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 advanced AI techniques are essential for resolving various problematic aspects emerging in the field of bioinformatics. This book covers the recent approaches in artificial intelligence and machine learning methods and their applications in Genome and Gene editing, cancer drug discovery classification, and the protein folding algorithms among others. Deep learning, which is widely used in image processing, is also applicable in bioinformatics as one of the most popular artificial intelligence approaches. The wide range of applications discussed in this book are an indispensable resource for computer scientists, engineers, biologists, mathematicians, physicians, and medical informaticists. Features: Focusses on the cross-disciplinary relation between computer science and biology and the role of machine learning methods in resolving complex problems in bioinformatics Provides a comprehensive and balanced blend of topics and applications using various advanced algorithms Presents cutting-edge research methodologies in the area of AI methods when applied to bioinformatics and innovative solutions Discusses the AI/ML techniques, their use, and their potential for use in common and future bioinformatics applications Includes recent achievements in AI and bioinformatics contributed by a global team of researchers

Phylogenetic presentation of medicinal plants and a chemotaxonomical rationale of antiviral, antibacterial, and antifungal action. Discusses chemical structure-activity relationship, pharmacokinetics, and oral bioavailability of antimicrobial principles Introduces the molecular mechanism of natural products on viruses, bacteria, and fungi. Contains a selection of botanical plates and useful bibliographic references A useful research tool for postgraduates, academics, and the pharmaceutical, herbal, or nutrition industries.

Phylogenetic presentation of medicinal plants and a chemotaxonomical rationale of antiviral, antibacterial, and antifungal action. Discusses chemical structure-activity relationship, pharmacokinetics, and oral bioavailability of antimicrobial principles Introduces the molecular mechanism of natural products on viruses, bacteria, and fungi. Contains a selection of hand-made botanical plates and useful bibliographic references A useful research tool for postgraduates, academics, and the pharmaceutical, herbal, or nutrition industries.

Describes the ways Vitamin C can inhibit, perturb or retard the growth and spread of cancer through changing the ways cancers respond to different doses and treatmentsSumarizes the results of clinical trialsOutlines therapeutical usesChapters by an international team of researchers.

Methodologies for Biosimilar Product Development covers the practical and challenging issues that are commonly encountered during the development, review, and approval of a proposed biosimilar product. These practical and challenging issues include, but are not limited to the mix-up use of interval hypotheses testing (i.e., the use of TOST) and confidence interval approach, a risk/benefit assessment for non-inferiority/similarity margin, PK/PD bridging studies with multiple references, the detection of possible reference product change over time, design and analysis of biosimilar switching studies, the assessment of sensitivity index for assessment of extrapolation across indications without collecting data from those indications not under study, and the feasibility and validation of non-medical switch post-approval. Key Features: Reviews withdrawn draft guidance on analytical similarity assessment. Evaluates various methods for analytical similarity evaluation based on FDA's current guidelines. Provides a general approach for the use of n-of-1 trial design for assessment of interchangeability. Discusses the feasibility and validity of the non-medical switch studies. Provides innovative thinking for detection of possible reference product change over time. This book embraces innovative thinking of design and analysis for biosimilar studies, which are required for review and approval of biosimilar regulatory submissions.

Medicinal Chemistry: A Look at How Drugs Are Discovered is written for those who are interested in learning how drugs are discovered. Compared to other books on the market, this text takes a different approach by presenting the subject on chemical reaction mechanism terms, which ideally makes the subject matter more interesting and easier to comprehend. The authors describe the drug discovery process, from advancing an initial lead to the approval process, and include drug discovery sources. Additional features: Explains medicinal chemistry on chemical mechanism terms, allowing for a more interesting and easier to comprehend text Includes valuable insights toward the various pathways taken at pharmaceutical industries in drug discoveries Improved by including questions raised and suggestions made from students in the authors' medicinal chemistry classes This book will benefit both upper level undergraduates and graduates studying in the fields of medicinal chemistry and drug discovery, as well as scientists working in the pharmaceutical industry.

Renowned experts give all essential aspects of the techniques and applications of graft copolymers based on polysaccharides. Polysaccharides are the most abundant natural organic materials and polysaccharide based graft copolymers are of great importance and widely used in various fields. Natural polysaccharides have recently received more attention due to their advantages over synthetic polymers by being non-toxic, biodegradable and available at low cost. Modification of polysaccharides through graft copolymerization improves the properties of polysaccharides. Grafting is known to improve the characteristic properties of the backbones. Such properties include water repellency, thermal stability, flame resistance, dye-ability and resistance towards acid-base attack and abrasion. Polysaccharides and their graft copolymers find extensive applications in diversified fields. Applications of modified polysaccharides include drug delivery devices, controlled release of fungicides, selective water absorption from oil-water emulsions, purification of water etc.

This volume addresses efforts to overcome the shortcomings of conventional dosage forms by exploiting the principles of nanoscience to deliver drugs for medical treatment. Nanodispersions are an important aspect because they possess globules/particles in sizes usually below 1000 nm in which the drug is dispersed in a continuous medium employing surface-active agents as stabilizers. With chapters written by experienced scientists and researchers in the field, this volume provides an abundance of information on various aspects of nanodispersions for drug delivery. The book is divided into several sections: nanoemulsions, nanosuspensions, and diverse dispersed systems. The chapters detail what nanodispersions have demonstrated in the past and what they are expoected to continue to do in the future as the technology further evolves. Key features: * Provides an overview of nanoemulsions for drug delivery * Introduces the general principles, classification, and methods of preparation of nanoemulsion-based drug delivery systems * Presents information relevant to specific routes of applications of nanoemulsions * Looks at the various aspects of nanosuspensions, including their formulation components, preparation methods, unique features, methods of characterization, and applications in various routes of administration * Explores nanomicellar approaches for drug delivery * Discusses the preparation, applications, and clinical considerations of nanogels for drug delivery

The new volume takes an interdisciplinary look at current technical challenges and recent developmental trends in microbial biotechnology. It covers an avalanche of new information available through research by focusing on a broad spectrum of issues on different microorganisms and their recent applications and implications in agriculture, soil science and forestry, industry, and public health and medicine. Microbes present in our immediate environment have a direct or indirect influence leading to either a harmful or beneficial effect. Microbial Biotechnology: Technological Challenges and Developmental Trends is divided into four major sections that focus on Part I: Antimicrobial Agents: Role and Applications in Medicine and Health Care Part II: Role of Microorganisms in Agriculture and Plant Biotechnology Part III: Microbial Enzymes and Their Potential Industrial Applications Part IV: Microorganisms in Environment: Role and Industrial Applications Topic include organic chemistry, biomass conversion, optimal production processes for different microbes, screening methods, and application of omics approaches such as (meta) genomics, proteomics, and metabolomics, or other biotechnology tools, to provide a deeper understanding of the microbial-based new and emerging products, trends, processes, and technologies. The chapters present unbiased original research results on microbes by incorporating case studies wherever appropriate. Providing research findings applicable to the development of new methodologies, applications, and technologies, the book will be a valuable resource for people working in various fields of microbiology.

Drug Discovery with Privileged Building Blocks traces back PharmaBlock's founding philosophy of designing privileged building blocks. High-quality building blocks are crucial not only to biological activities of different molecules but also to ADMET properties, which eventually will impact the success rate of drug discovery projects. A thorough study of how building blocks perform in drug molecules and a regular analysis of new building block structures in the latest researches have proven to be a fruitful strategy to generate novel building blocks. Using this strategy, PharmaBlock has supplied the drug industry with a great number of building blocks, which are increasingly being adopted by drug hunters, and these are identified in this book. Each chapter may be read and studied without learning the previous chapters. This book will be a good starting point for novice medicinal chemists, and veteran medicinal chemists will find it useful as well. Key Feature The book covers privileged building blocks appearing most frequently on patents for novel drugs. The latest relevant tactics are explained in the context of drug design and medicinal chemistry. Key synthesis, especially large-scale synthesis, is described. The most recent literature references are cited.

Over the past decade, major advancements in the understanding of the molecular mechanisms and pathophysiology of pulmonary hypertension occurred in parallel with the discovery and development of new therapies. Pharmacological agents that modulate the main pathophysiological pathways of pulmonary arterial hypertension have changed the course of this devastating disease by relieving symptoms and improving and prolonging patients lives.

The first part of the book covers definition, classification, pathophysiology, pathology, biomarkers and animal models of pulmonary hypertension, thus laying the conceptual basis for what follows. The middle section provides an overview of the established therapies, such as calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and inhaled nitric oxide. The concluding section explores novel pathways and emerging therapeutic approaches including soluble guanylate cyclase stimulators, Rho-kinase inhibitors, inhibitors of serotonin receptors and transporters, peptide growth factors, vasoactive peptides, modulators of redox equilibrium and cyclic nucleotides homeostasis, as well as immunosuppressive and anti-proliferative agents. Particular attention is given to clinical applications of these experimental therapies. "

Discusses endogenous benzodiazepine-like substances - what do they do, do they affect the anti-anxiety drugs and their adverse effects? Presents information on the enigmatic prolonged benzodiazepine withdrawal syndrome Describes the compounds acting at the BDZ binding sites, both exogenous (classical BDZ drugs and BDZ from food and plants) and endogenous (endozepines) Assesses the putative interactions in physiology, pathology and pharmacology of the compounds acting at the BDZ binding sites

Discusses endogenous benzodiazepine-like substances - what do they do, do they affect the anti-anxiety drugs and their adverse effects? Presents information on the enigmatic prolonged benzodiazepine withdrawal syndrome Describes the compounds acting at the BDZ binding sites, both exogenous (classical BDZ drugs and BDZ from food and plants) and endogenous (endozepines) Assesses the putative interactions in physiology, pathology and pharmacology of the compounds acting at the BDZ binding sites

Cassia is an indigenous plant in Africa, Latin America, Northern Australia and Southeast Asia. Several Cassia species are of high commercial and medicinal significance since they are used as spices and in traditional medicines. Currently plants from genus Cassia is in great demand due to their immense medicinal properties. Cassia species have various pharmacological activities such as antibacterial, analgesic, antiinflammatory, antiarthritic, hepatoprotective, antitumor, antifertility, antifungal, antioxidant, antileishmaniatic, antimicrobial, CNS and hypoglycaemic activitiy. Different class of compounds reported from Cassia species are anthraquinones, phenolics, flavonoids, chromenes, terpenes, proanthocyanidins, coumarins, chromones and lignans. The taxonomy and nomenclature of Cassia species are quite complex. It is very difficult to differentiate them due to their overlapping morphological characters and close similarities. This usually leads to misidentification and misinterpretation of the components. Features: Presents collection of Ayurvedic features and scientific evidence of most important medicinal plants of Cassia species Chemical signatures for identification of Cassia species Easy to use analytical procedure for quality control of Cassia species and its products.

This new volume focuses on clinical biochemistry fundamentals, cell culture techniques, and drug discovery and development concepts. It deals with three different fields of clinical research: cell culture, clinical biochemistry, and drug discovery and development. The book introduces cell animal and bacterial culture techniques and their potential uses as well as cell culture techniques. The biochemistry aspect of the book covers the principles of clinical biochemistry and biochemical analysis, biochemical aids to clinical diagnosis, measurement, and quality control. The book also presents important concepts in cell membrane receptor signal transduction pathways as drug targets. The drug development focus of the book discusses the fundamentals of human disease and drug discovery. Various in silico, in vitro, and in vivo approaches for drug discovery are examined, along with a discussion on drug delivery carriers and clinical trials. Overall, the volume provides an overview of the journey from clinical fundamentals to clinical output.

The history of patent harmonization is a story of dynamic actors, whose interactions with established structures shaped the patent regime. From the inception of the trade regime to include intellectual property (IP) rights to the present, this book documents the role of different sets of actors - states, transnational business corporations, or civil society groups - and their influence on the structures - such as national and international agreements, organizations, and private entities - that have caused changes to healthcare and access to medication. Presenting the debates over patents, trade, and the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement), as it galvanized non-state and nonbusiness actors, the book highlights how an alternative framing and understanding of pharmaceutical patent rights emerged: as a public issue, instead of a trade or IP issue. The book thus offers an important analysis of the legal and political dynamics through which the contest for access to lifesaving medication has been, and will continue to be, fought. In addition to academics working in the areas of international law, development, and public health, this book will also be of interest to policy makers, state actors, and others with relevant concerns working in nongovernmental and international organizations.

Updating and expanding the scope of topics covered in the previous edition, Percutaneous Absorption: Drugs, Cosmetics, Mechanisms, Methods, Fifth Edition supplies new chapters on topics currently impacting the field including cutaneous metabolism, skin contamination, exposure to protein allergens, in vitro absorption methodology and the percutaneous absorption of chemical mixtures. Complete with studies on the role of the skin as a key portal of entry for chemicals into the body, this book serves as a detailed reference source for recent advances in the field, as well as an experimental guide for laboratory personnel. Key Features: Details in vivo and in vitro methods for measuring absorption, dermal decontamination, mechanisms of transdermal delivery, and the relationship of transepidermal water loss to percutaneous absorption Considers a range of mathematical models, the safety evaluation of cosmetic ingredients, the absorption of hair dyes, nanoparticles for drug delivery, and other novel methods of drug delivery Discusses topics including skin metabolism, the skin reservoir, and the effects of desquamation on absorption

A contribution to the series on Natural Products Chemistry of Global Plants, Natural Products Chemistry of Botanical Medicines from Cameroon focuses on the sources and chemistry of natural products from plants in Cameroon, West Africa. The plants selected offer an opportunity to trace a route through history from ancient civilizations to the modern day, showing the important value to man of natural products in medicines and in foods. This book highlights how many of the extracts from Cameroon are today associated with important drugs, nutrition products, beverages, perfumes, cosmetics and pigments, as well as presenting their complex chemistry and structure. Key Features: Forms an important part of the series on Natural Products Chemistry of Global Plants, as Cameroon is a country with rich experience in the use of medicinal plants and with a wide diversity of botanical resources Addresses the current development of pharmacognosy research in Cameroon Provides readers with updated information on the chemistry and pharmacology of natural products with pharmaceutical potential Covers an extensive range of chemical, botanical and pharmacological diversities Xavier Siwe Noundou is a Scholar/Scientist based at Rhodes University in Grahamstown, South Africa. He has been a EU FP7 Marie Curie Fellow (2015-2016), Kaposvar University in Hungary (2015, 2016), Trakia Univesity in Bulgaria (2016), TWAS Fellow (2013), National Research Foundation South Africa Fellow (2014-2016). Dr Noundou works on Medicinal Chemistry focusing on Chemistry, Pharmacognosy and Nanotechnology. His main research interests include terrestrial natural products chemistry (from Cameroon and South Africa) and marine natural products chemistry (from the South African coastline): bioactive metabolites isolated as potential antiparasitic, antimicrobial, antiviral and antiproliferative candidates. He is author of more than forty scientific publications in his field of expertise.

Vitamin C holds a unique place in scientific and cultural history. In this book, a group of leading scientific researchers describe new insights into the myriad ways vitamin C is employed during normal physiological functioning. In addition, the text provides an extensive overview of the following: the rationale for utilizing vitamin C in the clinic, updates on recent uses of vitamin C in cancer treatment through high-dose intravenous therapies, the role vitamin C plays in the treatment of sepsis and infectious disease, management of the ways vitamin C can improve stem cell differentiation, as well as vitamin C use in other important health situations. Features Includes chapters from a team of leading international scholars Reviews the history and recent research on the functions, benefits, and uses of vitamin C Focuses special attention on the way vitamin C can be used in the treatment of cancers Discusses how vitamin C can be employed against infectious disease

The cost for bringing new medicine from discovery to market has nearly doubled in the last decade and has now reached $2.6 billion. There is an urgent need to make drug development less time-consuming and less costly. Innovative trial designs/ analyses such as the Bayesian approach are essential to meet this need. This book will be the first to provide comprehensive coverage of Bayesian applications across the span of drug development, from discovery, to clinical trial, to manufacturing with practical examples. This book will have a wide appeal to statisticians, scientists, and physicians working in drug development who are motivated to accelerate and streamline the drug development process, as well as students who aspire to work in this field. The advantages of this book are: Provides motivating, worked, practical case examples with easy to grasp models, technical details, and computational codes to run the analyses Balances practical examples with best practices on trial simulation and reporting, as well as regulatory perspectives Chapters written by authors who are individual contributors in their respective topics Dr. Mani Lakshminarayanan is a researcher and statistical consultant with more than 30 years of experience in the pharmaceutical industry. He has published over 50 articles, technical reports, and book chapters besides serving as a referee for several journals. He has a PhD in Statistics from Southern Methodist University, Dallas, Texas and is a Fellow of the American Statistical Association. Dr. Fanni Natanegara has over 15 years of pharmaceutical experience and is currently Principal Research Scientist and Group Leader for the Early Phase Neuroscience Statistics team at Eli Lilly and Company. She played a key role in the Advanced Analytics team to provide Bayesian education and statistical consultation at Eli Lilly. Dr. Natanegara is the chair of the cross industry-regulatory-academic DIA BSWG to ensure that Bayesian methods are appropriately utilized for design and analysis throughout the drug-development process.

Drug development is an iterative process. The recent publications of regulatory guidelines further entail a lifecycle approach. Blending data from disparate sources, the Bayesian approach provides a flexible framework for drug development. Despite its advantages, the uptake of Bayesian methodologies is lagging behind in the field of pharmaceutical development. Written specifically for pharmaceutical practitioners, Bayesian Analysis with R for Drug Development: Concepts, Algorithms, and Case Studies, describes a wide range of Bayesian applications to problems throughout pre-clinical, clinical, and Chemistry, Manufacturing, and Control (CMC) development. Authored by two seasoned statisticians in the pharmaceutical industry, the book provides detailed Bayesian solutions to a broad array of pharmaceutical problems. Features Provides a single source of information on Bayesian statistics for drug development Covers a wide spectrum of pre-clinical, clinical, and CMC topics Demonstrates proper Bayesian applications using real-life examples Includes easy-to-follow R code with Bayesian Markov Chain Monte Carlo performed in both JAGS and Stan Bayesian software platforms Offers sufficient background for each problem and detailed description of solutions suitable for practitioners with limited Bayesian knowledge Harry Yang, Ph.D., is Senior Director and Head of Statistical Sciences at AstraZeneca. He has 24 years of experience across all aspects of drug research and development and extensive global regulatory experiences. He has published 6 statistical books, 15 book chapters, and over 90 peer-reviewed papers on diverse scientific and statistical subjects, including 15 joint statistical works with Dr. Novick. He is a frequent invited speaker at national and international conferences. He also developed statistical courses and conducted training at the FDA and USP as well as Peking University. Steven Novick, Ph.D., is Director of Statistical Sciences at AstraZeneca. He has extensively contributed statistical methods to the biopharmaceutical literature. Novick is a skilled Bayesian computer programmer and is frequently invited to speak at conferences, having developed and taught courses in several areas, including drug-combination analysis and Bayesian methods in clinical areas. Novick served on IPAC-RS and has chaired several national statistical conferences.

This book provides insight into the world of pharmaceutical quality systems and the key elements that must be in place to change the business and organizational dynamics from task-oriented procedure-based cultures to truly integrated quality business systems that are self-detecting and correcting. Chapter flow has been changed to adopt a quality systems organization approach, and supporting chapters have been updated based on current hot topics including the impact of the worldwide supply chain complexity and current regulatory trends. Key Features: Presents insight into the world of pharmaceutical quality systems Analyzes regulatory trends and expectations Includes approaches and practices used in the industry to comply with regulatory requirements Discusses recent worldwide supply chain issues Delivers valuable information to a worldwide audience regarding the current GMP practices in the industry

Phylogenetic presentation of medicinal plants and a chemotaxonomical rationale of antiviral, antibacterial, and antifungal action. Discusses chemical structure-activity relationship, pharmacokinetics, and oral bioavailability of antimicrobial principles Introduces the molecular mechanism of natural products on viruses, bacteria, and fungi. Contains a selection of hand-made botanical plates and useful bibliographic references A useful research tool for postgraduates, academics, and the pharmaceutical, herbal, or nutrition industries.

This forward-looking book focuses on the recent advances in nanomedicine and drug delivery. It outlines the extraordinary new tools that have become available in nanomedicine and presents an integrated set of perspectives that describe where we are now and where we should be headed to put nanomedicine devices into applications as quickly as possible, while also considering the possible dangers of nanomedicine. The book considers the full range of nanomedicinal applications that employ molecular nanotechnology inside the human body, from the perspective of a future practitioner in an era of widely available nanomedicine. Written by some of the most innnovative minds in medicine and engineering, this unique volume will help professionals understand cutting-edge and futuristic areas of research that can have tremendous payoff in terms of improving human health. Readers will find insightful discussions of nanostructured intelligent materials and devices that are considered technically feasible and which have a high potential to produce advances in medicine in the near future. Topics include: Health benefits of phytochemicals and the application of colloidal delivery systems Study of non-covalent attachment of recombinant targeting proteins to polymer-modified Adenoviral gene delivery vectors The role of nanoparticles as adjuvants for mucosal vaccine delivery Poly(amido-amine)s as delivery styems for biologically active substances Antimicrobial activity of silver nanoparticles Nanomedicine in the use of cancer treatment Dendrimers, capsules based on lipid vesicles for drug delivery Many other recent achievements