Frontiers of Neurology and Neuroscience Series Editor: Bogousslavsky, J., Editors: Woodbury-Harris, K. M. , Vol. 25: Clinical Trials in the Neurosciences , Published by Karger , Basel, Switzerland , 2009 , Hard cover 2009-04-02 USD 228.00, ISSN 1660-4431

This is the recent volume in the series Frontiers of Neurology and Neuroscience. Like previous volumes, this is a brief (approximately 200 pages) multi-author review aimed mainly, as indicated by the flyer, at clinical neurologists. As there are over 30 chapters, each chapter is relatively short. The present volume addresses the question of clinical trials. Although its focus is disorders of the central nervous system, the discussion of trial methodology is generally applicable to all clinical areas. The book systemically covers all stages of drug development up to the point of obtaining a marketing licence, and does not deal with postmarketing surveillance and pharmacovigilance. After two brief introductory chapters, which have the role of ‘setting the scene’, there are four chapters devoted to preclinical trials. These interesting chapters consider animal studies from the point of view of the design of subsequent clinical trials and the translation of information obtained from animal models into the clinical situation. The remainder of the book is devoted to the assessment of the efficacy and safety of drugs in human populations. Phase I and II trials are considered together, describing the principles of design and data analysis. There is a helpful chapter on biomarkers in neurology, discussing the features and roles of biomarkers in general, followed by examples in neurodegenerative diseases and stroke. The next two sections take up the bulk of the book: discussion of issues relating to Phase III trials. The first two chapters in this section deal with regulatory requirements in the USA and Europe. This is followed by a general discussion of design, analysis, clinical end-points and data management. A large section of the book is specifically devoted to multicentre trials, discussing principles of design and analysis, recruitment, obtaining informed consent, the role of local ethics committees (‘institutional review boards’ in the USA), budgeting, medical monitoring, and general management. An interesting section is devoted to special populations, such as patients suffering from progressive neurological diseases, children, neurological emergencies when the patients are unable to give consent, and trials with a genetic focus. Finally, there are chapters discussing the potential role of brain imaging in clinical trials and a chapter on training issues.

Overall, this is a broadly-based book whose major virtue is placing the placebo-controlled randomized trial, ‘the gold standard’ for the assessment of the efficacy and safety of new therapeutic agents, into the general context of the process of drug development. However, although the large field covered has the advantage of giving a general perspective, inevitably this is achieved at the expense of factual detail and in-depth analysis. Furthermore, the reference to neurosciences is rather arbitrary: although some chapters are clearly related to some neurological disorders (mainly neurodegenerative diseases and stroke), many do not have such a focus and relate to trial principles and practice in general. Thus, issues of clinical neurology serve as illustrations rather than providing the main focus of the book. Indeed, many neurological disorders (e.g. multiple sclerosis, epilepsy) with huge on-going clinical trial activity, hardly receive a mention. In conclusion, this is a useful overview of clinical trial methodology and some issues associated with it in general, but it provides only limited information about clinical trial activity related to disorders of the central nervous system. A minor quibble: this is an almost entirely American book (out of 45 authors there is only one from Europe), and even the chapter on European regulatory requirements is written by an American. I think that the general appeal of the book, at least on this side of the Atlantic, would have been enhanced by a more international authorship.