Fundamentals of Clinical Trials

Abstract

The clinical trial is “the most definitive tool for evaluation of the applicability of clinical research.” It represents “a key research activity with the potential to improve the quality of health care and control costs through careful comparison of alternative treatments” [1]. It has been called on many occasions, “the gold standard” against which all other clinical research is measured. Although many clinical trials are of high quality, a careful reader of the medical literature will notice that a large number have deficiencies in design, conduct, analysis, presentation, and/or interpretation of results. Improvements have occurred over the past few decades, but too many trials are still conducted without adequate attention to the fundamental principles. Certainly, numerous studies could have been improved if the authors had had a better understanding of the fundamentals. Since the publication of the first edition of this book in 1981, a large number of other texts on clinical trials have appeared, most of which are indicated here [2–21]. Several of them, however, discuss only specific issues involved in clinical trials. Additionally, many are no longer current. The purpose of this fifth edition is to update areas in which major progress has been made since the publication of the fourth edition. We have revised most chapters considerably. Because it was becoming unwieldy, we divided the chapter on monitoring response variables into two chapters, one on monitoring committees and the other on monitoring approaches. We also added a chapter on regulatory issues. Importantly, two new authors are now involved. This brings fresh perspectives to a book originally published over three decades ago. In this book, we hope to assist investigators in improving the quality of their clinical trials by discussing fundamental concepts with examples from our experience and the literature. The book is intended both for investigators with some clinical trial experience and for those who plan to conduct a trial for the first time. It is also intended to be used in the teaching of clinical trial methodology and to assist members of the scientific and medical community who wish to evaluate and interpret published reports of trials. Although not a technically oriented book, it may be used as a reference for graduate courses in clinical trials. Those readers who wish to consult more technical books and articles are provided with the relevant literature.