Wages Nolan A, Conaway Mark R
Division of Translational Research and Applied Statistics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Pharm Stat. 2013 Jul-Aug;12(4):217-24. doi: 10.1002/pst.1575. Epub 2013 Jun 3.
In studies of combinations of agents in phase I oncology trials, the dose-toxicity relationship may not be monotone for all combinations, in which case the toxicity probabilities follow a partial order. The continual reassessment method for partial orders (PO-CRM) is a design for phase I trials of combinations that leans upon identifying possible complete orders associated with the partial order. This article addresses some practical design considerations not previously undertaken when describing the PO-CRM. We describe an approach in choosing a proper subset of possible orderings, formulated according to the known toxicity relationships within a matrix of combination therapies. Other design issues, such as working model selection and stopping rules, are also discussed. We demonstrate the practical ability of PO-CRM as a phase I design for combinations through its use in a recent trial designed at the University of Virginia Cancer Center.
在肿瘤学I期试验中对联合用药进行研究时，并非所有联合用药的剂量-毒性关系都是单调的，在这种情况下，毒性概率遵循偏序关系。偏序连续重新评估方法（PO-CRM）是一种用于联合用药I期试验的设计方法，它依赖于识别与偏序相关的可能的全序关系。本文讨论了在描述PO-CRM时以前未涉及的一些实际设计考虑因素。我们描述了一种选择可能排序的适当子集的方法，该方法是根据联合治疗矩阵内已知的毒性关系制定的。还讨论了其他设计问题，如工作模型选择和停止规则。我们通过弗吉尼亚大学癌症中心最近设计的一项试验中对PO-CRM的应用，展示了其作为联合用药I期设计的实际能力。
