Maintenance therapy with oral 6-mercaptopurine (6MP) for pediatric patients with acute lymphocytic leukemia (ALL) is crucial for maintaining a durable remission, and poor adherence is associated with an increased risk of relapse. Although self-reporting is a convenient and inexpensive method to monitor 6MP intake, it frequently leads to over-estimation of drug compliance, according to results from a longitudinal study published in Blood.
Wendy Landier, PhD, RN, of the University of Alabama at Birmingham, and co-authors compared self-reporting with an electronic monitoring system to determine the accuracy of self-reporting and identify factors that predict over-reporting of drug compliance in a population of 416 pediatric patients with ALL. They found that nearly 85 percent of self-reporting pediatric patients overestimated 6MP intake at least some of the time, and that approximately one-quarter of patients (23.6%) over-reported intake on ≥5 days each month for at least half of the study months.
“[Health-care providers] need to exercise caution in relying only upon patients’ [and/or] parents’ report of medication intake in the clinical setting,” Smita Bhatia, MD, MPH, a co-author of the study, told ASH Clinical News.
The prospective study enrolled patients from a Children’s Oncology Group study (AALL03N1) who had been diagnosed with ALL at ≤21 years of age. Patients were in first remission and were receiving maintenance chemotherapy that included self- or parent/caregiver-administered oral 6MP. The median patient age was 6 years (range = 2-20 years), 66.6 percent were male, and most were Hispanic (37%) or non-Hispanic white (35.6%).
Each patient received 6MP in a prescription bottle fitted with a Medication Events Monitoring System™ (MEMS) TrackCap® that logged the date and time of each bottle opening. Those logs were then compared with self-reported intake data collected via questionnaire at 29, 57, 113, and 141 days of treatment.
Parents completed the questionnaire for patients <12 years old, and both parents and patients completed it for those 12 to 17 years old. Researchers later chose to include only patient-reported outcomes for the latter age cohort, as the responses were highly correlated. Patients ≥18 years old completed the questionnaire themselves.
The authors collected intake data for a total of 1,344 patient-months.
Patients reported that they had taken 6MP for 92.6 percent of the total treatment days. However, MEMS data revealed that prescription bottles were opened on only 83.7 percent of total treatment days. Given this disparity, patients were characterized as follows:
- perfect reporters (self-reports matched MEMS record each month): 50 (12%)
- over-reporters (self-reports exceeded MEMS record by ≥5 days for at least half of the study months): 98 (23.6%)
- under-reporters (self-report was less than MEMS record in all study months): 2 (0.5%)
- other (patients with a combination of over- or under-reporting during the study period): 266 (63.9%)
For 95.1 percent (n=253) of patients classified as “other,” self-reported 6MP intake exceeded electronic monitoring by ≥1 day in ≥1 study months.
According to multivariable regression analysis, over-reporters were more likely to:
- be of non-white race
- Hispanic: odds ratio (OR) = 2.4 (95% CI 1.1-5.1; p=0.02)
- Asian: OR=3.1 (95% CI 1.2-8.3; p=0.02)
- African-American: OR=5.4 (95% CI 2.3-12.8; p=0.0001)
- have paternal education less than college level: OR=1.4 (95% CI 1.0-2.0; p=0.05)
- be 6MP non-adherent: OR=9.4 (95% CI 5.1-17.5; p<0.0001)
“Our findings are consistent with reports in other pediatric chronic illness populations that have shown minority race/ethnicity and lower parental education level to be factors associated with poor medication adherence,” the authors noted.
Compared with perfect reporters, most over-reporters had MEMS-based adherence rates below 95 percent (0% vs. 78.6%; p<0.001). In a subgroup analysis of 77 non-adherent over-reporters, the authors observed a negative correlation between mean adherence rate and number of days of over-reporting (p<0.0001).
“Despite the simplicity and convenience of self-report, our findings suggest that self-report may not be a reliable measure [and that] alternative methods for identifying non-adherent patients in the clinical setting are needed,” the authors concluded. Based on these results, they are developing a prediction tool to assist clinicians in identifying patients who are at increased risk for 6MP non-adherence so interventions can be targeted to the most vulnerable patients.
The study is limited by the unreliability of the MEMS data, as the system cannot determine whether a child actually swallowed the medication after opening the bottle. In addition, self-reporting is subject to recall bias and bias due to a parent or patient wanting to please a clinician with responses, which can encourage over-reporting.
Landier W, Chen Y, Hageman L, et al. Comparison of self-report and electronic monitoring of 6MP intake in childhood ALL: a Children’s Oncology Group study. Blood. 2017 February 2. [Epub ahead of print]