Joint detection of important biomarkers and optimal dose-response model using penalties

被引：3

作者：

Vandenhende, F.

Eilers, P.

Ledent, E.

Renard, D.

Tibaldi, E.

机构：

[1] Eli Lilly & Co, Global Stat, Mont St Guibert, Belgium

[2] Leiden Univ, Dept Med Stat, NL-2300 RA Leiden, Netherlands

来源：

STATISTICS IN MEDICINE | 2007年 / 26卷 / 27期

关键词：

biomarkers; penalty; dose-response;

D O I：

10.1002/sim.2960

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. (C) 2007 John Wiley & Sons, Ltd.

引用

页码：4876 / 4888

页数：13

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