Creating and Validating Child Adverse Event Reporting in Oncology Trials

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DESCRIPTION: 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 wil 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. This new study with 6 Children's Oncology Group (COG) sites extends our team's current research with pediatric clinicians that identified 62 subjective AEs from the CTCAE that 7- to 20- year olds in cancer treatment could be expected to validly rate, and which could serve as the basis for designing a pediatric patient-report CTCAE (PRO-CTCAE) measure. This 5-year study includes 3 aims. In Aim 1, we will design both English and Spanish versions of a pediatric and caregiver-proxy version of the PRO- CTCAE by translating the 62 subjective AEs into child-friendly terms and create companion interview questions that are comprehensible to children and their caregiver-proxies. In Aim 2, we will use cognitive interviewing methods to evaluate how well children and caregiver-proxies understand and respond to the PRO-CTCAE questions. Strata will represent different cancer types and different age ranges. Aim 3 is a longitudinal study to evaluate the reliability, validity and responsiveness of the PRO-CTCAE measures with newly diagnosed children in cancer treatment, stratified by age and cancer types. We will also assess concordance of AE ratings by caregiver-proxies, clinicians and children over time and changing clinical conditions. This study constitutes a first step towards our long term research goal of documenting the differences in care management and outcomes when the PRO-CTCAE is incorporated into cancer clinical trials.