False Positive Cardiotoxicity Events in Cancer-Related Clinical Trials: Risks Related to Imperfect Noninvasive Parameters

被引:14
作者
Ewer, Michael S. [1 ]
Herson, Jay [2 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Cardiol, Div Med, 1400 Pressler St,Ste 18-500, Houston, TX 77030 USA
[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA
关键词
Adverse drug reactions; Cardiac monitoring in clinical trials; Cardiac ultrasound; Cardiotoxicity; False positive tests; PERTUZUMAB PLUS TRASTUZUMAB; EARLY BREAST-CANCER; CARDIAC SAFETY; CHEMOTHERAPY; COMBINATION; DOXORUBICIN; PACLITAXEL;
D O I
10.1159/000495147
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. (c) 2019 S. Karger AG, Basel
引用
收藏
页码:324 / 329
页数:6
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