Textbook of Clinical Trials

Textbook of Clinical Trials

Editors: David Machin, Simon Day, Sylvan Green (John Wiley & Sons, Ltd, 2004), 428 pages, hardcover, ISBN: 0471987875, 150

This varied book comprises 22 chapters written by 40 contributors, in addition to introductory and general information. The chapters are grouped into seven therapeutic divisions: cancer, cardiovascular, dentistry and maxillofacial, dermatology, psychiatry, reproductive health, and respiratory.

The editors devote a chapter to the history of clinical trials, high-lighting ways in which the practice of medicine in a range of chosen therapeutic areas has been influenced. Another chapter, dealing with general issues, covers Phases I to IV clinical trials, the designs of trials, randomized treatment allocation, endpoints, data monitoring, clinical trial reporting, data management, and analysis. Some of this information repeats in the other chapters.

The authors of the remaining 20 chapters have provided some very detailed information related to their specialities. The nature of the different diseases and how these have influenced the philosophy and design of research in the various therapeutic areas is especially enlightening. Those who enjoy reading about detailed medical science and the etiology of human disease will not be disappointed. The histories of clinical trials in areas such as breast cancer are covered. Also explained is why the skills of the investigator are far more important in surgical interventions than drug interventions.

Greater consideration could have been given to the fact that clinical research has undergone many changes in its fairly short history; in recent years, certainly in the developed world (especially the U.S., EU, CEE, and Japan), clinical trials have been subject to ever-increasing regulatory standards. Compliance with legally enforced international and national clinical trial regulations is required in most countries. The ethics of performing research on human subjects is rightly given very careful consideration, too, especially where trials may involve the substitution of effective therapy with inactive placebo, and should have been better reflected in the writing.

Some meaningful discussions on Good Clinical Practice (GCP), which is now a legal requirement in many countries, would also have benefitted readers. The philosophy and principles of GCP cover a very wide area involving compliance with ethical, scientific, and regulatory standards. A trial should only be performed in accordance with a written, approved protocol and undertaken by personnel who are suitably qualified. Freely given written consent should be obtained from every subject volunteer prior to participation, and the confidentiality of their records should be protected. Trial documentation should be accurate, verifiable and recoverable over a required time. The supply and usage of investigational products should comply with manufacturing and quality standards. There should be systems and procedures, especially regarding trial data, that assure the quality of every aspect of the trial. This is important to include for any textbook on clinical trials.

GCP regulations help to protect the rights, safety, and well-being of clinical trial subjects by requiring that trials are properly designed, conducted, recorded, and reported according to internationally recognized principles. Such regulations further protect public health by ensuring that the results of clinical trials are collected, recorded, and analyzed in accordance with those principles so that they can be audited and verified before being used to impact on public health. For example, the publication of a report that changes prescribing practice or as evidence to support applications to place medicines on the market. In the former case, we are reminded of the recent publicity surrounding the discredited research supposedly linking autism to the MMR vaccine.

GCP is an important first rule for all those wishing to initiate clinical trials, and as such it would have been helpful if this had been recognized and discussed. It is certainly true that within the EU, those who perform hospital-initiated and academic clinical trials after May 2004 will be required to comply with these legally enforced standards. Due to the perceived differences in the standards which have previously applied to nonpharma-sponsored trials, the book misses an opportunity of helping those involved in clinical research to recognize the need for all individuals and organizations to comply with Good Clinical Practice.

In summary, Textbook of Clinical Trials is a very interesting book in which the editors could have supplied more up to date information, especially regarding the statutory standards for the planning, conducting, and reporting of clinical trials.

Nigel J. Crosslandis the QA Director at the Crossland Consultancy, Swettenham Village, UK. Email: nigel.crossland@btinternet.com