Lack of Concordance in Symptomatic Adverse Event Reporting by Children, Clinicians, and Caregivers: Implications for Cancer Clinical Trials

David R. Freyer, Cancer and Blood Disease Institute, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA.
Li Lin, Department of Population Health Sciences, Duke University School of Medicine, Durham, NC.
Jennifer W. Mack, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA.
Scott H. Maurer, UPMC Children's Hospital and University of Pittsburgh School of Medicine, Pittsburgh, PA.
Molly McFatrich, Duke University School of Medicine, Durham, NC.
Justin N. Baker, Division of Quality of Life and Palliative Care, St Jude Children's Research Hospital, Memphis, TN.
Shana S. Jacobs, Division of Oncology, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC.
Nicole Lucas, Duke University, Durham, NC.
Janice S. Withycombe, School of Nursing, Clemson University, Clemson, SC.
Deborah Tomlinson, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada.
Katie Rose Villabroza, Children's Hospital Los Angeles, Los Angeles, CA.
Mia K. Waldron, Department of Nursing Science, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC.
Pamela S. Hinds, Department of Nursing Science, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC.
Bryce B. Reeve, Departments of Population Health Sciences and Pediatrics, Duke University School of Medicine, Durham, NC.

Document Type

Journal Article

Publication Date

3-16-2022

Journal

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

DOI

10.1200/JCO.21.02669

Abstract

PURPOSE: To examine concordance in symptomatic adverse event (AE) grading using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) for clinicians and its patient-reported outcome (PRO) versions for children (Ped-PRO-CTCAE) and caregivers (Ped-PRO-CTCAE [Caregiver]). METHODS: Children age 7-18 years with a first cancer diagnosis, their clinicians, and caregivers completed CTCAE-based measures before starting a treatment course (T1) and after the treatment (T2). Grades (0-3) were assigned by each reporter for 15 core AEs spanning physical and mental health. Mean grades were compared between reporters using two-sample -tests; agreement was estimated using weighted kappa (κ) statistics. Multivariable mixed regression models were used to evaluate associations of clinical factors with AE reporting concordance. Significance was set at α = .05 (two-sided). RESULTS: There were 438 child-clinician-caregiver triads with complete data at either T1 or T2. For children, the mean age was 13 years (standard deviation = 3.4), 53.7% were male, 32.6% non-White, and 56.4% had leukemia/lymphoma. At T1, clinician mean AE grades were significantly lower (ie, better) than children for all AEs and remained significantly lower at T2 except for constipation, nausea, anorexia, neuropathy, and anxiety. Caregiver mean AE grades were similar to children at T1 and significantly higher (ie, worse) at T2 for nausea, vomiting, anorexia, pain, fatigue, anxiety, and depression. Agreement for child-clinician grading was poor-to-fair at T1 (κ range, 0.08-0.34) and T2 (0.11-0.35), and for child-caregiver, was fair-to-good at T1 (0.34-0.65) and T2 (0.24-0.60). No factors were consistently associated with reporter concordance across AEs. CONCLUSION: Compared with children, symptomatic AEs were consistently under-reported by clinicians with low agreement and over-reported by caregivers with low-moderate agreement. Direct reporting by children using Ped-PRO-CTCAE or similar measures should be routinely incorporated for toxicity assessment in clinical trials.

Department

Pediatrics

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