A benchmark for dose finding studies with continuous outcomes
A benchmark for dose finding studies with continuous outcomes
复制标题
DOI：
10.1093/biostatistics/kxy045
复制
发表时间：
2020-04-01
期刊：
影响因子：
2.1
通讯作者：
Paoletti, Xavier
中科院分区：
文献类型：
--
作者：
Mozgunov, Pavel;Jaki, Thomas;Paoletti, Xavier
评估任何设计性能的一个重要工具是 O'Quigley 等人提出的最佳基准（2002 年。剂量发现研究中的非参数优化设计。生物统计学 3, 51-56），它提供了给定情况下设计性能的上限。原始基准只能应用于具有二元终点的剂量探索研究。然而，人们对涉及连续结果的剂量探索研究越来越感兴趣，但尚未制定此类研究的基准。我们表明，原始基准及其由 Cheung 的扩展（2014 年。复杂剂量发现研究的简单基准。生物识别 70, 389-397），当从不同的角度来看时，可以推广到具有多个离散和连续结果的各种设置。我们说明并比较了具有连续毒性终点的剂量发现 I 期临床试验和具有二元毒性和连续疗效终点的 I/II 期试验中基准的性能。我们表明，所提出的基准在这些情况下提供了准确的上限，并作为评估设计的强大工具。
An important tool to evaluate the performance of any design is an optimal benchmark proposed by O'Quigley and others (2002. Non-parametric optimal design in dose finding studies. Biostatistics 3, 51-56) that provides an upper bound on the performance of a design under a given scenario. The original benchmark can only be applied to dose finding studies with a binary endpoint. However, there is a growing interest in dose finding studies involving continuous outcomes, but no benchmark for such studies has been developed. We show that the original benchmark and its extension by Cheung (2014. Simple benchmark for complex dose finding studies. Biometrics 70, 389-397), when looked at from a different perspective, can be generalized to various settings with several discrete and continuous outcomes. We illustrate and compare the benchmark's performance in the setting of a dose finding Phase I clinical trial with a continuous toxicity endpoint and a Phase I/II trial with binary toxicity and continuous efficacy endpoints. We show that the proposed benchmark provides an accurate upper bound in these contexts and serves as a powerful tool for evaluating designs.