JSM 2004 - Toronto

Abstract #301441

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Activity Number: 307
Type: Contributed
Date/Time: Wednesday, August 11, 2004 : 8:30 AM to 10:20 AM
Sponsor: Biopharmaceutical Section
Abstract - #301441
Title: Rank-based Estimate of Four-parameter Logistic Model with Application in Pharmaceutical Sciences
Author(s): Kimberly Crimin*+ and Thomas Vidmar and Joseph McKean
Companies: Pfizer Inc. and Pfizer Inc. and Western Michigan University
Address: Eastern Point Rd., Groton, CT, 06340,
Keywords: rank-based estimate ; IC50 ; four-parameter logistic
Abstract:

In the pharmaceutical industry, the calculation of inhibitory concentration that results in a response of 50% (IC50), is performed thousands of times every day. The nonlinear model most often used to performed this calculation is a four-parameter logistic, suitably parameterized to estimate the IC50 directly. When performing these calculations in a high-throughput mode, each and every curve cannot be studied in detail. Outliers in the responses are a common problem. A robust estimation procedure to perform this calculation is desirable. We are proposing a rank-based estimate of the four-parameter logistic model that is analogous to least squares, except a norm other than the Euclidean norm is used. We illustrate this robust procedure with several examples from pharmaceutical industry. When no outliers are present in the data, the robust estimate of IC50 is comparable to the least squares estimate and when outliers are present in the data, the robust estimates is more accurate. We also provide a robust goodness-of-fit test and present the results from a small simulation study.

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