Virtual Reality to Improve Social Perspective Taking in Youth With Disruptive Behavior Disorders
Phase: NA
Conditions: Conduct Disorder, Child, Adolescent, Attention Deficit and Disruptive Behavior Disorders, Child Behavior Disorders, Virtual Reality, Social Perception, Magnetic Resonance Imaging
Sponsor: Indiana University

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Virtual Reality to Improve Social Perspective 
Taking in Youth with Disruptive Behavior Disorders 
 
Tom Hummer, PhD 
Department of Psychiatry, Indiana University School of Medicine 
 
Health Information and Translational Sciences 
Room 1001R 
410 W. 10th Street 
Indianapolis, IN 46202 
 
 
 
 
 
 
 
 
 
 
 
William Kronenberger, PhD, IUSM Department of Psychiatry 
Dawn Neumann, PhD, IUSM Department of Physical Medicine and Rehabilitation 
Susan Perkins, PhD, IUSM Department of Biostatistics 
Zeb Wood, MS, IUPUI School of Informatics and Computing  
 
 
 
 
Support Provided by: 
National Institute of Mental Health 
 
 
 
 
 
 

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Table of Contents: 
 
Study Schema 
1.0 
Background & Rationale 
2.0 
Objective(s) 
3.0 
Outcome Measures 
4.0 
Eligibility Criteria 
4.1 
Inclusion Criteria 
4.2 
Exclusion Criteria 
5.0 
Study Design 
6.0 
Recruitment & Enrollment/Randomization 
7.0 
Study Procedures 
8.0 
Study Calendar 
9.0 
Reportable Events 
10.0 Data Safety Monitoring 
11.0 Study Withdrawal/Discontinuation 
12.0 Statistical Considerations 
13.0 Data Management 
14.0 Privacy/Confidentiality Issues 
15.0 Follow-up and Record Retention 
16.0 References 
 
 
 

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1.0 
Background & Rationale 
 
Oppositional defiant disorder (ODD) and conduct disorder (CD), collectively known as disruptive 
behavior disorders (DBDs), involve persistent physical or verbal confrontations, antisocial 
behavior, and emotional outbursts. Despite a range of biological and environmental risk factors 
for DBD, social-cognitive impairments are a common link, and improving these deficits should 
be beneficial for all patients with DBD. 
 
Children and adolescents with DBD have deficits in social perspective taking that contribute 
significantly to these behavior problems.1, 2 Perspective taking is the ability to perceive the world 
from another person’s point of view,3-6 including making inferences about the capabilities, 
feelings, and expectations of others.7, 8 It is often measured via self-report measures such as 
the Perspective Taking subscale of the Interpersonal Reactivity Index.9  
 
Perspective taking requires substantial motivation and cognitive resources and can be difficult to 
achieve, particularly for children.10, 11 A failure to understand or value another person’s 
perspective inhibits helping behavior without clear direct benefits.12, 13 Perspective taking skills 
are related to empathic concern, which encompasses feelings of sympathy and concern for 
unfortunate others,14 and theory of mind, the ability to accurately infer others’ mental states, 
such as intentions.15, 16 Negative attribution biases are more likely in individuals with poor 
theory of mind.15, 17  Thus, improving children’s perspective-taking skills should allow them to 
better understand a counterpart’s thinking and intentions, increasing empathic concern, and 
reducing hostile attribution biases–and therefore improving the likelihood that prosocial 
behavior occurs. 
 
In the brain, perspective taking engages circuitry underlying empathic concern and theory of 
mind. In fMRI studies, imagining pain to the self or other, often in conjunction with images 
depicting painful scenarios, engages a network of regions including anterior insula, dorsal 
anterior cingulate cortex (dACC), somatosensory cortex, supramarginal gyrus, and amygdala.18-
22 A meta-analysis by Lamm et al.21 detected that dACC and bilateral anterior insula, the regions 
most commonly activated in response to other’s pain, also show strong responses to self-
perspective pain. However, in youth with DBD, there is a decreased response to other-
perspective pain in dACC and anterior insula, despite no change or a heightened response to 
self-perspective pain.23-25 
 
Current treatments to address DBD include a range of pharmaceutical options, one-on-one 
therapies, and extended prevention programs. For instance, outpatient therapy options include 
parent management training, which focuses on parent-child interactions, and cognitive-
behavioral therapies that specifically target emotion regulation and social problem-solving.26, 27  
Strategies to improve children’s social perspective taking include social skills training, video 
modeling, acting classes, role-playing, mindfulness training, and parental conversational 
techniques.2, 4, 28-38 However, these strategies often require continued engagement, motivation, 
and interest from children, and they can be difficult to implement in a self-directed or 
individualized manner. 
 
To address these concerns, software interventions have shown some promise to improve 
perspective taking. In a recent adult study,30 users could inhabit the first-person perspective 
(via a computer screen) of a negotiation counterpart by experiencing parts of their day. This 

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alternative perspective was found to improve perspective taking and result in more equitable 
conflict resolution relative to text instructions or other ways of learning about the counterpart. 
With virtual reality (VR), research in adults has found that inhabiting the virtual body of a 
member of a specified outgroup reduces stereotypes and increases positive feelings for the 
elderly,39 different races,40 and patients with schizophrenia41 or colorblindness.42 Enacting long-
term cognitive or behavioral changes is difficult in children with DBD, and we do not expect 
small doses to have an extended long-term impact. However, our hope is that extended VR 
software packages can be developed to work over the long-term, likely in conjunction with 
more traditional therapy strategies. 
 
VR has exciting therapeutic potential to address perspective-taking deficits because it provides 
naturalistic yet controlled environments in which users can experience interactions from multiple 
viewpoints. VR interventions typically provide better generalization to real-world behavioral 
changes compared to traditional methods.43 VR has an advantage over traditional interventions 
because it provides an embodied experience that is a middle ground between therapy room 
settings and the real world (e.g., school, home) where problematic behaviors occur. Our own 
preliminary data with a VR school cafeteria environment indicates that children find VR to be 
enjoyable and easy to use, and it invokes real-world reactions—youth with greater conduct 
problems interpreted encounters with virtual counterparts as more hostile.  
 
In this investigation, we will build upon our current VR design using an Oculus Quest virtual 
reality headset. After experiencing virtual interpersonal conflicts, subjects will re-experience 
scenarios in one of two manners: an enriched perspective from the virtual counterpart’s point-
of-view, with internal dialogue and background information; or a control perspective, which 
replays the original point-of-view. During this proof-of-concept phase, our primary target is 
social perspective taking. We will assess functional engagement of this target by quantifying (1) 
the ability to recognize and understand the virtual counterpart’s perspective; and (2) the neural 
response (in pain circuitry) to pain experienced by the virtual counterpart, a common marker 
for perspective taking that is abnormal in DBD.23, 24, 44 
 
Medical Device:  
 
The Oculus Quest virtual reality headset will be categorized as a medical device for this 
investigation. Oculus Quest is commercially available for use by all ages and does not present 
any serious risks to the health, safety, or welfare of subjects. The headset is a standalone 
device with goggles and headphones that is used outside the laboratory for both educational 
and entertainment purposes (for video games, movies, sporting events, etc.). It is similar to 
other commercially available VR headsets. When using the Oculus Quest, visual stimuli are 
presented via the goggles along with corresponding sounds. With this investigation, we will 
program software to present virtual scenarios to participants for short periods at a time (<3 
minutes). A minority of participants may experience VR sickness during their experience, which 
is similar to motion sickness (e.g., mild nausea or lightheadedness). These effects are 
temporary and dissipate soon after removing the headset, which can be easily done at any 
time. In addition, these effects are no different than could be experienced if the participant was 
using the headset outside the laboratory for entertainment purposes. 
 
 
 

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2.0 
Objectives 
 
To investigate the impact of virtually experiencing alternative perspectives on social 
perspective-taking mechanisms, we will target the following specific aims in youth aged 9-12 
who have been diagnosed with a disruptive behavior disorder. 
 
Aim 1: To determine if experiencing alternate perspectives within a VR scenario (with internal 
dialogue and background context) engages social perspective-taking processes in youth with 
disruptive behavior disorders. 
 
Aim 2: To evaluate whether VR perspective-taking scenarios increase neural sensitivity to pain 
experienced by virtual counterparts. 
 
 
3.0 
Outcome Measures 
 
Primary Outcome Measure: VR Perspective Taking Scale 
This scale measures the degree to which participants understand the perspective of their virtual 
counterpart. It will be completed after each VR scenario, both pre- and post-intervention. Each 
participant’s change score will be as Post-treatment (Endpoint; following all VR) vs. Pre-
treatment (Baseline; after first scenario). The Cohen’s d effect size will be calculated using the 
difference in mean change scores between treatment and control conditions (e.g., [MeanEnriched 
Post-Pre – MeanControl Post-Pre] / SDpooled), resulting in an effect size measurements for both scales 
with each treatment condition.  
 
Primary Outcome Measure: Acknowledgement of Other Perspective Scale 
This scale allows participants to rate the relative importance of the virtual counterpart’s 
perspective with a scenario-specific question. It will be completed after each VR scenario, both 
pre- and post-intervention. Each participant’s change score will be as Post-treatment (Endpoint; 
following all VR) vs. Pre-treatment (Baseline; after first scenario). The Cohen’s d effect size will 
be calculated using the difference in mean change scores between treatment and control 
conditions (e.g., [MeanEnriched Post-Pre – MeanControl Post-Pre] / SDpooled), resulting in an effect size 
measurements for both scales with each treatment condition.  
 
Primary Outcome Measure: Neural response to Self vs. Other Pain 
This is an fMRI measure of brain function while imagining pain happening to oneself or the 
virtual counterpart. Following standard preprocessing of fMRI data, we will calculate the 
regression coefficient for each stimulus type (Self Pain; Self No Pain; Other Pain; Other No 
Pain). We will extract mean activity from a priori regions-of-interest (ROIs), established as 10-
mm radius spheres around MNI coordinate peaks in dACC (-2,33,40) and anterior insula (left: -
40,22,0; right: 39,23,-4), which were identified as key regions for pain response in a recent 
meta-analysis. Brain activity will be quantified by contrasting self-perspective pain (Self Pain vs. 
Self No Pain) with other-perspective pain (Other Pain vs. Other No Pain). Cohen’s d effect size 
will be calculated separately for each treatment and each ROI. For more traditional statistical 
measures, a 2x3 (pain perspective condition by group) within-subjects ANOVA test will be 
performed on data from each ROI. 
 
 

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4.0 
Eligibility Criteria 
4.1 
Inclusion Criteria 
Children: 
• Aged 9-12 at time of enrollment 
• English-speaking 
• Meet DSM-5 criteria for oppositional defiant disorder (ODD), conduct disorder 
(CD), or Other Specified or Unspecified Disruptive, Impulse-Control, and 
Conduct Disorder 
• Right-handed 
• Estimated full-scale IQ greater than 70 
 
Parents/Guardians: 
• English-speaking 
• Must live with child participant 
• Reliable reporter of child's personality and behavior 
 
4.2 
Exclusion Criteria 
Children:  
• Bipolar disorder, any disorder involving psychosis, pervasive developmental 
disorders, current or past substance use disorder, or current major depressive 
disorder 
• History of neurological problems (e.g., epilepsy, traumatic brain injury) 
• Contraindications for MRI 
• Sibling who has participated in this study 
• Experience negative side effects during use of virtual reality (e.g., VR 
sickness) 
• In opinion of investigator, cannot complete study procedures or is 
inappropriate for study participation 
 
 
 
5.0 
Study Design 
 
This project will examine how levels of a virtual reality treatment that provides users with the 
alternate perspective of an interpersonal interaction impacts psychological and neurobiological 
markers of perspective taking. Prior to Visit 3, participants will be randomly assigned to 
different VR perspective conditions, stratified by sex, presence/absence of ADHD diagnosis, and 
ODD/CD diagnosis, via an a priori randomization chart. An equal number of youth will be 
randomly assigned to either the alternate perspective condition or control condition. Assignment 
will be sealed for the experimenter until immediately prior to Visit 3 (for visit preparation, 
experimenter must be unblinded). Visits 1 and 2 will be identical for both groups. At Visit 3, the 
initial VR scenarios and assessments will be identical. The participant will then re-experience the 
VR scenarios depending on their assigned condition. Additional VR assessments and the MRI 
scan will be identical for both groups. 
 

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6.0 
Recruitment & Enrollment/Randomization 
 
 
Participants will be recruited in a variety of manners, including direct contact and flyers at the 
Riley Child and Adolescent Psychiatry Clinic (RCAPC) and Eskenazi Health, print and radio 
advertisements, community flyers, work with local organizations, and potential contact through 
recruitment services and health databases.  
 
At the RCAPC, all clinical psychologists, psychiatrists, and social workers at the clinic will be 
informed of the study and provided informational flyers for patients, which will also be posted in 
the waiting room. The same will occur at Eskenazi Health. Providers may also post a brief 
description of the study along with our contact information, links to our lab Facebook page and 
REDCap landing page (described below), and a QR code linked to our REDCap Landing Page in 
their virtual waiting rooms seen by patients waiting for their remote visits to begin. 

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We will also recruit subjects from a medical records review with information provided to us by 
the IU Health Research Data Extraction process. The IU Health Information team will evaluate 
the medical records from the RCAPC and provide our study team the general information 
(name, MRN#, birthdate, date of diagnosis, etc.) and contact information of patients who meet 
our study’s inclusion and exclusion criteria. Once provided with a list of children who may match 
our study’s qualifications, we will reach out to parents via the contact information provided to 
describe our study and gauge their interest in participating, through a postcard mailed to their 
address and then follow-up with phone calls or emails, or via direct email contact. 
 
Paper flyers will also be posted in public arenas around the Indianapolis area, including libraries, 
bus stops, coffee shops, and other community boards. Flyers may also be posted in IUPUI and 
IU Health facilities, or additional local child mental health facilities where permission has been 
provided. Flyers will also be provided to current subjects who indicate an interest in providing 
information to other interested subjects. We will also contact local organizations, including local 
schools and summer camps. Potential participants and parents will be asked to email or call our 
recruitment-designated email address and/or phone number. 
 
We may partner with community organizations who may post information about our study on 
their social media sites (Facebook, Instagram, Twitter, etc.). These posts may include study 
details, pertinent inclusion/exclusion information, study contact information including our 
recruitment website, and will not emphasize payment for participation. Partner organizations 
may also provide contact information of potentially interested parties. The research team can 
then initiate contact with potential subjects to gauge their interest in participating in our study.  
 
We will also recruit parents/guardians of potential participants via study information provided to 
the All IN for Health Research and Clinical Studies database (https://allin4health.info/) and the 
ResearchMatch database (https://www.researchmatch.org/). The All IN for Health Research and 
Clinical Studies database is powered by TrialX iConnect and provides a list of active studies 
being conducted in Indiana by faculty at Indiana University and other research institutions in 
the surrounding area. Anyone can browse studies by location, keywords, health topics, or 
conditions and directly contact the study team. ResearchMatch is a similar database, although 
national in scope. Another aspect of the All IN for Health database and ResearchMatch is their 
volunteer registry. Researchers can browse users who have agreed to input their medical 
history, and request to contact those who might match the qualifications for our study. Some 
study flyers will also include a QR code directing participants to our information on these sites. 
 
Study information will be included in the iConnect All IN for Health e-updates newsletter, 
emailed bi-monthly to more than 32,000 subscribers which includes those in the All IN for 
Health volunteer database. The newsletter shares what’s going on in the community to improve 
Indiana health. Study information will also be posted from the iConnect social media accounts 
(Facebook, Instagram, Twitter, etc).  
 
A study posting with a brief description of the study will also be sent to IUHealth News, which is 
sent to all IUHealth employees. 
 
We will post study information to online community boards, such as craiglist.org, nuvo.net, IU 
classified pages, and similar sites.  

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Information about the study and a link to our All IN For Health page and our REDCap landing 
page will also be posted on our lab website, on our lab Facebook page, and on the IU School of 
Medicine Facebook page. Members of the study team may also share or post information about 
the study on their personal social media sites. This information will note that the study is paid 
but will not include specific payment information (e.g., dollar amounts). 
 
We will also recruit parents/guardians of potential participants via social media. We will run 
Facebook ads from our lab account and from the IUSM account that show information about 
the study to targeted Facebook users. Our target user will be adults in Indianapolis with 
children ages 9 – 12. If a user would like more information and clicks on the post, they will be 
directed to one of two places: either our study’s All IN for Health Research and Clinical Studies 
website where there is an opportunity to contact the study team directly, or to our REDCap 
landing page where there’s an opportunity to answer some brief eligibility questions then 
contact the study team. The REDCap page will ask broad, preliminary questions related to study 
criteria, but these responses will not be used to assess eligibility. We will reach out to 
individuals who provide contact information via the REDCap page, in order to provide additional 
study information. 
 
IndyVRstudy.com is our study website that displays information about the study (what’s 
involved, who is eligible, etc.) and information about the research team (contact info, link to our 
lab Facebook page). There are also multiple buttons that redirect visitors to our REDCap landing 
page for additional information. The site will be used with word-of-mouth recruitment, on social 
media posts, and with other recruitment materials as study contact information.  
 
 
Parents and children will also be recruited via an online blog post by the Indy’s Child magazine. 
This blog post will include information about the study and links to the lab Facebook page as 
well as the All IN For Health page. If interested, potential subjects will be able to enter their 
information via All IN For Health. This blog post will target our specific demographic of parents 
in the Indianapolis area.  
 
We will also use on-air radio and tv commercials to recruit potential subjects. This ad will briefly 
describe the study, potentially mention compensation, and direct those interested to reach out 
by phone or email or to visit our recruitment website (IndyVRstudy.com).  
 
Digital ads containing a brief description of the study with a hyperlink to our recruitment 
website will be displayed on the WFYI website, as well as sent out in e-newsletters to WFYI 
subscribers.  
 
We will also run a people-based marketing campaign. Digital ads such as emails, social media, 
website banner ads etc. will be presented to parents and teachers in the Indianapolis area who 
voluntarily submitted their information to a media habit database managed by Cumulus Media. 
The research team does not have access to this database and will only learn identifying 
information of those included in the campaign audience if one chooses to express interest in the 
research via phone, email, All IN for Health or REDCap Landing Page.   
 
If a parent expresses interest in the study via phone or email, we will contact them via phone to 
describe the study and ensure the child meets inclusion/exclusion criteria. We will ask them 

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screening questions derived from DSM-5 criteria for oppositional defiant disorder, as well as 
excluded disorders (e.g., neurodevelopmental disorders, current depression). If they potentially 
qualify via review by the PI and clinical co-Is, they will be scheduled for their screening session. 
We will send directions and informed consent and assent forms for them to review (these will 
be reviewed and signed in person). We will provide reminder contacts (email or phone, as 
preferred) at least one week prior to their session date.  
 
Participants may also opt-in to text reminders about study visits. When scheduling the first visit, 
we will ask questions whether they want to be texted from our Google Voice account. We will 
note that messages will only be sent from lab-issued devices and we will delete all contacts and 
contact info from devices following completion of their participation. However, Google Voice 
may maintain a call history with the account. 
 
All text messages will be sent from our Google Voice number via the lab tablets. These tablets 
are password-protected, and any contacts with study participants made via the Google Voice 
account, including texts and contact info, will be deleted upon completion of the subject’s 
participation. 
 
Participants will be instructed that if they need to contact the study team on the day of their 
study visit (e.g., if they are running late), to call or text us via our Google Voice number, which 
can be connected to our lab tablets. 
 
For Visit 3, we will remind parents of the information they completed on the Medication Log 
(see Visit 2 Study Procedures), as it would be helpful for the same medications to be used at 
that visit. However, we will caution that they should use their best judgement and follow 
doctor’s orders when providing medication, and that this is not a study requirement. 
 
Randomization will occur only for those participants that meet all inclusion/exclusion criteria 
following the first study visit and are able to be scheduled. A randomization table will be created 
by our statistical team, stratified by sex, ADHD status, and ODD/CD diagnosis to create equal 
numbers of boys and girls in each condition. This assignment will be sealed to the research 
team until within 24 hours of the third study visit. 
 
Previously active subjects whose visits were cancelled due to the COVID-19 outbreak will be 
permitted to restart all study procedures, including being reconsented using the most recent 
informed consent documents. 
 
 
7.0 
Study Procedures 
 
 
Visit 1 
 
Visit 1 procedures may take place over a single visit or may be broken up into multiple visits for 
ease of scheduling. In addition, some procedures may be carried out remotely to limit in-person 
interactions and reduce infection risks associated with COVID-19. For remote participation, the 
order of Visit 1 procedures (following informed consent) may be altered. All in-person study 
procedures will take place at Goodman Hall. For all visits, we will follow up-to-date IU and IU 

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Health safety guidelines, which may require children and parents to wear masks while in 
Goodman Hall. 
 
The consent and assent procedures will be carried out prior to any study procedures. These 
may be carried out in person or remotely. Parents will provide written consent for their own and 
their child’s participation. Children will provide written assent. For participants conducting the 
process in person, these forms will be presented in a private room to both parents and children 
together, and they will be given the opportunity to ask investigators any questions they may 
have. For participants and parents undergoing the process remotely, they will be sent a link to a 
REDCap survey. The person obtaining consent will conduct the consent and assent processes 
over the phone or video link (e.g., Zoom) while parents and children view documents 
electronically. All signatures will be obtained and recorded electronically and parents will be sent 
a copy of all signed documents via email or regular mail, as preferred. 
 
Following the consent/assent process, we will collect personal information, including parent and 
child names, dates of birth, and the child’s birthplace. This information will be maintained on a 
secure REDCap database, separate from personal health information and research databases. If 
the REDCap database is not available, we will take the information on a paper form, which will 
be shredded after entering the information into REDCap. 
 
At the beginning of each remote study visit, the researcher will confirm the exact location of the 
subjects for safety purposes. If this is the same as the address provided on the form, that will 
be noted. If not, the subject’s address will be written on paper or a white board and will be 
shredded after the visit.  
 
Parents and child participants will undergo a semi-structured clinical interview, the K-SADS-PL, 
with a trained clinician, social worker, or clinical graduate student. This interview may be 
conducted in-person or remotely and may be scheduled on a separate day if necessary. This 
process is started by the completion of the DSM-5 Self-Rated Level 1 Cross-Cutting 
Symptom Measure questionnaire, which asks about the presence of child mental health 
symptoms over the previous two weeks. The interview allows the clinician to complete a 
diagnostic checklist. Parent(s) will be informed about results of the K-SADS clinical interview 
after it has been completed. If follow-up treatment is desired, we will provide information about 
local mental health treatment options. If requested, a brief written summary will be provided. 
 
After the interview, in-person subjects will be given a short break. Snacks and small trinkets 
(~$1) may be given to the child to help motivate them and maintain attention. These may also 
be given out at Visits 2 and 3. 
  
Parents and children will also complete surveys. Survey questions will be presented and 
recorded via REDCap or the IU Qualtrics system, an online survey system. For remote 
participation, these surveys can be completed prior to the K-SADS-PL clinical interview. Prior to 
the clinical interview, the DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure will be 
administered electronically. For in-person visits, both parents and children will complete surveys 
via electronic tablets (paper copies of surveys will be used if tablets are not functioning 
properly). Paper forms will be provided only if the electronic system is not working.  

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Children will first complete a practice survey to become familiar with the mechanics of using the 
tablet to answer questions. This practice will consist of all question types found in the surveys 
below.  
 
Children will then complete the following surveys, expected to last 30 minutes in duration: 
 
1. A child version of the Interpersonal Reactivity Index (IRI), which provides subscales for 
Perspective Taking, Fantasy, Empathetic Concern, and Personal Distress. 
2. NIH Toolbox Perceived Hostility, Perceived Rejection, and General Life 
Satisfaction Fixed Forms 
3. The Inventory of Callous-Unemotional Traits, a 24-item questionnaire to provide an 
assessment of the child’s callous and unemotional traits among antisocial youth. 
4. Media Exposure Questionnaire. This questionnaire is a modified version of the Media 
Exposure Measure, which quantifies the child’s television, video game and VR exposure. 
5. Virtual Reality Experience Survey, which quantifies how much previous experience the 
child has had using virtual reality and specifies how often the technology was used for certain 
activities. 
6. Video Game Motivations and Desires. This 30-item survey measures children’s reasons 
for playing video games, based on the GAMES survey of video game motives and preferences. 
7. UPPS-P Impulsive Behavior Scale. This 20-item self-report measures personality traits 
that lead to impulsive-type behavior. 
 
 
For in-person participation, children will complete the K-BIT-2 IQ test45 upon completion of 
surveys. If surveys are completed remotely, this IQ test will be conducted during the in-person 
portion of Visit 1.  
 
Parents will complete separate surveys. These surveys include the following: 
 
1. Demographics – Parents will report background information on their child and the family, 
including age, sex, grade, handedness, and parental income and employment. This 
questionnaire also collects information on the child’s medical history, primarily focusing on 
mental health treatment.  
2. Parent Pubertal Development Scale, which measures the child’s stage of development. 
3. NIH Toolbox Emotion Battery Ages 8-12 Parent Report, which includes surveys 
assessing the child’s Positive Affect, General Life Satisfaction, Emotional Support, Friendship, 
Loneliness, Perceived Rejection, Perceived Hostility, Self-Efficacy, Sadness, Perceived Stress, 
Fear, and Anger 
4. The Outburst Monitoring Scale (OMS),46 which measures the child’s verbal, physical, 
property, and self-directed aggression. 
5. Media Exposure Questionnaire. This questionnaire is a modified version of the Media 
Exposure Measure, which quantifies the child’s television and video game exposure. 
6. Virtual Reality Experience Survey, which quantifies how much previous experience the 
child has had using virtual reality and specifies how often the technology was used for certain 
activities. 
7. Family Environment Scale (FES): Short Version,47 a 9 item questionnaire designed to 
assess personal relationships and the overall social environment of a family through three 
categories: interpersonal relationships, growth, and organization/structure.  

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8. The Sleep Disturbance Scale for Children,48 a 27 item questionnaire used to gauge 
overall sleep habits and disorders in children. This scale uses five subdomains: initiating and 
maintaining sleep, breathing, arousal, sleep wake transitions, excessive somnolence and 
hyperhidrosis.  
9. The Indiana Institute of Biomedical Imaging Sciences (IIBIS) MRI Safety Screening Form 
to confirm that there are no MRI contraindications (paper only) 
 
Remaining procedures require in-person participation. Participants will practice using the Oculus 
Quest VR headset, which includes goggles and headphones. As part of this practice, participants 
will develop their virtual avatar, which will be used during virtual scenarios at the next visit and 
may be provided to them prior to the second visit. To increase identification with their virtual 
self, participants will be directed to create a virtual avatar that best resembles them (sex, hair 
color/length, skin tone, choice of t-shirt). Following this use, child participants will complete the 
Simulation Sickness Questionnaire,49 which quantifies physical symptoms such as general 
discomfort, nausea, and dizziness. If there is time, parents may also be provided the 
opportunity to wear the headset. 
 
Lastly, participants will visit and lay in a mock scanner, to increase their comfort with the MRI 
scanner. The mock scanner provides a similar environment and can play similar noises as the 
real scanner. 
 
If there are concerns about potential signal loss from orthodontics or implants that are MRI-
safe, the participant may also receive a brief (roughly 10 minute) MRI scan to assess the extent 
of signal loss in the brain. 
 
For all parent and child surveys, subjects may be asked to retake all or parts of these surveys 
where there may have been errors (e.g., technical difficulties or noncompliance), as determined 
by the research team. 
 
If the VR practice or avatar creation could not be completed during Visit #1, it can be 
completed at the beginning of Visit #2.  
 
Visit 2 
 
Participants will undergo an MRI scan that will last about 1 hour. Prior to the scan, the parent 
and child will complete the Indiana Institute of Biomedical Imaging Sciences (IIBIS) MRI 
Safety Screening Form to confirm that there are no MRI contraindications. They will also 
complete the Medication Log form to indicate what medications or caffeine the subject had 
taken that day. This information will also be provided to parents during the reminder call or 
email for Visit 3, with a request that the same substances be utilized at Visit 3 if possible. 
 
Participants will also see examples of stimuli that they will view during the scan and be 
instructed on what the MRI task will entail. They will practice button-press tasks as well. 
 
MRI scans will take place on a research-dedicated 3T Siemens Magnetom Prisma MRI scanner 
at Goodman Hall. First, we will conduct a 3D magnetization prepared rapid gradient echo 
(MPRAGE) scan for individual anatomical reference, comprised of 160 sagittal slices with 
1.0x1.0x1.2 mm voxel dimension. In the scanner, images will be presented via E-prime 

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software and back-projected to participants. Functional scans will be acquired using T2*-
weighted gradient spin echo-planar imaging (EPI) sequence with TR/TE 1200/29 ms for 54 axial 
slices and voxel size of 2.5x2.5x2.5 mm. 
 
The fMRI task employs a paradigm that has compared self vs. other perspective taking in the 
response to painful stimuli.18-21 A mixed block fMRI design will be used, with two 8-minute runs 
of our task. There are four conditions: self pain, self no pain, other pain, and other no pain. 
Each block (40sec duration) will be either “Self” or “Other,” as indicated by task instructions 
prior to the block (“Imagine these situations are happening to you/him/her) and an image of 
the virtual avatar (virtual self or virtual counterpart; image remains in corner throughout block). 
Within the block, participants will be shown Pain images (e.g., hand slammed in door) and No 
Pain images (e.g., hand on door handle) (3 each/block; 2sec duration; jittered interstimulus 
interval 2-5sec).18-20 There will be 6 blocks of each type during both 8-minute runs (96 total 
trials/run), with block order pseudorandomized across participants.  
 
An additional task will present subjects with child faces with different emotional faces and ask 
them to respond to specific questions that probe emotion recognition, empathy, or the sex of 
the face. 
 
After the MRI, the subject will be presented with a series of images. They will then determine 
which of the images they saw while completing the tasks in the MRI. This task measures how 
well subjects were attending to stimuli during the brain scan.   
 
Visit 3 
 
Participants will take part in the VR task with the Oculus Quest VR headset. We will fit the 
headgear to the child and ensure that it is comfortable. Subjects will remain seated while 
interacting with the virtual world and use hand-held controls to move or control objects. 
Subjects can turn their head to look in any direction in the virtual world. Using state-of-the-art 
‘Oculus Touch’ hand-held controllers that react to hand movements, the user will be able to 
move and interact with virtual objects and characters. Headphones play auditory stimuli. 
 
Children will first explore the virtual cafeteria for three minutes to allow them to understand 
hand controls and become acquainted with the environment before starting the task scenarios. 
They may ask questions and talk with investigators during this time, who will ensure that 
subjects are able to use controls and move around in the environment properly. 
 
The virtual environment is a school cafeteria setting. Following practice, participants will take 
part in three scenarios in the school cafeteria. Each scenario will last up to two minutes. In two 
scenarios, after the subject hears the school bell ring, the goal is to place trash on their 
cafeteria tray and take the tray to the trash. In a third scenario, the subject is directed to clean 
up the mess at their table. Once the task is complete, the scenario will be complete. In each 
scenario, virtual characters will populate the environment to make it more realistic, including 
some characters (students) who will also be returning their trays. However, the social 
environments will differ, and each scenario includes a virtual counterpart that interferes with 
the goal.  
 

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After each scenario, children will remove the headset and complete questions via electronic 
tablet. First, they will complete our VR Perspective Taking Scale, which assesses how well 
they understand the virtual counterpart’s perspective. Next, they will complete a question for 
the Acknowledgement of Other Perspective Scale, which reflects the relative importance 
given to the perspective of the participant and the virtual counterpart. 
 
They will also complete a Post-scenario Survey regarding how they interpreted the intentions 
of the virtual counterpart (Were any of the characters trying to be nice to you? Were any of the 
characters trying to be mean to you?) and real-life responses (Would you be mad if this 
happened in real life? Would you try to hit other characters if this happened in real life?). 
Responses will be provided on a continuous sliding scale from 0 to 100 with labeled endpoints. 
We will also quickly assess current mood state (happy, sad, stressed, frustrated, calm) on 
sliding scales and complete the Simulation Sickness Questionnaire and a VR Usability 
Survey. 
 
Following completion of each scenario, subjects will then experience the scenario again. Each 
subject will be randomly assigned to the (a) Alternate Perspective or (b) Control Perspective. In 
the Alternate Perspective condition, participants will experience the scenarios again from the 
virtual counterpart’s perspective within the VR system. The Control Perspective will repeat the 
initial interaction from the same perspective. After each scenario, participants will answer 
questions identical to those after initial scenarios: the VR Perspective Taking Scale and the 
Acknowledgement of Other Perspective Scale, as well as questions about character 
intent, real-life responses, mood, the Simulation Sickness Questionnaire, and VR 
Usability. 
 
If errors with the VR technology are observed, subjects may restart the scenarios and 
subsequent surveys. 
 
Parents will also once again complete the Indiana Institute of Biomedical Imaging Sciences 
(IIBIS) MRI Safety Screening Form and the Medication Log.  
 
Participants will be instructed about the MRI task and will briefly practice again. Participants will 
then undergo an MRI scan for about 1 hour. This scan may not be performed if the previous 
scan (at Visit 2) was not completed successfully. This scanning session will be identical to Visit 
2, including an anatomical scan and functional scans in which participants will see images of 
painful and non-painful actions, under conditions where they are told to imagine scenes 
happening to themselves or the virtual counterpart, as well as the emotional face task.  
 
After the scan, participants will be presented with images and asked to identify which ones they 
remember from the MRI scan.  
 
Following the MRI scan, children will complete an end-of-study Usability and Environmental 
Presence survey, that asks additional questions about overall usability, environmental 
presence (how “real” the environment feels), and opinions on its helpfulness. Investigators will 
then answer any questions that they may have about their involvement or the VR scenarios.  
 

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At the beginning of each in-person visit, parents are to complete the Parent/Guardian Safety 
Contact Sheet. This asks for the parent/guardian’s name and phone number where they can 
be reached for the duration of the visit. This form gets shredded after each visit. 
 
Prior to receiving compensation for the visit, the parent and child will be asked briefly about 
real-life situations that prompted recent arguments. The responses will be recorded by the 
researcher and used to develop content for the next phase of research.  
 
At the end of each visit, parents and children will then be compensated and thanked for their 
time. A school note will be provided upon request confirming the child attended our study visit. 
 
Compensation 
Participants will be compensated at the completion of each study visit. For remote participation, 
compensation will be provided via electronic gift cards. Children will receive $75 for Visit 1 ($25 
for surveys, $25 for K-SADS-PL, $25 for VR practice/MRI mock scanner), $100 for Visit 2 
(including $75 for MRI), and $150 for Visit 3 (including $75 for VR procedures and $75 for 
MRI). Parents will receive $25 for Visit 1. In addition, a parking voucher will be provided for 
each study visit. If a participant withdraws prior to completion of all visit procedures (including 
Visit 1 procedures scheduled on a separate day), they will be compensated only for tasks that 
have been completed. Parking will be compensated in full for each visit regardless of which 
tasks have been completed. 
 
8.0 
Study Calendar 
 
 
Phone Screen (Expected duration 10-15 minutes) 
 
--------------Variable time to Visit 1; Up to 6 months-------------- 
 
Visit 1 (Expected duration 3-4 hours) 
 
Procedures may be split into multiple visits 
 
1. Informed Consent/Assent* 
2. K-SADS-PL* 
3. Parent/Child surveys* 
4. IQ test 
5. VR Practice & Avatar Creation 
6. Mock Scanner 
 
*May be conducted remotely 
 
--------------Up to 6 weeks from K-SADS-PL until Visit 2-------------- 
 
Visit 2 (Expected duration 2 hours) 
1. MRI Scan 
 
--------------Up to 2 weeks until Visit 3-------------- 
 

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Visit 3 (Expected duration 2-3 hours) 
1. VR Scenarios & Assessments 
2. VR Scenarios (Assigned Perspective Condition) & Assessments 
3. MRI Scan 
 
 
 
 
9.0 
Reportable Events 
 
All serious adverse events (SAEs) and Unanticipated Problems Involving Risks to Subjects or 
Others (UPIRTSO) will be immediately reported to the Indiana University Institutional Review 
Board (IRB) within 5 working days; other adverse events or protocol deviations will be reported 
to the IRB based on IRB guidelines (typically reported at the time of renewal). We will also 
 
 
Visit 1 
Visit 2 
Visit 3 
Parent & Child: K-SADS Clinical Interview 
X 
 
 
Parent: Demographics; Outburst Monitoring Scale; NIH Toolbox 
Emotion Battery; Media Exposure Questionnaire; VR 
Experience Survey; Family Environment Scale; Sleep 
Disturbances Scale for Children 
X 
 
 
Child: Interpersonal Reactivity Index; NIH Toolbox measures; 
Inventory of Callous-Unemotional Traits; Media Exposure 
Questionnaire; VR Experience Survey;  
Video Game Motivations and Desires Scale; 
Impulsive Behavior Scale 
X 
 
 
Parent & Child: MRI Screening Form 
X 
X 
X 
Child: VR Practice & Avatar Creation 
X 
 
 
Child: Simulation Sickness Questionnaire 
X 
 
X 
Child: Mock Scan 
X 
 
 
Child: MRI Scan 
 
X 
X 
Child: VR task & assessments (VR Perspective Taking Scale; 
Acknowledgement of Other Perspective Scale; Post-scenario 
Survey; Mood state; VR Usability & Environmental Presence)  
 
 
X 
 

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report to the NIMH program officer within 10 working days. An example of a rare but serious 
adverse event is injury from metal objects in the proximity of the MRI scanner. Mild, temporary 
VR sickness (e.g., nausea) will be considered an adverse event but not a serious adverse event. 
 
Any adverse events (serious or not), as well as the progress of the study will be reviewed and 
discussed in detail at the meetings of our DSMB. Non-serious adverse events or protocol 
deviations will be reported to the IRB based on IRB guidelines (typically reported at the time of 
renewal). 
 
For all AEs and SAEs deemed unexpected and/or unrelated to the study, a summary will be 
submitted to the NIMH PO with the annual progress report. Protocol violations will also be 
included in this annual progress report. Temporary suspension of the study will be reported to 
NIMH within three working days, along with a statement of the reason(s) for the action. 
 
 
10.0 Data Safety Monitoring 
 
PI Dr. Hummer, in consultation with co-Investigators Dr. Kronenberger and Dr. Neumann, is 
responsible for data and safety monitoring and ensuring that the protocol is being properly 
followed, with independent oversight also provided by a local Data and Safety Monitoring Board 
(DSMB). Data quality, subject recruitment, accrual, retention, outcome and adverse event (AE) 
data, procedures designed to protect the privacy of subjects, and subject satisfaction will be 
monitored. Any unanticipated problems encountered or observed by research staff will be 
promptly reported to Dr. Hummer. If Dr. Hummer will be unavailable for contact for an 
extended period while study procedures are ongoing, he will designate a co-investigator to be 
the primary contact for research staff should such problems arise. 
 
Co-investigators Dr. Kronenberger and Dr. Neumann will help Dr. Hummer distinguish serious 
from non-serious adverse events, as well as relatedness to study participation. SAE's will be 
graded based on the Mild-Moderate-Severe grading scale. The scale is as follows: Mild - no 
limitation of usual activities, Moderate - some limitation of usual activities, or Severe - inability 
to carry out usual activities. 
 
Any adverse events (serious or not), as well as the progress of the study will be reviewed and 
discussed in detail at the meetings of our ad hoc DSMB.  These meetings will occur at least 
once every six months.  Additional meetings will be scheduled “as needed.”  This board consists 
of experts in child psychology, information technology, clinical trials, and biostatistics. This 
DSMB is currently headed by Dr. Flora Hammond (Professor of Physical Medicine & 
Rehabilitation). 
 
A report is generated on this study from each meeting, which will be shared with the NIMH 
program staff. The reports contain a summary of enrolled, discontinued, and recruited subjects, 
a list of any adverse events and details reviewed by the DSMB.  Any findings, concerns or 
recommendations of the DSMB, along with an action plan for how to implement those 
recommendations, will be provided. 
 
Dr. Hummer’s lab team (research assistant, research coordinator, postdoctoral fellow, volunteer 
student researchers) will meet weekly discuss study progress and issues, and all study 

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personnel (PI, co-investigators, research staff) will meet semi-annually to review data, number 
of subjects, responses observed, and any concerns not otherwise addressed (i.e., other than 
adverse events or protocol deviations). At weekly lab meetings, a different co-investigator will 
be involved once a month, so each co-investigator will be present at least once every 3-4 
months, in addition to semi-annual meetings. 
 
Each meeting will have specific time dedicated to any issues in study data that pertain to safety 
of subjects. Any safety issue that requires temporary suspension of the study will be reported to 
the IRB and NIMH within three working days, along with a statement of the reason(s) for the 
action. In addition, Dr. Hummer and research staff will review study enrollment at weekly lab 
meetings and compare present status to enrollment targets. Data will be presented on 
enrollment numbers, screen fails, and withdrawn subjects, as well as race/ethnicity and sex of 
subjects. If necessary, we will modify recruitment efforts in order to maintain ability to reach 
target enrollment for race, ethnicity, and sex. 
 
All study staff, including the PI, will complete (and as needed, renew) required training 
regarding the protection of human subjects, informed consent procedures, and confidentiality. 
This training includes completion of CITI (Social/Behavioral/Educational Researchers) and Good 
Clinical Practice training. The trial will not begin until researchers have completed the Good 
Clinical Practice training.  
 
 
11.0 Study Withdrawal/Discontinuation 
 
A child participant or their parent may withdraw from the study at any time by letting the 
research team know they wish to discontinue their participation. The participant(s) will be paid 
for their time completed in the study. 
 
Participants will be precluded from continuing the intervention if they report adverse health 
consequences from using virtual reality equipment during practice or intervention. In addition, 
inability to complete the MRI scan, including claustrophobia or an unforeseen health 
consequence, will also halt a subject’s participation. 
 
If a worsening of DBD symptoms is identified via voluntary report or visit assessments, the 
family will be queried to determine the nature of symptoms, including relationship and proximity 
to study procedures. Dr. Hummer and clinical psychologists on the team will review these data, 
and if a worsening of symptoms is judged to be significant and likely related to study 
participation, the subject will be discontinued from participation. Additionally, depending on the 
severity of symptoms, the subject may be offered or referred for further evaluation of 
symptoms; the urgency of this evaluation will depend on the nature and severity of symptoms 
but may range from a standard outpatient visit to an urgent/emergent evaluation. 
 
12.0 Statistical Considerations 
 
We will enroll 95 children in order to target 40 completers (n = 20/group, allowing for 15-20% 
screen fail and 15-20% attrition). Attrition (apart from screen fails) will occur between the two 
scanning visits, which are only one week apart and are expected to be due to noncompliance or 
in-scanner subject motion that renders data unusable. Attrition rates are not expected to 

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change from year to year, as subjects will remain active only from the time of screening to Visit 
3 (up to 8 weeks).  
 
In similar research, pre/post correlations of 0.72 and 0.89 were found for measures of Theory 
of Mind (closely related to social perspective taking) in a VR intervention for social cognition 
training.50 In research by co-I Dr. Neumann involving a multi-session skill-building 
intervention,51 pre/post scores had a correlation of 0.69 on the Perspective Taking subscale of 
the Interpersonal Reactivity Index. Here, we use a more conservative estimate for a pre/post 
correlation of social perspective taking of 0.6. With 20 subjects per group and assuming an 
ANCOVA model (specified below) is used with a pre/post correlation for social perspective 
taking of 0.6 an effect size of 0.73 (observed for the meanness rating in the preliminary study) 
can be detected between two groups with 80% power using a two-sided two-sample t-test with 
alpha level of 0.05.  
 
For each primary outcome measure, a separate linear mixed model will be employed to 
determine predictors of post-treatment scores, with pre-treatment scores, condition, time, 
group, and a time-by-condition interaction term as regressors. Time-by-condition is a regressor 
to account for potential improvements in perspective taking with treatment (since there are two 
conflict scenarios presented). From this model, using appropriate contrast statements we can 
both test for the primary endpoint (change at end of Scenario 3) and examine trends over time 
between the three groups. We will also conduct with fMRI data a 2x3 (pain perspective 
condition by group) within-subjects ANOVA on data from each ROI.   
 
Across the entire sample, we will calculate the correlation of IRI Perspective Taking with our 
pre-treatment VR Perspective Taking and AOP scales, to further validate these measures. 
Similarly, we will assess the relationship between target engagement measures with VC 
Intentions and Real-life Responses. Exploratory regression analyses will also examine whether 
target engagement measures are associated with age, sex (to address sex as a biological 
variable), IQ, task completion, mood, callous-unemotional traits, past experience with video 
games or VR, or Environmental Presence (each variable examined separately due to the small 
sample sizes). Finally, we will conduct whole-brain fMRI analysis (2x3 pain perspective 
condition-by-group ANOVA), in order to identify neural changes in areas outside our primary 
ROIs (cluster-corrected p<.05). 
 
 
13.0 Statistical Data Management 
 
The PI and primary research assistant are responsible for overseeing data collection and 
accuracy of record keeping and the researchers will convey an attitude that the data 
management procedures be treated with unwavering gravity, therefore maintaining a high level 
of quality for this project. A rigorous and systematic approach to data management is critical for 
the quality of any study. The substantial effort and resources that will be devoted to collecting 
data in this project will be matched by an equally substantial commitment of effort and 
resources to edit, verify, correct, update, and assemble the resulting data files. By limiting the 
amount of data that must be entered by hand, we aim to minimize the chances for errors data 
entry. Our data management system incorporates quality control at every juncture from data 
collection through analysis.  We have found that this bottom-up approach to data quality is 
essential, since there is no single procedure that will verify and correct erroneous data.  

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Data for the the K-SADS-PL will be collected by clinicians and recorded either electronically or 
on a paper checklist/questionnaire. The K-BIT-2 IQ test responses and results will likewise be 
initially recorded on paper. These responses will be entered into our REDCap database, with 
double-entry of data to confirm accuracy of entry. For remaining surveys, either remote 
electronic devices or in-person electronic tablets will be used to administer testing instruments 
via the IU Qualtrics system, which will directly record responses to our electronic database. 
These data will be stored electronically in REDCap, IU Box Health, or Microsoft Secure Storage. 
The storage location will be backed up automatically. In addition, MRI data will be stored on 
IU’s Geode system, which is backed up automatically and can seamlessly be integrated with 
IU’s high-performance computing systems. These data will be merged for analysis, with full 
datasets maintained on secure systems if containing identifiable information. Analysis of de-
identified data will take place on local computers and the IU Research Desktop. Prior to the 
enrollment of the first participant, these databases will be thoroughly tested to ensure they are 
working properly, recording and storing data as intended. The study data manager will regularly 
query the data for completeness, consistency, and accuracy to allow for prompt data quality 
management, generate monthly data completeness reports for discussion at monthly meetings 
of the investigators and research assistant (with more frequent communication as needed), and 
implement study closeout. 
 
14.0 Privacy/Confidentiality Issues 
 
Subject procedures will take place in private rooms, with only research staff present. MRI scans 
will take place in a dedicated research MRI suite at the IU Center for Neuroimaging with trained 
clinical staff with appropriate privacy and confidentiality training. 
 
Any information obtained about subjects from this research, including answers to 
questionnaires, medical history, and cognitive status will be kept confidential, with the 
exception of information that meets mandatory reporting requirements within the state of 
Indiana (e.g., indications of child abuse/neglect (including sexual abuse) and threats of 
immediate harm to self or others). Confidentiality is protected by omission of individual 
identifiers associated with study responses in research databases. Subjects’ identities will not be 
revealed in any description or publication of this research. De-identified data will be shared with 
the NIMH Data Archive (NDA). For this purpose, the child’s name, date of birth, and birthplace 
will be used to establish a global unique identifier (GUID) in the NDA. The tool to create the 
GUID is used on a local computer, so no identifiable information will be shared with NIMH. 
 
Subjects are free not to participate in the study, and they may continue in the study even if 
they do not want de-identified data shared with the NIMH Data Archive. Additionally, other 
procedures to ensure confidentiality will follow the regulations and policies of the Indiana 
University School of Medicine. 
 
For MRI scheduling purposes, we are required to share the child’s name and birthdate with the 
Research MRI team. All members of this team are trained research technicians with up-to-date 
training in research compliance, including HIPAA. This information will be sent in accordance 
with IU HIPAA policies for electronic communications, including labeling this email as 
“Confidential.” This personally identifiable information will not be included with MRI scan files. 

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All records with identifiable information will be maintained in a secure location, with access 
limited to study personnel. All electronic records will be encrypted or stored on an encrypted 
device. The electronic database used to house these data until analyses are needed will be 
created uniquely for this project. The database will be password protected and only certain 
research personnel will be given access to the database.  This will protect the electronic data 
from any unauthorized persons entering the dataset and jeopardizing the integrity of the data 
or engaging in some sort of malicious piracy. Any electronic protected health information (PHI) 
will be stored in REDCap, IU Box Health, or Microsoft Secure Storage.  
Any physical study records that link individual identifiers with study identification numbers will 
be maintained in a locked file cabinet in a locked office, and computer data will be kept on 
secure, password-protected servers. Electronic data linking identifiable information to study 
identification numbers will be stored on REDCap, IU Box health, or Microsoft Secure Storage. 
Only select research personnel will have access to these linkages. Linkages between individual 
identifiers and study identification numbers will be destroyed at the conclusion of the 
investigation.  
 
To protect against digital threats to confidentiality, three types of security are employed: 
• 
The data system is only accessible to investigators and study staff by a unique identifier 
and password, via an encrypted internet connection that is secured by a 256-bit SSL 
certificate. Each user’s access to data, modules and files is limited to the items to which 
they are assigned.  
• 
Next, the network is protected by a firewall to prevent access by unauthorized users, 
and data is stored in a secure Microsoft SQL Server database that is electronically and 
physically restricted to key study personnel. Regular backups of the database are 
compressed and encrypted before being securely stored at an off-site facility. Data 
system developers use their best good faith effort to implement policies necessary to 
minimize the possibility of unauthorized access pursuant to the “Security of Information 
Technology Resources” policy IT-12 of Indiana University 
(http://informationpolicy.iu.edu/policies/IT12) and follow the pre-established guidelines 
for handling electronic institutional and personal information as set forth by the Indiana 
University Information Policy Office 
(http://informationpolicy.iu.edu/resources/safedata/guidelines.shtml).  
 
 
15.0 Follow-up and Record Retention 
 
The active study duration is expected to last three years, although data analysis will continue 
beyond that period. Linkages between individual identifiers and study identification numbers will 
be removed at the conclusion of the investigation. De-identified information may be archived 
and accessed for an indefinite period of time. Study records with identifiable information (e.g., 
copies of Informed Consent documents) will be retained throughout data collection, analysis, 
and manuscript development, and will be destroyed as recommended by NIH guidelines. 
 
 
16.0 References 
 

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