PAPER SPOTLIGHT

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 %) overreported 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 / caregiveradministered 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 patientreported 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 ( selfreports exceeded MEMS record by ≥5 days for at least half of the study months ): 98 ( 23.6 %)

• under-reporters ( selfreport was less than MEMS record in all study months ): 2 ( 0.5 %)

• other ( patients with a combination of overor 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

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Hispanic : odds ratio ( OR ) = 2.4 ( 95 % CI 1.1-5.1 ; p = 0.02 )

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Asian : OR = 3.1 ( 95 % CI 1.2-8.3 ; p = 0.02 )

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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 overreporters 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 selfreport , 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 nonadherence 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 .

REFERENCE

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 ]