CONTINUAL REASSESSMENT METHOD - A PRACTICAL DESIGN FOR PHASE-1 CLINICAL-TRIALS IN CANCER
CONTINUAL REASSESSMENT METHOD - A PRACTICAL DESIGN FOR PHASE-1 CLINICAL-TRIALS IN CANCER
复制标题
DOI：
10.2307/2531628
复制
发表时间：
1990-03-01
期刊：
影响因子：
1.9
通讯作者：
FISHER, L
中科院分区：
文献类型：
--
作者：
OQUIGLEY, J;PEPE, M;FISHER, L
本文着眼于癌症I期临床试验设计和分析的新方法。这种方法背后的基本思想和动机源于试图将剂量探索实验的需要与既定医疗实践的伦理要求相协调。有人认为，对于这些试验的剂量毒性曲线的特定形状是没有什么兴趣。注意力集中于确定具有特定目标毒性水平的剂量，并集中于目前所有现有证据表明是该水平的最佳估计的剂量。这种方法不仅明确地试图满足道德要求，而且还能够使用其唯一要求是本地（即，在对应于目标毒性水平的剂量附近），它们合理地很好地近似于毒性反应的真实概率。虽然可以设想大量的模型，但我们看一个特别简单的模型。广泛的模拟表明，该模型具有真实的承诺。
This paper looks at a new approach to the design and analysis of Phase I clinical trials in cancer. The basic idea and motivation behind the approach stem from an attempt to reconcile the needs of dose-finding experimentation with the ethical demands of established medical practice. It is argued that for these trials the particular shape of the dose toxicity curve is of little interest. Attention focuses rather on identifying a dose with a given targeted toxicity level and on concentrating experimentation at that which all current available evidence indicates to be the best estimate of this level. Such an approach not only makes an explicit attempt to meet ethical requirements but also enables the use of models whose only requirements are that locally (i.e., around the dose corresponding to the target toxicity level) they reasonably well approximate the true probability of toxic response. Although a large number of models could be contemplated, we look at a particularly simple one. Extensive simulations show the model to have real promise.