Abstract #301004

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JSM 2003 Abstract #301004
Activity Number: 296
Type: Contributed
Date/Time: Tuesday, August 5, 2003 : 2:00 PM to 3:50 PM
Sponsor: Biopharmaceutical Section
Abstract - #301004
Title: Statistical Properties of In Vitro Assay Test-Retest Studies Used in Drug Discovery Research
Author(s): Brian J. Eastwood*+
Companies: Eli Lilly & Company
Address: Statistical and Mathematical Sciences, Indianapolis, IN, 46285-0001,
Keywords: agreement measures ; reliability ; test-retest studies ; in vitro assay
Abstract:

Test-retest studies have been proposed for examination of intra-assay variation in potency estimates derived from concentration-response assays (Eastwood et al. 2001, 2002). These studies supplement simpler studies designed to estimate the signal window (Sittampalam et al. 1997) and Z-factor (Zhang et al. 1998) criterion used in validation of high-throughput screening single-concentration assays. The standard protocol is to test 20-30 compounds in each of two runs of the assay to examine the assay variability. The analysis methods, adapted from Bland and Altman (1986), give three summary measures: the Limits of Agreement, Mean Ratio and Minimum Significant Ratio. These outcomes have been shown to identify unacceptable assays that otherwise would pass the single point signal window and Z-factor acceptance criterion (Eastwood 2002). In this presentation the statistical properties of the test-retest study outcomes are examined, and the proposed target criterion for each outcome is judged for suitability.


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