Michael S Ewer1, Jay Herson2. 1. Department of Cardiology, Division of Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, mewer@mdanderson.org. 2. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Abstract
PURPOSE: Cardiac ultrasound provides important structural and functional information that makes identification of cardiac abnormalities possible. Left ventricular ejection fraction (LVEF) provides the most commonly used parameter for recognition of treatment-related cardiac dysfunction. Random reading variance and physiologic factors influence LVEF and make the reported value imperfect. We attempt to quantitate the likelihood of false positive events by computer simulation. METHODS: We simulated four visits on hypothetical trials. We assumed a baseline LVEF of 55% and normal distribution with regard to reading error and physiologic variation. 1,000 trials of sample size 1,500 were simulated. In a separate simulation, 1,000 patients entered with LVEFs of 45, 43, and 41% to estimate true positive incidence. RESULTS: At each examination, less than 1.0% of false positives were noted. The cumulative false positive rate over four visits was 3.60%. True cardiotoxicity identification is satisfactory only when LVEF declines substantially. CONCLUSION: A 3.60% false positive rate in trials where the expected level of toxicity is low suggests that false positives are troubling and may exceed true positive results. Strategies to reduce the number of false positive results include making confirmatory studies mandatory. Evaluating increases along with decreases obtains some estimation of variance.
PURPOSE: Cardiac ultrasound provides important structural and functional information that makes identification of cardiac abnormalities possible. Left ventricular ejection fraction (LVEF) provides the most commonly used parameter for recognition of treatment-related cardiac dysfunction. Random reading variance and physiologic factors influence LVEF and make the reported value imperfect. We attempt to quantitate the likelihood of false positive events by computer simulation. METHODS: We simulated four visits on hypothetical trials. We assumed a baseline LVEF of 55% and normal distribution with regard to reading error and physiologic variation. 1,000 trials of sample size 1,500 were simulated. In a separate simulation, 1,000 patients entered with LVEFs of 45, 43, and 41% to estimate true positive incidence. RESULTS: At each examination, less than 1.0% of false positives were noted. The cumulative false positive rate over four visits was 3.60%. True cardiotoxicity identification is satisfactory only when LVEF declines substantially. CONCLUSION: A 3.60% false positive rate in trials where the expected level of toxicity is low suggests that false positives are troubling and may exceed true positive results. Strategies to reduce the number of false positive results include making confirmatory studies mandatory. Evaluating increases along with decreases obtains some estimation of variance.
Authors: Chau Dang; Michael S Ewer; Suzette Delaloge; Jean-Marc Ferrero; Ramon Colomer; Luis de la Cruz-Merino; Theresa L Werner; Katherine Dadswell; Mark Verrill; Daniel Eiger; Sriparna Sarkar; Sanne Lysbet de Haas; Eleonora Restuccia; Sandra M Swain Journal: Cancers (Basel) Date: 2022-05-24 Impact factor: 6.575
Authors: Nathalie I Bouwer; Agnes Jager; Crista Liesting; Marcel J M Kofflard; Jasper J Brugts; Jos J E M Kitzen; Eric Boersma; Mark-David Levin Journal: Breast Date: 2020-04-16 Impact factor: 4.380