The 2-sample problem for failure rates depending on a continuous mark: an application to vaccine efficacy
The 2-sample problem for failure rates depending on a continuous mark: an application to vaccine efficacy
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DOI：
10.1093/biostatistics/kxm028
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发表时间：
2008-04-01
期刊：
影响因子：
2.1
通讯作者：
Sun, Yanqing
中科院分区：
文献类型：
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作者：
Gilbert, Peter B.;Mckeague, Ian W.;Sun, Yanqing
艾滋病毒疫苗预防感染的效果可能取决于暴露病毒的基因变异。本文讨论了使用感染疫苗有效性试验参与者的HIV序列数据的问题，以(1)比忽略序列数据的程序更有效地测试疫苗有效性，以及(2)评估疫苗有效性对感染HIV毒株与疫苗中包含的HIV毒株的差异的依赖性。由于每个HIV基因组中的数百个氨基酸位点被测序，自然会将遗传差异视为伴随每次失败(感染)时间的连续标记变量。问题(1)和(2)然后可以通过测试疫苗组和安慰剂组的标记特定危险函数的比率是统一的还是独立于标记来解决。我们为这些零假设开发了非参数和半参数检验，并开发了用于估计特定于标记的相对风险的非参数技术。建立了该过程的渐近性质。此外，这些方法在模拟中进行了研究，并应用于在第一次HIV疫苗疗效试验中收集的HIV基因序列数据。
The efficacy of an HIV vaccine to prevent infection is likely to depend on the genetic variation of the exposing virus. This paper addresses the problem of using data on the HIV sequences that infect vaccine efficacy trial participants to (1) test for vaccine efficacy more powerfully than procedures that ignore the sequence data and (2) evaluate the dependence of vaccine efficacy on the divergence of infecting HIV strains from the HIV strain that is contained in the vaccine. Because hundreds of amino acid sites in each HIV genome are sequenced, it is natural to treat the genetic divergence as a continuous mark variable that accompanies each failure (infection) time. Problems (1) and (2) can then be approached by testing whether the ratio of the mark-specific hazard functions for the vaccine and placebo groups is unity or independent of the mark. We develop nonparametric and semiparametric tests for these null hypotheses and nonparametric techniques for estimating the mark-specific relative risks. The asymptotic properties of the procedures are established. In addition, the methods are studied in simulations and are applied to HIV genetic sequence data collected in the first HIV vaccine efficacy trial.