Clinical Evaluation of Psychotropic Drugs: Principles and Guidelines
Clinical Evaluation of Psychotropic Drugs: Principles and Guidelines
RF Prien and DS Robinson, editors
New York: Raven Press; 1994, 669 pages
This book reflects several decades of active development in psychotropic drug evaluation. The first modern, randomized, double-blind controlled trial of a psychotropic drug was conducted in the early 1950s (Schou’s evaluation of anti-manic lithium). Since the first methodological book on evaluation, edited by Cole and Gerrard (1959), several international statements of expectations have been published describing how psychotropic drug evaluations should take place. The present volume represents a culmination of the US national effort to establish guidelines for clinical evaluation of psychotropic drugs. Academic, clinical, pharmaceutical, regulatory and public health sectors, as well as several other disciplines contributed to this unfolding over the years.
This book was initiated in 1990 by the establishment of a task force on guidelines for clinical evaluation of psychotropic drugs; the American College of Neuropsychopharmacology (ACNP) and the National Institute of Mental Health (NIMH) collaborated. While the recent international volume (Grof et al 1993) focuses on education, the Prien and Robinson book appears more appropriate for experienced investigators. It often deals with issues and problems that would confound the novice looking for guidance in a maze of clinical trials.
Clinical Evaluation of Psychotropic Drugs: Principles and Guidelines is a resource that reflects the knowledge and experience of a wide group of US experts. The contributing authors number exactly 100, and the list reads almost like a “Who is Who” in US psychopharmacology. The book is as multi-authored as one could possibly imagine. An editorial group provided overall leadership. The ACNP taskforce advised on content and authorship of the book, and reviewed initial chapter drafts. Subsequent drafts were circulated to outside reviewers specializing in particular fields. Those of us foolish enough to engage in multi-authored writings will appreciate the challenges and the extensive nature of this process.
The book is divided into three main sections of increasing length. The first section, “Historical Perspectives”, describes the context of the book by providing a historical overview of clinical psychopharmacological research and guidelines. It also describes the decision-making process of establishing the efficacy and safety of psychotropics. The second section, “General Principles in the Evaluation of Psychotropic Drugs”, contains a broad outline of developments and issues of clinical methodology, and provides direction in research principles, study design and implementation, presentation of study findings, and ethical considerations involving drug evaluations. The third and most extensive section,”Specific Patient Groups: Application of General Methodologic Principles”, addresses methodologic developments and recommends clinical evaluation of specific diagnostic and age populations. This section builds on the ideas expounded in the preceding sections. A predecessor of this book, entitled Principles and Problems in Establishing the Efficacy of Psychotropic Agents and edited by Jerome, Levin, Burtrum, Schiele, Lorraine and Bouthelet, was published in 1971. The present book can be seen as an extensive revised and updated version of that first comprehensive volume, and it documents the advancement in the clinical trial methodology of psychopharmacology over the past 25 years.
This outstanding book will be essential for anyone actively involved in psychotropic drug trials. I found three parts particularly intriguing. First, the sections on ethical and legal considerations, which have become particularly heated during this time of political correctness, are of great interest. Second, the sections on maintenance (prophylactic) trials in general and in specific patient groups are also fascinating. If recent developments are indicators, there will be a major expansion in die area of testing, in particular because of the clinical need, and the widespread use of long-term treatments. Third, some of the innovative ideas that may improve and hasten the evaluation of new drugs are of interest. The desire for innovative approaches is driven by a new emphasis on cost containment as well as by the increasing importance awarded to treatment effectiveness, rather than relying solely on randomized, controlled trials for proof of efficacy.
It is clear that we are going through a stage of developing new methodology, and are questioning older ideas. It seems likely that in the future we will view the traditional, randomized, clinical trial as a necessary but insufficient technique in providing comprehensive evaluation. The Bayesian approach is becoming more common in clinical trials, with a de-emphasis on the frequentist approach. Increased attention is being paid to the problems of statistical analysis of longitudinal data, and the techniques of integrating information through meta-analysis. Researchers have become increasingly concerned about the limitations of generalized clinical trials in clinical practice. New strategies, envisaged in the World Health Organization (WHO) guidelines, are being proposed, ranging from the value of vigorously-collected observational data to the use of clinical databases and new strategies of cross design synthesis.
In a book of this size, with several contributing authors, it is to be expected that everything will not emerge perfectly, and that one will encounter allusions to the same issues a number of times (e.g., the complex placebo issue). It is also inevitable that, when a book is in preparation for several years, certain issues are dated by the time of publication. This is the case with the incorrect statement that the regulatory agencies in Europe do not require proof of prophylactic efficacy for new antidepressants. It is also of interest that the authors, although referring to the traditional phases of evaluation, have not structured the book following the four classical phases, as in previous books on clinical trials. Although this excellent book could not be useful to a psychopharmacological novice, it will be of much value to experienced investigators for years to come.