How to use frailtypack for validating failure-time surrogate endpoints using individual patient data from meta-analyses of randomized controlled trials
How to use frailtypack for validating failure-time surrogate endpoints using individual patient data from meta-analyses of randomized controlled trials
复制标题
如何使用 frailtypack 使用随机对照试验荟萃分析中的个体患者数据来验证失败时间替代终点
DOI：
10.1371/journal.pone.0228098
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
V. Rondeau
中科院分区：
文献类型：
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作者：
C. Sofeu;V. Rondeau
背景与目的有效替代终点的使用可以加速III期临床试验的进展。已经提出了许多验证方法，其中最流行的是基于两步分析策略的荟萃分析。对于两个失效时间终点，通常考虑两个相关性测量，个体水平的Kendall τ和试验水平的校正R2（adjRtrial2）。然而，adjRtrial2并不总是可用的，主要是由于模型估计的限制。最近，我们提出了一个一步验证方法的基础上联合脆弱模型，目的是减少估计问题和估计偏差的代孕评价标准。该模型具有较强的鲁棒性，在仿真研究中获得了满意的结果。本研究旨在推广这种新的替代终点验证方法，使该方法在一个用户友好的R包。方法我们在frailtypack R包中提供了许多工具，包括更灵活的功能，用于使用多个随机临床试验的数据验证候选替代终点。结果我们实现了替代阈值效应，它与Rtrial2结合使用，以决定替代终点的有效性。由于frailtypack，还可以使用在替代终点上观察到的治疗效果来预测新试验中对真实终点的治疗效果。留一交叉验证可用于评估使用联合代理模型的预测的准确性。其他工具包括数据生成、模拟研究和图形表示。我们用真实的数据和模拟数据说明了新函数的使用。结论本文提出了新的有吸引力的和良好的开发工具，验证故障时间替代端点。
Background and Objective The use of valid surrogate endpoints can accelerate the development of phase III trials. Numerous validation methods have been proposed with the most popular used in a context of meta-analyses, based on a two-step analysis strategy. For two failure time endpoints, two association measures are usually considered, Kendall’s τ at individual level and adjusted R2 (adjRtrial2) at trial level. However, adjRtrial2 is not always available mainly due to model estimation constraints. More recently, we proposed a one-step validation method based on a joint frailty model, with the aim of reducing estimation issues and estimation bias on the surrogacy evaluation criteria. The model was quite robust with satisfactory results obtained in simulation studies. This study seeks to popularize this new surrogate endpoints validation approach by making the method available in a user-friendly R package. Methods We provide numerous tools in the frailtypack R package, including more flexible functions, for the validation of candidate surrogate endpoints using data from multiple randomized clinical trials. Results We implemented the surrogate threshold effect which is used in combination with Rtrial2 to make decisions concerning the validity of the surrogate endpoints. It is also possible thanks to frailtypack to predict the treatment effect on the true endpoint in a new trial using the treatment effect observed on the surrogate endpoint. The leave-one-out cross-validation is available for assessing the accuracy of the prediction using the joint surrogate model. Other tools include data generation, simulation study and graphic representations. We illustrate the use of the new functions with both real data and simulated data. Conclusion This article proposes new attractive and well developed tools for validating failure time surrogate endpoints.
(2)基于身体部位特征点和形状信息的模型步态认证研究
DOI：
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发表时间：
2015
期刊：
影响因子：
--
作者：
井元大輔;黒沢健至;土屋兼一;黒木健郎;秋葉教充;角田英俊
通讯作者：
角田英俊