This study revealed significant attention and behavioral improvements among childhood cancer survivors who participated in a year-long MPH trial. These findings indicate that benefits previously demonstrated during acute trials14–16
are sustained throughout a maintenance trial that more closely approximates real-world prescription practices. Often, these improvements in cancer survivors, who were identified as experiencing attention and learning problems, resulted in normalization of performance, in which post-test scores were in the average range relative to same-age peers. In addition, benefits were observed across home and school settings and across performance-based and observational measures.
Among childhood cancer survivors prescribed MPH, significant improvements were identified on the primary outcome measure, a performance measure of sustained attention, as well as on parent, teacher and self-report measures of attention and on parent report of behavior problems and social competencies. On the performance measure of attention, there was also evidence for improved processing speed. In contrast, the cancer survivors not participating in the MPH trial showed improvements on parent report measures of attention, behavior problems, and social competencies but were unable to demonstrate improvement on any indices of the performance measure of sustained attention, the teacher or self-report measures of attention regulation. Notably, neither group demonstrated significant change on either the measure of intellectual functioning (ie, IQ) or academic skills. As mentioned in the Methods, the sample size for this study was designed to detect a difference of effective size of 0.46 with 80% power, such that there may be insufficient power to detect differences smaller than 0.46.
Lack of convergent evidence from teacher, self-report, or performance measures for the parent-rated finding in the cancer control group calls into question the reliability of that finding. It may be that parents tend to accommodate to deficits exhibited by their children, such that there is less reporting of problems over time. Teachers, who have other students to serve as a benchmark for typical behavior, may not be subject to this drift. Alternatively, there may have been contextual factors that created a response bias at the time of baseline assessment. Pretesting for both groups took place during overt screening to participate in a stimulant medication trial. It may be that this context created greater motivation to report problems at pretesting than post- testing, resulting in some decline in parent-reported problems for both groups. Regardless of the source of potential parent-reporting error, these findings highlight the importance of using multiple methods of measurement, preferably ratings from multiple types of informants and performance-based measures. Had this study relied on parental report, we may have erroneously concluded that childhood cancer survivors show attention and behavioral improvement irrespective of stimulant medication use.
The findings in this study are consistent with the ADHD literature that support the long-term efficacy of MPH.26–28
MPH benefits in children diagnosed with ADHD are most frequently found on measures of attention and concentration as well as on observable classroom and social behaviors.10
Improved processing speed in the MPH group is also consistent with findings in the ADHD literature.10
Increased processing speed may be a separate MPH benefit and/or may serve to mediate improvement in attention. Similar to the findings of this study in cancer survivors, there is less evidence to support academic benefits associated with MPH use in the ADHD literature.29–30
Although disappointing, this finding may relate to the way in which academic outcomes are measured.
In this study, the academic measure assessed basic skill acquisition (eg, single-word reading and mathematical computation). Despite an inability to detect improvements on this measure, many parents reported that children participating in the MPH trial experienced an improvement in school grades related to behaviors, such as planning ahead for projects, studying in advance for tests, and remembering to complete and turn in assignments. These behaviors, which may be considered executive aspects of school performance, were notassessed in this study. Future studies may be able to detect improvements in academic skills if they include measures that assess executive components of academic performance.
The findings of this study should be considered in the context of potential study limitations. Although earlier phases of the overarching study included randomized, placebo-controlled trials, the study phase discussed here was a prospective, longitudinal, open-label trial. Because participants were not randomly assigned to the MPH or control group, there is the possibility for introduction of assignment bias. That said, the groups were found to be balanced on those factors most consistently associated with cognitive late effects (eg, age at treatment, treatment intensity, time since treatment)2
and did not demonstrate any differences on psychometric measures at baseline. Given that these children were already identified as MPH responders in a short trial, ethical standards precluded random assignment to a 12-month placebo condition. With an open-label study design, there is also potential for biases in rater reporting, such as placebo effects in parents and teachers aware of medication status. The strong and consistent finding of group differences on the primary outcome measure (ie, CPT), not subject to rater biases, adds convergent support for the rater-based findings. There was a 25% attrition rate, and those who did not complete the MPH trial had higher informant-rated attention problems at baseline, which has been shown to predict better MPH response.31
Therefore, it is possible that the response rate in the MPH group is an underestimate. As discussed earlier in the Discussion section, this study also lacked measures of executive function, which may have added value in detecting MPH benefits on the basis of the ADHD literature.32–33
Overall, the findings of this study are encouraging, as they put forward an empirically supported intervention for childhood cancer survivors who experience attention and learning problems. Cognitive deficits are well established in this population,1–3
yet there are few empirically supported options for intervention. Initial findings from MPH trials indicated acute benefits for cancer survivors14–16
; this is the first time that long-term effectiveness has been demonstrated in a prospective, longitudinal trial. In this study, benefits were found not only for attention regulation but also for social skills and for internalizing and externalizing behavior problems. Coupled with other recently published findings that indicate the relative safety of MPH for cancer survivors with respect to adverse effects34
these results indicate that MPH may be recommended as a treatment option to families searching for a means to mitigate the impact of cognitive late effects experienced by their children. For survivors who demonstrate attention problems, MPH may be an integral component of the treatment plan that would also likely include academic accommodations.