Current Projects

Epilepsy Adherence in Children with Technology (eACT)

Non-adherence to antiepileptic drugs (AEDs) is a common problem (i.e., 58% of patients have some level of non-adherence) for young children with newly diagnosed epilepsy, with potentially devastating consequences. AED non-adherence is associated with a 3-fold increased risk of seizures, poor quality of life, inaccurate clinical decision-making, and higher healthcare utilization and costs.

One of the primary barriers to adherence is forgetting, which may be particularly amenable to mHealth (mobile technology in healthcare) interventions. Despite the critical need to develop and implement interventions to improve adherence, there are few family-based interventions for young children with epilepsy and their families, with the exception of our work.

Although highly promising, this intervention requires six in-person sessions, which can be impossible for families who lack routine access to tertiary specialty care due to time, financial, or transportation constraints. Thus, unmet medical and psychosocial needs of the underserved pediatric epilepsy population are perpetuated and compounded by limited access to this state-of-the-art care.

Our overall goal in this multisite study is to test a mHealth adherence intervention that is easily accessible using a stepped up care model based on individual needs. This stepped up care model will conserve patient, family, and provider time, costs and resources.

We have completed the first phase of this work and incorporated the feedback we gathered from caregivers during focus groups and usability studies to develop:

• Education microlearning sessions
• Automated digital reminders
• Individualized adherence feedback reports to improve adherence
• Telehealth problem-solving sessions

The second phase of this study will consist of a 2-stage, sequential, multiple-assignment, randomized trial (SMART) to evaluate the effectiveness of mHealth intervention strategies for improving AED adherence in parents/legal guardians of young children with epilepsy.

We plan to recruit a total of 600 participants across all collaborating study sites, with approximately 150 at each of four sites: Cincinnati Children’s, Medical University of South Carolina, Children’s Hospital of Orange County, and Nationwide Children’s Hospital.

Enrolled caregivers will complete study questionnaires and be asked to start using electronic adherence monitors (e.g., pillbox or pill bottle) at the time of data enrollment during the baseline period. Only participants who demonstrate adherence <95% will be randomized to either the control group or treatment group in Stage 1. n SMART Stage 1 (3-months), caregivers of non-adherent children (< 95%) are randomized to a mHealth education module and automated digital reminders (control) or the mHealth education module, automated digital reminders, and individualized adherence feedback based on real-time adherence monitoring (treatment) to address the primary barrier of forgetting.

At the beginning of SMART Stage 2, caregivers randomized to the treatment group who demonstrate continued non-adherence (<95%; non-response) by the end of Stage 1 undergo a second randomization to either 1) continued individualized adherence feedback or 2) individualized adherence feedback augmented with a mHealth problem-solving module (translated from the PIs existing RCTs) and two therapist-guided Skype sessions. The primary outcome is electronically monitored adherence. Secondary outcomes include seizure severity/frequency, quality of life and healthcare utilization. These data will then be examined, analyzed, and used to evaluate study aims including efficacy, effectiveness, and predictors of treatment responsiveness.

Project Details

• More Information: To learn more about the eACT study, follow this link.
• Collaborators: To hear from study collaborator, Matt Schmidt, PhD, University of Florida, follow this link.
• Funding: R01NR017794-01A; Fostering medication adherence in children with epilepsy using mHealth technology.
• Outcomes and Publications
  • Modi, AC; Patel, AD; Stevens, J; Smith, G; Huszti, H; Guilfoyle, SM; Mara, CA; Schmidt, M; Wagner, JL. The psychosocial impact of COVID-19 within the first six months of the pandemic on youth with epilepsy and their caregivers. Epilepsy Behav. 2021 Apr;117:107855.

Diabetes Journey

Type 1 diabetes (T1D) treatment adherence is complex and involves glucose monitoring, counting carbohydrates, and intensive insulin delivery via injections or insulin pump in response to food intake, exercise, and illness to achieve near-normal blood glucose levels. T1D treatment adherence is challenging, especially during adolescence, which can lead to suboptimal blood glucose levels that severely compromises health, and in some cases, leads to premature death.

Several interventions for adolescents with T1D exist, but none have focused on adherence barriers. The Barriers to Diabetes Adherence scale assesses these important targets for tailored adherence interventions, including stress/burnout and time pressure/planning (e.g., skills related to executive functioning). These adherence barriers are significantly associated with non-adherence, higher glycemic levels, and lower quality of life; however, no interventions address these two barriers in research or clinical practice.

The overall objective of this study is to use patient-report of adherence barriers to identify intervention targets that will guide the integration of a novel tailored intervention into clinical care to improve adherence, glycemic levels, and quality of life.

There are several aims of our multi-site R01. First, we plan to reliably integrate patient-reported questionnaires, including the Barriers to Diabetes Adherence scale, into routine care in two, large T1D centers.

Second, our existing intervention, Epilepsy Journey will be modified to Diabetes Journey. This intervention includes mobile health modules addressing barriers related to stress/burnout and time pressure/planning with accompanying telemedicine sessions with a therapist. We will use expert feedback to modify the modules and then conduct usability testing with 10 adolescents with T1D to ensure the modules are easy to navigate, engaging, and relevant to teens with T1D.

Third, we will conduct a pilot clinical trial of Diabetes Journey. Our goal is to evaluate how well Diabetes Journey helps to improve stress/burnout and time pressure/planning (e.g., executive functioning) in 256 adolescents with T1D and whether adolescents think Diabetes Journey is helpful and acceptable. Adolescents who experience elevated adherence barriers during routine T1D clinic visits will be randomized to:

1. Diabetes Journey
2. Enhanced standard of care (e.g., website and 4 Zoom sessions with a certified diabetes educator)

Both interventions will be tailored to each adolescent’s reported barrier(s). We will also examine the impact of Diabetes Journey on adherence, glycemic control, and quality of life. We are currently actively recruiting participants for the RCT.

Project Details

• More Information: To learn more about the Diabetes Journey study, follow this link.
• Collaborators: Kimberly Driscoll, PhD, University of Florida.
• Funding: R01DK121295; Diabetes Journey: An Intervention to Improve Adherence Barriers for Adolescents with Type 1 Diabetes

BEAT (Behavioral Economics and Adherence in Teens)

There are no efficacious adherence interventions for adolescents with epilepsy. This gap is remarkable as low motivation and susceptibility to peer influence make adolescents more likely to engage in behaviors that have immediate rewards, especially in the context of their peers (e.g., skipping AEDs when out with friends), and less likely to worry about future negative consequences (e.g., having a seizure).

Not surprisingly, adherence worsens during adolescence, further increasing the risk of poor health outcomes during this developmental period. However, leveraging social norms comparison methods (i.e., feedback about someone else’s behavior related to one’s own behavior) from behavioral economics offers a unique opportunity to capitalize on the increased importance of peer influence, while simultaneously targeting the low motivation characteristic of adolescents.

We are addressing our study aims through an iterative process, including an adolescent focus group (ORBIT Phase 1a: Define; n=8), extended formative usage evaluation (ORBIT Phase 1b: Refine; n=10) and a pilot RCT of the final mHealth social norms intervention (ORBIT Phase II: Pilot; n=138). We have completed Phase 1a and 1b and recruitment for the RCT has been completed. We are currently wrapping up study completion for our ongoing RCT. Data cleaning and analysis will follow.

Project Details

• Funding: R21NR017633-01; Improving Drug Adherence Using mHealth and Behavioral Economics in Adolescents with Epilepsy

Complete Projects

Validation of the PedsQL™ Epilepsy Module

Children and adolescents with epilepsy are at risk for poor health related quality of life (HRQOL). Generic measures of HRQOL may not capture unique aspects of functioning in this population, which are necessary for gauging clinical outcomes and response to treatment. Current epilepsy-specific HRQOL measures, which are responsive to the disease and its treatments, have significant limitations, including no self-report and parent-proxy versions for certain ages (e.g., self-report for 2-10 year olds, parent-proxy report for 2-4 year olds), no parent-proxy and self-reports developed in parallel, or exclusion of individuals with cognitive impairments.

The aim of this project was to develop an epilepsy-specific HRQOL measure that includes self-report and parent proxy versions that can be used across the developmental spectrum. Focus groups and cognitive interviews with patients with epilepsy and their caregivers identified important content areas based on their personal experiences as well as ways to refine the measures. We then tested the draft measures of the PedsQL™ Epilepsy Module across five epilepsy centers in the US, including Cincinnati Children’s, Medical University of South Carolina, University of Wisconsin, Children’s Hospital of Orange County, and Cook Children’s Hospital. The national validation sample include 430 youth with epilepsy and their caregivers. Psychometric analyses revealed a strong measure with reliable scales: Impact, Cognitive, Sleep, Executive Functioning, and Mood/Behavior. Self-report versions were created for youth 5-7, 8-12, 13-17, and 18-25 years of age. Parent-proxy versions were created for caregivers of youth 2-4, 5-7, 8-12, 13-17, and 18-25 years of age.

Project Details

• Outcomes and Publications
• Visit this website to submit a request for the PedsQL™ Epilepsy Module.
• Varni, JW; Junger, KF; Kellermann, T; Barrett Grossman, L; Wagner, J; Mucci, GA; Guilfoyle, SM; Smith, G; Zupanc, ML; & Modi, AC. PedsQL™ Cognitive Functioning Scale in Youth with Epilepsy: Reliability and Validity. Epilepsy and Behavior. 2020; 103 (Pt A).
• Junger, K.W., Modi, A.C., Guilfoyle, S.M., Smith, G., Wagner, J., Mucci, G.A., Huszti, H. & Mara, C.A.. Establishing Clinical Cutoffs for the PedsQL Epilepsy Module. Epilepsy and Behavior. 2019; 99.
• Modi, AC; Junger, KF; Mara, C; Kellermann, T; Barrett, L; Wagner, J; Mucci, GA; Bailey, L; Almane, D; Guilfoyle, SM; Urso, L; Hater, B; Hustzi, H; Smith, G; Herrmann, B; Perry, MS; Zupanc, M; & Varni, JW. Validation of the PedsQL™ Epilepsy Module: A Pediatric Epilepsy-specific Health-related Quality of Life Measure. Epilepsia. 2019; 58(11), 1920-1930.

Supporting Treatment Adherence Regimens: The STAR Trial

Obtaining and maintaining complete seizure freedom is compromised by the high rate of non-adherence to antiepileptic drug (AED) therapy, documented in 58% of children with new-onset epilepsy during their first six months of therapy. AED non-adherence is associated with continued seizures, a three-fold risk for mortality and high healthcare costs. Thus, improving pediatric AED non-adherence is of utmost importance. Despite the critical need to develop and implement interventions to improve adherence, no methodologically rigorous randomized controlled trial (RCT) has focused on improving AED adherence in children.

The purpose of this study was to test the efficacy of an adherence intervention addressing pediatric AED nonadherence. Two hundred newly diagnosed patients and their families were recruited during routine epilepsy clinic visits to participate in the study. Participants were either monitored over time or randomized into one of two groups. Those randomized to treatment participated in eight sessions over four months (six face-to-face, two phone). Families in treatment were followed for three additional time points after treatment ends. Recruitment for this study ended in December 2018. We are currently analyzing this data. Our methods paper was recently published.

Project Details

• Funding: R01HD073115; Supporting Treatment Adherence Regimens in Pediatric Epilepsy

Epilepsy Journey

Adolescents with epilepsy are at significant risk for poor social and academic outcomes, neurobehavioral comorbidities (i.e., internalizing and externalizing symptoms), and poor treatment adherence. Studies have shown that one potential reason for these poor outcomes are deficits in executive functioning (EF), defined as the skills necessary for goal-directed and complex activities, including problem-solving, initiation, monitoring, organization, planning, self-regulation and working memory.

EF deficits have been documented in 1/3 of youth with epilepsy, which is 3 times the prevalence in healthy youth. Evidence-based interventions to improve EF could play a critical role in preventing adverse outcomes (e.g., psychological comorbidities, non-adherence to the treatment regimen) and promoting optimal functioning in adolescents with epilepsy; however none exists for this vulnerable population.

The aim of the study was to develop an individually-tailored intervention to improve EF in adolescents with epilepsy (Epilepsy Journey) through an iterative, patient-centered process that includes:

1. Identification of the unique needs of adolescents with epilepsy and their families based on focus group feedback (Phase 1)
2. Usability testing of a revised intervention protocol to elicit feedback on the applicability, content, and individualized approach (Phase 2)

Our primary outcomes from this study have been published and we are examining our secondary outcomes currently.

Project Details

• Funding: R21HD083335-01; Web-based Intervention to Improve Executive Functioning in Teens with Epilepsy

Neuroimaging Biomarkers for Executive Functioning in Adolescents with Epilepsy (fMRI study)

Despite medical advances in the treatment of seizures, adolescents with epilepsy often have poor behavioral outcomes, and demonstrate poor adherence to the medical treatment. Deficits in executive functioning skills (i.e. problem-solving, initiation, planning/organization, monitoring, self-regulation and working memory) likely underlie these poor outcomes. Executive function deficits are common in youth with epilepsy and are a strong predictor of long-term neurobehavioral problems in children with seizures.

In this study, we used neuroimaging in adolescents with epilepsy to establish a biomarker for executive function deficits in this population. We collected structural and functional neuroimaging data from approximately 40 adolescents with epilepsy and 20 healthy controls in the same age range. We are analyzing abnormalities in specific brain networks that have been suggested to underlie executive function in healthy children and adults. We are also evaluating multi-method measurement of EF using neuropsychological testing, questionnaires, and imaging. Overall, our goal is to understand the neural basis of these deficits to facilitate improved prediction of who will benefit from EF interventions. Several papers and posters have been published from this study.

Text-messaging & Adherence Pilot Study (TAPS Study)

The purpose of the study was to test the feasibility and acceptability of five different text-messaging or application-based interventions to improve adolescent AED non-adherence. Twenty-five families were randomized to one of five interventions:

1. Adolescent text only
2. Adolescent and caregiver text plus communication
3. Adolescent application only
4. Adolescent and caregiver application plus communication
5. Epilepsy application for adolescents only

Primary caregivers and adolescents completed baseline assessment measures, as well as post-treatment and follow-up assessments. Patients were followed for approximately 3 months. The primary outcome measure was electronically-monitored adherence using MEMS TrackCaps or a SimpleMed. Data have been published.

Adolescent Adherence to Antiepileptic Drugs Study: The AAA Study

Few studies have been conducted with adolescents with epilepsy to examine rates, patterns, and predictors of non-adherence to AED therapy using objective methods (i.e., electronic monitors). The purpose of this study was to examine adherence over time to AED therapy using objective electronic monitors and identify predictors of non-adherence in adolescents with epilepsy. Sixty adolescents and their primary caregivers completed questionnaires and had their adherence monitored over the course of one year. We are working on examining the data and are interested in identifying individual (e.g., internalizing/externalizing problems, risk-taking, treatment responsibility, self-management behaviors), family (e.g., conflict), medical (e.g., side effects, seizure), and sociodemographic variables (e.g., socioeconomic status, age) predictors of adherence over one year. Several papers and posters have been published from these data.

Adherence and Barriers in Children with Epilepsy: The ABC Study

The ABC study, which was completed in 2011, focused on examining patterns of adherence rates over time for children with new-onset epilepsy and identifying the factors that best predict adherence to antiepileptic drug therapy for children with epilepsy over time. We recruited 124 participants, who used electronic monitors, to assess adherence over time and completed questionnaires to assess psychosocial variables (e.g., barriers, knowledge, parenting stress, family functioning, child psychopathology) over 10 time points. Findings from this longitudinal dataset have been published and presented at various regional and national conferences.