Joint detection of important biomarkers and optimal dose–response model using penalties (original) (raw)

Statistics in Medicine, 2007

Abstract

We propose a method to jointly detect influential biomarkers and estimate how they change with dose. The assessment is made in dose‐ranging trials collecting multiple outcomes for efficacy, safety, pharmacokinetics or pharmacodynamics. We regress all these outcomes versus a non‐parametric transformation of the dose. The regression coefficients and the parameters from the dose–response model are simultaneously estimated using a penalized alternating least‐squares method. We illustrate the technique with a phase I clinical trial and a metabonomic experiment in rats. Copyright © 2007 John Wiley & Sons, Ltd.

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