Chen Bingshu E, Kramer Joan L, Greene Mark H, Rosenberg Philip S
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20852, USA.
Biometrics. 2008 Mar;64(1):172-9. doi: 10.1111/j.1541-0420.2007.00868.x. Epub 2007 Aug 3.
We develop methods for competing risks analysis when individual event times are correlated within clusters. Clustering arises naturally in clinical genetic studies and other settings. We develop a nonparametric estimator of cumulative incidence, and obtain robust pointwise standard errors that account for within-cluster correlation. We modify the two-sample Gray and Pepe-Mori tests for correlated competing risks data, and propose a simple two-sample test of the difference in cumulative incidence at a landmark time. In simulation studies, our estimators are asymptotically unbiased, and the modified test statistics control the type I error. The power of the respective two-sample tests is differentially sensitive to the degree of correlation; the optimal test depends on the alternative hypothesis of interest and the within-cluster correlation. For purposes of illustration, we apply our methods to a family-based prospective cohort study of hereditary breast/ovarian cancer families. For women with BRCA1 mutations, we estimate the cumulative incidence of breast cancer in the presence of competing mortality from ovarian cancer, accounting for significant within-family correlation.
当个体事件发生时间在聚类内相关时,我们开发了用于竞争风险分析的方法。聚类在临床遗传学研究和其他场景中自然出现。我们开发了累积发病率的非参数估计器,并获得了考虑聚类内相关性的稳健逐点标准误差。我们针对相关竞争风险数据修改了两样本Gray检验和Pepe-Mori检验,并提出了在一个标志性时间点累积发病率差异的简单两样本检验。在模拟研究中,我们的估计器渐近无偏,并且修改后的检验统计量控制了I型错误。各自两样本检验的功效对相关程度的敏感度不同;最优检验取决于感兴趣的备择假设和聚类内相关性。为了说明目的,我们将我们的方法应用于一项基于家庭的遗传性乳腺癌/卵巢癌家庭前瞻性队列研究。对于携带BRCA1突变的女性,我们估计了在存在卵巢癌竞争死亡率的情况下乳腺癌的累积发病率,同时考虑了家庭内的显著相关性。