This book examines the sequence of events and methodology in the industrial clinical research process; a reference for multidisciplinary personnel. It is the conceptual framework involving the philosophical, economic, political, historical, regulatory, planning, and marketing aspects of the process.

'Bad Science' hilariously exposed the tricks that quacks and journalists use to distort science, becoming a 400,000 copy bestseller. Now Ben Goldacre puts the $600bn global pharmaceutical industry under the microscope. What he reveals is a fascinating, terrifying mess. Doctors and patients need good scientific evidence to make informed decisions. But instead, companies run bad trials on their own drugs, which distort and exaggerate the benefits by design. When these trials produce unflattering results, the data is simply buried. All of this is perfectly legal. In fact, even government regulators withhold vitally important data from the people who need it most. Doctors and patient groups have stood by too, and failed to protect us. Instead, they take money and favours, in a world so fractured that medics and nurses are now educated by the drugs industry. The result: patients are harmed in huge numbers. Ben Goldacre is Britain's finest writer on the science behind medicine, and 'Bad Pharma' is the book that finally prompted Parliament to ask why all trial results aren't made publicly available - this edition has been updated with the latest news from the select committee hearings. Let the witty and indefatigable Goldacre show you how medicine went wrong, and what you can do to mend it.

The growth of the pharmaceutical industry over the past decade is astounding, but the impact of this growth on statistics is somewhat confusing. While software has made analysis easier and more efficient, regulatory bodies now demand deeper and more complex analyses, and pharmacogenetic/genomic studies serve up an entirely new set of challenges. For more than two decades, Statistics in the Pharmaceutical Industry has been the definitive guide to sorting through the challenges in the industry, and this Third Edition continues that tradition. Updated and expanded to reflect the most recent trends and developments in the field, Statistics in the Pharmaceutical Industry, Third Edition presents chapters written by experts from both regulatory agencies and pharmaceutical companies who discuss everything from experimental design to post-marketing studies. This approach sheds light on what regulators consider acceptable methodologies and what methods have proven successful for industrial statisticians. Both new and revised chapters reflect the increasingly global nature of the industry as represented by authors from Japan and Europe, the increasing trend toward non-inferiority/equivalence testing, adaptive design in clinical trials, global harmonization of regulatory standards, and multiple comparison studies. The book also examines the latest considerations in anti-cancer studies. Statistics in the Pharmaceutical Industry, Third Edition demystifies the approval process by combining regulatory and industrial points of view, making it a must-read for anyone performing statistical analysis at any point in the drug approval process.

The third edition of Evaluating Research by Francis C. Dane and Elliot Carhart provides students with the skills to read and evaluate research studies. Aimed at courses where it is more important for students to develop an understanding of methods, rather than conduct their own research, this book covers all aspects of reading social, behavioral, and health science research from the basics, such as the structure of reports and accessing research, as well as overviews of the main types of research methods. The authors emphasize critical reading skills to enable students to become experts in evaluating research, so students can decide whether to incorporate that research into their future professional activities. Each chapter includes an overview at the beginning and exercises at the end to reinforce the content learned. Starting from the basic principles of why we do research, the book moves readers through the practicalities of finding studies to the principles of the scientific method and how to break down and analyze research reports. New to the third edition, Understanding Checks placed throughout each chapter help students cement their learning. The organization of the book is now more logical, with a new chapter on accessing research up front and ending with a chapter on statistical analyses. New research examples throughout, including such topical examples as mindfulness, college attendance, and bias in healthcare, help students see the relevance of research in their lives.

This volume takes an in-depth look at the potential pharmacological applications of 11 important antidiabetic plants, examining their antihyperglycemic, hypoglycemic, and anti-lipidemic properties along with current genome editing research perspectives. Plant natural products, or phytoconstituents, are promising candidates for antidiabetic pharmacological actions. The phytoconstituents, such as i' avonoids, terpenoids, saponins, carotenoids, alkaloids and glycosides, play vital roles in the current and future potent antidiabetic drug development programs Each chapter reviews a particular plant with antidiabetic properties, explaining the therapeutic aspects, its active antidiabetic compounds, and relevant genome editing technology. The specific plants discussed include Azadirachta indica (commonly known as neem, nimtree or Indian lilac), Gymnema sylvestre (commonly called gymnema, Australian cowplant, and Periploca of the woods), Syzygium cumini (commonly known as Malabar plum, Java plum, black plum, jamun or jambolana), Ceylon cinnamon (or true cinnamon, as opposed to cassia cinnamon), insulin plant (or Costus pictus), Trigonella foenum-graecum (better known as fenugreek), Mulberry, Nigella sativa L. (black caraway, also known as black cumin, nigella, kalojeera, kalonji or kalanji), Aegle marmelos (L.) (commonly known as bael (or bili or bhel), also Bengal quince, golden apple, Japanese bitter orange, stone apple or wood apple), Ficus benghalensis (the banyan, banyan fig and Indian banyan), and of course, garlic (Allium sativum). Antidiabetic Plants for Drug Discovery: Pharmacology, Secondary Metabolite Profiling, and Ingredients with Insulin Mimetic Activity will serve as a valuable source of information for students, drug researchers, medical practitioners, diabetic patients, and many others in the effort to gain understand of how these plant drug molecules can help fight diabetes.

What is research and how does it work in the context of nursing, health and social care? This introductory guide provides you with a concise overview of the different research methods and terminology that you will come across when undertaking research in any course related to nursing, health and social care. The book's easy-to-follow structure takes you from research novice to confident researcher, helping you to make sense of research and understand how it is implemented in healthcare practice. The new edition includes: Updates in light of the 2018 NMC standards, with more information on the impact of GDPR, consent and vulnerable groups, Personal and Public Involvement (PPI), and work-based projects. Improved case examples of real research, with more on group work, poster presentations, research output and dissemination, literature reviews, and dissertations. Upgraded activities that include reflective exercises, critical appraisal tools, a dissemination plan, and a glossary, all in the book. This is essential reading for undergraduate and postgraduate students within the health and therapy professions, nurses, midwives, physiotherapists, radiographers, occupational therapists, speech and language therapists, and paramedics.

Gives a convenient summary of trials in Gynecologic Oncology Supplies an invaluable revision primer for those undertaking certification Provides a uniquely up-to-date resource

New discoveries in the field of stem cells increasingly dominate the news and scientific literature revealing an avalanche of new knowledge and research tools that are producing therapies for cancer, heart disease, diabetes, and a wide variety of other diseases that afflict humanity. The Handbook of Stem Cells integrates this exciting area of life science, combining in two volumes the requisites for a general understanding of adult and embryonic stem cells. Organized in two volumes entitled Pluripotent Stem Cells & Cell Biology and Adult & Fetal Stem Cells, this work contains contributions from the world s experts in stem cell research to provide a description of the tools, methods, and experimental protocols needed to study and characterize stem cells and progenitor populations as well as a the latest information of what is known about each specific organ system.
* Provides comprehensive coverage on this highly topical subject
* Contains contributions by the foremost authorities and premiere names in the field of stem cell research
*Companion website - http: //booksite.elsevier.com/9780123859426/- containsover 250 color figures in presentation format"

Organic chemistry research has moved rapidly toward synthesis and medicinal application of nitrogen-containing compounds such as triazenes, triazines, and hydroxytriazenes due to their excellent biological activities. Many of them are presently in clinical trials. Triazene compounds have excellent medicinal properties and limited toxicity. Hydroxytriazenes are excellent chelating agents for transition metals. Newer studies show very promising biological and medicinal applications of these classes of compounds. Hydroxytriazenes and Triazenes: The Versatile Framework, Synthesis, and Medicinal Applications highlights synthetic methods, recent advances, and potential applications of triazines, triazenes, and hydroxytriazenes. This book includes holistic information on synthetic methods for novel compounds based on this moiety, up-to-date information on the how and why of their diverse or even multitargeted medicinal application, and future state of the art of both aspects. Other features include: Highlights recent advances and diverse possible applications of biological functions Covers the chemistry of triazine, triazene, and hydroxytriazene systems On the basis of in silico predictions, the book highlights synthetic methods and their applications A valuable source of information for those actively engaged in medicinal chemistry, drug discovery, and synthetic organic chemistry

Include advance knowledge and detailed developments in natural product science Discusses about the most important phytopharmaceuticals used in pharmaceutical industries Explores the analysis and classification of novel plant-based medicinal compounds Includes standardization, quality control, global trade of natural products Gives a deep understanding related to recent advances in the herbal medicines to treat various ailments Discusses about national and WHO regulations and policies related to herbal medicine Covers the complete profile of some important traditional medicinal plants especially their historical background, biology and chemistry

Provides a comprehensive review of challenges and opportunities as related to the applications of big data, AI, and machine learning in the entire spectrum of drug R&D Discusses regulatory developments in leveraging big data and advanced analytics in drug review and approval Offers a balanced approach to data science organization build Presents real-world examples of AI-powered solutions to a host of issues in the lifecycle of drug development Affords sufficient context for each problem and provides detailed description of solutions suitable for practitioners with limited data science expertise

Survival analysis generally deals with analysis of data arising from clinical trials. Censoring, truncation, and missing data create analytical challenges and the statistical methods and inference require novel and different approaches for analysis. Statistical properties, essentially asymptotic ones, of the estimators and tests are aptly handled in the counting process framework which is drawn from the larger arm of stochastic calculus. With explosion of data generation during the past two decades, survival data has also enlarged assuming a gigantic size. Most statistical methods developed before the millennium were based on a linear approach even in the face of complex nature of survival data. Nonparametric nonlinear methods are best envisaged in the Machine Learning school. This book attempts to cover all these aspects in a concise way. Survival Analysis offers an integrated blend of statistical methods and machine learning useful in analysis of survival data. The purpose of the offering is to give an exposure to the machine learning trends for lifetime data analysis. Features: Classical survival analysis techniques for estimating statistical functional and hypotheses testing Regression methods covering the popular Cox relative risk regression model, Aalen's additive hazards model, etc. Information criteria to facilitate model selection including Akaike, Bayes, and Focused Penalized methods Survival trees and ensemble techniques of bagging, boosting, and random survival forests A brief exposure of neural networks for survival data R program illustration throughout the book

Statistical Approaches in Oncology Clinical Development : Current Paradigm and Methodological Advancement presents an overview of statistical considerations in oncology clinical trials, both early and late phase of development. It illustrates how novel statistical methods can enrich the design and analysis of modern oncology trials. The authors include many relevant real life examples from the pharmaceutical industry and academia based on their first-hand experience. Along with relevant references, the book highlights current regulatory views. The book covers all aspects of cancer clinical trial starting from early phase development. The early part of the book covers novel phase I dose escalation design, exposure response analysis, and innovative phase II design. This includes early development strategy for cancer immunotherapy trials. The contributors also emphasized the role of biomarker and modern era of precision medicine. The second part focuses on the late stage development. This includes the application of adaptive design, safety analysis, and quality of life (QoL) data analysis. The final part discusses current regulatory perspective and challenges. Features: Covers a wide spectrum of topics related to real-life statistical challenges in oncology clinical trials. Provides a comprehensive overview of novel statistical methods to improve trial design and statistical analysis. Detailed case studies illustrate the real life applications. Satrajit Roychoudhury is a Senior Director and a member of the Statistical Research and Innovation group in Pfizer Inc. Prior to joining; he was a member of Statistical Methodology and consulting group in Novartis. He has 11 years of extensive experience in working with different phases of clinical trial. His area of research includes early phase oncology trials, survival analysis, model informed drug development, and use of Bayesian methods in clinical trials. He is industry co-chair for the ASA Biopharmaceutical Section Regulatory-Industry Workshop and has provided statistical training in major conferences including the Joint Statistical Meetings, ASA Biopharmaceutical Section Regulatory-Industry Workshop, and ICSA Applied Statistics Symposium. Soumi Lahiri has 12 years of extensive experience in working different therapeutic areas. She is the former Director of Biostatistics in Clinical Oncology, GlaxoSmithKline. She has also worked in the oncology division of Novartis Pharmaceutical Company for two years. She is an active member of the ASA Biopharmaceutical section and former chair of the membership committee.

Cluster Randomised Trials, Second Edition discusses the design, conduct, and analysis of trials that randomise groups of individuals to different treatments. It explores the advantages of cluster randomisation, with special attention given to evaluating the effects of interventions against infectious diseases. Avoiding unnecessary mathematical detail, the book covers basic concepts underlying the use of cluster randomisation, such as direct, indirect, and total effects. In the time since the publication of the first edition, the use of cluster randomised trials (CRTs) has increased substantially, which is reflected in the updates to this edition. There are greatly expanded sections on randomisation, sample size estimation, and alternative designs, including new material on stepped wedge designs. There is a new section on handling ordinal outcome data, and an appendix with descriptions and/or generating code of the example data sets. Although the book mainly focuses on medical and public health applications, it shows that the rigorous evidence of intervention effects provided by CRTs has the potential to inform public policy in a wide range of other areas. The book encourages readers to apply the methods to their own trials, reproduce the analyses presented, and explore alternative approaches.

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. Features Provides the first book and a single source of information on RWE in drug development Covers 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 insights Offers a balanced discussion of practical RWE issues at hand and technical solutions suitable for practitioners with limited data science expertise

The biological function of clusterin (CLU, also known as ApoJ, SGP2, TRPM2, CLI) has been puzzling researchers since its discovery and characterization in the early 1980s. Approaches such as cloning, expression and functional characterization of the different protein products generated by the CLU gene have now produced a critical mass of information of tremendous biological importance that are teaching us an important lesson in molecular biology of gene expression regulation. This volume brings together the contributions of top researchers in the field, providing an overview and synthesis of the latest thought and findings relating to CLU.

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.

This book is a continuation of the book Medicine Researcher Biographical Sketches and Research Summaries which compiles biographical sketches of top professionals in the field of medicinal research, as well as research summaries from a number of different focuses in this important field.

We have surpassed the omics era and are truly in the Age of Molecular Therapeutics. The fast-paced development of SARS-CoV-2 vaccines, such as the mRNA vaccines encoding the viral spike protein, demonstrated the need for and capability of molecular therapy and nanotechnology-based solutions for drug delivery. In record speed, the SARS-CoV-2 viral RNA genome was sequenced and shared with the scientific community, allowing the rapid design of molecular therapeutics. The mRNA vaccines exploit the host cell endoplasmic reticulum to produce viral spike proteins for antigen presentation and recognition by the innate and adaptive immune system. Lipid nanoparticles enable the delivery of the fragile, degradation-sensitive nucleic acid payloads. Molecular-based therapeutics and nanotechnology solutions continue to drive the scientific and medical response to the COVID-19 pandemic as new mRNA, DNA, and protein-based vaccines are developed and approved and the emergency use approved vaccines are rapidly manufactured and distributed throughout the globe. The need for molecular therapies and drug delivery solutions is clear, and as these therapies progress and become more specialized there will be important advancements in organelle targeting. For example, using organelle targeting to direct lipid nanoparticles with mRNA payloads to the endoplasmic reticulum would increase the efficacy of mRNA vaccines, reducing the required dose and therefore the biomanufacturing demand. Likewise, improving the delivery of DNA therapeutics to the nucleus would improve efficacy. Organelles and molecules have always been drug targets, but until recently we have not had the tools or capability to design and develop such highly specific therapeutics. Organelle targeting has far-reaching implications. For example, mitochondria are central to both energy production and intrinsic apoptosis. Effectively targeting and manipulating mitochondria has therapeutic applications for diseases such as myopathies, cancer, neurodegeneration, progerias, diabetes, and the natural aging process. The SARS-CoV-2 vaccines that exploit the endoplasmic reticulum (for mRNA vaccines) and the nucleic translational process (DNA vaccines) attest to the need for organelle and molecular therapeutics. This book covers the status, demand, and future of organelle- and molecularly targeted therapeutics that are critical to the advancement of modern medicine. Organelle and molecular targeting is the drug design and drug delivery approach of today and the future; understanding this approach is essential for students, scientists, and clinicians contributing to modern medicine.

For more than a century, bioactive heterocycles have formed one of the largest areas of research in organic chemistry. They are important from a biological and industrial point of view as well as to the understanding of life processes and efforts to improve the quality of life. Heterogeneous Catalysis: A Versatile Tool for the Synthesis of Bioactive Heterocycles highlights the recent methodologies used in the synthesis of such bioactive systems and focuses on the role of heterogeneous catalysis in the design and synthesis of various biologically active heterocyclic compounds of pharmacological interest. Topics include: Synthetic protocols for the construction of heterocyclic systems employing silica-bound catalysts Recent advances in heterogeneous copper-catalyzed reactions for the synthesis of bioactive heterocycles Features of silica-based heterogeneous catalysts, such as abundance, ease of use, and stability Ultrasound as an effective tool for accelerating reactions Organic transformations catalyzed by nano-ZnO as a valuable heterogeneous catalyst Heterogeneous catalysts employed in the synthesis of coumarins Heterocyclizations in the presence of silver salts Home-made organometallic silica sources, known as silatranes Reflecting the focused studies currently conducted in these areas, the book also examines anticancer, antifungal, antibacterial, anti-HIV, anti-inflammatory, antioxidant, and many more biological activities of heterocyclic compounds. It is essential reading for postgraduate and research scholars in the fields of biochemistry, chemical biology, medicinal chemistry and pharmaceutical chemistry.

This book is devoted to the problems of oxidation chemical reactions and addresses bimodal reaction sequences. Chemical reactions of oxidation, occurring under certain conditions and in multicomponent systems are complex processes. The process of the oxidation essentially changes in the presence and contact of the solid substances with reactants. The role of solid substances and the appearance of this phenomenon in oxidation reaction are discussed. The reader will understand the "driving forces" of this phenomenon and apply it in practice. Written for chemists, physicists, biologists and engineers working in the domain of oxidation reactions. Key Selling Features: Covers the historical background, modern state of the art, and perspectives in investigations of the coupling between heterogeneous and homogeneous reactions Discusses the feasible pathways of the coupling of heterogeneous and homogeneous reactions in oxidation in man-made and natural chemical systems Addresses the abundance, peculiarities and mechanisms of the bimodal reaction sequences in oxidation with dioxygen in recent decades Discusses the existence of the bimodal reaction sequences in chemical systems investigations in atmospheric chemistry and heterogeneous photocatalysis Presented in a simple concise style, accessible for both specialists and non-specialists

The concepts of estimands, analyses (estimators), and sensitivity are interrelated. Therefore, great need exists for an integrated approach to these topics. This book acts as a practical guide to developing and implementing statistical analysis plans by explaining fundamental concepts using accessible language, providing technical details, real-world examples, and SAS and R code to implement analyses. The updated ICH guideline raises new analytic and cross-functional challenges for statisticians. Gaps between different communities have come to surface, such as between causal inference and clinical trialists, as well as among clinicians, statisticians, and regulators when it comes to communicating decision-making objectives, assumptions, and interpretations of evidence. This book lays out a path toward bridging some of these gaps. It offers ? A common language and unifying framework along with the technical details and practical guidance to help statisticians meet the challenges ? A thorough treatment of intercurrent events (ICEs), i.e., postrandomization events that confound interpretation of outcomes and five strategies for ICEs in ICH E9 (R1) ? Details on how estimands, integrated into a principled study development process, lay a foundation for coherent specification of trial design, conduct, and analysis needed to overcome the issues caused by ICEs: ? A perspective on the role of the intention-to-treat principle ? Examples and case studies from various areas ? Example code in SAS and R ? A connection with causal inference ? Implications and methods for analysis of longitudinal trials with missing data Together, the authors have offered the readers their ample expertise in clinical trial design and analysis, from an industrial and academic perspective.

The primary aim of Writing Research is to create a frame of reference for writing research from a number of approaches to inquiry; and for a number of purposes. The content is directed to identifying principles for writing from within commonly used methodologies and methods in health research, which will guide writers to transform research data into written forms. The emphasis will be on the writing task, not on how to conduct the research, which follows after research data has been collected. The explanatory aspects of the content of the book will assist researchers in the development of research proposals and those who critique or review research for any purpose. The theory and practice of research writing are comprehensively covered. Information on how to arrange material for specific purposes is provided. A range of commonly used research approaches is encompassed, and the writing task is discussed from within each. The writing process is linked to a philosophical basis of the research approach.

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, including Issues regarding ICH E17 Implementation MRCT Design and Analysis Methodologies Perspectives from authorities in regulatory agencies, as well as statisticians practicing in the medical product industry Many examples of real-life applications based on actual MRCTs.

A clear and practical guide to completing a literature review in nursing and healthcare studies. Providing you with straightforward guidance on how to successfully carry out a literature review as part of your research project or dissertation, this book uses examples and activities to demonstrate how to complete each step correctly, from start to finish, and highlights how to avoid common mistakes. Perfect for any nursing or healthcare student new to literature reviews and for anyone who needs a refresher on this important topic. The third edition includes: Expert advice on selecting and researching a topic A chapter outlining the different types of literature review you may come across Increased focus on Critical Appraisal Tools and how to use them effectively New real-world examples presenting best practice Instructions on writing up and presenting the final piece of work