Biomedical Engineering Reference
In-Depth Information
Given the high attrition rate of late-stage clinical trials with MTAs,
there is a great need to enhance the robustness of early clinical trials
to address the objectives key to future directions: credentialing the
agent, optimizing the dose and schedule, obtaining preliminary proof
of concept for the target, and identifying patient selection markers
for further studies. For most MTAs, incorporation of biomarkers to
characterize the tumors and the drug effect on molecular levels is
not only desirable but also indispensible for successful transition
from target discovery to target validation and clinical benefit.
In response to the need for improving the efficiency of drug
development, FDA's critical pathway initiative was launched in 2004,
with the primary objective to foster collaboration between academic
and industry partners as well as regulatory authorities, in order to
integrate preclinical scientific process with all stages of clinical trials.
Key areas identified as high priority include better development and
utilization of biomarker of safety and efficacy.
This chapter will provide definitions of key biomarkers used
in drug development, the potential utility of the biomarkers in
different stages of clinical trials and the current challenges and
future directions.
3.2 A Few Deiniions and General Concepts
Proper use of biomarkers should start with a clear understanding
of the nature and the intended use of various markers in clinical
trials and treatment decisions. Biomarkers are commonly defined
as “…a characteristic that is objectively measured and evaluated as
an indicator of normal biologic processes, pathogenic processes, or
pharmacologic responses to a therapeutic intervention.”
1
Definitions
of various biomarkers and the terminology for steps in clinical
and analytical validations have been reviewed in several guideline
reports.
2,3
The main concepts for markers commonly used in clinical
trials for cancer drugs are defined below.
Based on the purposes in clinical studies, biomarkers can be
categorized in a few types:
•
Pharmacodynamics
): Changes in
molecular measurements due to the drug effect (e.g.,
markers
(PD
Markers
