A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial.
A dose-finding design for dual-agent trials with patient-specific doses for one agent with application to an opiate detoxification trial.
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DOI：
10.1002/pst.2181
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发表时间：
2022-03
影响因子：
1.5
通讯作者：
Jaki T
中科院分区：
文献类型：
--
作者：
Mozgunov P;Cro S;Lingford-Hughes A;Paterson LM;Jaki T
人们对研究几种治疗组合的早期剂量发现临床试验越来越感兴趣。虽然这种设置的大多数剂量发现设计是为肿瘤学试验提出的，但相应的设计在其他治疗领域也是必不可少的。此外，人们越来越认识到推荐针对患者的剂量/组合，而不是推荐给所有晚期患者的单一靶点，而不管他们的特征如何。在本文中，我们提出了一个剂量发现设计的双重药物联合试验的动机是阿片类药物解毒试验。该试验的显著特征是，一种化合物的（连续）剂量由临床医生外部确定，并且对每个患者都是个体化的。试验的目的是确定给药函数，为每个患者推荐第二种化合物的最佳剂量。通过模拟研究，我们发现所提出的设计结果具有较高的个人剂量推荐精度，并且对模型错误规范和外部定义剂量分布的假设具有鲁棒性。
There is a growing interest in early phase dose-finding clinical trials studying combinations of several treatments. While the majority of dose finding designs for such setting were proposed for oncology trials, the corresponding designs are also essential in other therapeutic areas. Furthermore, there is increased recognition of recommending the patient-specific doses/combinations, rather than a single target one that would be recommended to all patients in later phases regardless of their characteristics. In this paper, we propose a dose-finding design for a dual-agent combination trial motivated by an opiate detoxification trial. The distinguishing feature of the trial is that the (continuous) dose of one compound is defined externally by the clinicians and is individual for every patient. The objective of the trial is to define the dosing function that for each patient would recommend the optimal dosage of the second compound. Via a simulation study, we have found that the proposed design results in high accuracy of individual dose recommendation and is robust to the model misspecification and assumptions on the distribution of externally defined doses.
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