Mark J. van der Laan - Böcker

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.

During the last decades, there has been an explosion in computation and information technology. This development comes with an expansion of complex observational studies and clinical trials in a variety of fields such as medicine, biology, epidemiology, sociology, and economics among many others, which involve collection of large amounts of data on subjects or organisms over time. The goal of such studies can be formulated as estimation of a finite dimensional parameter of the population distribution corresponding to the observed time- dependent process. Such estimation problems arise in survival analysis, causal inference and regression analysis. This book provides a fundamental statistical framework for the analysis of complex longitudinal data. It provides the first comprehensive description of optimal estimation techniques based on time-dependent data structures subject to informative censoring and treatment assignment in so called semiparametric models. Semiparametric models are particularly attractive since they allow the presence of large unmodeled nuisance parameters.These techniques include estimation of regression parameters in the familiar (multivariate) generalized linear regression and multiplicative intensity models. They go beyond standard statistical approaches by incorporating all the observed data to allow for informative censoring, to obtain maximal efficiency, and by developing estimators of causal effects. It can be used to teach masters and Ph.D. students in biostatistics and statistics and is suitable for researchers in statistics with a strong interest in the analysis of complex longitudinal data.

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.

During the last decades, there has been an explosion in computation and information technology. This development comes with an expansion of complex observational studies and clinical trials in a variety of fields such as medicine, biology, epidemiology, sociology, and economics among many others, which involve collection of large amounts of data on subjects or organisms over time. The goal of such studies can be formulated as estimation of a finite dimensional parameter of the population distribution corresponding to the observed time- dependent process. Such estimation problems arise in survival analysis, causal inference and regression analysis. This book provides a fundamental statistical framework for the analysis of complex longitudinal data. It provides the first comprehensive description of optimal estimation techniques based on time-dependent data structures subject to informative censoring and treatment assignment in so called semiparametric models. Semiparametric models are particularly attractive since they allow the presence of large unmodeled nuisance parameters. These techniques include estimation of regression parameters in the familiar (multivariate) generalized linear regression and multiplicative intensity models. They go beyond standard statistical approaches by incorporating all the observed data to allow for informative censoring, to obtain maximal efficiency, and by developing estimators of causal effects. It can be used to teach masters and Ph.D. students in biostatistics and statistics and is suitable for researchers in statistics with a strong interest in the analysis of complex longitudinal data.

Parts II-IX handle complex data structures and topics applied researchers will immediately recognize from their own research, including time-to-event outcomes, direct and indirect effects, positivity violations, case-control studies, censored data, longitudinal data, and genomic studies.

Parts II-IX handle complex data structures and topics applied researchers will immediately recognize from their own research, including time-to-event outcomes, direct and indirect effects, positivity violations, case-control studies, censored data, longitudinal data, and genomic studies.

This textbook for graduate students in statistics, data science, and public health deals with the practical challenges that come with big, complex, and dynamic data.