Statistical Monitoring of Heteroscedastic Dose-Response Profiles from High-Throughput Screening

摘要

In pharmaceutical drug discovery and agricultural crop product discovery, in vivo bioassay experiments are used to identify promising compounds for further research. The reproducibility and accuracy of the bioassay is crucial to be able to correctly distinguish between active and inactive compounds. In the case of agricultural product discovery, a replicated dose-response of commercial crop protection products is assayed and used to monitor test quality. The activity of these compounds on the test organisms, the weeds, insects, or fungi, is characterized by a dose-response curve measured from the bioassay. These curves are used to monitor the quality of the bioassays. If undesirable conditions in the bioassay arise, such as equipment failure or problems with the test organisms, then a bioassay monitoring procedure is needed to quickly detect such issues. In this article we illustrate a proposed nonlinear profile monitoring method to monitor the variability of multiple assays, the adequacy of the dose-response model chosen, and the estimated dose-response curves for aberrant cases in the presence of heteroscedasticity. We illustrate these methods with in vivo bioassay data collected over one year from DuPont Crop Protection.