Advancing strategies to improve chemotherapy adherence in young children with ALL: Understanding the role of behavioral parenting skills and daily barriers to identify novel intervention targets Free

Introduction: Adherence to oral anti-cancer therapies is a critical concern in pediatric oncology, and studies consistently document high rates of clinically significant non-adherence. For the most common pediatric cancer, acute lymphoblastic leukemia (ALL), children who miss just 10% of chemotherapy have a nearly 4-fold risk of cancer relapse. We hypothesize that we can reduce preventable pediatric morbidity and mortality through focusing on a novel target – behavioral parenting skills – as a modifiable mechanism to improve medication adherence in young children. Previous studies have typically relied on one-time global measures, making it difficult to discern the precise parenting experiences that are linked to medication adherence. Specifically, we sought to advance intervention development through answering two key questions: (1) what precise parenting behaviors are most effective at facilitating quick and calm chemotherapy administration to children; and (2) what daily family experiences increase risk of nonadherence? In these analyses we move beyond retrospective self-report and enhance innovation and rigor through direct observation and daily diary methods to collect objective data to characterize the specific parenting experiences at the episode and daily levels that shape medication adherence in young children.

Methods: We recruited caregivers of pediatric patients (ages 3 – 9 years) who had been diagnosed with ALL and were receiving cancer treatment at Roswell Park Comprehensive Cancer Center in Buffalo, NY or Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, in Atlanta, GA. To examine episode-level parent behaviors during medication administration we asked parents to record one instance of medication administration at home using GoPro recording devices. Video data were coded by three coders using the Dyadic Parent-Child Interaction Coding System (DPICS) to classify parenting skills observed during medication administration. Guided by the Family Ecological Model we focused on key parent behaviors (direct commands, indirect commands, unlabeled praise, labeled praise, and negative talk). To examine contextual barriers to adherence we used daily survey methods and asked parents to complete a daily evening survey for 14 days. The daily survey used validated scales to capture challenging child behavior, burden of parenting tasks, and parental stress. Parents were also asked to use Medication Event Monitoring System (MEMS) electronic pill bottle caps to monitor chemotherapy adherence for the 14-day daily survey period.

Results: Of 54 eligible families, 43 (80%) families enrolled in the study. Eighty-two percent of participants were mothers (mean age = 35 years). Eighteen percent of participants described themselves as Hispanic, 18% identified as Black, and 68% as White. Forty-five percent of parents had a high school diploma or less. Of the child patients, 48% were female, with a mean age of 5 years old. More than half (55%) of child patients' health care coverage was provided by public health insurance, mainly Medicaid. Mean time since diagnosis was about 16 months. For the observation data we used quasi-Poisson regressions to account for the highly skewed and over dispersed count distribution of time to ingestion. Unlabeled praise, direct commands, and indirect commands were associated with longer time to ingestion. For the daily diary data, participants completed on average 11.20 daily surveys resulting in 504 survey days completed. MEMS derived adherence data indicated that 32% of the sample had missed chemotherapy doses (Mean adherence rate = 92.16%; SD = 16.58; Range: 28%-100%). Using multilevel logistic regression models to account for days nested within participants, children were more likely to miss chemotherapy doses on days when their parent reported challenging child behavior, higher parenting task burden, and higher perceived stress (Odds Ratios 1.85, 1.79, 1.05).

Conclusions: Direct observation and daily assessments revealed that some commonly used parenting strategies are associated with prolonged medication ingestion and that heightened daily stress and burden are linked to missed chemotherapy. These findings highlight modifiable targets for future behavioral interventions, suggesting that tailored interventions may improve adherence and ultimately reduce preventable relapse and morbidity in pediatric ALL.