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A Comparative Study of Model-Based Dose-Finding Methods for Two-Agent Combination Trials

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Frontiers of Biostatistical Methods and Applications in Clinical Oncology

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Abstract

Little is known about the relative relationships of the operating characteristics for rival model-based dose-finding methods for two-agent combination phase I trials . In this chapter, we focus on the model-based dose-finding methods that have been recently developed. We compare the recommendation rates for true maximum tolerated dose combinations (MTDCs) and over dose combinations (ODCs) among these methods under 16 scenarios with 3 × 3, 4 × 4, 2 × 4, and 3 × 5 dose combination matrices through comprehensive simulation studies. We found that the operating characteristics of the dose-finding methods varied depending on (1) whether the dose combination matrix is square or not, (2) whether the true MTDCs exist within the same group consisting of the diagonals of the dose combination matrix, and (3) the number of true MTDCs. We also discuss the details of the operating characteristics and the advantages and disadvantages of the dose-finding methods compared.

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Acknowledgements

The views expressed here are the result of independent work and do not represent the viewpoints or findings of the Pharmaceuticals and Medical Devices Agency. This work was partially supported by JSPS KAKENHI [Grant Number 15K15948] (Grant-in-Aid for Young Scientists B). This work was partially supported by JSPS KAKENHI [Grant Number 17K00045] (Grant-in-Aid for Scientific Research C).

Author information

Authors and Affiliations

  1. Department of Biostatistics and Bioinformatics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8654, Japan

    Akihiro Hirakawa

  2. Biostatistics Group, Office of New Drug V, Pharmaceuticals and Medical Devices Agency, 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo, 100-0013, Japan

    Hiroyuki Sato

Authors
  1. Akihiro Hirakawa
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  2. Hiroyuki Sato
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Corresponding author

Correspondence to Akihiro Hirakawa .

Editor information

Editors and Affiliations

  1. Graduate School of Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    Shigeyuki Matsui

  2. Cancer Research and Biostatistics, Seattle, Washington, USA

    John Crowley

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Hirakawa, A., Sato, H. (2017). A Comparative Study of Model-Based Dose-Finding Methods for Two-Agent Combination Trials. In: Matsui, S., Crowley, J. (eds) Frontiers of Biostatistical Methods and Applications in Clinical Oncology. Springer, Singapore. https://doi.org/10.1007/978-981-10-0126-0_4

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