EYE-TRAC Advance: Technology Verification (ETA-TV) Cohort 2
Phase: NA
Conditions: Eye-tracking
Sponsor: Stanford University

EYE-TRAC Advance: Technology Verification 
(ETA-TV) Cohort 2 
NCT02877732 
April 12, 2016 
Jamshid Ghajar, MD, PhD, Principal Investigator 
Stanford University 
Stanford, California 94305 

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JAMSHID GHAJAR, MD, PHD, FACS 
Clinical Research Protocol 
EYE-TRAC ADVANCE: TECHNOLOGY VERIFICATION COHORT 2 
 
 
Protocol Number: 
ETA-TV 
Version: 
2.3 
Version Date: 
April 12, 2016 
Investigational Device: 
EYE-SYNC 
Study Phase: 
Feasibility/Exploratory 
Sponsor: 
Jamshid Ghajar, MD, PhD, FACS 
Stanford Concussion and Brain Performance Center 
1050 Arastradero Road, Suite A 233 
Palo Alto, CA 94304 
Funding Organization: 
Office of Naval Research 
Site Investigator: 
Name: 
Title: 
Telephone: 
Fax: 
E-mail: 
 
Approval: 
 
 
Site Investigator Signature (Name and Title) 
Date 
 
This confidential information about feasibility/exploratory study is provided for the 
exclusive use of investigators of the EYE-SYNC Goggles and is subject to recall at 
any time. The information in this document may not be disclosed unless federal or 
state law or regulations require such disclosure. Subject to the foregoing, this 
information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information. 

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PROTOCOL AGREEMENT 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and 
providing Dr. Ghajar and the Stanford Concussion and Brain Performance Center with 
complete and timely information, as outlined in the protocol. It is understood that all 
information pertaining to the study will be held strictly confidential and that this 
confidentiality requirement applies to all study staff at this site. Furthermore, on behalf of 
the study staff and myself, I agree to maintain the procedures required to carry out the 
study in accordance with accepted GCP principles and to abide by the terms of this 
protocol. 
 
Protocol Number: ETA-TV_34662 
 
Protocol Title: EYE-TRAC Advance: Technology Verification 
Version: 2.3 
Protocol Date:  April 12th, 2016 
 
 
 
Investigator Signature 
Date 
 
 
Print Name and Title 
Site # 
  
 
Site Name            
 
Site Contact         
 
Address 
  
 
 
 
 
 
 
 
Phone Number     
 
Email 
  
 

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TABLE OF CONTENTS 
1.0 
PURPOSE OF THE INVESTIGATION ....................................................................... 10 
1.1 
Name of investigational device ...................................................................................... 10 
1.2 
Intended use of the investigational device ................................................................... 10 
1.3 
Objectives of the clinical investigation .......................................................................... 10 
1.3.1 
Primary objectives ............................................................................................................ 10 
1.4 
Anticipated duration of the clinical investigation ........................................................ 10 
2.0 
CLINICAL PROTOCOL............................................................................................. 10 
2.1 
Protocol number and title ............................................................................................... 10 
2.2 
Protocol version number and date ................................................................................. 10 
2.3 
Study design ...................................................................................................................... 11 
2.3.1 
General study design........................................................................................................ 11 
2.3.2 
Study design schematic ................................................................................................... 11 
2.4 
Subject selection............................................................................................................... 13 
2.4.1 
General characteristics of the proposed subject population(s) .................................. 13 
2.4.2 
Anticipated number of research subjects ...................................................................... 13 
2.4.3 
Inclusion criteria ............................................................................................................... 13 
2.4.4 
Exclusion criteria .............................................................................................................. 14 
2.5 
Study Procedures.............................................................................................................. 14 
2.5.1 Visit 1 ..................................................................................................................................... 15 
2.5.2 Visits 2, 3 and 4 ..................................................................................................................... 15 
2.5.3 
Withdrawal of subjects .................................................................................................... 16 
2.6 
Study Outcome Evaluations ............................................................................................ 17 
2.6.1 
Study endpoints ................................................................................................................ 17 
2.6.2 
Planned Data Analysis and Sample Size Determination .............................................. 17 
2.6.3 
Data and Safety Monitoring and Training ..................................................................... 18 
3.0 
RISK ANALYSIS ...................................................................................................... 18 
3.1 
Anticipated risks ............................................................................................................... 18 
3.2 
Adverse event reporting .................................................................................................. 19 
3.2.1 
Adverse event definitions ............................................................................................... 19 
3.2.2 
Recording and assessment of adverse events .............................................................. 19 
3.2.3 
Causality and severity assessment ................................................................................. 20 
3.2.4 
Reporting adverse events to the FDA ............................................................................ 20 
3.2.5 
Reporting adverse events to the responsible IRB ......................................................... 20 
3.3 
Withdrawal of subjects due to adverse events ............................................................. 20 
4.0 
DESCRIPTION OF THE INVESTIGATIONAL DEVICE ............................................... 21 
5.0 
MONITORING PROCEDURES ................................................................................ 21 
6.0 
INFORMED CONSENT ........................................................................................... 21 
7.0 
IRB INFORMATION ............................................................................................... 22 
8.0 
ADDITIONAL RECORDS AND REPORTS ................................................................ 22 
8.1 
Data handling and record-keeping ................................................................................. 22 
8.2 
Record maintenance and retention ............................................................................... 22 

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LIST OF ABBREVIATIONS 
ADD 
ADHD 
AE 
Attention Deficit Disorder 
Attention Deficit Hyperactivity Disorder 
Adverse Event 
ANAM 
The Automated Neuropsychological Assessment Metrics 
ANAM-SRT 
The Automated Neuropsychological Assessment Metrics Simple 
Reaction Time Subtest 
CCS 
Concussion Subject 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTR 
DEMTM 
Control Subject 
Developmental Eye MovementTM 
ETA 
EYE-TRAC Advance 
ETA-TV 
EYE-TRAC Advance: Technology Verification 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HX 
History 
ICC 
Intra-class Correlation Coefficient 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
PHI 
Personal Health Information 
PI 
Principal Investigator 
SCAT 
Sports Concussion Assessment Tool 
SSRI 
Selective Serotonin Re-uptake Inhibitor 
UADE 
Unanticipated Adverse Device Event 

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PROTOCOL SYNOPSIS 
 
TITLE 
EYE-TRAC Advance: Technology Verification 
SPONSOR 
Jamshid Ghajar, MD, PhD, FACS 
PRINCIPAL 
INVESTIGATOR 
Jessica Little, PhD 
FUNDING 
ORGANIZATION 
Office of Naval Research 
NUMBER OF SITES 
4-5 
RATIONALE 
There is a lack of understanding regarding the mechanisms that cause 
concussive signs and symptoms, and there is no definitive consensus 
on how to best evaluate or treat an individual with concussion. As a 
result, it is difficult to evaluate when it is necessary for an athlete to be 
removed from play after a possible head injury. Current sideline 
assessments may be subject to the athlete’s lack of effort during 
baseline testing, leading to inaccurate interpretation post-concussion, or 
learning effects. To avoid inaccurate variability in performance that 
may complicate trainers’ decisions, there is a high demand for an 
objective sideline measure to better determine the outcome of an 
athletic head injury. 
The current EYE-TRAC Advance (ETA) study uses a predictive visual 
tracking paradigm to measure gaze error variability. The addition of 
EYE-TRAC Advance: Technology Verification (ETA-TV) will help to 
fill knowledge gaps that exist in the current ETA protocol and 
contribute to the overall goal of accurately assessing possible 
impairment following a force to the head. 
STUDY DESIGN 
This is a prospective multi-center cohort feasibility and exploratory 
study. 
PRIMARY 
OBJECTIVE 
We propose to prospectively study a cohort of 18-25-year-old athletes 
to establish the reliability of EYE-SYNC data and the utility of the 
EYE-SYNC goggles as a sideline concussion assessment tool. A 
clinical research study will be conducted to 1) determine if eye- 
tracking, assessed on the sideline by EYE-SYNC goggles, is a potential 
marker of injury that can be used in conjunction with other sideline 
evaluations to inform decisions regarding removal of athletes from play 
and 2) to use the EYE-SYNC goggle data as a post- injury recovery 
curve monitor. 
SECONDARY 
OBJECTIVES 
To describe interrelationships among relevant variables used to 
describe concussion and EYE-SYNC. 

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NUMBER OF 
SUBJECTS 
N = 100 (50 Concussion Subjects, 50 Controls) 
* Please note that we will continue to consent subjects, until we are 
able to complete 100 eligible participants for Cohort 2. 
SUBJECT 
SELECTION 
CRITERIA 
Inclusion Criteria: Athletes between the age of 18 – 25-years-old. 
20/30 or better eyesight (corrected vision allowed). English fluency. 
CCS - those who experience impact where concussion is highly 
suspected as evidenced by impairment on any of the SCAT-3 Domains: 
Symptoms, Immediate Memory, Physical Signs, and Orientation.  CTR 
- a teammate of the CCS who did not experience impact but who was 
participating in the same sport and session along with the injured 
teammate at the time of injury. 
Exclusion Criteria: Clinical diagnosis of a neurological condition 
including the following: Stroke, Multiple Sclerosis, Epilepsy, Brain 
Tumor/Cancer, dyslexia, Nystagmus and/or other major neurological 
condition. Clinical diagnosis of any of the following eye-sight 
abnormalities: Uncorrected Amblyopia, Uncorrected Myopia, 
Uncorrected Presbyopia, Uncorrected Farsightedness or Uncorrected 
Astigmatism. Psychiatric history with any of the following: 
LIFETIME a. Clinical diagnosis of a Psychotic Disorder, Bipolar 
Disorder: LIFETIME b. Clinical diagnosis of ADHD or ADD: 
LIFETIME LAST YEAR c. Clinical diagnosis of Major Depressive 
Disorder d. Clinical diagnosis of Substance Abuse Disorder within the 
LAST YEAR. e. Major Anxiety Disorder within the LAST YEAR. 
MEDICATION g. Use of a psychotropic medication. Cannot have 
participated previously in any ETA-TV study visits (for instance, a 
subject that has completed any study visit as a control subject cannot 
participate as a concussed subject at a later time point).. 
INVESTIGATIONAL 
DEVICE / 
INTENDED USE 
The EYE-SYNC® portable assessment system consists of two primary 
components enclosed in a portable aluminum case. The eye tracker is a 
handheld isolated display environment with embedded eye tracking 
sensors. The eye tracker is connected to a high-performance Windows 
tablet though a customized docking station. Included accessories with 
EYE-SYNC are a U.S. tablet power supply adapter and disposable 
sanitary masks. Subjects are asked to follow a dot as it moves on the 
screen. 
DURATION OF 
SUBJECT 
PARTICIPATION 
AND DURATION 
OF STUDY 
The proposed study will occur within an 18-month window. 
Active enrollment will continue through the last month of the study or 
intended sample size is reached. 
Subject participation begins with enrollment, followed by baseline 
testing, and follow-up assessments (2 days post-injury, 7 days post- 
injury (+/- 1 day); and 14 days post-injury (+/- 3 days)). Testing 
follows consent for all subjects and continues through last 

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practice/game in study period. Study windows are only to be used in 
rare situations. Please discuss with Stanford Principal 
Investigator/Study Sponsor for approval. 
CONCOMMITANT 
MEDICATIONS 
No psychotropic medication. 
EFFICACY 
EVALUATIONS 
DEM: The Developmental Eye Movement Test is an evaluation of 
saccadic eye movements. In this test, the subject reads the numbers 
presented on a card from left to right and top to bottom as quickly as 
he/she can without making any errors. 
ANAM-SRT: The Automated Neuropsychological Assessment 
Metrics (ANAM) is a computerized neurocognitive assessment tool 
designed to measure a wide range of cognitive functions. The Simple 
Reaction Time subtest is used as an index of attention (i.e., reaction 
time and vigilance) and visuo-motor response timing. 
SCAT-3: The Sport Concussion Assessment Tool (SCAT) is a widely 
used sideline concussion assessment tool used to evaluate the presence 
of neurocognitive impairment following a concussion. In the symptom 
evaluation, the subject self-reports the presence and severity of 22 
concussion- related symptoms on a likert scale from 0-6. The SCAT3 
tests the subject’s orientation using Maddocks questions, and also 
includes the administration of the Standardized Assessment of 
Concussion (SAC). The SAC includes sections that test immediate 
memory and balance (modified BESS). 
PRIMARY 
ENDPOINT 
Our primary endpoint will be the acquisition of sufficient data to 
establish integrity and reliability of EYE-SYNC data and to compare 
and characterize trajectories of EYE-SYNC measurements in injured 
versus non-injured athletes. 
SECONDARY 
ENDPOINTS 
Our secondary endpoint will be to characterize interrelationships 
among variables relevant to concussion including DEM, ANAM-SRT, 
and SCAT-3 scores with EYE-SYNC. 
OTHER 
EVALUATIONS 
History and Demographics 
SAFETY 
EVALUATIONS 
N/A – EYE-SYNC is a minimal-risk noninvasive assessment tool, not 
an invasive assessment or treatment modality. 
PLANNED INTERIM 
ANALYSES 
When approximately 50% of subjects have completed the study, an 
interim analysis for safety will be conducted. Serious adverse events 
will be monitored by all site Investigators, Dr. Jamshid Ghajar, and the 
Stanford Concussion and Brain Performance Center (SCBPC) 
Coordinators on an ongoing basis throughout the study. 
 

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STATISTICS 
Primary Analysis 
Plan and Rationale 
for Number of 
Subjects 
Descriptive Statistics: We will provide descriptive statistics for all 
subjects included in our study. Specifically, for continuous variables 
such as age, and scores from DEM, ANAM-SRT, SCAT-3, and EYE- 
SYNC, we will provide means, medians, standard deviations and 
interquartile ranges. For categorical variables such as race, ethnicity 
and previous history of injury, we will present frequency distributions. 
We will utilize graphical tools such as histograms and box plots to 
describe distributions of continuous variables. If needed to adhere to 
modeling assumptions, we may consider transformations of outcomes, 
such as a log transformation. 
Handling of Missing Data: We anticipate minimal missing data in this 
study. We expect that a small proportion of subjects recruited for the 
longitudinal study (1%) will not complete all visits. We will fully 
describe missing data for each variable and any pertinent patterns of 
missingness (e.g., how missingness is related to specific baseline 
measurements or time, if at all).  The statistical methods we propose 
are particularly flexible for missing data and allow for systematic 
missingness that is related to observed features. 
Statistical Tools for Each Aim: Our first aim addresses the integrity of 
data generated by EYE-SYNC. Specifically, in Aim 1A, we will 
characterize the feasibility of collecting and generating data in real- 
time as injuries occur by considering the proportion of time we are able 
to collect 3 subsequent measures using EYE-SYNC on the sideline in 
the field from a case using data from cases included in Cohort 2 
(described above). We deem EYE-SYNC to be a promising tool to be 
used on the field if we are able to make use of it 90% of the time. This 
will be tested using a one-sided exact binomial test. With 50 cases, we 
have excellent power to evaluate feasibility.  More specifically if we 
use a decision rule such that we conclude EYE-SYNC to be a 
promising and practical tool to be used in the field if we have complete 
information on 40 of the 50 cases, we have over 95% power when the 
true rate of complete data is 90% with a type I error of 0.04 under the 
null hypothesis that an unacceptable rate of complete data is 70%. 
The goal of Aim 2 is to assess whether data from EYE-SYNC 
correlates with clinically meaningful endpoints. To that end, we will 
create Cohort 2 by collecting data (in replicates of 3) at immediately 
post impact, 2 days from injury, 7days from injury and 14 days from 
injury from 50 cases (defined as those who experience impact where 
concussion is highly suspected) and 50 matched controls (a teammate 
who did not experience impact but who was participating in the same 
sport and session along with the injured teammate at the time of 
injury). Using mixed effects regression techniques, we will examine 
whether the trajectory of EYE-SYNC changes over time for those 
injured differs significantly from those who were not injured.  In 

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addition, we will characterize trajectories of change in EYE-SYNC 
over time for those injured and for athletes who are injury free. Such 
models account for the correlation of scores within a subject over time 
as well as for the matched pairing of cases and their corresponding 
teammates. In addition, such models are robust to assumptions 
regarding missing data. 
The goal of Aim 3 is to describe interrelationships among relevant 
variables used to describe concussion and EYE-SYNC. This aim is 
fairly exploratory but will pave the way for future studies. We will rely 
on mixed effects techniques to characterize relationships of interest. 

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1.0 
PURPOSE OF THE INVESTIGATION 
1.1 
Name of investigational device 
EYE-SYNC® 
1.2 
Intended use of the investigational device 
We intend to conduct a clinical trial including 50 Concussion Subjects and 50 Controls to 
compare trajectories of EYE-SYNC measurements in injured versus non-injured athletes 
and characterize variables related to concussion in relation to EYE-SYNC data. 
 
1.3 
Objectives of the clinical investigation 
1.3.1 Primary objectives 
Specific Aim 1: Establish integrity and reliability of EYE-SYNC data 
 Specific Aim 1A: Characterize feasibility of collecting data using EYE-SYNC in 
real-time on the field. 
 
Specific Aim II: Compare and characterize trajectories of EYE-SYNC measurements in 
injured versus non-injured athletes. 
 
Specific Aim III: Characterize interrelationships among variables relevant to concussion 
including DEM, ANAM-SRT and SCAT-3 scores and EYE-SYNC. 
1.4 
Anticipated duration of the clinical investigation 
The proposed study will occur within an 18-month window. Active enrollment will 
continue through the last month of the study or intended sample size is reached. 
 
2.0 
CLINICAL PROTOCOL 
2.1 
Protocol number and title 
ETA-TV_34662: EYE-TRAC Advance: Technology Verification 
2.2 
Protocol version number and date 
Version 1.0, October 26, 2015 
Version 2.0 January 26, 2015 
Version 2.1 March 17, 2016 
Version 2.2 April 4th, 2016 
Version 2.3 April 12th, 2016 

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2.3 
Study design 
2.3.1 General study design 
This is a prospective multi-center cohort feasibility and exploratory study. 
 
2.3.2 Study design schematic 
The proposed study will occur within an 18-month window. Subject participation begins 
with enrollment, followed by baseline testing, and follow-up assessments. 
Figure 1. Eighteen-month study plan 
 
Month of Study 
Study Element 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13-18 
IRB and Regulatory Approval: initiate 
at study onset and projected to allow 
enrollment* within 3 to 4 months 
Recruitment Activities: outreach to 
team stakeholders regarding study and 
logistics 
Active Enrollment: informed consent 
process continues to last month of study 
or intended study size is reached 
Subject Testing: testing follows 
consent for all subjects until last game 
in study period. 
Data Analysis and Publications: data 
analysis will begin as testing initiates 
and may continue beyond 18 months 

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Figure 2. Sample Individual Subject Study Timeline 
 
Cohort 2 
N=50 CCS 
N=50 CTR 
Impact Sustained 
Phase 
Prior to 
game 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Post-Concussion 
Immediate at Sideline – EYE- 
SYNC, Level of Alertness. 
Within 3 hrs* – SCAT-3, ANAM- 
SRT, DEM 
Post Concussion 2 
days 
Post 
Concussio 
n 7 days** 
(+/- 1 day) 
CCS&CTR 
Post 
Concussion 
14 days** 
(+/- 3 days) 
CCS&CTR 
CCS 
CTR 
CCS 
CTR 
Informed Consent 
X 
Inclusion and Exclusion 
Criteria and 
demographics 
X2 
X3 
History of injury 
X 
X 
SCAT-3 Symptom 
X1 
X 
X 
X 
X 
X 
SCAT-3 Balance, 
Orientation and 
Immediate Memory 
X1 
X 
X 
X 
X 
X 
DEM 
X 
X 
X 
X 
X 
X 
ANAM-SRT 
X 
X 
X 
X 
X 
X 
Level of Alertness 
questions4 
X5 
X 
X 
X 
X 
X 
EYE-SYNC (3 times 
consecutively) 
X5 
X 
X 
X 
X 
X 
*DEM, SCAT-3, ANAM-SRT must be performed within 3 hours of impact for Concussed subject (CCS) and within 3 
hours post competition or practice for the control subject. 
** The study window is only to be used for rare situations where the subject is unable to be seen on the exact date they 
are scheduled to come in. Please notify the site Investigator immediately for approval if subject needs to be seen within 
the study window that is provided. 
1. 
Those that display impairment on any of the SCAT-3 domains: Symptoms, Immediate Memory, 
Physical Signs and Orientation will be registered as CCS subject. 
2. 
CTR subjects: Those that meet the inclusion and exclusion criteria under cohort 2 (section 2.4.3 and 
2.4.4), was actively participating in the same game along with the CCS subject at the time of injury. 
3. 
During Visit 2, before performing any study procedures CCS subject must meet all the inclusion and 
exclusion criteria under cohort 2 (section 2.4.3 and 2.4.4). If subject does not meet all the criteria, CCS 
subject will be a screen failure. If possible, perform CTR study assessment after confirming that CCS is 
eligible to continue participation on Visit 2. 
4. 
Level of Alertness questions must always be completed before performing the EYE-SYNC 
5. 
EYE-SYNC must be performed at sideline immediately post impact. 

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2.4 
Subject selection 
2.4.1 General characteristics of the proposed subject population(s) 
Male and female athletes, aged 18-25 years, will be recruited from athletic programs at 
collaborating study sites for Cohort 2. 
2.4.2 Anticipated number of research subjects 
Throughout the course of 18 months, the study will enroll 100 subjects in Cohort 2. 
Cohort 2 will include 100 subjects; 50 Concussion Subjects (CCS) who have sustained an 
impact where concussion is highly suspected, as evidenced by impairment on either of 
the SCAT-3 domains: Symptom, Physical Signs, Orientation, Immediate Memory and 50 
control subjects (CTR) who are teammates of the CCS and who did not experience 
impact, but who were participating in the same sport and session along with the injured 
CCS at the time of injury. 
2.4.3 Inclusion criteria 
 Athletes between the age of 18-25 years-old 
 20/30 or better eyesight (corrected vision allowed). 
 English fluency. 
 CCS - those who experience impact where concussion is highly suspected as 
evidenced by impairment in any of the SCAT-3 Domains: Symptoms, Physical Signs, 
Immediate Memory and Orientation. An Injured Athlete is concussed if he/she is 
FAIL on the Physical Signs, Score = 0 on the Orientation or Scoring below the cutoff 
scores on the Symptom Checklist and/or Immediate memory SCAT-3 domains. 
 
o Symptoms: Rating of 2 or higher on any of the following items: 
▪ 
Headaches 
▪ 
Nausea or Vomiting 
▪ 
Dizziness 
▪ 
Balance Problems 
▪ 
Blurred Vision 
▪ 
Feeling Slowed Down 
▪ 
Feeling like “in a fog” 
▪ 
“Don’t feel right” 
 
o Physical Signs: 
▪ 
Balance (Leg Stances): Number of Error(s) on any of the following 
7 subtests classifies a subject as concussed. 
I. 
Double Leg Stance: At least 3 errors 
II. 
Single Leg Stance: At least 3 errors with either 
dominant or non-dominant foot 
III. 
Tandem Stance: At least 3 errors or more. 
▪ 
Balance (Tandem Gait): FAIL on at least 2 of 4 trials: 
I. 
FAIL per trial: more than 14 seconds to complete a 
trial 

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II. 
FAIL per trial, if one or more of the following 
errors are made 
a) If step off the line; 
b) Separation between heel and toe 
c) Touch/grab the examiner or an object 
o Orientation: Score = 0 on any of the following 5 items 
▪ 
Date: Score = 0 (any date different from current) 
▪ 
Month: Score = 0 (any month different from current) 
▪ 
Day of the week: Score = 0 (any different from current) 
▪ 
Year: Score = 0 (any different from current) 
▪ 
Time: Score = 0 AND answer is MORE than + or – 1 hour apart 
from the correct time. 
o Immediate Memory 
▪ 
Recall Total Score = less than 13 words recalled. 
 
 CTR - a teammate of the CCS who did not experience impact but who was 
actively participating in the same sport and session along with the injured 
teammate at the time of injury 
2.4.4 Exclusion criteria 
 Clinical diagnosis of a neurological condition including the following: Stroke, 
Multiple Sclerosis, Epilepsy, Brain Tumor/Cancer, dyslexia, Nystagmus and/or 
Other major neurological condition. 
 Clinical diagnosis of any of the following eye-sight abnormalities: Uncorrected 
Amblyopia, Uncorrected Myopia, Uncorrected Presbyopia, Uncorrected 
Farsightedness, Uncorrected Astigmatism. 
 Psychiatric history with any of the following: 
LIFETIME 
a. Clinical diagnosis of a Psychotic Disorder, Bipolar Disorder 
b. Clinical diagnosis of ADHD or ADD 
Within LAST YEAR 
c. Clinical diagnosis of Major Depressive Disorder 
d. Clinical diagnosis of Substance Abuse Disorder 
e. Clinical Diagnosis of Major Anxiety Disorder. 
MEDICATION 
f. Use of a psychotropic medication 
 Cannot have participated previously in any ETA-TV study visits (for instance, a 
subject that has completed any study visit as a control subject cannot participate 
as a concussed subject at a later time point). 
 
2.5 
Study Procedures 
Post-concussion immediate and scheduled follow-up visits 
Data Collection: 

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2.5.1 Visit 1 
1. Visit 1 occurs immediately post-impact. The “Immediate” time frame for “post 
impact” is quantified as taking place as part of the naturalistic evaluation of the 
athlete suspected of sustaining a concussion. This will likely be immediately after 
the identification of a “hit” or other event that would lead to an athlete being 
evaluated for a possible concussion. At Visit 1, Level of Alertness, EYE-SYNC, 
DEM, ANAM-SRT, and SCAT-3: Symptom reporting, Physical Signs, Orientation, 
and Immediate Memory will be obtained (the above tests in combination will be 
referred to as ‘Testing Battery’). 
a. Post-impact the subject undergoes EYE-SYNC measurement immediately at 
the sideline. EYE-SYNC to be performed 3 times consecutively. 
b. Individuals enrolled as a Concussed Subject (CCS) are defined as those who 
experience impact where concussion is highly suspected as evidenced by 
impairment on any one of the SCAT-3 domains: Symptoms, Immediate 
Memory, Physical Signs or Orientation 
c. For each CCS subject enrolled, immediately enroll a Control Subject (CTR). A 
CTR subject is defined as a teammate who did not experience impact, but who 
was actively participating in the same sport and session along with the injured 
teammate at the time of injury. The CTR subject also receives the Testing 
Battery. Prior to performing the Testing Battery, ensure the CTR subject meets 
the Inclusion and Exclusion criteria – Cohort 2 as per section 2.4.3 and 2.4.4. 
d. CTR subject will complete Demographics during Visit 1. 
 
2.5.2 Visits 2, 3 and 4 
1. CCS must meet the inclusion and exclusion criteria prior to performing any 
assessments on Visit 2 (2 days post-injury). If CCS is ineligible, both CCS and CTR 
will discontinue participation in the study. 
2. History of injury data for CCS and CTR subjects are collected during Visit 2. 
3. Following CCS eligibility to continue participation in study, testing battery will be 
performed by both CCS and CTR. 
4. During Visit 3 and Visit 4, all the assessments in the testing battery will be 
completed both by CCS and CTR. 
 
The Day of injury is Day 1. Following visit 1, the testing battery will be collected for both 
the CCS and the CTR subject at three additional time points. Visit 2 will occur at 2 days 
post-injury. Visit 3 at 7 days post-injury (+/- 1 day), and Visit 4 at 14 days post-injury (+/- 
3 days). It’s important that subjects are seen exactly at 2, 7, and 14 days post-injury. For 
instance, if subject sustains an injury on January 3, 2016 – Visit 2 will be on January 5th, 
visit 3 will be on January 10th and visit 4 will be January 17th. 
 
The study windows are meant for unforeseen circumstances. Please notify the site 
Investigator for approval if the subject needs to be seen within the study window. 
 
During all the visits in cohort 2 EYE-SYNC must be performed after administering level 
of alertness questionnaire and to be performed 3 times consecutively. 

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Please note: If a CTR subject sustains a concussion at any point while enrolled as a 
control, he/she will be withdrawn from the study and the paired CCS subject will 
continue on with the study visits without a CTR subject. The CTR subject will not be 
allowed to enroll as a CCS subject for the study. 
 
If a CCS subject sustains a second concussion, he/she will be withdrawn from the study 
and the paired CTR subject will continue on with the study visits without a CCS subject. 
3.0.1 Withdrawal of subjects 
If a subject first agrees to participate and then changes his/her mind, the subject is free to 
withdraw consent and discontinue participation at any time. The subject’s decision will 
not affect his/her ability to receive medical care and the subject will not lose any benefits 
to which he/she would otherwise be entitled. 
 
If a subject decides to withdraw consent to participate in this study, the subject should 
notify the site Investigator. The subject may ask to have their data withdrawn from the 
study database. The subject has the right to refuse to allow his/her data to be studied now 
or saved for future study. 
 
The Protocol Director may also withdraw a subject from the study without consent for 
one or more of the following reasons: 
 
 Failure to follow the instructions of the Protocol Director and study staff (non- 
compliance). 
 The Protocol Director decides that continuing participation could be harmful to 
the subject. 
 Pregnancy 
 The subject becomes no longer eligible to complete follow-up sessions due to no 
longer meeting eligibility requirements. 
 Need of treatment not allowed in the study. 
 The study is cancelled. 
 Other administrative reasons. 
 Unanticipated circumstances. 
If subjects are withdrawn from the study due to non-compliance or protocol director 
decision the subject will have the option to withdraw the data. 

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3.1 
Study Outcome Evaluations 
3.1.1 Study endpoints 
Our primary endpoint will be the acquisition of sufficient data to establish integrity and 
reliability of EYE-SYNC data and to compare and characterize trajectories of EYE- 
SYNC measurements in injured versus non-injured athletes. 
Our secondary endpoint will be to characterize interrelationships among variables 
relevant to concussion including DEM, ANAM-SRT, and SCAT-3 scores with EYE- 
SYNC. 
If subjects are withdrawn from the study due to non-compliance or Protocol Director 
decision the subject will have the option to withdraw the data as described above. 
3.1.2 Planned Data Analysis and Sample Size Determination 
Descriptive Statistics: We will provide descriptive statistics for all subjects included in 
our study. Specifically, for continuous variables such as age, and scores from DEM, 
ANAM-SRT, SCAT-3, and EYE-SYNC, we will provide means, medians, standard 
deviations and interquartile ranges. For categorical variables such as race, ethnicity and 
previous history of injury, we will present frequency distributions. We will utilize 
graphical tools such as histograms and box plots to describe distributions of continuous 
variables. If needed to adhere to modeling assumptions, we may consider 
transformations of outcomes, such as a log transformation. 
 
Handling of Missing Data: We anticipate minimal missing data in this study. We expect 
that a small proportion of subjects recruited for the longitudinal study (1%) will not 
complete all visits. We will fully describe missing data for each variable and any 
pertinent patterns of missingness (e.g., how missingness is related to specific baseline 
measurements or time, if at all). The statistical methods we propose are particularly 
flexible for missing data and allow for systematic missingness that is related to observed 
features. 
 
Statistical Tools for Each Aim: Our first aim addresses the integrity of data generated by 
EYE-SYNC. Specifically, in Aim 1A, we will characterize the feasibility of collecting 
and generating data in real-time as injuries occur by considering the proportion of time 
we are able to collect 3 subsequent measures using EYE-SYNC on the sideline in the 
field from a case using data from cases included in Cohort 2 (described above).  We 
deem EYE-SYNC to be a promising tool to be used on the field if we are able to make 
use of it 90% of the time. This will be tested using a one-sided exact binomial test. With 
50 cases, we have excellent power to evaluate feasibility. More specifically if we use a 
decision rule such that we conclude EYE-SYNC to be a promising and practical tool to 
be used in the field if we have complete information on 40 of the 50 cases, we have over 
95% power when the true rate of complete data is 90% with a type I error of 0.04 under 
the null hypothesis that an unacceptable rate of complete data is 70%. 

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The goal of Aim 2 is to assess whether data from EYE-SYNC correlates with clinically 
meaningful endpoints. To that end, we will create Cohort 2 by collecting data (in 
replicates of 3) Immediately Post Impact, 2 days from injury, 7 days from injury and 14 
days from injury from 50 cases (defined as those who experience impact where 
concussion is highly suspected) and 50 matched controls (a teammate who did not 
experience impact but who was participating in the same sport and session along with the 
injured teammate at the time of injury). Using mixed effects regression techniques, we 
will examine whether the trajectory of EYE-SYNC changes over time for those injured 
differs significantly from those who were not injured. In addition, we will characterize 
trajectories of change in EYE-SYNC over time for those injured and for athletes who are 
injury free. Such models account for the correlation of scores within a subject over time 
as well as for the matched pairing of cases and their corresponding teammates. In 
addition, such models are robust to assumptions regarding missing data. 
The goal of Aim 3 is to describe interrelationships among relevant variables used to 
describe concussion and EYE-SYNC. This aim is fairly exploratory but will pave the 
way for future studies. We will rely on mixed effects techniques to characterize 
relationships of interest 
3.1.3 Data and Safety Monitoring and Training 
The research team will consist of investigators and research assistants familiar with the 
administration of EYE-SYNC goggles, desktop eye-tracking, and ANAM-SRT. 
Appropriate personnel will undergo extensive training in the administration of 
Developmental Eye Movement Test (DEM) and SCAT3 to establish high inter-rater 
reliability. Additionally, the Stanford will provide Academic Research Organization 
services (coordination and monitoring), data management and statistical analysis. 
 
3.0 
RISK ANALYSIS 
3.1 
Anticipated risks 
All of the research procedures are minimal risk and non-invasive. This is not a treatment 
study and no alternative procedures or courses of treatment are available. The only 
alternative for subjects is to not participate. No standard treatment will be withheld. 
However, all research is subject to some minimal risk and may include: 
 
1) Some of the interviews/questionnaires will ask personal information. All personal 
information is treated as confidential and will be de-identified. 
 
2) Subjects may experience some fatigue as a result of participating in some of the 
cognitive tests. The amount of fatigue may be similar to, i.e. studying for an 
exam, or attending a class. 
 
3) Subjects may experience some watering of the eyes from keeping their eyes open 
during administration of the EYE-SYNC test. Blinking can relieve this. 

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4) It may be inconvenient for subjects to travel to scheduled appointments, when 
travel is necessary. 
 
5) There may be risks or discomforts related to study procedures that are not 
currently foreseeable. 
 
3.2 
Adverse event reporting 
3.2.1 Adverse event definitions 
Unanticipated adverse device event (UADE): Any serious adverse event on health or 
safety or any life-threatening problem or death caused by, or associated with, a device, or 
any other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects. 
Associated with the investigational device: There is a reasonable possibility that the 
adverse event may have been caused by the investigational device. 
Life-threatening adverse event: Any adverse event that places the subject, in the view 
of either the investigator or the sponsor, at immediate risk of death from the event as it 
occurred. It does not include a reaction that, had it occurred in a more severe form, 
might have caused death. 
Serious adverse event: An adverse event is considered “serious” if, in the view of either 
the investigator or the sponsor, it results in any of the following outcomes: 
 death 
 a life-threatening AE 
 inpatient hospitalization or prolongation of existing hospitalization 
 a persistent or significant disability/incapacity 
 a congenital anomaly/birth defect. 
Unanticipated adverse event: Any adverse event, the nature, specificity, severity, or 
frequency of which is not consistent with the risk information in the clinical study 
protocol. 
3.2.2 Recording and assessment of adverse events 
All observed or volunteered adverse events (serious or non-serious) regardless of 
treatment group (Control or Concussed), if applicable, or suspected causal relationship to 
the investigational device or, if applicable, other study related procedure will be recorded 
in the subjects’ case histories. For all adverse events, sufficient information will be 
pursued and/or obtained so as to permit 1) an adequate determination of the outcome of 
the event (i.e., whether the event should be classified as a serious adverse event) and; 2) 
an assessment of the casual relationship between the adverse event and the investigational 
device or, if applicable, the other study treatment or diagnostic product(s). 
Adverse events felt to be associated with the investigational device or, if applicable, other 
study treatment or diagnostic product(s) will be followed until the event (or its sequelae) 
resolves or stabilizes at a level acceptable to the sponsor. 

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3.2.3 Causality and severity assessment 
The sponsor will promptly review documented adverse events and abnormal test findings 
to determine 1) if there is a reasonable possibility that the adverse event was caused by 
the investigational device or other study treatments; and 2) if the adverse event meets the 
criteria for a serious adverse event. 
If the sponsor’s final determination of causality is “unknown and of questionable 
relationship to the investigational device or other study treatments,” the adverse event 
will be classified as associated with the use of the investigational device or other study 
treatments for reporting purposes. If the sponsor’s final determination of causality is 
“unknown but not related to the investigational device or other study treatments,” this 
determination and the rationale for the determination will be documented in the 
respective subject’s case history. 
3.2.4 Reporting adverse events to the FDA 
For any observed or volunteered adverse event that is determined to be a UADE, the 
sponsor will submit an expedited safety report to the FDA’s Center for Devices and 
Radiological Health.  The expedited safety report will consist of: 
 a completed Form FDA 3500A 
 a cover letter analyzing the significance of the event 
A copy of this safety report will be provided to all participating study investigators. 
The completed Form FDA 3500A and cover letter will be submitted to the FDA as soon 
as possible and, in no event, later than 10 working days after the sponsor first receives 
notice of the adverse event. 
If, following receipt and investigation of follow-up information regarding an adverse 
event that was previously determined not to be a UADE, the sponsor determines that the 
event does meet the requirements for expedited reporting, the sponsor will submit a 
completed Form FDA 3500A and cover letter as soon as possible, but in no event later 
than 10 working days, after the determination is made. 
Subsequent to the initial submission of a completed FDA Form 3500A, the sponsor will 
submit additional information concerning the reported adverse event as requested by the 
FDA. 
3.2.5 Reporting adverse events to the responsible IRB 
For any adverse event determined to be a UADE, the sponsor will submit the completed 
Form FDA 3500A and cover letter to the IRB as soon as possible and, in no event, later 
than 10 working days after the sponsor first receives notice of the adverse event. 
Follow-up information to reported adverse events will be submitted to the IRB as soon as 
the relevant information is available. 
3.3 
Withdrawal of subjects due to adverse events 
If a subject is withdrawn from continued exposure to the investigational device or, if 
applicable, other study treatment or diagnostic product(s) due to an observed or 
volunteered adverse event, appropriate reports will be filed with the FDA and IRB, the 
subject’s withdrawal will not affect his/her ability to receive future medical care, and the 
subject will not lose any benefits to which he/she would otherwise be entitled. 

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SYNC
 
Adverse events or abnormal test findings felt to be associated with the investigational 
device or, if applicable, other study treatment or diagnostic product(s) will be followed 
until the adverse event (or its sequelae) or the abnormal test finding resolves or stabilizes 
at a level acceptable to the sponsor. 
The subject may ask to have their data withdrawn from the study database. The subject 
has the right to refuse to allow his/her data to be studied now or saved for future study. 
 
4.0 
DESCRIPTION OF THE INVESTIGATIONAL DEVICE 
The EYE- 
® portable assessment system consists of two primary components 
enclosed in a portable aluminum case. The eye tracker is a handheld isolated display 
environment with embedded eye tracking sensors. The eye tracker is connected to a high- 
performance Windows tablet though a customized docking station. Included accessories 
with EYE-SYNC are a U.S. tablet power supply adapter and disposable sanitary masks. 
Subjects are asked to follow a dot as it moves on the screen. 
 
5.0 
MONITORING PROCEDURES 
Monitoring of the study for compliance with the clinical protocol will be conducted 
periodically (at a minimum, annually) by qualified staff of the Stanford Concussion and 
Brain Performance Center. The address of the Stanford Concussion and Brain 
Performance Center is listed below. 
Stanford Concussion and Brain Performance Center 
1050 Arastradero Road, Suite A233 
Palo Alto, CA 94304 
Phone: +1.650.497.7045 
Fax: +1.650.498.2566 
 
The sponsor\ and the collaborating institution study sites will permit direct access of the 
study monitors and appropriate regulatory authorities to the study data and to the 
corresponding source data and documents to verify the accuracy of this data. 
 
6.0 
INFORMED CONSENT 
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH 
GCP, US Code of Federal Regulations for Protection of Human Subjects (21 CFR 
50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), the Health Insurance Portability 
and Accountability Act (HIPAA, if applicable), and local regulations. 
The Sponsor will prepare the informed consent form (ICF) and HIPAA authorizations 
based on samples attached, and provide the documents to their local IRB or Central IRB 
for approval. The written consent document will embody the elements of informed 
consent as described in the International Conference on Harmonization and will also 
comply with local regulations. The Sponsor will retain an IRB-approved copy of the ICF 
in the study master file. A copy of he approved ICF and HIPAA will be submitted to 
Stanford. 
A properly executed, written, informed consent will be obtained from each subject prior 
to entering the subject into the trial. Information should be given in both oral and written 
form and subjects must be given ample opportunity to inquire about details of the study. 

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A copy of the signed consent form will be given to the subject and the original will be 
maintained with the subject’s records. 
 
7.0 
IRB INFORMATION 
The protocol and consent form will be reviewed and approved by the IRB of each 
participating center prior to study initiation. UADEs will be reported to the IRB in 
accordance with the standard operating procedures and policies of the IRB, and the 
Investigator will keep the IRB informed as to the progress of the study. The Investigator 
will obtain assurance of IRB compliance with regulations. 
Any documents that the IRB may need to fulfill its responsibilities (such as protocol, 
protocol amendments, consent forms, information concerning patient recruitment, 
payment or compensation procedures, or other pertinent information) will be submitted to 
the IRB.  The IRB’s written unconditional approval of the study protocol and the 
informed consent form will be in the possession of the Investigator before the study is 
initiated. The IRB’s unconditional approval statement will be transmitted by the 
Investigator to the Stanford Concussion and Brain Performance Center prior to the site 
initiation visit. This approval must refer to the study by exact protocol title and number 
and should identify the documents reviewed and the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without 
prior written IRB approval except when necessary to eliminate immediate hazards to the 
patients or when the change(s) involves only logistical or administrative aspects of the 
study. Such modifications will be submitted to the IRB and written verification that the 
modification was submitted and subsequently approved should be obtained. 
The IRB must be informed of revisions to other documents originally submitted for 
review; new information that may affect adversely the safety of the patients of the 
conduct of the study; an annual update and/or request for re-approval; and when the study 
has been completed. 
 
8.0 
ADDITIONAL RECORDS AND REPORTS 
8.1 
Data handling and record-keeping 
A Case Report Form will be completed for each subject enrolled into the study. The site- 
investigator will review, approve and sign/date the completed CRF; the sponsor’s 
signature serving as attestation of the sponsor’s responsibility for ensuring that all data 
entered on the CRF are complete, accurate and authentic. 
Source Data are the clinical findings and observations and test data, and other 
information contained in Source Documents. Source Documents are the original records 
(and certified copies of original records); including, but not limited to, hospital medical 
records, physician or office charts, physician or nursing notes, subject diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, x-rays, etc. When applicable, information recorded on the CRF shall match 
the Source Data recorded on the Source Documents. 
8.2 
Record maintenance and retention 
The sponsor will maintain records to include: 

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 
Any FDA correspondence (e.g., Form FDA 3500A, notice of device recall or 
disposition, and failure to obtain informed consent reports) 
 
IRB correspondence (including approval notifications) related to the clinical 
protocol; including copies of adverse event reports and annual or interim reports. 
 
Current and past versions of the IRB-approved clinical protocol and corresponding 
IRB-approved consent form(s) and, if applicable, subject recruitment 
advertisements 
 
Signed Investigator’s Agreements 
 
Curriculum vitae (all research staff at site) 
 
Certificates of required training (e.g., human subject protections, Good Clinical 
Practice, etc.) for sponsor and listed sub-investigators and staff 
 
Normal value(s)/range(s) for medical/laboratory/technical procedures or tests 
included in the clinical protocol 
 
Instructions for on-site preparation and handling of the investigational device and 
other study-related materials 
 
Signed informed consent forms 
 
Completed Case Report Forms 
 
Source Documents or certified copies of Source Documents 
 
Monitoring visit reports 
 
Copies of sponsor correspondence to sub-investigators, including notifications of 
adverse event information 
 
Subject screening and enrollment logs 
 
Subject identification code list 
 
Investigational device accountability records 
 
Interim data analysis report(s) 
 
Final clinical study report. 
All subject-specific data and Case Report Forms (CRFs) will be coded with a non- 
identifiable subject number, and the subject identification code list, will be stored so as to 
protect the subjects’ confidentiality. Specifically, each subject is assigned an ID number 
that is kept separate from the subject's personal health information (PHI). Subject names 
or other directly identifiable information will not appear on any reports, publications, or 
other disclosures of clinical study outcomes. 
 
Confidentiality of all subject-specific data and CRFs will be maintained by using only 
computers for data storage that are password protected and accessible only to study 
personnel; anonymizing all data if used for publishing the results of the study; keeping all 
data storage media, like CDs, memory sticks, and printouts within locked areas. Only the 
study personnel will have access to any data being stored. Electronic files are protected 
using password protection and paper records in locked rooms. The Principal Investigator 
may share the results of these studies with the subjects and/or their caring physician if 
clinically warranted and authorized. 

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The Sponsor will retain the specified records and reports for a minimum of three years 
past the completion of the research.