Improving the Sensitivity and Accuracy of Adverse Event (AE) Reporting in Pediatric Oncology Clinical Trials

Cooperative group oncology clinical trials have led to dramatic improvements in the survival outcomes of children with cancer. However, the large number of side effects from treatment, coupled with a growing list of ways to report treatment toxicities, has called into question the accuracy of adverse event (AE) reporting in pediatric clinical trials.

In most cooperative oncology group pediatric trials, including those performed by the Children’s Oncology Group (COG), AEs are reported manually by clinical research associates via case report forms using the National Cancer Institute Common Terminology Criteria for Adverse Events system. Yet, despite extensive time required for AE reporting, there is growing evidence that AEs may be underreported or reported incorrectly in pediatric cancer clinical trials.

Tamara P. Miller, MD, MSCE, and researchers at the Center for Childhood Cancer Research (CCCR) performed chart review for 12 different AEs for pediatric patients enrolled on a COG Phase III clinical trial for pediatric acute myeloid leukemia (AML). Chart abstraction was performed on over 200 patients who underwent multiple rounds of chemotherapy for AML. The reports of AEs on the clinical trial were then compared to the results of the chart review. Results from this analysis showed the current system of AE reporting on cooperative group oncology trials had less than 50 percent sensitivity for 8 of 12 AEs and a demonstrable false positive rate.

Studies are currently underway to develop new methods to improve the sensitivity and accuracy of AE reporting in clinical trials for children with cancer.