Multiple hypotheses testing procedures in clinical trials and genomic studies.

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.