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Dose Finding for Joint Assessment of Both Efficacy and Toxicity

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Modern Dose-Finding Designs for Cancer Phase I Trials: Drug Combinations and Molecularly Targeted Agents

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Abstract

Traditionally, phase I trials are designed to determine the MTD of a new agent based solely on toxicity, regardless of the efficacy. The determination of an optimal dose based on the joint assessment of toxicity and efficacy of the drug in phase I dose-finding trials may be reasonable in some cases. The various types of incorporation of toxicity and efficacy outcomes into dose-finding methods have been developed. Among them, in this chapter, we overview four methods: (i) the bivariate continual reassessment method, (ii) Bayesian method based on the efficacy–toxicity trade-off, (iii) Bayesian method for evaluating binary toxicity and continuous efficacy outcomes, and (iv) the method based on the Bayesian Model Averaging (BMA).

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Author information

Authors and Affiliations

  1. Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Akihiro Hirakawa

  2. Pharmaceuticals and Medical Devices Agency, Tokyo, Japan

    Hiroyuki Sato

  3. Division of Biostatistics, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Takashi Daimon

  4. Department of Biostatistics, Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan

    Shigeyuki Matsui

Authors
  1. Akihiro Hirakawa
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  2. Hiroyuki Sato
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  3. Takashi Daimon
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  4. Shigeyuki Matsui
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Corresponding author

Correspondence to Akihiro Hirakawa .

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Hirakawa, A., Sato, H., Daimon, T., Matsui, S. (2018). Dose Finding for Joint Assessment of Both Efficacy and Toxicity. In: Modern Dose-Finding Designs for Cancer Phase I Trials: Drug Combinations and Molecularly Targeted Agents. SpringerBriefs in Statistics(). Springer, Tokyo. https://doi.org/10.1007/978-4-431-55573-5_3

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