Adherence, Medication, Epilepsy
Conditions
Keywords
adolescents, behavioral economics, mHealth
Brief summary
Non-adherence to antiepileptic drug therapy is a significant problem for adolescents with epilepsy and has a critical impact on health and patient-reported outcomes. Evidence-based adherence interventions are lacking in this population and are critically needed. This proposal seeks to develop and evaluate a mHealth social norms adherence intervention for adolescents with epilepsy.
Detailed description
Non-adherence to antiepileptic drugs (AEDs) is a common problem (i.e., 58% of patients have some level of non-adherence) for 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. While reminder strategies (e.g., automated digital reminders) are effective for the most common adherence barriers of forgetting and busy schedules, they are likely to be ineffective in increasing motivation. Leveraging social norms comparison methods (i.e., feedback about someone else's behavior related to one's own behavior) offers an opportunity to capitalize on the increased importance of peer influence while simultaneously targeting the low motivation characteristic of adolescents. Recent data in adolescents indicates that social norms interventions have incremental value and improve health behaviors above and beyond standard feedback without peer comparisons. Consistent with the ORBIT model for behavioral intervention development, our aims are to: 1) develop a feasible, accessible, and acceptable mHealth social norms intervention for improving AED adherence in adolescents with epilepsy and 2) obtain preliminary efficacy data and effect sizes for a future clinical trial. We conducted a pilot RCT of an mHealth social norms intervention (ORBIT Phase II). Adolescents with epilepsy who demonstrate non-adherence (\< 95% adherence based on PI's previous RCTs; 58% of sample) during baseline will be randomized to either 1) mHealth social norms (automated digital reminders, individualized adherence feedback, and social norms feedback) or 2) control (automated digital reminders and individualized adherence 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. If successful, the results of this study would have a large impact on pediatric epilepsy, with the potential to change clinical practice for treating non-adherence by reducing common barriers to behavioral health care. Because minimal clinician time is required, our mHealth social norms intervention also has potential for sustainability and broad dissemination for epilepsy and other pediatric conditions
Interventions
Reminders from electronic monitors via texts or alarms/lights
Feedback report on individual adherence behaviors
Feedback report on individual adherence behaviors compared to other adolescents with epilepsy
Sponsors
Study design
Intervention model description
This is 2-arm randomized controlled clinical trial to improve adherence in adolescents with epilepsy
Eligibility
Inclusion criteria
* Ages 13-17 * Confirmed diagnosis of epilepsy * Antiepileptic drug monotherapy * Ability to read and speak English
Exclusion criteria
* No significant developmental delay (e.g., autism, moderate/severe developmental or intellectual disability) or comorbid medical diagnoses (e.g., diabetes)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Electronically Monitored Adherence | Month 7 | A total mean adherence rates will be calculated based on daily adherence rates captured through the SimpleMed Pillboxes or AdhereTech bottles. Scores range from 0-100%, with higher scores representing better adherence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Seizure Severity-Clinician Report | Month 9 | The Global Assessment of Severity of Epilepsy (GASE) is a one item clinician-rated measure of seizure severity. The total score ranges from 1-7, with higher scores representing more severe epilepsy |
| Seizure Severity-Parent Report | Month 9 | The Seizure Severity Scale-Adapted for Children is a caregiver-reported questionnaire, which is 9-items and assess seizure severity, including intrusiveness, frequency, length, and disruptiveness of seizures. A total score is calculated, ranging from 0-3, with higher scores representing worse seizure severity. |
| PedsQL Epilepsy Module - Parent Report | Month 9 | The PedsQL-Epilepsy Module is a 29 item measure with several subscales (Impact, Cognitive, Executive Functioning, Sleep, Mood/Behavior) will be used. Scores range from 0-100 for each subscale, with higher scores representing better quality of life. |
| PedsQL Epilepsy Module-Adolescent Report | 9-month | The PedsQL Epilepsy Module is a 29-item health-related quality of life instrument with five subscales, including Impact, Cognitive, Executive Functioning, Sleep, and Mood/Behavior). Scores range from 0-100, with higher scores representing better quality of life. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Satisfaction-Teen Report Total Score | Month 7 | Adolescents completed this study specific Satisfaction measure, which was 23-items. This measure assesses satisfaction with the intervention content, relevance, helpfulness, and ease of use. Assessment of perceptions of the impact of what was learned from the intervention were also assessed. Eighteen of the items used a Likert format with the following ratings: Strongly Disagree, Disagree, Agree, and Strongly Agree. A total scale was calculated for the 18 items, which ranges from 18-72, with higher scores reflecting higher satisfaction. Finally, five open-ended items assessing what was most and least helpful about the intervention, what changes adolescents want to see in the intervention, and any additional input. |
Countries
United States
Participant flow
Pre-assignment details
We had a run-in period, in which 64 participants were not randomized to either control or treatment groups. The primary participants in this study were adolescents and caregivers did not receive the intervention. Caregivers completed parental permission (consent) forms, demographic information related to their child and provided data for two of the secondary outcomes.
Participants by arm
| Arm | Count |
|---|---|
| Control Group Automated reminders and individualized adherence feedback reports
Automated Digital Reminders: Reminders from electronic monitors via texts or alarms/lights
Individualized Adherence Feedback Report: Feedback report on individual adherence behaviors | 21 |
| Treatment Group Automated reminders and individualized adherence feedback reports with social norms comparisons
Automated Digital Reminders: Reminders from electronic monitors via texts or alarms/lights
Individual Adherence Feedback Report with Social Norms: Feedback report on individual adherence behaviors compared to other adolescents with epilepsy | 19 |
| Not Randomized No interventions were provided to these participants as they demonstrated high adherence and were not eligible for randomization based on the run-in period. | 64 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Weaned from medicine | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 5 |
| Overall Study | Withdrawn by study staff due to non-compliance with study procedures | 2 | 1 | 12 |
Baseline characteristics
| Characteristic | Control Group | Treatment Group | Not Randomized | Total |
|---|---|---|---|---|
| Age, Continuous | 15.2 years STANDARD_DEVIATION 1.2 | 14.9 years STANDARD_DEVIATION 3.2 | 15.6 years STANDARD_DEVIATION 1.4 | 15.4 years STANDARD_DEVIATION 1.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 18 Participants | 62 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Family Insurance Not insured | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Family Insurance Private | 10 Participants | 17 Participants | 43 Participants | 70 Participants |
| Family Insurance Public | 9 Participants | 2 Participants | 18 Participants | 29 Participants |
| Family Insurance Public and Private | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Monotherapy versus Polytherapy Monotherapy | 21 Participants | 17 Participants | 61 Participants | 99 Participants |
| Monotherapy versus Polytherapy Polytherapy | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Monotherapy versus Polytherapy Unknown | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Primary Caregiver Father/Stepfather | 4 Participants | 3 Participants | 2 Participants | 9 Participants |
| Primary Caregiver Mother/Stepmother | 16 Participants | 16 Participants | 51 Participants | 83 Participants |
| Primary Caregiver Other: Grandmother, Uncle, Aunt | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Caregiver Unknown | 0 Participants | 0 Participants | 11 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 3 Participants | 4 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 13 Participants | 15 Participants | 58 Participants | 86 Participants |
| Seizures in the Past 3 months No | 13 Participants | 13 Participants | 39 Participants | 65 Participants |
| Seizures in the Past 3 months Unknown | 0 Participants | 0 Participants | 11 Participants | 11 Participants |
| Seizures in the Past 3 months Yes | 8 Participants | 6 Participants | 14 Participants | 28 Participants |
| Seizure Type Focal | 5 Participants | 7 Participants | 9 Participants | 21 Participants |
| Seizure Type Generalized | 14 Participants | 9 Participants | 46 Participants | 69 Participants |
| Seizure Type Unclassified | 2 Participants | 3 Participants | 8 Participants | 13 Participants |
| Seizure Type Unknown | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 8 Participants | 9 Participants | 38 Participants | 55 Participants |
| Sex: Female, Male Male | 13 Participants | 10 Participants | 26 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 19 |
| other Total, other adverse events | 3 / 21 | 6 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 19 |
Outcome results
Electronically Monitored Adherence
A total mean adherence rates will be calculated based on daily adherence rates captured through the SimpleMed Pillboxes or AdhereTech bottles. Scores range from 0-100%, with higher scores representing better adherence.
Time frame: Month 7
Population: Adherence data missing for 2 participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Electronically Monitored Adherence | 45.5 units on a scale | Standard Deviation 32 |
| Treatment Group | Electronically Monitored Adherence | 50.5 units on a scale | Standard Deviation 37.4 |
PedsQL Epilepsy Module-Adolescent Report
The PedsQL Epilepsy Module is a 29-item health-related quality of life instrument with five subscales, including Impact, Cognitive, Executive Functioning, Sleep, and Mood/Behavior). Scores range from 0-100, with higher scores representing better quality of life.
Time frame: 9-month
Population: The flow diagram differs in sample size as one less adolescent completed this measure. Thus, the sample size is n=12.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | PedsQL Epilepsy Module-Adolescent Report | Cognitive | 73.6 score on a scale | Standard Deviation 19.9 |
| Control Group | PedsQL Epilepsy Module-Adolescent Report | Executive Functioning | 75.7 score on a scale | Standard Deviation 13.5 |
| Control Group | PedsQL Epilepsy Module-Adolescent Report | Sleep | 56.9 score on a scale | Standard Deviation 20.4 |
| Control Group | PedsQL Epilepsy Module-Adolescent Report | Mood/Behavior | 65.4 score on a scale | Standard Deviation 15.1 |
| Control Group | PedsQL Epilepsy Module-Adolescent Report | Impact | 80 score on a scale | Standard Deviation 13.5 |
| Treatment Group | PedsQL Epilepsy Module-Adolescent Report | Mood/Behavior | 71.9 score on a scale | Standard Deviation 28.2 |
| Treatment Group | PedsQL Epilepsy Module-Adolescent Report | Impact | 82.8 score on a scale | Standard Deviation 20.7 |
| Treatment Group | PedsQL Epilepsy Module-Adolescent Report | Cognitive | 71.6 score on a scale | Standard Deviation 26.1 |
| Treatment Group | PedsQL Epilepsy Module-Adolescent Report | Sleep | 67.7 score on a scale | Standard Deviation 27.2 |
| Treatment Group | PedsQL Epilepsy Module-Adolescent Report | Executive Functioning | 65.4 score on a scale | Standard Deviation 26.7 |
PedsQL Epilepsy Module - Parent Report
The PedsQL-Epilepsy Module is a 29 item measure with several subscales (Impact, Cognitive, Executive Functioning, Sleep, Mood/Behavior) will be used. Scores range from 0-100 for each subscale, with higher scores representing better quality of life.
Time frame: Month 9
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | PedsQL Epilepsy Module - Parent Report | Cognitive (parent) | 63.1 score on a scale | Standard Deviation 28.9 |
| Control Group | PedsQL Epilepsy Module - Parent Report | Executive functioning (parent) | 71.2 score on a scale | Standard Deviation 23.2 |
| Control Group | PedsQL Epilepsy Module - Parent Report | Sleep (parent) | 60.3 score on a scale | Standard Deviation 17.1 |
| Control Group | PedsQL Epilepsy Module - Parent Report | Mood/Behavior (parent) | 66.5 score on a scale | Standard Deviation 18.5 |
| Control Group | PedsQL Epilepsy Module - Parent Report | Impact (parent) | 83.3 score on a scale | Standard Deviation 15.5 |
| Treatment Group | PedsQL Epilepsy Module - Parent Report | Mood/Behavior (parent) | 67.2 score on a scale | Standard Deviation 23.2 |
| Treatment Group | PedsQL Epilepsy Module - Parent Report | Impact (parent) | 78.8 score on a scale | Standard Deviation 18 |
| Treatment Group | PedsQL Epilepsy Module - Parent Report | Cognitive (parent) | 72.4 score on a scale | Standard Deviation 19.8 |
| Treatment Group | PedsQL Epilepsy Module - Parent Report | Sleep (parent) | 65.1 score on a scale | Standard Deviation 22.2 |
| Treatment Group | PedsQL Epilepsy Module - Parent Report | Executive functioning (parent) | 72.3 score on a scale | Standard Deviation 23.9 |
Seizure Severity-Clinician Report
The Global Assessment of Severity of Epilepsy (GASE) is a one item clinician-rated measure of seizure severity. The total score ranges from 1-7, with higher scores representing more severe epilepsy
Time frame: Month 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Seizure Severity-Clinician Report | 2.5 score on a scale | Standard Deviation 1.3 |
| Treatment Group | Seizure Severity-Clinician Report | 2.4 score on a scale | Standard Deviation 1.2 |
Seizure Severity-Parent Report
The Seizure Severity Scale-Adapted for Children is a caregiver-reported questionnaire, which is 9-items and assess seizure severity, including intrusiveness, frequency, length, and disruptiveness of seizures. A total score is calculated, ranging from 0-3, with higher scores representing worse seizure severity.
Time frame: Month 9
Population: The number of participants analyzed does not match the participant flow as some participants did not complete this particular measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Seizure Severity-Parent Report | 0.98 score on a scale | Standard Deviation 0.55 |
| Treatment Group | Seizure Severity-Parent Report | 1.11 score on a scale | Standard Deviation 0.6 |
Satisfaction-Teen Report Total Score
Adolescents completed this study specific Satisfaction measure, which was 23-items. This measure assesses satisfaction with the intervention content, relevance, helpfulness, and ease of use. Assessment of perceptions of the impact of what was learned from the intervention were also assessed. Eighteen of the items used a Likert format with the following ratings: Strongly Disagree, Disagree, Agree, and Strongly Agree. A total scale was calculated for the 18 items, which ranges from 18-72, with higher scores reflecting higher satisfaction. Finally, five open-ended items assessing what was most and least helpful about the intervention, what changes adolescents want to see in the intervention, and any additional input.
Time frame: Month 7
Population: Participant numbers are lower than the Participant Flow data as some participants did not complete this particular measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Satisfaction-Teen Report Total Score | 53.5 score on a scale | Standard Deviation 9 |
| Treatment Group | Satisfaction-Teen Report Total Score | 50.8 score on a scale | Standard Deviation 6 |