chapter  6
30 Pages

Validation of Assays for the Bioanalysis of Novel Biomarkers: Practical Recommendations for Clinical Investigation of New Drug Entities

Biomarkers comprise a broad array of laboratory-based, physiological, and

behavioral characteristics that are measured as indicators of normal biological

processes, as pathogenic processes, or as pharmacological responses to

therapeutic interventions [1]. With few exceptions, such as viral load, biomarkers

are endogenous substances. Depending on the stage of drug development,

biomarker measurements can provide important mechanistic, efficacy, or toxicity

information. For example, biomarker data can be used to discover and select a

lead compound, generate pharmacokinetic/pharmacodynamic (PK/PD) models

[2,3] that aid in clinical trial design and expedite drug development, serve as

surrogates for a clinical or mortality endpoint [4], and optimize drug therapy

based on genotypic or phenotypic factors [5]. Additionally, biomarker data can

be useful to define which patients to enroll in a drug study or to stratify patients

within a clinical protocol.