USING THE QBEST EQUATION TO EVALUATE ELLAGIC ACID SAFETY DATA: GENERATING A QNOAEL WITH CONFIDENCE LEVELS FROM DISPARATE LITERATURE
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Doctor of Philosophy (PhD)
Dr. Robert A. Lodder
QBEST, a novel statistical method, can be applied to the problem of estimating the No Observed Adverse Effect Level (NOAEL or QNOAEL) of a New Molecular Entity (NME) in order to anticipate a safe starting dose for beginning clinical trials. The NOAEL from QBEST (called the QNOAEL) can be calculated using multiple disparate studies in the literature and/or from the lab. The QNOAEL is similar in some ways to the Benchmark Dose Method (BMD) used widely in toxicological research, but is superior to the BMD in some ways. The QNOAEL simulation generates an intuitive curve that is comparable to the dose-response curve. The NOAEL of ellagic acid (EA) is calculated for clinical trials as a component therapeutic agent (in BSN476) for treating Chikungunya infections. Results are used in a simulation based on nonparametric cluster analysis methods to calculate confidence levels on the difference between the Effect and the No Effect studies. In order to evaluate the statistical power of the algorithm, simulated data clusters with known parameters are fed into the algorithm in a separate study, testing the algorithm’s accuracy and precision “Around the Compass Rose” at known coordinates along the circumference of a multidimensional data cluster. The specific aims of the proposed study are to evaluate the accuracy and precision of the QBEST Simulation and QNOAEL compared to the Benchmark Dose Method, and to calculate the QNOAEL of EA for BSN476 Drug Development.
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Funding provided by the PhRMA Foundation, Grant 3048113957.
Dickerson, Cynthia Rose, "USING THE QBEST EQUATION TO EVALUATE ELLAGIC ACID SAFETY DATA: GENERATING A QNOAEL WITH CONFIDENCE LEVELS FROM DISPARATE LITERATURE" (2018). Theses and Dissertations--Pharmacy. 94.
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