Mobile Directly Observed Therapy: Monitoring and Improving Hydroxyurea Adherence in Pediatric Sickle Cell Patients

Abstract 2060

Sickle cell disease (SCD) is a serious inherited red blood cell disorder that results in significant morbidity and premature mortality. Hydroxyurea (HU) is an efficacious medicine that reduces pediatric SCD complications, but poor medication adherence is common and limits effective HU utilization.

Directly observing therapy (DOT) involves healthcare workers traveling to observe medication ingestion and it is a successful strategy used for anti-tuberculosis therapy. While DOT has the potential to improve adherence to chronic medications such as HU, high cost, inconvenience, and intrusiveness limit this strategy. We hypothesize that a modified version of DOT which uses mobile phones and computers (Mobile DOT), is feasible, can improve adherence, and is acceptable to patients and caregivers.

Patients with SCD were eligible for this 6-month pilot study if they were 1–22 years old, prescribed HU for ≥6 months, and had daily access to a mobile phone or computer capable of recording and submitting videos.

Mobile DOT participants record a daily video of their HU administrations with their phone or computer and submit these videos to a secure website for review. It does not require custom hardware or software. Participants receive automated daily reminder electronic messages. They are called to encourage adherence when needed and to provide them with technical support. Participants receive token monetary compensation when they meet adherence goals and complete surveys.

To measure adherence, this study used the Morisky Medication Adherence Scale (MMAS-4, score range 0–4), the medication possession ratio (MPR) calculated from prescription refill records, laboratory markers including hemoglobin F percentage (HgbF) and mean corpuscular volume (MCV) that increase with HU therapy, and direct observation. Participants completed the Abbreviated Treatment Satisfaction for Medication survey (TSQM-9) and a 12-question survey to measure satisfaction with HU and Mobile DOT respectively.

Investigators discussed this study with 19 prospective participants and 15 enrolled. Mean participant age was 13.7 years (SD ± 6.3 years, range 4–21 years). One participant withdrew because he lost computer access. Videos were approximately 10–30 seconds long and an investigator performed the observations, tracking, and phone calls in <1 hour each day. Most participants had Hemoglobin SS disease (n=11) and took HU for frequent pain crises (n=7) or acute chest syndrome (n=6).

At enrollment, mean MMAS-4 score was 2.0 (SD ± 0.4), indicating moderate self- reported adherence. MPR was 67% (SD ± 26%, range 18–100%). Laboratory markers indicated good adherence (MCV>100fL and HgbF>15%) in 3 participants, moderate adherence (MCV≥90fL and HgbF>12%) in 4 participants, and poor adherence (MCV<90fL or HgbF<12%) in 7 participants. The TSQM-9 survey showed participants had 79.5% (SD ± 20.4%) global HU satisfaction rate, they felt HU was 76.2% (SD ± 22.2%) effective, and they felt taking HU was 81.7% (SD ± 16.4%) convenient.

To date, all participants completed ≥30 days of the study. Direct observation showed that mean adherence was 92.1% (SD ± 0.7%, range 76–100%) at 30 days.

Seven participants thus far have completed ≥2 months on study and have additional survey and laboratory data. Mean adherence in these patients was 90.5% (SD ± 6%, range 80–100%) at 60 days. MMAS-4 scores decreased from 2.1 (SD ± 0.4) to 1.3 (SD ± 1.1), suggesting improved adherence. Laboratory markers also showed improved adherence trends. Mean MCV increased from 94.3fL (SD ± 4.2fL) to 101.2fL (SD ± 8.3fL) and mean HgbF increased from 10.0% (SD ± 5.6%) to 11.3% (SD ± 4.7%). Mobile DOT surveys showed that participants found Mobile DOT easy to use, took <5 minutes each day, helped remind them to take HU, and did not invade their privacy.

These results suggest that Mobile DOT is a feasible way to monitor and improve HU adherence in patients with pediatric SCD. Patients were willing to enroll on the study and surveys suggest that participants find Mobile DOT to be convenient, non-intrusive, and an acceptable. This strategy is potentially easy to disseminate because it does not include additional hardware or programming and requires minimal staff support. A larger clinical trial is needed to determine if long term Mobile DOT can impact clinical outcomes in pediatric SCD.