Targeted Methods for Biomarker Discovery

Abstract

The use of biomarkers in disease diagnosis and treatment has grown rapidly in recent years, as microarray and sequencing technologies capable of detecting biological signatures have become more effective research tools. In an attempt to create a level of quality assurance with respect to biological and more specifically biomarker research, the FDA has called for the development of a standard protocol for biomarker qualification (Food and Drug Administration 2006). Such a protocol would define “evidentiary” standards for biomarker usage in areas of drug development and disease treatment and provide a standardized assessment of a biomarker’s significance and biological interpretation. This is especially relevant for RCTs, where the protocol would prohibit the use of unauthenticated biomarkers to determine treatment regime, resulting in safer and more reliable treatment decisions (Food and Drug Administration 2006). Consequentially, identifying accurate and flexible analysis tools to assess biomarker importance is essential. In this chapter, we present a measure of variable importance based on a flexible semiparametric model as a standardized measure for biomarker importance. We estimate this measure with the TMLE.