Since the early 2000s, there has been increasing interest within the pharmaceutical industry in the application of Bayesian methods at various stages of the research, development, manufacturing, and health economic evaluation of new health care interventions. In 2010, the first Applied Bayesian Biostatistics conference was held, with the primary objective to stimulate the practical implementation of Bayesian statistics, and to promote the added-value for accelerating the discovery and the delivery of new cures to patients. This book is a synthesis of the conferences and debates, providing an overview of Bayesian methods applied to nearly all stages of research and development, from early discovery to portfolio management. It highlights the value associated with sharing a vision with the regulatory authorities, academia, and pharmaceutical industry, with a view to setting up a common strategy for the appropriate use of Bayesian statistics for the benefit of patients. The book covers: Theory, methods, applications, and computing Bayesian biostatistics for clinical innovative designs Adding value with Real World Evidence Opportunities for rare, orphan diseases, and pediatric development Applied Bayesian biostatistics in manufacturing Decision making and Portfolio management Regulatory perspective and public health policies Statisticians and data scientists involved in the research, development, and approval of new cures will be inspired by the possible applications of Bayesian methods covered in the book. The methods, applications, and computational guidance will enable the reader to apply Bayesian methods in their own pharmaceutical research.

Recent developments in the field of nutrition have led to increased interest in herbs and medicinal plants as phytochemical-rich sources for functional food, nutraceuticals, and drugs. As research sheds light on the therapeutic potential of various bioactive phytochemicals, the demand for plant extracts and oils has increased. Black cumin or black seeds (Nigella sativa) have particularly widespread nutritional and medicinal applications. In traditional medicine, black seeds are used to manage fatigue and chronic headache. Black seed oil is used as an antiseptic and analgesic remedy and for treatment of joint's pain and stiffness and can be mixed with sesame oil to treat dermatosis, abdominal disorders, cough, headache, fever, liver ailments, jaundice, sore eyes, and hemorrhoids. Thymoquinone, the main constituent in black seed volatile oil, has been shown to suppress carcinogenesis. Black cumin (Nigella sativa) seeds: Chemistry, Technology, Functionality, and Applications presents in detail the chemical composition, therapeutic properties, and functionality of high-value oils, phytochemicals, nutrients, and volatiles of the Nigella sativa seed. Organized by formulation (seeds, fixed oil, essential oil, and extracts), chapters break this seed down into its chemical constituents and explore their role in the development of pharmaceuticals, nutraceuticals, novel food, natural drugs, and feed. Following numerous reports on the health-promoting activities of Nigella sativa, this is the first comprehensive presentation of the functional, nutritional, and pharmacological traits of Nigella sativa seeds and seed oil constituents.

Molecular similarity searching is fast becoming a key tool in organic chemistry. In this book, the editor has brought together an international team of authors, each working at the forefront of this technology, providing a timely and concise overview of current research. The chapters focus principally on those methods which have reached sufficient maturity to be of immediate practical use in molecular design.

This volume begins with a short history of malaria and follows with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment, and then describes quinine's biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine's structure. It also covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of additional natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature's combinatorial library is challenging, it is very likely to yield new antimalarial drugs. This book thus ends by identifying ten natural products with development potential as clinical antimalarial agents.

Statistical Design, Monitoring, and Analysis of Clinical Trials, Second Edition concentrates on the biostatistics component of clinical trials. This new edition is updated throughout and includes five new chapters. Developed from the authors' courses taught to public health and medical students, residents, and fellows during the past 20 years, the text shows how biostatistics in clinical trials is an integration of many fundamental scientific principles and statistical methods. The book begins with ethical and safety principles, core trial design concepts, the principles and methods of sample size and power calculation, and analysis of covariance and stratified analysis. It then focuses on sequential designs and methods for two-stage Phase II cancer trials to Phase III group sequential trials, covering monitoring safety, futility, and efficacy. The authors also discuss the development of sample size reestimation and adaptive group sequential procedures, phase 2/3 seamless design and trials with predictive biomarkers, exploit multiple testing procedures, and explain the concept of estimand, intercurrent events, and different missing data processes, and describe how to analyze incomplete data by proper multiple imputations. This text reflects the academic research, commercial development, and public health aspects of clinical trials. It gives students and practitioners a multidisciplinary understanding of the concepts and techniques involved in designing, monitoring, and analyzing various types of trials. The book's balanced set of homework assignments and in-class exercises are appropriate for students and researchers in (bio)statistics, epidemiology, medicine, pharmacy, and public health.

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 is a comprehensive review of thrombin, especially as regulatory protease. The ready availability of highly purified thrombin has stimulated rapid advances in the cell biology of this important macromolecule. The text focuses on research findings from the discovery of thrombin by Andrew Buchanan in 1842 to the present. A substantial amount of this work was conducted by the author and his colleagues. His work on the purification of thrombin was seminal to much subsequent work on thrombin. This volume provides a framework for future studies now made possible by the discovery of the importance of exosites in the physiology of thrombin function. The current work describes the process of the development of an oral inhibitor of thrombin used in the prevention of thrombosis. Key Features Reviews the history of Thrombin (Fibrin Ferment) Documents the relation of protein engineering and chemical modification in the study of thrombin Summarizes the interaction of thrombin with fibrinogen and fibrin Outlines the role of exosites in thrombin function Describes the development of an oral inhibitor for thrombin

The proposed book is envisioned for the nascent and entry-level researchers who are interested to work in the field of drug delivery and its applications specifically for macrophage targeting. Macrophages have gained substantial attention as therapeutic targets for drug delivery considering their major role in health and regulation of diseases. Macrophage-targeted therapeutics have now added significant value to the lives and quality of life of patients, without undue adverse effects in multiple disease settings. We anticipate examining and integrating the role of macrophages in the instigation and advancement of various diseases. The major focus of the book is on recent advancements in various targeting strategies using delivery systems or nanocarriers followed by application of these nanocarriers for the treatment of macrophage associated disorders. Macrophage Targeted Delivery Systems is primarily targeted to Pharmaceutical Industry & Academia, Medical & Pharmaceutical Professionals, Undergraduate & Post graduate students and Research Scholars, Ph.D, post docs working in the field of medical and pharmaceutical sciences.

S. Ren and E.J. Lien: CaCo-2 cell permeability vs human gastrointestinal absorption: QSPR analysis.- J.C.G. Halford and J.E. Blundell: Pharmacology of appetite suppression.- B. Olivier, W. Soudijn and I. van Wijngaarden: Serotonin, dopamine and norepinephrine transporters in the central nervous system and their inhibitors.- D. Poyner, H. Cox, M. Bushfield, J.M. Treherne and M.K. Demetrikopoulos: Neuropeptides in drug research.- M. Kumari and M.K. Ticku: Regulation of NMDA receptors by ethanol.- H. Horikoshi, T. Hashimoto and T. Fujiwara: Troglitazone and emerging glitazones: new avenues for potential therapeutic benefits beyond glycemic control.- Rosamund C. Smith and Simon J. Rhodes: Applications of developmental biology to medicine and animal agriculture

This book collects information about the most popular ethnomedicinal plants, which are common in Turkey and around the world. It presents the ethnopharmacological records, in vivo and in vitro studies, side effects, chemical compositions and clinical studies of these medicinal plants. Its special focus is on the novel drug targets for disease and their possible mechanisms of action. It covers botanical descriptions the status of the plants, and food or drug interactions including precautions and warnings about the plants and the available market products. It provides an explanation of recorded and known plant administration dosages. Also, the gap between the traditional practice and scientific/clinical evidences in the use of ethnomedicinal plant is acknowledged. It is well known that traditional knowledge of the use of the medicinal plants in therapy is an important resource for the discovery of novel treatment options and drug targets. The main purpose of this book is to draw attention to ethnomedicinal plant species. Data on the therapeutic potentials of these medicinal plants can now be accessed from a single source. It provides an important resource for future research opportunities for harnessing the full potential of these plants.

This book presents a multidisciplinary assessment of the state of science in the use of systemic delivery technologies to deliver anti-aging therapeutics now under development. There is a gap between basic aging research and the development of intervention technologies. This major obstacle must be overcome before biogerontological interventions can be put into clinical practice. As biogerontology comes to understand aging as a systemic degenerative process, it is clear that there is a pressing need for technologies that enable cells and tissues in a fully developed adult body to be manipulated systemically to combat aging. The authors review advances in the chemistry and engineering of systemic delivery methods and analyze the strengths and limitations of each. The book is organized into six sections. The first offers an overview of the need for systemic delivery technologies alongside the development of anti-aging therapies and describes approaches that will be required for studying the properties and efficiency of carriers for systemic delivery. Sections II, III and IV describe recent advances in a range of strategies that may enable systemic delivery to help combat aging conditions ranging from cell senescence to decline in immune function and hormonal secretion. Section V discusses practical strategies to engineer and optimize the performance of delivery technologies for applications in systemic delivery, along with their working principles. The final section discusses technical and biological barriers that must be overcome as systemic delivery technologies move from research laboratory to clinical applications aimed at tackling aging and age-associated diseases.Benefiting scholars, students and a broader audience of interested readers, the book includes helpful glossary sections in each chapter, as well as sidebars that highlight important notes, and questions for future research.

Hepatitis C is a liver disease caused by the hepatitis C virus (HCV) and infects approximately 75 million individuals worldwide. It is also one of the major causes of liver cancer and liver transplants. The elucidation of the HCV genome, and the development of a whole cell system to study the virus spurred the search for novel direct acting antiviral drugs to cure this disease. This global effort culminated in the development of direct acting antiviral drugs that led to cure rates approaching 100% in all patient populations after only 8-12 weeks of therapy. These efforts resulted in one of the greatest achievements in public health and provides the potential for eliminating HCV as a major disease worldwide. This volume is aimed at a broad audience of academic and industrial scientists interested in the discovery and development of drugs to treat viral diseases and those interested in reading about one of the most unique accomplishments in biomedical research. The volume will provide a one of a kind reference work that highlights the many efforts, from the discovery of the HCV virus, to the invention of breakthrough medicines and their use in the real world to cure patients. It is the companion book to the volume "HCV: The Journey from Discovery to a Cure - Volume I".

In recent years, emerging trends in the design and development of drug products have indicated ever greater need for integrated characterization of excipients and in-depth understanding of their roles in drug delivery applications. This book presents a concise summary of relevant scientific and mechanistic information that can aid the use of excipients in formulation design and drug delivery applications. Each chapter is contributed by chosen experts in their respective fields, which affords truly in-depth perspective into a spectrum of excipient-focused topics. This book captures current subjects of interest - with the most up to date research updates - in the field of pharmaceutical excipients. This includes areas of interest to the biopharmaceutical industry users, students, educators, excipient manufacturers, and regulatory bodies alike.

Over the past three decades there have been new developments in therapeutic drug design. In Rational Drug Design: Methods and Protocols, expert researchers in the field detail many of the methodologies used to study rational drug design. These include methods such as virtual screening of chemical hits, rational lead discovery by high throughput screening, combinatorial and fragment based lead generation, peptide based drug discovery, and animal models of lead validation. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Rational Drug Design: Methods and Protocols seeks to aid scientists in the further study of rational drug design and future drug discovery.

This volume contains a collection of innovative techniques for studying targeted protein degradation. Chapters guide readers through heterobifunctional proteolysis-targeting chimeras (PROTACs) approaches, E3 ligase, E3 ligase-induced ubiquitylation, proteomic approaches, novel degrader molecules, molecular glue, and stabilize binding interaction between a target and E3 ubiquitin ligase. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Targeted Protein Degradation: Methods and Protocols aims to ensure successful results in this emerging field of drug discovery.

Can drug development and evaluation be improved by the use of positron emission tomography (PET)? PET is now well established and many PET centres participate in networks that warrant the quality of their research. PET allows one to follow the effect of a drug on a variety of patients' metabolic parameters. In addition, PET may be used to follow the fate in vivo of a compound, allowing visualisation of its binding to specific receptors and a direct study of the mechanism of drug action in normal and pathological situations. The book shows the fields in which PET offers new and unique information for the development of drugs (conception, toxicity, pharmacokinetics and metabolism, clinical research, and relations between clinical and biological effects) and evaluates fields in which PET may shorten the development time of drugs. Audience: Professionals in the pharmaceutical industry in all areas of drug discovery and pharmacology, pre-clinical testing, pharmacokinetics and metabolism, clinical evaluation, registration and regulatory affairs. Government health authority representatives who assess data and documentation on new drug development and radiopharmaceuticals. Academic experts concerned with any of these areas.

knowledge. This material provided has been collected from different sources. One important source is the material available from EURACHEM. Eurachem is a network of organisations in Europe having the objective of establishing a system for the international tra- ability of chemical measurements and the promotion of good quality practices. It provides a forum for the discussion of common problems and for developing an informed and considered approach to both technical and policy issues. It provides a focus for analytical chemistry and quality related issues in Europe. You can find more information about EURACHEM on the internet via "Eurachem -A Focus for Analytical Chemistry in Europe" (http: //www.eurachem.org). In particular the site Guides and Documents contains a number of different guides, which might help you to set up a quality system in your laboratory. The importance of quality assurance in analytical chemistry can best be described by the triangles depicted in Figs. 1 and 2. Quality is checked by testing and testing guaranties good quality. Both contribute to progress in QA (product control and quality) and thus to establishing a market share. Market success depends on quality, price, and flexibility. All three of them are interconnected. Before you can analyse anything the sample must be taken by someone. This must be of major concern to any analytical chemist. There is no accurate analysis wi- out proper sampling. For correct sampling you need a clear problem definition. There is no correct sampling without a clear problem definition

This book explains how peptide-based drug design works, what steps are needed to develop a peptide-based therapeutic, and challenges in synthesis as well as regulatory issues. It covers the design concept of peptide therapeutics from fundamental principles using structural biology and computational approaches. The chapters are arranged in a linear fashion. A fresh graduate or a scientist who works on small molecules can use this to follow the design and development of peptide therapeutics to use as understanding the basic concepts. Each chapter is written by experts from academia as well as industry. Rather than covering extensive literature, the book provides concepts of design, synthesis, delivery, as well as regulatory affairs and manufacturing of peptides in a systematic way with examples in each case. The book can be used as a reference for a pharmaceutical or biomedical scientist or graduate student who wants to pursue their career in peptide therapeutics. Some chapters will be written as a combination of basic principles and protocol so that scientists can adopt these methods to their research work. The examples provided can be used to perform peptide formulation considerations for the designed peptides. The book has nine chapters, and each chapter can be read as an independent unit on a particular concept.

This detailed book examines the main methods to study mammalian monoamine oxidases (MAOs), ranging from cell biology to computational chemistry. Beginning with techniques on how to obtain pure samples of MAO A and MAO B, the volume continues by covering assays and techniques used to measure MAO enzymatic activity and perform inhibition studies, methods to address cellular localization and function of MAOs, either in cell lines or in animal models, as well as computational methods applied to rational drug design approaches that are used to develop new MAO inhibitors. Written for the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step and readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Monoamine Oxidase: Methods and Protocols serves as a vital resource for scientists who are interested in studying MAOs and other similar amine oxidase enzymes.

This book provides an insight of relevant case studies and updated practices in "PharmaceuticalSupply Chains" (PharmSC) while addressing the most relevant topics within the COST Action "Medicines Shortages" (CA15105).The volume focuses on the most recent developments in the design, planning and scheduling ofPharmSC, broadening from the suppliers' selection to the impact on patients and healthcaresystems, addressing uncertainty and risk mitigation, and computational issues. It is directed at MSc/PhD students and young researchers (Post-Docs) in Pharmaceutics/Pharmaceutical sciences, Engineering fields, Economics/Management, as well as pharmaceutical decision makers, managers, and practitioners, and advanced readers demanding a fresh approach to decision making for PharmSC. The contributed chapters are associated with the homonymous COST Training Schools (TS), and the book creates a better understanding of the Action "Medicines Shortages" challenges and opportunities.

The inaugural volume in the Current Topics in Nonclinical Drug Development Series explores the critical issues and current topics in nonclinical drug development. This first volume covers individual topics and strategies in drug development from compound characterization to drug registration. Written by a variety of experts in the field, recent and rapid advances in technologies and associated changes in regulatory guidance are discussed. Additional features include: Deals with day-to-day issues in study design, evaluation of findings, and presentation of data. Explains new approaches in the development of medical devices. Includes dedicated chapters on the use of bioinformatics in drug development. Addresses strategies for photosafety testing of drugs. Current Topics in Nonclinical Drug Development, Volume I will aid toxicologists, toxicologic pathologists, consultants, regulators, Study Directors, and nonclinical scientists dealing with day-to-day issues in study design, evaluation of findings, and presentation of data. In addition, the book will be a valuable reference for academicians and graduate students pursuing research related to nonclinical drug development.

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.