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Lack of Concordance in Symptomatic Adverse Event Reporting by Children, Clinicians, and Caregivers: Implications for
David R Freyer1, Li Lin2, Jennifer W Mack3
1Cancer and Blood Disease Institute, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA.
Insights
Clinicians under-reported symptomatic adverse events (AEs) compared to children, while caregivers over-reported them. Patient-reported outcome measures are crucial for accurate AE assessment in pediatric cancer trials.
Area of Science:
- Oncology
- Clinical Trials
- Patient-Reported Outcomes
Background:
- Accurate assessment of symptomatic adverse events (AEs) is critical in pediatric cancer clinical trials.
- The Common Terminology Criteria for Adverse Events (CTCAE) is widely used, but its application via clinician versus patient-reported outcomes (PROs) needs evaluation.
- Understanding concordance between children, caregivers, and clinicians in grading AEs is essential for reliable toxicity assessment.
Purpose of the Study:
- To examine the concordance in symptomatic adverse event (AE) grading between clinicians, children (using Ped-PRO-CTCAE), and caregivers (using Ped-PRO-CTCAE [Caregiver]).
- To compare AE grading using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) across different reporter groups in pediatric cancer patients.
Main Methods:
- 438 child-clinician-caregiver triads with pediatric cancer diagnoses completed CTCAE-based measures at baseline (T1) and post-treatment (T2).
- Reporters assigned grades (0-3) for 15 core AEs; mean grades were compared using t-tests, and agreement was assessed using weighted kappa statistics.
- Multivariable mixed regression models evaluated factors associated with AE reporting concordance, with significance set at α = .05.
Main Results:
- Clinician-reported mean AE grades were significantly lower than children's at T1 and T2 (except for specific AEs).
- Caregiver mean AE grades were similar to children's at T1 but significantly higher at T2 for several AEs (nausea, pain, fatigue, anxiety, depression).
- Agreement between child-clinician grading was poor-to-fair (κ range, 0.08-0.35); child-caregiver agreement was fair-to-good (κ range, 0.24-0.65).
Conclusions:
- Symptomatic AEs were consistently under-reported by clinicians and over-reported by caregivers compared to children.
- Low agreement was observed between child and clinician AE grading.
- Routine incorporation of direct child reporting via Ped-PRO-CTCAE is recommended for toxicity assessment in pediatric cancer clinical trials.
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 t-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.
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