BAYESIAN METHODS FOR PHASE-I CLINICAL-TRIALS
BAYESIAN METHODS FOR PHASE-I CLINICAL-TRIALS
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DOI：
10.1002/sim.4780111011
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发表时间：
1992-07-01
影响因子：
2
通讯作者：
GREENHOUSE, JB
中科院分区：
文献类型：
--
作者：
GATSONIS, C;GREENHOUSE, JB
进行I期临床试验是为了确定一种新药的毒副作用的剂量-反应曲线，特别是估计最大耐受量(MTD)。在这篇文章中，我们采用贝叶斯方法来对MTD进行推断。利用广义先验，我们得到了MTD的后验分布，并研究了它的性质。我们还解决了为以特定剂量水平进入研究的新患者提供最新毒性风险评估的问题。这些评估将有助于决定研究、管理和道德方面的问题。我们的分析特别注意了推论和风险评估对剂量-反应关系的先验选择和模型选择的敏感性。
Phase I clinical trials are conducted to determine the dose-response curve of a new drug with respect to toxic side effects and, in particular, to estimate the maximum tolerated dose (MTD). In this paper we take a Bayesian approach to the problem of making inferences about the MTD. Working with broad classes of priors, we obtain the posterior distribution of the MTD and study its properties. We also address the question of providing updated assessments of the risk of toxicity for new patients entering the study at a specific dose level. These assessments would be useful in deciding issues of study management and ethics. Our analysis pays particular attention to the sensitivity of the inferences and risk assessments to the choice of prior and the choice of model for the dose-response relationship.