INTRODUCTION TO BIOMARKERS - Flow Cytometry in Drug Discovery and Development - page 59

of the biomarker assay and clinical studies assessing the biological variability. The
goal of the qualification is to obtain a consensus in the scientific community on
the validity of the biomarker for a particular use. One strategic approach to this is the
so-called “fit-for-purpose” biomarkers. Dr. Wagner describes biomarker qualification
as being “the evidentiary process of linking a biomarker with biological processes
and clinical end points” [22]. The aim of this qualification in clinical development is
to ensure that the intended use of the biomarker in a clinical study is supported by
evidence from earlier studies.
It will, however, take many years before the scientific community and FDA will
accept a newly discovered biomarker as a surrogate end point, and very few
biomarkers will ever reach this level of qualification. For this reason, most biomarkers
used in clinical development are used to support decision making in early clinical
development and will have undergone only limited qualification.
3.7 BIOMARKER IN CLINICAL DEVELOPMENT
Evaluation of biomarkers in clinical studies (early and late phases) is increasingly
becoming integral part of drug development, with considerable investment in
biomarker sample collection and testing. Development of biomarkers occurs in
different phases during drug development. Biomarker hypothesis should ideally be
generated in preclinical studies using in vitro and in vivo models, followed by assay
development and validation using healthy donor samples and archived samples from
clinical studies (retrospective analysis) [16]. The biomarker assay is further validated
in prospective studies and implemented in randomized control trials. The following
sections include a discussion of various aspects that play an important role in the
development of biomarkers in clinical studies.
3.7.1 Biomarker Strategies
The implementation of a biomarker strategy into a clinical study can often be a complex
process. The debate on potential utility of biomarkers that highlight the pros and cons of
including biomarker assessment in clinical studies iswell known and thought provoking
when one has tomake investment decisions [32, 33]. Inclusion of biomarker evaluation
in clinical studies could potentially affect cost, timelines, and enrollment (if sample
collection is mandatory). Therefore, the need and feasibility of biomarker evaluation
should be carefully investigated. Investment in biomarker measurement is questionable
if the scientific need is not strong. Most important aspect to consider during devel-
opment of a biomarker strategy is identification of the potential utility of the intended
biomarker/s i.e MOA or predictive or prognostic etc. Certain commercial aspects, such
as, potential of the biomarker/s to increase the market value of the drug and whether
they provide a competitive edge against drugs in the same class are also valid
considerations during drug development. The other important factors to consider for
implementing a biomarker strategy are the availability of relevant samples for
biomarker analysis, stability of the markers in these samples during shipment and
storage, and an appropriate assay system to accurately measure these biomarkers. If