Book Review

The Relevance of Ethnic Factors in the Clinical Evaluation of Medicines

N Engl J Med 1995; 332:829March 23, 1995

Article

The Relevance of Ethnic Factors in the Clinical Evaluation of Medicines
(CMR Workshop Series.) Edited by Stuart Walker. 262 pp. Boston, Kluwer Academic, 1994. $85. ISBN: 0-7923-8843-7

This book is a compilation of formal presentations and subsequent discussions from a two-day workshop held in London in the summer of 1993. “Ethnic factors” in the context of this book refers essentially to comparisons among Europe, North America, and Japan — the three regions with the highest rates of production and consumption of medicines. A stimulus for the workshop was the regulatory requirement for local replications of clinical studies, which increases the cost and effort of drug development. The speakers and authors represented here include leaders from the pharmaceutical industry, prominent experts from academia, members of the host organization, and some representatives of regulatory agencies. Many of the 19 chapters are worth reading.

The opening chapter by Edwards presents a viewpoint from industry, which is reflected by the statement that “most drugs have such a large benefit to toxic risk ratio that [ethnic] differences are rarely seen. The drugs that have a sharp dose response . . . are . . . used following individual titration (digoxin, warfarin).”

The issue of ethnic factors is approached in a variety of ways. Breimer presents an outline of genetic polymorphisms. Balant and Bechtel discuss differences within ethnic groups in dose–response studies and include some new examples of such differences. It is not the existence but the importance of such differences that is questioned in this book. Hirokawa and Dollery put the problem in focus from a new perspective in a chapter entitled “The Top 50 Drugs in the United Kingdom and Japan: Why Are They so Different?” The answer has many facets, as pointed out by several authors besides Hirokawa and Dollery. Clinical trials in Japan typically feature large numbers of participating centers with very few patients enrolled from each center. There is a reluctance to use placebos. More value may be placed on the safety of a drug than on its efficacy. A feature of evaluation is the usefulness of a drug; physicians are asked to give a global impression of a drug. The opportunity to prescribe a new drug tends to provide an economic benefit for the physician, even if a “new” drug is really only a minor novelty. In short, the nature of the drug market and the traditional dealings with medicines are different in Japan and in the West. Gennery describes what this means for a drug developer in Japan.

Naito, Henderson, and Harvey et al. all indicate clearly that pharmacogenetic differences are not the main reason for the differences in drug use in the West and in Japan, although there tend to be fewer types and a reduced frequency of adverse reactions in Japanese patients (Harvey et al.). One is left wondering how often routine clinical trials would uncover pharmacogenetic variants. Naito dismisses so-called ethnic differences; he emphasizes that the range of differences from person to person is much larger than the difference between population averages; such comparisons may be innocuous in biology, but, in my opinion, are misleading when one is dealing with drugs and side effects, which are much more likely to affect the extremes of the populations.

Two outstanding chapters explain global experiences and practices in industry, one by Patterson, and the other by Thompson. Patterson includes a delightful comparison between the organizational tasks of producing a car and of conducting clinical drug trials and producing the ensuing reports. Thompson concludes that “estimations of efficiency in general use [of drugs] are best made from large global trials that admit widely diverse patients and analyse results carefully by many defined factors.”

A final general discussion covers many topics and includes interesting questions and statements. However, there is no succinct summation of the meeting's achievements. The book ends with a summary of issues for further discussion.

Werner Kalow, M.D.
University of Toronto, Toronto, ON M5S 1A8, Canada