Biomarkers for Pharmacokinetic/Pharmacodynamic Modeling and Clinical Trial Simulations
Biomarkers have begun to assume their place in the drug development process
[1-6]. As has been discussed in some of the earlier chapters, when biomarkers are
(1) grounded in mechanism-based disease and therapeutic intervention theory, (2)
developed from discovery through preclinical assessments, and (3) measured with
good laboratory practice (GLP)-like analytical methods, they have the potential to
serve as a tool for early decision making and ultimately to become surrogate
endpoints that predict clinical endpoints. But more to the point for this chapter,
biomarkers have the potential to effectively lead drug development from drug-
target rationale to discovery to preclinical development to clinical develop-
ment to regulatory approval and labeling information via pharmaco-
kinetic/pharmacodynamic (PK/PD) modeling and clinical trial simulations.
Terms and deﬁnitions used in this chapter are those selected by the National
Institutes of Health Biomarkers DeﬁnitionsWorkingGroup . The term “clinical
endpoint” is used rather than clinical outcome to avoid discussions centering on
differences between clinical pharmacological and epidemiological perspectives.