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Recent Developments in the Use of Clinical Trials to Support Individualizing Therapies: A Regulatory Perspective

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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

This chapter covers a broad range of issues centered around the topic of optimizing therapies for individuals and the role of the clinical trial in reaching that goal. We describe how the clinical trial has been increasingly relied upon to provide the evidence for the patient level or patient marker level differential benefit or risk of therapies and how the study design choices can change depending upon the various study objectives. We consider the definition and role of prognostic and predictive classifiers or markers in the different clinical trial designs used for selecting and evaluating enriched study populations, and the difference between the retrospective and prospective approaches to evaluating differential treatment effects among marker subgroups. Some examples are given to illustrate the issues. Two of the most challenging aspects of identifying and validating a predictive marker are the simultaneous need to quantify the performance characteristics (sensitivity and specificity) of the classifier and the choice of whether the study design should include all comers or selection of the marker positive only subgroup. The motivation for these clinical trial approaches to individualizing therapy is to maximize the benefits and minimize the safety risks of therapies for patients.

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Author information

Authors and Affiliations

  1. Office of Biostatistics, FDA Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD, 20993-0002, USA

    Robert T. O’Neill

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  1. Robert T. O’Neill
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Correspondence to Robert T. O’Neill .

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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O’Neill, R.T. (2013). Recent Developments in the Use of Clinical Trials to Support Individualizing Therapies: A Regulatory Perspective. 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_4

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