A Multidimensional Electronic Hydroxyurea Adherence Intervention for Children With Sickle Cell Disease: Single-Arm Before-After Study

Background Hydroxyurea is a disease-modifying medication for patients with sickle cell disease (SCD). Despite demonstrated efficacy, hydroxyurea nonadherence in clinical practice is common and results in worse health outcomes for nonadherent patients. Mobile Directly Observed Therapy (Mobile DOT) is a pilot-tested, electronic, multidimensional hydroxyurea adherence intervention for children with SCD. Mobile DOT includes sending daily text message reminders to patients to take hydroxyurea, patients recording and sending daily videos that capture their hydroxyurea administrations for the research team to review and track adherence, providing personalized feedback to patients about their adherence, and providing small monetary incentives to patients if they achieve high hydroxyurea adherence. Objective This study aimed to determine if Mobile DOT increases hydroxyurea adherence in children with SCD and to explore its impact on hematologic and clinical outcomes. Methods This was a single-arm, 6-month intervention study of patients with SCD on hydroxyurea who were aged ≤19 years and reported having access to an electronic device. Participants’ hydroxyurea adherence when they received Mobile DOT was compared with their adherence 6 months before and after receiving Mobile DOT. Participants’ medication possession ratio (MPR) was calculated from their pharmacy dispensing records and was used to measure adherence. Laboratory and clinical outcomes were abstracted from participants’ electronic medical records. Infrequently hospitalized patients who received at least 160 days of the intervention were considered to be engaged participants. Results Of 91 patients who were approached, 55 enrolled and 34 engaged with Mobile DOT. The median age of the engaged participants was 10 years (range 2-18.8 years), and 21 (62%, 21/34) participants were male, 28 (82%, 21/34) had hemoglobin SS SCD, and 19 (56%, 19/34) were prescribed hydroxyurea for at least a year before enrollment. With Mobile DOT, engaged participants’ median MPR increased from 61.7% to 84.4% (P<.001) and significantly more (67% vs 30%; P=.002) achieved ≥80% hydroxyurea adherence compared with baseline values. Engaged participants’ mean fetal hemoglobin (HgbF) levels and mean corpuscular volumes (MCV) improved significantly after 6 months of Mobile DOT (P=.04 and P=.001, respectively), but their adherence, HgbF levels, and MCV returned to baseline values during the 6 months after the intervention. Hospitalizations and the clinical outcomes that were measured occurred infrequently during the study. Nonengagement was associated with being female and having a recent SCD complication. In addition, having insufficient electronic data, being unable to quickly complete Mobile DOT each day, and not perceiving that Mobile DOT was beneficial may have further decreased engagement. Conclusions Mobile DOT shows promise as an effective intervention for some children with SCD. Modifications that may improve recruitment, reduce attrition, and increase engagement were identified and could increase the impact that Mobile DOT has on children with SCD. Trial Registration ClinicalTrials.gov NCT02578017; https://clinicaltrials.gov/ct2/show/NCT02578017