New Methodologies and Evolving Regulatory Landscapes
Author: J. Rick Turner,Dilip R. Karnad,Snehal Kothari
At a time when the field of cardiac safety is going through important changes, this unique book provides the rationale for, and cutting-edge explanations of, new regulatory landscapes that will likely govern cardiac safety assessments globally for the foreseeable future. Exposure-response modeling is already being accepted by regulatory agencies in lieu of the traditional Thorough QT/QTc Study, and the Comprehensive in vitro Proarrhythmia Assay initiative is well under way. Developments in the field of cardiovascular safety are also described and discussed in the book. These include the search for more efficient ways to exonerate new drugs for type 2 diabetes from an unacceptable cardiovascular liability, how best to address off-target blood pressure increases induced by noncardiovascular drugs, and the continued evolution of the discipline of Cardio-oncology. “a resource that will likely serve as a standard for years to come” - Dr Jonathan Seltzer Therapeutic Innovation & Regulatory Science, 2017;51(2):180 “I have no hesitation in recommending this book as a valuable reference source” - Dr Rashmi Shah Journal for Clinical Studies, 2017;9(1):62-63
Assessment Methodologies for Noncardiac Drugs in Discovery, Development, and Postmarketing Surveillance
Author: J. Rick Turner,Todd A. Durham
Publisher: John Wiley & Sons
The serious nature of cardiovascular adverse drug reactions occurring in patients makes assessment of a drug's cardiac safety profile a high priority during both development and post-approval monitoring. Integrated Cardiac Safety provides necessary guidance and methodology for professionals assessing cardiac safety of drugs throughout all stages of the drug's life, from discovery and development through postmarketing research. This self-contained, reader-friendly text is valuable to professionals in the pharmaceutical, biotechnology, and CRO industries, pharmacologists, toxicologists, government officials, and students.
Drug Discovery and Evaluation has become a more and more difficult, expensive and time-consuming process. The effect of a new compound has to be detected by in vitro and in vivo methods of pharmacology. The activity spectrum and the potency compared to existing drugs have to be determined. As these processes can be divided up stepwise we have designed a book series "Drug Discovery and Evaluation" in the form of a recommendation document. The methods to detect drug targets are described in the first volume of this series "Pharmacological Assays" comprising classical methods as well as new technologies. Before going to man, the most suitable compound has to be selected by pharmacokinetic studies and experiments in toxicology. These preclinical methods are described in the second volume „Safety and Pharmacokinetic Assays". Only then are first studies in human beings allowed. Special rules are established for Phase I studies. Clinical pharmacokinetics are performed in parallel with human studies on tolerability and therapeutic effects. Special studies according to various populations and different therapeutic indications are necessary. These items are covered in the third volume: „Methods in Clinical Pharmacology".
The Propulsid and Seldane drug disasters could have easily been avoided with more rigorous safety pharmacology studies of these compounds prior to any human clinical trials. Unfortunately, safety pharmacology has been overlooked by all but a few developers. With recent drug withdrawals from the market and the implementation of the International Conference on Harmonization (ICH) guidelines, safety pharmacology will become a more important phase in drug development. Safety Pharmacology in Pharmaceutical Development and Approval spells out the whys and hows of safety pharmacology testing. The book covers the background, history, and concerns that have evolved from lackluster safety pharmacology activities in the past. It details regulatory requirements, provides comprehensive information on study designs, and covers both the required battery of studies and the supplemental, follow-up battery. Until recently, pharmacovigilance has been product-rather than utilization-oriented and often invisible in clinical medicine. It is clear that definitive safety pharmacology standards are needed to combat the increase in adverse reactions seen in the last 20 years. Giving you a head start in this emerging field, Safety Pharmacology in Pharmaceutical Development and Approval addresses how best to implement ICH safety standards and how to integrate pharmacology safety evaluations into existing safety evaluations.
Safety and Pharmacokinetic Assays ; with 125 Tables
Author: H. Gerhard Vogel
Publisher: Springer Science & Business Media
This book is a landmark in the continuously changing world of drugs. It is essential reading for scientists and managers in the pharmaceutical industry who are involved in drug finding, drug development and decision making in the development process.
With its focus on emerging concerns of kinase and GPCR-mediated antitarget effects, this vital reference for drug developers addresses one of the hot topics in drug safety now and in future. Divided into three major parts, the first section deals with novel technologies and includes the utility of adverse event reports to drug discovery, the translational aspects of preclinical safety findings, broader computational prediction of drug side-effects, and a description of the serotonergic system. The main part of the book looks at some of the most common antitarget-mediated side effects, focusing on hepatotoxicity in drug safety, cardiovascular toxicity and signaling effects via kinase and GPCR anti-targets. In the final section, several case studies of recently developed drugs illustrate how to prevent anti-target effects and how big pharma deals with them if they occur. The more recent field of systems pharmacology has gained prominence and this is reflected in chapters dedicated to the utility in deciphering and modeling anti-targets. The final chapter is concerned with those compounds that inadvertently elicit CNS mediated adverse events, including a pragmatic description of ways to mitigate these types of safety risks. Written as a companion to the successful book on antitargets by Vaz and Klabunde, this new volume focuses on recent progress and new classes, methods and case studies that were not previously covered.
An Introduction to Clinical Trials: Second Edition
Author: J. Rick Turner
Publisher: Springer Science & Business Media
New Drug Development: Second Edition provides an overview of the design concepts and statistical practices involved in therapeutic drug development. This wide spectrum of activities begins with identifying a potentially useful drug candidate that can perhaps be used in the treatment or prevention of a condition of clinical concern, and ends with marketing approval being granted by one or more regulatory agencies. In between, it includes drug molecule optimization, nonclinical and clinical evaluations of the drug’s safety and efficacy profiles, and manufacturing considerations. The more inclusive term lifecycle drug development can be used to encompass the postmarketing surveillance that is conducted all the time that a drug is on the market and being prescribed to patients with the relevant clinical condition. Information gathered during this time can be used to modify the drug (for example, dose prescribed, formulation, and mode of administration) in terms of its safety and its effectiveness. The central focus of the first edition of this book is captured by its subtitle, 'Design, Methodology, and Analysis'. Optimum quality study design and experimental research methodology must be employed if the data collected—numerical representations of biological information—are to be of optimum quality. Optimum quality data facilitate optimum quality statistical analysis and interpretation of the results obtained, which in turn permit optimum quality decisions to be made: Rational decision making is predicated on appropriate research questions and optimum quality numerical information. The book took a non-computational approach to statistics, presenting instead a conceptual framework and providing readers with a sound working knowledge of the importance of design, methodology, and analysis. Not everyone needs to be an expert in statistical analysis, but it is very helpful for work (or aspire to work) in the pharmaceutical and biologics industries to be aware of the fundamental importance of a sound scientific and clinical approach to the planning, conduct, and analysis of clinical trials.
The modern pharmacopeia has enormous power to alleviate disease, and owes its existence almost entirely to the work of the pharmaceutical industry. This book provides an introduction to the way the industry goes about the discovery and development of new drugs. The first part gives a brief historical account from its origins in the mediaeval apothecaries’ trade, and discusses the changing understanding of what we mean by disease, and what therapy aims to achieve, as well as summarising case histories of the discovery and development of some important drugs. The second part focuses on the science and technology involved in the discovery process: the stages by which a promising new chemical entity is identified, from the starting point of a medical need and an idea for addressing it. A chapter on biopharmaceuticals, whose discovery and development tend to follow routes somewhat different from synthetic compounds, is included here, as well as accounts of patent issues that arise in the discovery phase, and a chapter on research management in this environment. The third section of the book deals with drug development: the work that has to be undertaken to turn the drug candidate that emerges from the discovery process into a product on the market. The definitive introduction to how a pharmaceutical company goes about its business of discovering and developing drugs. The second edition has a new editor: Professor Raymond Hill ● non-executive director of Addex Pharmaceuticals, Covagen and of Orexo AB ● Visiting Industrial Professor of Pharmacology in the University of Bristol ● Visiting Professor in the School of Medical and Health Sciences at the University of Surrey ● Visiting Professor in Physiology and Pharmacology at the University of Strathclyde ● President and Chair of the Council of the British Pharmacological Society ● member of the Nuffield Council on Bioethics and the Advisory Council on Misuse of Drugs. New to this edition: Completely rewritten chapter on The Role of Medicinal Chemistry in the Drug Discovery Process. New topic - DMPK Optimization Strategy in drug discovery. New chapter on Scaffolds: Small globular proteins as antibody substitutes. Totally updated chapters on Intellectual Property and Marketing 50 new illustrations in full colour Features Accessible, general guide to pharmaceutical research and development. Examines the interfaces between cost and social benefit, quality control and mass production, regulatory bodies, patent management, and all interdisciplinary intersections essential to effective drug development. Written by a strong team of scientists with long experience in the pharmaceutical industry. Solid overview of all the steps from lab bench to market in an easy-to-understand way which will be accessible to non-specialists. From customer reviews of the previous edition: ‘... it will have everything you need to know on this module. Deeply referenced and, thus, deeply reliable. Highly Commended in the medicine category of the BMA 2006 medical book competition Winner of the Royal Society of Medicine Library Prize for Medical Book of the Year
A Comprehensive Guide to Toxicology in Nonclinical Drug Development, Second Edition, is a valuable reference designed to provide a complete understanding of all aspects of nonclinical toxicology in the development of small molecules and biologics. This updated edition has been reorganized and expanded to include important topics such as stem cells in nonclinical toxicology, inhalation and dermal toxicology, pitfalls in drug development, biomarkers in toxicology, and more. Thoroughly updated to reflect the latest scientific advances and with increased coverage of international regulatory guidelines, this second edition is an essential and practical resource for all toxicologists involved in nonclinical testing in industry, academic, and regulatory settings. Provides unique content that is not always covered together in one comprehensive resource, including chapters on stem cells, abuse liability, biomarkers, inhalation toxicology, biostatistics, and more Updated with the latest international guidelines for nonclinical toxicology in both small and large molecules Incorporates practical examples in order to illustrate day-to-day activities and the expectations associated with working in nonclinical toxicology
This one-stop reference systematically covers key aspects in early drug development that are directly relevant to the discovery phase and are required for first-in-human studies. Its broad scope brings together critical knowledge from many disciplines, ranging from process technology to pharmacology to intellectual property issues. After introducing the overall early development workflow, the critical steps of early drug development are described in a sequential and enabling order: the availability of the drug substance and that of the drug product, the prediction of pharmacokinetics and -dynamics, as well as that of drug safety. The final section focuses on intellectual property aspects during early clinical development. The emphasis throughout is on recent case studies to exemplify salient points, resulting in an abundance of practice-oriented information that is usually not available from other sources. Aimed at medicinal chemists in industry as well as academia, this invaluable reference enables readers to understand and navigate the challenges in developing clinical candidate molecules that can be successfully used in phase one clinical trials.
Drug Safety Evaluation Second Edition Shayne Cox Gad The updated and expanded safety guide to all aspects of the drug development process Drug Safety Evaluation, Second Edition presents an all-inclusive, practical guide for those who are responsible for ensuring the safety of drugs and biologics for patients, for health care providers, for those involved in the manufacture of medicinal products, and for all those who need to understand how the safety of these products is evaluated. This Second Edition has been extensively revised and expanded to respond to the many changes in regulatory requirements as well as pharmaceutical and technological developments. Drawing upon more than twenty years of experience, author Shayne Gad explains the scientific and philosophical bases for evaluating specific concerns (e.g., cardiovascular safety, immunogenicity, carcinogenicity, development toxicity, etc.) to provide both understanding and guidance for approaching new problems. Individual chapters address not only the general cases for safety evaluation of small and large molecules, but also all the significant major sub-cases: imaging agents, dermal and inhalation route drugs, vaccines, and gene-therapy products. Among the wide variety of topics covered are: Acute toxicity testing in pharmaceutical safety evaluation Genotoxicity Safety assessment of inhalant drugs Immunotoxicology in pharmaceutical development Large animal studies Evaluation of human tolerance and safety in clinical trials More pertinent and practical than ever to the industry, Drug Safety Evaluation, Second Edition provides a road map for safety assessment as an integral part of the development of new drugs and therapeutics.
A Comprehensive Guide to Toxicology in Preclinical Drug Development is a resource for toxicologists in industry and regulatory settings, as well as directors working in contract resource organizations, who need a thorough understanding of the drug development process. Incorporating real-life case studies and examples, the book is a practical guide that outlines day-to-day activities and experiences in preclinical toxicology. This multi-contributed reference provides a detailed picture of the complex and highly interrelated activities of preclinical toxicology in both small molecules and biologics. The book discusses discovery toxicology and the international guidelines for safety evaluation, and presents traditional and nontraditional toxicology models. Chapters cover development of vaccines, oncology drugs, botanic drugs, monoclonal antibodies, and more, as well as study development and personnel, the role of imaging in preclinical evaluation, and supporting materials for IND applications. By incorporating the latest research in this area and featuring practical scenarios, this reference is a complete and actionable guide to all aspects of preclinical drug testing. Chapters written by world-renowned contributors who are experts in their fields Includes the latest research in preclinical drug testing and international guidelines Covers preclinical toxicology in small molecules and biologics in one single source
These multidisciplinary presentations provide information essential to devising effective drug protocols in cardiovascular drug development, facilitating the approval process. Guides researchers and developers through the government drug approval process, facilitating development, minimizing costs, and harmonizing international standards employed in the creation of vital new cardiovascular therapies! Cardiovascular Drug Development explores the delicate balance of efficacy and safety that cardiovascular therapy must achieve to gain regulatory approval discusses the search for surrogates and the need in some areas for natural history endpoints reviews optimum strategies for protocol design in the development of drugs to treat hypertension, cardiac arrhythmias, heart failure, coronary artery disease, and hypercholesterolemia and other lipid disorders compares and contrasts the varying standards of evidence for drug approval in the United States, Europe, and Asia and more! Cardiovascular Drug Development will prove to be a valuable asset for cardiologists, pharmacologists and pharmacists, regulatory affairs specialists, and directors of research and development for pharmaceutical companies.
This book examines the background, industrial context, process, analytical methodology, and technology of metabolite identification. It emphasizes the applications of metabolite identification in drug research. While primarily a textbook, the book also functions as a comprehensive reference to those in the industry. The authors have worked closely together and combine complementary backgrounds to bring technical and cultural awareness to this very important endeavor while serving to address needs within academia and industry It also contains a variety of problem sets following specific sections in the text.
According to the Institute of Medicine (IOM) and U.S. Food and Drug Administration (FDA), 'developing new scientific approaches to detecting, understanding, predicting and preventing adverse events' was a critical path to the future of drug safety. This book brings together a collection of state-of-the-art chapters, written by experts in the drug safety field. It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment and promotes evidence-based toxicology. Each specific area of toxicology relevant for drug discovery is discussed in detail, including theory, experimental approaches and data interpretation supported by comprehensive up-to-date references. Many chapters provide fascinating case studies, which are of general interest for those who have basic science training and are interested in how chemicals interact with the human body.
Pregnancy stresses the heart and circulatory system. During pregnancy, blood volume increases by 30 to 50 percent. The amount of blood the heart pumps each minute also increases by 30 to 50 percent, and heart rate increases as well. These changes cause the heart to work harder, as do labor and delivery. This issue covers diagnosis and treatment of cardiac symptoms and cardiac emergencies during pregnancy.
Jonathan Gillard,Martin Graves,Thomas Hatsukami,Chun Yuan
Author: Jonathan Gillard,Martin Graves,Thomas Hatsukami,Chun Yuan
Publisher: Cambridge University Press
Stroke is a major cause of morbidity and mortality, with carotid disease representing an important contributory risk factor. This book is about the pathogenesis and management of carotid disease with specific focus on the role imaging has to play in the early recognition of symptomatic and asymptomatic disease as well as the treatment of the developed condition. Technological advances in imaging modalities now allow detailed analysis of the disease progression, the prediction of critical events leading to a stroke, as well as the identification of the most effective surgical or other interventional treatments. This book should be read by neurologists, cardiologists, vascular surgeons, neurosurgeons and radiologists involved in the care of patients with carotid disease, and also by researchers involved in the development of new therapeutic techniques and drugs.
Approval and Post Marketing Surveillance, Second Edition
Author: Shayne C. Gad
Publisher: CRC Press
Safety pharmacology is the evaluation and study of the pharmacological effects of a potential drug that are unrelated to the desired therapeutic effect. These effects often present a hazard—particularly in individuals with compromised or limited organ system functions. Safety Pharmacology in Pharmaceutical Development: Approval and Post Marketing Surveillance, Second Edition covers safety pharmacology from the regulatory requirements down to the studies that must be done to justify them. Using the author’s more than 30 years of direct experience, the book incorporates tricks and practical insights for making studies work and understanding why they fail. The second edition includes current regulations, including USFDA and those from Europe and Japan. Presenting a clear description of what is needed and why for supporting drug development, the book focuses on updated test methods, interpretation, and science. It covers the core and supplemental batteries of test procedures and how to do them and provides an overview of available facilities and contract organizations for performing studies.
David H. Chestnut,Cynthia A Wong,Lawrence C Tsen,Warwick D Ngan Kee,Yaakov Beilin,Jill Mhyre
Author: David H. Chestnut,Cynthia A Wong,Lawrence C Tsen,Warwick D Ngan Kee,Yaakov Beilin,Jill Mhyre
Publisher: Elsevier Health Sciences
From basic science to various anesthesia techniques to complications, the meticulously updated, fifth edition of Chestnut’s Obstetric Anesthesia: Principles and Practice, covers all you need to know about obstetric anesthesia. An editorial team of leading authorities presents the latest on anesthesia techniques for labor and delivery and medical disorders that occur during pregnancy. New chapters and rewritten versions of key chapters cover topics such as psychiatric disorders in the pregnant patient, neurologic disorders, and critical care of obstetric patients. It is an invaluable, comprehensive reference textbook for specialists in obstetric anesthesiology and obstetricians, as well as anesthesiology and obstetric residents. This book also serves as a clear, user-friendly guide for both anesthesiologists and obstetricians who are in clinical practice. Consult this title on your favorite e-reader, conduct rapid searches, and adjust font sizes for optimal readability. Get all the accuracy, expertise, and dependability you could ask for from the most important names in the fields of obstetric anesthesia and maternal-fetal medicine. Master the current best practices you need to know for treating the fetus and the mother as separate patients—each with distinct needs. Search and retain difficult concepts easily with the help of key point summaries in each chapter. Stay current on the latest advancements and developments with sweeping updates and new chapters on topics such as patient safety and team approach, transthoracic echocardiography and noninvasive measurement of cardiac output in obstetric patients, psychiatric disorders during pregnancy, neurologic injuries, and more. Prevent and plan for potential complications associated with the advancing age of pregnant women. An extensive, state-of-the art discussion of "critical care of obstetric patients" equips you to address any special considerations for this increasing segment. Know exactly how to proceed. An abundance of tables and boxes illustrate the step-by-step management of a full range of clinical scenarios. Choose the best drugs available while adhering to the most recent guidelines for obstetric anesthesia.