Computer-based Social Skills Training for Autism Spectrum Disorder
Phase: NA
Conditions: Autism Spectrum Disorder
Sponsor: BioStream Technologies, LLC

ClinicalTrials.gov 
Document Submission Cover Page 
 
 
Official Title of Study: Computer-based Social Skills Training for Autism Spectrum 
Disorder 
 
NCT Number of Study: NCT03672344 
 
Unique Protocol ID: 08012018A 
 
Document Title: Study Protocol (including Statistical Analysis Plan) 
 
Last Amended: May 7, 2019 
 
Study Sponsor: BioStream Technologies, LLC 
 
Note: Supplement to Statistical Analysis Plan Attached as Separate Document 

CONFIDENTIAL 
BIOSTREAM TECHNOLOGIES, LLC 
 Title: 
Computer-based social skills training for autism spectrum disorder 
Short Title 
Computer-based social skills training 
Device Name: 
BioStream Computer-Based Social Skills Training 
eIRB Number: 
 
Protocol 
Number: 
08012018A 
Protocol Date: 
8/6/18 
Amendment 1 Date: 10/16/18 
Amendment 3 Date: 4/29/19 
Amendment 2 Date:11/4/18 
Amendment 4 Date: 5/7/19 
Sponsor 
BioStream Technologies, LLC 
1700 Market Street, Suite 1005 
Philadelphia, PA 19103 
Sponsor Principal Investigator: Dr. Mary Jane Weiss 
 
Multi-Site Study  
 
 
 

 
 
 
 
 
 
 
 
 
 
ii
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................................ II 
ABBREVIATIONS AND DEFINITIONS OF TERMS............................................................................. IV 
ABSTRACT ................................................................................................................................................ V 
PROTOCOL SYNOPSIS ............................................................................................................................. 1 
TABLE 1: SCHEDULE OF STUDY PROCEDURES  (INITIAL SCREENING)...................................... 5 
TABLE 2: PHASE I SCHEDULE OF STUDY PROCEDURES  (HOME, SCHOOL, THERAPY 
CENTER, OR RESEARCH ORGANIZATION) ........................................................................................ 5 
TABLE 3: PHASE II SCHEDULE OF STUDY PROCEDURES ............................................................... 6 
(HOME, SCHOOL, THERAPY CENTER, OR RESEARCH ORGANIZATION) ................................... 6 
1 
BACKGROUND INFORMATION AND RATIONALE .................................................................... 7 
1.1 
INTRODUCTION .............................................................................................................................. 7 
1.2 
NAME AND DESCRIPTION OF INVESTIGATIONAL PRODUCT OR INTERVENTION ................................... 8 
1.3 
GAMEPLAY FREQUENCY ............................................................................................................... 11 
1.4 
RELEVANT LITERATURE AND DATA .............................................................................................. 11 
1.5 
COMPLIANCE STATEMENT ............................................................................................................ 15 
2 
STUDY OBJECTIVES ...................................................................................................................... 15 
2.1 
PRIMARY OBJECTIVE (OR AIM) ..................................................................................................... 15 
2.2 
SECONDARY OBJECTIVES (OR AIM) ............................................................................................... 16 
3 
INVESTIGATIONAL PLAN ............................................................................................................ 16 
3.1 
GENERAL SCHEMA OF STUDY DESIGN ........................................................................................... 16 
3.1.1 
Initial Screening ...................................................................................................................... 16 
3.1.2 
Phase I Visit 1 ......................................................................................................................... 17 
3.1.3 
BioStream Training Group ...................................................................................................... 17 
3.2 
ALLOCATION TO TREATMENT GROUPS AND BLINDING................................................................... 17 
3.3 
STUDY DURATION, ENROLLMENT AND NUMBER OF SITES .............................................................. 17 
3.3.1 
Duration of Study Participation ............................................................................................... 17 
3.3.2 
Total Number of Study Sites/Total Number of Subjects Projected ............................................. 18 
3.3.3 
Offer of Free BioStream Training and Follow-up Study to Control Group ................................ 18 
3.4 
STUDY POPULATION ..................................................................................................................... 18 
3.4.1 
Inclusion Criteria .................................................................................................................... 18 
3.4.2 
Exclusion Criteria ................................................................................................................... 19 
4 
STUDY PROCEDURES .................................................................................................................... 19 
4.1 
INITIAL SCREENING ...................................................................................................................... 19 
4.2 
IN-PERSON STUDY VISITS ............................................................................................................. 19 
4.3 
SUBJECT COMPLETION/WITHDRAWAL .......................................................................................... 20 
4.3.1 
Early Termination Study Visit .................................................................................................. 21 
5 
STUDY EVALUATIONS AND MEASUREMENTS ........................................................................ 21 
5.1 
SCREENING AND MONITORING EVALUATIONS AND MEASUREMENTS .............................................. 21 
5.1.1 
Initial Screening Interview ....................................................................................................... 21 
5.1.2 
ASD/ADHD Diagnosis Verification ......................................................................................... 21 
5.1.3 
Medication List ....................................................................................................................... 21 
5.1.4 
Video Game Interview Form (Parent-Report) .......................................................................... 21 
5.2 
EFFICACY EVALUATIONS .............................................................................................................. 21 
5.2.1 
Primary Endpoints .................................................................................................................. 21 
5.2.2 
Secondary Endpoints ............................................................................................................... 22 

 
 
 
 
 
 
 
 
 
 
iii
5.3 
BIOSENSOR DATA COLLECTION .................................................................................................... 22 
5.4 
SUBJECT AND PARENT INTERVIEWS .............................................................................................. 22 
5.4.1 
Subject Interviews/Surveys....................................................................................................... 22 
5.4.2 
Parent/Teacher/Therapist Interviews/Surveys and Equipment Handoff/Return .......................... 22 
STATISTICAL CONSIDERATIONS ....................................................................................................... 23 
5.5 
PRIMARY ENDPOINT ..................................................................................................................... 23 
5.6 
SECONDARY ENDPOINTS .............................................................................................................. 23 
5.7 
STATISTICAL METHODS ................................................................................................................ 23 
5.7.1 
Baseline Data .......................................................................................................................... 23 
5.7.2 
Efficacy Analysis ..................................................................................................................... 23 
5.7.3 
Safety Analysis ........................................................................................................................ 24 
5.8 
SAMPLE SIZE................................................................................................................................ 24 
5.9 
INTERIM ANALYSIS ...................................................................................................................... 24 
6 
SAFETY MANAGEMENT & REPORTING ................................................................................... 24 
6.1 
CLINICAL ADVERSE EVENTS ......................................................................................................... 24 
6.2 
ADVERSE EVENT REPORTING........................................................................................................ 24 
7 
STUDY ADMINISTRATION ........................................................................................................... 25 
7.1 
TREATMENT ASSIGNMENT METHODS ............................................................................................ 25 
7.1.1 
Randomization ........................................................................................................................ 25 
7.2 
DATA COLLECTION AND MANAGEMENT........................................................................................ 25 
7.3 
CONFIDENTIALITY ........................................................................................................................ 25 
7.4 
REGULATORY AND ETHICAL CONSIDERATIONS ............................................................................. 25 
7.4.1 
Data and Safety Monitoring Plan............................................................................................. 25 
7.4.2 
Risk Assessment....................................................................................................................... 25 
7.4.3 
Potential Benefits of Trial Participation ................................................................................... 26 
7.4.4 
Risk-Benefit Assessment........................................................................................................... 26 
7.5 
RECRUITMENT STRATEGY ............................................................................................................ 26 
7.6 
INFORMED CONSENT/ASSENT AND HIPAA AUTHORIZATION ......................................................... 27 
7.6.1 
Waiver of Assent ...................................................................................................................... 28 
7.7 
PAYMENT TO SUBJECTS/FAMILIES ................................................................................................ 28 
7.7.1 
Compensation ......................................................................................................................... 28 
8 
PUBLICATION ................................................................................................................................. 28 
9 
REFERENCES .................................................................................................................................. 28 
 

 
 
 
 
 
 
 
 
 
 
iv
ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADHD 
Attention Deficit/Hyperactivity Disorder 
AE 
Adverse event 
ASD 
Autism Spectrum Disorder 
BioStream 
BioStream Technologies, LLC 
BioStream Training 
BioStream Computer-Based Social Skills Training 
CAR 
Center for Autism Research 
CHOP 
The Children’s Hospital of Philadelphia 
C-JARS 
Childhood Joint Attention Rating Scale 
DAS-II 
Differential Ability Scales, 2nd Edition 
EOWPVT 
Expressive One-Word Picture Vocabulary Test, 4th 
Edition 
GLM 
General Linear Model 
IRB 
Institutional Review Board 
PI 
Principal Investigator 
PPVT 
Peabody Picture Vocabulary Test, 4th Edition  
SRS 
Social Responsiveness Scale 
Subject Computer Setup 
Laptop computer with integrated use of a consumer 
grade eye tracker connected to it via a USB connection 
SAE 
Serious Adverse Event 
TDC 
Typically Developing Children 
TOVA 
Test of Variables of Attention 

 
 
 
 
 
 
 
 
 
 
v
ABSTRACT 
Background: 
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized in part by 
difficulty in social interaction and communication [1], which can affect individuals’ 
employability, educational achievement, and quality of interpersonal relationships [2-4].  
Existing therapies targeting the deficits of the school-age population with ASD require 
significant therapist or educator time and are thus very costly, with estimates of the 
economic impact of caring for children with ASD ranging from ~$12B [5] to $61B annually 
[6]. Given this, as well as the fact that ASD affects 1 in 59 children in the United States [7], 
with identified prevalence rising [5], there is a pressing need for cost-effective, evidence-
based interventions to support the ASD community, and BioStream Technologies, LLC 
(BioStream), in collaboration with the Center for Autism Research (CAR) at the Children’s 
Hospital of Philadelphia (CHOP), has developed one such intervention: the BioStream 
Computer-Based Social Skills Training (BioStream Training). The intervention to be used in 
this protocol has been piloted at CHOP as part of an existing IRB protocol (eIRB #15-
12594). As part of that protocol, we have run 32 children (18 with ASD and 14 TDC) 
through procedures that to some degree are overlapping with the present protocol (up to 5 
study sessions of gameplay per subject).  
Primary and Secondary Aims:  
The objective of this study is to evaluate changes in subject performance on social skills 
assessments after engaging in BioStream Training, as compared to a group of subjects who 
were trained with an alternate control game, and to evaluate possible correlations in changes 
in social skills assessments with changes in subject gameplay performance. 
Study Design:  
This is a comparison group study during which subjects will engage with BioStream 
Training in a home, school, therapy center, or research organization setting and participate 
in social skills assessments, or will be exposed to an alternate computer video game in a 
home, school, therapy center, or research organization setting instead of the BioStream 
Training. 
Setting/Participants: 
All participants will participate in the study either in a home, school, therapy center, or 
research organization setting. The study will involve 150 subjects aged 4-14 with ASD. 
Study Interventions and Measures:  
BioStream Training is computer-based social skills training that includes interactive game-
like applications involving images, video, audio, and animation (e.g. animated characters). 
The main study outcome measures include both standard and experimental social skills 
assessments (e.g. a dyadic interaction task with a member of the study team). 

 
 
 
 
 
 
1 
PROTOCOL SYNOPSIS 
Study Title 
Computer-based social skills training for autism spectrum disorder 
Funder 
BioStream Technologies, LLC 
Clinical Phase 
N/A 
Study Rationale 
Autism spectrum disorder (ASD) is a neurodevelopmental disorder 
characterized in part by difficulty in social interaction and 
communication, which can affect individuals’ employability, 
educational achievement, and quality of interpersonal relationships. 
Existing therapies targeting the deficits of the school-age population 
with ASD require significant therapist or educator time and are thus 
very costly. Given this, as well as the fact that ASD affects 1 in 59 
children in the United States according to the Center for Disease 
Control, there is a pressing need for cost-effective, evidence-based 
interventions to support the ASD community, and BioStream 
Technologies, LLC (BioStream), in collaboration with the Center 
for Autism Research (CAR) at the Children’s Hospital of 
Philadelphia (CHOP), has developed one such intervention: the 
BioStream Computer-Based Social Skills Training (BioStream 
Training). 
Study Objective(s) 
Primary  
To evaluate changes in subject performance on various social skills 
assessments (including eye-tracking, dyadic interaction, SRS, 
Ekman 60 Faces Test) after engaging in BioStream Training, 
including in comparison to an alternate game. 
Secondary 
To observe changes in subject gaze patterns during social skills 
assessments after engaging in BioStream Training, including in 
comparison to an alternate game. 
To observe possible correlations in changes in social skills 
assessments with changes in subject gameplay performance. 
Test Article(s) 
(If Applicable) 
BioStream Training is computer-based social skills training that 
includes interactive game-like applications involving images, video, 
audio, and animation (e.g. animated characters). 
Study Design 
Comparison Group 
Subject Population 
key criteria for 
Inclusion and 
Exclusion: 
Inclusion Criteria 
1. Ages 4-14. 
2. Meets diagnostic criteria for ASD. 
3. Estimated intelligence standard score of at least 40 (can be 
substituted for a receptive language score such as PPVT or use 

 
 
 
 
 
 
2 
of the Differential Ability Scales, 2nd Edition (DAS-II)). 
4. Parent reports difficulty with at least one of two social skills (via 
modified questions from the Social Responsiveness Scale) 
5. English as the child’s primary/first language (key measures used 
in the study do not have alternate language versions). 
6. Attains a score equal to or less than 75% correct on the Ekman 
60 Faces Test. 
7. The parent who completes the questionnaires needs to be 
proficient in English. 
8. Has successfully played a video game using a Microsoft Xbox 
game controller, Sony PlayStation game controller, or other 
comparable game controller. 
9. Parental/guardian permission (informed consent) and if 
appropriate, child assent. 
10. Wi-Fi internet connection at subject’s home/school/therapy 
center/research organization available for use by study laptop 
computer. 
 
Exclusion Criteria 
1. History of seizures. 
2. History of traumatic brain injury or other significant medical or 
neurological abnormality affecting motor or higher cortical 
functioning. 
3. Certain visual, auditory, DSM 5, or conduct disorders (see   
below). 
4. A visual disorder that cannot be corrected through the use of 
corrective lenses to a level of 20-40 in both eyes. 
5. Use of corrective visual lenses that would significantly impede 
the valid collection of visual attention and gaze pattern data 
during dyadic interaction tasks. 
6. Auditory impairment (that cannot be corrected by a hearing aid) 
that would significantly impede the valid collection of test 
measures. 
7. Profound intellectual disability or sensory-motor difficulties that 
would preclude valid use of diagnostic instruments and/or use of 
a computer or mobile computing device. 
8. A DSM 5 disorder or other psychiatric symptoms that would 
interfere with the participant’s ability to participate in the study 
(e.g., active psychosis), per parent report. 
9. History of one or more psychiatric hospitalizations. 
10. Presence of significant symptoms of a conduct disorder. 

 
 
 
 
 
 
3 
Number Of Subjects 
 
150 subjects with subject participation at home, school, therapy 
center, or research organization. 
Study Duration 
The study is comprised of two phases. For Phase I, each subject’s 
participation in BioStream Training or the alternate game will last 
for up to 6.67 to 33.33 hours over a 28-day period (up to 20 game 
play sessions, up to 5 days per week for between 20 minutes and 
100 minutes per training session or alternate game session) plus 
approximately 8 hours of assessment and other study related 
activities. Each parent’s participation will last for approximately 
4.25 total hours over the 28 day period excluding time spent for 
oversight of the subject during the BioStream Training or during 
play of the alternate game.  
For Phase II, each subject’s participation in BioStream Training or 
the alternate game will last for up to 6.67 to 33.33 hours over a 28 
day period (up to 20 game play sessions, up to 5 days per week for 
between 20 minutes and 100 minutes per training session or 
alternate game session) plus about 5 hours of assessment and other 
study related activities. Each parent’s participation will last for 
about 2.5 total hours over the 28 day period excluding time spent 
for oversight of the subject during the BioStream Training or during 
play of the alternate game. It is not required that Phase II begin 
immediately upon completion of Phase I. 
Study Phases 
Phase I 
 Initial Screening 
 Visit  1 – Informed Consent, Ekman 60 Faces Test, PPVT  
 Visit 2 – Assessments and Surveys (Baseline) 
 Week 1 (following Visit 2) – Gameplay – daily transmission of 
game data 
 Week 1 – Survey – data transmission 
 Visit  3 – Assessments and Surveys 
 Week 2 – Gameplay – daily transmission of game data 
 Week 2 – Survey – data transmission 
 Visit  4 – Assessments and Surveys 
 Week 3 – Gameplay – daily transmission of game data 
 Week 3 – Survey – data transmission 
 Visit  5 – Assessments and Surveys 
 Week 4 – Gameplay– daily transmission of game data 
 Week 4 – Survey – data transmission 
 Visit  6 – Assessments and Surveys 
(Note: Phase II may not begin immediately following phase I) 
Phase II 
 Week 1 – Gameplay – daily transmission of game data 
 Week 1 – Survey – data transmission 
 Visit  1 – Assessments and Surveys 

 
 
 
 
 
 
4 
 Week 2 – Gameplay – daily transmission of game data 
 Week 2 – Survey – data transmission 
 Visit  2 – Assessments and Surveys 
 Week 3 – Gameplay – daily transmission of game data 
 Week 3 – Survey – data transmission 
 Visit  3 – Assessments and Surveys 
 Week 4 – Gameplay– daily transmission of game data 
 Week 4 – Survey – data transmission 
 Visit  4 – Assessments and Surveys 
Efficacy Evaluations 
The primary efficacy endpoints will be: 
The mean change from baseline score on the following assessments 
based on post-final game play session assessment compared to the 
alternate game group: 
a. Subject gaze patterns as measured by video eye tracking 
assessment. 
b. Subject gaze patterns as measured by the dyadic 
interaction task. 
c. Mean change in baseline score on the Ekman 60 Faces 
Test. 
d. Mean change in baseline score on the TOVA. 
e. Mean change in baseline score on the SRS. 
Secondary endpoints: 
The mean change from baseline score on the following assessments 
based on post-final game play session assessment compared to the 
alternate game group: 
a. Subject gaze patterns as measured on the videos of 
emotional expression assessment. 
b.   Subject responses to the CJARS survey. 
Pharmacokinetic 
Evaluations 
N/A 
Safety Evaluations 
Subjects will always be supervised by a parent, teacher, or therapist 
(therapist includes Registered Behavior Technicians, assistant 
speech pathologists, assistant behavior analysts (BCABA), and 
teaching assistants) during use of the BioStream training and 
alternative game. Clinical adverse events (AEs) will be monitored 
throughout the study through parent reporting in the case of at home 
use and through teacher reporting in the case of in school use. Since 
the study procedures are not greater than minimal risk, AEs are not 
expected. 
   Statistical And                
Analytic Plan 
Paired-sample t-tests will be used to measure changes from baseline 
within each group, and independent sample t-tests will be used to 
measure changes from baseline relative to the alternate game group 
for all endpoints.  

 
 
 
 
 
 
5 
For all endpoints, we will determine whether there were observable 
changes in scores from baseline or relative to the alternate game 
group and whether these changes are statistically significant. 
Significance will be set at p<0.05 Multiplicity of primary endpoints 
will be managed via statistical corrections. 
DATA AND SAFETY 
MONITORING PLAN 
The PI will periodically review the data collection and storage 
practices associated with this study and determine whether changes 
to enhance confidentiality and privacy are required. The PI will 
frequently monitor the quality control of the data with staff and 
research assistants. 
All written or electronic forms (except Informed Consent Forms and 
Assent Forms) will employ a unique alphanumeric identifier; in no 
case will the participant's name or other identifying information 
appear on these forms. The user ID for the BioStream Training and 
alternate game shall use the same unique alphanumeric identifier. 
The study team will accomplish this on all parent/guardian or 
teacher  or therapist questionnaires (as applicable) which have lines 
for child and parent name by applying a label with unique 
alphanumeric identifier and instructing parents/guardians or teacher 
or therapists to use generic labels (e.g., biological mother) rather 
than writing their names. The PI will keep a master list containing 
PHI and subject ID number separate from coded data forms, which 
will be maintained in a locked file drawer, cabinet, or lock box in 
the PI’s office. Only the PI will have access to this location. The 
master list will be maintained on a separate password-protected 
computer and be stored in an encrypted password protected file. 
Video recordings will stored on password-protected and/or 
encrypted data storage devices including computers, external hard 
drives, and/or flash drives only accessible by members of the study 
team. 
TABLE 1: SCHEDULE OF STUDY PROCEDURES  
(INITIAL SCREENING) 
 
Estimated time 
Parent or subject? 
Informed Consent 
15 minutes 
Parent 
Review of Inclusion/Exclusion Criteria 
(Initial Screening Interview) 
15 minutes 
Parent 
Video Game Interview Form (Parent-Report) 
15 minutes 
Parent 
TABLE 2: PHASE I SCHEDULE OF STUDY PROCEDURES  
(HOME, SCHOOL, THERAPY CENTER, OR RESEARCH ORGANIZATION) 
 
Estimated time (total 
over all visits) 
Parent or subject? 
Visits applicable 
(Total 6 Visits) 
Informed Consent/Assent 
(if applicable) 
30 minutes 
Parent and subject 
Visit 1 

 
 
 
 
 
 
6 
Peabody Picture 
Vocabulary Test (PPVT) 
20 minutes 
Subject 
Visit 1 
Ekman 60 Faces Test 
10 minutes 
Subject 
Visit 1 
SRS (Parent-Report) 
50 minutes 
Parent 
Visits 2-6 
C-JARS (Parent-Report) 
50 minutes 
Parent 
Visits 2-6 
Dyadic Interaction Task 
50 minutes 
Subject 
Visits 2-6 
Eye Tracking Video 
Assessment 
50 minutes 
Subject 
Visits 2-6 
Ekman 60 Faces Test 
50 minutes 
Subject 
Visits 2-6 
Emotional Expression 
Video Assessment  
50 minutes 
Subject 
Visits 2-6 
TOVA 
109 minutes 
Subject 
Visits 2-6 
Game and equipment 
introduction (if applicable) 
40-60 minutes 
Parent 
Visit 1 
BioStream Training 
6.67-33.33 hours 
Subject 
Over a period of 28 
days following Visit 2 
Weekly 
Parental/Teacher/Therapist 
Survey 
20 minutes 
Parent 
1 survey/per week 
Subject Interview/Survey 
(if applicable) 
40 minutes 
Subject 
Visits 3 - 6 
Parent/Teacher/Therapist  
Interview/Survey (if 
applicable) 
40 minutes 
Parent 
Visits 3 - 6 
Equipment return (if 
applicable) 
5 minutes 
Parent 
Visit 6 
TOTAL 
13.48 hours – 41.15 
hours 
Subject 
 
TOTAL 
~4.25 hours* 
Parent 
*Excludes time spent 
for oversight of 
subject during 
BioStream Training 
 
TABLE 3: PHASE II SCHEDULE OF STUDY PROCEDURES  
(HOME, SCHOOL, THERAPY CENTER, OR RESEARCH ORGANIZATION) 
 
Estimated time (total 
over all visits) 
Parent or subject? 
Visits applicable 
(Total 4 Visits) 
SRS (Parent-Report) 
40 minutes 
Parent 
All Visits 
C-JARS (Parent-Report) 
40 minutes 
Parent 
All Visits 
Dyadic Interaction Task 
40 minutes 
Subject 
All Visits 
Eye Tracking Video 
Assessment 
40 minutes 
Subject 
All Visits 
Ekman 60 Faces Test 
40 minutes 
Subject 
All Visits 
Emotional Expression 
Video Assessment  
40 minutes 
Subject 
All Visits 
TOVA 
87 minutes 
Subject 
All Visits 
BioStream Training 
6.67-33.33 hours 
Subject 
Over a period of 28 

 
 
 
 
 
 
7 
days 
Weekly 
Parental/Teacher/Therapist 
Survey 
20 minutes 
Parent 
1 survey/per week 
Subject Interview/Survey 
(if applicable) 
40 minutes 
Subject 
All Visits 
Parent/Teacher/Therapist 
Interview/Survey (if 
applicable) 
40 minutes 
Parent 
All Visits 
Equipment return (if 
applicable). 
5 minutes 
Parent 
Visit 4 
TOTAL 
11.45 hours – 38.12 
hours 
Subject 
 
TOTAL 
~2.5 hours* 
Parent 
*Excludes time spent 
for oversight of 
subject during 
BioStream Training 
 
1 
BACKGROUND INFORMATION AND RATIONALE 
1.1 Introduction 
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized in part by 
difficulty in social interaction and communication [1], which can affect individuals’ 
employability, educational achievement, and quality of interpersonal relationships [2-4]. 
Existing therapies targeting the deficits of the school-age population with ASD require 
significant therapist or educator time and are thus very costly. Given this, as well as the fact 
that ASD affects 1 in 59 children in the United States according to the Center for Disease 
Control, there is a pressing need for cost-effective, evidence-based interventions to support 
the ASD community. 
BioStream Technologies, LLC (BioStream), in collaboration with the Center for Autism 
Research (CAR) at the Children’s Hospital of Philadelphia (CHOP), has developed one such 
intervention: the BioStream Computer-Based Social Skills Training (BioStream Training). 
The intervention to be used in this protocol has been piloted at CHOP as part of an existing 
IRB protocol (eIRB #15-12594). As part of that protocol, we have run 32 children (18 with 
ASD and 14 TDC) through procedures that to some degree are overlapping with the present 
protocol (up to 5 study sessions of gameplay per subject). 
The primary objective of this study is to evaluate changes in subject performance on social 
skills assessments after engaging in BioStream Training, including in comparison to an 
alternate game. The secondary objective of this study is to evaluate changes in subject gaze 
patterns during social skills assessments after engaging in BioStream Training, including in 
comparison to an alternate game and to evaluate possible correlations in changes in social 
skills assessments with changes in subject gameplay performance. 
Subject computer gameplay data (including game performance, game usage, and eye 
tracking data), certain subject assessment data, and certain subject survey data, may be 

 
 
 
 
 
 
8 
collected and stored using a laptop computer with integrated use of a consumer grade eye 
tracker connected to it via a USB wired connection (Subject Computer). All data collected 
and stored on the Subject Computer will be de-identified data.  
Certain subject assessment and survey data may also be collected manually using a 
handwritten paper-based data collection method and stored digitally through use of digital 
scanning.  
Additionally, subject eye contact video recording data may also be collected using a video 
camera and/or video camera embedded glasses worn by any member of the study team 
during real world dyadic interaction task assessment. This data will not be stored on or 
collected using the Subject Computer. This data will be stored on a separate computer 
and/or computer data storage device maintained by any member of the study team. 
This data may also be sent to HIPAA compliant third parties including therapist 
practitioners or research organizations. These HIPAA compliant third parties, blinded 
to the study group of each subject, will be used to annotate the video recordings of the 
dyadic interaction task assessments including for subject eye contact during the task. 
Certain Parent assessment and survey data may be collected using a computer (excluding 
the Subject Computer except in the case of the Weekly Parental/Teacher/Therapist 
Survey) and/or manually using handwritten paper-based data collection methods. The parent 
or teacher or therapist (as applicable) may complete a Weekly Parental/Teacher/Therapist 
Survey using a form on the Subject Computer. This survey is configured so that only de-
identified data may be included in the survey or associated with the survey. 
1.2 Name and Description of Investigational Product or Intervention 
The study intervention is the BioStream Computer-Based Social Skills Training (BioStream 
Training). BioStream Training is computer-based social skills training that includes 
interactive game-like applications involving images (e.g. photos and/or videos of people 
making different emotional expressions), animation (e.g. animated characters), video (e.g. 
tutorials), and audio (e.g. sound effects). Subjects can interact with portions of BioStream 
Training using an eye tracker (i.e. by using their gaze as a real-time input to the game-like 
applications). 
Computer tasks will involve presenting various stimulus types to the participant. These will 
include action sequences, designed to be very engaging, and social sequences, designed to 
task users with social skills exercises. 
Audiovisual stimuli: The social stimuli will include photographs and videos as well as 
animated characters. Animated social stimuli will include various characters that may 
interact with the user, may present the user with tasks, and may guide the user in tasks. 
Characters may socially interact with the user by eye contact, facial expression, body 
language, and speech. 
The non-social stimuli will include computer graphics of various environments in which the 
user will navigate and interact in different ways including collection of items that the user 
may use in the game-like application segment. Parents/guardians will be given the 

 
 
 
 
 
 
9 
opportunity to see examples of the pictures and graphics that will be shown to their child as 
part of the consent process.  
Computer interaction sessions will take place in the home and/or school environment. 
Subjects will sit facing a computer, tablet, or smartphone screen and be positioned so that 
the eye tracking device can obtain measurements. Subjects may be provided headphones to 
wear during the computer interaction to enable audio listening without disturbing others in 
the home, school, therapy center, or research organization environment. Subjects may be 
provided with a computer mouse, computer keyboard, touchscreen, and/or game controller 
device. Subjects may be presented with multiple action and social sequences. Perspectives in 
the computer application may include first-person and third-person views. An eye tracker 
will record participants’ gaze patterns. Participants’ use of the controls in the game-like 
application—computer mouse, computer keyboard, touchscreen, and/or game controller 
device—will be recorded. All measurements will be taken in real time and may affect the 
stimuli presented. 
Action Sequences: Subjects will view and navigate animated environments on the screen. 
Action sequences may include items that can be obtained and used for special abilities in the 
game environment. Subjects may be instructed to use the controls for abilities including 
turn, run, jump, obtain item, and use item. Any or all behavioral measures will be used to 
determine engagement, including game performance data and attention from eye gaze data. 
Social Sequences: Subjects will be presented with social tasks in the context of gameplay 
which may include normative eye contact, facial emotion recognition, joint attention 
exercises, perspective taking exercises, vocal emotion recognition, and normative internal 
and external emotional response in social interactions. Social sequences may include 
simulated interaction with social stimuli presenting different personality traits such as 
extraversion, caution, and aggression. Social sequences may vary and change based on real-
time behavioral measurements (including eye tracking measurements/data) and may include 
the following examples. Subjects may be encouraged to use appropriate eye contact with 
social stimuli; eye contact will be measured with the eye tracker. Subjects may be prompted 
to identify the emotion presented by social stimuli based on facial expression. Subjects may 
be prompted to identify the emotion presented by social stimuli based on vocal expression. 
Subjects may be instructed to use the controls including the game controller to choose 
responses in recognition tasks. General emotions to recognize may include pleasantness, 
unpleasantness, and neutrality. Specific emotions to recognize may include happiness, 
surprise, sadness, anger, fear, and disgust. 
Data Transfer and Storage: Subject computer gameplay data (including game 
performance, game usage, and eye tracking data), certain subject assessment data, and 
certain subject survey data, may be collected and stored using a laptop computer with 
integrated use of a consumer grade eye tracker connected to it via a USB wired connection 
(Subject Computer). Additionally, the parent, teacher, or therapist (as applicable) may 
complete a Weekly Parental/Teacher/Therapist Survey using a form on the Subject 
Computer. This survey is configured so that only de-identified data may be included in the 
survey or associated with the survey.  All data collected and stored on the Subject 
Computer will be de-identified data. 

 
 
 
 
 
 
10
De-identified study data collected and stored on the Subject Computer may at any time be 
copied (including for backup purposes or remote data analysis purposes) to a computer data 
storage device (including a USB flash drive or external computer hard drive) or to a separate 
computer, by any member of the study team by establishing a wired connection between the 
computer data storage device or separate computer and the Subject Computer (or direct 
connection in the case of a USB Flash Drive) to manually copy the de-identified study data 
from the Subject Computer to such device or computer. This data may at any time be 
transferred by any member of the study team to the Sponsor including for backup and 
analysis purposes to ensure data integrity. 
Additionally, the Subject Computer may be configured to manually enable transmission 
and/or automatically and regularly provide for transmission, of de-identified study data to 
the Sponsor’s computer (including for backup and analysis purposes) using a wireless 
communication link (which may include use the parent/guardian home’s, the school’s, the 
therapy center’s or the research organizations, as applicable, Wi-Fi internet connection) 
between the Subject Computer and the Sponsor’s computer. No subject’s internet protocol 
address (IP Address) will be collected or stored by the Sponsor at any time including as 
a result of this communication link. This de-identified study data may be retransmitted to 
any member of the study team electronically or via access to a password protected web 
interface, for backup purposes, analysis purposes, study monitoring purposes (including in 
the case of the Weekly Parental/Teacher/Therapist Survey), or for use in determining the 
necessity of teacher, therapist, parent and/or subject follow up to prompt subject compliance 
with the study protocol. 
Sponsor may provide a web interface for password protected access by any or select 
members of the study team that shows and/or permits the download of, subject de-identified 
study data using secure channels which may include secure FTP or HTTPS. The Sponsor 
may electronically send to any member of the study team reports containing subject de-
identified study data. The Sponsor may otherwise electronically communicate subject de-
identified study data to any member of the study team. The communication of this de-
identified study data to any member of the study team will facilitate monitoring for 
compliance and data integrity in a real-time fashion.  
Sponsor may notify any member of the study team about any subject ID numbers that failed 
to play the intervention or the alternate game over any 24-hour period. Any member of the 
study team may reach out to subjects and/or parents and teachers or therapists (as 
applicable) to remind them to play (by phone, email, and/or text message). Subjects will also 
have the opportunity to contact any or select members of the study team through phone or 
email if any questions arise.  
The Sponsor may, from time to time, transmit updates to the software installed on the 
Subject Computer using the communication link described above. 
Alternate Comparison Game: 
The BioStream Training is being compared to a modified version of the BioStream Training, 
which will not include the same therapeutic exercises. The game will be played by subjects 
in the non-intervention group for the same length of playing time and at the same frequency, 

 
 
 
 
 
 
11
as the BioStream Training intervention group. It will require a similar game controller 
device as that which is used by the intervention group and will be computer based. The 
Sponsor may also use as the alternate comparison game any video game that is rated E 
(Everyone) by the Entertainment Software Rating Board. 
1.3 Gameplay Frequency 
The study is comprised of two phases.  
For Phase I, each subject’s participation in BioStream Training or play of the alternate game 
will last for up to 6.67 to 33.33 hours over a 28 day period comprised of up to 20 game play 
sessions, up to 5 days per week for between 20 minutes and 100 minutes per game play 
session. The subject will be permitted to complete each daily session through use of the 
BioStream Training or use of the alternate game at different times throughout each day at 
the subject’s discretion. 
For Phase II, each subject’s participation in BioStream Training or play of the alternate 
game will last for up to 6.67 to 33.33 hours over a 28 day period comprised of up to 20 
game play sessions, up to 5 days per week for between 20 minutes and 100 minutes per 
game play session. The subject will be permitted to complete each daily session through use 
of the BioStream Training or use of the alternate game at different times throughout each 
day at the subject’s discretion. 
1.4 Relevant Literature and Data 
BioStream Training builds on prior literature and shows promise because (1) it incorporates 
computer games, a medium shown to be particularly promising for helping children with 
ASD; (2) it leverages educational and behavioral concepts shown to be effective in training 
social skills; and (3) the social skills currently targeted by BioStream Training, eye contact 
and emotion recognition, have been shown to be trainable in ways that lend themselves to 
eye tracking technology. 
(1) Video game format 
Computers have been shown to be promising teaching tools for children with ASD, and 
virtual social interactions are thought to have significant potential for improving their real-
world social skills [8]. Survey data of subjects that have participated in the BioStream 
Training has yielded encouraging data with respect to engagement.   
(2) Educational and behavioral concepts 
BioStream Training leverages the fact that many of the principles shown by research to be 
effective in teaching and shaping behavior, both generally and in the context of specific 
social skills, can be directly incorporated into computer-based training. Such principles, 
including discrete trial training, differential reinforcement, and shaping, are central to 
BioStream Training, and have an established evidence base, maximizing the likelihood that 
it will prove efficacious [8, 9]. 
(3) Social skills targeted, and description of BioStream Training exercises 

 
 
 
 
 
 
12
BioStream Training applies these principles to target social skills including (a) eye contact, 
and (b) emotion recognition. These have been selected because: they are critical social skills 
in which children with ASD underperform their typically developing peers; they have been 
shown to be trainable using methods that can be mimicked in computer-based training [8]; 
and their training can be augmented through the incorporation of gaze control.  
(a) Eye contact is the act of looking at someone’s eyes during a social interaction. It is 
important for conveying attention and for communicating social and emotional information 
[10, 11]. Deficits in eye contact are one of the most notable indicators of ASD [12]. 
Nevertheless, discrete trial-based training of eye contact is effective, with such interventions 
having demonstrated increases in eye contact [12, 13]. BioStream Training includes 
exercises uniquely enabled by gaze control technology that are focused on leveraging these 
established approaches to help children with ASD improve at making eye contact. For 
example, during some discrete trials, a character begins speaking to the player, and the 
player must then look at part of the character’s face (e.g. whole face, upper part of the face, 
eyes) within a certain time increment, for a few seconds, in order to receive a reward. 
(b) Emotion recognition is the ability to identify human emotions, most typically from facial 
expressions, and is a crucial component of social development [14]. A meta-analysis found 
that children with autism underperform their typically developing peers on emotion 
recognition tasks [15]. There is a pressing need to adapt traditional, manual therapeutic 
approaches targeting emotion recognition skills to more standardized, computerized delivery 
platforms. Interventions to date have been effective at driving improvements, some even 
using video game-based training approaches [8, 14, 16]. BioStream Training leverages one 
of the more advanced psychophysical paradigms to come out of the experimental 
psychology literature on face processing: the use of gaze-contingent blurring of facial 
images, often called the “bubble paradigm.” [17, 18] For example, during some exercises, 
the participant interacts with an animated character whose face is fully or partially blurred. 
The player must use their gaze to unblur key facial features in order identify the character’s 
emotion. Then, the player must select the matching emotion from a set of real children’s 
faces. 
Assessments 
Social Responsiveness Scale-Parent (SRS [19]). The SRS is a parent-report questionnaire 
that asks parents to rate the frequency of reciprocal social behaviors, communication, and 
repetitive and stereotypic behaviors in their child. The questionnaire yields a single 
summary score that can be used as an index of the child’s severity of social deficits. This 
will be completed by a parent during each in-person visit or by telephone with a member of 
the study team. 
 
Childhood Joint Attention Rating Scale (C-JARS [20]): This is a parent-report measure of 
joint attention related behaviors in verbal children and adolescents with ASD. This will be 
completed by a parent during each in-person visit or by telephone with a member of the 
study team. 
 
Dyadic Interaction Task: There is a lack of standardized validated reference standards for 
assessing communication-based autism symptoms [21, 22]. Because of this, an exceptionally 

 
 
 
 
 
 
13
large array of assessments is used in the literature. In fact, there are only three standardized 
tools that have been used in more than 2% of recent trials of autism interventions (none of 
which are used in more than 7% of studies) [21]. Therefore, in order to determine how we 
would assess communication skills we worked closely with our team of certified Applied 
Behavioral Analysis (ABA) therapists, who have years of experience working with children 
with ASD, and consulted the literature. The task we have constructed follows the Contextual 
Assessment of Social Skill [23] and procedures developed by Reilly et al [24]. It involves a 
structured play scenario, which is standard in other similar studies [21, 25-28]. 
 
This is an interaction between the subject and a member of the study team where the study 
team member poses questions to the subject while the interaction is video recorded. 
Questions may include but are not limited to the following: 
 
What is your birthday? How old are you? 
What do you like to do at school? What do you like about ____? 
What is your least favorite thing at school? 
What do you like to do at home? 
Do you like any sports such as…”? 
Do you have any favorite movies? What’s [that movie] about? 
What’s your favorite program on TV? What’s [that show] about? 
 
In addition to answering questions, subjects may be asked to respond to certain prompts in 
the context of the dyadic interaction task, sometimes repeatedly. For example, a subject may 
be prompted to request an object from the study team member conducting the interaction, 
return the object, and then request that object again.  
 
Further, a subject may be asked by the study team member questions about an object 
presented. An example of this is a task in which an item is presented to the subject, after 
presentation, the subject is asked if they would like it placed in a group of items later to be 
provided to the subject to create something (such as a structure, in the case of building 
blocks, or 3D art, by laying out different types of objects on a platform such as white board). 
As the task continues different additional questions are posed to the subject such as the 
following (in the case of building blocks): 
1) “What’s your favorite color?” 
2) “What do you like to build with blocks?” 
3) “What are you going to build with your blocks?  
4) “Which shape block do you like the best?” 
5) “What do you think you’re going to build today with these blocks?” 
After completion of the task, the subject is then permitted to complete the activity, which in 
the above example, is using the building blocks to create something. Each dyadic interaction 
will last up to 10 minutes. 
 
During the Dyadic Interaction Task the study team member sits directly across from the 
subject while wearing a pair of video recording glasses (with the lenses in place or removed) 
that has a video camera embedded in the bridge of the glasses (such as the Pivothead Kudo 
Glasses or the Pivothead Durango Glasses) [26, 27]. The study team member activates the 

 
 
 
 
 
 
14
video recording function of the glasses prior to starting the task so that the entire task is 
recorded. Alternatively or in conjunction with the video recording glasses, single or multiple 
video cameras may be used to record the task. 
 
Following each Dyadic Interaction Task the video recording file is transferred from the 
glasses to a data storage device and/or computer maintained by the study team member for 
subsequent analysis. This analysis may include use of video annotating software such as the 
BORIS or ELAN video annotating software to annotate different conditions within each 
frame or group of frames of the video recording which conditions may include: the 
orientation of the subject’s face is oriented towards the camera, the orientation of the 
subject’s face is not oriented towards the camera, the orientation of the subject’s eyes are 
oriented directly toward the camera, the orientation of the subject’s eyes are not oriented 
directly toward the camera, and the subject matter of the video is not applicable. Any 
member of the study team or third parties with HIPPA compliant policies and procedures, 
blinded to the study group of each subject, may engage in the above-described annotation 
including therapist practitioners or research organizations.  
 
Eye Tracking Video Assessment: This task involves the subject viewing social scenes and 
other types of scenes on a computer monitor while eye gaze patterns and fixations on social 
(i.e. face) and non-social portions of the scene are measured using an eye tracker. This is 
similar to eye tracking assessments used in ASD diagnosis research in which measurements 
of the percent of time looking at faces and eyes while watching video clips are obtained. 
[29] 
 
Ekman 60 Faces Test: (Ekman & Freisen 1976 [30]), using a selection of 60 photographs 
from Ekman’s Pictures of Facial Affect [30]. These images have been used in several studies 
of emotion recognition [31, 32]. Subjects will be presented with 60 photographs of different 
individuals expressing different emotions and asked to label each of the photographs in 
terms of the emotion expressed with one of the six standard emotional labels: happiness, 
sadness, anger, surprise, disgust, and fear. This assessment may be administered by 
computer and the study team member administering the assessment may assist in entry of 
the subject’s selection. 
 
Emotional Expression Video Assessment: This task involves the subject viewing videos of 
scenes where actors exhibit a specific emotion and following each video the subject is asked 
to label the emotion presented from a group of choices (ie. happiness, sadness, anger, 
surprise, disgust, and fear) during the assessment eye gaze patterns and fixations are 
measured using an eye tracker. This is similar to the Ekman 60 Faces Test but adds a level 
of realism as the emotions expressed are in video form. This is also similar to eye tracking 
assessments used in ASD diagnosis research in which measurements of the percent of time 
looking at faces and eyes while watching video clips are obtained [29]. 
 
Test of Variables of Attention (TOVA [33]): The TOVA is a highly reliable, computerized 
neuropsychological measure of sustained attention and response inhibition. This continuous 
performance measure presents a target and non-target stimulus, and children are instructed 
to only press the button when they see the target presented. Study members will ask and take 

 
 
 
 
 
 
15
note of the subject’s caffeine consumption the day of administration of each TOVA and may 
note the subject’s amount of sleep the night before administration of each TOVA and 
incidental use of antihistamines or anxiolytic medications, as caffeine consumption, amount 
of sleep, and use of use of antihistamines or anxiolytic medications, can impact the 
outcomes of the test. 
 
Peabody Picture Vocabulary Test, 4th Edition (PPVT [34]): The PPVT-4 scale is a norm-
referenced, wide-range instrument for measuring the receptive (hearing) vocabulary of 
children and adults. Enlarged and colorized, this PPVT edition is available in two parallel 
forms (form A and form B) that are administered individually. Each form contains training 
items and 228 test items, each consisting of four full-color pictures as response options on a 
page. For each item, the examiner says a word, and the examinee responds by selecting the 
picture that best illustrates that word’s meaning. 
 
Video Recording of Study Visits: All study team member visits to the home, school, therapy 
center, or research organization may be video recorded using a single or multiple video 
cameras and tripods. 
Data Collection – Behavioral Data 
Eye Tracking: Study participants will be positioned so measurements can be obtained using 
an eye tracking device available for purchase by consumers e.g. the Tobii Eye Tracker 4C. 
This device uses a camera to measure eye positions and gaze direction to trace where study 
participants are focused (point of gaze) as they look at stimuli presented on a screen. The 
device may also measure pupil dilation.  
Behavior: Recorded behavioral measures may include computer mouse click, computer 
keyboard/touchscreen keystroke, touchscreen contact, and game controller game play data. 
1.5 Compliance Statement 
The investigators will perform the study in accordance with this protocol, will obtain 
consent and assent, and will report unanticipated problems involving risks to subjects or 
others in accordance with IRB Policies and Procedures and all federal requirements. 
Collection, recording, and reporting of data will be accurate and will ensure the privacy, 
health, and welfare of research subjects during and after the study.  
2 
STUDY OBJECTIVES 
2.1 Primary Objective (or Aim) 
The primary objective of this study is to determine whether 6.67 to 33.33 hours of 
BioStream Training improves the performance of children with ASD on social skills 
assessments including in comparison to an alternate game. Specifically with respect to the 
following: 
The mean change from baseline score on the following assessments based on post-final 
game play session assessment compared to the alternate game group: 

 
 
 
 
 
 
16
a. Subject gaze patterns as measured by video eye tracking assessment. 
b. Subject gaze patterns as measured by the dyadic interaction task. 
c. Mean change in baseline score on the Ekman 60 Faces Test. 
d. Mean change in baseline score on the TOVA. 
e. Mean change in baseline score on the SRS. 
2.2 Secondary Objectives (or Aim) 
The secondary objectives are to observe changes in subject gaze patterns during additional 
social skills assessments after engaging in BioStream Training, including in comparison to 
an alternate game. 
Specifically with respect to the following: 
The mean change from baseline score on the following assessments based on post-final 
game play session assessment compared to the alternate game group: 
 
a. Subject gaze patterns as measured on the videos of emotional expression assessment. 
b. Subject responses to the CJARS survey. 
 
3 
INVESTIGATIONAL PLAN 
3.1 General Schema of Study Design 
This protocol is a comparison group controlled trial of a computer-based social skills 
training intervention. The BioStream Training is being compared to a modified version of 
the BioStream Training, which will not include the same therapeutic exercises or any video 
game that is rated E (Everyone) by the Entertainment Software Rating Board. The game will 
be played by subjects in the non-intervention group for the same length of playing time and 
at the same frequency, as the BioStream Training intervention group. It will require a similar 
game controller device as that which is used by the intervention group and will be computer 
based.  
3.1.1 
Initial Screening 
Potential subjects will be first screened by any study team member in an in-person or 
telephone interview with the parent/guardian. After written informed consent is obtained to 
the initial screening (in the case of an in-person interview) or verbal informed consent is 
obtained to the initial screening (in the case of a telephone interview), protocol inclusion and 
exclusion criteria will be reviewed with the parent/guardian. The parent/guardian will also 
be asked for a list of the medications the subject is currently taking and that information will 
be recorded. A subset of questions from the SRS will be asked as part of the screening. The 
parent/guardian will also be asked if the subject has a diagnosis of ADHD and if so, that will 
be noted.  
Prospective Study Participant Initial Screening Form.  This short questionnaire will be 
administered to the parent/guardian in-person or by telephone prior to the study visit to 

 
 
 
 
 
 
17
query their children’s video game playing habits.  This questionnaire should take less than 
15 minutes to complete.  Questions related to the inclusion/exclusion criteria will also be 
asked to determine eligibility. 
3.1.2 
Phase I Visit 1 
Parental/guardian permission (informed consent) and, if applicable, child assent, will be 
obtained. Subjects will participate in social skills assessments. The subject will participate in 
the Peabody Picture Vocabulary Test, 4th Edition [34]. If the study team member determines 
that the subject’s intelligence standard score is below 40, then the subject will not be able to 
continue to be included in the study per the exclusion criteria (see page 4). The subject will 
participate in the Ekman 60 Faces Test. If the subject score is greater than 75% correct, then 
the subject will not be able to continue to be included in the study per the exclusion criteria. 
Additionally, to confirm certain inclusion criteria, the parent/guardian will be required to 
present the study team member with a note from a licensed medical professional indicating 
the subject has been diagnosed with ASD and also if the subject has been diagnosed with 
ADHD. The study team member will inspect the note, but will not take possession of it. The 
study team member will provide training to the parent/guardian (in the case of in-home use) 
or the teacher (in the case of in school use) or the therapist (in the case of therapy center use) 
regarding use of the Subject Computer, and review the protocol for the subject’s training or 
use of the alternate game (as applicable). 
3.1.3 BioStream Training Group  
The BioStream Training group will undergo an estimated 40-60 minute training session on 
how to use the BioStream Training game. Further details on further assessments conducted 
during the visits can be found in section 4.2. 
3.1.4 Alternate Game Group  
The alternate game group will undergo an estimated 40-60 minute training session on how 
to use the alternate game on the first visit. Otherwise, their visits will be exactly the same as 
the BioStream Training Group. Further details on further assessments conducted during the 
visits can be found in section 4.2 
3.2 Allocation to Treatment Groups and Blinding 
Subjects will be randomly assigned to one of the two groups (BioStream Training group, or 
alternate game group) as an ongoing process throughout enrollment. 
3.3 Study Duration, Enrollment and Number of Sites 
3.3.1 Duration of Study Participation 
Enrollment for this study will last 18 months (starting on August 7, 2018 and ending on 
February 7, 2020). When a subject is enrolled, their first home visit will be within four 
weeks of their enrollment. Each phase lasts four weeks, but it is possible there will be delays 
of up to four weeks between phases for some participants. Therefore, for each subject, we 
expect to have all of our data for both phases 16 weeks from the date of enrollment at the 
latest. We expect the study to be complete by the beginning of February of 2020 at the latest. 

 
 
 
 
 
 
18
Expected time commitment for parents and subjects for each phase can be found in tables 1 
and 2 on pages 4-6. 
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 
There will be 10 sites for this study. Each site is an operating public school, private school, 
therapy center, therapist practitioner, or research organization where a therapist practitioner 
provides regular treatment for children with autism or regularly conducts research involving 
children with autism. Therefore, we expect to potentially enroll up to 150 subjects. 
3.3.3 Offer of Free BioStream Training and Follow-up Study to Control Group 
If funding permits, at the end of Phase II of the study, the study Sponsor would like to invite 
all participants in the control group (alternate game group) to participate in the BioStream 
Training. The study team will collect performance data on these participants over the course 
of 2 months. The study PI will submit a detailed protocol amendment to the IRB for 
approval prior to enrolling any of the control group participants in this study. Participant 
permission to be contacted regarding this additional part of the project is included in the 
consent form attached to this IRB package. 
3.4 Study Population 
3.4.1 Inclusion Criteria 
1) Parental/guardian permission (informed consent) and if appropriate, child assent. 
2) The parent who participates in the screening, completes the questionnaires, and provides 
informed consent must be proficient in English. 
3) Age 4 years 0 months up to 14 years, 11 months, and 29 days.   
4) English as the child’s primary/first language (the intervention does not currently have 
alternate language versions). 
 
5) Capable of using a handheld video game controller (as reported by parent). 
 
6) Has successfully played a video game using a Microsoft Xbox game controller, Sony 
PlayStation game controller, or other comparable game controller. 
 
7) Parent reports AT LEAST ONE of the following: 
 
a) Score of ≤ 2 on a modified version of Question 15 of the Social Responsiveness 
Scale (SRS) (“Is able to understand the meaning of other people’s facial 
expressions.”) 
 
b) Score of ≥ 2 on a modified version of Question 16 of the Social Responsiveness 
Scale (SRS) (“Avoids eye contact.”) 
 
8) Confirmed diagnosis of ASD from a licensed medical professional.  
 

 
 
 
 
 
 
19
9) Estimated intelligence standard score of at least 40 (can be substituted for a receptive 
language score such as PPVT or use of the Differential Ability Scales, 2nd Edition 
(DAS-II)). 
 
10) Attains a score equal to or less than 75% correct on the Ekman 60 Faces Test. 
3.4.2 Exclusion Criteria 
1) History of seizures. 
2) History of traumatic brain injury or other significant medical or neurological 
abnormality affecting motor or higher cortical functioning. This includes gestational age 
below 32 weeks or perinatal injury, where the risk for brain injury is greatly increased. 
Rationale: a primary aim of the study is to identify sequences in our game-like 
applications that are appealing to youth with ASD; it is not clear that individuals with 
any type of acquired brain injury would provide useful data on what appeals to an 
individual with ASD.  
3) A visual disorder that cannot be corrected through the use of corrective lenses to a level 
of 20-40 in both eyes. 
4) Use of corrective visual lenses that would significantly impede the valid collection of 
visual attention and gaze pattern data during dyadic interaction tasks. 
5) Auditory impairment (that cannot be corrected by a hearing aid) that would significantly 
impede the valid collection of test measures. 
6) Profound intellectual disability or sensory-motor difficulties that would preclude valid 
use of diagnostic instruments and/or use of a computer or mobile computing device. 
7) A DSM 5 disorder or other psychiatric symptoms that would interfere with the 
participant’s ability to participate in the study (e.g., active psychosis), per parent report. 
8) History of one or more psychiatric hospitalizations. 
9) Presence of significant symptoms of a conduct disorder. 
Subjects that do not meet all of the enrollment criteria may not be enrolled. Any violations 
of these criteria must be reported in accordance with IRB Policies and Procedures.  
4 
STUDY PROCEDURES 
4.1 Initial Screening 
See section 3.1.1 for a full description of the initial screening. 
4.2 In-Person Study Visits 
During the in-person study visits, parents and subjects will complete the following 
assessments, described in section 1.4 unless otherwise noted. Tables 1 and 2 also show 
details on the schedule of all in-person assessments for both phases. 

 
 
 
 
 
 
20
Social Responsiveness Scale – Parent (SRS) – 10 minutes, parent only  (may be 
administered by phone). 
Childhood Joint Attention Rating Scale (C-JARS) – 10 minutes, parent only (may be 
administered by phone). 
Dyadic Interaction Task – 10 minutes, subject only. 
Eye Tracking Video Assessment – 10 minutes, subject only. 
 
Ekman 60 Faces Test – 10 minutes, subject only. 
 
Emotional Expression Video Assessment – 10 minutes, subject only. 
 
Test of Variables of Attention (TOVA) – 22 minutes, subject only. 
 
An introduction to game and equipment (Only Phase I Visit 1) – 40 – 60 minutes, with the 
parent/guardian, teacher, or therapist. 
 
Subject Interview/Survey (described in section 5.4.1) – 10 minutes, subject only. 
 
Parent/Teacher/Therapist Interview/Survey (described in section 5.4.2) – 10 minutes, parent, 
teacher, or therapist only. 
 
Video Recording of Study Visits: All study team member visits to the home, school, or 
therapy center may be video recorded using a single or multiple video cameras and tripods. 
Please note that for subjects who are using the BioStream Training in their school, therapy 
center or research organization, their parent/guardian only needs to be present for the first 
visit. After that visit, surveys involving the parent including the Social Responsiveness Scale 
and Childhood Joint Attention Rating Scale can be conducted over the phone. 
4.3 Subject Completion/Withdrawal 
Study participants may withdraw from the study at any time. They may also be discontinued 
from the study: 
1) For failing to meet all inclusion criteria. 
2) For meeting an exclusion criterion. 
3) For not adhering to scheduled visits (at the discretion of the PI). 
4) For failing to comply with study requirements (at the discretion of the PI). 
5) For reasons of safety or for administrative reasons (at the discretion of the PI). 
6) If the participant is otherwise not well-suited for further participation in the study (at the 
discretion of the PI). 

 
 
 
 
 
 
21
4.3.1 Early Termination Study Visit 
Subject Exit Interview/Survey 
In the case that a subject decides to leave the study early, the subject will be asked to 
complete a final interview. This interview will discuss the reasons for leaving the study, will 
be completely voluntary, and may be discontinued at any time during the interview by the 
subject. 
Parent Exit Interview/Survey 
In the case that a subject decides to leave the study early, the parent/guardian will also be 
asked to complete a final interview. This interview will discuss the reasons for the subject 
leaving the study, will be completely voluntary, and may be discontinued at any time during 
the interview by parent/guardian. 
5 
STUDY EVALUATIONS AND MEASUREMENTS 
5.1 Screening and Monitoring Evaluations and Measurements 
5.1.1 Initial Screening Interview 
See section 3.1.1 for a full description of the initial screening. 
5.1.2 ASD/ADHD Diagnosis Verification 
To confirm certain inclusion criteria, during the first visit the parent/guardian will be 
required to present the study team member with a note from a licensed medical professional 
indicating the subject has been diagnosed with ASD and also if the subject has been 
diagnosed with ADHD. The study team member will inspect the note, but will not take 
possession of it. 
5.1.3 Medication List 
During the initial screening, the parent/guardian will be asked for a list of the subject’s 
medications in the initial screening in order to determine the medication’s possible impact 
on the therapeutic outcomes and research outcomes. 
5.1.4 Video Game Interview Form (Parent-Report) 
Parents or teachers or therapists will complete a weekly survey on the laptop provided by the 
Sponsor. The survey will ask questions concerning the subject’s enjoyment and progress 
with the training as well as administration in the home or school environment. Survey is 
fully described in section 5.4.2. 
5.2 Efficacy Evaluations 
5.2.1 Primary Endpoints 
Please see the primary endpoints listed on page 3-4. 

 
 
 
 
 
 
22
5.2.2 Secondary Endpoints 
Please see the secondary endpoints listed on page 3-4. 
5.3 Biosensor Data Collection 
 Eye Tracking: Study participants will be positioned so measurements can be obtained 
using an eye tracking device available for purchase by consumers Tobii Eye Tracker 
4C, or another device of a similar nature. This device uses a camera to measure eye 
positions and gaze direction to trace where study participants are focused (point of 
gaze) as they look at stimuli presented on a screen. The device may also measure 
pupil dilation.  
 Behavior: Recorded behavioral measures may include computer mouse click, 
computer keyboard/touchscreen keystroke, touchscreen contact, and game controller 
game play data. 
5.4 Subject and Parent Interviews 
5.4.1 Subject Interviews/Surveys 
At each study visit and at other times during the course of the study, the subject will 
participate in brief interviews and/or surveys (which may be conducted in-person or by 
phone by any member of the study team) including questions about their enjoyment of 
BioStream Training or alternate game. These interviews will provide an opportunity for 
subjects to share feedback about BioStream Training with the study team and compare that 
feedback to feedback regarding the alternate game. All interviews and surveys will be 
configured (if computer based) so as to include only de-identified subject data. If the surveys 
are in paper form, the study team member conducting the surveys will only record data in 
such a manner so that it is de-identified. All such paper based surveys may be converted to 
digital format (including by use of a scanner) and transmitted to the Sponsor. Additionally, 
the subject may be asked to complete a brief survey about BioStream Training and/or the 
alternate game on the Subject Computer which may be transmitted to the Sponsor as 
described in Section 1.2 Data Transfer and Storage. 
5.4.2 Parent/Teacher/Therapist Interviews/Surveys and Equipment Handoff/Return 
At each study visit and at other times during the course of the study, the parent/guardian (in 
the case of the at-home subjects) or teacher or therapist (in the case of in-school subjects or 
in-center subjects) will participate in brief interviews and/or surveys (which may be 
conducted in-person or by phone) including questions about the subject’s enjoyment of 
BioStream Training or alternate game. These interviews will provide an opportunity for 
parents/guardians or teachers or therapists (as applicable) to share feedback about BioStream 
Training and/or alternate game with the study team. All interviews and surveys will be 
configured (if computer based) so as to include only de-identified subject data. If the surveys 
are in paper form, study team member conducting the surveys will only record data in such a 
manner so that it is de-identified. All such paper based surveys may be converted to digital 
format (including by use of a scanner) and transmitted to the Sponsor. Additionally, the 
parent/guardian or teacher or therapist (as applicable) may be asked to complete a brief 
survey about BioStream Training, the alternate game, and/or provide observational 

 
 
 
 
 
 
23
information 
regarding 
the 
subject 
(including 
in 
the 
form 
of 
a 
Weekly 
Parental/Teacher/Therapist survey), on the Subject Computer which may be transmitted to 
the Sponsor as described in Section 1.2 Data Transfer and Storage. The interviews and 
surveys will provide an opportunity for parents/guardians or teachers or therapists (as 
applicable) to share feedback about the at-home, in-school, or in-center administration 
process (as applicable) with the study team. 
Additionally, the parent/guardian or teacher or therapist (as applicable) will be provided 
with at-home  or in-school or in-center equipment (such as a laptop, an eye tracker, such as 
the Tobii Eye Tracker 4C, and a game controller, such as an Xbox 360 Controller), as well 
as instructions regarding at-home or in-school or in-center administration of BioStream 
Training or alternate game. The parent/guardian or teacher or therapist (as applicable) will 
return the equipment to the study team at the appropriate in-person visit. 
STATISTICAL CONSIDERATIONS 
5.5 Primary Endpoint 
Paired-sample t-tests will be used to measure changes from baseline within each group, and 
independent sample t-tests will be used to measure changes from baseline relative to the 
alternate game group for all endpoints.  
For all endpoints, we will determine whether there were statistically significant changes in 
scores from baseline or relative to the alternate game group. Significance will be set at 
p<0.05. Multiplicity of primary endpoints will be managed via statistical corrections. 
5.6 Secondary Endpoints 
See statistical analysis for primary endpoints listed above. 
5.7 Statistical Methods 
5.7.1 Baseline Data  
Baseline and demographic characteristics will be summarized by standard descriptive 
summaries (e.g. means and standard deviations for continuous variables such as age and 
percentages for categorical variables such as gender). 
5.7.2 Efficacy Analysis 
The primary analysis will be based on all subjects randomized at the initial visit for who 
initial visit and final visit data is collected.   
Paired-sample t-tests will be used to measure changes from baseline within each group, and 
independent sample t-tests will be used to measure changes from baseline relative to the 
alternate game group for all endpoints.  
 
For all endpoints, we will determine whether there were statistically significant changes in 
scores from baseline or relative to the alternate game group. Significance will be set at 
p<0.05. Multiplicity of primary endpoints will be managed via statistical corrections. 
 

 
 
 
 
 
 
24
Secondary endpoints will be evaluated in a similar manner. Analysis will include all subjects 
for who initial visit and final visit data is collected. The treatment and control groups will be 
compared using t-tests as described above. 
5.7.3 Safety Analysis 
Clinical AEs will be monitored throughout the study. All SAEs will be reported to the IRB 
in accordance with IRB policies. AEs that are not serious will be summarized in narrative or 
other format and submitted to the IRB at the time of continuing review. Since the study 
procedures are not greater than minimal risk, AEs are not expected. See section 6.2 on page 
22 for further details. 
5.8 Sample Size 
This study will enroll up to 150 participants (see section 3.3.1 for details in enrollment 
timeline).  
5.9 Interim Analysis 
No interim efficacy analyses or corresponding stopping rules are proposed. Interim safety 
analyses will consist of ongoing reviews of AEs (if any) and will result in stopping the study 
only if life-threatening or serious diseases are found to be caused by the study, which is not 
anticipated. 
6 
SAFETY MANAGEMENT & REPORTING 
6.1 Clinical Adverse Events 
Clinical (AEs) will be monitored throughout the study. Since the study procedures are not 
greater than minimal risk, AEs are not expected. If any unanticipated problems related to the 
research involving risks to subjects or others happen during the course of this study 
(including SAEs) they will be reported to the IRB. As with any computer video 
game, seizure is a rare risk and possible SAE. However, subjects are required to have played 
video games in the past and a history of seizures excludes participants from taking part in 
this study. 
6.2 Adverse Event Reporting 
If, at any time, during any BioStream Training session or play of the alternate game session, 
the parent/guardian or teacher or therapist (as applicable) observes the subject displaying 
seizure symptoms, or becoming agitated, frustrated, disturbed, or in any other manner being 
negatively impacted (including in a manner that may pose a risk to the subject’s safety or 
well-being or the safety or well-being of others) or in their judgment, believes the subject 
will or may become negatively impacted in any way (including in a way that may pose a risk 
to the subject’s safety or well-being or the safety or well-being of others), they will 
immediately discontinue the session, stop the subject from engaging in any further sessions, 
and contact the Principal Investigator to inform him or her of this occurrence. AEs that are 
not serious but that are notable and could involve risks to subjects will be summarized in 
narrative or other format and submitted to the IRB at the time of continuing review.  

 
 
 
 
 
 
25
7 
STUDY ADMINISTRATION 
7.1 Treatment Assignment Methods 
7.1.1 Randomization 
Subjects will be randomly assigned to one of the two groups (BioStream training group, or 
alternate game group) as an ongoing process throughout enrollment. 
7.2 Data Collection and Management 
See page 8 and pages 19-20 for information on data collection and management. 
7.3 Confidentiality 
All written or electronic forms (except Informed Consent Forms and Assent Forms) will 
employ a unique alphanumeric identifier; in no case will the participant's name or other 
identifying information appear on these forms. The user ID for the BioStream Training and 
alternate game shall use the same unique alphanumeric identifier. The study team will 
accomplish this on all parent/guardian or teacher or therapist questionnaires (as applicable) 
which have lines for child and parent name by applying a label with unique alphanumeric 
identifier and instructing parents/guardians or teacher or therapist to use generic labels (e.g., 
biological mother) rather than writing their names. The PI will keep a master list containing 
PHI and subject ID number separate from coded data forms, which will be maintained in a 
locked file drawer, cabinet or lock box in the PI’s office. Only the PI will have access to this 
location. The master list will be maintained on a separate password-protected computer and 
be stored in an encrypted password protected file. Video recordings will stored on password-
protected and/or encrypted data storage devices including computers, external hard drives, 
and/or flash drives only accessible by members of the study team including the Sponsor’s 
study team members. Any member of the study team or third party with HIPPA compliant 
policies and procedures, blinded to the study group of each subject, may engage in in video 
recording annotation including therapist practitioners or research organizations. The Sponsor 
may collect and store all de-identified data on password-protected and/or encrypted data 
storage devices including computers, external hard drives, and/or flash drives. 
7.4 Regulatory and Ethical Considerations 
7.4.1 Data and Safety Monitoring Plan 
The PI will periodically review the data collection and storage practices associated with this 
study and determine whether changes to enhance confidentiality and privacy are required. 
The PI will frequently monitor the quality control of the data with staff and research 
assistants. 
7.4.2 Risk Assessment 
Use of BioStream Training or Alternate Game: The tasks associated with use of the 
BioStream Training or alternate game can produce feelings of frustration, anxiety, stress and 
fatigue including eye fatigue. These risks are no greater than those associated with minimal 
risk studies. As with any computer video game, seizure is a rare risk and possible SAE. 

 
 
 
 
 
 
26
However, subjects are required to have played video games in the past and a history of 
seizures excludes participants from taking part in this study. 
Psychological Stress and Anxiety: Due to the length of time associated with the assessments, 
some participants may experience fatigue, anxiety, or stress. Participants will be allowed to 
take breaks and stop at any time. Additionally, the presentation of unpleasant stimuli 
(including social interactions that are challenging for some youth with ASD) might be 
distressing to some participants. To minimize risk associated with the presentation of 
unpleasant stimuli, several precautions will be taken: (i) only members of the study team 
that are trained to conduct study visits by a Board Certified Behavior Analyst with 
experience in working with children with ASD, will conduct study visits, (ii) 
Parents/guardians will be shown examples of stimuli as part of the consent process and will 
be asked whether they feel confident that their child will not find these overly distressing, 
(iii) the parent/guardian or teacher or therapist (as applicable) will be instructed and agree to 
oversee gameplay to look for signs of distress in the subject and the tasks will be stopped if 
the subject appears distressed or requests to stop.  
Risks Associated with Behavioral Data Collection: These risks are no greater than those 
associated with minimal risk studies. 
Breach of Confidentiality: Confidentiality is carefully guarded to address issues of privacy 
and insurability. In particular, each subject is assigned a unique alphanumeric identifier 
immediately upon recruitment. Although a list linking the study number to the subject’s 
name is maintained for future studies and contact, the name does not appear on any other 
document (other than Informed Consent Forms and Assent Forms). The families are 
informed of this link and are assured that only the PI has access to that list. The purpose of 
the list linking study ID number to the name is to record who we have already recruited so 
that we accidentally do not re-approach any family. 
7.4.3 Potential Benefits of Trial Participation 
There is no direct benefit to participation in this study, however it is possible that progress 
made during the training could be generalizable as a therapeutic benefit. Subjects will 
receive collateral benefits. We anticipate indirect benefits to the community of people with 
ASD at large. Researchers will be able to increase their understanding of the behavioral 
foundations of this disorder as well as the propensity of people with ASD towards specific 
game-like applications, which may be translated into improved future treatments. In 
addition, it could significantly advance development of an intervention and/or diagnostic 
tool to help children with ASD.  
7.4.4 Risk-Benefit Assessment 
It is hoped that the knowledge gained will indirectly benefit the participants as well as the 
larger community of people with ASD. The risks of the study procedures including the 
effects of behavioral measurements and assessments are all considered minimal risk. 
7.5 Recruitment Strategy 
In-home Subject Recruitment 

 
 
 
 
 
 
27
With respect to members of the study team that have a therapy practice that includes in-
home patients, in-school patients, or in-center patients, they will recruit from within their 
patient base for in-home study subjects.  
Additionally, recruitment will occur through phone and in-person outreach by study team 
members to organizations that serve the needs of families of children with ASD to help 
identify families that may have an interest participating in the study. Such organizations will 
provide a study team member’s contact information to those families that they, in their 
discretion, decide to contact that express an interest in learning more about the study. The 
study team will not receive the names or telephone numbers of potential study participants 
without their verbal consent to share that information.  
Study team members may also engage in outreach through their personal and professional 
network of contacts to help identify families that may have an interest participating in the 
study. Such contacts will provide a study team member’s contact information to those 
families that they, in their discretion, decide to contact that express an interest in learning 
more about the study. The study team will not receive the names or telephone numbers of 
potential study participants without their verbal consent to share that information. 
In-school, and In-center Subject Recruitment 
Schools, therapy centers, and research organizations that serve the needs of children with 
ASD or conduct research involving children with ASD will be approached by the Sponsor to 
source potential subjects. These organizations will approach parents of potential subjects 
and assess interest in the project and ask permission to connect to the study team. No 
additional subject information, excluding information collected in the ordinary course of 
operations, will be collected before this permission is given. 
7.6 Informed Consent/Assent and HIPAA Authorization 
After a thorough discussion of the study and its procedures, the parent/legal guardian will be 
consenting and giving permission for their child to participate in this study. Children ages 7 
to 14 entering the study will give their assent to participate.   
Initial Interview Phase. When a parent/legal guardian expresses interest in having their child 
participate in the study, an in-person meeting or telephone call will be set up by a member of 
the study team to review the study details, risks, benefits, financial considerations, and 
HIPAA procedures that are in place to insure privacy and confidentiality. The member of the 
study team will explain that an initial eligibility interview needs to be conducted as a first 
step, and they will be told that all information collected will be kept strictly confidential. 
The nature of the risks and benefits of participating in the screening interview will be 
explained. The parent/legal guardian will then undergo a short (up to 30 min) in-person or 
by phone screening interview to determine study eligibility. The specific inclusion or 
exclusion criteria in question will be described, and the parent/legal guardian will have an 
opportunity to ask questions. After the results of initial interview phase are received and 
evaluated, the parent/legal guardian will be contacted again with the results. The parent/legal 
guardian will be informed of specific inclusion or exclusion criteria that are not met/met 
based on this more detailed review. 

 
 
 
 
 
 
28
In-Person Study Phase. After the initial interview phase, those parents/legal guardians of 
children that met the study inclusion and exclusion criteria in the initial interview phase and 
who are interested in participating in the study will be scheduled for have their first visit in 
the home, school, therapy center, or research organization (as applicable). Upon the study 
team member’s arrival at the subject’s home, school, therapy center, or research 
organization (as applicable), the first agenda item will be a face-to-face conversation with 
the parent/legal guardian to review the study protocol. The parent/legal guardian will then be 
asked to read the consent forms. Prior to signing the forms, the study team member will 
encourage the parent/legal guardian to ask as many questions as they wish, until they fully 
understand all aspects of the study, including its risks and benefits, as well as the time 
demands and inconveniences of study participation. This is critical, as it does not benefit the 
parent/legal guardian or the researchers to have a misunderstanding at this phase as to what 
full study participation entails. The study team member will also remind the parent/legal 
guardian that the subject’s participation in the study is voluntary and that the parent/legal 
guardian or child can terminate participation at any time with no obligations to continue and 
no penalties whatsoever. Refusal to participate will in no way influence the individual’s 
relationship with the study team member.  In addition, if the participants’ parent/legal 
guardian is an employee of the study team member’s organization or Sponsor, they will be 
informed that their participation will not affect their performance evaluations or employment 
and that the study data will not be shared with their supervisor. 
7.6.1 Waiver of Assent 
A waiver of assent is requested for the initial screening phase of the study. The short 
screening interview will be conducted with parent/legal guardian in-person, and the child 
may not be present to provide assent. 
7.7 Payment to Subjects/Families 
7.7.1 Compensation 
As compensation for time and expenses, child participants will be provided with a gift card 
upon the completion of each phase of the study. The total value of each gift card provided to 
each subject over the course of this study will not exceed $50 per completion of each phase 
of the study. Gift cards may be for retailers such as Amazon and Target. In addition, each 
study participant will be provided with a gift card not to exceed $5 to retailers such as 
Amazon and Target for each time he or she completes the TOVA assessment. 
8 
PUBLICATION 
At appropriate scientific junctures, results from these studies will be presented at scientific 
forums (e.g. national meetings). Similarly, as results are achieved that deserve to be shared 
with the greater scientific community, they will be submitted for publication in appropriate 
peer review journals. They may also be presented in book chapters. In all cases, data on 
specific participants will be stripped of all protected or identifiable health information. 
9 
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29
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ClinicalTrials.gov 
Document Submission Cover Page 
 
 
Official Title of Study: Computer-based Social Skills Training for Autism Spectrum 
Disorder 
 
NCT Number of Study: NCT03672344 
 
Unique Protocol ID: 08012018A 
 
Document Title: Supplement to Statistical Analysis Plan 
 
Document Date: April 25, 2022 
 
Study Sponsor: BioStream Technologies, LLC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Supplement to Statistical Analysis Plan 
In addition to the statistical analyses described in the original study protocol, a 2 
(Time) × 2 (Condition) mixed ANOVA was conducted to test for between-group 
differences in Ekman-60 scores from pre- to post-intervention. Mixed ANOVAs also will 
be used to test for between-group differences in Social Responsiveness Scale (SRS) 
and Child Joint Attention Rating Scale (C-JARS) scores from pre- to post-intervention. 
Significance will be set at p < 0.05.