secondary analyses will be conducted using the 6-month 
IMAGE-HN evaluable set: 
1. We will model change in IMAGE-HN score from baseline to 6-month follow-up using a LMER 
model with a factor for trial arm, the randomization stratification variables of site and free flap 
reconstruction, and pre-specified baseline covariates including baseline IMAGE-HN score, 
gender, education, employment, tumor location, and adjuvant therapy. Cluster-specific random 
effects will be included assuming an exchangeable correlation structure. 
2. We will model change in IMAGE-HN score from baseline across all timepoints using GEEs and 
LMER models as described. Additional model terms for time (discrete), and trial arm-by-time 
interaction will be included. 
 
All analyses described will be repeated using the per-protocol analysis set. 
 
To evaluate the inferential impact of eliminating unit non-response in our primary analysis, the following 
additional sensitivity analyses will be performed using the FAS: (1) any trial participant missing the 6-
month follow-up survey will be counted as having a 6-month total score equal to the baseline total score 
(no change from baseline); and (2) any trial participant missing the 6-month follow-up survey will be 
counted as having a 6-month total score equal to the maximum total score. Trial participants without a 
baseline survey will be excluded from these analyses. 
 
9.4.3 ANALYSIS OF SECONDARY ENDPOINTS 
Secondary endpoints for changes in stigma, depression, anxiety, suicidal ideation, social isolation, and 
QOL will be analyzed with similar approaches. Covariates prognostic for each of these secondary 
endpoints will be pre-specified prior to formulation of the final SAP. 
 
We will perform a causal mediation analysis105 to evaluate the degree to which the effect of treatment 
(BRIGHT) on the primary outcome (change in IMAGE-HN scores between baseline and 6-month follow-

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
47 
up) is mediated by changes in candidate mechanism of change variables (between baseline and 3-month 
follow-up, covariates). We will use structural equation modeling to perform mediation analysis for each 
of the following mechanism of change variables: (1) BICSI Positive Rational Acceptance score;55 (2) BICSI 
Avoidance score;55 (3) BICSI Appearance Fixing score;55 and (4) Automatic Thoughts Questionnaire 
score.96 This approach allows for ease of interpretation and estimation in Mplus. Model fit will be 
assessed using chi-square, comparative fit index (>0.95), root mean square of approximation (<0.06), 
and standardized root mean square residual (<0.08).106,107 Missing data will be handled with maximum 
likelihood estimation.108 If we encounter challenges in model stability, we will use Baron and Kenny’s 
approach.109 The following regression analyses will be performed: (i) the outcome (IMAGE-HN score) is 
regressed on a treatment group indicator (BRIGHT, AC) to obtain a regression model measure of the 
intervention effect; (ii) the candidate mediator (e.g., BICSI Avoidance score) is regressed on the 
treatment group indicator (BRIGHT, AC) to obtain a measure of the intervention’s effect on the 
covariate; and (iii) the outcome (IMAGE-HN score) is regressed on both the treatment group indicator 
(BRIGHT, AC) and the candidate mediator (e.g., BICSI Avoidance score). We will conclude that the 
candidate mediator in fact mediates the effects of the intervention if: (1) in both analyses (i) and (ii), the 
treatment group indicator is significant; and (2) in analysis (iii), the candidate mediator is significant and 
the coefficient estimate of the treatment group indicator is smaller in absolute value than its 
counterpart in analysis (i). If we detect mediation, we will consider Sobel’s test to assess the significance 
of the mediation effect. We will examine standardized coefficients for the direct pathways and the 
mediation pathways to compare the strength of each. If the cluster effect is significant, we will conduct 
multilevel mediation analysis for partially nested data.110 The study design consideration and analytic 
plan follow recommended criteria to provide evidence for mechanism of change above and beyond 
statistical mediation.111 We will also explore mediation analysis using multiple mediators.112,113 Finally, to 
better understand the temporal dynamics of causal intervention effects, we will adapt Goldsmith’s 
approach to: (1) examine the intervention effect on outcomes at different time points; (2) examine the 
intervention effect on hypothesized mediators at different time points; (3) examine the relation of the 
mediator to the outcome at different time points; and (4) determine if there is temporal variation in the 
mediating process.114 If there is temporal variation in the mediating process, we will fit a multilevel 
mediation model using the approach described by Preacher.115 
 
9.4.4 SAFETY ANALYSES 
All patients in the SAS will be evaluated for safety and toxicity. Adverse events, SAEs and will be 
summarized. Safety analyses will include the following summaries: 
• 
AEs, including severity and relationship to a study intervention 
• 
SAEs, including relationship to a study intervention 
 
9.4.5 PLANNED INTERMIN ANALYSES 
N/A 
9.4.6 SUB-GROUP ANALYSES 
Treatment heterogeneity will be evaluated by conducting the following sub-group analyses of the 
primary and secondary endpoints:  
• 
Age: > 65 years vs < 65 years 
• 
Race: white vs non-white 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
48 
• 
Gender: male vs female 
• 
Education: < high school vs > high school 
• 
Employment status: disability/unemployed vs working vs retired 
• 
Tumor location: upper aerodigestive tract cancer vs salivary/facial cutaneous cancer 
• 
Reconstruction: non-free flap reconstruction vs free flap reconstruction 
• 
Adjuvant Therapy: none vs radiation therapy/chemoradiation 
9.4.7 EXPLORATORY ANALYSES 
N/A 
 
 
9.5 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
9.5.1 SINGLE IRB COORDINATION 
The study will be conducted under a single IRB study with MUSC IRB serving as the IRB of record. The 
MUSC IRB will initiate the reliance agreements with each relying institution, that each relying 
institution will be responsible for performing a local context review of the study to ensure that the 
protocol is appropriate and reasonable for their respective study populations. The structure and 
organization of the study team is shown is described below. 
 
1. Administrative Sites. The overall administration of the study will occur at MUSC. 
 
2. Data Coordinating Sites. MUSC will serve as the data coordinating site. Study documents will 
originate from MUSC and be disseminated to each site. 
 
3. Participating Sites. In this multisite clinical trial comparing BRIGHT with AC, eligible patients with 
clinically significant HNC-related BID will be recruited from MUSC, HFH, and WUSM. Study procedures 
and assessments will be conducted at each site as described in the protocol. 
 
4. Separate Laboratory and Testing Centers. There are no separate laboratory and testing centers. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
49 
5. Study Team Composition. The organization of the study team is shown in Figure 8. For the conduct of 
the trial, the structure of each study team is identical (site PI, psychologist, HNC Clinical staff, and 
program coordinator). 
 
The study will be coordinated as an sIRB study with the following communication plan. Study documents 
will be maintained in a HIPAA-compliant and secure shared folder (MUSC Box) to which all non-MUSC 
study personnel will be given download access. Interactions among sites will be coordinated through 
site PIs via secure email, telephone call, or video telemedicine sessions (e.g., Microsoft Teams). 
9.5.2 INFORMED CONSENT PROCESS 
9.5.2.1 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. 
9.5.2.2 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 designated to perform informed consent. A study team member will answer any questions 
Fig 8. Organization of study team 
Evan Graboyes, MD, MPH
Biostatistics (MUSC)
-Elizabeth Hill, PhD (Co-I; lead 
biostatistician)
-Kent Armeson (data monitoring)
HFH Study Team
-Steve Chang, MD (Co-I; site PI)
-Psychologists (BRIGHT delivery)
-HNC Clinical Staff (AC delivery)
-Program Coordinator
MUSC Study Team
-Evan Graboyes, MD, MPH (PI, site PI)
-Psychologists (BRIGHT delivery)
-HNC Clinical Staff (AC delivery)
-Program Coordinator
WUSM Study Team
-Patrik Pipkorn, MD, MSCI (Co-I; site PI)
-Psychologists (BRIGHT delivery)
-HNC Clinical Staff (AC delivery)
-Program Coordinator
Co-Investigators
(MUSC, HFH, WUSM)
-Katherine Sterba, PhD, MPH (MUSC)
-Kenneth Ruggiero, PhD (MUSC)
-Elizabeth Hill, PhD (MUSC)
-Steven Chang, MD (HFH)
-Patrik Pipkorn, MD, MSCI (WUSM)
Principal Investigator (MUSC)

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
50 
about the 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 a private research space at each 
site (if in-person) or via secure telemedicine platform (if electronic informed consent). Only the study 
participant will provide informed consent. The signed copy of the informed consent document will be 
stored in the study binder in each patient’s section. Subjects will be allowed up to one week to decide 
whether to participate in the study. If required by the site, 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. 
9.5.3 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, or other relevant regulatory or oversight 
bodies. 
9.5.4 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 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 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. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
51 
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. 
9.5.5 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. 
 
9.5.6 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator 
Evan Graboyes, MD, MPH, FACS 
Medical University of South Carolina  
135 Rutledge Ave, MSC 550 
Charleston, SC 29425 
843-792-0719 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
52 
graboyes@musc.edu 
 
9.5.7 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. 
 
9.5.8 CLINICAL MONITORING 
N/A 
 
9.5.9 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 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 9.5.10, 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. 
9.5.10 DATA HANDLING AND RECORD KEEPING  
9.5.10.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
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 eCRF derived 
from source documents will be consistent with the data recorded on the source documents.  

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
53 
 
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. 
9.5.10.2 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. 
9.5.11 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). 
9.5.12 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 9.5.4. 
9.5.13 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. 
9.6 
ADDITIONAL CONSIDERATIONS 
N/A 
9.7 
ABBREVIATIONS AND SPECIAL TERMS 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
54 
Table 9. Abbreviations and Special Terms 
AC 
Attention Control 
AE 
Adverse Event 
AJCC 
American Joint Committee on Cancer 
BICSI 
Body Image Coping Strategies Inventory 
BID 
Body Image-Related Distress 
CBT 
Cognitive Behavioral Therapy 
CFR 
Code of Federal Regulations 
BRIGHT 
Building a Renewed ImaGe after Head & neck cancer Treatment 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
DSMP 
Data Safety Monitoring Plan 
eCRF 
Electronic Case Report Form 
EHR 
Electronic Health Record 
EORTC 
European Organisation for Research and Treatment of Cancer 
FAS 
Full Analysis Set 
GEE 
Generalized Estimating Equation 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
HNC 
Head and Neck Cancer 
ICC 
Intracluster Correlation Coefficient 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation  
IMAGE-HN Inventory to Measure and Assess imaGe disturbancE-Head & Neck 
IRB 
Institutional Review Board 
ITT 
Intention-To-Treat 
LMER 
Linear Mixed Effect Regression 
MUSC 
Medical University of South Carolina 
MyCB 
MyChangedBody 
NCI 
National Cancer Institute 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
ORHP 
Office for Human Research Protections 
PI 
Principal Investigator 
PROM 
Patient-Reported Outcome Measure 
PRMOIS 
Patient-Reported Outcomes Measurement Information System 
QOL 
Quality of Life 
RCT 
Randomized Clinical Trial 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Safety Analysis Set 
SF 
Short Form 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
55 
US 
United States 
 
 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
56 
9.8 
PROTOCOL AMENDMENT HISTORY 
 
Table 10. Protocol Amendment History 
Version 
Date 
Description of Change  
Brief Rationale 
2.0 
8 December 
2022 
See attached separate document 
describing protocol changes 
See attached separate 
document describing protocol 
changes 
3.0 
8 February 
2023 
See attached separate document 
describing protocol changes 
See attached separate 
document describing protocol 
changes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
57 
10 REFERENCES 
1. 
Cohen EE, LaMonte SJ, Erb NL, et al. American Cancer Society Head and Neck Cancer 
Survivorship Care Guideline. CA Cancer J Clin 2016; 66:203-239. 
 
2. 
Nekhlyudov L, Lacchetti C, Davis NB, et al. Head and Neck Cancer Survivorship Care 
Guideline: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of 
the American Cancer Society Guideline. J Clin Oncol 2017; 35:1606-1621. 
 
3. 
Fingeret MC, Nipomnick S, Guindani M, Baumann D, Hanasono M, Crosby M. Body image 
screening for cancer patients undergoing reconstructive surgery. Psychooncology 2014; 
23:898-905. 
 
4. 
Macias D, Hand BN, Pipkorn P, et al. Association of Inventory to Measure and Assess imaGe 
Disturbance - Head and Neck Scores With Clinically Meaningful Body Image-Related Distress 
Among Head and Neck Cancer Survivors. Front Psychol 2021; 12:794038. 
 
5. 
Fingeret MC, Teo I, Goettsch K. Body image: a critical psychosocial issue for patients with 
head and neck cancer. Curr Oncol Rep 2015; 17:422. 
 
6. 
Fingeret MC, Yuan Y, Urbauer D, Weston J, Nipomnick S, Weber R. The nature and extent of 
body image concerns among surgically treated patients with head and neck cancer. 
Psychooncology 2012; 21:836-844. 
 
7. 
Rhoten BA, Murphy B, Ridner SH. Body image in patients with head and neck cancer: a 
review of the literature. Oral Oncol 2013; 49:753-760. 
 
8. 
Macias D, Hand BN, Maurer S, et al. Factors Associated With Risk of Body Image-Related 
Distress in Patients With Head and Neck Cancer. JAMA Otolaryngol Head Neck Surg 2021; 
147:1019-1026. 
 
9. 
Buckwalter AE, Karnell LH, Smith RB, Christensen AJ, Funk GF. Patient-reported factors 
associated with discontinuing employment following head and neck cancer treatment. Arch 
Otolaryngol Head Neck Surg 2007; 133:464-470. 
 
10. 
Osazuwa-Peters N, Simpson MC, Zhao L, et al. Suicide risk among cancer survivors: Head and 
neck versus other cancers. Cancer 2018; 124:4072-4079. 
 
11. 
Cognetti DM, Villaflor VM, Fakhry C, Miller MC, Malloy KM. Survivorship support in head and 
neck cancer: American Head and Neck Society survey. Head Neck 2020. 
 
12. 
Huang S, Liu HE. Effectiveness of cosmetic rehabilitation on the body image of oral cancer 
patients in Taiwan. Support Care Cancer 2008; 16:981-986. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
58 
13. 
Chen SC, Huang BS, Lin CY, et al. Psychosocial effects of a skin camouflage program in female 
survivors with head and neck cancer: A randomized controlled trial. Psychooncology 2017; 
26:1376-1383. 
 
14. 
Melissant HC, Jansen F, Eerenstein SEJ, et al. A structured expressive writing activity 
targeting body image-related distress among head and neck cancer survivors: who do we 
reach and what are the effects? Support Care Cancer 2021. 
 
15. 
Ellis MA, Sterba KR, Brennan EA, et al. A Systematic Review of Patient-Reported Outcome 
Measures Assessing Body Image Disturbance in Patients with Head and Neck Cancer. 
Otolaryngol Head Neck Surg 2019; 160:941-954. 
 
16. 
Graboyes EM, Maurer S, Park Y, et al. Evaluation of a novel telemedicine-based intervention 
to manage body image disturbance in head and neck cancer survivors. Psychooncology 
2020; 29:1988-1994. 
 
17. 
Folkman S. Positive psychological states and coping with severe stress. Soc Sci Med 1997; 
45:1207-1221. 
 
18. 
David D, Montgomery GH. The Scientific Status of Psychotherapies: A New Evaluative 
Framework for Evidence-Based Psychosocial Interventions. Clin Psychol Sci Prac 2011; 18:89-
99. 
 
19. 
David D, Szentagotai A. Cognitions in cognitive-behavioral psychotherapies; toward an 
integrative model. Clin Psychol Rev 2006; 26:284-298. 
 
20. 
Murphy R, Cooper Z, Hollon SD, Fairburn CG. How do psychological treatments work? 
Investigating mediators of change. Behav Res Ther 2009; 47:1-5. 
 
21. 
Powers MB, de Kleine RA, Smits JAJ. Core Mechanisms of Cognitive Behavioral Therapy for 
Anxiety and Depression: A Review. Psychiatr Clin North Am 2017; 40:611-623. 
 
22. 
Dobson KS. The science of CBT: toward a metacognitive model of change? Behav Ther 2013; 
44:224-227. 
 
23. 
Hofmann SG, Asmundson GJ, Beck AT. The science of cognitive therapy. Behav Ther 2013; 
44:199-212. 
 
24. 
Cash TF, Smolak L. Body Image: A Handbook of Science, Practice, and Prevention. New York: 
Guilford Press, 2012:490. 
 
25. 
Kayser K, Brydon DM, Moon H, Zebrack B. Institutional capacity to provide psychosocial care 
in cancer programs: Addressing barriers to delivering quality cancer care. Psychooncology 
2020; 29:1995-2002. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
59 
26. 
Wampold BE. How important are the common factors in psychotherapy? An update. World 
Psychiatry 2015; 14:270-277. 
 
27. 
Graboyes EM, Hand BN, Ellis MA, et al. Validation of a Novel, Multidomain Head and Neck 
Cancer Appearance- and Function-Distress Patient-Reported Outcome Measure. Otolaryngol 
Head Neck Surg 2020; 163:979-985. 
 
28. 
Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2019. 
CA Cancer J Clin 2019; 69:363-385. 
 
29. 
Tota JE, Best AF, Zumsteg ZS, Gillison ML, Rosenberg PS, Chaturvedi AK. Evolution of the 
Oropharynx Cancer Epidemic in the United States: Moderation of Increasing Incidence in 
Younger Individuals and Shift in the Burden to Older Individuals. J Clin Oncol 2019; 37:1538-
1546. 
 
30. 
Melissant HC, Jansen F, Eerenstein SE, et al. Body image distress in head and neck cancer 
patients: what are we looking at? Support Care Cancer 2021; 29:2161-2169. 
 
31. 
Kissane DW, Patel SG, Baser RE, et al. Preliminary evaluation of the reliability and validity of 
the Shame and Stigma Scale in head and neck cancer. Head Neck 2013; 35:172-183. 
 
32. 
Branch L, C. F, McQuestion M. An Investigation into Body Image Concerns in the Head and 
Neck Cancer Population Receiving Radiation or Chemoradiation Using the Body Image Scale: 
A Pilot Study. Journal of Medical Imaging and Radiation Sciences 2017; 48:169-165. 
 
33. 
Clarke SA, Newell R, Thompson A, Harcourt D, Lindenmeyer A. Appearance concerns and 
psychosocial adjustment following head and neck cancer: A cross-sectional study and nine-
month follow-up. Psychol Health Med 2014; 19:505-518. 
 
34. 
Chen SC, Yu PJ, Hong MY, et al. Communication dysfunction, body image, and symptom 
severity in postoperative head and neck cancer patients: factors associated with the amount 
of speaking after treatment. Support Care Cancer 2015; 23:2375-2382. 
 
35. 
Hung TM, Lin CR, Chi YC, et al. Body image in head and neck cancer patients treated with 
radiotherapy: the impact of surgical procedures. Health Qual Life Outcomes 2017; 15:165. 
 
36. 
Chen C, Cao J, Wang L, Zhang R, Li H, Peng J. Body image and its associated factors among 
Chinese head and neck cancer patients undergoing surgical treatment: a cross-sectional 
survey. Support Care Cancer 2019. 
 
37. 
Graboyes EM, Hill EG, Marsh CH, Maurer S, Day TA, Sterba KR. Body Image Disturbance in 
Surgically Treated Head and Neck Cancer Patients: A Prospective Cohort Pilot Study. 
Otolaryngol Head Neck Surg 2019; 161:105-110. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
60 
38. 
Rhoten BA, Deng J, Dietrich MS, Murphy B, Ridner SH. Body image and depressive symptoms 
in patients with head and neck cancer: an important relationship. Support Care Cancer 
2014; 22:3053-3060. 
 
39. 
Hopwood P, Fletcher I, Lee A, Al Ghazal S. A body image scale for use with cancer patients. 
Eur J Cancer 2001; 37:189-197. 
 
40. 
Graboyes EM, Hill EG, Marsh CH, et al. Temporal Trajectory of Body Image Disturbance in 
Patients with Surgically Treated Head and Neck Cancer. Otolaryngol Head Neck Surg 2020; 
162:304-312. 
 
41. 
Sherman KA, Przezdziecki A, Alcorso J, et al. Reducing Body Image-Related Distress in 
Women With Breast Cancer Using a Structured Online Writing Exercise: Results From the My 
Changed Body Randomized Controlled Trial. J Clin Oncol 2018; 36:1930-1940. 
 
42. 
Jarry JL, Ip K. The effectiveness of stand-alone cognitive-behavioural therapy for body 
image: a meta-analysis. Body Image 2005; 2:317-331. 
 
43. 
Jarry JL, Berardi K. Characteristics and effectiveness of stand-alone body image treatments: 
a review of the empirical literature. Body Image 2004; 1:319-333. 
 
44. 
Fingeret MC, Teo I, Epner DE. Managing body image difficulties of adult cancer patients: 
lessons from available research. Cancer 2014; 120:633-641. 
 
45. 
Alleva JM, Sheeran P, Webb TL, Martijn C, Miles E. A Meta-Analytic Review of Stand-Alone 
Interventions to Improve Body Image. PLoS One 2015; 10:e0139177. 
 
46. 
Lewis-Smith H, Diedrichs PC, Halliwell E. Cognitive-behavioral roots of body image therapy 
and prevention. Body Image 2019; 31:309-320. 
 
47. 
Blashill AJ, Safren SA, Wilhelm Set al. Cognitive behavioral therapy for body image and self-
care (CBT-BISC) in sexual minority men living with HIV: A randomized controlled trial. Health 
Psychol 2017; 36:937-946. 
 
48. 
Newell RJ. Altered body image: a fear-avoidance model of psycho-social difficulties following 
disfigurement. J Adv Nurs 1999; 30:1230-1238. 
 
49. 
Bessell A, Brough V, Clarke A, Harcourt D, Moss TP, Rumsey N. Evaluation of the 
effectiveness of Face IT, a computer-based psychosocial intervention for disfigurement-
related distress. Psychol Health Med 2012; 17:565-577. 
 
50. 
Faraji J, Mahdavi A, Samkhaniyan E, Asadi SH, Dezhkam N. A review of the effectiveness of 
cognitive-behavioral group therapy on the reduction of body image concern in patients with 
breast cancer. J Med Life 2015; 8:82-86. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
61 
51. 
Fadaei S, Janighorban M, Mehrabi T, Ahmadi SA, Mokaryan F, Gukizade A. Effects of 
cognitive behavioral counseling on body Image following mastectomy. J Res Med Sci 2011; 
16:1047-1054. 
 
52. 
Hummel SB, van Lankveld J, Oldenburg HAS, et al. Efficacy of Internet-Based Cognitive 
Behavioral Therapy in Improving Sexual Functioning of Breast Cancer Survivors: Results of a 
Randomized Controlled Trial. J Clin Oncol 2017; 35:1328-1340. 
 
53. 
Lewis-Smith H, Diedrichs PC, Rumsey N, Harcourt D. Efficacy of psychosocial and physical 
activity-based interventions to improve body image among women treated for breast 
cancer: A systematic review. Psychooncology 2018; 27:2687-2699. 
 
54. 
Bessell A, Moss TP. Evaluating the effectiveness of psychosocial interventions for individuals 
with visible differences: a systematic review of the empirical literature. Body Image 2007; 
4:227-238. 
 
55. 
Cash TF, Santos MT, Williams EF. Coping with body-image threats and challenges: validation 
of the Body Image Coping Strategies Inventory. J Psychosom Res 2005; 58:190-199. 
 
56. 
Ellis MA, Sterba KR, Day TA, et al. Body Image Disturbance in Surgically Treated Head and 
Neck Cancer Patients: A Patient-Centered Approach. Otolaryngol Head Neck Surg 2019; 
161:278-287. 
 
57. 
Cho J, Fingeret MC, Huang SC, Liu J, Reece GP, Markey MK. Observers' response to facial 
disfigurement from head and neck cancer. Psychooncology 2018. 
 
58. 
Klimek P, Wilhelm S, Safren SA, Blashill AJ. Cognitive Behavioral Therapy for Body Image and 
Self-Care (CBT-BISC) among Sexual Minority Men Living with HIV: Skills-Based Treatment 
Mediators. Cognit Ther Res 2020; 44:208-215. 
 
59. 
Melnyk SE, Cash TF, Janda LH. Body image ups and downs: prediction of intra-individual 
level and variability of women's daily body image experiences. Body Image 2004; 1:225-235. 
 
60. 
Blakey SM, Reuman L, Buchholz JL, Abramowitz JS. Experiential avoidance and dysfunctional 
beliefs in the prediction of body image disturbance in a nonclinical sample of women. Body 
Image 2017; 22:72-77. 
 
61. 
Yamani Ardakani B, Tirgari B, Roudi Rashtabadi O. Body image and its relationship with 
coping strategies: The views of Iranian breast cancer women following surgery. Eur J Cancer 
Care (Engl) 2020; 29:e13191. 
 
62. 
Stefan S, Cristea IA, Szentagotai Tatar A, David D. Cognitive-behavioral therapy (CBT) for 
generalized anxiety disorder: Contrasting various CBT approaches in a randomized clinical 
trial. J Clin Psychol 2019; 75:1188-1202. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
62 
63. 
van Beugen S, Ferwerda M, Hoeve D, et al. Internet-based cognitive behavioral therapy for 
patients with chronic somatic conditions: a meta-analytic review. J Med Internet Res 2014; 
16:e88. 
 
64. 
David JM, Ho AS, Luu M, et al. Treatment at high-volume facilities and academic centers is 
independently associated with improved survival in patients with locally advanced head and 
neck cancer. Cancer 2017; 123:3933-3942. 
 
65. 
Graboyes EM, Ellis MA, Li H, et al. Racial and Ethnic Disparities in Travel for Head and Neck 
Cancer Treatment and the Impact of Travel Distance on Survival. Cancer 2018; 124:3181-
3191. 
 
66. 
Implementing Cancer Survivorship Care Planning. Washington, DC: National Academies 
Press, 2007. 
 
67. 
Burris JL, Andrykowski M. Disparities in mental health between rural and nonrural cancer 
survivors: a preliminary study. Psychooncology 2010; 19:637-645. 
 
68. 
Allison PJ, Edgar L, Nicolau B, Archer J, Black M, Hier M. Results of a feasibility study for a 
psycho-educational intervention in head and neck cancer. Psychooncology 2004; 13:482-
485. 
 
69. 
Budhrani-Shani P, Chau NG, Berry DL. Psychosocial distress and the preferred method of 
delivery of mind-body interventions among patients with head-and-neck cancer. Patient 
Relat Outcome Meas 2018; 9:129-136. 
 
70. 
Wootton R, Bahaadinbeigy K, Hailey D. Estimating travel reduction associated with the use 
of telemedicine by patients and healthcare professionals: proposal for quantitative synthesis 
in a systematic review. BMC Health Serv Res 2011; 11:185. 
 
71. 
Doolittle GC, Spaulding AO. Providing Access to Oncology Care for Rural Patients via 
Telemedicine. J Oncol Pract 2006; 2:228-230. 
 
72. 
Agnisarman SO, Chalil Madathil K, Smith K, Ashok A, Welch B, McElligott JT. Lessons learned 
from the usability assessment of home-based telemedicine systems. Appl Ergon 2017; 
58:424-434. 
 
73. 
Andersson G, Cuijpers P, Carlbring P, Riper H, Hedman E. Guided Internet-based vs. face-to-
face cognitive behavior therapy for psychiatric and somatic disorders: a systematic review 
and meta-analysis. World Psychiatry 2014; 13:288-295. 
 
74. 
Eldredge L, Markham C, Ruiter R, Fernandez ME, Kok G, Parcel G. Planning Health Promotion 
Interventions: An Intervention Mapping Approach. San Francisco, CA: Jossey-Bass, 2016. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
63 
75. 
Graboyes EM, Maurer S, Balliet W, et al. Efficacy of a Brief Tele-Cognitive Behavioral 
Treatment vs Attention Control for Head and Neck Cancer Survivors With Body Image 
Distress: A Pilot Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg 2022. 
 
76. 
Hatcher RL, Gillaspy JA. Development and validation of a revised short version of the 
Working Alliance Inventory. Psychotherapy Research 2006; 16:12–25. 
 
77. 
Nilsen ML, Clump DA, 2nd, Kubik M, et al. Prevision of multidisciplinary head and neck 
cancer survivorship care during the 2019 novel coronavirus pandemic. Head Neck 2020; 
42:1668-1673. 
 
78. 
Huang VW, Imam SA, Nguyen SA. Head and neck survivorship care in the times of the SARS-
CoV-2 pandemic. Head Neck 2020; 42:1664-1667. 
 
79. 
Greenbaum Z. How well is telepsychology working? Available at: 
https://www.apa.org/monitor/2020/07/cover-telepsychology. Accessed April 8 2021. 
 
80. 
Murphy R, Calugi S, Cooper Z, Dalle Grave R. Challenges and Opportunities for enhanced 
cognitive behaviour therapy (CBT-E) in light of COVID-19. The Cognitive Behaviour Therapist 
2020:1-31. 
 
81. 
Crawford A, Serhal E. Digital Health Equity and COVID-19: The Innovation Curve Cannot 
Reinforce the Social Gradient of Health. J Med Internet Res 2020; 22:e19361. 
 
82. 
Holmes C. Guide to Finding the Best Cell Phone Coverage. March 2, 2021. Available at: 
https://www.whistleout.com/CellPhones/Guides/Coverage. Accessed April 1 2021. 
 
83. 
Carroll KM, Rounsaville BJ. Efficacy and effectiveness in developing treatment manuals. In: 
Nezu AM, Nezu CM, eds. Evidence-Based Outcome Research: A Practical Guide to 
Conducting Randomized Controlled Trials of Psychosocial Interventions. New York: Oxford 
University Press, 2008. 
 
84. 
Freedland KE, King AC, Ambrosius WT, et al. The selection of comparators for randomized 
controlled trials of health-related behavioral interventions: recommendations of an NIH 
expert panel. J Clin Epidemiol 2019; 110:74-81. 
 
85. 
Waller G, Stringer H, Meyer C. What cognitive behavioral techniques do therapists report 
using when delivering cognitive behavioral therapy for the eating disorders? J Consult Clin 
Psychol 2012; 80:171-175. 
 
86. 
Carroll KM, Nich C, Sifry RLet al. A general system for evaluating therapist adherence and 
competence in psychotherapy research in the addictions. Drug Alcohol Depend 2000; 
57:225-238. 
 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
64 
87. 
Hansen WB, Malotte CK, Fielding JE. The bogus pipeline revisited: the use of the threat of 
detection as a means of increasing self-reports of tobacco use. J Appl Psychol 1985; 70:789-
792. 
 
88. 
Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of 
life: the remarkable universality of half a standard deviation. Med Care 2003; 41:582-592. 
 
89. 
Pilkonis PA, Choi SW, Reise SP, et al. Item banks for measuring emotional distress from the 
Patient-Reported Outcomes Measurement Information System (PROMIS(R)): depression, 
anxiety, and anger. Assessment 2011; 18:263-283. 
 
90. 
Beck AT, Steer RA, Ranieri WF. Scale for Suicide Ideation: psychometric properties of a self-
report version. J Clin Psychol 1988; 44:499-505. 
 
91. 
Beck AT, Steer RA. Manual for the Beck Scale for Suicide Ideation. San Antonio, TX: 
Psychological Corporation, 1991. 
 
92. 
Beck AT, Brown GK, Steer RA, Dahlsgaard KK, Grisham JR. Suicide ideation at its worst point: 
a predictor of eventual suicide in psychiatric outpatients. Suicide Life Threat Behav 1999; 
29:1-9. 
 
93. 
Hahn EA, DeWalt DA, Bode RK, et al. New English and Spanish social health measures will 
facilitate evaluating health determinants. Health Psychol 2014; 33:490-499. 
 
94. 
Bode RK, Hahn EA, DeVellis R, Cella D, Patient-Reported Outcomes Measurement 
Information System Social Domain Working G. Measuring participation: the Patient-
Reported Outcomes Measurement Information System experience. Arch Phys Med Rehabil 
2010; 91:S60-65. 
 
95. 
Bjordal K, de Graeff A, Fayers PM, et al. A 12 country field study of the EORTC QLQ-C30 
(version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head 
and neck patients. EORTC Quality of Life Group. Eur J Cancer 2000; 36:1796-1807. 
 
96. 
Netemeyer RG, Williamson DA, Burton S, Biswas D, Jindal S, Landreth S. Psychometric 
properties of shortened versions of the automatic thoughts questionnaire. Educational and 
Psychological Measurement 2002; 62:111-129. 
 
97. 
Decker SE, Nich C, Carroll KM, Martino S. Development of the Therapist Empathy Scale. 
Behav Cogn Psychother 2014; 42:339-354. 
 
98. 
Devilly GJ, Borkovec TD. Psychometric properties of the credibility/expectancy 
questionnaire. J Behav Ther Exp Psychiatry 2000; 31:73-86. 
 
99. 
Duggan C, Parry G, McMurran M, Davidson K, Dennis J. The recording of adverse events 
from psychological treatments in clinical trials: evidence from a review of NIHR-funded 
trials. Trials 2014; 15:335. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
65 
 
100. 
Esplen MJ, Wong J, Warner E, Toner B. Restoring Body Image After Cancer (ReBIC): Results 
of a Randomized Controlled Trial. J Clin Oncol 2018; 36:749-756. 
 
101. 
Eldridge SM, Ashby D, Feder GS, Rudnicka AR, Ukoumunne OC. Lessons for cluster 
randomized trials in the twenty-first century: a systematic review of trials in primary care. 
Clin Trials 2004; 1:80-90. 
 
102. 
Baldwin SA, Murray DM, Shadish WRet al. Intraclass correlation associated with therapists: 
estimates and applications in planning psychotherapy research. Cogn Behav Ther 2011; 
40:15-33. 
 
103. 
Adjusting for Covariates in Randomized Clinical Trials for Drugs and Biological Products, 
Guidance for Industry, Revision 1. In: US Department of Health and Human Services FaDA, 
Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, ed., 
2021. 
 
104. 
Harrell FE, Slaughter JC. Biostatistics for Biomedical Research. In: Slaughter FHJ, ed., 2022. 
 
105. 
MacKinnon DP, Fairchild AJ, Fritz MS. Mediation analysis. Annu Rev Psychol 2007; 58:593-
614. 
 
106. 
Kline RB. Principles and Practice of Structural Equation Modeling. New York, NY: The 
Guilford Press, 2016. 
 
107. 
Hooper D, Coughlan J, Mullen M. Structural Equation Modelling: Guidelines for Determining 
Model Fit. Electronic Journal of Business Research Methods 2008; 6:53-60. 
 
108. 
Molenberghs G, Kenward MG. Missing Data in Clinical Studies. West Sussex, England: John 
Wiley & Sons, 2007. 
 
109. 
Baron RM, Kenny DA. The moderator-mediator variable distinction in social psychological 
research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 1986; 
51:1173-1182. 
 
110. 
Lachowicz MJ, Sterba SK, Preacher KJ. Investigating multilevel mediation with fully or 
partially nested data. Group Processes & Intergroup Relations 2015; 18:274-289. 
 
111. 
Kazdin AE. Mediators and mechanisms of change in psychotherapy research. Annu Rev Clin 
Psychol 2007; 3:1-27. 
 
112. 
Daniel RM, De Stavola BL, Cousens SN, Vansteelandt S. Causal mediation analysis with 
multiple mediators. Biometrics 2015; 71:1-14. 
 
113. 
VanderWeele TJ, Vansteelandt S. Mediation Analysis with Multiple Mediators. Epidemiol 
Methods 2014; 2:95-115. 

BRIGHT 
 
Version 3.0  
Protocol #103733 
 
8 February 2023 
Based on the NIH Protocol Template for Behavioral and Social Sciences Research 
 
66 
 
114. 
Goldsmith KA, MacKinnon DP, Chalder T, White PD, Sharpe M, Pickles A. Tutorial: The 
practical application of longitudinal structural equation mediation models in clinical trials. 
Psychol Methods 2018; 23:191-207. 
 
115. 
Preacher KJ, Zyphur MJ, Zhang Z. A general multilevel SEM framework for assessing 
multilevel mediation. Psychol Methods 2010; 15:209-233.