A Novel Statistical Approach To NOAEL: QBEST Applied To Dosing Of Ellagic Acid
The accuracy and precision of the QBEST Simulation and QNOAEL compared to the Benchmark Dose Method are evaluated, and the NOAEL of ellagic acid will be calculated for clinical trials of its use as a component therapeutic agent (in BSN476) for treating Chikungunya infections.
Abstract
QBEST, a novel statistical method, can be applied to the problem of estimating the No Observed Adverse Effect Level (NOAEL) 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 (BMD) and is superior to the BMD in others. The Benchmark Dose Method is currently widely used in toxicological research. 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. The QNOAEL simulation generates an intuitive curve that is comparable to the dose-response curve. The NOAEL of ellagic acid (EA) will be calculated for clinical trials of its use as a component therapeutic agent (in BSN476) for treating Chikungunya infections. This will be the first published application of QBEST to the problem of NOAEL determination. 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.