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Activity Number:
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166
- Non-Clinical Statistics, Personalized Medicine, and Other Topics
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Type:
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Contributed
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Date/Time:
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Tuesday, August 10, 2021 : 10:00 AM to 11:50 AM
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Sponsor:
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Biopharmaceutical Section
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Abstract #318138
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Title:
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Quadratic Slope-Ratio Model for Nonlinear Dose-Response of CBPA Assay
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Author(s):
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Ming Luo*
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Companies:
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AbbVie
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Keywords:
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Slope-ratio Model;
Quadratic Dose-response Function;
Relative Potency;
Similarity of Bioassay;
Proportional Drug Effect;
CBPA
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Abstract:
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Commonly used slope-ratio model for bioassay is applicable only in "linear dose range", which usually represents a small part of the dynamic range of the assay responses. Here we propose a non-linear extension of the slope-ratio model based on proportional drug effect assumption. In this approach, the drug dose-response curves are modeled by a pre-selected specific non-linear function that applied on both reference standards and test samples. Relative potency of sample over reference is controlled by a proportion parameter applied on dose levels. The model fitting process is to utilize a modified Gauss-Newton method to iteratively search for such function and the proportion parameter. The fitness of the model and the similarity of the assay is evaluated based on F-test of model comparisons over unrestricted quadratic model and means model. Examples are given for the application of the proposed method. Usually, the specific non-linear function is selected as a quadratic function to ensure the convergence of the model fitting. In this case, we need also to check the monotonicity of the fitted quadratic model over the assay data range.
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Authors who are presenting talks have a * after their name.
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