Human Subjects

(source: Responsible Conduct of Research Education Committee. (2007). Resources. Retrieved July 15, 2007, from http://www.rcrec.org/resources.htm)

Advances in human health and welfare ultimately depend on research with human subjects. However, historically, not all human studies have been justifiable and useful. Some of the best known examples of human cruelty in the name of research occurred in Nazi Germany. Documentated instances of cruelty were the basis for the Nuremberg trials, and the subsequent development of the Nuremberg Code (1949), the first international codification of minimal expectations for the conduct of research involving human subjects. The Code delineates that experiments involving human subjects should occur only in the context of a clear, scientific rationale, and only with subjects who have freely chosen to participate.

Harm to unwilling subjects under the guise of research has not been unique to Nazi Germany. Recognition of problematic studies published in medical and scientific journals in the U.S. resulted in the appointment of a federal commission to identify fundamental principles that should govern human subjects studies. The final product of this commission was the Belmont Report (1979), which defined three ethical principles that now guide studies with human subjects.

Principles of Human Subjects

At least three important premises underlie these principles. The first is that studies involving human subjects are necessary for improvements in health and welfare. Second, to conduct such research is a privilege, not a right, extended to researchers by society, institutions, and the research subjects themselves. Finally, neither the risks nor the costs of any reseach study should outweigh the likely benefits.

  • Respect for persons. This conveys at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection.
  • Beneficence. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: do not harm, as well as work to maximize possible benefits and minimize possible harms.
  • Justice. The selection of research subjects needs to be scrutinized in order to determine whether some classes (e.g. particular racial and ethnic minorities) are being systematically selected simply because of their easy availability or their manipulability, rather than for reasons directly related to the problem being studied. Finally, whenever research supported by public funds leads to the development of therapeutic devices and procedures, justice demands both that these not provide advantages only to those who can afford them, and that such research should not unduly involve persons from groups unlikely to be among the beneficiaries of subsequent applications of the research.

Guidelines

Research that involves humans is subject to regulation. Applicable regulations include requirements for adherence to approved research protocols, maintenance of documentation and records, obtaining approval prior to initiation of changes, and reporting of adverse events. Investigators are responsible for identifying all applicable regulations and complying with them.

Think about issues of responsibile conduct.

Responsible conduct of research involving human subjects requires more than just complying with regulations. The decision to involve human subjects carries ethical as well as regulatory responsibilities to protect the welfare and interests of those subjects, to design the study so as to minimize risks to subjects, and to obtain adequate training for protecting the interests and welfare of the research subjects. Factors to be considered include changes in our best understanding of science, the risks and potential benefits of the study, and alternative methods for conducting the research.

Make sure the use of human subjects is both justifiable and necessary.

A prerequisite for responsibile research involving humans is a realistic examination of the probability and magnitude of both the risks and the benefits of the research. It is not enough that a proposed study is found to be justifiable; it is also necessary to consider whether alternative methods would be preferable. Can the same information be obtained with less cost or risk by a less invasive study, by the use of fewer subjects, or by studies of other species?

Informed consent

Investigators conducting a research study with human subjects have an absolute responsibility to ensure that consent to participate has been given freely and is based on an understanding of the risks and benefits. The Belmont principle of 'respect for persons' requires that researchers avoid invading privacy, maintain confidentiality of data, and obtain informed consent. Federal regulations outline numerous requirements for informed consent, including general requirements and documentation.

Informed consent is often needed even for studies in the social sciences that impose little or no inconvenience, but still present the risk of a loss of privacy or confidentiality. Ultimtaely, it must be up to the research subject, not the research investigator, to decide whether the costs or risks are outweighed by the benefits of participation.

Not all subjects are able to give true informed consent. For all subject populations in which autonomy is diminished, research investigators are responsible for meeting ethical and regulatory obligations to protect the right for self-determination of any prospective or current research subject.

Children also require special consideration. Parents can give permission for their child's participation in research. However, depending on age and maturity level of the child, it may also be appropriate to obtain consent from the child.

The most viable indication of 'informed consent' is a document to be signed by the research subject. This document is important because it provides a consistent body of information that the investigator has agreed is necessary for individuals to provide their informed consent. To ensure that the subject fully understands the terms of consent, a dialogue with the potential subject is necessary both prior to and during the study. Particularly if circumstances change during the course of a study, the investigator has an obligation to provide new information and ensure that the subject is still willing to participate. Informed consent is not a single event, but an ongoing process.