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genotyping, where assurance of the accuracy of the genotyping method may require
confirmation by another technology or by dideoxy sequencing (considered the golden
standard) before a patient is enrolled.
As discussed earlier in this chapter, very few biomarkers will ever reach the status
of a surrogate end point. In our experience, most biomarkers in late clinical
development will be used either for inclusion/exclusion (e.g., genotyping and gene
expression) or for demonstrating that the expected effect on the biomarker is detected.
Inclusion/exclusion biomarkers are critical for the clinical study enrollment. The
information showing the expected PD effect is mostly used to add valuable informa-
tion to the mechanism of action in an NDA application.
3.8 CONCLUSIONS
Incorporation of biomarkers may add complexity and cost early in drug development;
however, biomarkers can help select therapeutic agents with better chances for
success. A carefully planned biomarker strategy with proper implementation is the
key to increase the success rate of a drug with high probability of clinical benefit.
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