mHealth adherence in pediatric epilepsy: Outcomes of a sequential, multiple assignment, randomized trial (SMART)

Nonadherence to antiseizure medications in pediatric epilepsy affects ~60% of youth. The aim of this multisite two-stage sequential, multiple assignment, randomized trial (SMART) was to evaluate the effectiveness of mHealth intervention strategies for improving adherence in caregivers of young children with epilepsy, particularly those who are underserved. It was hypothesized that participants initially randomized to treatment would exhibit significantly greater improvements in adherence compared to an active control group at the end of stage 1. Secondary outcomes included longitudinal adherence, seizure freedom/severity, and health-related quality of life.

Participants across four epilepsy centers were recruited (n = 461, mean age = 7.6 ± 3.0 years, 51% males, 62% White non-Hispanic, 71% underserved). Baseline questionnaires were completed, and electronic adherence monitors were provided. Three intervention strategies were embedded in this SMART: (1) active control (mHealth education + automated digital reminders), (2) treatment (mHealth education + automated digital reminders + individualized adherence feedback) in stage 1 continuing in stage 2 regardless of responsiveness in stage 1, and (3) treatment in stage 1 continuing in stage 2 if patient is responsive in stage 1 or augmented by problem-solving if patient is nonresponsive in stage 1. Active intervention was 5 months, with two posttreatment follow-ups. Standard analysis of covariance was conducted for the primary aim. Secondary analyses compared mean change from baseline associated with each intervention strategy.

The treatment group had significantly better mean adherence percentage change from baseline to the end of stage 1 compared to the active control group (13.2% vs. 3.1% change, t = 2.82, p = .005, d = .37). Adherence rates declined over time across all SMART strategies. An increased probability of seizure freedom at 6 and 12 months across all SMART strategies was found.

This pediatric epilepsy SMART trial demonstrated adherence improvements for the treatment group that did not persist over time. Improvements in seizure freedom that were independent of SMART strategy were also identified. mHealth education, automated digital reminders, and individualized adherence feedback appear to have been efficacious.