Describing the feasibility and acceptability of an electronic adherence monitor to measure hydroxyurea adherence among youth with sickle cell disease Free

Background:

Prescription and claims data suggest hydroxyurea (HU) adherence is low among >50% of youth with sickle cell disease (SCD) and impacts clinical outcomes. Feasible and accurate HU adherence measures are needed to identify those in need of adherence intervention and to determine the success of adherence-promoting interventions. Unfortunately, prescription, claims, and laboratory data (mean corpuscular volume, fetal hemoglobin) may not be practical for use and/or may not accurately identify individuals who are non-adherent to HU in clinical practice.

Electronic monitors (EM) are a gold standard medication adherence measure, but EM use has been limited in younger children on hydroxyurea as existing EM are not compatible with liquid medication formulations. To address this gap, our team developed a compatible EM for use in a randomized clinical trial of an HU adherence intervention. This EM is secured to the outside of any medication container, including liquid medication, clicked when HU is administered, and connected through cellular data to allow for real-time adherence data upload to a secure, cloud-based dashboard. Understanding how these compatible EM are received and utilized by youth with SCD and their caregivers is needed to inform design improvements and ensure that they are a reliable and valid method to identify youth who could benefit from HU adherence intervention. Thus, the aims of this study were to describe the feasibility and acceptability of these EM and to describe HU adherence captured by these EM.

Methods: Participants were primary caregivers (CG) of children with SCD aged <11 years and adolescents and young adults (AYA) aged 11-25 years with SCD who enrolled in the Applying Directly Observed Therapy to Hydroxyurea to Realize Effectiveness trial at three sites (NCT: 06264700). Participants were provided with an EM and instructions for how it at enrollment. Demographic data were self-reported by CG and abstracted by electronic medical review for AYA. EM use and adherence data were abstracted from the secure dashboard for the 30 days after enrollment and prior to randomization to the two study arms. Acceptability and the self-reported impact of the EM on HU adherence were assessed via Likert survey at 30-120 days, when randomization to the adherence intervention or attention control occurred. The survey used was a modified acceptability survey for electronic adherence interventions that has been used in previous studies.

Feasibility was defined as ≥80% of subjects using their EM ≥1 time in the first 30 days. The EM was considered acceptable if ≥80% agreed the EM was easy to use, non-invasive, and that they would be willing to continue to use it. Subjects (or their young children taking HU) were defined as adherent to HU if they used the EM for ≥24 days (80%) during the 30-days.

Results: We enrolled 59 subjects (53% AYA; 65% female, 2% non-binary). Of AYA subjects (78% hemoglobin (Hb)SS, 16% HbSC, 3% HbSβ⁺-thalassemia, 3% HbSβ⁰-thalassemia), 21 (66%) were 11-17, and 11 (34%) were 18-25 years of age. Of CG (whose children had HbSS (82%), HbSC (11%), HbSβ⁰-thalassemia(4%), other genotypes (4%)), 6 (22%) were 18-30, and 21 (78%) were ≥31 years.

We had 46 (78%) complete the survey and 45 (98%) agreed/strongly agreed the EM was easy to use, 42 (91%) agreed/strongly agreed it was non-invasive, and 35 (76%) agreed/strongly agreed that they would be willing to continue using the EM. Furthermore, 70% agreed/strongly agreed the EM improved their adherence.

Of those enrolled, 51 (86%) used their EM monitor ≥1 time. Median HU adherence by EM was 40% (IQR: 10-63%) and 11 (19%) were considered adherent to HU.

Discussion: Despite previous challenges using EM to quantify adherence for youth with SCD, our findings suggest that using this EM to track HU adherence is feasible, at least in the short term. While many users reported device acceptability and that the device increased their HU adherence, EM data suggests that additional adherence support is needed for many youth with SCD and that there are opportunities to improve the EM to increase how long it is used. This study was limited by a small sample size, short duration, and the variability in the timing of survey administration. Studies are ongoing to determine the accuracy of these EM, their longer-term feasibility, and their ability assess the efficacy of adherence interventions.