Adaptive phase I–II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies.

Targeted agents and immunotherapies have revolutionized cancer treatment, offering promising options for various cancer types. Unlike traditional therapies the principle of "more is better" is not always applicable to these new therapies due to their unique biomedical mechanisms. As a result, variou...

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Published in:Clinical Trials Vol. 21; no. 3; pp. 298 - 308
Main Authors: Zang, Yong, Guo, Beibei, Qiu, Yingjie, Liu, Hao, Opyrchal, Mateusz, Lu, Xiongbin
Format: review tables/charts Journal Article
Published: Sage Publications, Ltd. Jun2024
Online Access:View this record in EBSCOhost
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      dt: Jun2024
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      pub: Sage Publications, Ltd.
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        10.1177/17407745231220661
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        atl: Adaptive phase I–II clinical trial designs identifying optimal biological doses for targeted agents and immunotherapies.
      aug:
        au:
          Zang, Yong
          Guo, Beibei
          Qiu, Yingjie
          Liu, Hao
          Opyrchal, Mateusz
          Lu, Xiongbin
        affil: Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN, USA
      sug:
        subj:
          Clinical Trials
          Immunotherapy
          Dosage Forms
          Adaptation, Physiological
          Drug Efficacy
          Patient Safety
          Drug Toxicity
          Survival Analysis
          Quality of Life
          Dose-Response Relationship, Drug
      ab: Targeted agents and immunotherapies have revolutionized cancer treatment, offering promising options for various cancer types. Unlike traditional therapies the principle of "more is better" is not always applicable to these new therapies due to their unique biomedical mechanisms. As a result, various phase I–II clinical trial designs have been proposed to identify the optimal biological dose that maximizes the therapeutic effect of targeted therapies and immunotherapies by jointly monitoring both efficacy and toxicity outcomes. This review article examines several innovative phase I–II clinical trial designs that utilize accumulated efficacy and toxicity outcomes to adaptively determine doses for subsequent patients and identify the optimal biological dose, maximizing the overall therapeutic effect. Specifically, we highlight three categories of phase I–II designs: efficacy-driven, utility-based, and designs incorporating multiple efficacy endpoints. For each design, we review the dose–outcome model, the definition of the optimal biological dose, the dose-finding algorithm, and the software for trial implementation. To illustrate the concepts, we also present two real phase I–II trial examples utilizing the EffTox and ISO designs. Finally, we provide a classification tree to summarize the designs discussed in this article.
      pubtype: Academic Journal
      doctype:
        review
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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