Guidelines for the Design of Clinical Studies for the Development and Validation of Therapeutically Relevant Biomarkers and Biomarker-Based Classification Systems

  • Richard M. Simon
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Standards for the development of therapeutically relevant biomarkers and biomarker-based classification systems are lacking. The literature of prognostic marker studies for breast cancer is inconsistent, and few such markers have been adopted for widespread use in clinical practice. This is problematic, as many patients are over-treated and many others are treated ineffectively. The deficiencies in clinical development of biomarkers may become more severe as DNA microarrays and proteomic technologies provide many new candidate markers and therapeutics become more molecularly targeted. In this chapter we address some common problems with developmental marker studies and provide recommendations for the design of clinical studies for the development and validation of robust, reproducible, and therapeutically relevant biomarkers and biomarker-based classification systems. The design of validation studies is addressed for (1) identifying node-negative breast cancer patients who do not require systemic chemotherapy; (2) identifying node-positive breast cancer patients who do not benefit from standard chemotherapy; and (3) identifying node-positive breast cancer patients who benefit from a new molecularly targeted therapeutic.

Key Words

Biomarkers microarrays classification systems clinical trial design 


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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Richard M. Simon
    • 1
  1. 1.Biometric Research BranchNational Cancer InstituteBethesdaUSA

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