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Multiple Hypotheses Testing Procedures in Clinical Trials and Genomic Studies

机译:临床试验和基因组研究中的多重假设检验程序

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We review and compare multiple hypothesis testing procedures used in clinical trials and those in genomic studies. Clinical trials often employ global tests, which draw an overall conclusion for all the hypotheses, such as SUM test, Two-Step test, Approximate Likelihood Ratio test (ALRT), Intersection-Union Test (IUT), and MAX test. The SUM and Two-Step tests are most powerful under homogeneous treatment effects, while the ALRT and MAX test are robust in cases with non-homogeneous treatment effects. Furthermore, the ALRT is robust to unequal sample sizes in testing different hypotheses. In genomic studies, stepwise procedures are used to draw marker-specific conclusions and control family wise error rate (FWER) or false discovery rate (FDR). FDR refers to the percent of false positives among all significant results and is preferred over FWER in screening high-dimensional genomic markers due to its interpretability. In cases where correlations between test statistics cannot be ignored, Westfall-Young resampling method generates the joint distribution of P-values under the null and maintains their correlation structure. Finally, the GWAS data from a clinical trial searching for SNPs associated with nephropathy among Type 1 diabetic patients are used to illustrate various procedures.
机译:我们回顾并比较了临床试验和基因组研究中使用的多种假设检验程序。临床试验通常采用整体测试,这些测试针对所有假设得出总体结论,例如SUM测试,两步测试,近似似然比测试(ALRT),交叉口联合测试(IUT)和MAX测试。在同质治疗效果下,SUM和两步测试功能最强大,而在具有非同质治疗效果的情况下,ALRT和MAX测试则非常可靠。此外,在测试不同的假设时,ALRT对于不相等的样本大小具有鲁棒性。在基因组研究中,采用逐步程序得出标记特异性的结论,并控制家族的错误率(FWER)或错误发现率(FDR)。 FDR是指所有重要结果中假阳性的百分比,由于其可解释性,在筛选高维基因组标记时,FDR优于FWER。在无法忽略测试统计数据之间的相关性的情况下,Westfall-Young重采样方法会在零值以下生成P值的联合分布,并保持其相关性结构。最后,从临床试验中搜索与1型糖尿病患者的肾病相关的SNP的GWAS数据用于说明各种程序。

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