论文标题
使用具有异质效用的替代物测试治疗效果
Using a Surrogate with Heterogeneous Utility to Test for a Treatment Effect
论文作者
论文摘要
确定有效的替代标记物的主要好处是能够在以后的试验中使用它来测试以较短的随访时间或更少的成本来测试治疗效果。但是，以前的工作表明了替代标记的效用中潜在的异质性。当存在这种异质性时，使用替代物来测试治疗效果的现有方法，同时忽略这种异质性可能会导致对治疗效果的结论，尤其是当新研究中的患者人群与用于评估替代标记效用的研究的特征不同时。在本文中，我们使用替代标记信息为替代效用的异质性而开发了一种针对治疗效果的新型测试。我们将测试程序与使用主要结果信息（黄金标准）和使用替代标记信息但忽略异质性的测试进行比较。我们证明了我们的方法的有效性，并得出了估计量和方差估计值的渐近特性。仿真研究检查了我们的测试程序的有限样本特性，并证明我们提出的方法何时可以优于忽略异质性的测试方法。我们使用来自AIDS临床试验的数据说明了我们的方法，以使用CD4计数作为RNA的替代标记来测试治疗效果。
The primary benefit of identifying a valid surrogate marker is the ability to use it in a future trial to test for a treatment effect with shorter follow-up time or less cost. However, previous work has demonstrated potential heterogeneity in the utility of a surrogate marker. When such heterogeneity exists, existing methods that use the surrogate to test for a treatment effect while ignoring this heterogeneity may lead to inaccurate conclusions about the treatment effect, particularly when the patient population in the new study has a different mix of characteristics than the study used to evaluate the utility of the surrogate marker. In this paper, we develop a novel test for a treatment effect using surrogate marker information that accounts for heterogeneity in the utility of the surrogate. We compare our testing procedure to a test that uses primary outcome information (gold standard) and a test that uses surrogate marker information, but ignores heterogeneity. We demonstrate the validity of our approach and derive the asymptotic properties of our estimator and variance estimates. Simulation studies examine the finite sample properties of our testing procedure and demonstrate when our proposed approach can outperform the testing approach that ignores heterogeneity. We illustrate our methods using data from an AIDS clinical trial to test for a treatment effect using CD4 count as a surrogate marker for RNA.
