Patient-Reported Outcomes in Pediatric Oncology

More than 40 000 children undergo cancer treatment in the United States annually,¹ and all patients experience symptoms and adverse effects from their therapy or their disease.Clinical use of patient-reported outcomes (PROs), which are standardized reports of a patient’s health condition directly from the patient, has the potential to alleviate some of this experience, allow patients and their caregivers to feel more in control of their well-being, help their health care team better control symptoms, and improve outcomes. In adults, using PRO tools to monitor symptoms and toxic effects during chemotherapy improves patients’ quality of life, decreases their number of hospitalizations, and lengthens their life.^2,3

However, despite the benefits seen in adult patients with cancer and the fact that multiple stakeholders, such as the US Institute of Medicine and the American Cancer Society, have called the integration of PRO measures into pediatric research and care essential,⁴ the use of patient-reported outcomes to track symptoms and adverse effects in pediatric oncology is rare. This absence may be driven, in some part, by the complication introduced by the fact that in pediatrics, the health care relationship is not a dyad; it is a triad: patient, caregiver, and clinician. Historically, parents and caregivers are the primary drivers of health care and are intimately involved in the conversations around symptom control and medication management. Although many validated patient-reported outcome instruments developed for pediatric patients include both patient and proxy versions, limited guidance governs how to integrate the existence of both, particularly in the setting of discrepant reports, into research and clinical care.

Mack and colleagues,⁵ in this issue of JAMA Pediatrics, take the first important steps in rectifying that knowledge gap. This study provides the groundwork to insist that where pediatric self-report is possible, it should be elicited directly from the pediatric patient with cancer as opposed to their caregivers. Enabling self-report in this population is important because we know that children can underreport their symptom severity during the clinical interview to avoid complaining or “bothering” the physician or in an effort to protect their family from worry.⁶ Qualitative data have also shown us that children interpret symptoms as an essential part of treatment for cancer and thus may not disclose them if they think symptoms are necessary for cure.⁷ Other work has demonstrated that children can feel silenced by their clinicians.⁸ Unfortunately, we know that uncontrolled symptoms result in poor experiences, poor quality of life, morbidity, and sometimes death.⁹

It is commonly accepted that children who are 8 years or older are reliably able to self-report symptoms and health-related quality of life, and some measures, such as the one used by Mack et al,⁵ can be considered valid for even younger children. The PRO instruments are designed to be specific to the developmental stage of the patient using techniques such as standardized pictures (eg, FACES scores), modified Likert scales, fewer questions, and age-appropriate language.¹⁰ This approach offers a systematic and reliable way of measuring the patient experience that is likely more sensitive than the training we receive as clinicians or as parents in child development and developmentally appropriate communication around illness. Although attributing any discrepancies between child and proxy report to a child’s misunderstanding of the questions may be tempting, the extensive evaluation and cognitive interviewing that instrument validation entails ensures that children are able to understand and interpret questions appropriately. As such, as the authors point out, any discrepancy between child and proxy report should not be fully attributed to child miscomprehension of the questions.

The work by Mack and colleagues⁵ moves beyond simply identifying the systematic discrepancy in patient vs proxy reports and develops an understanding of what psychological and social factors generate it: That the lens through which caregivers view their ill children is a critical aspect in interpreting how they report their children’s symptoms. This is an important finding. Proxy report of symptoms is influenced not just by the child’s experience but by the proxy’s own health state and, perhaps, their own expectations for illness and symptom trajectory. Discordance between patient and proxy reports is most pronounced during times of high symptom burden. Consistent with previous work, more patient-proxy agreement is seen in more observable domains, such as mobility, than is documented in the less visible ones, such as emotional state. These findings have ramifications for how best to interpret and use proxy reports in the setting of a child who is too young or too ill to provide their own self-report. It is essential that we use these findings to guide the thoughtful inclusion of symptom items and domains for patients for whom we must rely on proxy report, and it is necessary to continue to build the framework on which we interpret those reports.

Similarly, it is necessary to examine the discordance that arises between patient and clinician symptom grading. In adults, oncologists have higher symptom-grading thresholds¹¹ and underestimate symptom severity compared with patient self-report. Much as in the setting of patient and proxy discordance, we need to understand what factors drive this nonagreement. It is likely that clinicians, caregivers, and patients all provide a needed piece of the clinical picture, and it is necessary to determine how best to fit these pieces of data together holistically.

Previous work has highlighted the interest that patients, families, and clinicians show in the use of these metrics for routine pediatric cancer care⁸ and suggest that patient-reported outcomes can be used as a dynamic clinical tool to optimize symptom management. Determining how best to incorporate the child’s voice into their care is essential. Eliciting the child’s perspective can help to identify trends in symptoms and adverse effects that are not immediately evident,⁸ promote enhanced communication with the treating team, increase patient and family engagement in care,^12,13 and ultimately lead to better clinical outcomes. Children undergoing chemotherapy are able to complete symptom assessments in multiple domains at multiple points during chemotherapy with excellent enrollment rates and minimal attrition.⁸ However, a challenge in pediatrics has been determining how to balance proxy and patient reports when they both exist. Mack and colleagues⁵ provide evidence that the criterion or gold standard, even in the case of pediatric patients, should be the patient report.

There is no substitute for collecting this information directly from patients.^5,14 When patient self-report is not possible—as is the case in young or ill children—it is critical that we continue to evaluate the role of proxy report and build on the existing evidence. Using PROs has the potential to enhance the way we deliver care to children with cancer, understand their experience, optimize adjunctive or supportive care, decrease adverse events, and positively affect clinical outcomes. Given the benefits that patient-reported symptom monitoring has conferred in the adult oncology population, it is imperative that we determine how best to deploy and interpret these methods in children with cancer.