In a study reported in the Journal of Clinical Oncology, David R. Freyer, DO, MS, and colleagues found that clinicians consistently undergraded—and caregivers frequently overgraded—the severity of adverse events experienced by children with cancer.
Study Details
The study included 438 child-clinician-caregiver triads enrolled at nine North American pediatric oncology centers between October 2016 and October 2018. Children were aged 7 to 18 years (mean age = 13 years) with a first diagnosis of cancer; 56% had leukemia or lymphoma. Adverse events were assessed 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]). Grades of 0 to 3 for 15 core adverse events were recorded prior to starting a treatment course (T1) and after the treatment course (T2). The adverse events consisted of nausea, vomiting, anorexia, abdominal pain, constipation, diarrhea, oral mucositis, cough, pain, headache, neuropathy, fatigue, insomnia, anxiety, and depression. Significance of comparisons in mean grades was set at P = .05. Concordance was measured using weighted kappa statistics, with concordance being poor for kappa < 0.20, fair for ≥ 0.20 to < 0.40, moderate for ≥ 0.40 to < 0.60, good for ≥ 0.60 to < 0.80, and very good for ≥ 0.80.
Compared with children, symptomatic adverse events 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.— David R. Freyer, DO, MS, and colleagues
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Key Findings
Clinicians' mean grades at T1 were significantly lower than children’s grades for all adverse events. Clinicians' grades remained significantly lower than children’s grades at T2 for all adverse events except constipation, nausea, anorexia, neuropathy, and anxiety.
Caregivers' mean grades at T1 were significantly lower than children’s grades for constipation, diarrhea, cough, headache, neuropathy, and insomnia, and higher for depression. At T2, caregivers' grades were higher than children’s grades for nausea, vomiting, anorexia, pain, fatigue, anxiety, and depression.
Agreement for child-clinician grading was poor to fair at T1 (kappa range = 0.08–0.34) and T2 (kappa range = 0.11–0.35). Agreement for child-caregiver grading was fair to good at T1 (kappa range = 0.34–0.65) and T2 (kappa range = 0.24–0.60).
At T1 and T2, the mean numbers of adverse events reported by children were 6.13 and 6.13, compared with 2.99 and 3.78 by clinicians and 5.98 and 7.00 by caregivers.
The investigators concluded, “Compared with children, symptomatic adverse events 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.”
Dr. Freyer, of the Cancer and Blood Disease Institute, Children’s Hospital Los Angeles and Keck School of Medicine, University of Southern California, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.
