Feasibility of Electronic Directly Observed Therapy for Pediatric Leukemia Patients

Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer, accounting for approximately 3000 cases per year. Although the cure rate of pediatric ALL exceeds 80% in developing countries, treatment usually lasts 2.5–3.5 years and consists of a prolonged maintenance therapy phase. This phase consists is a 20 to 32 month regimen of daily oral 6-mercaptopurine (6MP), weekly oral methotrexate, monthly intravenous vincristine, and monthly oral steroid pulses. It is estimated that non-adherence rates range from 10–40%, which increase the risk of relapse and have a negative impact on disease free survival. Prior studies show that directly observed therapy (DOT) is the most effective way to improve medication adherence, and it is widely used in anti-tuberculosis and anti-retroviral therapy. DOT is defined as a strategy for ensuring patient compliance with therapy, where a healthcare worker watches the patient swallow each dose of a prescribed medication. While DOT may be a successful strategy for pediatric ALL, cost, inconvenience, perceived intrusiveness, and stigma relating to frequent visits by healthcare workers make it less viable strategy for pediatric ALL patients. A modified version of DOT utilizes existing cellular and computer technology (Mobile DOT) to view patients taking their medications over the internet without the need for custom hardware or programming. This technique is being studied in the pediatric sickle cell population, and preliminary results show adherence rates of ≥90%. The primary aim of this study is to see if Mobile DOT is a feasible and acceptable way to monitor pediatric ALL patients' 6MP adherence.

This was a 30-day pilot study. ALL patients in their first remission were recruited if they were between 1–22 years of age, were in maintenance therapy for ≥1 month, and had daily access to a phone or computer capable of recording and submitting videos to Mobile DOT. We instructed participants how to submit the videos and they received daily reminders alerts as text messages and emails to take their medication. As adherence measures, we used direct observation and self-reported adherence using the Moriskey Medication Adherence Surveys (MMAS-4). The MMAS-4 is a validated adherence survey on a scale of 0–4, where lower scores indicate higher adherence. We measured Mobile DOT participant satisfaction with a 12 question Likert scale survey at the end of the study. Participants received a small monetary compensation for completing surveys and if they achieved ≥90% adherence for the 30 days.

We approached 20 prospective participants and 11 enrolled. Two subjects withdrew from the study; one was withdrawn because he was instructed to stop 6MP therapy due to myelosuppression and the other was withdrawn because his software was incompatible with our system.

At enrollment, mean MMAS-4 score was 0.8 (SD ± 1.2, range 0–3), suggesting good overall adherence. By the end of study, MMAS-4 score trended toward improvement to 0.3 (SD ± 0.5, range: 0–1). Of the participants with moderate adherence (scores 2–3, n=3), all improved to good adherence (score 0–1) at the end of the study.

Mean adherence measured with direct observation was 27.0/30 (SD ± 2.5 range 23–30) or 90.0% (SD ± 8.3% range 76–100%).

Survey data shows that most patients (n=5) found Mobile DOT and the alerts to be helpful. Also, most participants (n=8) found that Mobile DOT took less than five minutes each day and did not invade privacy. All participants agreed that Mobile DOT was easy to use.

This study suggests that Mobile DOT is a feasible way to monitor medication adherence in pediatric ALL patients. In addition, we found pediatric ALL patients had high adherence rates and most found Mobile DOT to be acceptable. These results suggest that Mobile DOT may be an effective strategy to ensure adequate 6MP medication adherence in pediatric ALL throughout maintenance therapy.

No relevant conflicts of interest to declare.