Investigation of Two Swallowing Therapy Models During Radiation Therapy for Head and Neck Cancer
Phase: NA
Conditions: Head Neck Cancer
Sponsor: Stanford University

Protocol version 9/Version date 8/June/2021
 
 
 
1 
Investigation of Two Swallowing Therapy Models during Radiation Therapy for 
Head and Neck Cancer   
Document History 
Notes 
Version 1       Date: 26 Mar 2019 
Initial Approval 
Version 2       Date: 01 Apr 2019 
Revision includes: 
• 
Inclusion/ exclusion criteria (removed repeated 
criteria from the protocol, and pregnant women 
exclusion) 
• 
Removed AE/SAE reporting  
• 
Clarified randomization technique 
• 
Added demographic survey and INFO 25 
• 
Modified paper logging form to include date and 
participation name and modified technology 
survey to include 2 additional questions. 
Version 3       Date: 28 May 2019 
Revision includes:  
• 
Formatting changes 
• 
Updated study calendar and measurement time 
points to clarify all discrepancies 
• 
Updated regulatory considerations such as site 
communication and data monitoring to  include 
management of the various subsites. 
Version 4      Date: 1 JUL 2019 
Revision includes:  
• 
Updating study calendar to clarify procedure 
collection time window- 4 week +/- 2 days, 7 
week +/- 2 days, 19 week +/- 1 month, 1 year +/- 
1 month 
• 
Updated study calendar to allow for baseline 
MBSS to occur up to 2 days after start of 
radiation. 
• 
Updated section 11.3 to explain how data will be 
managed and stored. 
• 
Added pre-screening survey (appendix M) to 
allow researchers to ask eligibility questions 
prior to consent. 
Version 5     Date: 10 JAN 2020 
Revision includes: 
• 
Formatting Changes 
• 
Removed Appendix B (Patient Demographics) 
due to redundancy and clarified data points 
collected in demographic and medical history 
section of study calendar 
• 
Removed inconsistencies by adding DIGEST, 
PAS, and INFO 25 in the study calendar 
• 
Clarified wording of active study duration as 
being seven weeks 
• 
Removal of wording that had mistakenly been 
carried over from the previous feasibility study, 
such as the tracking of patient oral intake and 
some app feedback functionalities 
• 
Clarification that MBSS videos from all sites 
will be stored on Stanford Medicine Box until 
study conclusion 

 
 
 
Protocol version 9/Version date 8/June/2021 
 
 
 
2 
 
 
 
 
 
Version 6.     Date 12 Oct 2020 
Revision includes: 
• 
Added procedure to provide study patients with 
standard scale to measure MIO during video 
visits  
• 
Addition of list of  participating centers 
(subsites) 
Version 7     Date 9 Dec 2020 
Revision Includes: 
• 
Change in sub-site Principle Investigator at Fox 
Chase Cancer center from Barbara Ebersole to 
Kathleen Donocoff  
Version 8.     Date 29 Mar 2021 
Revision Includes; 
• 
Update to PI oversite plan for subsites.  
Version 9.    Date 8 June 2021 
Revision Includes: 
• 
Change in Sub-site Principle investigator at Fox 
Chace Cancer Center from Kathleen Donocoff 
to Liane McCarroll. 

 
 
 
Protocol version 9/Version date 8/June/2021 
 
 
 
3 
Investigation of Two Swallowing Therapy Models during Radiation Therapy for Head and 
Neck Cancer 
 
Coordinating Center 
Stanford Cancer Institute 
900 Blake Wilbur Drive 
Stanford, CA 94305 
 
Protocol Director  
Heather Starmer 
900 Blake Wilbur Drive 
Stanford, CA 94305 
 
 
hstarmer@stanford.edu 
 
Co-Investigators 
F. Christopher Holsinger 
Beth Beadle 
875 Blake Wilbur Drive 
Stanford, CA 94305 
 
 
 
 
Biostatistician 
Alex McMillan, PhD 
Senior Research Scientist 
Department of Biomedical Data Science 
Stanford University School of Medicine 
Medical School Office Building 
1265 Welch Road 
 
Stanford CA, 94305 
 
Study Coordinator 
TBD 
 
 
Version 9 / Version Date: (8-Jun-2021) 
 
List of Participating Centers: 
Massachusetts Eye & Ear/ Harvard  
PI: Tessa Goldsmith 
 
Fox Chase Cancer Center 
PI: Liane McCarroll 

 
 
 
Protocol version 9/Version date 8/June/2021 
 
 
 
4 
TABLE OF CONTENTS 
 
INVESTIGATION OF TWO SWALLOWING THERAPY MODELS DURING RADIATION 
THERAPY FOR HEAD AND NECK CANCER .......................................................................... 3 
PROTOCOL DIRECTOR ............................................................................................................ 3 
CO-INVESTIGATORS................................................................................................................. 3 
BIOSTATISTICIAN ...................................................................................................................... 3 
STUDY COORDINATOR ............................................................................................................ 3 
PROTOCOL SYNOPSIS ............................................................................................................. 8 
SCHEMA ..................................................................................................................................... 10 
....................................................................................................................................................... 10 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ............................................ 11 
1. 
OBJECTIVES ..................................................................................................................... 12 
PRIMARY OBJECTIVE ................................................................................................................. 12 
1.2. 
SECONDARY OBJECTIVES ............................................................................................... 12 
AIM 2: TO EVALUATE THE IMPACT OF THE “HNC VIRTUAL COACH” 
PROGRAM ON THE PREVALENCE, CHARACTERISTICS, AND SEVERITY OF 
DYSPHAGIA THREE MONTHS POST-TREATMENT IN PATIENTS UNDERGOING 
RADIATION THERAPY FOR HEAD AND NECK CANCER. ........................................... 12 
2. 
BACKGROUND ................................................................................................................. 12 
2.1 
STUDY DISEASE ............................................................................................................. 12 
2.3 
RATIONALE .................................................................................................................... 15 
2.4 
STUDY DESIGN .............................................................................................................. 17 
2.5 
CORRELATIVE STUDIES BACKGROUND .......................................................................... 17 
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES ...................... 17 
REFER TO THE PARTICIPANT ELIGIBILITY CHECKLIST IN APPENDIX A. ......... 17 
3.2 
INFORMED CONSENT PROCESS ....................................................................................... 17 
3.3       RANDOMIZATION PROCEDURES ....................................................................................... 18 
3.4 
STUDY TIMELINE ........................................................................................................... 18 
4. 
TREATMENT PLAN ......................................................................................................... 18 
4.1 
CRITERIA FOR REMOVAL FROM STUDY .......................................................................... 22 
4.2 
ALTERNATIVES .............................................................................................................. 22 
5. 
INVESTIGATIONAL AGENT/DEVICE/PROCEDURE INFORMATION ............... 22 
5.1 
 INVESTIGATIONAL AGENT/DEVICE/PROCEDURE ........................................................... 22 
5.2 
AVAILABILITY ............................................................................................................... 23 
THE MOBILE APPLICATION WILL BE PROVIDED BY VIBRENT HEALTH. .......... 23 
5.3 
AGENT ORDERING ......................................................................................................... 23 
6. 
ADVERSE EVENTS AND REPORTING PROCEDURES ........................................... 23 
6.1 
POTENTIAL ADVERSE EVENTS ....................................................................................... 23 

 
 
 
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5 
6.2 
ADVERSE EVENT REPORTING......................................................................................... 24 
7. 
STUDY CALENDAR ......................................................................................................... 25 
FOOTNOTE:............................................................................................................................... 25 
1. 
PROCEDURES TO BE COMPLETED ANY TIME PRIOR TO START OF 
RADIATION TREATMENT. IF SOC PROCEDURES ARE COMPLETED PRIOR TO 
CONSENT, THEY CAN BE INCLUDED, AND DO NOT NEED TO BE REPEATED. ... 25 
2. 
PROCEDURES TO BE COMPLETED DURING WEEK 4 OF RADIATION 
TREATMENT (+/- 2 DAYS). .................................................................................................... 25 
3. 
PROCEDURES TO BE COMPLETED DURING FINAL WEEK OF RADIATION 
TREATMENT (+/- 2 DAYS). .................................................................................................... 25 
4. 
PROCEDURES TO BE COMPLETED 3 MONTHS AFTER END OF RADIATION, 
IDEALLY WITHIN (+/- 2 WEEKS). HOWEVER, IF THE PROCEDURES CANNOT BE 
COMPLETED DURING THAT WINDOW (+/-) 1 MONTH IS ACCEPTABLE. .............. 26 
5. 
PROCEDURES TO BE COMPLETED 1 YEAR AFTER END OF RADIATION (+/- 1 
MONTH). ..................................................................................................................................... 26 
6. 
PRE-STUDY MBSS SHOULD OCCUR PRIOR TO START OF RADIATION 
TREATMENT, BUT CAN ALSO OCCUR WITHIN 2 DAYS AFTER START OF 
RADIATION. .............................................................................................................................. 26 
8. 
MEASUREMENTS ............................................................................................................ 27 
8.1  
PRIMARY OUTCOME MEASURE ...................................................................................... 27 
(a) 
8. 1.2 Measurement Definition ....................................................................................................................... 27 
(b) 
8.1.3 Measurement Methods ........................................................................................................................... 27 
(c) 8.1.4 Measurement Time Points .......................................................................................................................... 27 
8.2A  SECONDARY OUTCOME MEASURES (THESE MEASURES, IN COMBINATION, PROVIDE A 
COMPREHENSIVE EVALUATION OF SWALLOWING PHYSIOLOGY, ITS FUNCTIONAL IMPACT, AND 
PATIENT PERCEPTION.) ............................................................................................................... 27 
(d) 
8.2a.2 Measurement Definition ..................................................................................................................... 27 
(e) 
8.2a.3 Measurement Methods ........................................................................................................................ 28 
(f) 
8.2a.4 Measurement Time Points ....................................................................................................................... 28 
8.2B  
SECONDARY OUTCOME MEASURE .................................................................................. 28 
(g) 
8.2b.2 Measurement Definition ..................................................................................................................... 28 
(h) 
8.2b.3 Measurement Methods ........................................................................................................................ 28 
(i) 
8.2b.4 Measurement Time Points ....................................................................................................................... 28 
8.2C  
SECONDARY OUTCOME MEASURE .................................................................................. 28 
(j) 
8.2c.2 Measurement Definition ........................................................................................................................... 28 
(k) 
8.2c.3 Measurement Methods ......................................................................................................................... 28 
(l) 
8.2c.4 Measurement Time Points ....................................................................................................................... 29 
8.2D  SECONDARY OUTCOME MEASURE .................................................................................. 29 
(m) 
8.2d.2 Measurement Definition ..................................................................................................................... 29 
(n) 
8.2d.3 Measurement Methods ........................................................................................................................ 29 
8.2D.4 MEASUREMENT TIME POINTS ......................................................................................... 29 
8.2E  
SECONDARY OUTCOME MEASURE .................................................................................. 29 
(o) 
8.2e.2 Measurement Definition ...................................................................................................................... 29 
(p) 
8.2e.3 Measurement Methods ......................................................................................................................... 29 

 
 
 
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(q) 
8.2e.4 Measurement Time Points .................................................................................................................. 29 
8.2F  
SECONDARY OUTCOME MEASURE .................................................................................. 29 
(r) 
8.2f.2 Measurement Definition ............................................................................................................................ 30 
(s) 
8.2f.3 Measurement Methods ............................................................................................................................... 30 
(t) 
8.2f.4 Measurement Time Points ........................................................................................................................ 30 
8.2G  SECONDARY OUTCOME MEASURE .................................................................................. 30 
(u) 
8.2g.2 Measurement Definition ..................................................................................................................... 30 
(v) 
8.2g.3 Measurement Methods ........................................................................................................................ 30 
(w) 
8.2g.4 Measurement Time Points ................................................................................................................. 30 
9. 
MULTISITE REGULATORY CONSIDERATIONS ..................................................... 30 
11.1 
MONITORING PLAN ........................................................................................................ 30 
11.2  PROTOCOL REVIEW AND AMENDMENTS ............................................................................ 31 
11.3  DATA MANAGEMENT ......................................................................................................... 31 
11.4 
STUDY DOCUMENTATION .............................................................................................. 32 
11.5 
SITE COMMUNICATION .................................................................................................. 33 
10. 
STATISTICAL CONSIDERATIONS .......................................................................... 33 
10.1 
STATISTICAL DESIGN ..................................................................................................... 33 
(x) 
Randomization ...................................................................................................................................................... 33 
RANDOMIZATION WILL BE CARRIED OUT USING PRE-PRINTED LISTS WITH 
BLOCK SIZE OF 4 VIAONCORE........................................................................................... 33 
10.4 
PRIMARY ANALYSIS ....................................................................................................... 33 
(y) 
Analysis Population ............................................................................................................................................. 33 
(z) 
Analysis Plan .......................................................................................................................................................... 34 
12.5 
SECONDARY ANALYSIS .................................................................................................. 34 
(aa) 
12.5.1 Analysis Population ............................................................................................................................... 34 
(bb) 
12.5.2  Analysis Plan ........................................................................................................................................... 34 
12.6  
SAMPLE SIZE .................................................................................................................. 34 
(cc) 
12.6.1 Accrual estimates ................................................................................................................................... 34 
(dd) 
12.6.2 Sample size justification ..................................................................................................................... 34 
(ee) 
12.6.3 Effect size justification ......................................................................................................................... 34 
13. 
REFERENCES ................................................................................................................ 35 
APPENDICES ............................................................................................................................. 43 
APPENDIX A: PARTICIPANT ELIGIBILITY CHECKLIST ............................................................. 43 
SUPPORTING DOCUMENTATION* ...................................................................................... 43 
APPENDIX B: PATIENT DEMOGRAPHICS ............................... ERROR! BOOKMARK NOT DEFINED. 
APPENDIX C: PATIENT COMFORT WITH TECHNOLOGY ............................................................... 45 
1. 
DO YOU OWN EITHER AN ANDROID OR APPLE-IOS BASED SMARTPHONE OR TABLET? .. 45 
2. 
DO YOU HAVE ACCESS TO AN INTERNET CONNECTION OR A SUFFICIENT MONTHLY DATA 
PLAN (~200MB/MONTH) OR GREATER? ................................................................................... 45 
APPENDIX D: PAPER LOGGING FORM ......................................................................................... 46 
PARTICIPANT NAME: ______________________________________ ..................................... 46 
APPENDIX E: MD ANDERSON DYSPHAGIA INVENTORY ............................................................. 47 
APPENDIX F: FUNCTIONAL ORAL INTAKE SCALE (FOIS) .......................................................... 49 
APPENDIX G: PERFORMANCE STATUS SCALE – HEAD AND NECK .............................................. 50 
APPENDIX H: PENETRATION ASPIRATION SCALE ....................................................................... 51 

 
 
 
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APPENDIX I: MODIFIED BARIUM SWALLOW IMPAIRMENT PROFILE (MBS-IMP) ........................ 52 
APPENDIX J: DYNAMIC IMAGING GRADE OF  SWALLOWING TOXICITY ...................................... 53 
APPENDIX K: INFO 25 SURVEY ................................................................................................. 54 
....................................................................................................................................................... 54 
APPENDIX L: DEMOGRAPHIC SURVEY ....................................................................................... 56 
....................................................................................................................................................... 56 
APPENDIX M: PRE-SCREENING QUESTIONNAIRE ........................................................................ 57 

 
 
 
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PROTOCOL SYNOPSIS 
In the table below summarize the basic aspects of this research. This is to be used as a 
quick reference guide. Remove any section that is not relevant to the research.  
 
 
TITLE 
Using mobile health technology to 
enhance adherence and improve 
swallowing outcomes in patients 
undergoing radiation therapy for head 
and neck cancer 
INVESTIGATIONAL PRODUCT OR 
PROCEDURE 
Vibrent mobile application 
PRIMARY OBJECTIVE(S) 
To evaluate the impact of the “HNC 
Virtual Coach” mobile application on 
patient adherence to a prescribed 
swallowing therapy protocol. 
SECONDARY OBJECTIVE(S) 
To evaluate the impact of the “HNC 
Virtual Coach” program on the 
prevalence, characteristics, and 
severity of dysphagia three months 
post-treatment in patients undergoing 
radiation therapy for head and neck 
cancer. 
TREATMENT SUMMARY 
Participants in the experimental arm 
(Group A) will receive a comprehensive 
swallowing rehabilitation app (“HNC 
Virtual Coach”). The paper group 
(Group B) will be given paper exercise 
logs to fill out. 
SAMPLE SIZE  
176 
STATISTICAL CONSIDERATIONS 
88 patients will be enrolled in each arm.  
This number will provide 80% power to 
detect a 15 percentage point difference 
between groups.  This calculation is 
made assuming 33% adherence in arm 
B and a standard deviation of 32 based 
on prior studies.  This sample size 
includes the addition of 20% to account 
for anticipated drop out. 
 
The proposed research is a RCT with a 
primary aim of determining if a mobile 
application may enhance adherence to 
swallowing therapy in patients 
undergoing radiation for head and neck 
cancer thus improving swallowing 

 
 
 
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outcomes.  Analysis of the primary 
endpoint (adherence) will be carried out 
using logistic regression, comparing 
arms A and B.  A secondary endpoint 
will be the average percent adherence 
per week.  Analysis of the secondary 
adherence endpoint will be carried out 
using a linear mixed effect model with 
weekly adherence as a dependent 
variable, a patient-specific random 
intercept, treatment arm as the primary 
predictor, and week as a fixed 
(categorical) effect. We will also 
explore the impact of the mobile app on 
a variety of swallowing outcomes 
including diet level, patient perception, 
and physiological measures.  Analysis 
of these endpoints will be carried out 
using logistic regression comparing 
arms A and B. 

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SCHEMA
Potential 
participants
≥ 18 
years of 
age
Fluent 
English 
speaker
Capableof 
providing 
informed 
consent
Newly 
diagnosed non-
metastatic HNC 
requiring 
bilateral neck 
radiation 
No prior history 
of surgery or 
radiation of the 
head and neck for 
another 
malignancy
Previously untreated  
HNCdiagnosis requiring a 
definitive course of 
radiotherapy of 60Gy or 
greater.
Study subjects who 
have either an 
Android or Apple iOS-
based smartphone or 
tablet
Access 
to a 
sufficien
t 
monthly 
data 
plan 
Candidates 
enrolled and 
randomized 
(n=176)
Arm A 
(n=88)
7 week treatment 
Primary outcome 
measured 
(adherence)
2-3 months post 
treatment 
secondary outcomes 
measured
(MBS)
1 year follow up
f
Arm B 
(n=88)
h
7 week treatment 
Primary outcome 
measured 
(adherence)
2-3 months post treatment 
Secondary outcomes 
measured
(MBS)

Protocol version 9/Version date 8/June/2021
 
 
 
11
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
Include additional abbreviations as needed.  Remove any unnecessary abbreviations. 
 
AE 
Adverse events 
DIGEST 
Dynamic Imaging Grade of Swallowing 
Toxicity 
DoD 
Department of Defense 
DSMC 
Data Safety Monitoring Committee 
EPHI 
Electronic Protected Health Information 
FEES 
Fiberoptic endoscopic evaluation of 
swallowing 
FOIS 
Functional Oral Intake Score 
GCP 
Good clinical practice 
Gy 
Gray 
HNC 
Head and neck cancer 
HPV 
Human papilloma virus 
IMRT 
Intensity modulated radiation therapy 
LHS 
Learning Healthcare System 
MASA 
Mann Assessment of Swallowing Ability 
MBS 
Modified barium swallow 
MBS-ImP 
Modified barium swallow impairment profile 
MDADI 
MD Anderson Dysphagia Inventory 
NIH 
National Institutes of Health 
PAS 
Penetration Aspiration Scale 
PHI 
Protected Health Information 
PI 
Principal investigator 
PSS-HN 
Performance Status Scale Head and Neck 
Reps 
Repetitions 
SLP 
Speech language pathologist 
SRC 
Scientific review committee 
TORS 
Transoral robotic surgery 
WHO 
World Health Organization 
UNK 
Unknown 
WBC 
White blood cell 
WHO 
World Health Organization 
 

 
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1. 
OBJECTIVES 
 
Primary Objective  
 
Our objective is to conduct a randomized controlled trial to test the impact of the “HNC Virtual 
Coach” mobile application on adherence to prophylactic swallowing therapy during head and 
neck radiation. Prior studies have demonstrated the value of mobile health technologies in 
improving patient adherence in a variety of settings, including exercise programs (Guarino et al., 
2016; Hui et al., 2016, Carter et al 2013). Preliminary feasibility data collected by our study team 
demonstrated the “HNC Virtual Coach” program could be easily integrated into standard care 
and lead to high levels of patient engagement in their swallowing exercise program. (Starmer 
2017)  Our central hypothesis is that patients randomized to use the “HNC Virtual Coach” 
application will demonstrate better adherence to swallowing exercises, translating to better 
functional swallowing outcomes, than patients receiving usual care. We propose to achieve our 
objective by pursuing the following specific aims. 
 
Aim 1: To evaluate the impact of the “HNC Virtual Coach” mobile application on patient 
adherence to a prescribed swallowing therapy protocol. 
 
1.2. 
Secondary Objectives 
 
 
Aim 2: To evaluate the impact of the “HNC Virtual Coach” program on the prevalence, 
characteristics, and severity of dysphagia three months post-treatment in patients 
undergoing radiation therapy for head and neck cancer. 
 
2. 
BACKGROUND 
 
2.1 
Study Disease 
 
Head and neck cancer (HNC) is the 6th most common type of cancer in the world and has 
recently seen a dramatic rise in the United States secondary to oropharyngeal tumors related to 
the human papillomavirus (HPV) (Chaturvedi et al., 2008).  Patients with HPV-associated HNC 
tend to be younger and healthier at diagnosis than patients with “traditional” head and neck 
cancer risk factors related to alcohol and tobacco consumption (Gillison et al., 2008).  Hence, the 
majority of patients who will develop HNC in 2018 (and beyond) will have fewer competing 
morbidities than traditional patients and are expected to have long lifespans in which to develop 
potential toxicity of treatment.  In addition, patients with HPV-associated HNC have markedly 
better oncologic outcomes, when matched with other variables, compared to traditional HNC 
(Fakhry et al., 2008).  Overall, the need to providing effective cancer therapy, with minimal side 
effects, is especially important in this cohort of modern patients with HNC.   
For patients with newly diagnosed HNC, treatment may include surgery, radiation, and/or 
chemotherapy, often delivered in combination.  The majority of patients receive radiation 
therapy at some point in their treatment, either as definitive treatment or in the post-operative 

 
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setting.  All of the modalities have their own distinct set of potential acute and long-term side 
effects, and the combination of therapies can also contribute to long-term toxicity (Rosenthal 
2014; Gane et al 2017).  Modern advancements in surgery (namely, transoral robotic surgery, 
TORS), radiation therapy (namely, intensity-modulated radiation therapy, IMRT), and 
chemotherapy (namely, the use of novel systemic agents) all have shared minimizing toxicity as 
a primary goal.  However, treatment still has significant impact on quality of life as noted by 
multiple studies (Ringash 2015; Jones 2017; Achim 2017).   
 
Dysphagia is one of the most common sequelae of HNC and its treatment. The increased use of 
definitive radiation-based treatment (without surgery) to allow for organ preservation has led to a 
growing awareness of the potential for dysphagia from this approach. This is likely related to 
radiation fibrosis and changes in innervation of the muscles of swallowing (King et al., 2016).  
The use of radiation and chemotherapy has been beneficial in sparing the consequences of 
surgery and removal of tissues involved in swallowing; however, the preservation of an organ 
when treating HNC does not necessarily equate to the preservation of function.  A substantial 
body of evidence suggests that patients receiving non-surgical treatment for HNC are at risk for 
both acute toxicities and long-term alteration of swallow function (Starmer et al., 2014; 
Hutcheson et al., 2012; Eisbruch et al., 2002). Such alterations may contribute to long-term 
decrements in health status and quality of life (Daugaard et al., 2017; Silveira et al., 2015; 
Ringash 2015). It has become increasingly apparent that prevention of dysphagia through active 
participation in prophylactic swallowing therapy with speech-language pathologists (SLP) can 
positively affect these outcomes (Carroll 2008; Kotz 2012; Carnaby-Mann 2012). 
 
The data supporting the use of prophylactic swallowing exercises includes multiple outcome 
measurements.  Carroll and colleagues (2008) demonstrated that individuals performing 
swallowing exercises prior to and during chemoradiation demonstrated more normal tongue base 
apposition to the posterior pharyngeal wall during swallowing as well as more normal epiglottic 
inversion three months after treatment than did a matched group of patients who started exercises 
after completion of radiation suggesting the beneficial impact of preventative exercises on 
physiology. Further, Kotz and colleagues (2012) demonstrated more favorable diet levels 3-6 
months following completion of treatment in patients completing preventative exercises.  
Carnaby-Mann (2012) used post-treatment muscle size/composition as measured by MRI as the 
primary outcome measure comparing preventative treatment with sham treatment and monitored 
care. In the active treatment arm in which patients performed swallowing exercises twice daily 
over the duration of treatment, there was less structural change in the genioglossus, hyoglossus, 
and myohyloid muscles than in the other two treatment groups.  A composite measure was 
designed to designate a favorable swallowing-related outcome, and included weight loss <10%, 
maintenance of oral diet, and a change of <10 points on the Mann Assessment of Swallowing 
Ability (MASA).  In the active treatment arm, 86% achieved this desirable outcome, while only 
47% in the other groups achieved this.  There was a 36% absolute risk reduction for loss of 
swallowing ability when participating in preventative exercise. These results serve as strong 
evidence that patients receiving non-operative HNC treatment should be engaged in swallowing 
therapy prior to the start of radiation.   
 
Swallowing therapy may include a number of interventions, including compensatory strategies 
that work to impact bolus flow, as well as exercises which aim to influence swallowing 

 
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physiology.  Swallowing exercises are typically selected by a SLP based on physiologic findings 
during an instrumental swallowing evaluation; modified barium swallow (MBS) or flexible 
fiberoptic endoscopic evaluation of swallowing (FEES).  Exercises are designed to improve the 
safety and/or efficiency of the swallow and may target structures such as the tongue, pharyngeal 
constrictors, and suprahyoid musculature.  Exercises such as the effortful swallow, Mendelsohn 
maneuver, and the Masako technique have been shown to be effective in improving the strength 
of the muscles of deglutition (Lazarus 2002, Hoffman 2012, Fujiu 1996). Additionally, in the 
case of patients undergoing radiation therapy, range of motion stretches may target structures 
within the field of radiation, such as the tongue and the masseter muscles (Logemann 1997).  
Dysphagia exercises are typically trained by the SLP with the patient doing the majority of 
exercises at home. 
 
Patient adherence to treatment recommendations requires that patients be active participants in 
their care.  Prior studies of adherence in the exercise literature show that adherence rates tend to 
be poorer in patients engaging in home exercise programs than those receiving clinical therapy 
(Forkan 2006, Hardage 2007).  In addition, for patients with HNC, oncologic treatment itself 
may be cumbersome (including multiple daily appointments) and painful, and patient 
understanding of treatment recommendations can be lacking.  Increasing patient comprehension 
of the importance of swallowing intervention is critical for improving adherence.  Multiple 
recent reports have demonstrated that adherence to swallowing therapy recommendations is poor 
in patients with HNC (Table 1).  
 
Table 1: Studies reporting adherence rates to swallowing therapy 
 
Reference 
Population 
Adherence rate 
Wall, 2017 
Head and neck cancer 
radiation 
27% 
Cnossen, 2017 
Head and neck cancer 
radiation 
38-70% 
Mortensen, 2015 
Head and neck cancer 
radiation 
33-53% 
Shinn, 2013 
Head and neck cancer 
radiation 
13-45% 
Kotz, 2012 
Head and neck cancer 
radiation 
31% 
 
These studies repeatedly demonstrate that ~2/3 of patients do not follow through with 
recommended swallowing therapy protocols, demonstrating the critical need for head and neck 
care teams need to determine strategies that facilitate patient adherence.  Prior work by our team 
has focused on clinical models and the inclusion of the SLP in the multidisciplinary care team as 
one strategy to help enhance patient understanding of the importance of prophylactic swallowing 
intervention (Starmer et al., 2011).  In addition, through collaborations within the 
multidisciplinary team, our group is assessing strategies to minimize treatment toxicity, such as 
pain, using gabapentin to block nerve related pain and optimize functionality (Yang et al., 2016; 
Starmer et al., 2014).  With this proposal, we further advance this initiative by using a mobile 
health application specifically designed to address these issues to assist in difficulty performing 

 
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15
the exercises, remembering the exercises, and understanding the rationale for the exercises.  
The World Health Organization (WHO) has classified factors that may impact patient adherence 
into five distinct groupings: patient-related, socio-economic, therapy-related, condition-related, 
and health care system related factors (Sabate 2003).  While many of these factors cannot be 
regulated by the health care team, others such as therapy-related and health care system factors 
may be manipulated to optimize adherence.  Mobile health technology has been proposed as a 
tool to influence such barriers to adherence.  There are multiple studies that have shown the 
positive impact of mobile health technology, including use in methadone clinics and asthma 
management clinics (Guarino et al., 2016; Hui et al., 2016).  With regard to exercise programs, 
use of mobile applications has been associated with higher levels of exercise in contrast to paper 
logging programs.  Carter et al. (2013) reported nearly double the rates of exercise program 
retention at 6 months (93% versus 53%) and nearly triple the exercise logged (92 days versus 29 
days) when a mobile health application was integrated into a weight loss program, leading to a 
greater degree of weight loss and BMI change. 
 
2.2 
Study Agent/Device/ProcedureThe “HNC Virtual Coach” program has been developed in 
conjunction with Vibrent Health (www.vibrenthealth.com), a cloud-based precision health 
platform for individual and population health. The Vibrent team has partnered with stakeholders 
across the healthcare ecosystem to advance disease prevention and treatment based on real-world 
evidence and scientific rigor. Vibrent has experience with leading edge technologies for both 
commercial contracts and academic grant projects including adaptive algorithms, wireless 
wearables and medical devices, passive sensing, predictive modeling, machine learning, adaptive 
tailored messaging, dynamic automated care planning, big health data system integration, 
genomics, and more.  Vibrent was recently chosen by the National Institutes of Health (NIH) to 
provide the technology backbone for its historic Precision Medicine Initiative 
(www.joinallofus.org), engaging millions of Americans over the next ten years. This 
groundbreaking effort aims to engage more than one million participants to understand how 
genomics, lifestyle, behavioral, and environmental factors impact an individual’s health.  For the 
purpose of the current investigation, Vibrent Health will partner with head and neck cancer 
teams at a number of National Cancer Institute designated Comprehensive Cancer Centers to 
optimize and evaluate a precision health platform to facilitate patient adherence to swallowing 
exercises and optimize functional swallowing outcomes. 
 
2.3 
Rationale 
This protocol seeks to address the issue of low adherence to swallowing exercises by 
implementing a customizable mobile application (“HNC Virtual Coach”) as an adjunct to routine 
clinic visits and instruction from SLPs.  Prior studies which have demonstrated improved 
adherence in the setting of weight loss and non-cancer medical management suggest that this 
approach is feasible; our hypothesis is that a mobile health application will improve adherence to 
swallowing exercises.  However, performance of the exercises is not the only endpoint.  Multiple 
studies have shown that improved exercise adherence results in notable benefits with regard to 
swallowing function.  Our second hypothesis is that increased adherence to swallowing exercises 
will then lead to preservation of functional swallowing physiology and subsequently to increased 
swallowing safety, efficiency, and patient perceived quality of life. 
The “HNC Virtual Coach” application, tailored to patients with HNC, will monitor patient 
progress while also providing a direct line of communication to health care providers should any 

 
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16
questions or concerns arise concerning their treatment. The mobile application will also feature 
instructional videos that describe the swallowing exercises in detail, providing patients with 
another resource to help improve their overall rehabilitation experience. Finally, home practice 
reminders and prompts will be used to help patients integrate the exercises into their daily 
routine.  We seek to demonstrate that use of the “HNC Virtual Coach” program will be 
associated with greater adherence to home exercise protocols as measured by logged exercises 
completed.  This hypothesis is based on our preliminary feasibility data and patient feedback 
regarding the value of the application to their treatment (Starmer et al 2017).  Specific feedback 
from participants in the feasibility trial included:  
 
Feasibility trial participant feedback 
“ I felt like my therapist was with me every day doing my exercises.  All of my family and 
friends felt like they knew her.” 
“The app was good because it made me feel like if I didn’t do the exercises, the teacher 
would yell at me.” 
“I knew when to do my exercises.  Keeping everything in one place was very helpful.” 
“It is easy, you don’t have to be computer literate to use it.” 
 
A feasibility study investigating the approach of using a mobile technology application (in 
general) and the “Swallow for Life” swallowing therapy application (specifically) in patients 
with HNC has recently been completed through a collaboration between Stanford University and 
Johns Hopkins University, under the guidance of PI Heather Starmer.  A total of 36 patients were 
enrolled in this feasibility study in less than one year, demonstrating our ability to accrue the 
required number of patients to complete this investigation and the level of interest from the 
patients.  The majority of patients were diagnosed with oropharyngeal squamous cell carcinoma 
(83%), and most received chemoradiation as their primary treatment (75%).  Overall, there were 
7004 entries into the mobile application, including exercise adherence data, weight, and quality 
of life surveys.  At least two exercise sessions per day were entered by 25% of participants and at 
least one session per day was logged by 53% of participants.  While a 53% partial adherence rate 
may seem meager, prior studies demonstrated adherence rates closer to 30-40% (Table 1).  Thus, 
while not directly comparable, there is reason to believe that use of this mobile application may 
in fact be an effective tool to enhance adherence.  Only 20% of participants did not meaningfully 
engage with the application (i.e. less than 10 logs total over study duration).  The average 
number of exercise sessions logged was 44; however if those who did not engage with the 
application were excluded from analysis, this number rose to 60 sessions logged.  On average, 
participants logged their weight 27 times and their pain 65 times over the course of the study.  
Intra-app surveys regarding failure to log exercises were completed 71 times by 23 unique 
patients.  Entries revealed the majority of patients had completed the exercises but forgot to log 
them (70%) suggesting that actual adherence rates may have been underestimated in this series.  
Other reasons for failure to log included; time constraints (13%), fatigue (6%), pain (6%), 
app/internet issues (4%), and lack of understanding of the exercises (1%).  Exit interviews of 
patients revealed overall satisfaction with the app.  Features cited as most beneficial included: 
use of videos to reinforce exercise technique, reminders to keep on track with exercises, and a 
feeling of increased accountability.  Based on the outcomes of this study and the feedback 
received from patients, our study team has worked extensively with the Vibrent program 
development team to optimize the mobile application for the purpose of this clinical trial.  

 
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17
Revisions include: simplification of the logging system, patient customization of reminders, 
reducing unnecessary notifications, and improving the user interface.  While this feasibility trial 
was not designed to determine relative adherence between patients using the app and those 
receiving standard care, preliminary data suggest this intervention may be an effective adjunct to 
standard treatment, thus prompting the need for further investigation. 
 
2.4 
Study Design 
For clinicaltrials.gov and Stanford Clinical Trials Directory compliance  
 
State the primary purpose for the protocol from the following choices:  
Supportive Care: protocol designed to evaluate one or more interventions where the primary 
intent is to maximize comfort, minimize side effects or mitigate against a decline in the subject’s 
health or function.  In general, supportive care interventions are not intended to cure a disease.  
 
 State the interventional model from these choices:  
Parallel: one of two groups in parallel for duration of study.  
 
State the number of intervention arms.  
2 
 
State whether the study will be masked (at least one party is unaware of the treatment)  
Single Blind: one party is unaware of the intervention assignment,  
 
State whether the study is randomized.  
Participants will be randomized to treatment arms 
 
State type of primary outcome or outcome that the protocol is designed to evaluate:  
Efficacy  
 
2.5 
Correlative Studies Background 
Provide background information on each planned correlative study including the biologic 
rationale and hypotheses as well as the relevant preclinical and clinical data.   
 
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
 Refer to the Participant Eligibility Checklist in Appendix A.  
 
3.1 
Inclusion/ Exclusion Criteria We have decided not to duplicate the inclusion/exclusion 
criteria here, please refer to Appendix A. 
 
3.2 
Informed Consent Process 
All participants must be provided a consent form describing the study with sufficient information 
for participants to make an informed decision regarding their participation.  Participants must 
sign the IRB approved informed consent prior to participation in any study specific procedure. 
The participant must receive a copy of the signed and dated consent document.  The original 

 
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signed copy of the consent document must be retained in the medical record or research file.  
 
3.3       Randomization Procedures 
Following enrollment, randomization will be carried out using pre-printed lists with block size of 
4 through OnCore.  Clinical research coordinators will complete the randomization process after 
consent completed. 
 
3.4 
Study Timeline 
Primary Completion: 
The study will reach primary completion 24 months from the time the study opens to accrual. 
 
Study Completion: 
The study will reach study completion 36 months from the time the study opens to accrual. 
 
4. 
TREATMENT PLAN 
We propose a randomized control trial with two arms; the experimental “HNC Virtual Coach” 
app group (Group A, n=88), and a paper logging control group (Group B, n=88). In clinical 
practice, many patients would not even complete paper log forms, therefore the act of logging 
alone may inflate adherence values.  However, the ability to measure adherence across study 
groups required some level of logging to minimize the potential for recall bias.  As a result, 
inclusion of the paper logging groups appeared to be the best compromise for comparing our 
experimental intervention with usual care. We hypothesize that those participants in Group A 
will complete a higher percentage of prescribed exercises than those in group B.  Additionally, 
we hypothesize that those individuals in Group A will have more favorable swallowing 
outcomes as defined below.  
 
 
Participants in the experimental arm (Group A) will receive a comprehensive swallowing 
rehabilitation app (“HNC Virtual Coach”). The paper group (Group B) will be given paper 
exercise logs to fill out.  All patients will consult with a SLP prior to the initiation of radiation 
therapy.  At that time, baseline evaluations of swallowing function (outlined below) will be 
performed. All participants will be educated regarding potential radiation-related side effects and 
trained in the same series of swallowing exercises by the SLP.  In order to ensure fidelity of the 
target interventions, each SLP involved in this study will complete training with the site PI to 
ensure exercises and logging are being instructed according to the protocol.  SLPs will ensure 
that the patient is able to return demonstrate each exercise during their visit. 
 
 
Patients with elevated risk for developing dysphagia post-radiation will be the target of 
this intervention.  This includes individuals with primary head and neck tumors in the oral 
cavity, oropharynx, nasopharynx, larynx, and hypopharynx requiring bilateral neck radiation.  
Patients with recurrent disease will be excluded from participation.  Detailed inclusion and 
exclusion criteria can be found in Appendix A.  Patients will be screened for eligibility, 
consented, enrolled, and randomized prior to the initiation of radiation therapy. Eligibility 
screening will be conducted through weekly screening of radiation oncology clinics, new patient 
referrals and tumor board patient lists.  Those individuals identified as candidates for the study 
will be contacted by study personnel and educated regarding the trial.  Interested participants will 

 
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be consented using an IRB approved consent form. Informed consent will explain to participants 
that they will receive an intervention to support their swallowing therapy during radiation.  
Following enrollment, randomization will be carried out using pre-printed lists with random 
block size. Subjects will meet with a member of the research team for a baseline visit that will 
review details on how to download and use the application or how to complete paper exercise 
logs.  Written instructions regarding the app will be provided for patient reference at home. 
Participants will then be instructed to use the “HNC Virtual Coach” app in order to log daily 
exercises over the course of their treatment.  All study subjects will proceed to routine clinical 
care, consisting of standard fractionated radiotherapy with or without concurrent chemotherapy 
(based on standard clinical indications).  Participants in the experimental arm will be asked to 
use the “HNC Virtual Coach” program as an adjunct to standard care during treatment. The 
active study duration for each participant will begin on the first day of radiation. All participants 
will receive standard care with the SLP with planned clinical visits scheduled at the beginning of 
radiation, mid-way through radiation, and at the conclusion of radiation. 
 
We have developed a demographic information instrument to allow us to properly describe our 
cohort and to examine possible effects of these factors on adherence and functional outcome 
measures. (Appendix L) Variables of interest include age, sex, ethnicity, disease stage, disease 
site, HPV status, education level, marital status, distance from home to treatment center, and 
insurance status.  Additionally, participants will be asked to rate their comfort level with 
smartphone technology using a visual analogue scale (Appendix C).  These will be completed at 
the time of study enrollment, prior to randomization. 
 
Participants will be asked to complete and log their swallow exercises using either the Vibrent 
application or paper forms throughout the duration of radiation therapy. The Vibrent application 
will time stamp the date and time of data entry for secondary analysis to determine whether 
logging occurs on a daily basis or in batch. Paper logs will be collected by study personnel and 
entered into a central Redcap database. Each patient’s program will ask the patient to complete 3 
sets of ten repetitions of four different exercises, twice each day: Jaw stretches, Effortful 
Swallow, Mendelsohn Maneuver, and the Masako Maneuver. These maneuvers have all been 
well described and validated in the literature for patients undergoing treatment for head and neck 
cancer (Pauloski 2008).  
 
Participants in the experimental arm (Group A) will receive a notification reminder to complete 
target exercises as well as a link to a video workout twice each day through the mobile 
application. Additional educational videos will also be made available through the “HNC Virtual 
Coach” program to support the patient with treatment-related toxicities that may impact exercise 
adherence during radiation (such as pain, fatigue, and xerostomia). All of these exercises and 
additional information are within the normal standard of care and are simply facilitated outside 
of the clinical setting by the “HNC Virtual Coach” program.  When two sequential exercise 
sessions in a row are not completed, the application will push a survey to the participant to 
ascertain the reason why the sessions were not completed. Available options will include: 1) 
Didn’t have time, 2) Pain, 3) Not feeling well/no energy, 4) Don’t know how to do them, 5) 
Don’t think they are necessary, 6) Issues with technology, and 7) Other.  Based on participant 
responses, the study team will have the option to push information to the participant to address 
cited issues. During the baseline visit, the patients will be instructed that this mode of 

 
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communication is not intended to substitute the standard modes of communication with their 
provider, or obviate the need for scheduled follow-up visits.  The communication portal rather 
serves as a real-time feedback component on the patients “out of clinic” course of treatment.  
Instructions will be given regarding any emergencies, with directions to not communicate via the 
system and to call 911 or go to the emergency room.  In addition to these features, the app will 
also collect data regarding pain on a scale of 1-10 daily, where 1=no pain and 10=severe pain.  
This will allow investigators to monitor pain as a variable that may impact adherence.  
Additionally, in order to evaluate the relative role of oral intake during treatment, participants 
will be asked to rate their oral intake for nutrition/hydration as “all”, “some”, or “none” on a 
daily basis. 
 
Participants in the paper control group (Group B) will be asked to log exercises on provided 
logging sheets (Appendix D).  Both groups will be asked to rate their pain on a scale of 1-10 
daily when they log their exercises either on the control app or on their paper logging sheets.  We 
acknowledge that there are limitations to relying on patient logging as a measure of adherence.  
Unfortunately, there is no gold standard for measuring exercise adherence. A number of patient 
reported surveys have been reported in the literature; however these have been shown to have 
limited reliability and validity (McLean 2017).  In the absence of validated, reliable measures of 
adherence, patient logging remains the mainstay for measuring adherence in the majority of the 
exercise literature. The reliance on patient logging across treatment arms will minimize the risk 
for reporting bias in this study. 
 
Aim 1: To evaluate the impact of the “HNC Virtual Coach” mobile application on patient 
adherence to a prescribed swallowing therapy protocol. 
 
Primary outcome variable: Overall adherence to prescribed exercise protocol measured as 
percentage of prescribed exercises completed over a seven-week period. (i.e. if participants are 
asked to complete 6 sets of 10 reps of each exercise daily for 7 weeks, maximum potential would 
be 420 sets). 
 
Aim 2: To evaluate the impact of the “HNC Virtual Coach” program on the prevalence, 
characteristics, and severity of dysphagia in patients undergoing radiation therapy for 
head and neck cancer. 
 
Secondary outcome variables: 
Patient reported:  
MD Anderson Dysphagia Inventory (MDADI) (Appendix E) 
 
Clinician reported: 
Functional Oral Intake Score (FOIS) (Appendix F) 
Performance Status Scale – Head and neck (PSS HN) (Appendix G) 
 
Functional measures obtained during videofluoroscopic swallowing studies (VFSS): 
Penetration Aspiration Scale (PAS) (Appendix H) 
Individual item and composite scores of the Modified Barium Swallow Impairment Profile 
(MBS-ImP)  (Appendix I) 

 
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Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) severity scores (Appendix J) 
Maximal interincisor distance  
 
 
See study calendar for when these outcome measures will be collected 
 
 
Modified barium swallow procedure:  All MBS studies will follow a standard protocol.  
Additional boluses or strategies may be employed by the treating clinician only after completion 
of the study trials outlined below.  Examinations will be conducted using a minimum of 30 
frames per second and recorded for review purposes. Studies will be saved in AVI or MPEG 
format. Patients will be evaluated while seated in lateral and frontal views with views to include 
the soft palate superiorly, the cricopharyngeus inferiorly, the lips anteriorly, and the cervical 
spine posteriorly. A penny will be taped to the participant’s chin during the evaluation to provide 
calibration for measurements performed following the MBS. Varibar contrast will be used in 
trials as outlined below: 
 
Lateral view: 5cc Varibar thin liquid X2 
 
 
 
 
10cc Varibar thin liquid X1 
 
 
 
 
20cc Varibar thin liquid X1 
 
 
 
 
Ungraded cup sip Varibar thin liquid X2 
 
 
 
 
5cc Varibar pudding X2 
 
 
 
 
½ graham cracker coated with 3ml Varibar pudding X1 
 
Frontal view:  20cc Varibar thin liquid bolus X1 
 
MBS videos from all sites may be stored in Stanford Medicine Box until the study’s completion. 
The modified barium swallow videos will then be reviewed by a Stanford MBS-ImP trained SLP 
blinded to treatment group.  
 
The MD Anderson Dysphagia Inventory (MDADI) was selected to capture and quantify the 
patient perception of swallowing dysfunction.  It is a 20-item patient reported survey that 
measures the impact of dysphagia on patients with HNC.  Each item is rated on a scale of 1-5 
with lower numbers indicating poorer function.  Mean subscale scores are multiplied by 20 to 
provide a final score between 20-100.  This scale has been validated as a reliable tool to measure 
the impact of dysphagia on head and neck cancer patients (Chen 2001).   
 
 
In order to describe patient diet levels, the Functional Oral Intake Scale was selected.  
The FOIS is a 7-point ordinal scale used to describe oral intake where lower scores reflect more 
limited oral intake and higher scores reflect more normal diet levels. Originally validated in 
patients with dysphagia following stroke, the FOIS was found to have very good inter-rater 
reliability and validity (Crary 2005).  It has been used extensively in studies of dysphagia in the 
head and neck cancer population.  
 
 
The Performance Status Scale – Head and Neck (PSS-HN) was chosen to provide 
additional detail regarding diet and eating restrictions. This measure has been validated and 
shown to have good correlation with other measures of function in this population (List 1990). 
 
 
In order to measure physiologic swallow function during MBS studies, three assessment 

 
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tools were chosen.  The Penetration Aspiration Scale is an 8-point interval scale used to describe 
degree of bolus entry into the laryngeal vestibule and patient response to this material.  Lower 
scores reflect more normal function.  It has been shown to have favorable intra- and inter- judge 
reliability (Rosenbek 1996).  
 
 
The Modified Barium Swallow Impairment Profile is a tool designed to quantify degree 
of impairment on 13 individual physiologic components visualized during a modified barium 
swallow where higher numbers reflect greater dysfunction.  This tool correlates significantly 
with other measures of swallowing including penetration aspiration scores, diet scores, and 
quality of life (Martin-Harris 2008). 
 
 
The Dynamic Imaging Grade of Swallowing Toxicity was established to rate the safety 
and efficiency of the pharyngeal swallow during modified barium swallow studies using the 
National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) 
framework.  The scale has been shown to correlate with the MBSImp composite score, MDADI, 
and oral intake levels (Hutcheson 2017). 
 
 
These measures, in combination, provide a comprehensive evaluation of swallowing 
physiology, its functional impact, and patient perception. 
4.1 
Criteria for Removal from Study 
Treatment failure is not a study endpoint. Study subjects will be removed when requested by 
study subjects.Cessation of the research procedure will not affect the routine clinical care a study 
subject receives as the study subject will still be receiving standard of care through their 
regularly scheduled clinic appointments. The use of the VibrentTM mobile application will only 
serve as an adjunct to this standard of care. 
4.2 
Alternatives 
The alternative to participation in this trial is standard clinical care. 
 
5. 
INVESTIGATIONAL AGENT/DEVICE/PROCEDURE INFORMATION 
5.1 
 Investigational Agent/Device/Procedure   
The “HNC Virtual Coach” program has been developed in conjunction with Vibrent Health 
(www.vibrenthealth.com), a cloud-based precision health platform for individual and population 
health. The Vibrent team has partnered with stakeholders across the healthcare ecosystem to 
advance disease prevention and treatment based on real-world evidence and scientific rigor. 
Vibrent has experience with leading edge technologies for both commercial contracts and 
academic grant projects including adaptive algorithms, wireless wearables and medical devices, 
passive sensing, predictive modeling, machine learning, adaptive tailored messaging, dynamic 
automated care planning, big health data system integration, genomics, and more.  Vibrent was 
recently chosen by the National Institutes of Health (NIH) to provide the technology backbone 
for its historic Precision Medicine Initiative (www.joinallofus.org), engaging millions of 
Americans over the next ten years. This groundbreaking effort aims to engage more than one 
million participants to understand how genomics, lifestyle, behavioral, and environmental factors 
impact an individual’s health.  For the purpose of the current investigation, Vibrent Health will 
partner with head and neck cancer teams at a number of National Cancer Institute designated 

 
Protocol version 9/Version date 8/ June/2021
 
 
 
 
23
Comprehensive Cancer Centers to optimize and evaluate a precision health platform to facilitate 
patient adherence to swallowing exercises and optimize functional swallowing outcomes. 
 
For clinicaltrials.gov and Stanford Clinical Trials Directory compliance  
 
 
Intervention Description  
Participants in the experimental arm (Group A) will receive a notification reminder to complete 
target exercises as well as a link to a video workout twice each day through the mobile 
application. Additional educational videos will also be made available through the “HNC Virtual 
Coach” program to support the patient with treatment-related toxicities that may impact exercise 
adherence during radiation (such as pain, fatigue, and xerostomia). All of these exercises and 
additional information are within the normal standard of care and are simply facilitated outside 
of the clinical setting by the “HNC Virtual Coach” program.  When two sequential exercise 
sessions in a row are not completed, the application will push a survey to the participant to 
ascertain the reason why the sessions were not completed. Available options will include: 1) 
Didn’t have time, 2) Pain, 3) Not feeling well/no energy, 4) Don’t know how to do them, 5) 
Don’t think they are necessary, 6) Issues with technology, and 7) Other.  Based on participant 
responses, the study team will have the option to push information to the participant to address 
cited issues. During the baseline visit, the patients will be instructed that this mode of 
communication is not intended to substitute the standard modes of communication with their 
provider, or obviate the need for scheduled follow-up visits.  The communication portal rather 
serves as a real-time feedback component on the patients “out of clinic” course of treatment.  
Arms/Groups if arms or groups have been specified for the protocol, all arms must be described 
and have at least one intervention (unless arm type is "No Intervention") and each intervention 
must be assigned to at least one arm. 
 
5.2 
Availability 
The mobile application will be provided by Vibrent Health. 
 
5.3 
Agent Ordering 
The application will be downloaded from standard app stores with the assistance of the research 
coordinator. 
 
 
6. 
ADVERSE EVENTS AND REPORTING PROCEDURES 
6.1 
Potential Adverse Events 
No medical risks are expected to result from the use/implementation of the VibrentTM mobile 
application. The risk associated for all participants will not be greater than that of routine care for 
head and neck cancer patients receiving radiation therapy.  No direct risk is anticipated for 
completion of questionnaires or use of mobile applications as patients already have familiarity 
with these devices throughout their daily lives. 
 

 
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6.2 
Adverse Event Reporting 
Since this is a low-risk study with no anticipated adverse events (AE) related to the intervention, 
we will not be collecting any AEs or SAEs.  
 

 
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7. 
STUDY CALENDAR 
Schedules shown in the Study Calendar below are provided as an example and should be 
modified as appropriate. 
    
Pre-
Study1 Wk 
1 
Wk 
2 
Wk 
3 
Wk 
 42 
Wk 
5 
Wk 
6 
Wk 
73 
Wk 
194 
1 
Year5 
 
Optimize mobile application7 
 
X7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Paper Logs12 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic Survey 
(Appendix L)9 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history10 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Technology comfort scale 
(Appendix C)8 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MD Anderson Dysphagia 
Inventory (Appendix E) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
INFO 25 (Appendix K) 
X 
 
 
 
 
 
 
 
X 
 
 
Functional oral intake score 
(Appendix F) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
Performance status scale H&N 
(Appendix G) 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
Weight 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
Maximal inter-incisor distance 
(mm)13 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
Modified barium swallow11 
 
X6 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
Footnote: 
1. Procedures to be completed any time prior to start of radiation treatment. If SOC procedures are 
completed prior to consent, they can be included, and do not need to be repeated. 
2. Procedures to be completed during Week 4 of radiation treatment (+/- 2 days). 
3. Procedures to be completed during final week of radiation treatment (+/- 2 days). 

 
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4. Procedures to be completed 3 months after end of radiation, ideally within (+/- 2 weeks). 
However, if the procedures cannot be completed during that window (+/-) 1 month is acceptable. 
5. Procedures to be completed 1 year after end of radiation (+/- 1 month). 
6. Pre-study MBSS should occur prior to start of radiation treatment, but can also occur within 2 
days after start of radiation.  
7. For patients randomized in the app arm of the study. 
8. Part of the technology survey questions (the first 2 questions) are in the “pre-screening survey.” 
When the patient is completing the technology survey, the first 2 questions can be left blank if the 
participant has already answered them in the pre-screening survey (Appendix M).   
9. In addition to Appendix L, the following demographic information will be collected from source 
documentation: date of birth, age at enrollment, miles from residence to treatment center 
10. Medical History: tumor site, TNM staging (8th edition), AJCC stage, HPV status, Primary 
treatment, Prescribed radiation dose (Gy), and Chemotherapy/Systemic Treatment 
11. Modified Barium Swallow Study metrics (Appendix I) completed along with Penetration 
Aspiration Scale (Appendix H) and DIGEST scores (Appendix J)  
12. For patients randomized to paper log arm of the study. 
13. Provide patients with standard scale to measure MIO during video visits (via mail or during in-
person visit) 

 
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8. 
MEASUREMENTS 
For clinicaltrials.gov and Stanford Clinical Trials Directory compliance  
Primary Outcome Measure Definition: Overall adherence to prescribed exercise protocol 
measured as percentage of prescribed exercises completed over a seven-week period. (i.e. if 
participants are asked to complete 6 sets of 10 reps of each exercise daily for 7 weeks, maximum 
potential would be 420 reps). 
* Title: Exercise adherence 
* Time Frame: At the end of the 7 week treatment period 
* Safety Issue: No 
 
8.1  
Primary Outcome Measure  
Adherence to prescribed exercise protocol 
 
 
(a) 8. 1.2 Measurement Definition 
 
Overall adherence to prescribed exercise protocol measured as percentage of prescribed 
exercises completed over a seven-week period. (i.e. if participants are asked to complete 6 sets of 
10 reps of each exercise daily for seven weeks, maximum potential would be 420 reps). 
 
 
(b) 8.1.3 Measurement Methods 
 
Participants will be asked to complete and log their swallow exercises using the either the 
Vibrent application or paper forms throughout the duration of radiation therapy and for 1 month 
after the completion of therapy. The Vibrent application will time stamp the date and time of 
data entry for secondary analysis to determine whether logging occurs on a daily basis or in 
batch. Paper logs will be collected by study personnel weekly and entered into a central Redcap 
database. 
 
(c) 8.1.4 Measurement Time Points 
Adherence measures will be obtained at the conclusion of the 7-week treatment period.   
 
8.2a  Secondary Outcome measures (These measures, in combination, provide a 
comprehensive evaluation of swallowing physiology, its functional impact, and 
patient perception.) 
 
Patient reported:  
MD Anderson Dysphagia Inventory (MDADI)  
 
(d) 8.2a.2 Measurement Definition 
 
The MD Anderson Dysphagia Inventory (MDADI) was selected to capture and quantify the 
patient perception of swallowing dysfunction.  It is a 20-item patient reported survey that 

 
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measures the impact of dysphagia on patients with HNC. Each item is scored on a 5 point scale 
with 1=lower function and 5=higher function. Possible scores range from 20-100 with higher 
scores indicating more normal swallowing function.  Mean scores will be assessed for each 
treatment group at the time of each assessment.  Standard deviation and 95% CI will be reported. 
 
(e) 8.2a.3 Measurement Methods 
 
MDADI: Each item is rated on a scale of 1-5 with lower numbers indicating poorer function.  
Mean subscale scores are multiplied by 20 to provide a final score between 20-100.  All 
participants will complete on paper forms. 
 
 
(f) 8.2a.4 Measurement Time Points 
 
Please see study schedule for the measurement time points. 
8.2b  Secondary Outcome measure 
 
Functional Oral Intake Score (FOIS) 
 
(g) 8.2b.2 Measurement Definition 
In order to describe patient diet levels, the Functional Oral Intake Scale was selected.  The FOIS 
is a 7-point ordinal scale used to describe oral intake where lower scores reflect more limited oral 
intake and higher scores reflect more normal diet levels.  The mean group FOIS score will be 
reported as well as standard deviation and 95% CI at each assessment (see study calendar).  
 
(h) 8.2b.3 Measurement Methods 
FOIS score will be given by the treating clinician based on patient reported diet level. 
 
(i) 8.2b.4 Measurement Time Points 
Please see study schedule for the measurement time points. 
 
8.2c  
Secondary Outcome measure 
Performance Status Scale – Head and neck (PSS HN) 
 
(j) 8.2c.2 Measurement Definition 
The Performance Status Scale – Head and Neck (PSS-HN) was chosen to provide additional 
detail regarding diet and eating restrictions. The three items which will be administered include 
“eating in public”, “understandability of speech”, and “normalcy of diet”.  Each item ranges 
from 0-100 with higher numbers reflecting more normal function.  The mean group score will be 
reported as well as standard deviation and 95% CI at each assessment (see study calendar). 
 
(k) 8.2c.3 Measurement Methods 
PSS-HN will be completed by the treating clinician based on patient reports. 
 

 
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(l) 8.2c.4 Measurement Time Points 
Please see study schedule for the measurement time points. 
 
8.2d  Secondary Outcome measure 
Functional measures obtained during videofluoroscopic swallowing studies (VFSS) 
Penetration Aspiration Scale (PAS) 
 
(m) 8.2d.2 Measurement Definition 
In order to measure physiologic swallow function during MBS studies, three assessment tools 
were chosen.  The Penetration Aspiration Scale is an 8-point interval scale used to describe 
degree of bolus entry into the laryngeal vestibule and patient response to this material. Higher 
numbers reflect more severe laryngeal penetration/aspiration.  The mean group score for most 
severe PAS will be reported as well as standard deviation and 95% CI at each assessment (see 
study calendar). 
 
(n) 8.2d.3 Measurement Methods 
MBS ratings (PAS, MBS-Imp, DIGEST) will be rated by clinicians blinded to group assignment 
based on review of videotaped assessments. 
 
8.2d.4 Measurement Time Points 
Please see study schedule for the measurement time points. 
8.2e  
Secondary Outcome measure 
Functional measures obtained during videofluoroscopic swallowing studies (VFSS) 
Individual item and composite scores of the Modified Barium Swallow Impairment Profile 
(MBS-ImP) 
 
(o) 8.2e.2 Measurement Definition 
The Modified Barium Swallow Impairment Profile is a tool designed to quantify degree of 
impairment on 13 individual physiologic components visualized during a modified barium 
swallow where higher numbers reflect greater dysfunction.  The mean group score for the 
composite oral component and pharyngeal component will be reported as well as standard 
deviation and 95% CI at each assessment (see study calendar). 
 
(p) 8.2e.3 Measurement Methods 
MBS ratings (PAS, MBS-Imp, DIGEST) will be rated by clinicians blinded to group assignment 
based on review of videotaped assessments. 
 
(q) 8.2e.4 Measurement Time Points 
Please see study schedule for the measurement time points. 
 
8.2f  
Secondary Outcome measure 
Functional measures obtained during videofluoroscopic swallowing studies (VFSS) 
Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) severity scores 

 
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(r) 8.2f.2 Measurement Definition 
The Dynamic Imaging Grade of Swallowing Toxicity was established to rate the safety and 
efficiency of the pharyngeal swallow during modified barium swallow studies using the National 
Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) framework.  
This scale provides a safety impairment score, an efficiency impairment score, and an overall 
score.  Lower numbers on this scale are indicative of more normal function.  The mean group 
impairment scores will be reported as well as standard deviation and 95% CI at each assessment 
(see study calendar). 
 
(s) 8.2f.3 Measurement Methods 
MBS ratings (PAS, MBS-Imp, DIGEST) will be rated by clinicians blinded to group assignment 
based on review of videotaped assessments. 
 
(t) 8.2f.4 Measurement Time Points 
Please see study schedule for the measurement time points. 
 
 
8.2g  Secondary Outcome measure 
Maximal interincisal opening 
 
 
(u) 8.2g.2 Measurement Definition 
Maximal interincisor distance will be reported in mm as the space between the bottom of the 
upper incisor and the top of the lower incisor.  In patients missing dentition, 10mm will be 
deducted from this value for each missing incisor to represent the average incisal height. 
 
(v) 8.2g.3 Measurement Methods 
Standard mm measuring tools will be used. 
 
(w) 8.2g.4 Measurement Time Points 
Please see study schedule for the measurement time points. 
 
 
9. 
MULTISITE REGULATORY CONSIDERATIONS 
 
The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will be the 
monitoring board for this study, please refer to the Data and Safety Monitoring Committee SOP 
for more information.  
 
11.1 
Monitoring plan 
 

 
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The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will be the 
monitoring entity for this study. The DSMC will audit study-related activities approximately 
once per year to determine whether the study has been conducted in accordance with the 
protocol, local standard operating procedures, FDA regulations, and Good Clinical Practice 
(GCP).  This may include review of the following types of documents participating in the study: 
regulatory binders, case report forms, eligibility checklists, and source documents.  In addition, 
the DSMC will regularly review protocol deviations from all sites associated with the research to 
ensure the protection of human subjects. Results of the DSMC audit will be communicated to the 
IRB and the appropriate regulatory authorities at the time of continuing review, or in an 
expedited fashion, as needed.  
 
The Stanford Cancer Institute research team will conduct bi-annual audits of sub-site 
enrollment and regulatory compliance. This will include a review of one subject enrolled in that 
time period including case report forms, eligibility checklists, source documents and regulatory 
binders. If no subjects have been enrolled in this time period, the audit will be skipped until the 
next cycle. The research team will also review protocol deviations and communicate findings 
with the DSMC and IRB as appropriate. 
 
 
11.2  Protocol Review and Amendments 
 
The protocol, the proposed informed consent and all forms of participant information related to 
the study (e.g. advertisements used to recruit participants) will be reviewed and approved by the 
Stanford IRB and Stanford Cancer Institute Scientific Review Committee (SRC).  Any changes 
made to the protocol will be submitted as a modification and will be approved by the IRB prior 
to implementation.  The Protocol Director will disseminate the protocol amendment to all 
participating investigators.  Investigators will be expected to obtain IRB approval within 90 days 
for all amendments.   
 
11.3  Data management  
The Protocol Director, or his/her designee, will prepare and maintain adequate and accurate 
participant case histories with observations and data pertinent to the study.  Study specific Case 
Report Forms (CRFs) will document treatment outcomes for data analysis.   Case report forms 
will be developed using the REDCap database system and will be maintained by study personnel 
under the direction of the protocol director. CRFs will be kept in a locked office, only accessible 
to the research team. 
 
A chart with all of the relevant research patient information will be maintained for each patient at 
each institution, and the patient charts may be reviewed by Stanford for yearly audits. 
 
Study data will be collected and managed using REDCap (Research Electronic Data Capture). 
REDCap is a secure, web application designed to support data capture for research studies. It 
provides user-friendly, web-based case report forms, real-time data entry validation (e.g. for data 
types and range checks), audit trails and de-identified data export mechanism to common 
statistical packages (SPSS, SAS, Stata, R/S-Plus). The system was developed by a multi-

 
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institutional consortium which includes Stanford University and was initiated at Vanderbilt 
University. The database is hosted at the Stanford University School of Medicine secure data 
center. The system is protected by Secure Socket Layer (SSL) encryption and a strong web based 
authentication system. Data collection is customized for each study or clinical trial based on a 
study-specific data dictionary defined by the research team with guidance from the Stanford 
Center for Clinical Informatics REDCap administrator. Every personnel in the different sites is 
given access to only their specific site’s “Data Access Group” and can only see and enter 
information for their patients. The Stanford research team will manage this access. 
 
For patients randomized on the app arm of the study, some of their data will be captured via the 
VIbrent Health application. Vibrent Health has been deploying and managing solutions in highly 
regulated, highly secure, highly sensitive environments. Vibrent Health has supported and 
accredited solutions for the National Institute of Health (NIH), the US Army, commercial and 
military medical treatment facilities and hospitals. We understand the compliance requirements 
for these industries and the business requirements to protect the sensitive data that these 
businesses contain.  Vibrent Health currently uses Cyber Secure Amazon AWS Cloud 
infrastructure to host the Vibrent Platform.  Amazon AWS Cloud provides compliance with 
various Federal regulations that impact privacy and security requirements.  AWS Cloud is 
FedRAMP and FISMA certified and provides many other compliances and certifications such as 
HIPAA, SOC 1/2/3, PCI DSS Level 1, ISO 27001 and others.  AWS Data centers are housed in 
nondescript facilities and are not open to the public. 
 
Vibrent Coaching Platform (VCP) App is based on a three-tier architecture consisting of web, 
application and data tiers.  The data tier consists of an Amazon Web Services RDS Aurora Multi 
zone deployment. The database contains all data interactions with the patients. The data tier is 
deployed upon AWS Aurora product which is Amazon’s custom MySQL offering. 
 
 
11.4 
Study Documentation 
 
The Protocol Director and participating site investigators must maintain adequate and accurate 
participant case histories with observations and other data pertinent to the study.  Original source 
documents should be transcribed to REDCap in a timely manner and used to communicate study 
data to the lead site.  Source documents include hospital records, clinical charts, laboratory and 
pharmacy records, and recorded electronic data. Original source documents should be kept by 
each site, an must be provided to the lead site when requested. 
 
Participating Center’s PIs will be responsible for maintaining the clinical protocol and subjects’ 
study charts, assuring that consent is obtained and documented, and reporting the status of the 
trial in continuing renewals submitted to their IRB and trial monitoring group(s) as per their 
facility protocol.   Prior to a subsite’s start of enrollment, each subsite will be required to attend a 
teleconference where relevant Stanford research SOPs and documentation will be reviewed as 
mentioned in the Investigator Initiated Multisite Trial SOP.  
 
 
 

 
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11.5 
Site Communication 
 
When all participating institutions have successfully received IRB approval and have started 
enrolling patients, teleconferences to discuss participants and study-related matters will be held 
at least every two months, although calls may occur more frequently if needed.   
Teleconferences will be coordinated by Research staff at a participating institution; PIs, Research 
Coordinators, Nurses, and Co-Investigators if needed will participate.  Any issues with patient 
compliance, database entry, or other items will also be discussed in these calls.  Calls may 
include review by PIs of subject data to assure validity as well as the safety of subjects; and the 
progress of the trial may also be discussed.  At times of study renewal or more frequently if 
needed, PIs may review safety reports and clinical trial efficacy endpoints and confirm that the 
safety outcomes favor continuation of the study.  
 
 
10. 
STATISTICAL CONSIDERATIONS 
 
10.1 
Statistical Design 
The proposed research is a RCT with a primary aim of determining if a mobile application may 
enhance adherence to swallowing therapy in patients undergoing radiation for head and neck 
cancer thus improving swallowing outcomes.  Analysis of the primary endpoint (adherence) will 
be carried out using logistic regression, comparing arms A and B.  A secondary endpoint will be 
the average percent adherence per week.  Analysis of the secondary adherence endpoint will be 
carried out using a linear mixed effect model with weekly adherence as a dependent variable, a 
patient-specific random intercept, treatment arm as the primary predictor, and week as a fixed 
(categorical) effect. We will also explore the impact of the mobile app on a variety of 
swallowing outcomes including diet level, patient perception, and physiological measures.  
Analysis of these endpoints will be carried out using logistic regression comparing arms A and 
B. 
 
(x) Randomization 
Randomization will be carried out using pre-printed lists with block size of 4. 
 
10.4 
Primary Analysis  
Analysis of the primary endpoint (adherence) will be carried out using logistic regression, 
comparing arms A and B.  Analysis of the secondary adherence endpoint will be carried out 
using a linear mixed effect model with weekly adherence as a dependent variable, a patient-
specific random intercept, treatment arm as the primary predictor, and week as a fixed 
(categorical) effect. 
 
(y) Analysis Population 
Analysis will include all participants. 
 

 
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34
(z) Analysis Plan 
As above 
 
12.5 
Secondary Analysis 
We will also explore the impact of the mobile app on a variety of swallowing outcomes 
including diet level, patient perception, and physiological measures.  Analysis of these endpoints 
will be carried out using logistic regression comparing arms A and B. 
 
(aa) 
12.5.1 Analysis Population 
Analysis will include all participants. 
 
(bb) 
12.5.2  Analysis Plan 
As above 
 
12.6  Sample Size 
(cc) 
12.6.1 Accrual estimates 
 
 
Accrual estimates are based upon average clinical volumes at three participating institutions over 
the past 3 years. 
 
(dd) 
12.6.2 Sample size justification 
 
88 patients will be enrolled in each arm.  This number will provide 80% power to detect a 15 
percentage point difference between groups. This sample size includes the addition of 20% to 
account for anticipated drop out. 
 
(ee) 
12.6.3 Effect size justification 
This calculation is made assuming 33% adherence in arm B and a standard deviation of 32 based 
on prior studies. 
 

 
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35
13. 
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APPENDICES 
APPENDIX A: Participant Eligibility Checklist  
 
Protocol Title: 
     Investigation of Two Swallowing Therapy Models 
during Radiation Therapy for Head and Neck 
Cancer   
 
 
Protocol Number: 
IRB-48015 
Principal 
Investigator: 
Heather Starmer 
 
II. Subject Information: 
 
Subject Name/ID: 
 
Gender:    
 Male     
 Female 
III. Study Information: 
SRC Approved 
 IRB Approved 
 Contract signed 
 
IV. Inclusion/Exclusion Criteria 
 
Inclusion Criteria 
(From IRB approved protocol) 
Yes 
No 
Supporting Documentation* 
1. Age ≥ 18 years 
 
 
      
2. Fluent English speaking 
subject 
 
 
      
3. Study subject capable of 
providing informed consent 
 
 
      
4. Patient with newly diagnosed 
non-metastatic head and neck 
cancer such as cancer of the 
oral cavity, oropharynx, 
nasopharynx, hypopharynx, 
and larynx that require bilateral 
neck radiation.  Individuals with 
unknown primary head and 
neck cancer with nodal disease 
necessitating bilateral radiation 
will also be included. 
 
 
      

 
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5. No prior history of surgery and/ 
or radiation of the head and 
neck for another malignancy 
 
 
      
6. Study subject with a previously 
untreated head and neck 
cancer diagnosis requiring a 
definitive course of 
radiotherapy requiring a 
prescribed dose of 60Gy or 
greater. 
 
 
      
Exclusion Criteria 
(From IRB approved protocol) 
Yes         No 
1. Lack of smartphone, tablet, or 
Internet connection. 
 
 
      
2. Patients with recurrent 
disease. 
 
 
      
3. Individuals with 
contraindications to radiation 
therapy. 
 
 
      
*All subject files must include supporting documentation to confirm subject 
eligibility.  The method of confirmation can include, but is not limited to, 
laboratory test results, radiology test results, subject self-report, and medical 
record review.   
IV.  Statement of Eligibility 
By signing this form of this trial I verify that this subject is [
 eligible / 
 ineligible] for 
participation in the study. This study is approved by the Stanford Cancer Institute 
Scientific Review Committee, the Stanford IRB, and has finalized financial and 
contractual agreements as required by Stanford School of Medicine’s Research 
Management Group.   
 
Treating Physician Signature: 
Date: 
Printed Name: 
 
Secondary Reviewer Signature: 
Date: 
Printed Name: 
 
Study Coordinator Signature: 
Date: 
Printed Name: 

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Appendix C: Patient Comfort with Technology
1. Do you own either an Android or Apple-iOS based smartphone or tablet?
Yes                                                
No
2. Do you have access to an internet connection or a sufficient monthly data 
plan (~200MB/month) or greater?
Yes                                                
No
3. Please mark on the line to indicate your comfort using technology.
Very uncomfortable
    
Very comfortable
4. Please mark on the line to indicate your comfort using your smartphone.
Very uncomfortable
                   
Very comfortable
5. Please mark on the line to indicate your comfort using your tablet.
Very uncomfortable
Very comfortable

 
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Appendix D: Paper logging form 
 
Exercise logging form: Please indicate the number of sets of exercises prescribed you 
completed and denote your level of pain after completing the sets of exercises with 1 being no 
pain, and 10 extreme:  
 
 
 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Date 
 
 
 
 
 
 
 
AM 
 
 
 
 
 
 
 
PM 
 
 
 
 
 
 
 
Pain 
Level (1-
10) 
 
 
 
 
 
 
 
 
 
 
 
 
Participant Name: ______________________________________    

 
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Appendix E: MD Anderson Dysphagia Inventory 
 
 
 
 
 
 
 
 
 

 
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Appendix F: Functional Oral Intake Scale (FOIS) 
 
Level 1:  Nothing by mouth 
Level 2: Tube dependent with minimal attempts of food or liquid 
Level 3: Tube dependent with consistent oral intake of food or liquid 
Level 4:  Total oral diet of a single consistency 
Level 5:  Total oral diet of multiple consistencies but requiring special preparation or 
compensations 
Level 6: Total oral diet of multiple consistencies without special preparation but with 
specific food limitations 
Level 7: Total oral intake without restrictions 
 
 

 
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Appendix G: Performance Status Scale – Head and Neck 
 
Eating in Public 
 
_____ No restriction of place, food, or companion (eats out at any opportunity) (100) 
 
_____ No restriction of place but restricts diet when in public(eats anywhere but may limit intake   
to less “messy” foods, e.g. liquids) (75) 
_____ Eats only in presence of selected persons in selected places (50) 
_____ Eats only at home in presence of selected persons (25) 
_____ Always eats alone (0) 
 
Understandability of speech 
 
_____ Always understandable (100) 
_____ Understandable most of the time; occasional repetition necessary (75) 
_____ Usually understandable; face to face contact necessary (50) 
_____ Difficult to understand (25) 
_____ Never understandable; may use written communication (0) 
 
Normalcy of diet 
 
_____ Full diet (no restrictions) (100) 
_____ Peanuts (90) 
_____ All meat (80) 
_____ Carrots, celery (70) 
_____ Dry bread and crackers (60) 
_____ Soft, chewable foods (e.g. macaroni, canned/soft fruits, cooked vegetables, fish, 
hamburger, small pieces of meat) (50) 
_____ Soft foods requiring no chewing (e.g. mashed potatoes, applesauce, pudding) (40) 
_____ Pureed foods (in blender) (30) 
_____ Warm liquids (20) 
_____ Cold liquids (10) 
_____ Nonoral feeding (tubefed) (0) 
 
 

 
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Appendix H: Penetration Aspiration Scale 
 
Score 
Characteristics 
1 
Does not enter airway 
2 
Enters airway, remains above cords, is ejected 
3 
Enters airway, remains above cords, not ejected 
4 
Enters airway, contacts cords, is ejected 
5 
Enters airway, contacts cords, not ejected 
6 
Enters airway, below cords, ejected out or into larynx 
7 
Enters airway, below cords, not ejected despite effort 
8 
Enters airway, below cords, no effort to eject 
 
 
 

 
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Appendix I: Modified Barium Swallow Impairment Profile (MBS-Imp) 
 
 

 
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Appendix J: Dynamic Imaging Grade of  Swallowing Toxicity 
 
 
 

 
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Appendix K: INFO 25 Survey 
 

 
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Appendix L: Demographic Survey 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix M: Pre-screening Questionnaire 
 
1. Do you own either an Android or Apple-iOS based smartphone or tablet? 
 
 
Yes                                                
No 
 
 
 
2. Do you have access to an internet connection or a sufficient monthly data plan 
(~200MB/month) or greater? 
 
 
Yes                                                
No