Dynamic Treatment Regimes

Statistical Methods for Dynamic Treatment Regimes shares state of the art of statistical methods developed to address questions of estimation and inference for dynamic treatment regimes, a branch of personalized medicine. This volume demonstrates these methods with their conceptual underpinnings and illustration through analysis of real and simulated data. These methods are immediately applicable to the practice of personalized medicine, which is a medical paradigm that emphasizes the systematic use of individual patient information to optimize patient health care. This is the first single source to provide an overview of methodology and results gathered from journals, proceedings, and technical reports with the goal of orienting researchers to the field. The first chapter establishes context for the statistical reader in the landscape of personalized medicine. Readers need only have familiarity with elementary calculus, linear algebra, and basic large-sample theory to use this text. Throughout the text, authors direct readers to available code or packages in different statistical languages to facilitate implementation. In cases where code does not already exist, the authors provide analytic approaches in sufficient detail that any researcher with knowledge of statistical programming could implement the methods from scratch. This will be an important volume for a wide range of researchers, including statisticians, epidemiologists, medical researchers, and machine learning researchers interested in medical applications. Advanced graduate students in statistics and biostatistics will also find material in Statistical Methods for Dynamic Treatment Regimes to be a critical part of their studies.

Dynamic Treatment Regimes: Statistical Methods for Precision Medicine provides a comprehensive introduction to statistical methodology for the evaluation and discovery of dynamic treatment regimes from data. Researchers and graduate students in statistics, data science, and related quantitative disciplines with a background in probability and statistical inference and popular statistical modeling techniques will be prepared for further study of this rapidly evolving field. A dynamic treatment regime is a set of sequential decision rules, each corresponding to a key decision point in a disease or disorder process, where each rule takes as input patient information and returns the treatment option he or she should receive. Thus, a treatment regime formalizes how a clinician synthesizes patient information and selects treatments in practice. Treatment regimes are of obvious relevance to precision medicine, which involves tailoring treatment selection to patient characteristics in an evidence-based way. Of critical importance to precision medicine is estimation of an optimal treatment regime, one that, if used to select treatments for the patient population, would lead to the most beneficial outcome on average. Key methods for estimation of an optimal treatment regime from data are motivated and described in detail. A dedicated companion website presents full accounts of application of the methods using a comprehensive R package developed by the authors. The authors’ website www.dtr-book.com includes updates, corrections, new papers, and links to useful websites.

Personalized medicine is a medical paradigm that emphasizes systematic use of individual patient information to optimize that patient's health care, particularly in managing chronic conditions and treating cancer. In the statistical literature, sequential decision making is known as an adaptive treatment strategy (ATS) or a dynamic treatment regime (DTR). The field of DTRs emerges at the interface of statistics, machine learning, and biomedical science to provide a data-driven framework for precision medicine. The authors provide a learning-by-seeing approach to the development of ATSs, aimed at a broad audience of health researchers. All estimation procedures used are described in sufficient heuristic and technical detail so that less quantitative readers can understand the broad principles underlying the approaches. At the same time, more quantitative readers can implement these practices. This book provides the most up-to-date summary of the current state of the statistical research in personalized medicine; contains chapters by leaders in the area from both the statistics and computer sciences fields; and also contains a range of practical advice, introductory and expository materials, and case studies.

This book illustrates numerous statistical practices that are commonly used by medical researchers, but which have severe flaws that may not be obvious. For each example, it provides one or more alternative statistical methods that avoid misleading or incorrect inferences being made. The technical level is kept to a minimum to make the book accessible to non-statisticians. At the same time, since many of the examples describe methods used routinely by medical statisticians with formal statistical training, the book appeals to a broad readership in the medical research community.

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. It presents a scientific roadmap to translate real-world data science applications into formal statistical estimation problems by using the general template of targeted maximum likelihood estimators. These targeted machine learning algorithms estimate quantities of interest while still providing valid inference. Targeted learning methods within data science area critical component for solving scientific problems in the modern age. The techniques can answer complex questions including optimal rules for assigning treatment based on longitudinal data with time-dependent confounding, as well as other estimands in dependent data structures, such as networks. Included in Targeted Learning in Data Science are demonstrations with soft ware packages and real data sets that present a case that targeted learning is crucial for the next generation of statisticians and data scientists. Th is book is a sequel to the first textbook on machine learning for causal inference, Targeted Learning, published in 2011. Mark van der Laan, PhD, is Jiann-Ping Hsu/Karl E. Peace Professor of Biostatistics and Statistics at UC Berkeley. His research interests include statistical methods in genomics, survival analysis, censored data, machine learning, semiparametric models, causal inference, and targeted learning. Dr. van der Laan received the 2004 Mortimer Spiegelman Award, the 2005 Van Dantzig Award, the 2005 COPSS Snedecor Award, the 2005 COPSS Presidential Award, and has graduated over 40 PhD students in biostatistics and statistics. Sherri Rose, PhD, is Associate Professor of Health Care Policy (Biostatistics) at Harvard Medical School. Her work is centered on developing and integrating innovative statistical approaches to advance human health. Dr. Rose’s methodological research focuses on nonparametric machine learning for causal inference and prediction. She co-leads the Health Policy Data Science Lab and currently serves as an associate editor for the Journal of the American Statistical Association and Biostatistics.

Reliably optimizing a new treatment in humans is a critical first step in clinical evaluation since choosing a suboptimal dose or schedule may lead to failure in later trials. At the same time, if promising preclinical results do not translate into a real treatment advance, it is important to determine this quickly and terminate the clinical evaluation process to avoid wasting resources. Bayesian Designs for Phase I–II Clinical Trials describes how phase I–II designs can serve as a bridge or protective barrier between preclinical studies and large confirmatory clinical trials. It illustrates many of the severe drawbacks with conventional methods used for early-phase clinical trials and presents numerous Bayesian designs for human clinical trials of new experimental treatment regimes. Written by research leaders from the University of Texas MD Anderson Cancer Center, this book shows how Bayesian designs for early-phase clinical trials can explore, refine, and optimize new experimental treatments. It emphasizes the importance of basing decisions on both efficacy and toxicity.

Cancer Clinical Trials: Current and Controversial Issues in Design and Analysis provides statisticians with an understanding of the critical challenges currently encountered in oncology trials. Well-known statisticians from academic institutions, regulatory and government agencies (such as the U.S. FDA and National Cancer Institute), and the pharmaceutical industry share their extensive experiences in cancer clinical trials and present examples taken from actual trials. The book covers topics that are often perplexing and sometimes controversial in cancer clinical trials. Most of the issues addressed are also important for clinical trials in other settings. After discussing general topics, the book focuses on aspects of early and late phase clinical trials. It also explores personalized medicine, including biomarker-based clinical trials, adaptive clinical trial designs, and dynamic treatment regimes.

This volume contains a selection of papers presented at the Second Seattle Symposium in Biostatistics: Analysis of Correlated Data. The symposium was held in 2000 to celebrate the 30th anniversary of the University of Washington School of Public Health and Community Medicine. It featured keynote lectures by Norman Breslow, David Cox and Ross Prentice and 16 invited presentations by other prominent researchers. The papers contained in this volume encompass recent methodological advances in several important areas, such as longitudinal data, multivariate failure time data and genetic data, as well as innovative applications of the existing theory and methods. This volume is a valuable reference for researchers and practitioners in the field of correlated data analysis.