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Oncology Clinical Trials in the Genomic Era

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Proceedings of the Fourth Seattle Symposium in Biostatistics: Clinical Trials

Part of the book series: Lecture Notes in Statistics ((LNSP,volume 1205))

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Abstract

Developments in genomics are providing a biological basis for the heterogeneity of clinical course and response to treatment that have long been apparent to clinicians. The ability to molecularly characterize human diseases presents new opportunities to develop more effective treatments and new challenges for the design and analysis of clinical trials.

In oncology, treatment of broad populations with regimens that benefit a minority of patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine.

We review prospective designs for the development of new therapeutics and predictive biomarkers to inform their use. We cover designs for a wide range of settings. At one extreme is the development of a new drug with a single candidate biomarker and strong biological evidence that marker negative patients are unlikely to benefit from the new drug. At the other extreme are phase III clinical trials involving both genome-wide discovery of a predictive classifier and internal validation of that classifier. We have outlined a prediction-based approach to the analysis of randomized clinical trials that both preserve the type I error and provide a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from a new regimen.

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Author information

Authors and Affiliations

  1. Biometric Research Branch, National Cancer Institute, Emmes Corporation, 9000 Rockville Pike, MSC7434, Bethesda, Rockville, MD, 20892-7434, USA

    Richard Simon

  2. Emmes Corporation, Rockville, MD, USA

    Jyothi Subramanian

Authors
  1. Richard Simon
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  2. Jyothi Subramanian
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Corresponding author

Correspondence to Richard Simon .

Editor information

Editors and Affiliations

  1. University of Washington, Department of Biostatistics, Seattle, 98195-7232, Washington, USA

    Thomas R. Fleming

  2. University of Washington, Department of Biostatistics, Seattle, 98195-7232, Washington, USA

    Bruce S. Weir

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Simon, R., Subramanian, J. (2013). Oncology Clinical Trials in the Genomic Era. In: Fleming, T., Weir, B. (eds) Proceedings of the Fourth Seattle Symposium in Biostatistics: Clinical Trials. Lecture Notes in Statistics(), vol 1205. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5245-4_5

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