False Positive Cardiotoxicity Events in Cancer-Related Clinical Trials: Risks Related to Imperfect Noninvasive Parameters.
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.
['Ewer|Michael S|MS|', 'Herson|Jay|J|']
D000970:Antineoplastic Agents D066126:Cardiotoxicity D002986:Clinical Trials as Topic D004452:Echocardiography D005189:False Positive Reactions D006801:Humans D015994:Incidence D009369:Neoplasms D012306:Risk D018487:Ventricular Dysfunction, Left
Cardiotoxicity Cardiac ultrasound Adverse drug reactions Cardiac monitoring in clinical trials False positive tests