Communications for Statistical Applications and Methods

The Korean Statistical Society (한국통계학회)
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An R package UnifiedDoseFinding for continuous and ordinal outcomes in Phase I dose-finding trials

  • Pan, Haitao (Department of Biostatistics, St Jude Children's Research Hospital) ;
  • Mu, Rongji (Clinical Research Center, Shanghai Jiao Tong University School of Medicine) ;
  • Hsu, Chia-Wei (Department of Biostatistics, St Jude Children's Research Hospital) ;
  • Zhou, Shouhao (Department of Public Health Sciences, Pennsylvania State University College of Medicine)
  • Received : 2021.11.22
  • Accepted : 2022.03.08
  • Published : 2022.07.31
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Abstract

Phase I dose-finding trials are essential in drug development. By finding the maximum tolerated dose (MTD) of a new drug or treatment, a Phase I trial establishes the recommended doses for later-phase testing. The primary toxicity endpoint of interest is often a binary variable, which describes an event of a patient who experiences dose-limiting toxicity. However, there is a growing interest in dose-finding studies regarding non-binary outcomes, defined by either the weighted sum of rates of various toxicity grades or a continuous outcome. Although several novel methods have been proposed in the literature, accessible software is still lacking to implement these methods. This study introduces a newly developed R package, UnifiedDoseFinding, which implements three phase I dose-finding methods with non-binary outcomes (Quasi- and Robust Quasi-CRM designs by Yuan et al. (2007) and Pan et al. (2014), gBOIN design by Mu et al. (2019), and by a method by Ivanova and Kim (2009)). For each of the methods, UnifiedDoseFinding provides corresponding functions that begin with next that determines the dose for the next cohort of patients, select, which selects the MTD defined by the non-binary toxicity endpoint when the trial is completed, and get oc, which obtains the operating characteristics. Three real examples are provided to help practitioners use these methods. The R package UnifiedDoseFinding, which is accessible in R CRAN, provides a user-friendly tool to facilitate the implementation of innovative dose-finding studies with nonbinary outcomes.

Keywords

Acknowledgement

The authors thank the associate editor and two reviewers for very insightful and constructive comments that substantially improved the article. The authors thank Dr. Vani Shanker and this Journal for editorial help on the manuscript. Pan and Hsu's research is partially supported by American Lebanese Syrian Associated Charities (ALSAC). Mu's research is partially supported by the National Natural Science Foundation of China (grant 11901519, grant 11801359) and the China Postdoctoral Science Foundation (grant 2019M661416).

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