Medication Adherence in Children, Adolescents and Adults With Neurofibromatosis Type 1(NF1) on Clinical Treatment Trials

Not Applicable

Completed

Conditions: Neurofibroma, Plexiform
Neurofibromatosis 1

Interventions: Behavioral: Medication Event Monitoring System (MEMS^TM)
Other: Questionnaires

Registration Number: NCT03531814

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

Neurofibromatosis type 1 (NF1) is a genetic disorder. It has a broad variety of effects on the body. Up to half of people with NF1 get plexiform neurofibromas (PNs). These are benign tumors. But they can have serious effects like pain and disfigurement. To treat PNs, a person may have to take medicine every day for a long period of time. Researchers think that it will be important for people to take the medicine regularly for it to work. They want to study how well people with NF1 follow their treatment plan for PNs.

Objective:

To study how often people with neurofibromatosis type 1 take medicine that has been prescribed to them for treating plexiform neurofibromas.

Eligibility:

People ages 3-59 already enrolled in an NF1 clinical trial

Design:

Participants will need access to the internet to do the study activities.

Parents or caregivers will do some study activities for child participants.

Participants will complete 5 questionnaires. They will take about 20 minutes total. The topics will be:

Demographic data

Recent life events

How much pain interferes with daily life

Ability to focus and pay attention to tasks

Emotional distress or depression

Participants will mark down every time they take a dose of the medicine in their clinical trial. They will use a form the researchers give them. The pill bottles they get in their trial will have a chip in the cap that will record when it is opened. Participants will keep a daily diary of their medicine. Their pills will be counted at clinical trial visits.

Participants may have more short questionnaires. They may have interviews by phone or video.

Detailed Description: Background:

* Neurofibromatosis type 1 (NF1) is a genetic disorder that affects approximately 1 in 3,500 individuals and is associated with a broad variety of symptoms and physical findings.

* Plexiform neurofibromas (PN) are histologically benign tumors which occur in 25-50% of patients with NF1 and can lead to significant morbidity.

* Oral therapeutic options for the treatment of plexiform neurofibromas are being actively developed, however early clinical data indicate that prolonged treatment over the course of months to years will likely be needed to maintain clinical efficacy

* Long-term medication adherence is an ongoing challenge for patients with many types of chronic illness, and clinical experience makes us strongly suspect patients with NF1 will likely have this issue as well.

* In other diseases, such as human immunodeficiency virus (HIV) and Acute Lymphoblastic Leukemia, decreased medication adherence has been associated with poorer clinical outcomes, and this may be the case for NF1 as well.

* The medication event monitoring systems (MEMS\^TM) uses a computerized method of tracking the dates and times of a pill bottle being opened and has been shown to be a more accurate measure of medication adherence than patient diaries or pill counts in other patient populations.

* Assessing medication adherence over time in this unique population will be essential for assessing any impact on medical outcomes, identifying potential behavioral interventions, and targeting patients most at risk for nonadherence moving forward.

Objective:

- To establish the feasibility of using MEMS\^TM to monitor medication adherence in the NF1 population

Eligibility:

* Subjects must have a diagnosis of NF1 and be between 3 and 59 years of age

* Participants must be enrolled on a clinical trial for an oral medication in pill (tablet or capsule) form directed at the treatment of plexiform neurofibroma(s)

Design:

* This single-site, longitudinal study will recruit children and adults with NF1 who are currently enrolled in a treatment protocol for a drug targeting PN volume reduction.

* MEMS\^TM caps will be used to monitor adherence over time along with patient diaries and pill counts.

* Patients with MEMS\^TM cap data indicating \<90% adherence at any study visit (typically across 3 - 6 cycles) will be administered a measure assessing barriers to adherence electronically and will be interviewed to evaluate what factors might contribute to decreased medication adherence and what potential interventions they consider useful.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pediatric Participants 8+ Years	Questionnaires	Questionnaires and use of the medication event monitoring system (MEMS\^TM)
Adult Participants	Medication Event Monitoring System (MEMS^TM)	Questionnaires and use of the medication event monitoring system (MEMS\^TM)
Adult Participants	Questionnaires	Questionnaires and use of the medication event monitoring system (MEMS\^TM)
Pediatric Participants 8+ Years	Medication Event Monitoring System (MEMS^TM)	Questionnaires and use of the medication event monitoring system (MEMS\^TM)

Primary Outcome Measures

Name	Time	Method
Median Number of Cycles Monitored for Participants From the Medication Event Monitoring System (MEMS^TM)	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	To monitor medication adherence the medication event monitoring system (MEMSTM) was used to track the dates and times a pill bottle was opened. We calculated the median number of cycles monitored for all patients.
Proportion of Enrolled Participants for Which we Are Able to Collect Data From the Medication Event Monitoring Systems (MEMS^TM) System for Two or More Cycles of Treatment (Target = 75%)	Two cycles, approximately 56 days	The proportion of enrolled participants are reported for individuals who had two full cycles of data recorded by the medication event monitoring systems (MEMS\^TM) system. To monitor medication adherence the medication event monitoring system (MEMSTM) used to track the dates and times a pill bottle was opened. At least 2 cycles of medication adherence are considered a success.

Secondary Outcome Measures

Name	Time	Method
Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Quality of Life (QOL) Patient-Reported Outcomes Measurement Information System (PROMIS) Depression T-scores	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS\^TM cap and PROMIS Depression Scores, Spearman correlation was used. For this analysis, MEMS\^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. PROMIS Depression raw scores were transformed to T-scores for analysis (mean: 50, standard deviation: 10, higher scores is more depression symptoms, T of 55 is the cut off for mild depressive symptoms).
ANOVA (Analysis of Variance) Comparing Average Adherence Measured by Medication Event Monitoring Systems (MEMS^TM), Medication Diary, and Pill Count	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), an range of approximately 112 days to 504 days	A repeated-measures ANOVA was used to compare three adherence assessment methods over time. The medication event monitoring system (MEMS\^TM) was used to track the dates and times a pill bottle was opened. The number of times the bottle was opened was divided by the total number of times the bottle should be opened according to provider instructions. Pill count was used to assess how many pills were returned at each restaging visit compared to the number that should be returned if all medication was taken as prescribed. The daily diary was completed by participants, documenting date and timing of doses. The mean of these numbers was computed across groups of cycles (1 cycle = 28 days) 1-4, 5-8, 9-12 and 13-18 for the MEMS\^TM, Pill Count, and Daily Diary.
Spearman Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Age	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS\^TM cap and age, Spearman correlation was used. For this analysis, MEMS\^TM was defined as the average mean adherence for cycles 1-4, cycles 5-8, cycles 9-12, and cycles 13-18. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average.
Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Quality of Life (QOL) Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference T-scores	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	Outcome measures correlations between 2 variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS\^TM cap \& PROMIS Pain Interference T- Scores (Same for all PROMIS measures) Spearman correlation was used. For this analysis, MEMS\^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-13hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle \& dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. PROMIS Pain Interference raw scores transformed to T-scores for analysis (mean:50,standard deviation: 10, higher scores is more pain interference, T of 55 is cutoff-mild pain interference).
Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Quality of Life (QOL) Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Interference T-scores	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS\^TM cap and PROMIS Cognitive Interference Scores, Spearman correlation was used. For this analysis, MEMS\^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. PROMIS Cognitive Interference raw scores were transformed to T-scores for analysis (mean: 50, standard deviation: 10, higher scores is more cognitive interference, T of 60 represents mild interference).
Barriers to Adherence Questionnaire	Baseline and follow-up (between cycles 8 and 12; or after cycle 18/when taken off of study (range of 224-504 days)	Participants completed a barriers questionnaire to assess barriers most frequently endorsed on the questionnaire. The questionnaire focused on any medication adherence issues during the trial (e.g., missed doses). Participants were given 16 possible reasons that they may have missed a dose and were asked to check all items that caused them to miss a dose of medication. Participants were also able to provide additional reasons for missing medication that were not on the form.
Medication Event Monitoring Systems (MEMS^TM) Cap and Rating of Overall Stress	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	To assess the relationship between the adherence method MEMS\^TM cap and rating of overall stress, Spearman correlation was used. Participants complete a 1-item question asking them to rate their stress from 0 - 10, with higher numbers being more stressed. MEMS\^TM was defined as the average mean adherence, an adherent dose was taken 11-13 hours from the prior correct dose. The mean was computed by dividing medication adherence across the cycle by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data.
Average Percent Medication Adherence Over Time Based on the Medication Event Monitoring Systems (MEMS^TM) Pill Cap Data	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	To monitor medication adherence the medication event monitoring system (MEMS\^TM) was used to track the dates and times a pill bottle was opened. The number of times the bottle was opened was divided by the total number of times the bottle should be opened according to provider instructions. The mean of these numbers was computed across groups of cycles 1-4, 5-8, 9-12 and 13-18. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. Higher number is better adherence.
Medication Event Monitoring Systems (MEMS^TM) Cap and Stressful Life Events: Number of Stressful Life Events Endorsed in the Life Events Checklist	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	To assess the relationship between the adherence method MEMS\^TM cap and stressful life events (i.e., the number of stressful life events endorsed in the Life Events Checklist), Spearman correlation was used. Participants complete a 22-item questionnaire to report stressful events that impact medication adherence. MEMS\^TM was defined as the average mean adherence, an adherent dose was taken 11-13 hours from the prior correct dose. The mean was computed by dividing medication adherence across the cycle by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data.
Spearman Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap for Years of Education	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS\^TM cap for years of education, Spearman correlation was used. For this analysis, MEMS\^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. Number of years of education was collected through participant self-report and was a continuous variable.
Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Barriers to Adherence Questionnaire	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days	The outcome measures Spearman correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. MEMS\^TM was defined as the average mean adherence, an adherent dose was taken 11-13 hours from the prior correct dose. The mean was computed by dividing medication adherence across the cycle by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data. Barriers to adherence was calculated by summing the number of barriers for each participant at follow-up. Participants were given 16 possible reasons that they may have missed a dose and were asked to check all items that apply to them.