A Prospective Multi-center Study Comparing the Performance of the Dysphagia Detection System (DDS) in Detecting Impaired Swallowing Safety and Efficiency as Compared to the Clinical Reference Method - Videofluoroscopic Swallowing Study
Phase: NA
Conditions: Stroke, Parkinson Disease, Multiple Sclerosis, Oropharyngeal Dysphagia, Alzheimer Disease, Dementia
Sponsor: Société des Produits Nestlé (SPN)

Nestlé Research Center – Lausanne 
RDCD-FM-8000-00001-Rev05  
Valid from November 2015 
 
 
Related to procedure Trial Protocol RDCD-SOP-8000-00001 
 
CONFIDENTIAL · This document may not be reproduced or disclosed to third parties without prior authorization 
 
 
 
 
 
 
 
 
Trial Protocol 
 
Trial N° 16.21.CLI 
NPDI Code N° DNHS-100135 
 
 
 
A prospective multi-center study comparing the performance of the  
Dysphagia Detection System (DDS) in detecting impaired swallowing 
safety and efficiency as compared to the clinical reference method - 
videofluorosopic swallowing study (VFSS) 
PORSCHE 
 
 
 
 
 
Version: 
Amendment  
N° 
02 
Date: 
25 September 2017  
Sponsor 
Nestec Ltd 
Avenue Nestlé 55 
CH-1800 Vevey 
Switzerland 
 
 

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TABLE OF CONTENTS 
 
1 
INVESTIGATOR SIGNATURE PAGE ..................................................................................... 5 
2 
SPONSOR TEAM SIGNATURE PAGE ................................................................................... 6 
3 
PROTOCOL AMENDMENT VERSION 02 .............................................................................. 7 
4 
ABBREVIATIONS ........................................................................................................... 15 
5 
SYNOPSIS ................................................................................................................... 16 
6 
TRIAL PLAN ................................................................................................................. 20 
7 
INTRODUCTION ............................................................................................................ 21 
8 
TRIAL OBJECTIVES AND ENDPOINTS .......................................................................... 22 
8.1 
Primary objective ........................................................................................................ 22 
8.2 
Primary endpoint ......................................................................................................... 22 
8.3 
Secondary objective .................................................................................................... 22 
8.4 
Secondary endpoints .................................................................................................. 23 
8.5 
Exploratory endpoints ................................................................................................. 23 
8.6 
Safety endpoints ......................................................................................................... 23 
9 
TRIAL DESIGN .............................................................................................................. 23 
10 
TRIAL POPULATION....................................................................................................... 24 
10.1 
Subject inclusion criteria ............................................................................................. 25 
10.2     Subject exclusion criteria ............................................................................................ 25 
10.3 
Subject discontinuation criteria ................................................................................... 25 
10.4 
Subject replacement ................................................................................................... 26 
10.5 
Sponsor Discontinuation Criteria ................................................................................ 26 
11 
INVESTIGATIONAL DEVICE .................................................................................... 26 
11.1 
Investigational Device Description .............................................................................. 26 
11.2 
Storage and Labeling .................................................................................................. 27 
11.3 
Device Accountability .................................................................................................. 27 
12 
TRIAL ASSESSMENTS AND PROCEDURES ........................................................................ 27 
12.1 
Screening .................................................................................................................... 27 
12.2 
Informed Consent ....................................................................................................... 27 
12.3 
Baseline Assessment .................................................................................................. 27 
12.4 
Preparation ................................................................................................................. 28 
12.5 
Swallow Exam ............................................................................................................. 28 
12.6 
VFSS Stopping Rules ................................................................................................. 29 
12.7 
Post-Exam .................................................................................................................. 29 
12.8 
Premature trial termination .......................................................................................... 29 
12.9 
Trial completion ........................................................................................................... 29 

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13 
DATA MANAGEMENT ..................................................................................................... 30 
13.1 
Data capture ............................................................................................................... 30 
13.2 
Access rights ............................................................................................................... 30 
13.3 
Coding ......................................................................................................................... 30 
13.4 
Database Lock ............................................................................................................ 30 
14 
STATISTICS ................................................................................................................. 30 
14.1 
Background ................................................................................................................. 30 
14.2 
Success criteria and hypothesis testing ...................................................................... 30 
14.3 
Threshold Optimization ............................................................................................... 31 
14.4 
Sample size calculations ............................................................................................. 31 
14.5 
Group Sequential Design ............................................................................................ 32 
14.6 
Interim analysis and Sample Size Reestimation ......................................................... 32 
14.7 
Central Blinded VFSS Assessors ............................................................................... 32 
14.8 
Datasets to be analyzed ............................................................................................. 32 
14.8.1 
Full analysis dataset ...................................................................................... 32 
14.8.2 
Safety analysis set ........................................................................................ 32 
15 
HANDLING OF ADVERSE EVENTS .................................................................................... 33 
15.1 
Definitions and assessment criteria ............................................................................ 33 
15.1.1 
Adverse event ............................................................................................... 33 
15.1.2 
Serious adverse event .................................................................................. 33 
15.1.3 
Unanticipated Adverse Device Effect (UADE) .............................................. 33 
15.1.4 
Anticipated Adverse Events .......................................................................... 34 
15.1.5 
Severity of adverse events ............................................................................ 34 
15.1.6 
Event Relatedness ........................................................................................ 34 
15.2 
Reporting of serious adverse events and unanticipated adverse device effects ........ 35 
15.2.1 
Reporting of serious adverse events and UADEs to Sponsor ...................... 35 
15.2.2 
Follow up of serious adverse events ............................................................. 35 
15.2.3 
Notification .................................................................................................... 35 
15.3 
Reporting .................................................................................................................... 36 
16 
RISK ANALYSIS ....................................................................................................... 36 
16.1 
Potential Risks ............................................................................................................ 36 
16.1.1 
VFSS Risks ................................................................................................... 36 
16.1.2 
Investigational Device Risks ......................................................................... 37 
16.2 
Potential Benefit .......................................................................................................... 37 
16.3 
Mitigation of Risk ......................................................................................................... 37 
16.4 
Risk Analysis Conclusion ............................................................................................ 38 
17 
SPONSOR AND INVESTIGATOR OBLIGATIONS ................................................... 38 
17.1 
Good Clinical Practice and Declaration of Helsinki ..................................................... 38 
17.2 
Independent Ethics Committee/Institutional Review Board Approval ......................... 38 
17.3 
Informed Consent ....................................................................................................... 38 
17.4 
Subject Confidentiality ................................................................................................ 39 

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17.5 
Data Reporting and Case Report Forms..................................................................... 39 
17.6 
Retention of Data ........................................................................................................ 39 
17.7 
Deviations from the Protocol/Protocol amendments ................................................... 40 
17.8 
Trial Monitoring ........................................................................................................... 40 
17.9 
Sponsor Audits ............................................................................................................ 40 
17.10 Regulatory Agency Inspections .................................................................................. 40 
17.11 Publications ................................................................................................................. 40 
17.12 Insurance Policy .......................................................................................................... 40 
18 
REFERENCES .............................................................................................................. 41 
19 
APPENDIX A: WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI ...... 42 
20 
APPENDIX B: PENTRATION ASPIRATION SCALE .................................................... 47 
 

10 
Date: 
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1 
INVESTIGATOR SIGNATURE PAGE 
PRINCIPAL INVESTIGATOR 
Name and Title: Dr. Richard Harvey, MD 
Institution: 
Shirley Ryan Abilitylab 
(Rehabilitation Institute of Chicago) 
Address: 
Chicago, IL 
Phone: 
312-238-1000 
Email: 
rharvev(a.sralab.orq 
I have read this protocol and agree to conduct the above mentioned trial as outlined herein within 
the agreed upon time frame. 
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3 
PROTOCOL AMENDMENT VERSION 02 
Section 
Change 
Rationale 
Synopsis 
Primary/Secondary 
Endpoints 
Removed mention of # of 
boluses following each 
endpoint. 
 
 
 
 
Changed the order of 
secondary endpoints: The 
sensitivity & specificity for 
swallow safety using 
moderate barium (MOD-Ba) 
is now secondary endpoint 
#2 followed by efficiency 
endpoints    
 
Reduced # of boluses 
per thin and mildly thick 
consistency.  Thus 
determined mention of 
bolus per consistency 
was redundant here. 
 
Aligned on clincial 
priority:  safety of 
swallowing has priority 
over efficiency of 
swallowing 
 
Synopsis 
Secondary 
Objective 
Added in Secondary 
Objective from Section 8.3 
Missing from Synopsis 
Synopsis 
Exploratory 
Endpoints 
Added additional 
Exploratory Endpoint:  
Impact of VFSS results on 
Nutritional Management 
Explore the relationship 
between VFSS findings 
and nutritional  decisions  
Synopsis 
Trial Design 
Removed ‘for thin (THIN-Ba 
boluses)’ from the statement 
‘The study is designed as 
operationally seamless to 
facilitate the updating of the 
threshold on the ROC curve 
for swallowing safety if 
required.  
Clarification that the 
design pertains to not 
just the thin boluses. 
Synopsis 
Trial Design 
Increase enrollment from 
800 to 900 (with a maximum 
enrollment increased from 
1150 to 1300).  
Update to statistical plan 
increased the number of 
study samples needed. 
Synopsis 
Trial Design 
Added ‘At the last interim 
analysis a sample-size re-
estimation will be carried out 
in order to compensate for 
design parameters like 
accuracy and prevalence 
that may be slightly different 
from the values assumed 
during trial design.’ 
Added clarification 
should design 
parameters assumed 
during the trial design 
not be met, then a 
sample size re-
estimation is necessary.  
Synopsis 
Procedure 
Decrease of boluses from 6 
to 5 thin barium stimulus 
and decrease from 6 to 4 
Sensitivity and specificity 
end-points are changed 
from evaluation at bolus 

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boluses of barium thickened 
to mildly thick 
(swallow) level to a 
patient level following 
FDA advice. 
 
The algorithms for THIN-
Ba, MILD-Ba and 
MODERATE-Ba are 
based on anaylsis of up 
to 4, 3 and 3 swallows 
per patients for each 
consistency respectively.  
One additional bolus in 
each consistency will be 
collected to compensate 
for bolus-level data lost 
due to unreadable VFSS 
signals 
 
(Rationale: According to 
the analysis of 
Exploratory trial with 
more than 4000 boluses, 
up to 14% of boluses 
were missing golden 
standard (VFSS)  rating 
mainly due to insufficient 
quality of VFSS videos). 
  
Synopsis 
Procedure 
4, 3 and 3 boluses for THIN-
Ba, MILD-Ba and MOD-Ba 
will be analyzed using the 
classifier algorithms for 
sensitivity/specificity results. 
According to the exploratory 
trial, VFSS data for safety or 
efficiency can be missing for 
up to 14% boluses due to 
quality of VFSS recording. 
To compensate for potential 
losses of boluses due to 
missing gold standard 
(VFSS) data, 5, 4 and 4 
boluses will be collected for 
the three consistencies 
respectively. 
 
Clarification of when subject 
will be followed after the 
study procedure.  Redefined 
‘within 2 business days’ and 
deleted ‘for approximately 1 
day’ after the study 
procedure. 
See above 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Standardized wording 
across the protocol of 
when a subject will be 
followed after the study 
procedure. 
Synopsis 
Trial Population 
Increase enrollment to 900 
(from 800) with a maximum 
Update to statistical plan 
increased the number of 

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enrollment increased to 
1300 from 1150).  
study samples needed. 
Synopsis 
Inclusion Criteria 
Removed from the patient 
group of stroke patients the 
qualifier of ‘with scores 0 or 
1 on question 1a of NIHSS’ 
Deemed duplicative with 
Inclusion Criteria : 
Subject able to give 
voluntary, written 
informed consent to 
participate in the clinical 
investigation and from 
whom consent has been 
obtained / or a consultee 
has consented on the 
subjects behalf in line 
with nationally agreed 
guidelines concerning 
adults unable to consent 
for themselves.  
Additionally not all sites 
use NIHSS scoring. 
Synopsis 
Trial Visits 
Added (up to 2 weeks prior) 
at end of the following 
sentence : Consent must be 
obtained prior to the study 
procedure. 
 
Clarification of when subject 
will be followed after the 
study procedure.  Redefined 
‘within 2 business days’ and 
deleted ‘for approximately 1 
day’ after the study 
procedure. 
Added clarification of 
time a subject may be 
consented prior to the 
study prodedure. 
 
Standardized wording 
across the protocol of 
timeframe a subject will 
be followed after the 
study procedure. 
Synopsis 
Statistical Method 
Change of specificity from 
‘of at least 55%’ to ‘greater 
than 50%’ 
The targeted sensitivity 
and specificity of about 
90%/ 60% is maintained, 
however to avoid 
substantial sample size 
increase due to change 
from bolus to patient 
level endpoint, use of a  
broader confidence 
interval is proposed for 
specificity.  
Synopsis 
Statistical Method 
Change of the type-I error 
from 5% to ‘2.5% (one-
sided)’. 
Clarification requested 
by FDA 
Synopsis 
Blinded Mid-
Course 
Enrichment  
 
  
Section header : Blinded Mid-
Course Enrichment is removed.  
 
The following is removed : A 
further inclusion/exclusion 
criteria based on the 
screening test (using 
Dysphagia screening as per 
usual site-specific protocol) 
As per FDA 
recommendation, The 
Blinded Mid-Course 
Enrichment is 
abandoned, but the 
study will continue to 
monitor the prevalence 
in the Trial.  The plan to 

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results may be imposed. 
This will be reflected in a 
formal protocol-amendment 
and will be implemented 
before the first interim 
analysis. 
 
Replaced by : 
The study population should 
be representative of the 
device intended use 
population (at risk of 
dysphagia).  According to 
the published literature, 
estimated prevalence of 
dysphagia in the target 
population varies from 20-
50%.   
The necessity to carry out 
VFSS may result in sites 
selecting patients at higher 
risk than in the intended 
target population (such as 
those already assessed by 
SLPs).   
We therefore blindly monitor 
the prevalence and retrain 
sites as necessary in order 
to ensure that they recruit 
at-risk patients (not only 
those already assessed as 
dysphagic by SLPs). 
 
consider change in 
recruitment criteria 
is also no longer relevant  
 
6 
Table 1 : 
Sequence of Study 
Procedures 
‘Swallow Exam of up to 5 
(not 6) sips of thin barium…’ 
and ‘Swallow Exam of up to 
4 (not 6) sips of mildly-thick 
barium 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sensitivity and specificity 
end-points are changed 
from evaluation at bolus 
(swallow) level to a 
patient level following 
FDA feedback. 
The algorithms for THIN-
Ba, MILD-Ba and 
MODERATE-Ba are 
based on anaylsis of up 
to 4, 3 and 3 swallows 
per patients for each 
consistency respectively.  
One additional bolus in 
each consistency will be 
collected to compensate 
for bolus-level data lost 
due to unreadable VFSS 
signals. 
 
 
Standardized wording 

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Clarification of when subject 
will be followed after the 
study procedure.  Redefined 
‘within 2 business days after 
the study procedure.’and 
deleted ‘approximately 1 day 
after all exams are 
complete.’  
across the protocol of 
when a subject will be 
followed after the study 
procedure. 
 
8.2 & 8.4 
Primary/Secondary 
Endpoints 
Removed mention of # of 
boluses following each 
endpoint. 
 
 
 
 
Changed the order of 
secondary endpoints: The 
sensitivity & specificity for 
swallow safety using 
moderate barium (MOD-Ba) 
is now secondary endpoint 
#2 folowed by efficiency 
endpoints    
  
Reduced # of boluses 
per thin and mildly thick 
consistency.  Thus, the 
mention of bolus per 
consistency was 
redundant here. 
 
To align on clincial 
priority:  safety of 
swallowing has priority 
over efficiency of 
swallowing. 
 
8.5 
Exploratory 
Endpoints 
Added additional 
Exploratory Endpoint:  
Impact of VFSS results on 
Nutritional Management (% 
patients with diet changes 
(advanced/more 
conservative)) 
Explore the relationship 
between VFSS findings 
and nutritional  decisions 
for future trials on 
dysphagia.   
9 
Procedure 
Decrease of boluses from 6 
to 5 thin barium stimulus 
and decrease from 6 to 4 
boluses of barium thickened 
to mildly thick. 
 
Added ‘4, 3 and 3 boluses 
for THIN-Ba, MILD-Ba and 
MOD-Ba will be analyzed 
using the classifier 
algorithms for 
sensitivity/specificity results. 
According to the exploratory 
trial, VFSS data for safety or 
efficiency can be missing for 
up to 14% boluses due to 
quality of VFSS recording. 
To compensate for potential 
losses of boluses due to 
missing gold standard 
(VFSS) data, 5, 4 and 4 
boluses will be collected for 
same as in the synopsis 
 
 
 
 
 
same as in the synopsis  

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the three consistencies 
respectively’. 
10 
Trial Population 
Increased enrollment to 900 
(from 800 ) with a maximum 
enrollment increased to 
1300 from 1150.  
same as in synopsis  
10.1 
Subject Inclusion 
Criteria 
Removed from the patient 
group of stroke patients the 
qualifier of ‘with scores 0 or 
1 on question 1a of NIHSS’ 
same as in synopsis 
12.1 
Screening 
Added a timeframe prior to 
study procedure may be 
consented ‘…provide their 
consent to particiapte in the 
study ‘within 2 weeks of the 
study procedure.’ 
Added clarification of 
time a subject may be 
consented prior to the 
study prodedure. 
 
12.3 
Baseline 
Assessment 
Removed the following data 
to be collected for stroke 
patients : Modified Rankin 
Scale and Barthal Index 
 
Added the following data to 
be collected for parkinson 
patients (if available) : 
Functional Independence 
Measurement 
The patient scales 
deemed necessary for 
data collection were 
reassessed. 
12.5 
Swallow Exam 
Up to 5 (not 6) boluses of 
thin barium and up to 4 (not 
6) boluses of mildly thick 
barium 
same as in synopsis 
12.7 
Post Exam 
Clarification of when subject 
will be followed after the 
study procedure.  Redefined 
‘within 2 business days’ and 
deleted ‘approximately 1 
business day’ after the study 
procedure. 
Standardized wording 
across the protocol of 
when a subject will be 
followed after the study 
procedure. 
14.2 
Success Criteria 
and hypothesis 
testing 
Change of specificity from 
‘of at least 55%’ to ‘greater 
than 50%’ 
 
Change of the type-I error 
from ‘5%’ to ‘2.5% (one-
sided)’. 
same as in synopsis 
 
 
 
same as in synopsis 
14.3 
Threshold 
Optimization 
Added: 
‘The study population should 
be representative of the 
device intended use 
population (at risk of 
dysphagia).  According to 
the published literature, 
estimated prevalence of 
dysphagia in the target 
population varies from 20-
same as in synopsis 

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50%.   
The necessity to carry out 
VFSS may result in sites 
selecting patients at higher 
risk than in the intended 
target population (such as 
those already assessed by 
SLPs).   
We therefore blindly monitor 
the prevalence and retrain 
sites as necessary in order 
to ensure that they recruit 
at-risk patients (not only 
those already assessed as 
dysphagic by SLPs).’ 
 
14.4  
(section 
removed) 
Blinded Mid-
Course 
Enrichment 
 
 
Section 14.4 : Blinded Mid-
Course Enrichment is removed.  
 
The following is removed : 
‘A further inclusion/exclusion 
criteria based on the 
screening test (using 
Dysphagia screening as per 
usual site-specific protocol) 
results may be imposed. 
This will be reflected in a 
formal protocol-amendment 
and will be implemented 
before the first interim 
analysis’. 
 
 
same as in synopsis 
14.4 
Sample Size 
Calculations 
 ‘if a high.risk population 
with at least 60% to 70% 
prevalence is sampled and if 
at least 30% of the swallows 
coming from Dysphagis 
patients show impaired 
safety’ changed to ‘If 
approximately 35% patients 
show impaired safety’ 
 
Change from ‘...then a 
power of 90% can be 
achieved with 700-800 (from 
500 to 600) subjects under a 
fixed design.  
 
Increased sample size : 
Considering that data from 
additional 100 to 200 
subjects may be used for 
threshold calibration, the 
starting  sample size is 900 
Clarification 
/simplification   
 
 
 
 
 
 
 
 
Revised power 
calculation   
 
 
 
 
Revised power 
calculation   
 
 
 
 

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(from 800) subjects.   
 
Added : A sample size re-
estimation will be carried out 
at the last interim analysis.  
 
 
 
Clarification of last 
interim analysis 
 
  
14.7 
Central Blinded 
VFSS Assessors 
Added ‘if the consensus can 
not be reached due to a 
noisy VFSS signal, the bolus 
will be rated as missing 
VFSS’. 
Added clarification for 
VFSS rating process  
14.8.1 
Full Analysis 
Dataset  
 
 ‘For this trial, ITT population 
is defined as the population 
able to complete ‘at least 3 
boluses’ is changed to ‘at 
least one’ THIN-Ba  bolus.’ 
 
 
Added : Missing data will be 
reported and sensitivity 
analysis carried out.   
 
Added : The THIN-Ba 
consistency boluses (up to 
4) with available 
simultaneous VFSS and 
DDS data per patient will be 
included into the analysis.  
As will the  MILD-Ba and the 
MOD-Ba consistency 
boluses (up to 3 each) with 
simultaneous VFSS and 
DDS data per patient.  
Reflect change of 
endpoint from bolus to 
patient level: algorithms 
should produce patient-
level result if at least one 
bolus is completed. 
 
Clarification    
 
 
 
 
Clarification  
17.6 
Retention of Data 
Change from ‘Records can 
be in paper or electronic 
format.’ to ‘The eTMF is the 
official regulatory file for the 
study and will be used for 
monitoring the study and by 
FDA for any inspections 
(audits) under the 
Bioresearch Monitoring 
(BIMO) program.  The only 
paper files included in the 
official regulatory file will be 
all original signed informed 
consent forms.’; (also added 
eTMF to Section 4: 
Abbreviations) 
Clarification of official 
records format for the 
study. 
 
 
 

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4 
ABBREVIATIONS 
 
 
AE 
Adverse Event 
 
 
CPM 
Clinical Project Manager 
CRA 
Clinical Research Associate (synonym: trial monitor) 
CRO 
Contract Research Organization 
CRF 
CSE 
DDS 
Case Report Form 
Clinical Swallow Evaluation  
Dysphagia Detection System 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EDQF 
EM 
eTMF 
FEES 
Electronic Data Query Forms 
Electromagnetic 
Electronic Trial Master File 
Fiberoptic Endoscopic Evaluation of Swallowing 
FIM 
GCP 
GSD 
HIPAA            
Functional Independence Measurement 
Good Clinical Practice 
Group Sequential Design 
Health Insurance Portability and Accountability Act 
 
 
 
 
 
 
ICH 
International Conference on Harmonization 
iDMC 
IDE 
IEC 
Independent Data Monitoring Committee 
Investigational Device Exemption 
Independent Ethics Committee 
IRB 
Institutional Review Board 
iSC 
ITT 
Independent Statistical Center 
Intent-To-Treat 
MBS 
MD 
NPV 
Modified Barium Swallow 
Medical Doctor 
Negative Predictive Value 
NRC 
Nestlé Research Centre 
 
 
PM 
Project Manager 
PP 
PPV 
RCRI               
Per-protocol 
Positive Predictive Value 
Regulatory & Clinical Research Institute, Inc. (CRO for this trial) 
ROC 
Receiver Operating Characteristic (curve) 
 
 
SAE 
Serious Adverse Event 
SLP 
SOP  
Speech Language Pathologist 
Standard Operating Procedures 
UADE             Unanticipated Adverse Device Effect  
 
 
 
TUC 
 
Thicken Up Clear 
 
VFSS              Videofluoroscopic Swallowing Study 
 
 
 

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5 
SYNOPSIS 
TRIAL TITLE  
A prospective multi-center single-blinded study comparing the performance of the Dysphagia Detection 
System (DDS) in detecting impaired swallowing safety and efficiency as compared to the clinical 
reference method - videofluoroscopic swallowing study (VFSS). 
TRIAL N°  
16.21.CLI  
TRIAL OBJECTIVES 
AND ENDPOINTS 
Primary objective 
The primary objective is to validate the DDS against the VFSS for detecting swallow safety problems 
using thin barium stimulus (THIN-Ba). 
 
 
Primary endpoint 
The primary efficacy of the DDS will be measured as specificity and sensitivity obtained from 
comparing the DDS predicted swallow safety outcome with the clinical reference standard VFSS 
swallow safety outcome (binary) for thin barium (THIN-Ba) boluses 
 
Secondary Objective 
The secondary objective is to validate the DDS against the VFSS for detecting swallow efficiency  
problems using thin stimulus (THIN-Ba) and swallowing safety and efficiency using mild and 
moderately thick stimuli.  
Swallowing efficiency described the ability to clear a bolus through the pharynx in 2 swallows or less 
without leaving residue in the throat. The impaired swallowing efficiency is defined as at least 50% 
residue as determined by VFSS. 
 
Secondary endpoints  
At the final analysis, if the primary endpoint meets statistical significance then formal testing and 
analysis for the following secondary endpoints will be carried out in a hierarchical fashion in the 
specified order:  
1. 
The sensitivity & specificity for swallow safety using mild barium (MILD-Ba)  
2. 
The sensitivity & specificity for swallow safety using moderate barium (MOD-Ba) 
3. 
The sensitivity & specificity for swallow efficiency using THIN-Ba  
4. 
The sensitivity & specificity for swallow efficiency using MILD-Ba 
5. 
The sensitivity & specificity for swallow efficiency using MOD-Ba  
 
Exploratory endpoints 
• 
Prevalence of boluses resulting in “grey” outcomes of the classifier for safety and efficiency of the 
swallows on thin (THIN-Ba) and thickened stimuli (MILD-Ba and MOD-Ba) 
• 
Prevalence of impaired swallowing safety and efficiency of the swallows of thin (THIN-Ba) and 
thickened stimuli (MILD-Ba and MOD-Ba) as determined by VFSS at bolus and participant levels. 
• 
Positive and Negative predictive value (PPV and NPV) of detecting swallow safety and efficiency 
problems using DDS and using THIN-Ba, MILD-Ba and MOD-Ba stimuli. 
• 
Prevalence of impaired swallowing safety and efficiency of the swallows of thin (THIN-Ba) and 
thickened stimuli as determined by VFSS at bolus and patient level by the following predetermined 
subgroups: stroke, other neurological diseases, other patients. 
• 
Timing and Outcome of the dysphagia screening as per usual care protocol of the study site 
• 
Timing and Outcome of the dysphagia Clinical Swallow Assessment (CSE) by SLP (speech 
language pathologist) where applicable as per usual care protocol of the study site 
• 
Impact of VFSS results on Nutritional Management  
• 
DDS accuracy in terms of AUC, sensitivity and specificity by sub-group (Stroke, Other 
Neurological Diseases and Others) for swallow safety and efficiency problems for all consistencies 
(THIN-Ba, MILD-Ba, MOD-Ba) 
 
Safety Endpoints 
All adverse events (AEs) will be observed during and within two business days following the study 
procedure. 
 
 

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TRIAL DESIGN 
An operationally seamless single-arm, prospective, multicenter, single-blinded for central outcomes 
assessors trial to test DDS in assessing swallowing safety and efficiency in patients at risk of 
oropharyngeal dysphagia. The study is designed as operationally seamless to facilitate the updating of 
the threshold on the ROC curve for swallowing safety if required and to validate the DDS classifier with 
a fixed threshold using an independent validation set. 
 
The study has been planned to enroll and study approximately 900 patients (maximum enrollment 
1300 ) with the possibility of early stopping for futility or success.  
 
The trial will start with the frozen classifier based on a fixed threshold derived using ROC curve from 
the completed exploratory trial.  The clinical trial will initially start as a 3-look group sequential design 
(GSD).  At the first interim, sensitivity and specificity will be calculated based on the fixed threshold. If 
the Area under the ROC curve at the first interim is above 75% but the sensitivity and/or specificity are 
low then the threshold will be revised based on the first interim data. In this case, the validation will 
exclude the data used for the first interim, i.e. the validation trial will start with the first patient enrolled 
after the first interim analysis data cut-off date. In case the fixed threshold from the completed 
exploratory trial data is not revised using the first interim data, the trial continues as planned.  At the 
last interim analysis a sample-size re-estimation wil be carried out in order to compensate for design 
parameters like accuracy and prevalence that may be slightly different from the values assumed during 
trial design. 
 
 
If the classifier cannot analyze the signal (e.g. due to signal-to-noise level), it will result in a “grey” 
outcome of the classifiers. The prevalence of “grey” outcomes among analyzed boluses for safety and 
efficiency classifier on thin (THIN-Ba) and thickened stimuli (MILD-Ba and MOD-Ba) at site level will be 
monitored centrally during the trial.   
 
Blinding: 
VFSS analysis, considered in this study as the clinical reference method (gold standard), will be 
performed by an independent and central VFSS assessment laboratory which will be blinded to the 
DDS results.  The interim analyses will be carried out in an unblinded fashion by an independent 
statistical center (iSC) while the interim decisions will be made by an independent data monitoring 
committee (iDMC). The iDMC will also monitor the prevalence of swallow safety problems in a blinded 
manner throughout the course of the Trial.  
 
Procedure:  
DDS signals and VFSS will be recorded simultaneously (for the same bolus) using barium contrast 
agent stimuli prepared in three consistencies: thin, mildly-thick and moderately-thick. Subjects will 
undergo VFSS with simultaneous DDS using up to 5 boluses of thin barium stimulus (“THIN-Ba”), and 
up to 4 boluses of barium thickened to mildly (“MILD-Ba”) thick and up to 4 boluses of moderately 
(“MODERATE-Ba”) thick barium consistencies using TUC (Resource Thicken Up Clear, Nestlé Health 
Science).  4, 3 and 3 boluses for THIN-Ba, MILD-Ba and MOD-Ba will be analyzed using the classifier 
algorithms for sensitivity/specificity results. According to the exploratory trial, VFSS data for safety or 
efficiency can be missing for up to 14% boluses due to quality of VFSS recording. To compensate for 
potential losses of boluses due to missing gold standard (VFSS) data, 5, 4 and 4 boluses will be 
collected for the three consistencies respectively .     
 
The DDS signals will be sent to a dedicated application software installed at the CRO, which interprets 
the acceleration data and displays the examination result. The VFSS recording will be sent to CRO 
and provided for blinded assessment by the independent central VFSS laboratory.  
 
Consent must be obtained within 2 weeks prior to the study procedure.  The study procedure of 
simultaneous VFSS and DDS measurement will be completed in one day and the subject will be 
followed within 2 business days after the study procedure to monitor for adverse events.  
 
 
TRIAL 
POPULATION 
The study has been planned to enroll and study approximately 900 (maximum enrollment 1300) 
patients at risk for oropharyngeal dysphagia of non-congenital, non-surgical, and non-oncologic origin 
that meet all the inclusion and exclusion criteria and are considered eligible to be entered into this 
clinical investigation.  

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INCLUSION 
CRITERIA 
• 
Adult subjects (over 18 years of age)  
• 
Hospitalized subjects or outpatients identified as at risk of oropharyngeal dysphagia (using 
local practice)  
• 
Patients belong to one of the following groups:  
o 
Stroke patients  
o 
Traumatic brain injury 
o 
PD (Parkinson Disease) stage III or higher by Hoehn and Yahr scale 
o 
MS (Multiple Sclerosis) above age 60  
o 
AD (Alzheimer Disease) or other Dementia  
o 
Other medically complex hospitalized subjects not covered by the exclusion criteria 
and identified as at risk of dysphagia  
• 
Subject is able to comply with VFSS protocol to diagnose dysphagia 
• 
Subject is able to give voluntary, written informed consent to participate in the clinical 
investigation and from whom consent has been obtained / or a consultee has consented on 
the subjects behalf in line with nationally agreed guidelines concerning adults unable to 
consent for themselves. 
 
EXCLUSION 
CRITERIA 
• 
Presence of nasogastric / nasojejunal feeding tube at the time of VFSS test  
• 
Currently has a tracheostomy, or has had a tracheostomy in the past year 
• 
Had posterior cervical spine surgery and/or carotid endarterectomy in the last 6 months 
• 
Had significant surgery to the mouth and/or neck, for example resection for oral or pharyngeal 
cancer, radical neck dissection, anterior cervical spine surgery, orofacial reconstruction, 
pharyngoplasty, or thyroidectomy. Routine tonsillectomy and/or adenoidectomy are not 
excluded 
• 
Experienced non-surgical trauma to the neck (e.g., knife wound) resulting in musculoskeletal 
or nerve injury in the neck. 
• 
Received radiation or chemotherapy to the oropharynx or neck for cancer. 
• 
Allergy to oral radiographic contrast media (specifically barium)  
• 
Distorted oropharyngeal anatomy (e.g. pharyngeal pouch) 
• 
Cognitive impairment that prevents them from being able to comply with study instructions 
and procedures  
• 
Known to be pregnant at the time of enrollment 
• 
Currently has significant facial hair at the location of sensor adherence and are 
unwilling/unable  to be shaved  
• 
Any patients the local investigator finds that participation would not be in patients’ best 
interest  
 
DEVICE 
Dysphagia Detection System (DDS)  
DEVICE 
DESCRIPTION 
The NHSc (Nestle Health Sciences) Dysphagia Detection System (DDS) is a portable, non-invasive 
device designed for use at the bedside. The investigational DDS has three basic components: a 
Sensor Unit (suspended on a necklace), a Sensor Fixation and a PC for collecting data. The Sensor 
Unit consists of a dual-axis accelerometer in a plastic housing that is attached to the front of a patient’s 
neck just below the thyroid cartilage by the single-use, disposable fixation unit (Sensor Fixation). The 
Sensor Unit is connected via a cable to an A/D converter which then connects via cable to the PC.  
The PC collects the examination data, which is then sent to dedicated application software (installed at 
the CRO), which interprets the acceleration data and displays the examination result.    
During an assessment, a patient takes a series of sips as directed by a clinician.  Each sip is 
processed and transferred to the application software on the PC. The data are stored and then sent to 
the CRO. These data are subsequently analyzed and the system outputs an assessment of swallowing 
safety and efficiency.  
STUDY DURATION 
This study is expected to require approximately 18 months to complete. 
TRIAL VISITS 
Consent must be obtained prior to the study procedure (up to 2 weeks prior).  The study procedure of 
simultaneous VFSS and DDS measurement will be completed in one day and the subject will be 
followed within 2 business days after the study procedure to monitor for adverse events. The sequence 
of Study Procedures is described in the Table 1. 
 

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STATISTICAL 
METHODS 
Success criteria and hypothesis testing  
The success criteria for the DDS device validation trial is that the sensitivity is greater than 80% with a 
specificity greater than 50%. Here the sensitivity and the specificity will be estimated using an 
independent validation dataset. Thus the following one-sided hypothesis testing will be carried out: 
 
𝐻𝐻0 :  𝐻𝐻0
𝑠𝑠𝑠𝑠 ∪  𝐻𝐻0
𝑠𝑠𝑠𝑠  vs.            
 
𝐻𝐻𝐴𝐴 :  𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 ∩  𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 
 
Where 
 𝐻𝐻0
𝑠𝑠𝑠𝑠 : Sensitivity ≤ 0.8;    𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 : Sensitivity > 0.8;  𝐻𝐻0
𝑠𝑠𝑠𝑠 : Specifictiy ≤ 0.50;   𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 : Sensitivity > 0.50 
 
 
The same hypothesis test as above will be applied to the secondary endpoints.  If the primary 
hypothesis meets statistical significance then hypothesis testing for secondary endpoints will be carried 
out in a hierarchical fashion to ensure that the type-I error is controlled at the 2.5% level (one-sided). 
  
Threshold optimization  
The validation trial will start with the frozen classifier based on a fixed threshold derived using the ROC 
curves obtained using the 10,000 test datasets following a random splitting (80:20) of the Phase-0 
data.  
 
At the first interim, sensitivity and specificity will be calculated based on the fixed threshold. If the Area 
under the ROC curve at the first interim is above 75% but the sensitivity and/or specificity are low then 
the threshold will be revised based on the first interim data. In this case, the validation will exclude the 
data used for the first interim, i.e. the validation trial will start with the first patient enrolled after the first 
interim analysis data cut-off date. In case the fixed threshold from the phase-0 data is not revised using 
the first interim data, the trial continues as planned.  
 
Power analysis using simulations (described in statistical plan) show the impact of prevalence on 
power. The targeted prevalence of swallow safety problems using THIN-Ba (primary endpoint) is 
between 0.3 and 0.4. Throughout the course of the trial prevalence of swallow safety and efficiency 
problems will be monitored closely by the Data Monitoring Committee (DMC) in a blinded fashion.   
 
The study population should be representative of the device intended use population (at risk 
of dysphagia).According to the published Literature, estimated prevalence of dysphagia in 
the target population varies from 20-50%. The necessity to carry out VFSS may result in 
sites selecting patients at higher risk than in the intended target population (such as those 
already assessed by SLPs). We therefore blindly monitor the prevalence and retrain sites as 
necessary in order to ensure that they recruit at-risk patients (not only those already 
assessed as dysphagic by SLPs). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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6 
TRIAL PLAN 
 Table 1: Sequence of Study Procedures 
 
 
 
 
Study Procedures 
Written informed consent 
Inclusion/exclusion criteria review 
Schedule VFSS with simultaneous DDS 
Prepare all swallowing substances and portion into cups: thin 
barium, and mildly and moderately -thick barium using a mixture 
of TUC and barium (can be done in advance as per study 
manual instructions)  
Swallow Exam of up to 5 sips of thin barium simultaneously 
recorded using both the VFSS and DDS 
Swallow Exam of up to 4 boluses of mildly-thick barium 
simultaneously recorded using both the VFSS and DDS  
Swallow Exam of up to 4 boluses of moderately-thick barium 
simultaneously recorded using both the VFSS and DDS  
Upload the subject’s study files (VFSS recording, DDS signal 
recording, acoustic soundtrack recording to a secure site for 
retrieval from the Sponsor or designee. 
AE assessment  within 2 business days following the study 
procedure 

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7 INTRODUCTION 
Oropharyngeal dysphagia is a symptom of a swallow dysfunction that provokes difficulty or inability 
to form or move the alimentary bolus safely from the mouth to the esophagus. It can include 
oropharyngeal aspiration (the entry of secretions, food, or drink from the oropharynx into the 
trachea or the lungs) and choking (the subsequent mechanical obstruction of pulmonary air flow)1.  
Oropharyngeal dysphagia is a prevalent condition in several at-risk populations. We focus on 
oropharyngeal dysphagia of non-congenital, non-surgical and non-oncological origin which is 
prevalent in post-stroke patients, patients with neurological or neurodegenerative diseases such as 
Parkinson disease (PD), multiple sclerosis (MS), critically ill patients in intensive care units (ICUs) 
and elderly patients especially  those with history of  community-acquired pneumonia.  
Oropharyngeal dysphagia is an important contributor to morbidity and mortality.  It leads to impaired 
quality of life and nutritional and respiratory complications associated with poorer prognosis.  Early 
identification of oropharyngeal dysphagia and aspiration risk is critical for management of 
dysphagia and its clinical consequences.  
A recent retrospective review of National Hospital Discharge Survey data demonstrated a 
significant association between dysphagia and both hospital length of stay and mortality in a 
heterogeneous hospital population. The same study estimated the national annual cost of 
dysphagia in hospitalized patients to be over $500 million.2 
 
The AHA Stroke and VA/DoD Stroke Rehabilitation Guidelines recommend assessment of 
swallowing before the patient begins eating, drinking, or receiving oral medications (AHA Class I; 
Level of Evidence B). Screening for dysphagia is also recommended by European Stroke 
Organization, NICE, and by German, Swiss and Austrian guidelines. The Joint Commission 
(JCAHO) 
guidelines 
state, 
“A 
screen 
for 
dysphagia 
should 
be 
performed 
on 
all 
ischemic/hemorrhagic stroke patients before [they are] given food, fluids, or medication by mouth.” 
Their rationale is that 27%-50% of stroke patients develop dysphagia, 43%-54% of stroke patients 
with dysphagia will experience aspiration, 37% of patients who develop aspiration will develop 
pneumonia, and if not part of a dysphagia diagnosis and treatment program, 3.8% of those will die. 
Other adverse effects that can be avoided include malnutrition and increased length of hospital stay.  
 
In a prospective 15-hospital study in North America, use of a formal dysphagia screening protocol, 
which incorporated an evidence-based screening tool, was associated with improved compliance 
with dysphagia screenings and a significantly reduced risk of pneumonia.3 
 
Although a wide variety of swallow screening and assessment tests are available for use, none 
have acceptable sensitivity and specificity to ensure accurate detection of dysphagia. 4 
 
Several reviews have shown a lack of consensus regarding the best screening instrument to use5,6,7. 
Most bedside swallowing examinations have been shown to lack sufficient sensitivity to be used for 
screening purposes, regardless of the patient populations examined. No bedside screening 
protocol has been shown to provide adequate predictive value for the presence of aspiration. 
Several  individual exam components have demonstrated reasonable sensitivity, but reproducibility 
and consistency of these protocols was not established6. Dysphagia screening validation studies 
reported in the literature have a number of serious limitations5. It is also important to note that 
between one-third and one-half of patients who aspirate following stroke are silent aspirators (i.e., 
penetration of food below the level of the true vocal cords, without cough or any outward sign of 
difficulty)4. 
 
In 2010, The Joint Commission withdrew the dysphagia screening performance standard for acute 
stroke because the National Quality Forum could not endorse it, stating that there are “no 

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standards for what constitutes a valid dysphagia screening tool, and no clinical trials have been 
completed that 
identify the optimal swallow screening”. Dysphagia screening was removed from the “Get with the 
Guidelines” stroke guidelines5. However, removal from the Joint Commission recommendations 
does not mean that screenings should not be performed, indeed the Joint Commission 
recommends further research to improve dysphagia screening methods. 
 
The Nestlé Health Science (NHSc) objective is to develop a new medical device - Dysphagia 
Detection System (DDS) - to provide clinicians with an objective and non-invasive method to detect 
impaired swallowing in patients at risk of oropharyngeal dysphagia of non-congenital and non-
surgical and non-oncological origin. A good screening test needs to have a high sensitivity and high 
negative predictive value (NPV)8. The operating characteristics of screening methods must be 
established against a clinical reference standard – validated, accurate and reliable dysphagia 
assessment methods. 
 
The DDS swallowing impairment detection algorithm has been developed in the exploratory (Phase 
0) clinical trial in 332 subjects and reached targeted performance characteristics. VFSS was used 
as clinical reference method. The DDS algorythms detect impaired swallowing safety and impaired 
swallowing efficiency at thin, mild and moderate stimuli (6 algorythms – for safety or efficiency for  
each of 3 consisetncies). Swallowing safety describes risk of penetration-aspiration which 
describes impaired airway protection. The impaired swallowing safety is defined as PAS ≥ 3. As 
determined by VFSS.  Swallowing efficiency described the ability to clear a bolus through the 
pharynx in 2 swallows or less without leaving residue in the throat. The impaired swallowing 
efficiency is defined as at least 50% residue as determined by VFSS.  
 
The purpose of this prospective clinical trial is to validate DDS against the clinical reference 
standard for detecting swallowing impairment (VFSS).  
 
 
8 
TRIAL OBJECTIVES AND ENDPOINTS 
8.1 Primary objective 
The primary objective is to validate the DDS against the VFSS for detecting swallow safety 
problems using thin stimulus (THIN-Ba). 
8.2 Primary endpoint 
The primary efficacy of the DDS will be measured as the sensitivity & specificity obtained from 
comparing the DDS predicted swallow safety outcome with the clinical reference standard VFSS 
swallow safety outcome (binary) for thin (THIN-Ba) boluses.  
 
Swallowing safety describes risk of penetration-aspiration which describes impaired airway 
protection. The impaired swallowing safety is defined as PAS ≥ 3 as determined by VFSS.  (The 
PAS - Pentration Aspiration Scale – is provided in the Appendix B) 
8.3 Secondary objective 
The secondary objective is to validate the DDS against the VFSS for detecting swallow efficiency  
problems using thin stimulus (THIN-Ba) and swallowing safety and efficiency using mild and 
moderately thick stimuli.  
Swallowing efficiency described the ability to clear a bolus through the pharynx in 2 swallows or 
less without leaving residue in the throat. The impaired swallowing efficiency is defined as at least 
50% residue as determined by VFSS. 
 

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8.4 Secondary endpoints  
At the final analysis, if the primary endpoint meets statistical significance then formal testing and 
analysis for the following secondary endpoints will be carried out in a hierarchical fashion in the 
specified order:  
1. 
The sensitivity & specificity for swallow safety using mild barium (MILD-Ba)  
2. 
The sensitivity & specificity for swallow safety using moderate barium (MOD-Ba) 
3. 
The sensitivity & specificity for swallow efficiency using THIN-Ba  
4. 
The sensitivity & specificity for swallow efficiency using MILD-Ba  
5. 
The sensitivity & specificity for swallow efficiency using MOD-Ba  
 
8.5 Exploratory endpoints 
The analysis on the following tertiary endpoints will be considered as exploratory: 
• 
Prevalence of boluses resulting in “grey” outcomes of the classifier for safety and efficiency of 
the swallows on thin (THIN-Ba) and thickened stimuli (MILD-Ba and MOD-Ba) 
• 
Prevalence of impaired swallowing safety and efficiency of the swallows of thin (THIN-Ba) and 
thickened stimuli (MILD-Ba and MOD-Ba) as determined by VFSS at bolus and participant 
levels. 
• 
Positive and Negative predictive value (PPV and NPV) of detecting swallow safety and 
efficiency problems using DDS and using THIN-Ba, MILD-Ba and MOD-Ba stimuli. 
• 
Prevalence of impaired swallowing safety and efficiency of the swallows of thin (THIN-Ba) and 
thickened stimuli as determined by VFSS at bolus and patient level by the following 
predetermined subgroups: stroke, other neurological diseases, other patients. 
• 
Timing and Outcome of the dysphagia screening as per usual care protocol of the study site 
• 
Timing and Outcome of the dysphagia Clinical Swallow Evaluation (CSE) by SLP (speech 
language pathologist) where applicable as per usual care protocol of the study site. 
• 
Impact of VFSS results on Nutritional Management (% patients with diet changes 
(advanced/more conservative)). 
• 
DDS accuracy in terms of AUC, sensitivity and specificity by sub-group (Stroke, Other 
Neurological Diseases and Others) for swallow safety and efficiency problems for all 
consistencies (THIN-Ba, MILD-Ba, MOD-Ba) 
8.6 Safety endpoints  
All adverse events (AEs) will be observed from the time the consent form is signed through the exit 
of the subject from the study. 
 
9 
TRIAL DESIGN 
An operationally seamless single-arm, prospective, multicenter, single-blinded for central outcomes 
assessors trial to test DDS in assessing swallowing safety and efficiency in patients at risk of 
oropharyngeal dysphagia.  
The study is designed as operationally seamless to facilitate the updating of the threshold on the 
ROC curve for swallowing safety for thin (THIN-Ba) boluses if required and to validate the DDS 
classifier with a fixed threshold using an independent validation set. 
 

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The trial will start with the frozen classifier based on a fixed threshold derived using ROC curve 
from the completed exploratory trial.  The clinical trial will initially start as a 3-look group sequential 
design (GSD).  At the first interim, sensitivity and specificity will be calculated based on the fixed 
threshold. If the Area under the ROC curve at the first interim is above 75% but the sensitivity 
and/or specificity are low then the threshold will be revised based on the first interim data. In this 
case, the validation will exclude the data used for the first interim, i.e. the validation trial will start 
with the first patient enrolled after the first interim analysis data cut-off date. In case the fixed 
threshold from the completed exploratory trial data is not revised using the first interim data, the trial 
continues as planned.  
 
If the classifier cannot analyze the signal (e.g. due to signal-to-noise level), it will result in a “grey” 
outcome of the classifier. The prevalence of “grey” outcomes among analyzed boluses for safety 
and efficiency classifier on thin (THIN-Ba) and thickened stimuli (MILD-Ba and MOD-Ba) at site 
level will be monitored centrally during the trial.   
 
Blinding  
VFSS analysis, considered in this study as the clinical reference method (gold standard), will be 
performed by an independent and central VFSS assessment laboratory which will be blinded to the 
DDS results.  The interim analyses will be carried out in an unblinded fashion by an independent 
statistical center (iSC) while the interim decisions will be made by an independent data monitoring 
committee (iDMC). The iDMC will also monitor the prevalence in a blinded manner throughout the 
course of the Trial.  
 
Procedure  
DDS signals and VFSS will be recorded simultaneously (for the same bolus) using barium contrast 
agent stimuli prepared in three consistencies: thin, mildly-thick and moderately-thick.  
Subjects will undergo VFSS with simultaneous DDS using up to 5 boluses of thin barium stimulus 
(“THIN-Ba”), and up to 4 boluses of barium thickened to mildly (“MILD-Ba”) thick and up to 4 
boluses of moderately (“MODERATE-Ba”) thick consistencies using TUC (Resource Thicken Up 
Clear, Nestlé Health Science).  
4, 3 and 3 boluses for THIN-Ba, MILD-Ba and MOD-Ba respectively  will be analyzed by 
algoriythms for sensitivity/specificity results. According to the exploratory trial, VFSS data for safety 
or efficiency can be missing for up to 14% boluses due to quality of VFSS recording. To 
compensate for potential losses of boluses due to missing gold standard (VFSS) data, 5, 4 and 4 
boluses will be collected for the three consistencies respectively.   
 
The DDS signals will be sent to dedicated application software installed at the CRO, which 
interprets the acceleration data and displays the examination result. The VFSS recording will be 
sent to CRO and provided for blinded assessment by the independent central VFSS laboratory.  
 
 
10 
TRIAL POPULATION 
The study has been planned to enroll and study approximately 900 patients at risk for 
oropharyngeal dysphagia of non-congenital, non-surgical, and non-oncologic origin that meet all the 
inclusion and exclusion criteria and are considered eligible to be entered into this clinical 
investigation (maximum enrollment 1300 with the possibility of early stopping for futility or success).  
 

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10.1 Subject inclusion criteria 
It is important to carefully consider whether a subject is suitable for enrollment into this clinical 
study. Fulfillment of the inclusion and exclusion criteria for each subject will be documented by a 
qualified member of the investigative staff before any study procedure is performed. 
• 
Adult subjects (over 18 years of age)  
• 
Hospitalized subjects or outpatients identified as at risk of oropharyngeal dysphagia (using 
local practice)  
• 
Patients belong to one of the following groups:  
o Stroke patients  
o Traumatic brain injury 
o PD (Parkinson Disease) stage III or higher by Hoehn and Yahr scale 
o MS (Multiple Sclerosis) above 60 y.o.  
o AD (Alzheimer Disease) or other Dementia  
o Other medically complex hospitalized subjects not covered by the exclusion criteria 
and identified as at risk of dysphagia  
• 
Subject is able to comply with VFSS protocol to diagnose dysphagia 
• 
Subject able to give voluntary, written informed consent to participate in the clinical 
investigation and from whom consent has been obtained / or a consultee has consented on 
the subjects behalf in line with nationally agreed guidelines concerning adults unable to 
consent for themselves. 
10.2 Subject exclusion criteria 
Any of the following criteria would render a subject ineligible for inclusion: 
• 
Presence of nasogastric / nasojejunal feeding tube at the time of VFSS test  
• 
Currently has a tracheostomy, or has had a tracheostomy in the past year. 
• 
Had posterior cervical spine surgery and/or carotid endarterectomy in the last 6 months. 
• 
Had significant surgery to the mouth and/or neck, for example resection for oral or 
pharyngeal cancer, radical neck dissection, anterior cervical spine surgery, orofacial 
reconstruction, 
pharyngoplasty, 
or 
thyroidectomy. 
Routine 
tonsillectomy 
and/or 
adenoidectomy are not excluded 
• 
Experienced non-surgical trauma to the neck (e.g., knife wound) resulting in 
musculoskeletal or nerve injury in the neck. 
• 
Received radiation or chemotherapy to the oropharynx or neck for cancer. 
• 
Allergy to radiographic contrast media (specifically barium)  
• 
Distorted oropharyngeal anatomy (e.g. pharyngeal pouch) 
• 
Cognitive impairment that prevents them from being able to comply with study instructions 
and procedures  
• 
Currently has significant facial hair at the location of sensor adherence and are 
unwilling/unable  to be shaved  
• 
Known to be pregnant at the time of enrollment. 
• 
Any patients the local investigator finds that participation would not be in patients’ best 
interest  
10.3 Subject discontinuation criteria 
  
A subject may be discontinued from the trial for the following reasons: 

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1. A subject can withdraw consent to participate the trial at any time without reprisal  
2. Investigator’s decision to discontinue subject’s participation to the trial if, to the opinion of 
the Investigator, continuation in the trial would be detrimental to the subject’s wellbeing. 
Should the Investigator’s decision be based on an AE or a SAE, this event must be reported 
in the appropriate manner 
3. Sponsor or Independent Ethics Committee (IEC)/Institutional Review Board (IRB) decides to 
terminate trial 
 
If the subject withdraws consent from the study, no further evaluations should be performed, and no 
additional data should be collected. The sponsor may retain and continue to use any data collected 
before such withdrawal of consent. 
10.4 Subject replacement 
Not applicable 
10.5 Sponsor Discontinuation Criteria 
Premature termination of this study may occur because of a regulatory authority decision, change 
in opinion of the IRB/IEC, study device safety problems, insufficient participant recruitment, when 
the safety of the participants is doubtful or at risk, respectively or at the discretion of Nestlé-
Investigator. In addition, Nestlé retains the right to discontinue development of the study device at 
any time. 
If a study is prematurely terminated or discontinued, Nestlé will promptly notify each study site 
investigator.  After notification, the investigator must contact all active participating subjects and the 
participating study team members/staff (if applicable) within two weeks. As directed by Nestlé, all 
study materials must be collected and all (e) CRFs completed to the greatest extent possible. 
 
11 
INVESTIGATIONAL DEVICE 
11.1 Investigational Device Description  
The NHSc Dysphagia Detection System (DDS) is a portable, non-invasive device designed for use 
at the bedside. The clinical trial will be performed with an investigational device architecture which 
is adapted to the constraints of the trial methodology (i.e. simultaneous measurement in VFSS 
suite).  
 
The investigational DDS has three basic components: a Sensor Unit (suspended on a necklace), a 
Sensor Fixation and a PC for collecting data. The Sensor Unit consists of a dual-axis accelerometer 
in a plastic housing that is attached to the front of a patient’s neck just below the thyroid cartilage by 
the single-use, disposable fixation unit (Sensor Fixation). The Sensor Unit is connected via a cable 
to an A/D converter which then connects via cable to the PC.  The PC collects the examination data, 
which is then sent to dedicated application software (installed at the CRO), which interprets the 
acceleration data and displays the examination result.    
 
During an assessment, a patient takes a series of sips as directed by a clinician.  Each sip is 
processed and transferred to the application software on the PC. The data are stored and then sent 
to the CRO. These data are subsequently analyzed and the system outputs an assessment of 
swallowing safety and efficiency.  
 

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11.2 Storage and Labeling  
Investigational device will be provided to the site(s) when all the mandatory trial documents have 
been made available. All components will be labeled as investigational. The investigational device 
components should be stored in secured location where only study personnel can access the 
device for use. 
 
11.3 Device Accountability   
The investigational device will be supplied to Investigator by and under the responsibility of the 
Sponsor. The Investigator at the trial site will inventory and acknowledge receipt of all shipments of 
investigational device. The Investigator will keep accurate records of the investigational device. 
These records will report any investigational device accidentally or deliberately destroyed. Device 
malfunctions or failures will be recordered. The investigational device will not be used outside of the 
study protocol.   
At trial closure, all used and unused study supplies and the investigational device will be counted 
and returned to the Sponsor, or destroyed with their written permission. Any discrepancies between 
the investigational device returned and the expected balance must be justified.  
 
12 
TRIAL ASSESSMENTS AND PROCEDURES 
12.1 Screening  
Subjects identified to have risk of dysphagia via the standard institutional screening / diagnostic 
methods will be assessed for study inclusion. Subjects appearing to meet all study inclusion and 
exclusion criteria will be approached to provide their consent to participate in the study within 2 
weeks of the study procedure.  
12.2  Informed Consent  
If a patient is deemed unable to provide informed consent, then consent must be obtained from a 
legally authorized representative, family member, or other locally recognized representative.  
Patients will be considered to be enrolled once their informed consent is signed.   
 
12.3 Baseline Assessment 
The subjects’ eligibility status will be documented on the Case Report Form (CRF). For women of 
childbearing potential a pregnancy test must be performed to confirm study eligibility. The date and 
result of the test will be recorded on the CRF. 
 
After obtaining confirmation of the subjects’ eligibility for study participation, the following data will 
be collected and recorded on the CRF: 
• 
Demographics  
• 
Relevant medical and surgical history 
• 
Primary admission diagnosis ( list of diagnosis of special interest: stroke, TBI, SCI (spinal 
cord injury), PD, MS, Dementia, Pneumonia, COPD)    
• 
Time from admission  to VFSS study procedure  
• 
Secondary diagnosis and dates of diagnosis (Y/N) :Stroke, PD, MS, Dementia, TBI, 
Pneumonia, COPD 
• 
Patients had invasive mechanically ventilated (Y/N, if yes duration of ventilaton)   
• 
Dysphagia screening by Nurses (date of latest screening  and results)  
• 
Dysphagia assessment by SLP (date of latest assessment and results)  

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• 
Recent Instrumental dysphagia diagnostics on file  (e.g. VFSS, FEES, other – date and 
results  
• 
Nutritional management   
• 
For stroke patients: NIH Stroke S (if available) 
• 
For parkinson patients: Funcitional Independence Measurement (if available) 
 
12.4 Preparation  
Prior to initiating any of the swallow exams the thin liquid barium, mildly-thick barium and  
moderately-thick barium swallowing substances will be prepared in accordance with the Validation 
Study Manual (provided to each site at the Site Initiation Visit).   The mixed consistencies can be 
stored unrefrigerated (room temperature) for up to 6 hours or If necessary, refrigerated  for up to 24 
hours and left at room temperature for approximately 20 minutes before administration to a study 
subject. (Re-refrigeration is not permitted). 
 
Approximately 5 oz of each of the substances will be poured into study supplied cups. The thin 
barium and mildly-thick barium will each be poured into cups, whereby the subject will take several 
sips of each of the substances from a cup. Moderately-thick barium  needs to be taken using a 
spoon.  
 
12.5 Swallow Exam  
At the time of the scheduled VFSS, the subjects will be brought to the VFSS suite and prepared for 
the study. 
DDS signals and VFSS will be recorded simultaneously (for the same bolus) using barium stimuli 
prepared in three consistencies: thin, mildly-thick and moderately-thick. The exams will be 
performed in the following order:  
1. Up to 5 boluses of thin barium simultaneously recorded by DDS and VFSS 
2. Up to 4 boluses of mildly-thick barium recorded by DDS and VFSS 
3. Up to 4 boluses of moderately-thick barium recorded by DDS and VFSS 
The thin barium, and mildly-thick barium tests will be administered using a cup. The moderately-
thick barium tests will be administered with a spoon.  
The full swallow should be recorded in a lateral view using continuous/25 or 30 frames per second 
screening.   
Subject should be positioned correctly throughout the swallow exam i.e. seat upright with a neutral 
head position.   
There should be no use of swallowing strategies throughout the study procedure e.g. head turns or 
chin tucks. 
 
Detailed instructions on how to perform the DDS procedure are included in the Study Manual.  
 
Only study personnel delegated and trained to properly apply the accelerometry sensor and 
operate the computer that will collect all channels of data (accelerometry, videofluoroscopy, audio 
soundtrack) will conduct the exams for this study.  An audio soundtack will be only used when 
necessary to identify the swallow on VFSS.   
 

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12.6 VFSS Stopping Rules  
• 
If the PAS is equal to or greater than 6 on 3 consecutive bolus trials of the same 
consistency, that consistency should be stopped and the investigator (or trained and 
authorized designee) can decide if it is safe to move to the next consistency or if the study 
needs to be stopped.  
 
o 
Penetration Aspiration Score Definitions: 
 
6: Material enters the airway, passes below the vocal folds, 
  and is ejected into the larynx or out of the airway. 
 
7: Material enters the airway, passes below the vocal folds & is not ejected from the 
trachea despite effort  
 
8: Material enters the airway, passes below the vocal folds & no effort is made to eject  
 
• 
A ‘Stop’ may be applied at any time if the Investigator (or trained and authorized designee) 
feels it is unsafe for the patient to continue.  
 
• 
If VFSS time exceeds 3 minutes the procedure must be stopped. 
 
 
If the VFS procedure is stopped due to any of these Stopping Rules, the 1 day follow-up visit must 
still be completed. 
 
12.7 Post-Exam  
After completion of all study-related testing, the site will stop the recording on the study computer 
and follow specified procedures for saving and uploading all study files to a secure transmission to 
the CRO as per the Study Manual. 
Subsequently, the site will follow their institution’s standard of care for further assessing swallowing 
impairment in subjects with suspected dysphagia. 
  
Follow-up with the study subject will be performed within 2 business days following completion of all 
the exams to collect data on AEs. If the subject is still hospitalized at this time, this data will be 
collected via an in-person interview. If the subject has been discharged at the time of follow-up, this 
data will be collected via a telephone interview. 
 
12.8 Premature trial termination  
Should it prove necessary to discontinue the trial prior to completion, the Sponsor will notify the 
Investigators and the appropriate entities including the IRB/IEC. All relevant trial documentation will 
be returned to the Sponsor.  The investigational device will be sent back. 
12.9 Trial completion  
After trial completion or termination the Investigator will inform the IEC/IRB of the end of the trial.  

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13 
DATA MANAGEMENT 
13.1 Data capture 
Data collected by the sites will be entered from the source document into an electronic Case Report 
Forms (eCRF) within a Title 21 CFR Part-11 compliant Electronic Data Capture system (EDC). 
Data should be entered in eCRFs within 7 days after the subject’s visit. 
eCRFs must be signed electronically by the Investigator. 
13.2 Access rights 
Designated site personnel will create a unique username and password and will be required to 
request access to the database.  Once the site personnel are trained access will be approved and 
the site personnel will have access the eCRF database. This username/password pair may be used 
by a single individual only; passwords must not be shared with any other person.  
13.3 Coding 
The following types of data will be coded using standard dictionaries detailed below.  
Type of data 
Dataset 
Dictionary 
Adverse Events 
AE 
MedDRA  
Serious Adverse Events 
AE 
MedDRA  
13.4 Database Lock 
Clinical database will be locked after review, query resolution, signatures of the eCRF and 
determination that clinical database is ready for analysis. 
Once the Trial is finished and database is locked, the Clinical Data Manager should follow the 
database unlock/relock process to document any further change. 
14 
STATISTICS 
14.1 Background 
The DDS classifier was built using data from around 300 subjects in a proof-of-concept trial 
using different bolus consistencies: thin barium (THIN-Ba), mildly thick barium (MILDBa) and  
moderately thick barium (MOD-Ba).  
 
This pivotal trial aims at validating the Dysphagia Detector System (DDS) with respect to the Video-
fluoroscopy test (gold-standard) in detecting swallow safety and efficiency impairments. The core 
component of the DDS is a statistical classifier algorithm that is able to predict the probability that a 
swallow was normal or with impaired safety and/or impaired efficiency based on the swallow 
signals captured using a dual-axis accelerometer sensor. 
 
14.2 Success criteria and hypothesis testing  
The success criteria for the DDS device validation trial is that the sensitivity is greater than 80% 
with a specificity greater than 50%. Here the sensitivity and the specificity will be estimated using 
an independent validation dataset. Thus the following one-sided hypothesis testing will be carried 
out: 

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𝐻𝐻0 :  𝐻𝐻0
𝑠𝑠𝑠𝑠 ∪  𝐻𝐻0
𝑠𝑠𝑠𝑠  vs.            
 
𝐻𝐻𝐴𝐴 :  𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 ∩  𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 
 
Where 
 
 𝐻𝐻0
𝑠𝑠𝑠𝑠 : Sensitivity ≤ 0.8;    𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 : Sensitivity > 0.8;  𝐻𝐻0
𝑠𝑠𝑠𝑠 : Specifictiy ≤ 0.50;   𝐻𝐻𝐴𝐴
𝑠𝑠𝑠𝑠 : Sensitivity > 0.50 
 
The same hypothesis test as above will be applied to the secondary endpoints. Hypothesis will be 
carried out in a hierarchical fashion to ensure that the type-I error is controlled at the 2.5% level 
(one-sided). 
 
14.3 Threshold Optimization  
The validation trial will start with the frozen classifier based on a fixed threshold derived from the  
Phase-0 (exploratory) trial data.  
 
At the first interim analysis, sensitivity and specificity will be calculated based on the fixed 
threshold. 
If the Area under the ROC curve at the first interim is above 75% but the sensitivity and/or 
specificity are low then the threshold will be revised based on the first interim data. In this case, the 
validation will exclude the data used for the first interim, i.e. the validation trial will start with the first 
patient enrolled after the first interim analysis data cut-off date. In case the fixed threshold from the 
phase-0 data is not revised using the first interim data, the trial continues as planned.  
 
Power analysis using simulations (described in statistical plan) show the impact of prevalence on 
power. The targeted prevalence of swallow safety problems using THIN-Ba (primary endpoint) is 
between 0.3 and 0.4. Throughout the course of the trial prevalence of swallow safety and efficiency 
problems will be monitored closely by the Data Monitoring Committee (DMC) in a blinded fashion.   
The study population should be representative of the device intended use population (at risk of 
dysphagia).According to the published Literature, estimated prevalence of dysphagia in the target 
population varies from 20-50%. The necessity to carry out VFSS may result in sites selecting 
patients at higher risk than in the intended target population (such as those already assessed by 
SLPs). We therefore blindly monitor the prevalence and retrain sites as necessary in order to 
ensure that they recruit at-risk patients (not only those already assessed as dysphagic by SLPs) 
 
14.4 Sample size calculations 
The power and the sample size to test the hypothesis depends on several unknown parameters: 
1. Subject level prevalence; 
2. The prevalence of impaired swallows conditional on subject having Dysphagia; 
3. The true sensitivity and specificity of the DDS device in detecting swallow impairment; and 
4. The optimum threshold on the ROC curve. 
 
Based on estimates from the exploratory study data, if the DDS is assumed to have  a sensitivity 
and specificity of at least 86% and 60% respectively and approximately 35% patients show 
impaired safety, then a power of 90% can be achieved with 700 to 800 subjects under a fixed 
design. Considering that data from additional 100 to 200 subjects may be used for threshold 
calibration, the starting  sample size is 900 subjects.  A sample size re-estimation will be carried out 
at the last interim analysis.  

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14.5 Group Sequential Design  
The clinical trial will initially start as a 3-look group sequential design (GSD).  The clinical trial will 
initially start as a 3-look GSD. Alpha-spending will be calculated using Lan-DeMets spending 
function (with O’Brien-Fleming parameter). At the first interim analysis (IA-1) the threshold on the 
ROC curve may be re-computed using the ROC curve generated using the IA-1 data, in which 
case, the validation trial would start afresh following IA-1 using a 2-look GSD. Data included in the 
IA-1 would no longer be used for the validation phase.  
14.6 Interim analysis and Sample Size Reestimation 
The overall subject-level prevalence of impaired safety and efficiency as determined by the central 
lab VFSS reading will be continuously monitored in a blinded fashion. The first interim analysis will 
be performed when the prevalence can be estimated using a 95% confidence interval of width no 
more than 15%. If the monitoring is carried out after every 50 subjects have completed the study, 
the first interim will be carried out around 200 subjects as reflected by the simulation.  
 
Due to uncertainties about the population parameters and their influence on the power, an adaptive 
sample size re-estimation (SSR) is proposed. Thus if after the first interim the trial continues as a 3-
look GSD without changing the threshold,  then a SSR would be done at the second interim 
analysis. If the threshold is changed at the first interim then the SSR will be carried out at the only 
interim analysis time for the freshly started validation trial post threshold re-calibration. SSR will be 
carried out using the promising zone approach16.  Details can be found in the statistical plan. 
 
The interim analyses will be carried out in an unblinded fashion by an independent statistical center 
(iSC) while the interim decisions will be made by an independent data monitoring committee 
(iDMC). The iDMC will also monitor the prevalence in a blinded manner throughout the course of 
the Trial. 
14.7 Central Blinded VFSS Assessors  
The Swallowing Rehabilitation Research Laboratory at the Toronto Rehabilitation Institute will be 
performing blinded VFSS assessment. CRO will organize transfer of blinded VFSS records analysis 
for the Assessors. The VFSS  records will be reviewed and analyzed by two trained raters 
independently of each other to identify penetration-aspiration score (PAS) and residue.  If there is 
disagreement between the two raters regarding penetration-aspiration status, a third trained rater 
will assess the VFSS(s) in question, and, if necessary, a meeting will be convened to obtain a 
consensus on any rating disagreements. If the concensus can not be reached due to a noisy VFSS 
signal, the bolus will be rated as missing VFSS. The Assessors will use a standardized protocol to 
ensure objectivity and consistency in the assessment of the VFSSs. Following analysis, they  will 
send the subjects’ VFSS results to the CRO.  
14.8 Datasets to be analyzed 
14.8.1 
Full analysis dataset 
For this trial, ITT population is defined as the population able to complete at least 1 THIN-Ba bolus.  
Missing data will be reported and sensitivity analysis carried out.  The analysis of primary and 
secondary endpoints will be performed to evaluate DDS performance and will be carried out using 
data from this population. The THIN-Ba consistency boluses (up to 4) with available simultaneous 
VFSS and DDS data per patient will be included into the analysis.  As will the  MILD-Ba and MOD-
Ba consistency boluses (up to 3 each) with simulultaneous VFSS and DDS  data per patient. 
 
14.8.2 
Safety analysis set 
Safety population includes all subjects with documented VFSS exam.  
 

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15 
HANDLING OF ADVERSE EVENTS 
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an adverse event (AE) or serious adverse event (SAE) as provided in this protocol. 
Adverse event information will be assessed from the time the subject signs the Informed 
Consent/HIPAA Form through the exit of the subject from the study. AEs will be recorded on the 
AE page of the (e)CRF.  
15.1 Definitions and assessment criteria  
15.1.1 
Adverse event 
An AE is any untoward medical occurrence experienced by a subject during this trial regardless of 
its relationship to the device. 
All AEs (regardless of suspected causality) will be assessed from the time the Informed Consent 
Form is signed through the exit of the subject from the study.  
All AEs will be assessed by the Investigator according to:  
• Whether the event is an unanticipated adverse device effect (UADE); 
• Whether the event is serious (SAE);  
• The severity of the event (mild, moderate, severe); and  
• The relationship of the event to the device and/or procedure (not related, possibly related, 
probably related, or definitely related).  
Information will also be collected on any treatment of the event and outcome/resolution status of 
the event. All data concerning AEs will be recorded on the AE CRF.  
All SAEs and UADEs will be reviewed by a Nestlé Health Science Medical Safety Officer (MSO). 
The MSO’s decisions regarding SAE status and device- or procedure-relatedness will be 
considered final for the purposes of data analysis, regulatory reporting, and publications. 
15.1.2 
Serious adverse event 
An AE is considered serious if it meets at least one of the following criteria:  
• led to death, or  
• led to serious deterioration in the health of the subject, that either resulted in:  
• 
a life-threatening illness or injury, or  
• 
a permanent impairment of a body structure or a body function, or  
• 
inpatient or prolonged hospitalization ≥ 24 hours, or transfer to the higher intensity of care 
unit/hospital  
• 
medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function, or 
• led to fetal distress, fetal death or a congenital abnormality or birth defect.  
 
15.1.3 
Unanticipated Adverse Device Effect (UADE) 
A UADE is any adverse device effect on health or safety or any life-threatening problem or death 
caused by, or associated with, a device, if that effect, problem, or death that is not previously 
identified in nature, severity, or degree of incidence in this Investigational Plan or informed consent, 

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or any other unanticipated serious problem associated with a device that relates to the rights, safety, 
or welfare of subjects (21 CFR 812.3(s)). The Sponsor or designee, in conjunction with the Medical 
Monitor, will assess all SAEs considered to be device-related to determine if they are reportable to 
the US Food and Drug Administration (FDA) as a UADE.  
The evaluation of “unanticipated” is based on current knowledge and applicable product information 
and will be assessed by the MSO of the Sponsor. 
 
15.1.4 
Anticipated Adverse Events  
AEs that are anticipated to occur during this clinical trial are believed to be consistent with those 
associated with underlying disease and/or dysphagia screening tests and VFSS or have been 
identified by the Sponsor as part of their risk assessment. Anticipated AEs include and are not 
limited to, the following:  
 
• Choking episode or airway obstruction event requiring emergency response  
• Fever  
• Congestion and/or shortness of breath  
• Chest pain  
• Anaphylactic reaction (allergy to the test stimuli)  
• New diagnosis of respiratory infection  
• Nausea and/or Constipation  
  
Potential AEs that may be specifically related to the investigational device (accelerometry 
device) include, but are not limited to, the following:  
• 
Allergy, skin reaction, or irritation to the adhesive used for the sensor fixation 
• 
Infection 
• 
Discomfort  
• 
Electrical shock 
• 
Electromagnetic (EM) emission interference with other devices leads to failure of life 
supporting device* 
*see Section 16.3 Mitigation of Risk 
15.1.5 
Severity of adverse events 
Severity of AEs will be graded according to the following criteria: 
Mild: 
Symptoms hardly perceived, only slight impairment of general well-being. 
Resolves without treatment and with no sequelae. 
Moderate: 
Clearly noticeable symptom, but tolerable without immediate relief. 
Severe: 
Overwhelming discomfort and has significant impact on the Subject’s usual 
activities and/or requires treatment. 
15.1.6 
Event Relatedness  
AEs will be judged by the Investigator as to their relatedness to the device and/or procedure using 
the following classifications: 
 
• 
Not related: An AE for which sufficient information exists to indicate that there is no causal 
connection between the event and the device or procedure. The AE is due to and readily 
explained by the subject’s underlying disease state or is due to concomitant medication or 
therapy not related to the use of the device or procedure. In addition the AE may not follow 
a reasonable temporal sequence following the procedure. 
 
• 
Possibly related: There is a reasonable possibility that the AE may have been primarily 
caused by the device or procedure. The AE has a reasonable temporal relationship to the 

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use of the device or procedure and follows a known or expected response pattern to device 
or procedure, but alternative etiology is equally or more likely compared to the potential 
relationship to the use of the device or procedure.  
 
• 
Probably related: There is a reasonable probability that the AE may have been primarily 
caused by the device or procedure. The AE has a reasonable temporal relationship to the 
use of the device or procedure and follows a known or expected response pattern to the 
device or procedure. Note: This definition assumes no alternative etiology is equally or more 
likely compared to the potential relationship to the use of the device or procedure. 
 
• 
Definitely related: The AE has a strong causal relationship to the device or procedure. The 
AE follows a strong temporal relationship to the use of the device or procedure, follows a 
known response pattern to the device or procedure, and cannot be reasonably explained by 
known characteristics of the subject’s clinical state or other therapies.  
 
Device-related Adverse Event: an AE is considered to be device-related when, in the judgment of 
the Investigator or the MSO, the clinical event has a reasonable time sequence associated with use 
of the device and is unlikely to be attributed to concurrent disease or other procedures or 
medications, or it is reasonable to believe that the device directly caused or contributed to the AE.  
 
Procedure-related Adverse Event: an AE is considered to be procedure-related when, in the 
judgment of the Investigator or the MSO, it is reasonable to believe that the event is associated with 
the procedure and is not specific to the device. Other products, surgical techniques, or medications 
required specifically for the procedure are likely to have contributed to the occurrence of the event. 
 
15.2 Reporting of serious adverse events and unanticipated adverse device effects 
15.2.1 
Reporting of serious adverse events and UADEs to Sponsor 
Upon awareness of an SAE or UADE, the investigator has to enter the data in the e-CRF within 24 
hours. Notification does not depend on whether there is a causal relationship with the study product 
or not, all SAEs have to be entered within 24 hours after awareness. All SAEs or UADEs occurring 
until the last trial visit will be similarly reported. 
Upon data entry, a first email will be automatically sent to the Clinical Safety Manager. Following 
emails will be automatically sent when changes or additional information are entered in the e-CRF.  
The investigator must electronically sign each SAE and UADE. 
In case the e-CRF is not functional, the Clinical Safety Manager must be notified of any SAE or 
UADE within 24 hours after awareness by the investigator per the fax and/or email address 
supplied in the source data worksheets. 
15.2.2 
Follow up of serious adverse events 
All SAEs and UADEs must be followed up until the outcome is resolved or stable. 
In case of SAE(s) persisting beyond trial termination, a follow up visit may be required. If further 
analyses are required for the evaluation of a potential cause-effect relationship between the device 
and the AE, all examinations and laboratory analyses will be documented in the (e)CRF or in an 
attached file.  
15.2.3 
Notification 
The Sponsor is responsible for the ongoing safety evaluation of the device. 
The Sponsor should promptly notify all concerned Investigator(s)/institution(s) and the Regulatory 
Authority(ies) of findings that could adversely affect the safety of subjects, impact the conduct of the 
trial, or alter IEC/IRB approval/favorable opinion to continue the trial. 

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15.3 Reporting 
Nestle Health Science must immediately conduct an evaluation of a UADE and must report the 
results of the evaluation to FDA, all reviewing IRBs, and participating investigators within 10 
working days after receiving notice of the effect. 
 
16 
RISK ANALYSIS  
16.1 Potential Risks  
There are potential risks associated with both VFSS and the study device.  
16.1.1 
VFSS Risks  
VFSS involves low levels of radiation exposure.  Researchers have quantified the median levels of 
radiation exposure associated with a VFSS in patient populations. Zammit-Maempel and 
colleagues9  reported a median exposure time of 171 seconds and an associated dose of 0.20 
millisieverts or mSv, while Moro and Cazzani10 reported a median exposure time of 149 seconds 
and an associated dose of 0.35 mSv.  
 
Based on the analysis of 3273 boluses of thin, mild and moderate stimuli from exploratory (Phase 0) 
trial, the mean VFSS duration per bolus was 3.1, 3.4 and 3.1 sec for healthy and 5.4, 6.3 and 4.9 
sec for impaired boluses for thin, mild and moderate stimuli respectively. Taking conservatively 
highest means of 3.4 sec and 6.3 sec as the reference for healthy and impaired boluses for all 
consistencies and assuming a high expected prevalence of impaired boluses of 40%, the mean 
radiation exposure time in the study is estimated to be 1.2 min per subject. Even more conservative 
calculation based onVFSS duration of mean plus two standard deviations per bolus as described 
above results in estimated VFSS duration of 2.7 min.  
 
In addition, the VFSS stopping rules in this study requires VFSS to be stopped after approximately  
total of 3 min of radiation exposure.  
 
Based on the above, the standardized VFSS protocol used in this study specified that all 
videofluoroscopic data must be collected with not more than 3 minutes of screening time. 
Interpolating from the relationship Moro published, VFSS time of 2.9 min (174 sec), relates to an 
effective dose of ~0.44 mSv11.  
 
On average, a U.S. resident receives an annual radiation exposure from natural sources of about  
3.1 mSv. In addition, man-made sources of radiation from medical, commercial and industrial 
activities contribute roughly 3.1 mSv more to our annual exposure.  Computed tomography (CT) 
scans, which account for about 1.5 mSv, are among the largest of these sources12.  
 
Radiation exposure during VFSS is approximately 30% of the CT radiation exposure and about 0.9% 
of the annual maximum permitted by the FDA radiation dose for radioactive drug research13. 
Comparing to background radiation, VFSS radiation exposure is equivalent to 1.7 months of natural 
exposure.  
 
  
Radiation Exposure 
(mSv) 
VFSS (3) 
0.44 
CT (Computer Tomography) (5) 
1.5 
Natural "background" radiation (5) 
3.1 

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FDA Regulations on Radioactive drugs research (6) 
  
Max radiation dose to whole body, active blood-forming 
organs, lens of the eye, and gonads 
  
Single dose  
35 
Annual and total dose commitment 
50 
Other organs  
  
Single dose  
50 
Annual and total dose commitment 
150 
 
One such strategy that is popularly used to decrease radiation exposure is reducing the pulse rate 
of the radiation beam emitted during VFSS. The emitted radiation beam can be either continuous or 
pulsed. When pulsed, the pulse rate is defined as the number of pulses per  second (pps) of the x-
ray beam. Pulse rates for fluoroscopy commonly include 30, 15, 7.5, and 4pps. Radiation exposure 
is reduced as pulse rate is reduced. Specifically, Aufrichtig et al showed average dose reductions of 
22% at 15pps and 49% at 7.5pps when compared to doses at 30pps. Decreasing pulse rate also 
has a direct and proportional effect on the number of unique images in which a swallow is captured. 
Since the oropharyngeal swallow only lasts approximately 1 second, when pulse rate is decreased 
from 30 to 15, the number of unique images available to judge swallowing impairment also 
decreases from 30 to 15. Bonilha and colleagues14 (2013) reported differences in both judgment of 
swallowing impairment and treatment recommendations when pulse rates are reduced from 30pps 
to 15pps to minimize radiation exposure.  Differences between PAS scores for the four pulse rates 
tested (e.g. 24% of disagreements between 30 vs 15 rates) indicate that pulse rate may have a 
high impact on attributes of the MBSS examination that are used to determine PO status14.   
 
The standardized VFSS protocol used in this study specified 30 pulse rates and 30 frames per 
second for all videofluoroscopic data must be collected.  
 
16.1.2 
 Investigational Device Risks  
Potential risks related to the investigational device (accelerometry device) include, but are not 
limited to, the following:  
• 
Allergy, skin reaction, or irritation to the adhesive used for the sensor fixation 
• 
Infection 
• 
Discomfort  
• 
Electrical shock 
• 
EM emission interference with other devices leads to failure of life supporting device* 
*see Section 16.3 Mitigation of Risk 
 
16.2 Potential Benefit  
There are no guaranteed benefits to participation in this study. The information gained from 
participation in this study will be used to validate a new non-invasive portable device to be used at 
the bed-side to detect impaired swallowing thereby it may benefit other patients with the same 
medical condition in future.  
 
16.3 Mitigation of Risk 
Adequate measures including eligibility criteria limitations and extensive bench testing, including 
electrical safety and EMC testing, biocompatibility assessment, functional testing, and software 
validation (e.g. EM emission interference with other devices), have been taken to minimize the 
above mentioned risks.  Investigational accelerometry device and VFSS have been used in the 

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exploratory study (Phase 0) with more than 300 subjects with no serious adverse events related to 
the device or the swallowing protocol observed. The minor design improvement in the new 
investigational device has no impact on device safety and performance.  
 
Site and Investigator selection criteria shall include the following:  
• 
Sites that have standardized procedures for, and are accustomed to, caring for patients with 
dysphagia  
• 
Sites that have SLP on staff, on-site or affiliated VFSS facilities and personnel  
The provision for each Investigator to have appropriate training on the investigational device 
constitutes additional efforts to minimize risk. Furthermore, any risks associated with participation in 
this clinical study will be minimized and managed in accordance with and full compliance to 
recognized Good Clinical Practices (GCP), 21 CFR Parts 11, 50, 54, 56, and 812; HIPAA; 
International Conference on Harmonization (ICH) E6 Good Clinical Practices, and International 
Organization for Standardization (ISO) 14155.  
 
16.4 Risk Analysis Conclusion  
The Sponsor believes that any additional risks beyond other screening tests for oropharyngeal 
dysphagia presented by this study are very low and that adequate testing, safeguards, and risk 
monitoring have been incorporated into the study to further minimize and mitigate the risks relative 
to the potential benefits that may be realized by participation in this study. Thus, the balance of 
potential risks and benefits associated with the accelerometry device supports further clinical 
research. 
 
 
17 
SPONSOR AND INVESTIGATOR OBLIGATIONS 
17.1 Good Clinical Practice and Declaration of Helsinki  
This trial will be conducted in compliance with the International Conference on Harmonization (ICH)  
guidelines and the ethical principles that have their origin in the Declaration of Helsinki (Appendix A) 
and its subsequent amendments.  
17.2 Independent Ethics Committee/Institutional Review Board Approval 
An appropriate IEC/IRB which conforms with the Declaration of Helsinki*and local laws must review 
and approve the protocol, informed consent, and any other relevant trial documentation prior to 
enrolment of subjects into the trial. Prior to trial initiation, the Sponsor must have received a letter 
documenting IEC/IRB approval that specifically identifies the protocol (title and protocol number). A 
list of IEC/IRB members and affiliations must also be provided to the Sponsor. During the course of 
the trial, the IEC/IRB must be notified of all subsequent additions to or changes in the trial protocol 
and the informed consent.  
Within 90 days of trial completion (last patient, last visit) or 15 days of early trial discontinuation, the 
Investigator, Sponsor or designee will inform the IEC/IRB of the end of the trial. 
Every SAE or unexpected AE that might affect subject safety must be brought to the attention of the 
IEC/IRB by the Sponsor/Investigator if required by the relevant IEC/IRB regulations. 
17.3 Informed Consent 
The Investigator or designee will ensure that each study subject, or his/her legally representative, is 
fully informed about the nature and objectives of the study and possible risks associated with 
participation and that signed informed consent is obtained from each potential subject prior to any 
trial related procedure in accordance with all applicable regulatory requirements. The informed 
consent process will be documented.  The informed consent document used in this study, and any 

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changes made during the course of the study, must be prospectively approved by the IRB/IEC and 
Nestlé before use. 
Each subject will be given oral and written information in an easily understandable language 
describing the nature and duration of the trial. This must take place under conditions where the 
subject has adequate time to consider the risks associated with trial participation.  
The informed consent will be signed by the subject (and/or legal authorized representative 
[guardian, next of kin, or other authorized individual] if applicable) and the Investigator or his/her 
designee. One signed copy  will be given to the subject and the original  will be kept in the 
Investigator's file at the trial site.  
17.4 Subject Confidentiality 
The Investigator will ensure protection of subject’s personal data and that all reports, publications, 
subject samples and any other disclosures, except where required by law are identified only by a 
subject identification number and site identification number to maintain subject confidentiality. All 
subject trial records will be kept safely in an access controlled area. Identification code lists linking 
subject names to subject identification numbers should preferably be stored separate from subject 
records. In case of data transfer Nestlé will maintain high standards of confidentiality and protection 
of subject personal data.  Clinical information will not be released without the written permission of 
the subject, except for monitoring by Regulatory Authorities or the trial Sponsor and their designees. 
17.5 Data Reporting and Case Report Forms 
The Investigator and/or designee will accurately, completely, and in a timely manner record data 
resulting from the execution of the protocol on paper or via electronic case report forms 
(CRFs/eCRFs, respectively) provided by the Sponsor. CRFs will be completed for each subject, all 
of which must be submitted/provided to the Sponsor at agreed upon intervals. 
Case report forms will be supplied in paper or in electronic (eCRF) format via a web-based 
application, and must be signed and dated by the Principal Investigator by handwritten or electronic 
signature as appropriate.  
17.6 Retention of Data 
The Investigator will maintain adequate trial records including eCRFs, medical records, laboratory 
reports, original signed informed consent forms, investigational product disposition records, safety 
reports, information regarding participants who discontinued and other pertinent data, such as 
letters and administrative documents exchanged between the Sponsor and the site.  The electronic 
Trial Master File (eTMF) is the official regulatory file for the study and will be used for monitoring 
the study and by FDA for any inspections (audits) under the Bioresearch Monitoring (BIMO) 
program.  The only paper files included in the official regulatory file will be all original signed 
informed consent forms. 
 
All trial records must be retained by the Investigator for the maximum period of time authorized by 
the hospital, institution or surgery. According to ICH GCP guidelines, essential documents should 
be retained until at least 2 years after the last approval of a marketing application in the EU and 
until there are no pending or contemplated marketing applications in the EU or at least 2 years 
have elapsed since the formal discontinuation of clinical development of the investigational product. 
These documents should be retained for a longer period however if required by the applicable local 
regulatory requirement(s) or according to the Clinical Trial Agreement with the Sponsor. It is the 
responsibility of the Sponsor to inform the Investigator/institution as to when these documents no 
longer need to be retained. 
 

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To avoid any possible errors, the Investigator must contact the Sponsor prior to destruction of any 
trial records or if leaving the institution where the trial was conducted. The Investigator will notify the 
Sponsor in the event of accidental loss or destruction of any trial records. 
17.7 Deviations from the Protocol/Protocol amendments 
The Investigator will not deviate from the protocol without prior written approval from the Sponsor. 
In case of medical emergencies, the Investigator will use medical judgment and will remove the 
participant from immediate hazard. The Sponsor and the IEC/IRB will be informed of type of 
emergency and course of action taken, according to local reporting requirements. 
Any permanent changes to the protocol will be formalized in an amended protocol which must be 
approved by the Sponsor and, if substantial as defined in directive 2001/20/EC, submitted for 
approval to the IEC/IRB and Health Authorities (the latter if applicable), prior to implementation. If 
the amendment results in a modification of trial treatment or subject assessments, a new version of 
the informed consent must be prepared and submitted for approval to the IEC/IRB and Health 
Authorities (the latter if applicable).  
17.8 Trial Monitoring 
At agreed upon times during the trial and after the trial has been completed, the Investigator will 
allow Sponsor representatives to periodically review the eCRF and corresponding office, hospital, 
and laboratory records (source documents) of each trial subject. Case report forms must be 
completed by the Investigator on a regular basis and prior to each monitoring visit. 
Monitoring visits allow the Sponsor or a mandated CRO to evaluate trial progress, verify accuracy 
and completeness of eCRFs, resolve any inconsistencies in the trial records, and ensure that all 
protocol requirements, applicable local laws, ICH guidelines, and Investigator obligations are 
fulfilled. 
17.9 Sponsor Audits 
During the trial or after the trial has been completed, the Investigator will allow Sponsor 
representatives or external auditors to conduct an audit of the trial. The purpose of the audit is to 
evaluate compliance with Good Clinical Practice (GCP) guidelines, applicable regulations, the trial 
protocol and the Sponsor's procedures, and to assess accuracy of the trial data.  
17.10 Regulatory Agency Inspections 
The Investigator may undergo a Regulatory Agency/IEC/IRB inspection during the trial or after the 
trial has been completed. The purpose of the inspection is to conduct an official review of 
documents, facilities, records, and any other resources that are deemed by the authority(ies) to be 
related to the clinical trial.  
Investigator and staff are expected to be available for the inspection and allow access to subject 
records supporting (e)CRFs and other trial-related documents. If given advance notice of this 
inspection, the Investigator must contact the Sponsor and CRO immediately.  IRB/IEC notification 
to be completed per local requirements. 
17.11 Publications 
All topics related to publication are developed in the Clinical Trial Agreement related to the study.  
17.12 Insurance Policy 
The Sponsor will subscribe a liability insurance covering his and the Investigator's responsibility as 
well as the responsibility of any person involved in the conduct of the trial, provided there is proper 
adherence to the protocol. An insurance certificate will be provided by the Sponsor to the IEC if 
required. 
 
 

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18 
REFERENCES 
 
1. 
Clavé, P. & Shaker, R. Dysphagia: current reality and scope of the problem Nat. Rev. 
Gastroenterol. Hepatol. 12, 259–270 (2015) 
2. 
Altman KW, Yu GP, Schaefer SD: Consequence of dysphagia in the hospitalized patient: 
Impact on prognosis and hospital resources. Arch Otolaryngol Head Neck Surg 2010; 
136:784–789 
3. 
Hinchey JA, Shephard T, Furie K et al. Stroke Practice Improvement Network Investigators. 
Formal dysphagia screening protocols prevent pneumonia. Stroke. 2005;36:1972–1976 
4. 
VA/DoD Clinical Practice Guideline for the October, 2010. Management of Stroke 
Rehabilitation 
5. 
Donovan N., Daniels S, Edmiaston J. et al. Dysphagia Screening: State of the Art : Invitational 
Conference Proceeding From the State-ofthe-Art Nursing Symposium, International Stroke 
Conference 2012. Stroke. 2013;44:000–000 
6. 
O’Horo J., Rogus-Pulia N., Garcia-Arguello L. et al. Bedside Diagnosis of Dysphagia: A 
Systematic Review. J Hosp Med. 2015 April ; 10(4): 256–265 
7. 
Kertscher B., Speyer R., Palmieri M. Bedside Screening to Detect Oropharyngeal Dysphagia 
in Patients with Neurological Disorders: An Updated Systematic Review. Dysphagia (2014) 
29:204–212 
8. 
Swets JA. The science of choosing the right decision threshold in highstakes diagnostics. Am 
Psychol. 1992;47:522–532. 
9. 
Zammit-Maempel, I., Chapple, C., & Leslie, P. (2007). Radiation dose in videofluoroscopic 
swallow studies. Dysphagia, 22(1), 13-15 
10. Moro, L., & Cazzani, C. (2006). Dynamic swallowing study and radiation dose to patients. 
[Studio dinamico della deglutizione e dose radiante al paziente]  Radiologia Medica, 111(1), 
123-129.  
11. Bonilha H.S, Humphries K,  Blair J, Hill E.G,  McGrattan K, Carnes B, Huda W, Martin-Harris B. 
Radiation Exposure Time during MBSS: Influence of Swallowing Impairment Severity, Medical 
Diagnosis, Clinician Experience, and Standardized Protocol Use. Dysphagia. 2013 March ; 
28(1): 77–85 
12. US NRC: Backgrounder on Biological Effects of Radiation http://www.nrc.gov/reading-rm/doc-
collections/fact-sheets/bio-effects-radiation.html 
13. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361. 
14. Bonilha H.S., Blair J, Carnes B, Huda W, Humphries K, McGrattan K, Michel Y, Martin-Harris 
B. Preliminary Investigation of the Effect of Pulse Rate on Judgments of Swallowing  
Impairment and Treatment Recommendations. Dysphagia. 2013 December ; 28(4) 
15. Bath P. M, Scutt P., Love J., Clavé P., Cohen D., Dziewas R., Iversen H.K., Ledl C., Ragab S., 
Soda H., Warusevitane A, Woisard V., Hamdy S. Pharyngeal Electrical Stimulation for 
Treatment of Dysphagia in Subacute Stroke: A Randomized Controlled Trial. Stroke. 
2016;47:00-00. 
16. C. R. Mehta and S. J. Pocock. “Adaptive increase in sample size when interim results are 
promising: a practical guide with examples”. In: Stat Med 30.28 (Dec. 2011), pp. 3267–3284. 
 
 

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19 
APPENDIX A: WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
 Ethical Principles for Medical Research Involving Human Subjects 
 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 
and amended by the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000  
53rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added) 
55th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added) 
59th WMA General Assembly, Seoul, Republic of Korea, October 2008 
64th WMA General Assembly, Fortaleza, Brazil, October 2013 
Preamble 
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement 
of ethical principles for medical research involving human subjects, including research on 
identifiable human material and data. 
The Declaration is intended to be read as a whole and each of its constituent paragraphs should be 
applied with consideration of all other relevant paragraphs. 
2. Consistent with the mandate of the WMA, the Declaration is addressed primarily to physicians. 
The WMA encourages others who are involved in medical research involving human subjects to 
adopt these principles.  
General Principles 
3. The Declaration of Geneva of the WMA binds the physician with the words, “The health of my 
patient will be my first consideration,” and the International Code of Medical Ethics declares that, “A 
physician shall act in the patient's best interest when providing medical care.” 
4. It is the duty of the physician to promote and safeguard the health, well-being and rights of 
patients, including those who are involved in medical research. The physician's knowledge and 
conscience are dedicated to the fulfillment of this duty. 
5. Medical progress is based on research that ultimately must include studies involving human 
subjects. 
6. The primary purpose of medical research involving human subjects is to understand the causes, 
development and effects of diseases and improve preventive, diagnostic and therapeutic 
interventions (methods, procedures and treatments). Even the best proven interventions must be 
evaluated continually through research for their safety, effectiveness, efficiency, accessibility and 
quality. 
7. Medical research is subject to ethical standards that promote and ensure respect for all human 
subjects and protect their health and rights. 
8. While the primary purpose of medical research is to generate new knowledge, this goal can 
never take precedence over the rights and interests of individual research subjects. 

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9. It is the duty of physicians who are involved in medical research to protect the life, health, dignity, 
integrity, right to self-determination, privacy, and confidentiality of personal information of research 
subjects. The responsibility for the protection of research subjects must always rest with the 
physician or other health care professionals and never with the research subjects, even though 
they have given consent. 
10. Physicians must consider the ethical, legal and regulatory norms and standards for research 
involving human subjects in their own countries as well as applicable international norms and 
standards. No national or international ethical, legal or regulatory requirement should reduce or 
eliminate any of the protections for research subjects set forth in this Declaration. 
11. Medical research should be conducted in a manner that minimises possible harm to the 
environment. 
12. Medical research involving human subjects must be conducted only by individuals with the 
appropriate ethics and scientific education, training and qualifications. Research on patients or 
healthy volunteers requires the supervision of a competent and appropriately qualified physician or 
other health care professional. 
13. Groups that are underrepresented in medical research should be provided appropriate access 
to participation in research. 
14. Physicians who combine medical research with medical care should involve their patients in 
research only to the extent that this is justified by its potential preventive, diagnostic or therapeutic 
value and if the physician has good reason to believe that participation in the research study will not 
adversely affect the health of the patients who serve as research subjects. 
15. Appropriate compensation and treatment for subjects who are harmed as a result of 
participating in research must be ensured. 
Risks, Burdens and Benefits 
16. In medical practice and in medical research, most interventions involve risks and burdens. 
Medical research involving human subjects may only be conducted if the importance of the 
objective outweighs the risks and burdens to the research subjects. 
17. All medical research involving human subjects must be preceded by careful assessment of 
predictable risks and burdens to the individuals and groups involved in the research in comparison 
with foreseeable benefits to them and to other individuals or groups affected by the condition under 
investigation. 
Measures to minimise the risks must be implemented. The risks must be continuously monitored, 
assessed and documented by the researcher.  
18. Physicians may not be involved in a research study involving human subjects unless they are 
confident that the risks have been adequately assessed and can be satisfactorily managed. 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of 
definitive outcomes, physicians must assess whether to continue, modify or immediately stop the 
study.  
 

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Vulnerable Groups and Individuals 
19. Some groups and individuals are particularly vulnerable and may have an increased likelihood 
of being wronged or of incurring additional harm. 
All vulnerable groups and individuals should receive specifically considered protection. 
20. Medical research with a vulnerable group is only justified if the research is responsive to the 
health needs or priorities of this group and the research cannot be carried out in a non-vulnerable 
group. In addition, this group should stand to benefit from the knowledge, practices or interventions 
that result from the research. 
Scientific Requirements and Research Protocols 
21. Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant sources of 
information, and adequate laboratory and, as appropriate, animal experimentation. The welfare of 
animals used for research must be respected. 
22. The design and performance of each research study involving human subjects must be clearly 
described and justified in a research protocol. 
The protocol should contain a statement of the ethical considerations involved and should indicate 
how the principles in this Declaration have been addressed. The protocol should include 
information regarding funding, sponsors, institutional affiliations, potential conflicts of interest, 
incentives for subjects and information regarding provisions for treating and/or compensating 
subjects who are harmed as a consequence of participation in the research study. 
In clinical trials, the protocol must also describe appropriate arrangements for post-trial provisions. 
Research Ethics Committees 
23. The research protocol must be submitted for consideration, comment, guidance and approval to 
the concerned research ethics committee before the study begins. This committee must be 
transparent in its functioning, must be independent of the researcher, the sponsor and any other 
undue influence and must be duly qualified. It must take into consideration the laws and regulations 
of the country or countries in which the research is to be performed as well as applicable 
international norms and standards but these must not be allowed to reduce or eliminate any of the 
protections for research subjects set forth in this Declaration.  
The committee must have the right to monitor ongoing studies. The researcher must provide 
monitoring information to the committee, especially information about any serious adverse events. 
No amendment to the protocol may be made without consideration and approval by the committee. 
After the end of the study, the researchers must submit a final report to the committee containing a 
summary of the study’s findings and conclusions.  
Privacy and Confidentiality 
24. Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information. 
Informed Consent 

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25. Participation by individuals capable of giving informed consent as subjects in medical research 
must be voluntary. Although it may be appropriate to consult family members or community 
leaders, no individual capable of giving informed consent may be enrolled in a research study 
unless he or she freely agrees. 
26. In medical research involving human subjects capable of giving informed consent, each 
potential subject must be adequately informed of the aims, methods, sources of funding, any 
possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and 
potential risks of the study and the discomfort it may entail, post-study provisions and any other 
relevant aspects of the study. The potential subject must be informed of the right to refuse to 
participate in the study or to withdraw consent to participate at any time without reprisal. Special 
attention should be given to the specific information needs of individual potential subjects as well as 
to the methods used to deliver the information. 
After ensuring that the potential subject has understood the information, the physician or another 
appropriately qualified individual must then seek the potential subject’s freely-given informed 
consent, preferably in writing. If the consent cannot be expressed in writing, the non-written consent 
must be formally documented and witnessed.  
All medical research subjects should be given the option of being informed about the general 
outcome and results of the study. 
27. When seeking informed consent for participation in a research study the physician must be 
particularly cautious if the potential subject is in a dependent relationship with the physician or may 
consent under duress. In such situations the informed consent must be sought by an appropriately 
qualified individual who is completely independent of this relationship. 
28. For a potential research subject who is incapable of giving informed consent, the physician 
must seek informed consent from the legally authorised representative. These individuals must not 
be included in a research study that has no likelihood of benefit for them unless it is intended to 
promote the health of the group represented by the potential subject, the research cannot instead 
be performed with persons capable of providing informed consent, and the research entails only 
minimal risk and minimal burden. 
29. When a potential research subject who is deemed incapable of giving informed consent is able 
to give assent to decisions about participation in research, the physician must seek that assent in 
addition to the consent of the legally authorised representative. The potential subject’s dissent 
should be respected. 
30. Research involving subjects who are physically or mentally incapable of giving consent, for 
example, unconscious patients, may be done only if the physical or mental condition that prevents 
giving informed consent is a necessary characteristic of the research group. In such circumstances 
the physician must seek informed consent from the legally authorised representative. If no such 
representative is available and if the research cannot be delayed, the study may proceed without 
informed consent provided that the specific reasons for involving subjects with a condition that 
renders them unable to give informed consent have been stated in the research protocol and the 
study has been approved by a research ethics committee. Consent to remain in the research must 
be obtained as soon as possible from the subject or a legally authorised representative. 
31. The physician must fully inform the patient which aspects of their care are related to the 
research. The refusal of a patient to participate in a study or the patient’s decision to withdraw from 
the study must never adversely affect the patient-physician relationship. 

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32. For medical research using identifiable human material or data, such as research on material or 
data contained in biobanks or similar repositories, physicians must seek informed consent for its 
collection, storage and/or reuse. There may be exceptional situations where consent would be 
impossible or impracticable to obtain for such research. In such situations the research may be 
done only after consideration and approval of a research ethics committee. 
Post-Trial Provisions 
34. In advance of a clinical trial, sponsors, researchers and host country governments should make 
provisions for post-trial access for all participants who still need an intervention identified as 
beneficial in the trial. This information must also be disclosed to participants during the informed 
consent process. 
Research Registration and Publication and Dissemination of Results 
35. Every research study involving human subjects must be registered in a publicly accessible 
database before recruitment of the first subject. 
36. Researchers, authors, sponsors, editors and publishers all have ethical obligations with regard 
to the publication and dissemination of the results of research. Researchers have a duty to make 
publicly available the results of their research on human subjects and are accountable for the 
completeness and accuracy of their reports. All parties should adhere to accepted guidelines for 
ethical reporting. Negative and inconclusive as well as positive results must be published or 
otherwise made publicly available. Sources of funding, institutional affiliations and conflicts of 
interest must be declared in the publication. Reports of research not in accordance with the 
principles of this Declaration should not be accepted for publication. 
Unproven Interventions in Clinical Practice 
37. In the treatment of an individual patient, where proven interventions do not exist or other known 
interventions have been ineffective, the physician, after seeking expert advice, with informed 
consent from the patient or a legally authorised representative, may use an unproven intervention if 
in the physician's judgment it offers hope of saving life, re-establishing health or alleviating 
suffering. This intervention should subsequently be made the object of research, designed to 
evaluate its safety and efficacy. In all cases, new information must be recorded and, where 
appropriate, made publicly available. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Nestlé Research Center 
Trial N° 16.21.CLI 
CH-1000 Lausanne 26 
Protocol Amendment Version N° 2   25 September 2017 
Switzerland 
Page 47 of 47 
 
CONFIDENTIAL · This document may not be reproduced or disclosed to third parties without prior authorization 
 
20 
 APPENDIX B: PENTRATION ASPIRATION SCALE  
 
Penetration Aspirtaion Scale1  
 
 
Reference 
1. 
Rosenbek J, Robbins J, Roecker E, Coyle J, Wood J. A penetration-aspiration scale. 
Dysphagia. 1996;11:93-98