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Robust and Efficient Assessment of Potency (REAP): A Quantitative Tool for Dose-response Curve Estimation

Authors :
Xinying Fang
J. Jack Lee
Chan Shen
Michael Wang
Shouhao Zhou
Hong Gang Wang
Xinyi Liu
Nikolay V. Dokholyan
Vernon M. Chinchilli
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

The median-effect equation has been widely used to describe the dose-response relationship and identify compounds that activate or inhibit specific disease targets in contemporary drug discovery. However, the experimental data often contain extreme responses, which may significantly impair the estimation accuracy and impede valid quantitative assessment in the standard estimation procedure. To improve the quantitative estimation of the dose-response relationship, we introduce a novel approach based on robust beta regression. Substantive simulation studies under various scenarios demonstrate solid evidence that the proposed approach consistently provides robust estimation for the median-effect equation, particularly when there are extreme outcome observations. Moreover, simulation studies illustrate that the proposed approach also provides a narrower confidence interval, suggesting a higher power in statistical testing. Finally, to efficiently and conveniently perform common lab data analyses, we develop a freely accessible web-based analytic tool to facilitate the quantitative implementation of the proposed approach for the scientific community.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........78819885434c264a69ad64ad0ead43f7
Full Text :
https://doi.org/10.1101/2021.11.20.469388