Research ethics is concerned with the moral principles and rules that govern the conduct of scientific study involving human subjects. Clinical research is essential to further our understanding of the causes of schizophrenia and the development of safe and effective treatments. But these ends cannot be pursued legitimately by any means. Clinical research must be conducted in a manner that protects the liberty and welfare interests of research subjects. Standards for the conduct of clinical research are set out in federal regulations and are enforced by institutional review boards. Clinicians who conduct research, or whose patients may be enrolled in such research by others, need an understanding of the regulation of clinical research, ethical principles and rules, and issues of special importance to psychiatric research.

The need for regulation of research by the State is often traced to unethical practices in the past. Unfortunately, medical history is replete with examples of research that fails to take adequate account of the rights and welfare of subjects (Moreno, 2001). For instance, at the Allen Memorial Institute in Montreal, Canada, in the 1950s and 1960s, Dr.Ewan Cameron used a variety of experimental techniques on psychiatric patients, including electric shocks; “psychic driving,” in which taped messages would be repeated for days at a time; and sensory deprivation. Later, experiments funded by the Central Intelligence Agency involved the administration of LSD (lysergic acid diethylamide) to patients.

The ethical failings of these experiments were multiple: informed consent was either not obtained or was inadequate; the interventions lacked a scientific basis; and patients were subjected to serious risks.

To protect research subjects, the State has established a system of oversight for clinical research in which the keystone is the institutional review board (IRB). IRBs are local committees that review research on human subjects for ethical acceptability. IRB approval is required for such research to be conducted. The first IRBs were federally mandated in 1966 and, by current estimates, there are 3,000–5,000 IRBs at universities, hospitals, and research institutions in the United States. The IRB must have at least five members, and include researchers, one or more community representatives, an ethicist or a lawyer, and in some cases a statistician. The IRB reviews the research protocol, the investigator’s brochure related to any study drugs, and the informed consent form to determine study acceptability. While the purview of the IRB includes both ethical and scientific issues, the review of scientific issues may be delegated to another more qualified body (e.g., an NIH [National Institutes of Health] Study Section).

In its review, the IRB ensures that the study complies with relevant regulations and guidelines (Emanuel, Wendler, & Grady, 2000). In the United States, all human subject research funded by the Federal government, or conducted at an institution that receives Federal funds, must comply with the Federal Common Rule (Title 45 CFR Part 46).

Other regulations define additional protections for pregnant women (referred to as Subpart B regulations), prisoners (Subpart C), and children (Subpart D). Despite repeated calls over the last 20 years, Federal regulations do not define additional protections for incapable adults,  including those incapacitated by mental illness (Karlawish,  2006).

TABLE 61.1.  Moral Principles and Rules for Clinical Research. Other relevant guidelines for clinical research include the World Medical Association’s Declaration of Helsinki, the Council for International Organizations of Medical Sciences’ International Ethical Guidelines for Biomedical Research Involving Human Subjects, and the International Conference on Harmonization’s Good Clinical Practice guidelines. Relevant regulations and guidelines, guidance, and educational materials are found at the website of the Office for Human Research Protection (http://www.hhs.gov/ohrp).

Clinical research is governed by three ethical principles: respect for persons; beneficence; and justice (Table 61.1). The principle of respect for persons means that the wishes of autonomous individuals ought to be taken seriously, and that persons incapable of autonomous choice are entitled to protection. It grounds requirements for free and informed consent from research participants and confidentiality of research information.

The principle of beneficence signifies that one must protect people from harm and, where possible, promote their benefit. It underpins the requirement that the benefits and harms of research participation stand in reasonable relation. The principle of justice implies that one must treat people fairly. It is the basis for the requirement that study selection procedures must be fair, neither unduly advantaging nor disadvantaging any relevant group of potential study participants.

The free and informed consent of research subjects must generally be sought prior to study participation. Prospective subjects must be informed of the purpose of the study, duration of participation, procedures to be administered, the benefits and harms of study participation, alternatives, and their rights as research subjects. A distinction may be drawn between the consent process and the consent form. The consent process is the ethically mandated dialogue between the clinical investigator and the prospective study participant regarding study participation.