Beat!: A Randomized Controlled Clinical Trial
Phase: NA
Conditions: Epilepsy, Adherence, Medication
Sponsor: Children's Hospital Medical Center, Cincinnati

 
Clinical Trials Title: Behavioral Economics and Adherence in Teens (BEAT!) 
NCT03958331 
Date Last Modified and Approved: 4/23/2020 (Version 5) 
NIH Grant Title: Improving Drug Adherence Using mHealth and Behavioral Economics in 
Adolescents with Epilepsy (R21NR017633) 
 
 
 

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CINCINNATI CHILDREN’S HOSPITAL MEDICAL CENTER 
STUDY PROTOCOL
Study Title: Beat!: A Clinical Trial
Principal Investigator: Avani C. Modi, Ph.D.
1.
ABSTRACT
Non-adherence to antiepileptic drugs (AEDs) is a common problem affecting 58% of youth 
with epilepsy, with potentially devastating consequences. Adolescents with epilepsy represent a 
particularly vulnerable group, given their increased independence, decreased parental 
supervision, higher risk for deficits in organization and memory, busy and changing schedules, 
low motivation, and increased susceptibility to peer influence. Existing adherence interventions 
in epilepsy are not designed to meet the unique challenges faced by adolescents, and there are 
no efficacious interventions for adolescents with epilepsy. Not surprisingly, without efficacious 
interventions, adherence worsens during adolescence, further increasing the risk of poor health 
outcomes during this developmental period. Data suggest that automated digital reminders and 
social norms feedback (i.e., feedback about someone else’s behavior related to one’s own 
behavior) could be effective strategies to improve adherence in adolescents with epilepsy. As 
such, our goal is to test the preliminary efficacy of a mHealth social norms intervention on AED 
adherence, seizure severity, and health-related quality of life (HRQOL) in adolescents with 
epilepsy. The first phase of this study (ORBIT Phase 1a-b) is almost complete and includes 
focus groups, usability testing, and extended formative usage evaluation. Data from these 
phases guided development of a social norms mHealth adherence intervention, which will be 
tested in this pilot randomized clinical trial (ORBIT Phase 2). Recruitment for the study will take 
place at Cincinnati Children’s Hospital Medical Center and Nationwide Children’s Hospital.
Enrolled adolescents and caregivers (n=138) will complete baseline questionnaires and 
electronically-monitored adherence will be collected during the one month baseline period. 
Adolescents with epilepsy who demonstrate non-adherence during this baseline (<95%) will be 
randomized to either 1) Group 1: control (automated digital reminders and individualized 
adherence feedback) or 2) Group 2: mHealth social norms (automated digital reminders, 
individualized adherence feedback, and social norms feedback). Both groups will receive active 
intervention for five months. Primary (i.e., electronically-monitored adherence) and secondary 
outcomes (i.e., seizure severity, HRQOL) will be assessed post-treatment and 3 months later, 
respectively. This project addresses the critical need for evidence-based adherence 
interventions in a high risk adolescent epilepsy population that have the potential to improve 
seizure severity and HRQOL. This study lays the foundation for larger clinical trials examining 
the efficacy of a mHealth social norms adherence intervention to improve adolescent epilepsy 
outcomes.
2. PURPOSE OF STUDY
The purpose of this study is to evaluate the feasibility, acceptability and preliminary efficacy of a 
social norms mHealth adherence intervention in adolescents with epilepsy. Specifically, our 
aims are as follows:
Aim 1: Examine the feasibility, accessibility, acceptability, and responsiveness of a 
mHealth social norms intervention to improve AED adherence for adolescents with 
epilepsy. H1: Adolescents with epilepsy will rate the intervention as highly feasible, easy to use, 
acceptable, and responsive to their needs.

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Epilepsy Outcomes:
Seizure severity, HRQOL
Adherence:
Antiepileptic Drugs
Aim 2: Examine the preliminary efficacy of the mHealth social norms intervention on 
AED adherence, seizure severity, and HRQOL in adolescents with epilepsy. H2a: 
Participants in the treatment group will demonstrate statistically significant improvements in 
adherence with corresponding medium/large effect sizes compared to the control group at post- 
treatment. H2b: Greater improvements in adherence, seizure severity, and HRQOL are 
expected at 3-month follow-up for the treatment versus control group.
3. BACKGROUND
Adherence is multi-factorial. The Pediatric Self-Management Model (Figure 1) is a 
comprehensive conceptual model that articulates the individual, family, community, and 
healthcare system factors that influence self-management behaviors (i.e., the interaction of 
health behaviors and related processes that patients and families engage in to care for a 
chronic condition and their subsequent impact on adherence and health outcomes).25 
Adherence behaviors are daily, complex, and multi-factorial. Thus, single component
Figure 1. Pediatric Self-Management Model
interventions are likely to only have minimal effects on adherence,31, 32 whereas multi-
component interventions that influence more than one factor are likely to have greater effects. 
Our recent review of self-management interventions in pediatric epilepsy, based on this model, 
concluded that we lack strong evidence for self-management interventions, largely due to small 
sample size studies or poor design.16 The focus of this proposal is to address the critical 
individual (i.e., forgetting, motivation, busy schedule) and community (i.e., peer influence) 
factors influencing adherence and self-management in adolescents with epilepsy.
Adolescents with epilepsy represent a high-risk population. Adolescence is often 
accompanied by susceptibility to peer influence, desire for autonomy, feelings of invincibility, 
and decreased parental monitoring.33 Adolescents are motivated by novel experiences and are 
predisposed to impulsive and risky behaviors due to an immature inhibitory control system.34 
This makes adolescents more likely to engage in behaviors that have immediate rewards, 
especially in the context of their peers (e.g., skipping taking medication when out with friends), 
and less likely to be concerned about the negative consequences of their decisions for the 
future (e.g., having a seizure).14, 17 Non-adherence to AEDs is a significant problem in 
adolescence.35 For adolescents with epilepsy, this is especially difficult due to seizure-related 
restrictions (e.g., no driving with active seizures) and the need for continued parental 
supervision to ensure safety (e.g., bathroom door open while bathing36), all while self-managing 
their AED. Seventy percent of adolescents with epilepsy have to be reminded to take their AED; 
however, they complain that their parents nag them and yet forget to take their AED without

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these reminders,35 suggesting the potential need for more developmentally acceptable 
alternatives, such as automated digital reminders. While digital reminders are likely beneficial to 
improve adherence, they are not helpful to adolescents who lack motivation to take their AEDs 
or abandon use of digital reminders over time (i.e., alarm fatigue37). It is well known that 
adolescence is characterized by strong influences of their peer group, and harnessing these 
influences may be critical to fostering greater adherence. Thus, additional strategies (e.g., social 
norms comparisons) that leverage the impact of peer relations may also be necessary to 
improve and sustain adolescent adherence. Despite the critical need for developmentally 
appropriate interventions to improve adherence in adolescents with epilepsy,38 few interventions 
exist. The limited AED adherence literature39-43 is characterized by small samples and 
interventions that are difficult to apply in clinical settings. Further, access to behavioral health 
providers who can target adherence behavioral change is limited for many adolescents with 
epilepsy.
Strategies to improve adherence
Social Norms Comparison: A novel approach of applying behavioral economic 
theories to adherence promotion. Behavioral economics, a scientific field that blends 
psychology, marketing, and economics to improve individual decision making,44 is receiving 
increased attention in healthcare.45, 46 Behavioral economic theories of decision making posit 
that social norms comparisons (i.e., feedback about someone else’s behavior related to one’s 
own behavior), may increase motivation and thus, be beneficial in improving adherence 
behaviors in adolescents.47 Social norms interventions rely upon the large influence of 
interpersonal factors on human behavior, which is especially salient in adolescence48. These 
interventions involve giving an individual feedback on how he/she performs compared to similar 
others (community factor of the Pediatric Self-Management Model), which can affect that 
individual’s subsequent behavior. Social norms interventions may exert positive effects through 
three psychological mechanisms. First, these interventions may provide social proof to the 
target individual.7 For example, an adolescent may recognize the importance of taking AEDs 
consistently when learning that other adolescents have reached this conclusion via the 
feedback (“You took 10 of 14 doses of your medicine in the past week! However, 4 out of 5 
male teens with epilepsy take medication more consistently than you do”). Social norms 
interventions may also enhance the self-efficacy of the target individual.8 An adolescent may be 
convinced that a consistent AED regimen is achievable when learning that other adolescents 
have already demonstrated high adherence. Finally, social norms interventions may motivate an 
adolescent to improve his/her standing relative to other adolescents. Many people view 
themselves as above average in a variety of domains.9 Therefore, receiving feedback on below 
average adherence levels may motivate an adolescent to improve the consistency of
medication-taking so that these positive self-perceptions can continue to be held. To date, social 
norms intervention studies have focused on improving clinician performance,49-51 reducing 
college students’ alcohol consumption,52 or changing behavior in non-health domains (e.g., 
energy conservation53). Specific to adolescents, social norms interventions are efficacious in 
decreasing underage drinking,54, 55 bullying in school,56 and changing food intake.57 Recent data 
focused on health behaviors (e.g., physical activity) in adolescents indicates that social norms 
interventions have incremental value and improve physical activity above and beyond standard 
feedback without peer comparisons.24 Specifically, adolescents who received feedback relative 
to their peers increased their steps relative to controls who only received feedback on their own 
behavior and decreased their steps (d=0.41). Further, social norms comparisons yielded 
significant improvement in academics for adolescents compared to criterion-based feedback 
(d=0.85).58 Finally, social norms interventions have been shown to reduce inappropriate 
antibiotic prescribing,51, 59 and these effects were maintained even twelve months after primary 
care clinicians stopped receiving peer comparison reports.60 Overall, these recent studies

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suggest the incremental value of social norms interventions that are clinically meaningful 
compared to feedback alone, with high potential for long-term benefits.
Because adolescents heavily weigh social pressure, identity, and sense of belonging 
when making health-related decisions, social norms comparisons may be an ideal 
method for targeting adherence-related motivation, and as a result, improve adherence 
among this population.17, 48, 61 In particular, social norms feedback can provide effective 
motivation, rarely targeted in adherence interventions,62 especially for those that perform below 
average (e.g., poor adherence). Descriptive norms (i.e., obtaining feedback about the average 
person) can boost performance,63-65 including adult diabetes adherence behaviors,66 while 
injunctive norms (i.e., obtaining feedback regarding the desirability of one’s performance) can 
help to maintain adaptive behaviors21-23 (e.g., high adherence). Notably, injunctive norms are 
intended to discourage high adherers from gravitating to the average level of performance.21, 51 
To date, there are no adolescent studies that have applied these principles to improve 
adherence behaviors. However, as mentioned above, the use of both injunctive and descriptive 
norms was beneficial in improving adolescent’s physical activity (e.g., steps).24 Our current 
proposal capitalizes on social norms comparisons to either improve poor adherence or maintain 
good adherence behaviors in epilepsy, which can then be disseminated to other chronic 
conditions.
Automated Digital Reminders: In addition to motivation, forgetting is an individual factor of 
the Pediatric Self-Management model and a primary barrier to adherence across pediatric 
chronic conditions.67, 68 While a recent meta-analysis of text-messaging interventions found that 
18 of 29 studies significantly improved short-term adherence, only 3 were pediatric focused and 
none were in epilepsy.69 Combined with the results of a recent review of digital reminders 
demonstrating that interventions were promising but lacked scientific rigor,70 these meta- 
analyses conclude that long-term rigorous RCTs with objective adherence measures are still 
needed to determine the efficacy of technology-focused adherence interventions in pediatric 
epilepsy.
Individualized Adherence Feedback: Given that patients often lack knowledge about their 
own adherence behaviors and patterns, intervention efficacy may be maximized when feedback 
is provided and individually-tailored.69 For example, an HIV adherence intervention study that 
provided electronically-monitored adherence feedback to non-adherent patients (< 95%) found 
a 10% improvement (i.e., 87% to 97%) in the treatment group versus 1% improvement (84% to 
85%) in the control group.71 Similar intervention effects have been demonstrated in pediatric 
asthma26, 72 and adult heart disease,73 suggesting this may be a beneficial component for an 
adherence intervention for adolescents with epilepsy. Our current proposal leverages the 
benefits of automated digital reminders in improving upon the logistical barrier to forgetting, as 
well as individualized feedback for improving self-monitoring. However, the inclusion of social 
norms comparisons could play a pivotal motivating role to improve adherence behaviors 
in adolescents with epilepsy.
mHealth as an optimal vehicle to deliver intervention strategies for adolescents.
Mobile Health (mHealth) offers a practical, feasible, culturally and developmentally acceptable, 
and cost-effective solution for forgetting by enabling the sending and receiving of automated 
digital reminders (e.g., texts, alerts). Given AED adherence is a daily behavior, mHealth tools 
also serve as a practical and logistical tool to target motivation by providing adherence 
feedback, with (treatment group) or without social norms comparisons (control group). A 2013 
review identified 160 commercially available adherence tools (i.e., digital reminders and/or 
medication tracking).74 mHealth tools are well-matched to the information consumption patterns 
of adolescents as approximately 90% have cell phones (73% smartphones), 90% of those with 
cell phones use text messaging,75 and 91% access the internet on their mobile device (with a 
notable increase in use for minority youth).75

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Scientific Premise. Adolescents with epilepsy demonstrate significant AED non-adherence, 
resulting in poor health outcomes. While adherence strategies exist to improve logistical barriers 
(e.g., forgetting) for adolescents, no adherence interventions focus on motivation. Use of a 
mHealth social norms intervention may leverage the important role of peer comparisons to 
motivate adherence change in adolescents. The proposed approach uses minimal resources 
(e.g., costs) and has greater reach, especially to adolescents without access to behavioral 
health care.76, 77 Because the intervention requires no clinician time and minimal participant 
burden, our social norms intervention has considerable potential for sustainability and 
dissemination for multiple pediatric conditions. If successful, study results would have a large 
impact on pediatric conditions affecting adolescents (e.g., epilepsy), with the potential to change 
clinical practice for treating non-adherence.
4. STUDY DESIGN
A pilot randomized clinical trial will be conducted in order to evaluate the preliminary efficacy of 
a mHealth social norms adherence intervention to improve electronically-monitored AED 
adherence to antiepileptic medications in 138 adolescents with epilepsy. For the purposes of 
this protocol, CCHMC will serve as the Primary Site. The term “Collaborating Site” refers to the 
external children’s hospital site working in collaboration with CCHMC on the study (Nationwide 
Children’s Hospital).
5. DURATION
Recruitment for the pilot RCT is estimated to take 7 months (approximately 10 patients per 
month at each site). The duration for participants is variable depending on their level of 
adherence during the baseline period. For enrolled participants who achieve electronically 
monitored adherence >95% in the baseline period, their study participation will be approximately 
1 month, with conclusion at the end of the baseline period. For participants with adherence
<95%, their participation will be 9 months (1 month baseline, 5 months of active intervention, 
and 3 months of follow-up).
6. SELECTION & RECRUITMENT OF PARTICIPANTS
Study Participants
Study participants will include approximately 138 adolescents with epilepsy between 13-17 
years old at CCHMC and Nationwide. Adolescents and caregivers will be recruited during 
routine medical appointments with neurology or epilepsy-related hospital visits and will meet the 
following inclusion/exclusion criteria:
Inclusion criteria
Child age 13-17 years old and their primary caregivers
On ≤2 antiepileptic drugs (AEDs)
Ability to read and speak English
Exclusion criteria
Significant developmental (e.g., autism spectrum disorder, moderate/severe 
developmental or intellectual disability) or comorbid medical diagnoses (e.g., diabetes)
Recruitment Procedures
Potential participants meeting eligibility criteria will be identified by a trained research 
coordinator in collaboration with the epilepsy team. If potential participants are eligible, a trained 
research coordinator will approach families during their medical clinic visit. A thorough overview 
of the study will be provided, including study procedures, benefits, and risks. All questions will

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be addressed and informed consent/assent will be obtained. Following informed consent from 
the caregiver/legal guardian and adolescent assent, SimpleMed electronic pillbox 
(www.vaica.com) and AdhereTech pill bottles (www.adheretech.com) will be provided, and 
baseline questionnaires will be completed via REDCap or using paper/pencil questionnaires 
either in person or by mail. Recruitment and retention materials can be found in the appendices, 
including flyers and study magnets (Appendices A and B and E).
7. PROCESS OF OBTAINING CONSENT
As noted above, once participants are identified as study eligible, they will be approached 
during their epilepsy clinic visit and provided a description of the study (e.g., study procedures, 
benefits, risks) by a trained research coordinator included on the approved IRB protocol. After 
addressing all questions from potential participants, informed consent/assent will be obtained by 
trained research staff. Consent forms will be signed electronically using REDCap, a secure web- 
based interface supported by the CCHMC Division of Biomedical Informatics in compliance with 
HIPAA designed to protect PHI in the electronic transfer and storage of the consent form.
Should technical issues arise with the REDCap interface, hard copies of consent forms may 
also be used. For all consent visits, all pertinent aspects of consent will be covered including 
study purpose, risks/benefits, confidentiality, and right to withdraw. Patients will be informed that 
their care at CCHMC or collaborating study site will not be affected by whether they choose to 
participate in the study.
When caregivers and adolescents agree to participate and sign an electronic consent/assent 
form via REDCap, they will have an opportunity to check a box stating that they agree to provide 
their consent/assent. There will also be fields for their typed name, date, and electronic 
signature to document the informed consent and assent process. Once the electronic form has 
been submitted, caregivers will receive a copy of the electronically signed and dated consent 
and assent forms via email.
Participants recruited in-person will complete the informed consent document in-person. For 
participants who decide to participate after the clinic visit, we will use telephonic electronic 
consent. Specifically, a member of the study team will provide a link to access the consent form 
in REDCap via email or text message. A hard copy of the consent form may also be mailed if 
necessary. During the consent/assent phone call, research staff will ensure all questions are 
answered. In compliance with CCHMC SOP Number 41-1.6, study staff will sign and date 
accordingly on the signature page of each form corresponding to the date the forms were 
received, not necessarily reviewed with the family. The method used to obtain participant 
consent will also be written on the Informed Consent Process Note.
8. STUDY PROCEDURES
This is a randomized controlled clinical trial to test the efficacy and effectiveness of a social 
norms mHealth adherence intervention. Potential participants will be identified by the study 
coordinator in collaboration with the epilepsy team at each site as noted above. After caregivers 
provide informed consent, baseline questionnaires will be completed via REDCap or using 
paper/pencil questionnaires (in person or by mail), including a demographics form and study 
measure questionnaires (see Measures section below). All measures will be hosted on 
REDCap, a secure web-based interface. The PI and her team have fully tested REDCap and 
will test prior to study implementation across all sites to ensure functionality. A medical chart 
review will also be conducted to gather information about seizures, medications, seizure 
etiology, comorbidities, and time since diagnosis. It is notable that the participating caregivers 
and adolescents must provide an email address for the online or paper/pencil questionnaires. If 
they do not have one, we will help them create one or we will text the link to their cellular 
phones, if needed.

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The Beat RCT design is illustrated in the Figure below. All participant families will complete a 1- 
month baseline period during which they will use electronic adherence monitoring (i.e., pillbox or 
pill bottle) to measures adherence. Participants who demonstrate adherence < 95% will move 
on to the active intervention for randomization. In the Active Intervention Stage (5-months), 
adolescents will be randomized to the control group (individualized feedback and automated 
digital reminders) or the treatment group (control condition plus social norms).

Automated Digital Reminders – Each adherence electronic monitor has the capability 
to provide automated digital reminders. As a part of the intervention, all teens 
randomized to intervention will have to option of selecting the type of automated digital 
reminders that they receive, which could include text messages (i.e., BEAT Study: This 
is a reminder for you to take your medicine) and/or device sounds/lights. These will be 
turned on immediately following the baseline period based on the participant’s 
preferences.

Individualized Adherence Feedback Reports - Individualized adherence feedback will 
be received by each teen once a week where he/she will be provided with information 
about his/her adherence levels over the previous 7 days based on his/her electronic 
adherence monitor. His/her family members and his/her health care providers will NOT 
receive this individualized adherence feedback from the study team. Outside of study 
procedures, the adolescent may or may not decide to share this information with those 
individuals. All individualized adherence feedback reports will be received on Monday. A 
separate portal has been developed by Bioinformatics at CCHMC to create the 
adherence feedback reports, as well as the social norms feedback reports below. Data 
from the SimpleMed pillbox via open application programming interface (PI) and 
AdhereTech via excel spreadsheets are merged to provide a calendar plot with the 
participant’s adherence data from the past week. The participant will receive a push 
notification to view their adherence from the past week and these will vary by week (see 
Table 1). It is notable that the participant must provide a cell phone number for the push 
notifications.

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
Social Norms Feedback Report – Individualized social norms feedback will be 
provided to every teen who is randomized to the treatment group. Specifically, each teen 
will receive weekly information about how his/her level of adherence over the prior 7 
days compares to other teens his/her age based upon previously published research by 
the PI. Feedback is provided in such a way that the adolescent receiving this feedback 
will not be able to identify specific individuals comprising the social comparison group. 
Examples of such feedback include informing the adolescent that “Most other teens with 
epilepsy …” and “Many other teens with epilepsy.” Adolescents will receive this feedback 
in both written form and visual images. His/her family members and health care 
providers will NOT receive this social norms feedback from the study team. Outside of 
study procedures, the adolescent may or may not decide to share this information with 
those individuals. Data from the SimpleMed pillbox via open API and AdhereTech via 
excel spreadsheets are merged to provide a graphic representation of how a 
participant’s adherence data from the past week compares to other teens. The 
participant will receive a push notification to view how their adherence levels compared 
to other teens. The example below demonstrates how the teen would receive the push 
notification, which leads to a message in which they need to log-in to a portal with their 
unique id and password in order to see their adherence feedback (i.e., control group) or 
social norms adherence feedback report (i.e., treatment group). These images are 
currently being finalized based on participant feedback from Orbit 1b.
After completion of the active intervention, automated digital reminders will be turned off, 
adherence feedback reports will cease to be sent, and social norms comparison will no longer 
be provided. Daily electronic adherence will be monitored until study completion. Additional 
questionnaires will be completed via REDCap or using paper/pencil questionnaires either in 
person or by mail at post-treatment (month 7), and 3-month follow- up (month 10).

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8.1 Data collection procedures and measures: Participants will complete a demographic 
questionnaire that provides general information about the child’s age, caregiver work history, 
family composition, socio-economic status, family history of seizures, history of seizures (e.g., 
type, who witness, when they occurred), and comorbid illnesses (e.g., learning disorders). In 
addition, caregivers and adolescents will complete the questionnaires detailed in the table 
below. An additional questionnaire related to the child’s seizure severity (one item) will be 
obtained from the child’s epilepsy provider. A medical chart review will also be conducted to 
describe key patient medical characteristics (e.g., epilepsy type and treatment, seizure 
frequency, quality of life, side effects, hospitalizations, emergency room visits, and telephone 
contacts to clinic staff between routine clinic visits). Chart reviews will cover the entire study 
period. See Table 2 for list. Due to the unexpected COVID-19 pandemic, we are also including a 
newly developed measure, the Impact of COVID-19 on Pediatric Epilepsy Management (ICPEM) 
to understand how COVID-19 is impacting our research participants and the outcomes of our 
study.  
Raw adherence data will be obtained from the SimpleMed pillbox and AdhereTech bottles and 
will be used as the primary outcome variable. Data from these devices is obtained real-time via 
blue-tooth and 4G technology and thus will require no additional burden for participants. They 
will simply put their anti-seizure medicine in the electronic monitor (those who already use 
bottles will be given an AdhereTech bottle and those who use pillboxes will be given SimpleMed 
pillboxes). As highlighted on their companies’ respective websites, the pillbox and bottles 
feature secure portals for the study team to access adherence data. In addition, the AdhereTech 
bottles feature a standard child-resistant caps. Instructions for using both devices will be 
provided to teens (see Appendix D).

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Table 2. Questionnaires
Questionnaire
# of items/Description/Score Used
Reliability/Validity
PRIMARY OUTCOME
SimpleMed+ Pillboxes
Daily objective adherence data; Score: % Adherence
N/A
Adherence
Self-Report Adherence91
1-item adherence item (caregiver and teen); Score: % 
Adherence
MEMS rho=0.46, p<.001
SECONDARY OUTCOMES
Seizure Severity
Global Assessment of severity 
of epilepsy (GASE)106
1-item clinician report of seizure severity
Clinical vars: (r>.30); 
ROC>.50
Seizure Severity Scale-Adapted 
for children107, 108
9-item caregiver report of seizure severity (e.g., 
intrusiveness, frequency, length, disruptiveness). 
Score: Total severity
α = 0.79
Quality of Life
PedsQL Epilepsy Module93, 109
29 items representing 5 domains of HRQOL (caregiver 
and teen); Scores: Impact, Cognitive, Sleep, 
Executive Functioning, and Mood/Behavior scales
α = 0.75-0.93
COVARIATES
Side effects
Pediatric Epilepsy Side Effects 
Questionnaire110
19 items assessing typical AED side effects (teen);
Score: Total Side Effect Score
α = 0.72-0.93
Demographics
Background Form
Child age, sex, and socioeconomic status (caregiver)
N/A
Medical variables
Medical Chart review
Seizure type, etiology, and treatment (e.g., AED)
N/A
COVID-19 Impact
Impact of COVID-19 on Pediatric 
Epilepsy Management (ICPEM)
25 item survey regarding personal/familial impact from 
COVID-19 Pandemic
N/A
MEDIATORS
Peer Influence111
Resistance to Peer Influence 
Scale
10-item measure with paired statements that best 
describes situations related to peer influence (teen); 
Score: Total Score
α = 0.74
Adherence 
Barriers
Pediatric Epilepsy Medication 
Self-Management 
Questionnaire68
27 items measuring medication self-management (teen 
and caregiver); Score: Barriers to Adherence Scale
α = 0.68-0.85
TREATMENT FEASIBILITY/ACCEPTABILITY/USABILITY
Usability
Revised Website/mHealth tool 
Evaluation Questionnaire 
(WEQ)84
8-item open-ended questions regarding the participant’s 
general experience with the mHealth tool, expectations, 
comfort of use, quality of the tool, connectedness and 
likes/ dislikes (teen).
N/A
System Usability Scale85
10-item scale that assessing the usability of an 
application or mHealth tool (adolescent)
N/A
Feasibility/ 
Acceptability
Revised Feasibility and 
Acceptability Questionnaire80, 112
37 item survey regarding satisfaction with content, 
relevance, helpfulness, ease of use, and likeability 
(teen). Five open ended questions also assess need for 
modifications and satisfaction.
N/A
8.1 Sample Size Considerations and Power Analysis:
Sufficient Power for RCT: Given timeline and resources proposed for this pilot RCT, we 
anticipate recruiting N=138 participants. We expect that 58% will have adherence <95%, leaving 
N=80 to be randomized. We conducted a Monte Carlo simulation in Mplus with N = 5000 
replications, assuming a total randomized sample of N=80, 25% attrition, proper handling of 
missing data, standardization of all analysis variables, and that baseline adherence, age, sex, 
side effects, cognitive/executive functioning, seizure type, and SES (covariates) will explain at 
least 40% of the post-treatment adherence error variance (based on our pilot data and previous 
studies1) Our analysis indicates that we will have at least 80% power to detect a post-treatment 
group difference effect size of d > 0.62 in adherence rates (i.e., approximately 15% difference in 
group adherence rates at post-treatment). Effect sizes for recently published social norms 
interventions have ranged from 0.4124 to 0.8558 when compared to those without social norms 
comparisons, and we have sufficient power to detect effects within the range of those published. 
The estimates of preliminary efficacy and variability of our social norms intervention that we 
obtain will be used to power for a future larger trial.
Randomization: At 1 month, we will randomize all patients who demonstrate adherence
<95% to either the control group (i.e., reminders, feedback) or treatment group (i.e., reminders, 
feedback with social norms comparisons) using stratified block randomization with two strata 
and blocks of size 2 or 4 chosen randomly within each stratum. Stratification will be based on 

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baseline adherence (i.e., > 80% or < 80%) and seizure severity (Global Assessment of 
Severity of Epilepsy; GASE scores 1-3 or 4-7). The PI will be blinded to study arm. The 80% 
criterion was selected based on our pilot data indicating that the median adherence rate for 
those randomized was 80%. Thus, the 95% adherence criterion is used to determine the 
eligibility of participants for randomization while the 80% criterion is used to balance 
intervention groups on baseline adherence within the randomization process. This 
randomization strategy will also minimize imbalance of the number of participants across 
groups. The randomization list will be held by an individual independent of the study to reduce 
any potential biases. Those who will be randomized will be notified of their randomization 
status within 48 hours. It is estimated that 58% of the sample will be eligible based on 
adherence <95% to be randomized to either the control group or intervention, yielding a final 
sample of n=80. Both groups will receive intervention for 5-months.
8.3. Data Analysis: All data analysis and management will occur at CCHMC. The Division of 
Behavioral Medicine and Clinical Psychology at CCHMC has developed a Divisional Data Core 
(DDC) in cooperation with the divisions of Biostatistics and Epidemiology and Bioinformatics to 
This group will provide quality reports to audit the data routinely, provide data for safety 
monitoring committee reports for the biostatisticians, and cleaning of the data.
Aim 1: Examine the feasibility, accessibility, acceptability, and responsiveness of a 
mHealth social norms intervention to improve AED adherence for adolescents with 
epilepsy. H1: Adolescents with epilepsy will rate the intervention as highly feasible, easy to use, 
acceptable, and responsive to their needs.
Analyses Aim 1: We will examine means and standard deviations of ratings completed by 
adolescents on the Adapted Feasibility and Acceptability Questionnaire, Revised 
Website/mHealth tool Evaluation Questionnaire (WEQ), and System Usability Scale. For the 
Adapted Feasibility and Acceptability Questionnaire, ratings of 3-4 are considered good. The 
WEQ is primarily qualitative in nature and will be used during Phase 1b modifications, as well as 
the RCT to obtain qualitative data on the use of the social norms mHealth tool. Finally, scores 
on the System Usability Scale85 ranging from 80-100 range indicate good to excellent usability.
Aim 2: Examine the preliminary efficacy of the mHealth social norms intervention on 
AED adherence, seizure severity, and HRQOL in adolescents with epilepsy. H2a: 
Participants in the treatment group will demonstrate statistically significant improvements in 
adherence with corresponding medium/large effect sizes compared to the control group at post- 
treatment. H2b: Greater improvements in seizure severity, HRQOL, and adherence are 
expected at 3-month follow-up for the treatment versus control group.
Analyses Aim 2: For the pilot RCT, adherence will be calculated using daily adherence data 
and collapsed for the one-month prior to treatment (baseline adherence) and the one-month 
following treatment (post adherence). For example, if a patient is prescribed their AED twice a 
day and takes 50 of their 60 doses in the month, their adherence rate would be 83.3% (total 
doses taken/total doses prescribed x 100%). For the follow-up period, three-month adherence 
will be calculated to assess sustainability of treatment effects. All analyses will be carried out 
with missing data assumed to be missing at random and handled via maximum likelihood 
estimation with auxiliary correlates113 within Mplus (Version 8) on the full randomized sample 
(N=80). An ANCOVA model will be used to test the primary hypothesis that the mHealth social 
norms group will demonstrate significantly higher adherence rates compared to the control 
group at post-treatment (one-month of adherence following intervention), after controlling for

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baseline adherence (1-month of adherence prior to intervention), age, sex, SES, seizure type, 
side effects, and cognitive/executive functioning114 (Aim 2, H2a). When examining our 
secondary outcomes (i.e., seizure severity, HRQOL) and adherence at 3-month follow-up (Aim 
2, H2b), the same statistical model and covariate logic employed for our primary hypothesis will 
be used in a longitudinal mixed model.
9. POTENTIAL BENEFITS
No immediate or direct benefits to patients participating in this study are expected. However, it 
is possible that participants will learn more information about epilepsy and have improved 
adherence as a result. The information obtained from this study can ultimately be used to 
increase knowledge in the scientific community about how to improve adherence in adolescents 
with epilepsy.
10. POTENTIAL RISKS, DISCOMFORTS, INCONVENIENCES, & PRECAUTIONS
There are minimal potential risks/discomforts/inconveniences to participants in this study, no 
greater than those encountered in routine behavioral assessment and clinical care. There are 
no medical risks. The study questionnaires have been used in research, including our own, 
without any reported negative effects; however, it is possible that a small group may feel 
uncomfortable responding to questions. Participants may decline answering questions that 
cause them to feel uncomfortable and will be reminded of this prior to each study visit.
Participants may also sometimes feel uncomfortable receiving performance feedback, but 
based upon our previous work in Phase 1 the seriousness of such a risk is low. Participants 
may also withdraw from the study at any time and will be informed of this right during the 
consent process.
If a participant is distressed by any study procedures, the site PI or designee at CCHMC will be 
contacted immediately to assess the situation. The study PI or their designee will provide 
appropriate referrals and/or intervention. Safety procedures for suicidal ideation and reports of 
abuse/neglect are delineated in our safety monitoring committee plan (See Appendix C). In both 
cases and similar to above, the study PI or their designee at each site will be contacted 
immediately and he/she will assess the risk profile of the caregiver and/or child participant with 
subsequent recommendations based on the level of risk.
There is also the risk of possible loss of privacy of data or loss of confidentiality. These risks are 
inherent in all research studies, and a statement to this effect will be included in the informed 
consent. Every effort will be made to ensure that all participant information will be kept 
confidential. A majority of this study is going to be conducted via mHealth. Participants will be 
accessing or receiving information from several different sources, including REDCap, and a 
portal created by CCHMC to receive push notifications related to their adherence feedback or 
social norms feedback reports, and the adherence monitoring portals for AdhereTech and 
SimpleMed. For each of these sites, we will use the participant’s ID number and not their name. 
For example, enrolled participants will be assigned a secure login ID and password by the study 
staff to access measures via REDCap. Each site will only be able to see their own site’s 
participants in REDCap, with the exception of the lead site (CCHMC). Participants will be asked 
not to share their ID or password with anyone else. Use of Protected Health Information (PHI) 
on online measures will be minimized and participants will not be asked to enter their last name, 
date of birth, or medical record number on the online measures. When the study is complete, 
the content of the site will be taken down. Setup is consistent with HIPAA guidelines and was 
designed to support projects that contain PHI and are subsequently subject to compliance with 
federal and state regulations regarding data of this type. For the individual adherence and social 
norms feedback reports, participants will be asked to provide a cell phone number to receive

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push notifications. Adolescents’ cell phone numbers will also be added into the portals 
maintained by Vaica and AdhereTech so that automated digital reminders can be sent to 
participants. This information and protection of the participant’s identify will be clarified in the 
informed consent and assent forms.
Finally, to communicate study related information across sites, our team will be using trello, a 
task management system that is frequently used by research teams. No identifying information 
will be entered into the trello system; however, we will be tracking participants through the study 
procedures using their study ID.
Notably, the only place the study ID will be linked to the name and demographics is the 
participant database, which is password protected, individually, at each site by the research 
team. No other individuals outside of the IRB-approved research team will have access to this 
participant database and these databases will NOT be shared across study sites.
11. RISK/BENEFIT ANALYSIS
There is minimal risk associated with study participation. If participants feel distressed as a 
result of their participation, they will be encouraged to discontinue. The PI (Avani C. Modi, PhD) 
and site PIs or their designee will be available to participants during study participation to 
assess for discomfort, safety, and risk, as needed. The minimal risks of this study do not 
outweigh the potential indirect benefits that may be gained through increasing knowledge about 
best practices for improving adherence to treatment and quality of life of adolescents with 
epilepsy.
12. DATA SAFETY AND MONITORING
This is a multisite observational study and is considered minimal risk. A Safety Monitoring 
Committee (SMC) is in place for this study and will review randomization, safety events, and 
study progress every 6 months following trial initiation. In addition, each site’s research team will 
monitor for safety and adverse events at each study visit. The SMC plan, which was approved 
by the National Institutes of Nursing Research, is attached in Appendix C. Dr. Modi (PI) and the 
PI at the collaborating site, as well as the members of the Data Safety Monitoring Plan will be 
responsible for monitoring the safety of participants and complying with all reporting 
requirements. Any serious adverse events will be reported immediately to the IRB as required 
by the hospital’s policy, as well as NINR.
13. PRIVACY AND CONFIDENTIALITY
All study personnel have been trained in data safety and monitoring, privacy and confidentiality, 
minimizing risks related to loss of privacy and confidentiality. We will closely monitor 
performance of our research personnel to ensure the strictest standards. Additional information 
related to privacy and confidentiality is noted above in section 10.
13.1 Data De-Identification: All data will be de-identified with the use of unique assigned study 
identifier codes. No other identifying data such as address, phone numbers, social security 
number, or zip code will be entered on electronic measures. Electronic data files (including 
downloads of data from REDCap measures) will only identify participants via study identifier 
codes and will be password protected. Electronic data files will be maintained on CCHMC hard 
drives.
Because this research study involves payment for participation, we are required by Internal 
Revenue Service (IRS) rules to collect and use participant’s social security number (SSN) or 
taxpayer identification number (TIN) in order to track the amount of money that we pay them.

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Unless they have given specific permission for another use of their SSN or TIN related to this 
research study, we will only use their SSN or TIN to keep track of how much money we pay 
them and their SSN or TIN will not be used as part of this research study.
13.2 Data Storage and Management: Informed consent documents and all electronically 
collected data will be maintained in REDCap, a secure web-based platform, and in a 
password- protected electronic database on CCHMC hard drives. Although CCHMC, as the 
Primary Site, will be the study management location, no patient information from other sites 
will be shared other than de-identified IDs. Paper informed consent documents will be 
maintained in locked storage cabinets, if they are needed, and will be kept separate from 
participant data.
Deidentified adherence data will be stored on their respective portals (AdhereTech, SimpleMed) 
and these data will be triangulated with a CCHMC developed portal to provide individualized 
adherence feedback reports, based on the participant’s cell phone number.
Trello (www.trello.com), a web-based project management tool, will be used to coordinate
study-related tasks across sites. No identifiable patient information will be saved in this platform. 
Medical chart data will be collected by trained study staff under the supervision of the PI. These 
risk protection methods have been effectively used by the PI and her collaborators for numerous 
studies.
Individual data will not be available to anyone not directly associated with the study. All study 
personnel have been trained in data safety and monitoring, privacy and confidentiality, 
minimizing risks related to loss of privacy and confidentiality. We will closely monitor 
performance of our research personnel to ensure the strictest standards. Study-related 
information will not be released without written permission of the participant.
14. COST OF PARTICIPATION
There are no costs for participation in this research study. Participants will be responsible for the 
usual costs of medical care.
15. PAYMENT FOR PARTICIPATION
Participants will be compensated for participation in the study in the form of a reloadable debit 
card (ClinCard).They will receive a handout that will explain how to use this card. A graduated 
incentive schedule will be used. Adolescents and caregivers (i.e., only one caregiver per family) 
will each receive $10 for completing baseline questionnaires, $15 for completing post-treatment 
questionnaires and $20 for completing the 3-month follow-up assessment. If the adolescent 
uses the electronic monitor for the duration of the study and returns the monitor at the end of the 
study, they will receive an additional $25. Thus, adolescents who comply with all study 
procedures can be compensated $70 and caregivers can be compensated up to $45 via their 
ClinCard. Because we are asking current active participants to complete the new COVID-19 
measure to asses for the acute effects of COVID-19, we will be compensating them an 
additional $5 for its completion. This will be part of the battery of questionnaires for those newly 
enrolled or future study visits for those enrolled, so no additional compensation will be given for 
its completion at those timepoints.