Perspectives in Biology and Medicine

SOME ETHICAL ISSUES IN RESEARCH INVOLVING HUMAN SUBJECTS* LEROYWALTERSÌ The definition of "research involving human subjects" (also called "human research" or "human experimentation") can be best approached by way of considering the concepts "therapy" and "research." In the biomedical and behavioral fields "therapy" refers to a class of activities designed solely to benefit an individual or all members of a group. In contrast, "research" refers to a class of scientific activities designed to develop or contribute to generalizable knowledge. Research involving human subjects, then, is the subcategory of research in which biologically human organisms are the objects of study. Two types of human research can be distinguished. Therapeutic research is performed primarily for the benefit of a patient-subject —whether by prevention, diagnosis, or treatment; at the same time, however, the intervention is undertaken in a controlled way, so that the knowledge gained from the investigation can be applied to other contexts or to future subjects and patients. An example of therapeutic research is a controlled clinical trial in which alternative treatments for cancer are administered to two groups of cancer patients in order to determine which treatment is the more effective. Nontherapeutic research, on the other hand, is performed primarily for the purpose of gaining new knowledge and not primarily for the benefit of the subject. For example, in an early phase of drug testing, investigational new drugs are administered to healthy volunteer subjects, whose participation in the research provides baseline data concerning the drugs' safety and toxicity in humans [1, pp. 25-26]. The primary emphasis in this essay is on biomedical rather than behavioral research since a more clearly defined ethical tradition and a richer ethical literature exist for the biomedical sphere. However, many *This essay is a revised version of a paper prepared in December 1975 under a contract with the National Commission for the Protection of Human Subjects. I wish to thank my colleagues at the Kennedy Institute and Professor Stephen Toulmin of the Commission staff for their helpful comments on earlier drafts of the essay. tDirector, Center for Bioethics, the Joseph and Rose Kennedy Institute, Georgetown University, Washington, D.C. 20057. Perspectives in Biology and Medicine ¦ Winter 1977 | 193 if not all of the ethical principles developed in the essay are also applicable to behavioral-research activities. The method of the essay is to analyze seven major ethical issues in human research with a view to identifying one or more ethical principles which are pertinent to each issue. Four of the issues—risk-benefit analysis, the selection of subjects, informed consent, and social control—are derived from the charge to the National Commission for the Protection of Human Subjects in Public Law 93-348. The issue of research design is closely related to risk-benefit analysis and the selection of subjects. The remaining two issues seem to the author to be of comparable significance. They raise two questions: Should human research be performed at all? and, What debt, if any, does society owe to injured research subjects? At the beginning of each section relevant passages from two major codes of research ethics and an important code of research regulations will be quoted. These quotations from the Nuremberg Code, the Declaration of Helsinki, and the May 30, 1974, DHEW guidelines concerning the "Protection of Human Subjects" [2] will serve to indicate how much attention recent ethical and legal codes have devoted to the various issues and will provide a point of departure for the further consideration of each issue. I. MoralJustification The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature. [Nuremberg Code, 1947, rule 2] ... It is essential that the results of laboratory experiments be applied to human beings to further scientific knowledge and to help suffering humanity . .. . In the field of clinical research a fundamental distinction must be recognized between clinical research in which the aim is essentially therapeutic for a patient, and clinical research the aim of which is purely scientific and without therapeutic value to the person subjected to the research. [Declaration of Helsinki, 1964, preface] This review shall determine . . . whether...