It is estimated that 80 to 90% of drugs under development never make it to the marketplace due to insufficient clinical activity, unacceptable toxicity, rapid appearance of drug resistance, or other factors that should be, at least partially, predictable from preclinical testing. This new text asks the question, "How can we use computational methods to improve the success rate in drug development?" Computer Techniques in Preclinical and Clinical Drug Development shows how modeling makes it possible to extract the maximum amount of information and predictive value from preclinical data. Computer modeling methods from the areas of pharmacokinetics, pharmacodynamics, cytokinetics, and inhibition kinetics of multi-enzyme pathways are all discussed in this unique reference source.

This book reviews the history, regulatory status, pharmacopeial specifications, and harmonization of pharmaceutical excipients in the United States and Europe, and provides a comprehensive understanding of the current scientific basis for safety evaluation and risk assessment. Examines excipients as a unique class of products and explores new procedures for determining toxicity! A timely and unique addition to the pharmaceutical literature, containing over 570 citations that support and enhance the text, Excipient Toxicity and Safety identifies the differences between excipients (inactive ingredients), food ingredients, and drug products evaluates issues of dose administration, species selection, and study design for various routes of exposure provides detailed information on the historical uses of excipients in drug formulations clarifies the Safety Committee of the International Pharmaceutical Excipients Council's (IPEC) guidelines and technical specifications for conducting tests for each route of exposure explains how data generated in toxicity models are applied to identify hazards in drug formulations details exposure assessment to link hazard identification with risk considers the requirements and importance of purity specifications and much more! Excipient Toxicity and Safety is a blue-ribbon reference ideal for pharmacists; toxicologists; pharmacologists; analytical chemists; quality control, quality assurance, and regulatory compliance managers; and upper-level undergraduate and graduate students in these disciplines.

Taking readers from the research laboratory to the bedside, this Second Edition compiles essential information on the pharmacodynamics of all major classes of the antimicrobial armamentarium including penicillins, cephalosposorins, cephamycins, carbapenems, monobactams, aminoglycosides, quinolones, macrolides, antifungals, antivirals, and emerging agents currently in development. Written by experienced professionals in the field, this guide uses an abundance of examples to depict methods to apply pharmacodynamic concepts to everyday clinical practice.

Sponsor companies and CROs alike will appreciate the industry-wide analysis, practical, how-to advice, and helpful charts and checklists provided by Outsourcing in Clinical Drug Development. A panel of experts discuss supplier identification and selection, financial considerations, and the ethical issues. They cover contracting out laboratory analysis, data management, and statistical services, and the effects of outsourcing on quality assurance. Whether readers are beginning to explore the possibility of outsourcing or already involved in long-term strategic outsourcing partnerships, this invaluable resource is a complete guide to the drug development outsourcing relationship.

Once the existence of free radicals was proven, an avalanche of studies on free radical-mediated biological processes ensued. The study of reactive oxygen and nitrogen species (ROS and RNS) is center stage in biological free radical investigations. Written by a biochemist, Signaling Mechanisms of Oxygen and Nitrogen Free Radicals discusses the regulatory functions of ROS and RNS in physiological and pathophysiological states. An exploration of the main questions of signaling mechanisms of reactive oxygen and nitrogen species in enzymatic processes, this book draws attention to the chemical mechanisms of these reactions. It elucidates the differences between signaling functions and damaging effects of ROS and RNS in biological systems. The text also covers free radical signaling processes catalyzed by enzymes, producers of superoxide and nitric oxide that are able to use produced ROS and RNS as signaling species in their own catalytic processes. It then examines ROS and RNS signaling produced by mitochondrial enzymes. The author explores signaling functions of ROS and RNS in enzymatic heterolytic reactions, supplying important data on ROS and RNS signaling in the catalysis by the enzymes which do not produce free radicals by themselves. He provides information on signaling by reactive oxygen and nitrogen species in apoptosis and aging/senescence and concludes with coverage of mechanisms of free radical signaling in enzymatic processes. The book provides new understanding of signaling functions in living organisms related to cardiovascular processes, cancer, inflammation, hereditary diseases, and their regulation of physiological functions such as development, aging, and senescence. This information can support the development of new drugs and novel treatment methods.

Monoclonal antibodies have had their impact on biomedical research for more than a decade. Beside their exuberant use as reagents, quite a number of diagnostic and therapeutic approaches have been followed and an impressive number of technological improvements, e.g., humanization, recombinant miniantibodies, have been elaborated to strengthen the principle. With respect to clinical applications, the first generation of antibody 'drugs' is yielding promising results while second and third generation antibody constructs are already underway. The book reviews the status of technological development and brings this into the perspective of clinical results. A rapidly growing amount of clinical data is collected in an expanding number of indications. Hence, the review of clinical study results has been grouped according to the fields of oncology and of chronic and acute inflammation. This book will be of interest to scientists working in the fields of oncology, immunology, internal medicine and clinical chemistry.

Increase in antibiotic resistance has forced researchers to develop new drugs against microorganisms. Lipopeptides are produced as secondary metabolites by some microorganisms. Computer-aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates provides the identification of novel ligands for different antimicrobial lipopeptides. Along with identification, it also provides some of the in silico drug design processes, namely homology modelling, molecular docking, QSAR studies, drug ADMET studies and pharmacophore studies to check the ligand-lipopeptide interaction. Some lipopeptides have shown anti-cancerous properties too, and this book discusses the required templates to design new drugs using computational techniques. Key Features: Focuses on the use lipopeptides as new antimicrobial compounds Presents the basics of in silico modelling for design and development of new drug molecules, and is therefore of interest to beginners in the field Provides a step-by-step process for identification of drug molecules and testing its efficacy in silico Couples with courses on patents and intellectual property rights

There is an increasing need for educational resources for statisticians and investigators. Reflecting this, the goal of this book is to provide readers with a sound foundation in the statistical design, conduct, and analysis of clinical trials. Furthermore, it is intended as a guide for statisticians and investigators with minimal clinical trial experience who are interested in pursuing a career in this area. The advancement in genetic and molecular technologies have revolutionized drug development. In recent years, clinical trials have become increasingly sophisticated as they incorporate genomic studies, and efficient designs (such as basket and umbrella trials) have permeated the field. This book offers the requisite background and expert guidance for the innovative statistical design and analysis of clinical trials in oncology. Key Features: Cutting-edge topics with appropriate technical background Built around case studies which give the work a "hands-on" approach Real examples of flaws in previously reported clinical trials and how to avoid them Access to statistical code on the book's website Chapters written by internationally recognized statisticians from academia and pharmaceutical companies Carefully edited to ensure consistency in style, level, and approach Topics covered include innovating phase I and II designs, trials in immune-oncology and rare diseases, among many others

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

The aim of this unique volume is to help medical researchers design clinical trials to improve survival, remission duration, or time to recurrence of disease. Written in a user-friendly step-by-step format, this work enables the researcher-with no background in statistics-to determine sample size and write statistical considerations for their protocols. It provides critical language which can help with FDA submissions and/or research grants. It also provides the mathematical justification of the material at a level consistent with one year of undergraduate mathematical statistics. It presents survival analysis methods at a more elementary level than any known text. Filled with tables, figures, plus an extensive appendix, this one-of-a-kind reference is an absolute must for all clinical researchers and biostatisticians.

Cancer Clinical Trials: Current and Controversial Issues in Design and Analysis provides statisticians with an understanding of the critical challenges currently encountered in oncology trials. Well-known statisticians from academic institutions, regulatory and government agencies (such as the U.S. FDA and National Cancer Institute), and the pharmaceutical industry share their extensive experiences in cancer clinical trials and present examples taken from actual trials. The book covers topics that are often perplexing and sometimes controversial in cancer clinical trials. Most of the issues addressed are also important for clinical trials in other settings. After discussing general topics, the book focuses on aspects of early and late phase clinical trials. It also explores personalized medicine, including biomarker-based clinical trials, adaptive clinical trial designs, and dynamic treatment regimes.

The purpose of this book is to provide information which supports the fact that rat hybridomas are no more difficult to develop than mouse hybridomas. This is the first book devoted to the development of rat hybridomas. It includes theories, step-by-step techniques, ingredients and apparatus. The focus of this work is on the antibody repertoire, the unique biological properties of rat immunoglobulins, the one-step purification procedure by immunoaffinity chromatography, the absence of C-type particles, and the easy production of large amounts of ascitic fluid containing rat MAb. This rare publication is an absolute must for all scientists using MAbs and those interested in the fields of immunology, biotechnology, and biochemistry.

"This is truly an outstanding book. [It] brings together all of the latest research in clinical trials methodology and how it can be applied to drug development.... Chang et al provide applications to industry-supported trials. This will allow statisticians in the industry community to take these methods seriously." Jay Herson, Johns Hopkins University The pharmaceutical industry's approach to drug discovery and development has rapidly transformed in the last decade from the more traditional Research and Development (R & D) approach to a more innovative approach in which strategies are employed to compress and optimize the clinical development plan and associated timelines. However, these strategies are generally being considered on an individual trial basis and not as part of a fully integrated overall development program. Such optimization at the trial level is somewhat near-sighted and does not ensure cost, time, or development efficiency of the overall program. This book seeks to address this imbalance by establishing a statistical framework for overall/global clinical development optimization and providing tactics and techniques to support such optimization, including clinical trial simulations. Provides a statistical framework for achieve global optimization in each phase of the drug development process. Describes specific techniques to support optimization including adaptive designs, precision medicine, survival-endpoints, dose finding and multiple testing. Gives practical approaches to handling missing data in clinical trials using SAS. Looks at key controversial issues from both a clinical and statistical perspective. Presents a generous number of case studies from multiple therapeutic areas that help motivate and illustrate the statistical methods introduced in the book. Puts great emphasis on software implementation of the statistical methods with multiple examples of software code (both SAS and R). It is important for statisticians to possess a deep knowledge of the drug development process beyond statistical considerations. For these reasons, this book incorporates both statistical and "clinical/medical" perspectives.

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

Participatory Visual Methodologies in Global Public Health focuses on the use of participatory visual methodologies such as photovoice, participatory video (including cellphilming or the use of cell phones to make videos), drawing and mapping in public health research. These approaches are modes of inquiry that can engage participants and communities, eliciting evidence about their own health and well-being, as well as modes of representation and modes of production in the co-creation of knowledge, and modes of dissemination in relation to knowledge translation and mobilization. Thus, the production by a group of girls or young women of a set of photos or videos from their own visual perspective can offer new evidence on how, for example, they see sexual violence. Unlike other data such as those collected through surveys or even conventional interviews, the images they have produced not only inform the empirical evidence, but also do not need to remain in a laboratory or the office of a researcher. They can, through exhibitions and screenings, reach various audiences: school or health personnel, parents and community members, and perhaps also policy-makers. This collection offers a critical overview for students, practitioners, researchers and policy-makers working in or concerned with the use of participatory methodologies in public health around the globe. This book was originally published as a special issue of Global Public Health.

This book examines developments in qualitative psychotherapeutic research. It focuses on different methods and aspects of clinical practice. These range from the experiences of service users and clinicians, examining in detail different aspects of how therapy gets done in practice, to critiquing the politics and ideologies of psychotherapy practice. It aims to reflect the diversity that characterises this developing field and to represent practice-based research carried out in different clinical settings, from different perspectives and in different sociocultural contexts. The wide range of research projects presented arise from a network of clinicians and psychotherapy researchers who have established an international transdisciplinary forum for dedicated qualitative research on a range of topics in the field of mental health, using a variety of methodologies and theoretical approaches. In the spirit of dialogue, this book further provides chapters written by key practitioners in the field of qualitative research in mental health discussing these contributions. This book was originally published as a special issue of the European Journal of Psychotherapy & Counselling.

Helping you become a creative, logical thinker and skillful "simulator," Monte Carlo Simulation for the Pharmaceutical Industry: Concepts, Algorithms, and Case Studies provides broad coverage of the entire drug development process, from drug discovery to preclinical and clinical trial aspects to commercialization. It presents the theories and methods needed to carry out computer simulations efficiently, covers both descriptive and pseudocode algorithms that provide the basis for implementation of the simulation methods, and illustrates real-world problems through case studies. The text first emphasizes the importance of analogy and simulation using examples from a variety of areas, before introducing general sampling methods and the different stages of drug development. It then focuses on simulation approaches based on game theory and the Markov decision process, simulations in classical and adaptive trials, and various challenges in clinical trial management and execution. The author goes on to cover prescription drug marketing strategies and brand planning, molecular design and simulation, computational systems biology and biological pathway simulation with Petri nets, and physiologically based pharmacokinetic modeling and pharmacodynamic models. The final chapter explores Monte Carlo computing techniques for statistical inference. This book offers a systematic treatment of computer simulation in drug development. It not only deals with the principles and methods of Monte Carlo simulation, but also the applications in drug development, such as statistical trial monitoring, prescription drug marketing, and molecular docking.

Covering all major arthropods of medical importance worldwide, this award-winning resource has established itself as a standard reference for almost 25 years. With the globilization of commerce and the world becoming more intimately connected through the everyday ease of travel, unknown arthropod species are being increasingly encountered. This means access to up-to-date, authoritative information in medical entomology has never been more important. Now in its seventh edition, this book maintains its well-acclaimed status as the ultimate easy-to-use guide to identify disease-carrying arthropods, the common signs and symptoms of vector-borne diseases, and the current recommended procedures for treatment. Includes an in-depth chapter with diagnostic aids to help physicians to recognize and accurately diagnose arthropod-related diseases and conditions more easily Updates all chapters with the latest medical and scientific findings, including Zika virus, red meat allergy, new viruses found in ticks, and vaccine development for malaria and dengue fever Presents a greater medical parasitology emphasis throughout Offers electronic downloads containing additional photographs of arthropod-caused diseases and lesions, as well as instructional videos with pest identification aids, basic entomology, and insect and pest ecology. Illustrated throughout with detailed color images to aid identification, The Goddard Guide to Arthropods of Medical Importance, Seventh Edition will remain an essential guide for physicians, public health officials, and pest control professionals.

The newer research areas in pharmaceutical sciences, particularly molecular modeling and simulations, prompted a more efficient drug discovery process. Informatics integrated with pharmaceutical sciences (cheminformatics and bioinformatics) became an essential component of drug research. Drug informatics such as genomics and proteomics assists in the Rational Drug Design (RDD). This emerging discipline is known as "Computer-Aided Drug Design" (CADD), which has profound application in RDD. The advanced and adequate practice in drug design informatics is essential for pharmacy graduates. Hence, a companion for acquiring knowledge on these concepts is vital. The students of B. Pharmacy, M. Pharmacy (Pharmaceutical Chemistry, Pharmacology, and Pharmaceutics), biotechnology, biomedical engineering and other interdisciplinary fields may find this book as a reference guide. The salient features of this book are: * Systematic and simple approach * Emphasis on traditional and modern drug design strategies * Comprehensive coverage for the current advances in the drug design * Experimental section to ensure hands-on-experience Note: T& F does not sell or distribute the Hardback in India, Pakistan, Nepal, Bhutan, Bangladesh and Sri Lanka.

Statistical Methods for Survival Trial Design: With Applications to Cancer Clinical Trials Using R provides a thorough presentation of the principles of designing and monitoring cancer clinical trials in which time-to-event is the primary endpoint. Traditional cancer trial designs with time-to-event endpoints are often limited to the exponential model or proportional hazards model. In practice, however, those model assumptions may not be satisfied for long-term survival trials. This book is the first to cover comprehensively the many newly developed methodologies for survival trial design, including trial design under the Weibull survival models; extensions of the sample size calculations under the proportional hazard models; and trial design under mixture cure models, complex survival models, Cox regression models, and competing-risk models. A general sequential procedure based on the sequential conditional probability ratio test is also implemented for survival trial monitoring. All methodologies are presented with sufficient detail for interested researchers or graduate students.

The Minipig in Biomedical Research is a comprehensive resource for research scientists on the potential and use of the minipig in basic and applied biomedical research, and the development of drugs and chemicals. Written by acknowledged experts in the field, and drawing on the authors global contacts and experience with regulatory authorities and the pharmaceutical and other industries, this accessible manual ranges widely over the biological, scientific, and practical uses of the minipig in the laboratory. Its coverage extends from the minipig s origins, anatomy, genetics, immunology, and physiology to its welfare, health, and husbandry; practical dosing and examination procedures; surgical techniques; and all areas of toxicity testing and the uses of the minipig as a disease model. Regulatory aspects of its use are considered.

The reader will find an extensive amount of theoretical and practical information in the pharmacology; ADME and toxicology chapters which will help scientists and managers when deciding which species to use in basic research; drug discovery and pharmacology; and toxicology studies of chemicals, biotechnology products and devices. The book discusses regulatory uses of minipigs in the evaluation of human and veterinary pharmaceuticals, medical devices, and other classes of xenobiotics. It describes features of normal health, normal laboratory values, and common diseases. It also carefully elucidates ethical and legal considerations in their supply, housing, and transport. The result is an all-inclusive and up to date manual about the experimental uses of the minipig that describes How to and Why and What to expect in the normal, combining enthusiasm and experience with critical assessment of its values and potential problems."

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

This is the first book that comprehensively and systematically describes the new technology of hydrophilic interaction liquid chromatography (HILIC). Hydrophilic interaction chromatography is a separation technique suitable for polar and hydrophilic compounds and orthogonal to reversed phase liquid chromatography. From small organic molecules to proteins, the text explores the many applications of HILIC in the analytical field. Winner of the President's Award for Excellence, the author explains how HILIC can significantly improve analytical throughput by shortening sample preparation procedure, which is one of the bottlenecks for drug discovery and development in the pharmaceutical industry.

Participatory Visual Methodologies in Global Public Health focuses on the use of participatory visual methodologies such as photovoice, participatory video (including cellphilming or the use of cell phones to make videos), drawing and mapping in public health research. These approaches are modes of inquiry that can engage participants and communities, eliciting evidence about their own health and well-being, as well as modes of representation and modes of production in the co-creation of knowledge, and modes of dissemination in relation to knowledge translation and mobilization. Thus, the production by a group of girls or young women of a set of photos or videos from their own visual perspective can offer new evidence on how, for example, they see sexual violence. Unlike other data such as those collected through surveys or even conventional interviews, the images they have produced not only inform the empirical evidence, but also do not need to remain in a laboratory or the office of a researcher. They can, through exhibitions and screenings, reach various audiences: school or health personnel, parents and community members, and perhaps also policy-makers. This collection offers a critical overview for students, practitioners, researchers and policy-makers working in or concerned with the use of participatory methodologies in public health around the globe. This book was originally published as a special issue of Global Public Health.

This book covers the broad field of cellular, molecular, preclinical, and clinical imaging either associated with or combined with photodynamic therapy (PDT). It showcases how this approach is used clinically for cancer, infections, and diseases characterized by unwanted tissue such as atherosclerosis or blindness. Because the photosensitizers are also fluorescent, the book also addresses various imaging systems such as confocal microscopy and small animal imaging systems, and highlights how they have been used to follow and optimize treatment, and to answer important mechanistic questions. Chapters also discuss how imaging has made important contributions to clinical outcomes in skin, bladder, and brain cancers, as well as in the development of theranostic agents for detection and treatment of disease. This book provides a resource for physicians and research scientists in cell biology, microscopy, optics, molecular imaging, oncology, and drug discovery.