Wiley Attrition in the Pharmaceutical Industry: Reasons, Implications, and Pathways Forward

With a focus on case studies of R&D programs in a variety of disease areas, the book highlights fundamental productivity issues the pharmaceutical industry has been facing and explores potential ways of improving research effectiveness and efficiency.• Takes a comprehensive and holistic approach to the problems and potential solutions to drug compound attrition• Tackles a problem that adds billions of dollars to drug development programs and health care costs• Guides discovery and development scientists through R&D stages, teaching requirements and reasons why drugs can fail• Discusses potential ways forward utilizing new approaches and opportunities to reduce attrition Review "Innovative drug discovery can only be partially guided by knowledge from known chemical and pharmacological space, so a level of attrition is therefore inevitable. This refreshingly readable book provides an engaging combination of background historical and current reasons for attrition, combined with a panorama of some of the possible ways to covert “attrition” into the informed risk-taking necessary for innovative drug discovery. The book is very logically presented across the phases of drug discovery out across the technologies an across the phases of drug discovery and thus builds in depth reference source especially for those entering the challenging environment of drug discovery. As the authors point out, converting molecules into drugs remains difficult and engaging in more projects as a way to ensure a minimal level of success is not sustainable, so challenging and understanding better the reasons for attrition are of fundamental importance. The reasons for attrition change over time as some factors, notably AMDE and PK are better understood. But an inability to accurately predict still hampers the industry. This book makes a very useful reference source by highlighting where progress is being made, for example, the AstraZeneca 5Rs approach or the translational data analysis by Pfizer showing three parameters which correlate combined confidence in pharmacology an exposure with confidence in Phase II success. The book then nicely moves the reader on from the improvements in Phase II attrition by asking the critical question, “Why do drugs fail in Phase III if efficacy failures in Phase II are being better managed?” One of the advantages of this book is that it not only provides a well written background review, but that it combines this with examples of where progress it still needed, something of particular importance as regulators increasingly place emphasis on safety profiles. Although the book does make some comments to other modalities, it focuses on small molecule drug discovery, for which the authors take the reader through all stages of drug discovery form target identification to post-marketing attrition with extensive use of informative case studies. These case studies are used to highlight where attrition has been reduced, where improvements are still needed, and for preclinical research in particular where attrition isn’t necessarily bad, but rather a consequence of innovative drug discovery, that is best managed in a structured approach where knowledge can be transferred between projects. As the pharmaceutical industry moves to a more fragmented but networked environment changes in the ways in which knowledge is acquired and transferred between companies will significantly change the ways in which attrition is confronted. This book is therefore an excellent source material that will be of great value to all those embarking in drug discovery in smaller more agile companies. As evidenced in Chapter 2, preclinical research has made significant inroads in managing attrition with structured approaches to ADME profiling and PK/PD modelling. This is picked up and integrated into more detailed discussion later in Chapters 7–10, covering reasons for attrition associated with the various technologies employed