Monte Carlo Simulation for the Pharmaceutical Industry

Author: Mark Chang
Publisher: CRC Press
ISBN: 9781439835937
Format: PDF, ePub
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Helping you become a creative, logical thinker and skillful "simulator," Monte Carlo Simulation for the Pharmaceutical Industry: Concepts, Algorithms, and Case Studies provides broad coverage of the entire drug development process, from drug discovery to preclinical and clinical trial aspects to commercialization. It presents the theories and methods needed to carry out computer simulations efficiently, covers both descriptive and pseudocode algorithms that provide the basis for implementation of the simulation methods, and illustrates real-world problems through case studies. The text first emphasizes the importance of analogy and simulation using examples from a variety of areas, before introducing general sampling methods and the different stages of drug development. It then focuses on simulation approaches based on game theory and the Markov decision process, simulations in classical and adaptive trials, and various challenges in clinical trial management and execution. The author goes on to cover prescription drug marketing strategies and brand planning, molecular design and simulation, computational systems biology and biological pathway simulation with Petri nets, and physiologically based pharmacokinetic modeling and pharmacodynamic models. The final chapter explores Monte Carlo computing techniques for statistical inference. This book offers a systematic treatment of computer simulation in drug development. It not only deals with the principles and methods of Monte Carlo simulation, but also the applications in drug development, such as statistical trial monitoring, prescription drug marketing, and molecular docking.

Adaptive Design Methods in Clinical Trials Second Edition

Author: Shein-Chung Chow
Publisher: CRC Press
ISBN: 1439839883
Format: PDF, Mobi
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With new statistical and scientific issues arising in adaptive clinical trial design, including the U.S. FDA’s recent draft guidance, a new edition of one of the first books on the topic is needed. Adaptive Design Methods in Clinical Trials, Second Edition reflects recent developments and regulatory positions on the use of adaptive designs in clinical trials. It unifies the vast and continuously growing literature and research activities on regulatory requirements, scientific and practical issues, and statistical methodology. New to the Second Edition Along with revisions throughout the text, this edition significantly updates the chapters on protocol amendment and clinical trial simulation to incorporate the latest changes. It also includes five entirely new chapters on two-stage adaptive design, biomarker adaptive trials, target clinical trials, sample size and power estimation, and regulatory perspectives. Following in the tradition of its acclaimed predecessor, this second edition continues to offer an up-to-date resource for clinical scientists and researchers in academia, regulatory agencies, and the pharmaceutical industry. Written in an intuitive style at a basic mathematical and statistical level, the book maintains its practical approach with an emphasis on concepts via numerous examples and illustrations.

Adaptive Design Theory and Implementation Using SAS and R Second Edition

Author: Mark Chang
Publisher: CRC Press
ISBN: 1482256606
Format: PDF, Docs
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Get Up to Speed on Many Types of Adaptive Designs Since the publication of the first edition, there have been remarkable advances in the methodology and application of adaptive trials. Incorporating many of these new developments, Adaptive Design Theory and Implementation Using SAS and R, Second Edition offers a detailed framework to understand the use of various adaptive design methods in clinical trials. New to the Second Edition Twelve new chapters covering blinded and semi-blinded sample size reestimation design, pick-the-winners design, biomarker-informed adaptive design, Bayesian designs, adaptive multiregional trial design, SAS and R for group sequential design, and much more More analytical methods for K-stage adaptive designs, multiple-endpoint adaptive design, survival modeling, and adaptive treatment switching New material on sequential parallel designs with rerandomization and the skeleton approach in adaptive dose-escalation trials Twenty new SAS macros and R functions Enhanced end-of-chapter problems that give readers hands-on practice addressing issues encountered in designing real-life adaptive trials Covering even more adaptive designs, this book provides biostatisticians, clinical scientists, and regulatory reviewers with up-to-date details on this innovative area in pharmaceutical research and development. Practitioners will be able to improve the efficiency of their trial design, thereby reducing the time and cost of drug development.

The R Book

Author: Michael J. Crawley
Publisher: John Wiley & Sons
ISBN: 1118448960
Format: PDF, Docs
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Hugely successful and popular text presenting an extensive and comprehensive guide for all R users The R language is recognized as one of the most powerful and flexible statistical software packages, enabling users to apply many statistical techniques that would be impossible without such software to help implement such large data sets. R has become an essential tool for understanding and carrying out research. This edition: Features full colour text and extensive graphics throughout. Introduces a clear structure with numbered section headings to help readers locate information more efficiently. Looks at the evolution of R over the past five years. Features a new chapter on Bayesian Analysis and Meta-Analysis. Presents a fully revised and updated bibliography and reference section. Is supported by an accompanying website allowing examples from the text to be run by the user. Praise for the first edition: ‘…if you are an R user or wannabe R user, this text is the one that should be on your shelf. The breadth of topics covered is unsurpassed when it comes to texts on data analysis in R.’ (The American Statistician, August 2008) ‘The High-level software language of R is setting standards in quantitative analysis. And now anybody can get to grips with it thanks to The R Book…’ (Professional Pensions, July 2007)

Mixed Effects Models for the Population Approach

Author: Marc Lavielle
Publisher: CRC Press
ISBN: 1482226510
Format: PDF
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Wide-Ranging Coverage of Parametric Modeling in Linear and Nonlinear Mixed Effects Models Mixed Effects Models for the Population Approach: Models, Tasks, Methods and Tools presents a rigorous framework for describing, implementing, and using mixed effects models. With these models, readers can perform parameter estimation and modeling across a whole population of individuals at the same time. Easy-to-Use Techniques and Tools for Real-World Data Modeling The book first shows how the framework allows model representation for different data types, including continuous, categorical, count, and time-to-event data. This leads to the use of generic methods, such as the stochastic approximation of the EM algorithm (SAEM), for modeling these diverse data types. The book also covers other essential methods, including Markov chain Monte Carlo (MCMC) and importance sampling techniques. The author uses publicly available software tools to illustrate modeling tasks. Methods are implemented in Monolix, and models are visually explored using Mlxplore and simulated using Simulx. Careful Balance of Mathematical Representation and Practical Implementation This book takes readers through the whole modeling process, from defining/creating a parametric model to performing tasks on the model using various mathematical methods. Statisticians and mathematicians will appreciate the rigorous representation of the models and theoretical properties of the methods while modelers will welcome the practical capabilities of the tools. The book is also useful for training and teaching in any field where population modeling occurs.

Markov Chain Monte Carlo in Practice

Author: W.R. Gilks
Publisher: CRC Press
ISBN: 9780412055515
Format: PDF, ePub, Docs
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In a family study of breast cancer, epidemiologists in Southern California increase the power for detecting a gene-environment interaction. In Gambia, a study helps a vaccination program reduce the incidence of Hepatitis B carriage. Archaeologists in Austria place a Bronze Age site in its true temporal location on the calendar scale. And in France, researchers map a rare disease with relatively little variation. Each of these studies applied Markov chain Monte Carlo methods to produce more accurate and inclusive results. General state-space Markov chain theory has seen several developments that have made it both more accessible and more powerful to the general statistician. Markov Chain Monte Carlo in Practice introduces MCMC methods and their applications, providing some theoretical background as well. The authors are researchers who have made key contributions in the recent development of MCMC methodology and its application. Considering the broad audience, the editors emphasize practice rather than theory, keeping the technical content to a minimum. The examples range from the simplest application, Gibbs sampling, to more complex applications. The first chapter contains enough information to allow the reader to start applying MCMC in a basic way. The following chapters cover main issues, important concepts and results, techniques for implementing MCMC, improving its performance, assessing model adequacy, choosing between models, and applications and their domains. Markov Chain Monte Carlo in Practice is a thorough, clear introduction to the methodology and applications of this simple idea with enormous potential. It shows the importance of MCMC in real applications, such as archaeology, astronomy, biostatistics, genetics, epidemiology, and image analysis, and provides an excellent base for MCMC to be applied to other fields as well.

Probability and Statistics for Computer Scientists Second Edition

Author: Michael Baron
Publisher: CRC Press
ISBN: 1498760600
Format: PDF, ePub, Docs
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Student-Friendly Coverage of Probability, Statistical Methods, Simulation, and Modeling Tools Incorporating feedback from instructors and researchers who used the previous edition, Probability and Statistics for Computer Scientists, Second Edition helps students understand general methods of stochastic modeling, simulation, and data analysis; make optimal decisions under uncertainty; model and evaluate computer systems and networks; and prepare for advanced probability-based courses. Written in a lively style with simple language, this classroom-tested book can now be used in both one- and two-semester courses. New to the Second Edition Axiomatic introduction of probability Expanded coverage of statistical inference, including standard errors of estimates and their estimation, inference about variances, chi-square tests for independence and goodness of fit, nonparametric statistics, and bootstrap More exercises at the end of each chapter Additional MATLAB® codes, particularly new commands of the Statistics Toolbox In-Depth yet Accessible Treatment of Computer Science-Related Topics Starting with the fundamentals of probability, the text takes students through topics heavily featured in modern computer science, computer engineering, software engineering, and associated fields, such as computer simulations, Monte Carlo methods, stochastic processes, Markov chains, queuing theory, statistical inference, and regression. It also meets the requirements of the Accreditation Board for Engineering and Technology (ABET). Encourages Practical Implementation of Skills Using simple MATLAB commands (easily translatable to other computer languages), the book provides short programs for implementing the methods of probability and statistics as well as for visualizing randomness, the behavior of random variables and stochastic processes, convergence results, and Monte Carlo simulations. Preliminary knowledge of MATLAB is not required. Along with numerous computer science applications and worked examples, the text presents interesting facts and paradoxical statements. Each chapter concludes with a short summary and many exercises.

Using R for Introductory Statistics Second Edition

Author: John Verzani
Publisher: CRC Press
ISBN: 1466590734
Format: PDF, ePub, Mobi
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The second edition of a bestselling textbook, Using R for Introductory Statistics guides students through the basics of R, helping them overcome the sometimes steep learning curve. The author does this by breaking the material down into small, task-oriented steps. The second edition maintains the features that made the first edition so popular, while updating data, examples, and changes to R in line with the current version. See What’s New in the Second Edition: Increased emphasis on more idiomatic R provides a grounding in the functionality of base R. Discussions of the use of RStudio helps new R users avoid as many pitfalls as possible. Use of knitr package makes code easier to read and therefore easier to reason about. Additional information on computer-intensive approaches motivates the traditional approach. Updated examples and data make the information current and topical. The book has an accompanying package, UsingR, available from CRAN, R’s repository of user-contributed packages. The package contains the data sets mentioned in the text (data(package="UsingR")), answers to selected problems (answers()), a few demonstrations (demo()), the errata (errata()), and sample code from the text. The topics of this text line up closely with traditional teaching progression; however, the book also highlights computer-intensive approaches to motivate the more traditional approach. The authors emphasize realistic data and examples and rely on visualization techniques to gather insight. They introduce statistics and R seamlessly, giving students the tools they need to use R and the information they need to navigate the sometimes complex world of statistical computing.

Optimal Design for Nonlinear Response Models

Author: Valerii V. Fedorov
Publisher: CRC Press
ISBN: 1439821518
Format: PDF, ePub, Mobi
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Optimal Design for Nonlinear Response Models discusses the theory and applications of model-based experimental design with a strong emphasis on biopharmaceutical studies. The book draws on the authors’ many years of experience in academia and the pharmaceutical industry. While the focus is on nonlinear models, the book begins with an explanation of the key ideas, using linear models as examples. Applying the linearization in the parameter space, it then covers nonlinear models and locally optimal designs as well as minimax, optimal on average, and Bayesian designs. The authors also discuss adaptive designs, focusing on procedures with non-informative stopping. The common goals of experimental design—such as reducing costs, supporting efficient decision making, and gaining maximum information under various constraints—are often the same across diverse applied areas. Ethical and regulatory aspects play a much more prominent role in biological, medical, and pharmaceutical research. The authors address all of these issues through many examples in the book.

Dose Finding by the Continual Reassessment Method

Author: Ying Kuen Cheung
Publisher: CRC Press
ISBN: 1420091514
Format: PDF, ePub
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As clinicians begin to realize the important role of dose-finding in the drug development process, there is an increasing openness to "novel" methods proposed in the past two decades. In particular, the Continual Reassessment Method (CRM) and its variations have drawn much attention in the medical community, though it has yet to become a commonplace tool. To overcome the status quo in phase I clinical trials, statisticians must be able to design trials using the CRM in a timely and reproducible manner. A self-contained theoretical framework of the CRM for researchers and graduate students who set out to learn and do research in the CRM and dose-finding methods in general, Dose Finding by the Continual Reassessment Method features: Real clinical trial examples that illustrate the methods and techniques throughout the book Detailed calibration techniques that enable biostatisticians to design a CRM in timely manner Limitations of the CRM are outlined to aid in correct use of method This book supplies practical, efficient dose-finding methods based on cutting edge statistical research. More than just a cookbook, it provides full, unified coverage of the CRM in addition to step-by-step guidelines to automation and parameterization of the methods used on a regular basis. A detailed exposition of the calibration of the CRM for applied statisticians working with dose-finding in phase I trials, the book focuses on the R package ‘dfcrm’ for the CRM and its major variants. The author recognizes clinicians’ skepticism of model-based designs, and addresses their concerns that the time, professional, and computational resources necessary for accurate model-based designs can be major bottlenecks to the widespread use of appropriate dose-finding methods in phase I practice. The theoretically- and empirically-based methods in Dose Finding by the Continual Reassessment Method will lessen the statistician’s burden and encourage the continuing development and implementation of model-based dose-finding methods.