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Aids clinical trials
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BOOK REVIEWS Aids Clinical Trials, Editors: Diane M. Finkelstein and David A. Schoenfeld, Wiley & Sons, New York, 1995, ISBN 0471588237 $49.95
John
Clinicians rely on the results of clinical trials to determine the treatment of patients. Unfortunately, the skills required to design and analyze trials are poorly taught and difficult to glean from the published reports of trials. This multiauthored book attempts to redress the balance by providing a comprehensive account of HIV clinical trial issues. The authors draw heavily on the large experience of the AIDS Clinical Trials Group at the National Institute of Health. The book provides a useful aid both to the clinical trialist and to those who need to evaluate the results of trials. The chapters vary in their relevance. Inevitably, as is the case for many multi-authored books, chapters assume different amount of background knowledge and there is much overlap from chapter to chapter. The book is an excellent manual for clinical trialists. A description of dose ranging (phase I) studies is given and the chapters on protocol development, data issues, interim monitoring, trial analysis, and economic analysis are very helpful. The excellent chapter on large simple trials describes some practical issues involved in organizing such trials which provide the best means of answering important strategic questions about therapy. The specialist chapters on pediatric, maternal-infant transmission, and obstetric issues also provide a useful review. A particularly helpful account was provided of the preliminary discussions underlying the design of the ACTG 076 trial which demonstrated that zidovudine reduced materno-fetal transmission. The authors describe the various trial designs that were discussed and point out how the final design was sufficiently simple to have the best chance of yielding a useful answer. The discussion of the FDA’s requirements for trials is illuminating. The description of the different routes to licensing drugs provides helpful insights into the manner in which new drugs have become available. The chapter also provides a valuable critique of the trials on ribavarin and inosine explaining why the drugs are believed to be ineffective in spite of apparently positive trial results. Other chapters attempt to discuss more controversial areas. For instance, the discussions by Amato on choice of endpoints and by De Gruttola on CD4 counts as endpoints are very interesting, but they do not address the key debate in the choice of end-points: is the use of any end-point other than death sufficiently reliable, in terms of assessing the overall benefits and risks of a therapy, to enable the trial to produce reliable data? Similarly, the chapter on the use of quality of life end-points though thought provoking, unfortunately did not provide the solution to the problem of how to measure quality of life in a clinical trial. The book ends with two chapters on the analysis of non-randomized observational data. These reviews are perhaps out of place in a book on clinical trials, Controlled Clinical Trials 18:460-463 (1997) 0 Elsevier Science Inc. 1997 655 Avenue of the Americas, New York, NY 10010
0197~2456/97/$17.00
Book Reviews
461
but they provide an interesting comparison with randomized trials. They describe the difficulties of interpreting observational studies and concentrate on the types of biases that can occur. It is a pity that the book contained no chapter on the role of overviews as a way of combining the results of many trials. Also, it is a pity that the book, although peppered with examples of different trials, did not mention more problems with individual trials, because problems are sometimes more informative than successes. These omissions are, however, minor and distract little from the book as a whole. The book provides a much needed authoritative account of many of the issues in AIDS clinical trials, and should prove useful to both clinicians and trialists. Tim EA Pete Abdel G Babiker Janet H Darbyshire MRC HIV Clinical Trials Centre University College London Medical School London, United Kingdom PII SO197-2456(96)00239-5 Clinical Research in Pharmaceutical Development edited by Barry Bleidt and Michael Montagne, Marcel Dekker, Inc., New York, 1996, 368 pages, ISBN: o-8247-9745-0, $135, hard cover. This is the 75th volume in a series entitled Drugs and the Pharmaceutical Sciences (James Swarbrick, Executive Editor, Marcel Dekker, Inc., New York). In this book, Bleidt and Montagne introduce the reader to (a) the growth of drug development and clinical research and (b) guidelines for organizing and performing research activities in the process of drug development and registration. The book is divided into five parts. Each chapter begins with a table of contents, allowing the reader to determine its scope quickly. In Part I, Chapter 1, Bleidt and Montagne review each of the remaining chapters in the book. The chapter ends with a table of citations of federal regulations applicable to clinical research. Chapter 2 briefly reviews the process of new product development at the molecular level. Part II consists entirely of one chapter written by A. Hofmann, who gives an account of his own laboratory experiences as a scientist involved in new drug discovery. Although Parts I and II are interesting, the theme of the book becomes much more evident beginning with the next section. Part III reviews the drug development process. Chapter 4 describes milestone events attributed to the development of clinical research methods, the evolution of clinical research in drug development and the emergence of federal regulatory involvement. This chapter is informative for its overview of the origins and growth of pharmaceutical research and of the expanding influence of today’s Food and Drug Administration. This chapter also exposes the reader to two themes that recur throughout the remainder of the book: informed consent and regulatory control in the drug development process. Chapter 5, which introduces the stages of pharmaceutical development, including brief descriptions of preclinical testing, clinical testing, and postmarketing surveillance, is a useful primer on the drug-approval process in the United States and
BOOK REVIEWS Aids Clinical Trials, Editors: Diane M. Finkelstein and David A. Schoenfeld, Wiley & Sons, New York, 1995, ISBN 0471588237 $49.95
John
Clinicians rely on the results of clinical trials to determine the treatment of patients. Unfortunately, the skills required to design and analyze trials are poorly taught and difficult to glean from the published reports of trials. This multiauthored book attempts to redress the balance by providing a comprehensive account of HIV clinical trial issues. The authors draw heavily on the large experience of the AIDS Clinical Trials Group at the National Institute of Health. The book provides a useful aid both to the clinical trialist and to those who need to evaluate the results of trials. The chapters vary in their relevance. Inevitably, as is the case for many multi-authored books, chapters assume different amount of background knowledge and there is much overlap from chapter to chapter. The book is an excellent manual for clinical trialists. A description of dose ranging (phase I) studies is given and the chapters on protocol development, data issues, interim monitoring, trial analysis, and economic analysis are very helpful. The excellent chapter on large simple trials describes some practical issues involved in organizing such trials which provide the best means of answering important strategic questions about therapy. The specialist chapters on pediatric, maternal-infant transmission, and obstetric issues also provide a useful review. A particularly helpful account was provided of the preliminary discussions underlying the design of the ACTG 076 trial which demonstrated that zidovudine reduced materno-fetal transmission. The authors describe the various trial designs that were discussed and point out how the final design was sufficiently simple to have the best chance of yielding a useful answer. The discussion of the FDA’s requirements for trials is illuminating. The description of the different routes to licensing drugs provides helpful insights into the manner in which new drugs have become available. The chapter also provides a valuable critique of the trials on ribavarin and inosine explaining why the drugs are believed to be ineffective in spite of apparently positive trial results. Other chapters attempt to discuss more controversial areas. For instance, the discussions by Amato on choice of endpoints and by De Gruttola on CD4 counts as endpoints are very interesting, but they do not address the key debate in the choice of end-points: is the use of any end-point other than death sufficiently reliable, in terms of assessing the overall benefits and risks of a therapy, to enable the trial to produce reliable data? Similarly, the chapter on the use of quality of life end-points though thought provoking, unfortunately did not provide the solution to the problem of how to measure quality of life in a clinical trial. The book ends with two chapters on the analysis of non-randomized observational data. These reviews are perhaps out of place in a book on clinical trials, Controlled Clinical Trials 18:460-463 (1997) 0 Elsevier Science Inc. 1997 655 Avenue of the Americas, New York, NY 10010
0197~2456/97/$17.00
Book Reviews
461
but they provide an interesting comparison with randomized trials. They describe the difficulties of interpreting observational studies and concentrate on the types of biases that can occur. It is a pity that the book contained no chapter on the role of overviews as a way of combining the results of many trials. Also, it is a pity that the book, although peppered with examples of different trials, did not mention more problems with individual trials, because problems are sometimes more informative than successes. These omissions are, however, minor and distract little from the book as a whole. The book provides a much needed authoritative account of many of the issues in AIDS clinical trials, and should prove useful to both clinicians and trialists. Tim EA Pete Abdel G Babiker Janet H Darbyshire MRC HIV Clinical Trials Centre University College London Medical School London, United Kingdom PII SO197-2456(96)00239-5 Clinical Research in Pharmaceutical Development edited by Barry Bleidt and Michael Montagne, Marcel Dekker, Inc., New York, 1996, 368 pages, ISBN: o-8247-9745-0, $135, hard cover. This is the 75th volume in a series entitled Drugs and the Pharmaceutical Sciences (James Swarbrick, Executive Editor, Marcel Dekker, Inc., New York). In this book, Bleidt and Montagne introduce the reader to (a) the growth of drug development and clinical research and (b) guidelines for organizing and performing research activities in the process of drug development and registration. The book is divided into five parts. Each chapter begins with a table of contents, allowing the reader to determine its scope quickly. In Part I, Chapter 1, Bleidt and Montagne review each of the remaining chapters in the book. The chapter ends with a table of citations of federal regulations applicable to clinical research. Chapter 2 briefly reviews the process of new product development at the molecular level. Part II consists entirely of one chapter written by A. Hofmann, who gives an account of his own laboratory experiences as a scientist involved in new drug discovery. Although Parts I and II are interesting, the theme of the book becomes much more evident beginning with the next section. Part III reviews the drug development process. Chapter 4 describes milestone events attributed to the development of clinical research methods, the evolution of clinical research in drug development and the emergence of federal regulatory involvement. This chapter is informative for its overview of the origins and growth of pharmaceutical research and of the expanding influence of today’s Food and Drug Administration. This chapter also exposes the reader to two themes that recur throughout the remainder of the book: informed consent and regulatory control in the drug development process. Chapter 5, which introduces the stages of pharmaceutical development, including brief descriptions of preclinical testing, clinical testing, and postmarketing surveillance, is a useful primer on the drug-approval process in the United States and