Medical Progress

Electronic Measurement of Medication Adherence in Pediatric Chronic Illness: A Review of Measures

Adolescents with epilepsy are at heightened risk for suboptimal anti-seizure medication (ASM) adherence; however, there is a paucity of adherence interventions for this age group. The current study aimed to identify a comprehensive and novel set of predictors of objective, electronically-monitored ASM adherence in adolescents with epilepsy.

Participants included 104 adolescents (13–17 years old; M = 15.36 ± 1.40), diagnosed with epilepsy and their caregivers. Cross-sectional data were collected from adolescents, caregivers, healthcare providers, and medical chart reviews, including demographics (i.e., age, race/ethnicity, sex, insurance status), the COVID-19 pandemic (i.e., participation before versus during), seizure characteristics (i.e., presence and severity), ASM side effects (Pediatric Epilepsy Side Effects Questionnaire), adherence motivation (1-item 6-point Likert scale item), and adherence barriers (Pediatric Epilepsy Medication Self-Management Questionnaire). Electronically-monitored adherence data was collected via the AdhereTech^TM pill bottle or the Vaica SimpleMed^TM pillbox over 30 days.

Adolescents demonstrated suboptimal adherence at 78 ± 31.6%, despite high ASM adherence motivation (M = 4.43 ± .94) and minimal adherence barriers (M = 35.64 ± 3.78). Hierarchical multiple regression, which included non-modifiable sociodemographic and medical variables (Block 1) and behaviorally modifiable psychosocial variables (Block 2) was significant, F(12,87) = 3.69, p < .001. Specifically, having private insurance (versus Medicaid or public insurance; t = −2.11, p = .038) and higher adherence motivation (t = 2.91, p = .005) predicted higher objective ASM adherence.

Routine assessment of adherence predictors is vital for the promotion of adherence among adolescents with epilepsy. Adolescent adherence motivation may be an important element of multi-component interventions focused on improving ASM adherence in adolescents with epilepsy.

The objective of this study was to evaluate the feasibility and acceptability of a dynamic, behavioral intervention to optimize medication adherence of adolescents and young adults (AYAs) with HIV newly initiating highly active antiretroviral therapy (HAART) and explore its efficacy on adherence and disease outcomes.

The two-arm randomized controlled trial piloted a brief, individualized intervention designed for direct integration into standard clinical care. In total, 32 AYAs with a confirmed HIV diagnosis, reportedly horizontally acquired, and recommended to initiate HAART completed a two-week placebo trial before HAART initiation and were subsequently randomized to standard of care or the individualized intervention. Adherence and disease outcomes were measured over the first six months of HAART.

Results supported the primary study aim regarding feasibility (recruitment = 89%, attendance = 81%–100%, intervention exercise completion = 100%) and acceptability (average favorable response = 89%). Data also supported the positive effect of the intervention on select HAART adherence measures and disease outcomes. Adherence (by pharmacy refill) declined in both groups; however, adherence declined more slowly in the intervention group versus standard of care (p < .001). In addition, 100% of participants receiving the intervention obtained an undetectable viral load by 3 months and maintained an undetectable viral load at 6 months (vs. 68.8% standard of care).

This is one of the first interventions to target adherence for AYAs with HIV newly initiating HAART and designed for delivery in existing clinical care settings. Future research will help confirm efficacy and the potential utility of the intervention in promoting HAART adherence from medication initiation and preventing the decrease in adherence often observed over time.

There is limited information on the impact of active education by a pharmacist in the population of pediatric patients with epilepsy (PWE) in China. The objective of this study was to assess the effect of education by pharmacists on medication adherence and percentage of valproic acid (VPA) samples reaching therapeutic reference range in these patients. This study was conducted at two teaching hospitals in Changsha, China. Patients were retrospectively identified from January 2016 to December 2017. Active education by a pharmacist in both oral and written formats was provided at the intervention hospital whereas standard passive pharmacist service (dispensing and answering questions) was provided at the control hospital. Medication adherence was assessed by the simplified medication adherence questionnaire (SMAQ), and serum concentrations of VPA were collected. The correlation between pharmacist education and medication adherence and percentage of VPA samples reaching therapeutic reference range were analyzed. A total of 2165 patients and 4343 serum VPA concentrations were included in the analysis. For the first therapeutic drug monitoring (TDM) measurement, there was no statistical difference between the two hospitals: 41.3% of VPA samples reached therapeutic range at the intervention hospital compared with 45.4% at the control hospital (χ² = 3.686, P > 0.05). After pharmacist intervention at the intervention hospital, however, there were significant differences in the percentage of therapeutic VPA samples reaching therapeutic range between the first and the second, third, fourth, and fifth TDM measurements (χ² = 9.756, P < 0.01; χ² = 22.840, P < 0.01; χ² = 15.816, P < 0.01; χ² = 27.613, P < 0.01).

Based on the SMAQ adherence assessment, adherence increased from a minimum of 56.0% to a maximum of 73.9% with stabilization during the last six months of follow-up at the intervention hospital. Both the medication adherence rate and the percentage of VPA samples reaching therapeutic range increased as the result of active education by a pharmacist, suggesting that continuous pharmacist intervention had a positive impact in outpatient pediatric PWE.

There is a lack of a standardized tool for adherence measurement in patients with epilepsy. Studies in children with epilepsy have reported adherence in 50–96.5%. The primary objective of this study was to identify predictors of nonadherence to antiepileptic drugs (AEDs) using two different methods in Jordanian children and adolescents with epilepsy.

Participants included 63 children and adolescents with epilepsy and their primary caregivers. Adherence measures included a subjective approach (using parent and child self-reports via Medication Adherence Report Scale (MARS)) and an objective method (measuring plasma levels of AEDs coupled with the application of population pharmacokinetic models to predict AED concentrations in the children). The Beliefs about Medicines Questionnaire (BMQ) was used to examine the association beliefs about medicines with nonadherence in the participating patients.

Measuring AEDs in plasma samples captured the highest percentage of nonadherence (36.2%). No significant agreement was found between the AED plasma level method and both the MARS (parent) and MARS (child). The overall nonadherence (combined methods) to AED therapy in children with epilepsy was 44.4%. Logistic regression analysis indicated that children with longer duration of disease were more likely (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.16–2.04) to be classified as nonadherent as were children whose parents have lower AED Necessity scores (OR: 0.68, 95% CI: 0.53–0.87) and higher AED Concerns (OR: 1.6, 95% CI: 1.26–2.04) as measured by the BMQ.

The use of a multimethod approach for assessing adherence increases sensitivity for detection of nonadherence to AEDs. Disease duration and parental necessity beliefs and concerns assessed by the BMQ-specific questionnaire were significant predictors of nonadherence to the AED therapy. The need for the development and implementation of interventions that can be employed to improve adherence within this pediatric population has been highlighted by the high levels of nonadherence identified.

We prospectively examined rates of outpatient oral medication adherence in children after hematopoietic stem cell transplant (post-HSCT). For 6 months after first discharge post-HSCT, 50 patients (aged 0 to 16 years) and their primary caregivers agreed to store 1 oral medication in an electronic pill bottle that date and time stamps each bottle opening. Demographics, disease, donor type, and prescribed post-HSCT medication regimen were collected via chart review. For each patient percent adherence was calculated by dividing the number of doses taken as indicated by the electronic pill bottle by the number of doses prescribed for the same time period. Average percent adherence ranged from 63% at 1 month after discharge to 57% at 6 months after discharge. For patients who received an allogeneic transplant, lower adherence was associated (P < .005) with higher infection rates, after controlling for age and time since transplant. No such relationship was observed for patients who received an autologous transplant. This study demonstrates that poor oral medication adherence is prevalent, persistent, and, for patients receiving an allogeneic transplant, associated with increased incidence of infections during the outpatient treatment period. This study highlights the need for further research examining factors that hinder medication adherence as well as monitoring, promoting, and intervening to maximize medication adherence throughout the HSCT course.

Nonadherence to asthma medications is well recognized. Interventions to improve adherence, however, have been only moderately successful and are not often adopted because of limited provider time, training, or institutional support. The potential for mobile communication technology to improve adherence has gathered sharply growing interest. Technology-based adherence tracking devices have been in existence for almost 3 decades, but have only recently reached a level of reliability and utility to be considered in allergy practice. Adherence intervention technology includes smartphones, apps, and a growing number of potential new asthma uses such as inhaler technique assessment, portable fractional exhaled nitric oxide devices, and GPS activity trackers with environmental contaminant alerts. As technology has advanced, new capability has emerged including drawing information from electronic health records to tailor automated interventions, give real-time feedback to patients, leverage incentives, utilize predictive logarithms that identify patients at exacerbation risk, and initiate an intervention. Technology development moves faster than clinical trial tests of these new interventions, and gaps in evidence will need to be closed. As researchers establish cost effectiveness, sustainability, and patient and provider acceptance, technology-based adherence intervention systems are likely to be increasingly adopted into small and large practice settings.