Some New Developments on Multiple Testing Procedures

Some New Developments on Multiple Testing Procedures
Author: Lilun Du
Publisher:
Total Pages: 134
Release: 2015
Genre:
ISBN:

In the context of large-scale multiple testing, hypotheses are often accompanied with certain prior information. In chapter 2, we present a single-index modulated multiple testing procedure, which maintains control of the false discovery rate while incorporating prior information, by assuming the availability of a bivariate p-value for each hypothesis. To find the optimal rejection region for the bivariate p-value, we propose a criteria based on the ratio of probability density functions of the bivariate p-value under the true null and non-null. This criteria in the bivariate normal setting further motivates us to project the bivariate p-value to a single index p-value, for a wide range of directions. The true null distribution of the single index p-value is estimated via parametric and nonparametric approaches, leading to two procedures for estimating and controlling the false discovery rate. To derive the optimal projection direction, we propose a new approach based on power comparison, which is further shown to be consistent under some mild conditions. Multiple testing based on chi-squared test statistics is commonly used in many scientific fields such as genomics research and brain imaging studies. However, the challenges associated with designing a formal testing procedure when there exists a general dependence structure across the chi-squared test statistics have not been well addressed. In chapter 3, we propose a Factor Connected procedure to fill in this gap. We first adopt a latent factor structure to construct a testing framework for approximating the false discovery proportion (FDP) for a large number of highly correlated chi-squared test statistics with finite degrees of freedom k. The testing framework is then connected to simultaneously testing k linear constraints in a large dimensional linear factor model involved with some observable and unobservable common factors, resulting in a consistent estimator of FDP based on the associated unadjusted p-values.

Multiple Testing Procedures with Applications to Genomics

Multiple Testing Procedures with Applications to Genomics
Author: Sandrine Dudoit
Publisher: Springer Science & Business Media
Total Pages: 611
Release: 2007-12-18
Genre: Science
ISBN: 0387493174

This book establishes the theoretical foundations of a general methodology for multiple hypothesis testing and discusses its software implementation in R and SAS. These are applied to a range of problems in biomedical and genomic research, including identification of differentially expressed and co-expressed genes in high-throughput gene expression experiments; tests of association between gene expression measures and biological annotation metadata; sequence analysis; and genetic mapping of complex traits using single nucleotide polymorphisms. The procedures are based on a test statistics joint null distribution and provide Type I error control in testing problems involving general data generating distributions, null hypotheses, and test statistics.

Multiple Testing Problems in Pharmaceutical Statistics

Multiple Testing Problems in Pharmaceutical Statistics
Author: Alex Dmitrienko
Publisher: CRC Press
Total Pages: 323
Release: 2009-12-08
Genre: Mathematics
ISBN: 1584889853

Useful Statistical Approaches for Addressing Multiplicity IssuesIncludes practical examples from recent trials Bringing together leading statisticians, scientists, and clinicians from the pharmaceutical industry, academia, and regulatory agencies, Multiple Testing Problems in Pharmaceutical Statistics explores the rapidly growing area of multiple c

New Developments in Multiple Testing and Multivariate Testing for High-dimensional Data

New Developments in Multiple Testing and Multivariate Testing for High-dimensional Data
Author: Zongliang Hu
Publisher:
Total Pages: 171
Release: 2018
Genre: Analysis of covariance
ISBN:

This thesis aims to develop some new and novel methods in advancing multivariate testing and multiple testing for high-dimensional small sample size data. In Chapter 2, we propose a likelihood ratio test framework for testing normal mean vectors in high-dimensional data under two common scenarios: the one-sample test and the two-sample test with equal covariance matrices. We derive the test statistics under the assumption that the covariance matrices follow a diagonal matrix structure. In comparison with the diagonal Hotelling's tests, our proposed test statistics display some interesting characteristics. In particular, they are a summation of the log-transformed squared t-statistics rather than a direct summation of those components. More importantly, to derive the asymptotic normality of our test statistics under the null and local alternative hypotheses, we do not need the requirement that the covariance matrices follow a diagonal matrix structure. As a consequence, our proposed test methods are very flexible and readily applicable in practice. Monte Carlo simulations and a real data analysis are also carried out to demonstrate the advantages of the proposed methods. In Chapter 3, we propose a pairwise Hotelling's method for testing high-dimensional mean vectors. The new test statistics make a compromise on whether using all the correlations or completely abandoning them. To achieve the goal, we perform a screening procedure, pick up the paired covariates with strong correlations, and construct a classical Hotelling's statistic for each pair. While for the individual covariates without strong correlations with others, we apply squared t statistics to account for their respective contributions to the multivariate testing problem. As a consequence, our proposed test statistics involve a combination of the collected pairwise Hotelling's test statistics and squared t statistics. The asymptotic normality of our test statistics under the null and local alternative hypotheses are also derived under some regularity conditions. Numerical studies and two real data examples demonstrate the efficacy of our pairwise Hotelling's test. In Chapter 4, we propose a regularized t distribution and also explore its applications in multiple testing. The motivation of this topic dates back to microarray studies, where the expression levels of thousands of genes are measured simultaneously by the microarray technology. To identify genes that are differentially expressed between two or more groups, one needs to conduct hypothesis test for each gene. However, as microarray experiments are often with a small number of replicates, Student's t-tests using the sample means and standard deviations may suffer a low power for detecting differentially expressed genes. To overcome this problem, we first propose a regularized t distribution and derive its statistical properties including the probability density function and the moments. The noncentral regularized t distribution is also introduced for the power analysis. To demonstrate the usefulness of the proposed test, we apply the regularized t distribution to the gene expression detection problem. Simulation studies and two real data examples show that the regularized t-test outperforms the existing tests including Student's t-test and the Bayesian t-test in a wide range of settings, in particular when the sample size is small.

Resampling-Based Multiple Testing

Resampling-Based Multiple Testing
Author: Peter H. Westfall
Publisher: John Wiley & Sons
Total Pages: 382
Release: 1993-01-12
Genre: Mathematics
ISBN: 9780471557616

Combines recent developments in resampling technology (including the bootstrap) with new methods for multiple testing that are easy to use, convenient to report and widely applicable. Software from SAS Institute is available to execute many of the methods and programming is straightforward for other applications. Explains how to summarize results using adjusted p-values which do not necessitate cumbersome table look-ups. Demonstrates how to incorporate logical constraints among hypotheses, further improving power.

Applications and Power Analysis of New Multiple Testing Procedures Based on the Covering Principle

Applications and Power Analysis of New Multiple Testing Procedures Based on the Covering Principle
Author: Yu Zhang
Publisher:
Total Pages: 71
Release: 2021
Genre: Multiple comparisons (Statistics)
ISBN:

Multiple comparison tests are quite prevalent in clinical trials to increase efficiency and the chance of finding treatment or drug effects. However, making multiple comparisons will lead to the potential inflation of the Type I error rate. How well one test procedure controls the rate of false-positive conclusions becomes the main concern nowadays. A novel method named Covering Principle has been proposed recently. It provides a new approach to designing multiple testing procedures from the angle of rejection regions in the sample space, rather than in the parameter space, which uses in the methods based on the closed testing and partitioning principle. This paper presented several cases studies and a simulation study using Holm's, Fixed and Fallback based on the Covering Principle. Meanwhile, the power comparison results between the Covering Principle and the graphical method are exhibited and analyzed in this paper.

Simultaneous Statistical Inference

Simultaneous Statistical Inference
Author: Thorsten Dickhaus
Publisher: Springer Science & Business Media
Total Pages: 182
Release: 2014-01-23
Genre: Science
ISBN: 3642451829

This monograph will provide an in-depth mathematical treatment of modern multiple test procedures controlling the false discovery rate (FDR) and related error measures, particularly addressing applications to fields such as genetics, proteomics, neuroscience and general biology. The book will also include a detailed description how to implement these methods in practice. Moreover new developments focusing on non-standard assumptions are also included, especially multiple tests for discrete data. The book primarily addresses researchers and practitioners but will also be beneficial for graduate students.

Group Sequential Methods with Applications to Clinical Trials

Group Sequential Methods with Applications to Clinical Trials
Author: Christopher Jennison
Publisher: CRC Press
Total Pages: 416
Release: 1999-09-15
Genre: Mathematics
ISBN: 9781584888581

Group sequential methods answer the needs of clinical trial monitoring committees who must assess the data available at an interim analysis. These interim results may provide grounds for terminating the study-effectively reducing costs-or may benefit the general patient population by allowing early dissemination of its findings. Group sequential methods provide a means to balance the ethical and financial advantages of stopping a study early against the risk of an incorrect conclusion. Group Sequential Methods with Applications to Clinical Trials describes group sequential stopping rules designed to reduce average study length and control Type I and II error probabilities. The authors present one-sided and two-sided tests, introduce several families of group sequential tests, and explain how to choose the most appropriate test and interim analysis schedule. Their topics include placebo-controlled randomized trials, bio-equivalence testing, crossover and longitudinal studies, and linear and generalized linear models. Research in group sequential analysis has progressed rapidly over the past 20 years. Group Sequential Methods with Applications to Clinical Trials surveys and extends current methods for planning and conducting interim analyses. It provides straightforward descriptions of group sequential hypothesis tests in a form suited for direct application to a wide variety of clinical trials. Medical statisticians engaged in any investigations planned with interim analyses will find this book a useful and important tool.

Handbook of Multiple Comparisons

Handbook of Multiple Comparisons
Author: Xinping Cui
Publisher: CRC Press
Total Pages: 418
Release: 2021-11-18
Genre: Mathematics
ISBN: 0429633882

Written by experts that include originators of some key ideas, chapters in the Handbook of Multiple Testing cover multiple comparison problems big and small, with guidance toward error rate control and insights on how principles developed earlier can be applied to current and emerging problems. Some highlights of the coverages are as follows. Error rate control is useful for controlling the incorrect decision rate. Chapter 1 introduces Tukey's original multiple comparison error rates and point to how they have been applied and adapted to modern multiple comparison problems as discussed in the later chapters. Principles endure. While the closed testing principle is more familiar, Chapter 4 shows the partitioning principle can derive confidence sets for multiple tests, which may become important as the profession goes beyond making decisions based on p-values. Multiple comparisons of treatment efficacy often involve multiple doses and endpoints. Chapter 12 on multiple endpoints explains how different choices of endpoint types lead to different multiplicity adjustment strategies, while Chapter 11 on the MCP-Mod approach is particularly useful for dose-finding. To assess efficacy in clinical trials with multiple doses and multiple endpoints, the reader can see the traditional approach in Chapter 2, the Graphical approach in Chapter 5, and the multivariate approach in Chapter 3. Personalized/precision medicine based on targeted therapies, already a reality, naturally leads to analysis of efficacy in subgroups. Chapter 13 draws attention to subtle logical issues in inferences on subgroups and their mixtures, with a principled solution that resolves these issues. This chapter has implication toward meeting the ICHE9R1 Estimands requirement. Besides the mere multiple testing methodology itself, the handbook also covers related topics like the statistical task of model selection in Chapter 7 or the estimation of the proportion of true null hypotheses (or, in other words, the signal prevalence) in Chapter 8. It also contains decision-theoretic considerations regarding the admissibility of multiple tests in Chapter 6. The issue of selected inference is addressed in Chapter 9. Comparison of responses can involve millions of voxels in medical imaging or SNPs in genome-wide association studies (GWAS). Chapter 14 and Chapter 15 provide state of the art methods for large scale simultaneous inference in these settings.