Chapman & Hall/CRC Biostatistics Series – serie

Real-world evidence (RWE) has been at the forefront of pharmaceutical innovations. It plays an important role in transforming drug development from a process aimed at meeting regulatory expectations to an operating model that leverages data from disparate sources to aid business, regulatory, and healthcare decision making. Despite its many benefits, there is no single book systematically covering the latest development in the field.Written specifically for pharmaceutical practitioners, Real-World Evidence in Drug Development and Evaluation, presents a wide range of RWE applications throughout the lifecycle of drug product development. With contributions from experienced researchers in the pharmaceutical industry, the book discusses at length RWE opportunities, challenges, and solutions.FeaturesProvides the first book and a single source of information on RWE in drug developmentCovers a broad array of topics on outcomes- and value-based RWE assessments Demonstrates proper Bayesian application and causal inference for real-world data (RWD)Presents real-world use cases to illustrate the use of advanced analytics and statistical methods to generate insightsOffers a balanced discussion of practical RWE issues at hand and technical solutions suitable for practitioners with limited data science expertise

Cure Models: Methods, Applications and Implementation is the first book in the last 25 years that provides a comprehensive and systematic introduction to the basics of modern cure models, including estimation, inference, and software. This book is useful for statistical researchers and graduate students, and practitioners in other disciplines to have a thorough review of modern cure model methodology and to seek appropriate cure models in applications. The prerequisites of this book include some basic knowledge of statistical modeling, survival models, and R and SAS for data analysis.The book features real-world examples from clinical trials and population-based studies and a detailed introduction to R packages, SAS macros, and WinBUGS programs to fit some cure models. The main topics covered include the foundation of statistical estimation and inference of cure models for independent and right-censored survival data, cure modeling for multivariate, recurrent-event, and competing-risks survival data, and joint modeling with longitudinal data, statistical testing for the existence and difference of cure rates and sufficient follow-up, new developments in Bayesian cure models, applications of cure models in public health research and clinical trials.

Bayesian adaptive designs provide a critical approach to improve the efficiency and success of drug development that has been embraced by the US Food and Drug Administration (FDA). This is particularly important for early phase trials as they form the basis for the development and success of subsequent phase II and III trials.The objective of this book is to describe the state-of-the-art model-assisted designs to facilitate and accelerate the use of novel adaptive designs for early phase clinical trials. Model-assisted designs possess avant-garde features where superiority meets simplicity. Model-assisted designs enjoy exceptional performance comparable to more complicated model-based adaptive designs, yet their decision rules often can be pre-tabulated and included in the protocol—making implementation as simple as conventional algorithm-based designs. An example is the Bayesian optimal interval (BOIN) design, the first dose-finding design to receive the fit-for-purpose designation from the FDA. This designation underscores the regulatory agency's support of the use of the novel adaptive design to improve drug development.FeaturesRepresents the first book to provide comprehensive coverage of model-assisted designs for various types of dose-finding and optimization clinical trialsDescribes the up-to-date theory and practice for model-assisted designsPresents many practical challenges, issues, and solutions arising from early-phase clinical trialsIllustrates with many real trial applicationsOffers numerous tips and guidance on designing dose finding and optimization trialsProvides step-by-step illustrations of using software to design trialsDevelops a companion website (www.trialdesign.org) to provide freely available, easy-to-use software to assist learning and implementing model-assisted designsWritten by internationally recognized research leaders who pioneered model-assisted designs from the University of Texas MD Anderson Cancer Center, this book shows how model-assisted designs can greatly improve the efficiency and simplify the design, conduct, and optimization of early-phase dose-finding trials. It should therefore be a very useful practical reference for biostatisticians, clinicians working in clinical trials, and drug regulatory professionals, as well as graduate students of biostatistics. Novel model-assisted designs showcase the new KISS principle: Keep it simple and smart!

Survival data analysis is a very broad field of statistics, encompassing a large variety of methods used in a wide range of applications, and in particular in medical research. During the last twenty years, several extensions of "classical" survival models have been developed to address particular situations often encountered in practice. This book aims to gather in a single reference the most commonly used extensions, such as frailty models (in case of unobserved heterogeneity or clustered data), cure models (when a fraction of the population will not experience the event of interest), competing risk models (in case of different types of event), and joint survival models for a time-to-event endpoint and a longitudinal outcome. Features Presents state-of-the art approaches for different advanced survival models including frailty models, cure models, competing risk models and joint models for a longitudinal and a survival outcome Uses consistent notation throughout the book for the different techniques presented Explains in which situation each of these models should be used, and how they are linked to specific research questions Focuses on the understanding of the models, their implementation, and their interpretation, with an appropriate level of methodological development for masters students and applied statisticians Provides references to existing R packages and SAS procedure or macros, and illustrates the use of the main ones on real datasetsThis book is primarily aimed at applied statisticians and graduate students of statistics and biostatistics. It can also serve as an introductory reference for methodological researchers interested in the main extensions of classical survival analysis.

Incidence rates are counts divided by person-time; mortality rates are a well-known example. Analysis of Incidence Rates offers a detailed discussion of the practical aspects of analyzing incidence rates. Important pitfalls and areas of controversy are discussed. The text is aimed at graduate students, researchers, and analysts in the disciplines of epidemiology, biostatistics, social sciences, economics, and psychology.Features: Compares and contrasts incidence rates with risks, odds, and hazards. Shows stratified methods, including standardization, inverse-variance weighting, and Mantel-Haenszel methods Describes Poisson regression methods for adjusted rate ratios and rate differences. Examines linear regression for rate differences with an emphasis on common problems. Gives methods for correcting confidence intervals. Illustrates problems related to collapsibility. Explores extensions of count models for rates, including negative binomial regression, methods for clustered data, and the analysis of longitudinal data. Also, reviews controversies and limitations. Presents matched cohort methods in detail. Gives marginal methods for converting adjusted rate ratios to rate differences, and vice versa. Demonstrates instrumental variable methods. Compares Poisson regression with the Cox proportional hazards model. Also, introduces Royston-Parmar models. All data and analyses are in online Stata files which readers can download.Peter Cummings is Professor Emeritus, Department of Epidemiology, School of Public Health, University of Washington, Seattle WA. His research was primarily in the field of injuries. He used matched cohort methods to estimate how the use of seat belts and presence of airbags were related to death in a traffic crash. He is author or co-author of over 100 peer-reviewed articles.

Review of the First Edition:The authors strive to reduce theory to a minimum, which makes it a self-learning text that is comprehensible for biologists, physicians, etc. who lack an advanced mathematics background. Unlike in many other textbooks, R is not introduced with meaningless toy examples; instead the reader is taken by the hand and shown around some analyses, graphics, and simulations directly relating to meta-analysis… A useful hands-on guide for practitioners who want to familiarize themselves with the fundamentals of meta-analysis and get started without having to plough through theorems and proofs.—Journal of Applied StatisticsStatistical Meta-Analysis with R and Stata, Second Edition provides a thorough presentation of statistical meta-analyses (MA) with step-by-step implementations using R/Stata. The authors develop analysis step by step using appropriate R/Stata functions, which enables readers to gain an understanding of meta-analysis methods and R/Stata implementation so that they can use these two popular software packages to analyze their own meta-data. Each chapter gives examples of real studies compiled from the literature. After presenting the data and necessary background for understanding the applications, various methods for analyzing meta-data are introduced. The authors then develop analysis code using the appropriate R/Stata packages and functions.What’s New in the Second Edition: Adds Stata programs along with the R programs for meta-analysis Updates all the statistical meta-analyses with R/Stata programs Covers fixed-effects and random-effects MA, meta-regression, MA with rare-event, and MA-IPD vs MA-SS Adds five new chapters on multivariate MA, publication bias, missing data in MA, MA in evaluating diagnostic accuracy, and network MASuitable as a graduate-level text for a meta-data analysis course, the book is also a valuable reference for practitioners and biostatisticians (even those with little or no experience in using R or Stata) in public health, medical research, governmental agencies, and the pharmaceutical industry.

This book covers classic epidemiological designs that use a reference/control group, including case-control, case-cohort, nested case-control and variations of these designs, such as stratified and two-stage designs. It presents a unified view of these sampling designs as representations of an underlying cohort or target population of interest. This enables various extended designs to be introduced and analysed with a similar approach: extreme sampling on the outcome (extreme case-control design) or on the exposure (exposure-enriched, exposure-density, countermatched), designs that re-use prior controls and augmentation sampling designs. Further extensions exploit aggregate data for efficient cluster sampling, accommodate time-varying exposures and combine matched and unmatched controls. Self-controlled designs, including case-crossover, self-controlled case series and exposure-crossover, are also presented. The test-negative design for vaccine studies and the use of negative controls for bias assessment are introduced and discussed.This book is intended for graduate students in biostatistics, epidemiology and related disciplines, or for health researchers and data analysts interested in extending their knowledge of study design and data analysis skills.This book Bridges the gap between epidemiology and the more mathematically oriented biostatistics books. Assembles the wealth of epidemiological knowledge about observational study designs that is scattered over several decades of scientific publications. Illustrates the performance of methods in real research applications. Provides guidelines for implementation in standard software packages (Stata, R).Includes numerous exercises, covering simple mathematical proofs, consideration of proposed or published designs, and practical data analysis.

Signal Detection for Medical Scientists: Likelihood Ratio Based Test-Based Methodology presents the data mining techniques with focus on likelihood ratio test (LRT) based methods for signal detection. It emphasizes computational aspect of LRT methodology and is pertinent for first-time researchers and graduate students venturing into this interesting field.The book is written as a reference book for professionals in pharmaceutical industry, manufactures of medical devices, and regulatory agencies. The book deals with the signal detection in drug/device evaluation, which is important in the post-market evaluation of medical products, and in the pre-market signal detection during clinical trials for monitoring procedures.It should also appeal to academic researchers, and faculty members in mathematics, statistics, biostatistics, data science, pharmacology, engineering, epidemiology, and public health. Therefore, this book is well suited for both research and teaching.Key Features:Includes a balanced discussion of art of data structure, issues in signal detection, statistical methods and analytics, and implementation of the methodsProvides a comprehensive summary of the LRT methods for signal detection including the basic theory and extensions for varying datasets that may be large post-market data or pre-market clinical trial dataContains details of scientific background, statistical methods, and associated algorithms that a reader can quickly master the materials and apply methods in the book on one’s own problems

Statistical methods that are commonly used in the review and approval process of regulatory submissions are usually referred to as statistics in regulatory science or regulatory statistics. In a broader sense, statistics in regulatory science can be defined as valid statistics that are employed in the review and approval process of regulatory submissions of pharmaceutical products. In addition, statistics in regulatory science are involved with the development of regulatory policy, guidance, and regulatory critical clinical initiatives related research. This book is devoted to the discussion of statistics in regulatory science for pharmaceutical development. It covers practical issues that are commonly encountered in regulatory science of pharmaceutical research and development including topics related to research activities, review of regulatory submissions, recent critical clinical initiatives, and policy/guidance development in regulatory science. Devoted entirely to discussing statistics in regulatory science for pharmaceutical development. Reviews critical issues (e.g., endpoint/margin selection and complex innovative design such as adaptive trial design) in the pharmaceutical development and regulatory approval process. Clarifies controversial statistical issues (e.g., hypothesis testing versus confidence interval approach, missing data/estimands, multiplicity, and Bayesian design and approach) in review/approval of regulatory submissions. Proposes innovative thinking regarding study designs and statistical methods (e.g., n-of-1 trial design, adaptive trial design, and probability monitoring procedure for sample size) for rare disease drug development. Provides insight regarding current regulatory clinical initiatives (e.g., precision/personalized medicine, biomarker-driven target clinical trials, model informed drug development, big data analytics, and real world data/evidence).This book provides key statistical concepts, innovative designs, and analysis methods that are useful in regulatory science. Also included are some practical, challenging, and controversial issues that are commonly seen in the review and approval process of regulatory submissions.About the authorShein-Chung Chow, Ph.D. is currently a Professor at Duke University School of Medicine, Durham, NC. He was previously the Associate Director at the Office of Biostatistics, Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA). Dr. Chow has also held various positions in the pharmaceutical industry such as Vice President at Millennium, Cambridge, MA, Executive Director at Covance, Princeton, NJ, and Director and Department Head at Bristol-MyersSquibb, Plainsboro, NJ. He was elected Fellow of the American Statistical Association and an elected member of the ISI (International Statistical Institute). Dr. Chow is Editor-in-Chief of the Journal of Biopharmaceutical Statistics and Biostatistics Book Series, Chapman and Hall/CRC Press, Taylor & Francis, New York. Dr. Chow is the author or co-author of over 300 methodology papers and 30 books.

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.

Clinical Trial Optimization Using R explores a unified and broadly applicable framework for optimizing decision making and strategy selection in clinical development, through a series of examples and case studies. It provides the clinical researcher with a powerful evaluation paradigm, as well as supportive R tools, to evaluate and select among simultaneous competing designs or analysis options. It is applicable broadly to statisticians and other quantitative clinical trialists, who have an interest in optimizing clinical trials, clinical trial programs, or associated analytics and decision making.This book presents in depth the Clinical Scenario Evaluation (CSE) framework, and discusses optimization strategies, including the quantitative assessment of tradeoffs. A variety of common development challenges are evaluated as case studies, and used to show how this framework both simplifies and optimizes strategy selection. Specific settings include optimizing adaptive designs, multiplicity and subgroup analysis strategies, and overall development decision-making criteria around Go/No-Go. After this book, the reader will be equipped to extend the CSE framework to their particular development challenges as well.

Praise for the first edition:"Given the author’s years of experience as a statistician and as a founder of the first DMC in pharmaceutical industry trials, I highly recommend this book—not only for experts because of its cogent and organized presentation, but more importantly for young investigators who are seeking information about the logistical and philosophical aspects of a DMC." -S. T. Ounpraseuth, The American Statistician In the first edition of this well-regarded book, the author provided a groundbreaking and definitive guide to best practices in pharmaceutical industry data monitoring committees (DMCs). Maintaining all the material from the first edition and adding substantial new material, Data and Safety Monitoring Committees in Clinical Trials, Second Edition is ideal for training professionals to serve on their first DMC as well as for experienced clinical and biostatistical DMC members, sponsor and regulatory agency staff. The second edition guides the reader through newly emerging DMC responsibilities brought about by regulations emphasizing risk vs benefit and the emergence of risk-based monitoring. It also provides the reader with many new statistical methods, clinical trial designs and clinical terminology that have emerged since the first edition. The references have been updated and the very popular end-of-chapter Q&A section has been supplemented with many new experiences since the first edition. New to the Second Edition: Presents statistical methods, tables, listings and graphs appropriate for safety review, efficacy analysis and risk vs benefit analysis, SPERT and PRISMA initiatives. Newly added interim analysis for efficacy and futility section. DMC responsibilities in SUSARs (Serious Unexpected Serious Adverse Reactions), basket trials, umbrella trials, dynamic treatment strategies /SMART trials, pragmatic trials, biosimilar trials, companion diagnostics, etc. DMC responsibilities for data quality and fraud detection (Fraud Recovery Plan) Use of patient reported outcomes of safety Use of meta analysis and data outside the trial New ideas for training and compensation of DMC membersJay Herson is Senior Associate, Biostatistics, Johns Hopkins Bloomberg School of Public Health where he teaches courses on clinical trials and drug development based on his many years experience in clinical trials in academia and the pharmaceutical industry.

Geospatial health data are essential to inform public health and policy. These data can be used to quantify disease burden, understand geographic and temporal patterns, identify risk factors, and measure inequalities. Geospatial Health Data: Modeling and Visualization with R-INLA and Shiny describes spatial and spatio-temporal statistical methods and visualization techniques to analyze georeferenced health data in R. The book covers the following topics: Manipulating and transforming point, areal, and raster data, Bayesian hierarchical models for disease mapping using areal and geostatistical data, Fitting and interpreting spatial and spatio-temporal models with the integrated nested Laplace approximation (INLA) and the stochastic partial differential equation (SPDE) approaches, Creating interactive and static visualizations such as disease maps and time plots, Reproducible R Markdown reports, interactive dashboards, and Shiny web applications that facilitate the communication of insights to collaborators and policymakers.The book features fully reproducible examples of several disease and environmental applications using real-world data such as malaria in The Gambia, cancer in Scotland and USA, and air pollution in Spain. Examples in the book focus on health applications, but the approaches covered are also applicable to other fields that use georeferenced data including epidemiology, ecology, demography or criminology. The book provides clear descriptions of the R code for data importing, manipulation, modelling, and visualization, as well as the interpretation of the results. This ensures contents are fully reproducible and accessible for students, researchers and practitioners.

Artificial Intelligence for Drug Development, Precision Medicine, and Healthcare covers exciting developments at the intersection of computer science and statistics. While much of machine-learning is statistics-based, achievements in deep learning for image and language processing rely on computer science’s use of big data. Aimed at those with a statistical background who want to use their strengths in pursuing AI research, the book:· Covers broad AI topics in drug development, precision medicine, and healthcare.· Elaborates on supervised, unsupervised, reinforcement, and evolutionary learning methods.· Introduces the similarity principle and related AI methods for both big and small data problems.· Offers a balance of statistical and algorithm-based approaches to AI.· Provides examples and real-world applications with hands-on R code.· Suggests the path forward for AI in medicine and artificial general intelligence.As well as covering the history of AI and the innovative ideas, methodologies and software implementation of the field, the book offers a comprehensive review of AI applications in medical sciences. In addition, readers will benefit from hands on exercises, with included R code.

Third-variable effect refers to the effect transmitted by third-variables that intervene in the relationship between an exposure and a response variable. Differentiating between the indirect effect of individual factors from multiple third-variables is a constant problem for modern researchers.Statistical Methods for Mediation, Confounding and Moderation Analysis Using R and SAS introduces general definitions of third-variable effects that are adaptable to all different types of response (categorical or continuous), exposure, or third-variables. Using this method, multiple third- variables of different types can be considered simultaneously, and the indirect effect carried by individual third-variables can be separated from the total effect. Readers of all disciplines familiar with introductory statistics will find this a valuable resource for analysis.Key Features:Parametric and nonparametric method in third variable analysisMultivariate and Multiple third-variable effect analysisMultilevel mediation/confounding analysisThird-variable effect analysis with high-dimensional data Moderation/Interaction effect analysis within the third-variable analysisR packages and SAS macros to implement methods proposed in the book

Add the Empirical Likelihood to Your Nonparametric ToolboxEmpirical Likelihood Method in Survival Analysis explains how to use the empirical likelihood method for right censored survival data. The author uses R for calculating empirical likelihood and includes many worked out examples with the associated R code. The datasets and code are available for download on his website and CRAN.The book focuses on all the standard survival analysis topics treated with empirical likelihood, including hazard functions, cumulative distribution functions, analysis of the Cox model, and computation of empirical likelihood for censored data. It also covers semi-parametric accelerated failure time models, the optimality of confidence regions derived from empirical likelihood or plug-in empirical likelihood ratio tests, and several empirical likelihood confidence band results.While survival analysis is a classic area of statistical study, the empirical likelihood methodology has only recently been developed. Until now, just one book was available on empirical likelihood and most statistical software did not include empirical likelihood procedures. Addressing this shortfall, this book provides the functions to calculate the empirical likelihood ratio in survival analysis as well as functions related to the empirical likelihood analysis of the Cox regression model and other hazard regression models.

Bayesian Modeling in Bioinformatics discusses the development and application of Bayesian statistical methods for the analysis of high-throughput bioinformatics data arising from problems in molecular and structural biology and disease-related medical research, such as cancer. It presents a broad overview of statistical inference, clustering, and classification problems in two main high-throughput platforms: microarray gene expression and phylogenic analysis.The book explores Bayesian techniques and models for detecting differentially expressed genes, classifying differential gene expression, and identifying biomarkers. It develops novel Bayesian nonparametric approaches for bioinformatics problems, measurement error and survival models for cDNA microarrays, a Bayesian hidden Markov modeling approach for CGH array data, Bayesian approaches for phylogenic analysis, sparsity priors for protein-protein interaction predictions, and Bayesian networks for gene expression data. The text also describes applications of mode-oriented stochastic search algorithms, in vitro to in vivo factor profiling, proportional hazards regression using Bayesian kernel machines, and QTL mapping.Focusing on design, statistical inference, and data analysis from a Bayesian perspective, this volume explores statistical challenges in bioinformatics data analysis and modeling and offers solutions to these problems. It encourages readers to draw on the evolving technologies and promote statistical development in this area of bioinformatics.

Bayesian analyses have made important inroads in modern clinical research due, in part, to the incorporation of the traditional tools of noninformative priors as well as the modern innovations of adaptive randomization and predictive power. Presenting an introductory perspective to modern Bayesian procedures, Elementary Bayesian Biostatistics explores Bayesian principles and illustrates their application to healthcare research.Building on the basics of classic biostatistics and algebra, this easy-to-read book provides a clear overview of the subject. It focuses on the history and mathematical foundation of Bayesian procedures, before discussing their implementation in healthcare research from first principles. The author also elaborates on the current controversies between Bayesian and frequentist biostatisticians. The book concludes with recommendations for Bayesians to improve their standing in the clinical trials community. Calculus derivations are relegated to the appendices so as not to overly complicate the main text.As Bayesian methods gain more acceptance in healthcare, it is necessary for clinical scientists to understand Bayesian principles. Applying Bayesian analyses to modern healthcare research issues, this lucid introduction helps readers make the correct choices in the development of clinical research programs.

Showcasing a discussion of the experimental process and a review of basic statistics, this volume provides methodologies to identify general data distribution, skewness, and outliers. It features a unique classification of the nonparametric analogs of their parametric counterparts according to the strength of the collected data. Applied Statistical Designs for the Researcher discusses three varieties of the Student t test, including a comparison of two different groups with different variances; two groups with the same variance; and a matched, paired group. It introduces the analysis of variance and Latin Square designs and presents screening approaches to comparing two factors and their interactions.

This volume describes how to conceptualize, perform, and critique traditional generalized linear models (GLMs) from a Bayesian perspective and how to use modern computational methods to summarize inferences using simulation. Introducing dynamic modeling for GLMs and containing over 1000 references and equations, Generalized Linear Models considers parametric and semiparametric approaches to overdispersed GLMs, presents methods of analyzing correlated binary data using latent variables. It also proposes a semiparametric method to model link functions for binary response data, and identifies areas of important future research and new applications of GLMs.

This remarkable text raises the analysis of data in health sciences and policy to new heights of refinement and applicability by introducing cutting-edge meta-analysis strategies while reviewing more commonly used techniques. Each chapter builds on sound principles, develops methodologies to solve statistical problems, and presents concrete applications used by experienced medical practitioners and health policymakers. Written by more than 30 celebrated international experts, Meta-Analysis in Medicine and Health Policy employs copious examples and pictorial presentations to teach and reinforce biostatistical techniques more effectively and poses numerous open questions of medical and health policy research.

R for Health Technology Assessment discusses the use of proper statistical software, specifically R, to perform the whole pipeline of analytic modelling in health technology assessment (HTA). It has been designed with the objective of establishing the use of R as the standard tool for HTA amongst academics, industry practitioners and regulators. It covers a lot of ground, starting with the necessary background in HTA, R and statistical inference, followed by various modelling tools, ranging from missing data, survival analysis and decision trees, through to multistate models and discrete event simulation. The methods are all illustrated with many detailed worked examples and case studies using real data, and there are detailed descriptions of the code and processes.Key Features:Introductory chapters on the various topics of the book, including HTA, R and statistical inferenceA wide range of common analytical tools used in HTA, from modelling for individual-level data, missing data, survival analysis, decision-modelling and network meta-analysisMore advanced and increasingly popular tools, such as those for population adjustment, discrete event simulation and the use of web applications as front-end for the overall statistical modellingMany detailed worked examples and case studies using real data to illustrate the methodologyFully integrated R code gives detailed guidance on implementation of the techniquesSupplemented by a website with additional resources, including annotated code and dataThis text is primarily aimed at modellers working in the field of HTA, regulators and reviewers of reimbursement dossiers and cost-effectiveness analyses. It also complements a wide range of undergraduate and graduate programmes in HTA, health and public health economics, as well as academic researchers in the field of statistical modelling for HTA.

Cancer is a dreaded disease. One in two people will be diagnosed with cancer within their lifetime. Medical Statistics for Cancer Studies shows how cancer data can be analysed in a variety of ways, covering cancer clinical trial data, epidemiological data, biological data, and genetic data. It gives some background in cancer biology and genetics, followed by detailed overviews of survival analysis, clinical trials, regression analysis, epidemiology, meta-analysis, biomarkers, and cancer informatics. It includes lots of examples using real data from the author’s many years of experience working in a cancer clinical trials unit. Features: A broad and accessible overview of statistical methods in cancer researchNecessary background in cancer biology and geneticsDetails of statistical methodology with minimal algebraMany examples using real data from cancer clinical trialsAppendix giving statistics revision.

With the critical role of statistics in the design, conduct, analysis and reporting of clinical trials or observational studies intended for regulatory purposes, numerous guidelines have been issued by regulatory authorities around the world focusing on statistical issues related to drug development. However, the available literature on this important topic is sporadic, and often not readily accessible to drug developers or regulatory personnel. This book provides a systematic exposition of the interplay between the two disciplines, including emerging themes pertaining to the acceleration of the development of pharmaceutical medicines to serve patients with unmet needs. Features: Regulatory and statistical interactions throughout the drug development continuum The critical role of the statistician in relation to the changing regulatory and healthcare landscapes Statistical issues that commonly arise in the course of drug development and regulatory interactions Trending topics in drug development, with emphasis on current regulatory thinking and the associated challenges and opportunities The book is designed to be accessible to readers with an intermediate knowledge of statistics, and can be a useful resource to statisticians, medical researchers, and regulatory personnel in drug development, as well as graduate students in the health sciences. The authors’ decades of experience in the pharmaceutical industry and academia, and extensive regulatory experience, comes through in the many examples throughout the book.

In the United States, a rare disease is defined by the Orphan Drug Act as a disorder or condition that affects fewer than 200,000 persons. For the approval of "orphan" drug products for rare diseases, the traditional approach of power analysis for sample size calculation is not feasible because there are only limited number of subjects available for clinical trials. In this case, innovative approaches are needed for providing substantial evidence meeting the same standards for statistical assurance as drugs used to treat common conditions. Innovative Methods for Rare Disease Drug Development focuses on biostatistical applications in terms of design and analysis in pharmaceutical research and development from both regulatory and scientific (statistical) perspectives. Key Features: Reviews critical issues (e.g., endpoint/margin selection, sample size requirements, and complex innovative design). Provides better understanding of statistical concepts and methods which may be used in regulatory review and approval. Clarifies controversial statistical issues in regulatory review and approval accurately and reliably. Makes recommendations to evaluate rare diseases regulatory submissions. Proposes innovative study designs and statistical methods for rare diseases drug development, including n-of-1 trial design, adaptive trial design, and master protocols like platform trials. Provides insight regarding current regulatory guidance on rare diseases drug development like gene therapy.

In the United States, a rare disease is defined by the Orphan Drug Act as a disorder or condition that affects fewer than 200,000 persons. For the approval of "orphan" drug products for rare diseases, the traditional approach of power analysis for sample size calculation is not feasible because there are only limited number of subjects available for clinical trials. In this case, innovative approaches are needed for providing substantial evidence meeting the same standards for statistical assurance as drugs used to treat common conditions. Innovative Methods for Rare Disease Drug Development focuses on biostatistical applications in terms of design and analysis in pharmaceutical research and development from both regulatory and scientific (statistical) perspectives. Key Features: Reviews critical issues (e.g., endpoint/margin selection, sample size requirements, and complex innovative design). Provides better understanding of statistical concepts and methods which may be used in regulatory review and approval. Clarifies controversial statistical issues in regulatory review and approval accurately and reliably. Makes recommendations to evaluate rare diseases regulatory submissions. Proposes innovative study designs and statistical methods for rare diseases drug development, including n-of-1 trial design, adaptive trial design, and master protocols like platform trials. Provides insight regarding current regulatory guidance on rare diseases drug development like gene therapy.

A disease is defined as rare if the prevalence is fewer than 200,000 in the United States. It is estimated that there are more than 7,000 rare diseases, which collectively affect 30 million Americans or 10% of the US population. This diverse and complex disease area poses challenges for patients, caregivers, regulators, drug developers, and other stakeholders. This book is proposedto give an overview of the common issues facing rare disease drug developers, summarize challenges specific to clinical development in small populations, discuss drug development strategies in the evolving regulatory environment, explain generation and utilization of different data and evidenceinside and beyond clinical trials, and use recent examples to demonstrate these challenges and the development strategies that respond to the challenges.Key Features:• Rare disease.• Drug development.• Innovative clinical trial design.• Regulatory approval.• Real-world evidence.

Advanced Statistics in Regulatory Critical Clinical Initiatives is focused on the critical clinical initiatives introduced by the 21st Century Cure Act passed by the United States Congress in December 2016. The book covers everything from the outline of the initiatives to analysis on the effect on biopharmaceutical research and development. Advanced Statistics in Regulatory Critical Clinical Initiatives provides innovative ways to resolve common challenges in statistical research of rare diseases such small sample sizes and provides guidance for combined use of data. With analysis from regulatory and scientific perspectives this book is an ideal companion for researchers in biostatistics, pharmaceutical development, and policy makers in related fields.Key Features:Provides better understanding of innovative design and analysis of each critical clinical initiatives which may be used in regulatory review/approval of drug development.Makes recommendations to evaluate submissions accurately and reliably.Proposes innovative study designs and statistical methods for oncology and/or rare disease drug development.Provides insight regarding current regulatory guidance on drug development such as gene therapy and rare diseases.

Global simultaneous development is becoming more necessary as the cost of developing medical products continues to grow. The strategy of using multiregional clinical trials (MRCTs) has become the preferred method for developing new medicines. Implementing the same protocol to include subjects from many geographical regions around the world, MRCTs can speed up the patient enrolment, thus resulting in quicker drug development and obtaining faster approval of the drug globally.After the publication of the editors’ first volume on this topic, there have been new developments on MRCTs. The International Council for Harmonisation (ICH) issued ICH E17, a guideline document on MRCTs, in November 2017, laying out principles on MRCTs. Beyond E17, new methodologies have been developed as well.Simultaneous Global New Drug Development: Multi-Regional Clinical Trials after ICH E17 collects chapters providing interpretations of principles in ICH E17 and new ideas of implementing MRCTs. Authors are from different regions, and from academia and industry. In addition, in contrast to the first book, new perspectives are brought to MRCT from regulatory agencies. This book will be of particular interest to biostatisticians working in late stage clinical development of medical products. It will also be especially helpful for statisticians in regulatory agencies, and medical research institutes.This book is comprehensive across the MRCT topic spectrum, includingIssues regarding ICH E17 ImplementationMRCT Design and Analysis MethodologiesPerspectives from authorities in regulatory agencies, as well as statisticians practicing in the medical product industryMany examples of real-life applications based on actual MRCTs