After introducing the basic concepts of stability testing, the book focuses on short-term stability studies and reviews several methods for estimating drug expiration dating periods. It then compares some commonly employed study designs and discusses both fixed and random batch statistical analyses. Following a chapter on the statistical methods for stability analysis under a linear mixed effects model, the book examines stability analyses with discrete responses, multiple components, and frozen drug products. In addition, the author provides statistical methods for dissolution testing and explores current issues and recent developments in stability studies.
To ensure the safety of consumers, professionals in the field must carry out stability studies to determine the reliability of drug products during their expiration period. This book provides the material necessary for you to perform stability designs and analyses in pharmaceutical research and development.
Focusing on normal, binary, ordinal, and survival data, the book explores a range of trials, including superiority, equivalence, non-inferiority, bioequivalence, and precision for both parallel group and crossover designs. The author discusses how trial objectives impact the study design with respect to the derivation of formulae for sample size calculations. He uses real-life studies throughout to show how the concepts and calculations can be employed.
This work underscores the importance of sample size calculation in the design of a clinical trial. With useful calculation tables throughout, it enables readers to quickly find an appropriate formula, formula application, and associated worked example.
Watch the author speak about this book at JSM 2012 in San Diego.
“...a grand feast for biostatisticians. It stands readyto satisfy the appetite of any pharmaceutical scientist with arespectable statistical appetite.” —Journal of ClinicalResearch Best Practices
The Third Edition of Design and Analysis of ClinicalTrials provides complete, comprehensive, and expanded coverageof recent health treatments and interventions. Featuring a unifiedpresentation, the book provides a well-balanced summary of currentregulatory requirements and recently developed statistical methodsas well as an overview of the various designs and analyses that areutilized at different stages of clinical research and development.Additional features of this Third Edition include:
• New chapters on biomarker development and targetclinical trials, adaptive design, trials for evaluating diagnosticdevices, statistical methods for translational medicine, andtraditional Chinese medicine
• A balanced overview of current and emerging clinicalissues as well as newly developed statistical methodologies
• Practical examples of clinical trials that demonstrateeveryday applicability, with illustrations and examples to explainkey concepts
• New sections on bridging studies and global trials, QTstudies, multinational trials, comparative effectiveness trials,and the analysis of QT/QTc prolongation
• A complete and balanced presentation of clinical andscientific issues, statistical concepts, and methodologies forbridging clinical and statistical disciplines
• An update of each chapter that reflects changes inregulatory requirements for the drug review and approval processand recent developments in statistical design and methodology forclinical research and development
Design and Analysis of Clinical Trials, Third Editioncontinues to be an ideal clinical research reference for academic,pharmaceutical, medical, and regulatory scientists/researchers,statisticians, and graduate-level students.
The Spanish flu of 1918-1920 was one of the greatest human disasters of all time. It infected a third of the people on Earth--from the poorest immigrants of New York City to the king of Spain, Franz Kafka, Mahatma Gandhi and Woodrow Wilson. But despite a death toll of between 50 and 100 million people, it exists in our memory as an afterthought to World War I.
In this gripping narrative history, Laura Spinney traces the overlooked pandemic to reveal how the virus travelled across the globe, exposing mankind's vulnerability and putting our ingenuity to the test. As socially significant as both world wars, the Spanish flu dramatically disrupted--and often permanently altered--global politics, race relations and family structures, while spurring innovation in medicine, religion and the arts. It was partly responsible, Spinney argues, for pushing India to independence, South Africa to apartheid and Switzerland to the brink of civil war. It also created the true "lost generation." Drawing on the latest research in history, virology, epidemiology, psychology and economics, Pale Rider masterfully recounts the little-known catastrophe that forever changed humanity.
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.
"A major work of interpretation of medical and social thought . . . this volume is also to be commended for its skillful, absorbing presentation of the background and the effects of this dread disease."—I.B. Cohen, New York Times
"The Cholera Years is a masterful analysis of the moral and social interest attached to epidemic disease, providing generally applicable insights into how the connections between social change, changes in knowledge and changes in technical practice may be conceived."—Steven Shapin, Times Literary Supplement
"In a way that is all too rarely done, Rosenberg has skillfully interwoven medical, social, and intellectual history to show how medicine and society interacted and changed during the 19th century. The history of medicine here takes its rightful place in the tapestry of human history."—John B. Blake, Science
The book focuses on issues occurring at various stages of clinical research and development, including early-phase clinical development (such as bioavailability/bioequivalence), bench-to-bedside translational research, and late-phase clinical development. Numerous examples illustrate the impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation. The author also offers recommendations regarding possible resolutions of the problems.
Written by one of the preeminent experts in the field, this book provides a useful desk reference and state-of-the art examination of problematic issues in clinical trials for scientists in the pharmaceutical industry, medical/statistical reviewers in government regulatory agencies, and researchers and students in academia.
Over the past fifty years, more than three hundred infectious diseases have either newly emerged or reemerged, appearing in territories where they’ve never been seen before. Ninety percent of epidemiologists expect that one of them will cause a deadly pandemic sometime in the next two generations. It could be Ebola, avian flu, a drug-resistant superbug, or something completely new. While we can’t know which pathogen will cause the next pandemic, by unraveling the story of how pathogens have caused pandemics in the past, we can make predictions about the future. In Pandemic: Tracking Contagions, from Cholera to Ebola and Beyond, the prizewinning journalist Sonia Shah—whose book on malaria, The Fever, was called a “tour-de-force history” (The New York Times) and “revelatory” (The New Republic)—interweaves history, original reportage, and personal narrative to explore the origins of contagions, drawing parallels between cholera, one of history’s most deadly and disruptive pandemic-causing pathogens, and the new diseases that stalk humankind today.
To reveal how a new pandemic might develop, Sonia Shah tracks each stage of cholera’s dramatic journey, from its emergence in the South Asian hinterlands as a harmless microbe to its rapid dispersal across the nineteenth-century world, all the way to its latest beachhead in Haiti. Along the way she reports on the pathogens now following in cholera’s footsteps, from the MRSA bacterium that besieges her own family to the never-before-seen killers coming out of China’s wet markets, the surgical wards of New Delhi, and the suburban backyards of the East Coast.
By delving into the convoluted science, strange politics, and checkered history of one of the world’s deadliest diseases, Pandemic reveals what the next global contagion might look like— and what we can do to prevent it.
Written by a top biostatistics researcher, Biosimilars: Design and Analysis of Follow-on Biologics is the first book entirely devoted to the statistical design and analysis of biosimilarity and interchangeability of biosimilar products. It includes comparability tests of important quality attributes at critical stages of the manufacturing processes of biologic products.
Connecting the pharmaceutical/biotechnology industry, government regulatory agencies, and academia, this state-of-the-art book focuses on the scientific factors and practical issues related to the design and analysis of biosimilar studies. It covers most of the statistical questions encountered in various study designs at different stages of research and development of biological products.
This text is intended for a broad audience as both an introduction to predictive models as well as a guide to applying them. Non-mathematical readers will appreciate the intuitive explanations of the techniques while an emphasis on problem-solving with real data across a wide variety of applications will aid practitioners who wish to extend their expertise. Readers should have knowledge of basic statistical ideas, such as correlation and linear regression analysis. While the text is biased against complex equations, a mathematical background is needed for advanced topics.
Taking into account the regulatory and scientific developments that have occurred since the second edition, Design and Analysis of Bioavailability and Bioequivalence Studies, Third Edition provides a complete presentation of the latest progress of activities and results in bioavailability and bioequivalence on regulatory requirements, scientific and practical issues, and statistical methodology.
New to the Third Edition
Four new chapters that present a thorough account of novel developments in the field New and updated sections that reflect recent advances in the statistical methodology in the design and analysis of bioavailability and bioequivalence studies Reorganization of the material into five parts, making it easier to access related information together Over 100 new references from the literature
Like its bestselling predecessors, this edition covers all of the statistical problems that may occur in the various stages of design and data analysis. Keeping the mathematics and statistics at a fundamental level, it continues to focus on practical concepts rather than technical details.
The real story of AIDS—how it originated with a virus in a chimpanzee, jumped to one human, and then infected more than 60 million people—is very different from what most of us think we know. Recent research has revealed dark surprises and yielded a radically new scenario of how AIDS began and spread. Excerpted and adapted from the book Spillover, with a new introduction by the author, Quammen's hair-raising investigation tracks the virus from chimp populations in the jungles of southeastern Cameroon to laboratories across the globe, as he unravels the mysteries of when, where, and under what circumstances such a consequential "spillover" can happen. An audacious search for answers amid more than a century of data, The Chimp and the River tells the haunting tale of one of the most devastating pandemics of our time.
The first several chapters focus on the fundamental theory behind adaptive trial design, the application of the Bayesian approach to adaptive designs, and the impact of potential population shift due to protocol amendments. The book then presents a variety of statistical methods for group sequential design, classical design, dose-finding trials, Phase I/II and Phase II/III seamless adaptive designs, multiple stage seamless adaptive trial design, adaptive randomization trials, hypotheses-adaptive design, and treatment-adaptive design. It also covers predictive biomarker diagnostics for new drug development, clinical strategies for endpoint selection in translational research, the role of independent data monitoring committees in adaptive clinical trials, the enrichment process in targeted clinical trials for personalized medicine, applications of adaptive designs that use genomic or genetic information, adaptive trial simulation, and the efficiency of adaptive design. The final chapters discuss case studies as well as standard operating procedures for good adaptive practices.
With contributions from leading clinical researchers in the pharmaceutical industry, academia, and regulatory agencies, this handbook offers an up-to-date, complete treatment of the principles and methods of adaptive design and analysis. Along with reviewing recent developments, it examines issues commonly encountered when applying adaptive design methods in clinical trials.
Features of the Fourth Edition include:New material on sample size calculations for chance-corrected agreement coefficients, as well as for intraclass correlation coefficients. The researcher will be able to determine the optimal number raters, subjects, and trials per subject.The chapter entitled “Benchmarking Inter-Rater Reliability Coefficients” has been entirely rewritten.The introductory chapter has been substantially expanded to explore possible definitions of the notion of inter-rater reliability.All chapters have been revised to a large extent to improve their readability.
In 1976 a deadly virus emerged from the Congo forest. As swiftly as it came, it disappeared, leaving no trace. Over the four decades since, Ebola has emerged sporadically, each time to devastating effect. It can kill up to 90 percent of its victims. In between these outbreaks, it is untraceable, hiding deep in the jungle. The search is on to find Ebola’s elusive host animal. And until we find it, Ebola will continue to strike. Acclaimed science writer and explorer David Quammen first came near the virus while he was traveling in the jungles of Gabon, accompanied by local men whose village had been devastated by a recent outbreak. Here he tells the story of Ebola—its past, present, and its unknowable future.
Extracted from Spillover by David Quammen, updated and with additional material.
Features of the Fourth Edition:
1. 78 new and revised entries have been added for a total of 308 chapters and a third volume has been added to encompass the increased number of chapters.
2. Revised and updated entries reflect changes and recent developments in regulatory requirements for the drug review/approval process and statistical designs and methodologies.
3. Additional topics include multiple-stage adaptive trial design in clinical research, translational medicine, design and analysis of biosimilar drug development, big data analytics, and real world evidence for clinical research and development.
4. A table of contents organized by stages of biopharmaceutical development provides easy access to relevant topics.
About the Editor:
Shein-Chung Chow, Ph.D.is currently an Associate Director, Office of Biostatistics, U.S. Food and Drug Administration (FDA). Dr. Chow is an Adjunct Professor at Duke University School of Medicine, as well as Adjunct Professor at Duke-NUS, Singapore and North Carolina State University. Dr. Chow is the Editor-in-Chief of the Journal of Biopharmaceutical Statistics and the Chapman & Hall/CRC Biostatistics Book Series and the author of 28 books and over 300 methodology papers. He was elected Fellow of the American Statistical Association in 1995.
In recent years, many pharmaceutical companies and clinical research organizations have been focusing on the development of traditional Chinese (herbal) medicines (TCMs) as alternatives to treating critical or life-threatening diseases and as pathways to personalized medicine.
Quantitative Methods for Traditional Chinese Medicine Development is the first book entirely devoted to the design and analysis of TCM development from a Western perspective, i.e., evidence-based clinical research and development. The book provides not only a comprehensive summary of innovative quantitative methods for developing TCMs but also a useful desk reference for principal investigators involved in personalized medicine.
Written by one of the world’s most prominent biostatistics researchers, the book connects the pharmaceutical industry, regulatory agencies, and academia. It presents a state-of-the-art examination of the subject for:Scientists and researchers who are engaged in pharmaceutical/clinical research and development of TCMs Those in regulatory agencies who make decisions in the review and approval process of TCM regulatory submissions Biostatisticians who provide statistical support to assess clinical safety and effectiveness of TCMs and related issues regarding quality control and assurance as well as to test for consistency in the manufacturing processes for TCMs
This book covers all of the statistical issues encountered at various stages of pharmaceutical/clinical development of a TCM. It explains regulatory requirements; product specifications and standards; and various statistical techniques for evaluation of TCMs, validation of diagnostic procedures, and testing consistency. It also contains an entire chapter of case studies and addresses critical issues in TCM development and FAQs from a regulatory perspective.
". . . [this book] should be on the shelf of everyone interestedin . . . longitudinal data analysis."
—Journal of the American Statistical Association
Features newly developed topics and applications of theanalysis of longitudinal data
Applied Longitudinal Analysis, Second Edition presentsmodern methods for analyzing data from longitudinal studies and nowfeatures the latest state-of-the-art techniques. The bookemphasizes practical, rather than theoretical, aspects of methodsfor the analysis of diverse types of longitudinal data that can beapplied across various fields of study, from the health and medicalsciences to the social and behavioral sciences.
The authors incorporate their extensive academic and researchexperience along with various updates that have been made inresponse to reader feedback. The Second Edition features six newlyadded chapters that explore topics currently evolving in the field,including:Fixed effects and mixed effects modelsMarginal models and generalized estimating equationsApproximate methods for generalized linear mixed effectsmodelsMultiple imputation and inverse probability weightedmethodsSmoothing methods for longitudinal dataSample size and power
Each chapter presents methods in the setting of applications todata sets drawn from the health sciences. New problem sets havebeen added to many chapters, and a related website features sampleprograms and computer output using SAS, Stata, and R, as well asdata sets and supplemental slides to facilitate a completeunderstanding of the material.
With its strong emphasis on multidisciplinary applications andthe interpretation of results, Applied LongitudinalAnalysis, Second Edition is an excellent book for courses onstatistics in the health and medical sciences at theupper-undergraduate and graduate levels. The book also serves as avaluable reference for researchers and professionals in themedical, public health, and pharmaceutical fields as well as thosein social and behavioral sciences who would like to learn moreabout analyzing longitudinal data.
Design and Analysis of Bridging Studies addresses the issues arising from bridging studies and multiregional clinical trials. For bridging studies, the book explores ethnic sensitivity, the necessity of bridging studies, types of bridging studies, and the assessment of similarity between regions based on bridging evidence. For multiregional clinical trials, the text considers regional differences, assesses the consistency of treatment effect across regions, and discusses sample size determination for each region.
Taking into account the International Conference Harmonisation (ICH) E5 framework for bridging studies, the book provides a unified summary of the growing literature and research activities in this area. It covers the regulatory requirements, scientific and practical issues, and statistical methodology for designing and evaluating bridging studies and multiregional clinical trials, with the goal of inspiring new research activities in the field.
· Downloadable data sets
· Library of computer programs in SAS, SPSS, Stata, HLM, MLwiN, and more
· Additional material for data analysis
Suitable for graduate students and researchers in statistics, the book presents thorough treatments of:
Statistical theories of likelihood-based inference with missing data Computational techniques and theories on imputation Methods involving propensity score weighting, nonignorable missing data, longitudinal missing data, survey sampling, and statistical matching
Assuming prior experience with statistical theory and linear models, the text uses the frequentist framework with less emphasis on Bayesian methods and nonparametric methods. It includes many examples to help readers understand the methodologies. Some of the research ideas introduced can be developed further for specific applications.
The development of therapeutic pharmaceutical compounds is becoming more expensive, and the success rates for getting such treatments approved for marketing and to the patients is decreasing. As a result, translational medicine (TM) is becoming increasingly important in the healthcare industry – a means of maximizing the consideration and use of information collected as compounds transition from initial lab discovery, through pre-clinical testing, early clinical trials, and late confirmatory studies that lead to regulatory approval of drug release to patients.
Translational Medicine: Strategies and Statistical Methods suggests a process for transitioning from the initial lab discovery to the patient’s bedside with minimal disconnect and offers a comprehensive review of statistical design and methodology commonly employed in this bench-to-bedside research.
Documents Alternative Research Approaches for Faster and More Accurate Data Judgment Calls
Elaborating on how to introduce TM into clinical studies, this authoritative work presents a keen approach to building, executing, and validating statistical models that consider data from various phases of development. It also delineates a truly translational example to help bolster understanding of discussed concepts.
This comprehensive guide effectively demonstrates how to overcome obstacles related to successful TM practice. It contains invaluable information for pharmaceutical scientists, research executives, clinicians, and biostatisticians looking to expedite successful implementation of this important process.
Too little salt in the diet can shift the body into semi-starvation mode and cause insulin resistance, and may even cause you to absorb twice as much fat for every gram you consume. Too little salt in certain populations can actually increase blood pressure, as well as resting heart rate. We need salt in order to hydrate and nourish our cells, transmit nerve signals, contract our muscles, ensure proper digestion and breathing, and maintain proper heart function. The Salt Fix will show how we wrongly demonized this essential micronutrient as well as explain what the current science really says about this misunderstood mineral and how to maximize its effect so you can enjoy ideal health and longevity.
Tricky concepts are illustrated and explained with clarity and precision, as The Human Brain Book looks at how the brain sends messages to the rest of the body, how we think and feel, how we perform unconscious actions (for example, breathing), explores the nature of genius, asks why we behave the way we do, explains how we see and hear things, and how and why we dream. Physical and psychological disorders affecting the brain and nervous system are clearly illustrated and summarized in easy-to-understand terms.
This book brings together a broad perspective of new quantitative methods in HIV/AIDS research, contributed by statisticians and mathematicians immersed in HIV research, many of whom are current or previous leaders of CFAR quantitative cores. It is the editors’ hope that the work will inspire more statisticians, mathematicians and computer scientists to collaborate and contribute to the interdisciplinary challenges of understanding and addressing the AIDS pandemic.
New to This Edition:
*Chapters on the political ecology of health; emerging infectious diseases and landscape genetics; food, diet, and nutrition; and urban health.
*Coverage of Middle East respiratory syndrome, Ebola, and Zika; impacts on health of global climate change; contaminated water crises in economically developed countries, including in Flint, Michigan; China's rapid industrial growth; and other timely topics.
*Updated throughout with current data and concepts plus advances in GIS.
*End-of-chapter review questions and suggestions for further reading.
*Section Introductions that describe each chapter.
*"Quick Reviews"--within-chapter recaps of key concepts.
*Bold-faced key terms and an end-of-book glossary.
Managerial Epidemiology for Health Care Organizations has introduced the science of epidemiology and population health to students and practitioners in health management and health services for over sixteen years. The book covers epidemiology basics, introducing principles and traditional uses, and then expertly showing its contemporary uses in planning, evaluating, and managing health care for populations and the practical application in health care management. The book’s practical and applied approach, with real-world examples sprinkled throughout, has made it the go-to book for managerial epidemiology and population health courses.
Since the second edition was published in 2005, the health care landscape has undergone significant changes. Passage of the Patient Protection and Affordable Care Act and the incorporation of ICD-10 have impacted the entire health care system. This newly updated third edition will address these two significant changes, as well as several others that have taken place. It also features new chapters on reimbursement approaches and managing infection outbreaks, as well as updates to the four case study chapters that anchor the book.Witness how epidemiological principles are applied to the delivery of health care services and the management of health care organizationsExamine the major changes brought on by the passage of health care reform and incorporation of ICD-10Discover the core epidemiology principles and see how they are applied in planning, evaluating, and managing health care for populations
If you’re a student or professional in any area of health services, including health administration, nursing, and allied health, then Managerial Epidemiology for Health Care Organizations is the perfect book for you. It successfully demonstrates how health care executives can incorporate the practice of epidemiology into their various management functions and is rich with current examples, concepts, and case studies that reinforce the essential theories, methods, and applications of managerial epidemiology.
In December 2013, a young boy in a tiny West African village contracted the deadly Ebola virus. The virus spread to his relatives, then to neighboring communities, then across international borders. The world’s first urban Ebola outbreak quickly overwhelmed the global health system and threatened to kill millions.
In an increasingly interconnected world in which everyone is one or two flights away from New York or London or Beijing, even a localized epidemic can become a pandemic. Ebola’s spread through West Africa to Nigeria, the United Kingdom and the United States sounded global alarms that the next killer outbreak is right around the corner—and that the world is woefully unprepared to combat a new deadly disease.
From the poorest villages of rural West Africa to the Oval Office itself, this book tells the story of a deadly virus that spun wildly out of control—and reveals the truth about how close the world came to a catastrophic global pandemic.
• Introduces requisite background to using NonlinearMixed Effects Modeling (NONMEM), covering data requirements, modelbuilding and evaluation, and quality control aspects
• Provides examples of nonlinear modeling concepts andestimation basics with discussion on the model buildingprocess and applications of empirical Bayesian estimates in thedrug development environment
• Includes detailed chapters on data set structure,developing control streams for modeling and simulation, modelapplications, interpretation of NONMEM output and results, andquality control
• Has datasets, programming code, and practice exerciseswith solutions, available on a supplementary website
Unlike natural disasters, whose destruction is concentrated in a limited area over a period of days, and illnesses, which have devastating effects but are limited to individuals and their families, infectious disease has the terrifying power to disrupt everyday life on a global scale, overwhelming public and private resources and bringing trade and transportation to a grinding halt.
In today's world, it's easier than ever to move people, animals, and materials around the planet, but the same advances that make modern infrastructure so efficient have made epidemics and even pandemics nearly inevitable. And as outbreaks of Ebola, MERS, yellow fever, and Zika have demonstrated, we are woefully underprepared to deal with the fallout. So what can -- and must -- we do in order to protect ourselves from mankind's deadliest enemy?
Drawing on the latest medical science, case studies, policy research, and hard-earned epidemiological lessons, Deadliest Enemy explores the resources and programs we need to develop if we are to keep ourselves safe from infectious disease. The authors show how we could wake up to a reality in which many antibiotics no longer cure, bioterror is a certainty, and the threat of a disastrous influenza pandemic looms ever larger. Only by understanding the challenges we face can we prevent the unthinkable from becoming the inevitable.
Deadliest Enemy is high scientific drama, a chronicle of medical mystery and discovery, a reality check, and a practical plan of action.