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Comparison Among Modified Continual Reassessment Methods with Different Dose Allocation Methods for Phase I Clinical Trials

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  • Jiacheng Xiao

    (Department of Financial and Actuarial Mathematics, Xi’an Jiaotong-Liverpool University, Suzhou 215123, China
    These authors contributed equally to this work.)

  • Weijia Zhang

    (Department of Financial and Actuarial Mathematics, Xi’an Jiaotong-Liverpool University, Suzhou 215123, China
    These authors contributed equally to this work.)

  • Rong Li

    (Department of Financial and Actuarial Mathematics, Xi’an Jiaotong-Liverpool University, Suzhou 215123, China)

  • Conghua Wen

    (Department of Financial and Actuarial Mathematics, Xi’an Jiaotong-Liverpool University, Suzhou 215123, China)

Abstract

The continual reassessment method (CRM) has been an essential Bayesian finding design in phase I clinical trials. It utilizes all the information in observed data which contributes to its essential operational characteristics. However, the CRM has been criticized for its aggressive dose escalation. Model-assisted methods including BOIN, Keyboard, and mTPI improved the safety while retaining relative efficiency. In this paper, we propose four models combining the structure of the CRM and model-assisted methods. We show that these models could operate with comparable CRM performance through simulations. The results suggest that two of the proposed methods outperformed the traditional methods with a higher percentage of correct selection of true maximum tolerated dose. In addition, the interval-based approaches offered by the new models with greater flexibility regarding target toxicity achieved an improvement in the adaptability of the dose-finding process in clinical trials.

Suggested Citation

  • Jiacheng Xiao & Weijia Zhang & Rong Li & Conghua Wen, 2025. "Comparison Among Modified Continual Reassessment Methods with Different Dose Allocation Methods for Phase I Clinical Trials," Mathematics, MDPI, vol. 13(5), pages 1-18, March.
    • Handle: RePEc:gam:jmathe:v:13:y:2025:i:5:p:863-:d:1605896
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    References listed on IDEAS

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    1. Mauro Gasparini & Jeffrey Eisele, 2000. "A Curve-Free Method for Phase I Clinical Trials," Biometrics, The International Biometric Society, vol. 56(2), pages 609-615, June.
    2. Ying Kuen Cheung & Rick Chappell, 2000. "Sequential Designs for Phase I Clinical Trials with Late-Onset Toxicities," Biometrics, The International Biometric Society, vol. 56(4), pages 1177-1182, December.
    3. Yuan, Ying & Yin, Guosheng, 2011. "Robust EM Continual Reassessment Method in Oncology Dose Finding," Journal of the American Statistical Association, American Statistical Association, vol. 106(495), pages 818-831.
    4. Yin, Guosheng & Yuan, Ying, 2009. "Bayesian Model Averaging Continual Reassessment Method in Phase I Clinical Trials," Journal of the American Statistical Association, American Statistical Association, vol. 104(487), pages 954-968.
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