Dose-finding designs for HIV studies
Dose-finding designs for HIV studies
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DOI：
10.1111/j.0006-341x.2001.01018.x
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发表时间：
2001-12-01
期刊：
影响因子：
1.9
通讯作者：
Fenton, T
中科院分区：
文献类型：
--
作者：
O'Quigley, J;Hughes, MD;Fenton, T
我们提出了一类简单的设计，可用于艾滋病毒的早期剂量探索研究。与癌症的I期设计相比，这样的设计有很多II期的味道。在试验期间获得疗效信息，其重要性与毒性相关信息相同。这里提出的设计顺序地结合了病毒减少所获得的信息。初始（损失）是从一些固定范围的剂量方案中给出的。剂量是根据其潜在毒性排序的。在任何剂量下，患者都可能出现以下三种结果之一：无法接受治疗（毒性），能够接受治疗但病毒载量减少不足（病毒失败），以及能够接受治疗并充分减少病毒载量（成功）。声波类设计的一个明确目标是确定导致最大成功率的剂量。在我们确定和讨论的某些假设下，我们可以获得有效的设计。在较弱的，有时更现实的假设下，我们仍然可以获得在识别水平时具有良好操作特性的设计，如果存在这样的水平，则具有一定或更大的成功率。如果没有这样一个水平，设计将提前结束，表明新的处理方法无效。
We present a class of simple designs that can be used in early dose-finding studies in HIV. Such designs, in contrast with Phase I designs in cancer, have a lot of the Phase II flavor about them. Information on efficacy is obtained during the trial and is as important as that relating to toxicity. The designs proposed here sequentially incorporate the information obtained on viral reduction. Initial (loses are given from some fixed range of dose regimens. The doses are ordered in terms of their toxic potential. At any dose, a patient can have one of three outcomes: inability to take the treatment (toxicity), ability to take the treatment but insufficient reduction in viral load (viral failure), and ability to take the treatment as well as a sufficient reduction of viral load (success). A clear goal for sonic class of designs would be the identification of the dose leading to the greatest percentage of successes. Under certain assumptions, which we identify and discuss, we can obtain efficient designs for this task. Under weaker, sometimes more realistic assumptions, we can still obtain designs that have good operating characteristics in identifying a level, if such a level exists, having some given or greater success rate. In the absence of such a level, the designs will come to an early closure, indicating the ineffectiveness of the new treatment.