Tamara P Miller1, Yimei Li2, Marko Kavcic2, Andrea B Troxel2, Yuan-Shun V Huang2, Lillian Sung2, Todd A Alonzo2, Robert Gerbing2, Matt Hall2, Marla H Daves2, Terzah M Horton2, Michael A Pulsipher2, Jessica A Pollard2, Rochelle Bagatell2, Alix E Seif2, Brian T Fisher2, Selina Luger2, Alan S Gamis2, Peter C Adamson2, Richard Aplenc2. 1. Tamara P. Miller, Yimei Li, Marko Kavcic, Yuan-Shun V. Huang, Rochelle Bagatell, Alix E. Seif, Brian T. Fisher, Peter C. Adamson, and Richard Aplenc, The Children's Hospital of Philadelphia; Yimei Li, Andrea B. Troxel, Rochelle Bagatell, Alix E. Seif, Brian T. Fisher, Selina Luger, Peter C. Adamson, and Richard Aplenc, University of Pennsylvania School of Medicine, Philadelphia, PA; Lillian Sung, The Hospital for Sick Children, Toronto, Ontario, Canada; Todd A. Alonzo and Michael A. Pulsipher, University of Southern California; Michael A. Pulsipher, Children's Hospital of Los Angeles, Los Angeles; Todd A. Alonzo and Robert Gerbing, Children's Oncology Group, Monrovia, CA; Matt Hall, Children's Hospital Association, Overland Park, Kansas; Marla H. Daves, Children's Healthcare of Atlanta, Atlanta, GA; Terzah M. Horton, Texas Children's Hospital, Houston, TX; Jessica A. Pollard, Seattle Children's Hospital, Seattle, WA; and Alan S. Gamis, Children's Mercy Hospital, Kansas City, MO. millertp@e-mail.chop.edu. 2. Tamara P. Miller, Yimei Li, Marko Kavcic, Yuan-Shun V. Huang, Rochelle Bagatell, Alix E. Seif, Brian T. Fisher, Peter C. Adamson, and Richard Aplenc, The Children's Hospital of Philadelphia; Yimei Li, Andrea B. Troxel, Rochelle Bagatell, Alix E. Seif, Brian T. Fisher, Selina Luger, Peter C. Adamson, and Richard Aplenc, University of Pennsylvania School of Medicine, Philadelphia, PA; Lillian Sung, The Hospital for Sick Children, Toronto, Ontario, Canada; Todd A. Alonzo and Michael A. Pulsipher, University of Southern California; Michael A. Pulsipher, Children's Hospital of Los Angeles, Los Angeles; Todd A. Alonzo and Robert Gerbing, Children's Oncology Group, Monrovia, CA; Matt Hall, Children's Hospital Association, Overland Park, Kansas; Marla H. Daves, Children's Healthcare of Atlanta, Atlanta, GA; Terzah M. Horton, Texas Children's Hospital, Houston, TX; Jessica A. Pollard, Seattle Children's Hospital, Seattle, WA; and Alan S. Gamis, Children's Mercy Hospital, Kansas City, MO.
Abstract
PURPOSE: Reporting of adverse events (AEs) in clinical trials is critical to understanding treatment safety, but data on AE accuracy are limited. This study sought to determine the accuracy of AE reporting for pediatric acute myeloid leukemia clinical trials and to test whether an external electronic data source can improve reporting. METHODS: Reported AEs were evaluated on two trials, Children's Oncology Group AAML03P1 and AAML0531 arm B, with identical chemotherapy regimens but with different toxicity reporting requirements. Chart review for 12 AEs for patients enrolled in AAML0531 at 14 hospitals was the gold standard. The sensitivity and positive predictive values (PPV) of the AAML0531 AE report and AEs detected by review of Pediatric Health Information System (PHIS) billing and microbiology data were compared with chart data. RESULTS: Select AE rates from AAML03P1 and AAML0531 arm B differed significantly and correlated with the targeted toxicities of each trial. Chart abstraction was performed on 204 patients (758 courses) on AAML0531. AE report sensitivity was < 50% for eight AEs, but PPV was > 75% for six AEs. AE reports for viridans group streptococcal bacteremia, a targeted toxicity on AAML0531, had a sensitivity of 78.3% and PPV of 98.1%. PHIS billing data had higher sensitivity (> 50% for nine AEs), but lower PPV (< 75% for 10 AEs). Viridans group streptococcal detection using PHIS microbiology data had high sensitivity (92.3%) and PPV (97.3%). CONCLUSION: The current system of AE reporting for cooperative oncology group clinical trials in pediatric acute myeloid leukemia underestimates AE rates. The high sensitivity and PPV of PHIS microbiology data suggest that using external data sources may improve the accuracy of AE reporting.
PURPOSE: Reporting of adverse events (AEs) in clinical trials is critical to understanding treatment safety, but data on AE accuracy are limited. This study sought to determine the accuracy of AE reporting for pediatric acute myeloid leukemia clinical trials and to test whether an external electronic data source can improve reporting. METHODS: Reported AEs were evaluated on two trials, Children's Oncology Group AAML03P1 and AAML0531 arm B, with identical chemotherapy regimens but with different toxicity reporting requirements. Chart review for 12 AEs for patients enrolled in AAML0531 at 14 hospitals was the gold standard. The sensitivity and positive predictive values (PPV) of the AAML0531 AE report and AEs detected by review of Pediatric Health Information System (PHIS) billing and microbiology data were compared with chart data. RESULTS: Select AE rates from AAML03P1 and AAML0531 arm B differed significantly and correlated with the targeted toxicities of each trial. Chart abstraction was performed on 204 patients (758 courses) on AAML0531. AE report sensitivity was < 50% for eight AEs, but PPV was > 75% for six AEs. AE reports for viridans group streptococcal bacteremia, a targeted toxicity on AAML0531, had a sensitivity of 78.3% and PPV of 98.1%. PHIS billing data had higher sensitivity (> 50% for nine AEs), but lower PPV (< 75% for 10 AEs). Viridans group streptococcal detection using PHIS microbiology data had high sensitivity (92.3%) and PPV (97.3%). CONCLUSION: The current system of AE reporting for cooperative oncology group clinical trials in pediatric acute myeloid leukemia underestimates AE rates. The high sensitivity and PPV of PHIS microbiology data suggest that using external data sources may improve the accuracy of AE reporting.
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