Methods and Applications of Statistics in Clinical Trials, Volume 2: Planning, Analysis, and Inferential Methods

Chapter 23

Microarray

Grier P. Page and Xiangqin Cui

In this review, we highlight some issues an investigator must consider when thinking about using expression arrays in a clinical trial. We present the material in a series of sections. Section 23.1 highlights previous uses of microarrays in clinical trials. Section 23.2 discusses expression microarrays, whereas other uses for microarrays are discussed in Section 23.3. Generating high-quality microarray data for these applications requires careful consideration of experimental design and conduct. The next sections highlight the steps in the planning and analysis of a microarray study. Section 23.4 discusses defining the objectives of the study, followed by experimental design, data extraction from images, microarray informatics, single-gene analysis, data annotation, analyses beyond a single gene, microarray result validation, and finally conclusions.

23.1 Introduction

Microarrays have been described as “the hottest thing in biology and medicine since the advent of the polymerase chain reaction a decade ago.” (Anonymous, 2001). This technology emerged circa 1996 [1,2] and had its first high-profile uses in 1998 and 1999 [3–5]. What is “hot” is that microarrays allow the simultaneous measurement of mRNA expression levels from thousands of genes from samples. DNA microarray studies have already been published for a variety of species, including human [6], mouse [7], rat [8], and have made major contributions to clinical trials [9,10], ...