A product of independent beta probabilities dose escalation design for dual-agent phase I trials.
A product of independent beta probabilities dose escalation design for dual-agent phase I trials.
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DOI：
10.1002/sim.6434
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发表时间：
2015-04-15
影响因子：
2
通讯作者：
Sweeting, Michael J.
中科院分区：
文献类型：
--
作者：
Mander, Adrian P.;Sweeting, Michael J.
双药试验现在在肿瘤学研究中越来越常见，并且在统计学文献中可以获得许多建议的剂量递增设计。尽管如此，从统计设计到实际应用的转化是缓慢的，正如在单药I期试验中所强调的那样，其中通常仍然使用基于3 + 3规则的设计。为了加快这一过程，新的剂量递增设计不仅需要在科学上有益，而且需要易于临床医生理解和实施。在本文中，我们提出了一个无曲线（非参数）设计的双药剂试验中，模型参数是在每个剂量组合的毒性概率。我们表明，它是相对平凡的临床医生的先验信念或历史信息被纳入模型和更新是快速和计算简单，通过使用共轭贝叶斯推理。通过仅考虑最大耐受轮廓分布的一组单调轮廓来确保单调性，这定义了剂量递增决策过程。可以围绕轮廓进行不同的实验，并且可以推荐多种剂量组合以推进II期。R、Stata和Excel的代码可供执行。© 2015作者。出版社：John Wiley & Sons Ltd
Dual-agent trials are now increasingly common in oncology research, and many proposed dose-escalation designs are available in the statistical literature. Despite this, the translation from statistical design to practical application is slow, as has been highlighted in single-agent phase I trials, where a 3 + 3 rule-based design is often still used. To expedite this process, new dose-escalation designs need to be not only scientifically beneficial but also easy to understand and implement by clinicians. In this paper, we propose a curve-free (nonparametric) design for a dual-agent trial in which the model parameters are the probabilities of toxicity at each of the dose combinations. We show that it is relatively trivial for a clinician's prior beliefs or historical information to be incorporated in the model and updating is fast and computationally simple through the use of conjugate Bayesian inference. Monotonicity is ensured by considering only a set of monotonic contours for the distribution of the maximum tolerated contour, which defines the dose-escalation decision process. Varied experimentation around the contour is achievable, and multiple dose combinations can be recommended to take forward to phase II. Code for R, Stata and Excel are available for implementation. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
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