DISCUSSION
Among patients treated with a DFCI ALL Consortium regimen, 25% [95%
CI, 14% – 37%] of caregivers report non-adherence to oral 6MP
during therapy. This rate is strikingly similar to Medication Event
Monitoring System (MEMS)-measured adherence rates from the
COG.3,6 Given that self-reported non-adherence has a
sensitivity as low as 53% but a positive predictive value nearing
95%,7 these data suggest that the frequency of
non-adherence in this cohort is likely an under-estimate of the true
prevalence, and even higher than the non-adherence rates observed in the
COG.
Similar to other studies, non-adherence was associated with parent
education level,3 and barriers to adherence included
6MP administration guidelines surrounding food and dairy intake. Only
49% of parents recognized “relapse” or “cancer returning” as risks
associated with non-adherence. Studies have demonstrated that patients
who understand the risks and benefits of following medication guidelines
are more likely to adhere to prescribed regimens.8 We
previously reported significant variability in approaches to patient
education surrounding oral chemotherapy across DFCI ALL Consortium
sites.9 Specifically, providers reported modifying
chemotherapy teaching based on their perceptions of patient
comprehension. Our finding that 25% of families in the DFCI cohort
reported non-adherence to 6MP suggests that more frequent
patient-provider contact, and individualized oral chemotherapy education
do not mitigate barriers to adherence.
This study was limited by its small sample size, cross-sectional nature,
and self-report adherence measure. Despite limitations, these
exploratory data demonstrate that 1 in 4 families self-report oral 6MP
non-adherence in the context of a chemotherapy regimen reliant on weekly
interactions with the medical team. These findings support the
generalizable nature of published non-adherence data across pediatric
oncology consortia, reinforcing the urgent need for healthcare delivery
intervention development to address non-adherence. Given that parental
education is associated with non-adherence across consortia, future
interventions targeting the efficacy of medical communication may be
warranted. A prospective investigation of oral chemotherapy adherence
using a MEMS-based approach is ongoing in the current DFCI ALL
Consortium trial 16-001 (NCT03020030).
Acknowledgements:
We would like to thank Dr. Smita Bhatia for sharing her expertise in
adherence research as well as her permission to adapt her adherence
survey instrument for this study.
JMK is supported by a National Institutes of Health KL2 award from the
Irving Institute for Clinical and Translational Research at Columbia
University Irving Medical Center (NIH-KL2TR001874)
MB is supported by a T32 award from The National Cancer Institute
Training Grant (T32CA094061).
KB is supported by a K07 award from the National Institutes of Health
(K07CA211847).