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Designs for Phase I Trials

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Designs for Clinical Trials

Abstract

This chapter surveys the recent development of dose-finding designs for phase I trials of chemotherapy, reviews the statistical theory of dose-finding, and outlines the basic concepts of methods for dealing with specific clinical settings such as late-onset toxicities, gradation of toxicity severity, and bivariate outcomes. We will compare some of the promising approaches via simulations in the context of a combination chemotherapy trial in patients with lymphoma. Our goal is to highlight the relative advantages of each method, and provide guidance on the scenarios where some methods are more appropriate than the others. We will explore the robustness of these methods under violations of their underlying assumptions, with a particular focus on the model-based continual reassessment method. Finally, we will discuss the challenge of implementing these novel designs in practice, and introduce an R package for the planning and implementation of the continual reassessment method in a phase I trial.

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Authors and Affiliations

  1. Department of Biostatistics, Columbia University, 722 West 168th Street, Room 641, New York, NY, 10032, USA

    Ying Kuen Cheung

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  1. Ying Kuen Cheung
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Correspondence to Ying Kuen Cheung .

Editor information

Editors and Affiliations

  1. Dana-Farber Cancer Institute, Harvard Medical School, Binney St. 44, Boston, 02115, Massachusetts, USA

    David Harrington

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Cheung, Y.K. (2012). Designs for Phase I Trials. In: Harrington, D. (eds) Designs for Clinical Trials. Applied Bioinformatics and Biostatistics in Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0140-7_1

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