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.
翻译:确定有效代用代用标记的主要好处是能够在今后试验时使用它来测试治疗效果,缩短跟踪时间或降低成本。然而,以前的工作表明,代用标记的使用可能存在异质性。当存在这种异质性时,使用代用代用标记测试治疗效果的现有方法可能会导致对治疗效果得出不准确的结论,特别是当新研究中的病人口与评估代用标记的效用所使用的研究有不同的特点组合时。我们在本文件中,我们开发了一种治疗效果的新测试,使用代用标记信息说明代用标记的异质性。我们将我们的测试程序与使用主要结果信息(古老标准)和使用代用标记信息的测试测试测试方法的测试方法相比较,但忽略了异质性性性。我们展示了我们的方法的有效性,并得出了我们估算和差异估计的缺损性特性。我们用代用代用代用标记的代用标记信息对治疗方法的定置样品特性进行了测试,并用测试了我们的临床试验方法,从测试了一种测试模型的方法来说明我们的临床治疗方法。