Book Review

The Ethics of Research Involving Human Subjects: Facing the 21st century

N Engl J Med 1997; 336:882-883March 20, 1997

Article

The Ethics of Research Involving Human Subjects: Facing the 21st century
Edited by Harold Y. Vanderpool. 531 pp. Frederick, Md., University Publishing Group, 1996. $59. ISBN: 1-55572-036-6

We stand at a pivotal moment in the history of human experimentation. Long-standing suspicions about research are fading, along with an unconditional commitment to informed consent. The distinction between investigation and therapy is blurring; fears about using subjects as guinea pigs are being superseded by a belief that investigational drugs deliver miracle cures. These attitudes originated with AIDS and have spread to almost all diseases with no known cure, including Alzheimer's disease and cancer. In a manner consistent with this orientation, the Food and Drug Administration's drug-approval procedures have been streamlined, there is a new emphasis on enrolling women in clinical trials, and federal regulations now allow for the waiver of informed consent to research under certain life-threatening situations. Nevertheless, and particularly as the 50th anniversary of the Nuremberg Code is commemorated, the grim record of abuse still seems relevant. The Willowbrook and Tuskegee studies and the radiation experiments remain salient experiences for many communities. The insights of Hans Jonas and Paul Ramsey have not been forgotten. Once human beings are viewed not as ends but as means to an end, even one so noble as curing disease, profound ethical problems inevitably arise.

This admirable collection of essays, skillfully assembled and annotated by Harold Vanderpool, explores these tensions in ways that clarify, often through disagreement, the ethical issues. The book will engage both readers who are knowledgeable about the field and those seeking an intelligent and sophisticated introduction.

The book's opening question is the most fundamental one: may the interest of the community outweigh a commitment to individual autonomy in human experimentation? Should the principle of informed consent ever be modified to promote medical progress? Robert Veatch steadfastly says no; it would be a “serious mistake” to conclude that “the interests of others in society . . . provide the basis for limiting autonomy.” Albert Jonsen argues otherwise. Although he opens his nuanced essay with a “confession of belief” in the view that “the voluntary consent of the subject is the absolutely essential feature . . . of the ethics of research with human subjects,” he does not make voluntary consent an absolute. We are entitled, even obligated, to undertake a weighing and balancing that analyzes the particular facts and circumstances of a case. “Quite specific harms to many may force us to contemplate exposing some to risks so that all might be saved.” His case in point, not unexpectedly, is a public health emergency in which a clinical trial would have potential therapeutic benefits for most people, albeit with a high risk for a few. Terrence Ackerman allies himself with Jonsen, respecting subjects' rights “in most circumstances while permitting minor compromises in the protection of subjects' interests when necessary for the conduct of research that may prevent or remove important harms to others.” In effect, the consensus on autonomy that once characterized bioethical thinking about human experimentation is splintering, with some ready to admit frankly utilitarian considerations.

The discussion of a second major question also reflects the altered perspective: To what degree, if any, should a commitment to autonomy be enforced in human experimentation in non-Western societies? The question is critical, for in the aftermath of AIDS, research in developing countries — practically for the first time — is directly relevant to a disease in developed countries. Robert Levine argues for the nonuniversality of the Nuremberg Code's insistence on voluntary consent. The code was “an American creation,” composed in reaction to the Nazi horrors. Like Jonsen, and along with Nicholas Christakis, Levine wants ethical decisions made case by case, not bound by absolute principles or dictated by what Levine derisively calls “Nuremberg fundamentalists.”

Carel IJsselmuiden and Ruth Faden disagree, convinced that “respect for persons, and its derivative first-person informed consent . . . is as valid in Africa and elsewhere in the world as it is in the West.” If anything, firsthand consent is more important in countries where “sexual abuse, wife battering, structural discrimination against women, corruption, and abuse of power” are even more commonplace than in the West.

The implications of confounding research with therapy emerge in other essays. Stuart Lind analyzes the rise of “fee-for-service research,” in which subjects pay to enroll in a protocol, so convinced are they of its therapeutic benefits. John La Puma explores the dangers of phase 4 postmarketing studies. Drug companies reimburse physicians for enrolling patients in these studies as a way of encouraging them to prescribe their agent rather than a competitor's. Benjamin Freedman links the inadequacy of the consent process in phase 1 trials of drugs for cancer to the misleading promise of cure and presents a model consent form to reduce the bias. Finally, Eric Juengst takes us into the 21st century with 10 ethical questions, many of them novel, raised by human-genome research. Decisions by individual subjects have important implications for their families, but whether or how the consent of all affected parties is to be obtained remains unclear.

The very richness of the analyses and the marked differences among the contributors demonstrate how high the stakes are in the ethics of human experimentation. The awesome power of research, the fragility of a concept such as voluntary consent, the international nature of both medicine and disease, and the strength of the profit motive in health care — all mean that the basic premises that should govern clinical research are unsettled. Some of us, particularly attuned to history, worry about a cyclical trend: abuse generates oversight, which in turn seems too restrictive and is relaxed, and then new abuses emerge. Others find such concern anachronistic and prefer case-by-case decision making to a rigid commitment to principle. To invoke the historian's ultimate bias, time will tell.

David J. Rothman, Ph.D.
Columbia College of Physicians and Surgeons, New York, NY 10032

Citing Articles (1)

Citing Articles

1. 1

   Ruudje C Cleophas, BL Ton J Cleophas. (1998) Informed Consent Under Scrutiny Suggestions for Improvement. Clinical Research and Regulatory Affairs 15:3-4, 225-236
   CrossRef