Statistical Issues in Drug Development

Drug-Drug Interactions in Pharmaceutical Development comprehensively reviews the relevant science, industrial practice, and regulatory agency positions on drug-drug interactions. It focuses on the evaluation of potential drug-drug interactions, allowing researchers to address risk factors before a drug is put to market. The book covers both clinical and nonclinical aspects for understanding drug-drug interactions as well as in vitro and in vivo studies for use in studying interactions at the drug discovery stage.

The essentials of drug metabolism vital to developing new therapeutic entities Information on the metabolism and disposition of candidate drugs is a critical part of all aspects of the drug discovery and development process. Drug metabolism, as practiced in the pharmaceutical industry today, is a complex, multidisciplinary field that requires knowledge of sophisticated analytical technologies and expertise in mechanistic and kinetic enzymology, organic reaction mechanism, pharmacokinetic analysis, animal physiology, basic chemical toxicology, preclinical pharmacology, and molecular biology. With chapters contributed by experts in their specific areas, this reference covers: * Basic concepts of drug metabolism * The role of drug metabolism in the pharmaceutical industry * Analytical techniques in drug metabolism * Common experimental approaches and protocols Drug Metabolism in Drug Design and Development emphasizes practical considerations such as the data needed, the experiments and analytical methods typically employed, and the interpretation and application of data. Chapters highlight facts, common protocols, detailed experimental designs, applications, and limitations of techniques. This is a comprehensive, hands-on reference for drug metabolism researchers as well as other professionals involved in pre-clinical drug discovery and development.

Studies in bioequivalence are the commonly accepted method to demonstrate therapeutic equivalence between two medicinal products. Savings in time and cost are substantial when using bioequivalence as an established surrogate marker of therapeutic equivalence. For this reason the design, performance and evaluation of bioequivalence studies have received major attention from academia, the pharmaceutical industry and health authorities. Bioequivalence Studies in Drug Development focuses on the planning, conducting, analysing and reporting of bioequivalence studies, covering all aspects required by regulatory authorities. This text presents the required statistical methods, and with an outstanding practical emphasis, demonstrates their applications through numerous examples using real data from drug development. Includes all the necessary pharmacokinetic background information. Presents parametric and nonparametric statistical techniques. Describes adequate methods for power and sample size determination. Includes appropriate presentation of results from bioequivalence studies. Provides a practical overview of the design and analysis of bioequivalence studies. Presents the recent developments in methodology, including population and individual bioequivalence. Reviews the regulatory guidelines for such studies, and the existing global discrepancies. Discusses the designs and analyses of drug-drug and food-drug interaction studies. Bioequivalence Studies in Drug Development is written in an accessible style that makes it ideal for pharmaceutical scientists, clinical pharmacologists, and medical practitioners, as well as biometricians working in the pharmaceutical industry. It will also be of great value for professionals from regulatory bodies assessing bioequivalence studies.

Breakthroughs in combinatorial chemistry and molecular biology, as well as an overall industry trend toward accelerated development, mean the rate of sample generation now far exceeds the rate of sample analysis in the pursuit of producing new and better pharmaceuticals. LC/MS is an analytical tool that helps the researcher identify the most promising sample early in the selection process, effectively creating a shortcut to finding new drugs. This book is the first to describe LC/MS applications within the context of drug development, including the discovery, preclinical, clinical, and manufacturing phases. In addition to the thorough technical analysis of this tool, LC/MS Applications in Drug Development provides perspective on the significant changes in strategies for pharmaceutical analysis. A process overview of drug development from an analytical point of view is provided along with essential data required to successfully bring a drug to market. The incorporation of LC/MS is illustrated from target to product. Chapters pertaining to the discovery process itself include: Proteomics Glycoprotein Mapping Natural Products Dereplication Lead Identification Screening Open-Access LC/MS In Vitro Drug Screening Written for both the analytical chemist who uses LC/MS applications and the pharmaceutical scientist who works with the drugs they produce, LC/MS Applications in Drug Development is the premier reference on the subject.

Early characterization of toxicity and efficacy would significantly impact the overall productivity of pharmaceutical R&D and reduce drug candidate attrition and failure. By describing the available platforms and weighing their relative advantages and disadvantages, including microarray data analysis, Genomics in Drug Discovery and Development introduces readers to the biomarker, pharmacogenomic, and toxicogenomics toolbox. The authors provide a valuable resource for pharmaceutical discovery scientists, preclinical drug safety department personnel, regulatory personnel, discovery toxicologists, and safety scientists, drug development professionals, and pharmaceutical scientists.

This book covers the unique application of flow cytometry in drug discovery and development. The first section includes two introductory chapters, one on flow cytometry and one on biomarkers, as well as a chapter on recent advances in flow cytometry. The second section focuses on the unique challenges and added benefits associated with the use of flow cytometry in the drug development process. The third section contains a single chapter presenting an in depth discussion of validation considerations and regulatory compliance issues associated with drug development.

Most medicines have never been adequately tested for safety and efficacy in pediatric populations and preterm, infants and children are particularly vulnerable to adverse drug reactions. Pediatric Drug Development: Concepts and Applications, Second Edition, addresses the unique challenges in conducting effective drug research and development in pediatric populations. This new edition covers the legal and ethical issues of consent and assent, the additional legal and safety protections for children, and the appropriate methods of surveillance and assessment for children of varying ages and maturity, particularly for patient reported outcomes. It includes new developments in biomarkers and surrogate endpoints, developmental pharmacology and other novel aspects of global pediatric drug development. It also encompasses the new regulatory initiatives across EU, US and ROW designed to encourage improved access to safe and effective medicines for children globally. From an international team of expert contributors Pediatric Drug Development: Concepts and Applications is the practical guide to all aspects of the research and development of safe and effective medicines for children.

Lipases and Phospholipases are key control elements in mammalian metabolism. They share many common features that set them apart from other metabolic enzyme classes, most importantly their association with biological membranes. Their potential as drug targets for the treatment of metabolic diseases is widely recognized, and the first lipase inhibitor drugs have been successfully introduced. Providing drug developers with a firm foundation for lipase-centered drug design, the editors of this volume have assembled experts from different scientific disciplines to create a comprehensive handbook for all pharmaceutical chemists, biochemists and physiologists working with lipases. The authors examine fundamental aspects of lipase function in vitro and in vivo, explaining how this knowledge may be used to develop lipase assays. They also treat the physiological roles of lipases in normal and disordered metabolism, as well as strategies to target lipases for the treatment of diabetes, obesity and related disorders. Additional topics include the application of phospholipases for liposome-based drug delivery and their use as diagnostic tools.

Statistical Thinking for Non-Statisticians in Drug Regulation, Second Edition, is a need-to-know guide to understanding statistical methodology, statistical data and results within drug development and clinical trials. It provides non-statisticians working in the pharmaceutical and medical device industries with an accessible introduction to the knowledge they need when working with statistical information and communicating with statisticians. It covers the statistical aspects of design, conduct, analysis and presentation of data from clinical trials in drug regulation and improves the ability to read, understand and critically appraise statistical methodology in papers and reports. As such, it is directly concerned with the day-to-day practice and the regulatory requirements of drug development and clinical trials. Fully conversant with current regulatory requirements, this second edition includes five new chapters covering Bayesian statistics, adaptive designs, observational studies, methods for safety analysis and monitoring and statistics for diagnosis. Authored by a respected lecturer and consultant to the pharmaceutical industry, Statistical Thinking for Non-Statisticians in Drug Regulation is an ideal guide for physicians, clinical research scientists, managers and associates, data managers, medical writers, regulatory personnel and for all non-statisticians working and learning within the pharmaceutical industry.

CONTEMPORARY ACCOUNTS IN DRUG DISCOVERY AND DEVELOPMENT A useful guide for medicinal chemists and pharmaceutical scientists Drug discovery is a lengthy and complex process that typically involves identifying an unmet medical need, determining a biological target, chemical library screening to identify a lead, chemical optimization, preclinical studies and clinical trials. This process often takes many years to complete, and relies on practitioners’ knowledge of chemistry and biology, but also—and perhaps more importantly—on experience. Improving the success rate in discovery and development through a thorough knowledge of drug discovery principles and advances in technology is critical for advancement in the field. Contemporary Accounts in Drug Discovery and Development provides drug discovery scientists with the knowledge they need to quickly gain mastery of the drug discovery process. A thorough accounting is given for each drug covered within the book, as the authors provide pharmacology, drug metabolism, biology, drug development, and clinical studies for every case, with modern drug discovery principles and technologies incorporated throughout. Contemporary Accounts in Drug Discovery and Development readers will also find Case histories used as an engaging way of learning about the drug discovery/development process Detailed biological rational and background information, drug design principles, SAR development, ADMET considerations, and clinical studies The full history of individual marketed small molecule drugs Coverage of drug candidates that have passed Phase I clinical trials with different modalities, such as antibody drug conjugates (ADC), proteolysis-targeting chimera (PROTAC), and peptide drugs The application of new technologies in drug discovery such as DNA-encoded libraries (DEL), positron emission tomography (PET), and physics-based computational modeling employing free energy perturbation (FEP) Contemporary Accounts in Drug Discovery and Development is a helpful tool for medicinal chemists, organic chemists, pharmacologists, and other scientists in drug research and process development. It may be considered essential reading for graduate courses in drug discovery, medicinal chemistry, drug synthesis, pharmaceutical science, and pharmacology. It is also a useful resource for pharmaceutical industry labs, as well as for libraries.