PRO-CTCAE: Creating and Validating Child Adverse Event Reporting in Oncology Trials


Approximately 15,780 children and adolescents, 19 years of age and younger, are diagnosed with cancer yearly, with the average age at diagnosis being 6 years of age. Around 40,000 pediatric cancer patients will undergo treatment, yearly. Childhood cancer, increasing in incidence and survival rates, has myriad effects on health related quality of life (HRQOL). Cancer chemotherapy is associated with many side effects, include fatigue, nausea, vomiting, emotional distress, altered sleep quality, and poor social well-being and physical health. There has been no decline in number of yearly diagnoses in 20 years.

This study constitutes a first step towards our long term research goal of documenting the differences in care management and outcomes when the Pediatric version of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (Pediatric PRO-CTCAE) is incorporated into pediatric cancer clinical trials. Over 60% of children diagnosed with cancer will participate in a clinical trial; the great majority of these children will experience multiple treatment-related adverse events that require intense supportive care. The Federal Government mandates for safety monitoring that all trials report adverse events (AEs); defined by the National Cancer Institute (NCI) as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medical treatment. The standard practice in oncology trials is for the clinician to grade all AEs using the standard NCI lexicon of the Common Terminology Criteria for Adverse Events (CTCAE), but multiple studies in adult cancer populations found that clinicians underreport the number and severity of symptoms compared to what patients report.

More than a third of the 790 AEs on the CTCAE have some subjective aspect to its identification, requiring patient-report to assure accuracy of the AE documentation. Given the known toxicity of cancer treatments on children’s lives, the child’s perspectives in grading subjective AEs must be integrated into AE reporting. Without including the child’s AE reports, the risk/benefit ratio of cancer treatments will not be accurately established. In a small number of studies comparing child, parent and clinician symptom ratings, clinicians were poor and caregivers only slightly better at recognizing the symptoms the children were experiencing. Across 8 Children’s Oncology Group (COG) sites, this study is evaluating the validity, reliability, and responsiveness of the Pediatric PRO-CTCAE. Additionally, we are assessing the congruence of AE ratings provided by the child/adolescent, the caregiver, and the clinician. 


  • Develop Pediatric and Proxy PRO-CTCAE Measures

  • Perform Cognitive Testing of the Pediatric PRO-CTCAE

  • Evaluate psychometric properties and agreement among Child, Proxy and Clinicians


  • We plan to use the PEPR study to fit several of the PROMIS Pediatric domains within a model based on the Theory of Unpleasant Symptoms. According to this theory, symptom characteristics (duration, quality, distress, intensity) are influenced by one or more of 3 factors (physiologic, psychological, and situational). Performance outcomes of the troubling symptoms include functional status, cognitive functioning, and physical performance

  •  We plan to measure all aspects of the framework: physiologic (hemoglobin), psychological (depression, anxiety), and situational (inpatient, outpatient, and point in therapy) and resulting symptoms (fatigue and co-occurring symptoms) and performance (physical function—mobility)

  • Understanding these associations will help develop interventions for children undergoing chemotherapy. Only by measuring and understanding the true scope of medication side effects (measured by Pediatric PRO-CTCAE) and their relationships with HRQOL domains (measured by PROMIS Pediatric measures) can clinicians adequately treat and ameliorate them

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