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The Minimum Significant Ratio: A Statistical Parameter to Characterize the Reproducibility of Potency Estimates from Concentration-Response Assays and Estimation by Replicate-Experiment Studies

Statistics and Information Sciences, Eli Lilly and Company, Indianapolis, Indiana; Eli Lilly and Company Lilly Corporate Center Indianapolis, IN 46285 bje{at}lilly.com

Mark W. Farmen

Philip W. Iversen

Statistics and Information Sciences, Eli Lilly and Company, Indianapolis, Indiana.

Trelia J. Craft

Cardiovascular Research, Eli Lilly and Company, Indianapolis, Indiana.

Jeffrey K. Smallwood

Kim E. Garbison

Neil W. Delapp

Lead Optimization Biology, Eli Lilly and Company, Indianapolis, Indiana.

Gerald F. Smith

Cardiovascular Research, Eli Lilly and Company, Indianapolis, Indiana.

The authors show by illustration that procedures used to validate the reliability of single-concentration high-throughput screens such as the signalwindowand Z' factor do not ensure sufficient reliability in potency estimates fromconcentration response assays. They develop theminimumsignificant ratio as a statistical parameter to characterize the fold change between 2 compounds run in the same experiment that can be considered a real difference and use this parameter to characterize the reliability of the assay. They adaptmethods described by Bland and Altman to develop a simple set of 2 experiments to estimate theminimum significant ratio and show that this protocol can identify assays that lack reproducibility. The methods are then extended to validate the equivalency of the same assay run by multiple laboratories.

Key Words: minimum significant ratio • replicate-experiment studies • potency reproducibility • statistical methods

This version was published on April 1, 2006

Journal of Biomolecular Screening, Vol. 11, No. 3, 253-261 (2006)
DOI: 10.1177/1087057105285611


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