ABSTRACT
Dose optimization requires careful pharmacokinetic (PK) and pharmacodynamic
(PD) analyses. Biomarkers are the basis of PD assessments and, more generally,
are of increased interest to enhance decision-making in drug development. The
focus of this chapter is on selected components of a suitable biomarker research
plan, critical for the development and success of biomarkers, especially novel
biomarkers. The elements that must be addressed by the research plan include
both method validation and biomarker qualification. Method validation is the
process of assessing the assay and its measurement performance characteristics,
and determining the range of conditions under which the assay will provide
reproducible data meeting the individual study objectives. Qualification is the
evidentiary process of linking a biomarker with biological processes and clinical
endpoints. For distal or disease-related biomarkers, there are four general
categories of increasing levels for qualification: exploration, demonstration,
characterization, and surrogacy. A biomarker research plan, like the validation
and qualification activities it describes, is a graded, “fit for purpose” process
dependent on the intended application. A biomarker research plan can describe
activities leading to one or more purposes, or may be iterative in nature, evolving
with the use of the biomarker.
