REGULATIONS The regulations set forth in this manual are based on the Belmont Report from the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the Code of Federal Regulations, Title 45 - Public Welfare, Part 46 - Protection of Human Subjects. The Belmont Report is a statement of general ethical principles that is meant to act as a guide in resolving ethical problems that surround the conduct of research with human subjects. The Belmont Report is concerned with the ethics of research, while Part 46 of Title 45 of the Code of Federal Regulations (which is based on the Belmont Report) addresses more specifically the recommended guidelines for the protection of human subjects. CODE OF FEDERAL REGULATIONS The federal regulations are disseminated by the Office for Protection from Research Risks (OPRR), an administrative unit within the Department of Health and Human Services, of the National Institutes of Health. The regulations apply to all research involving human subjects and provide definitions for the terms research and human subject. The regulations define research as a systematic investigation designed to develop or contribute to generalizable knowledge. Human subject is defined as a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual, or identifiable private information. The federal regulations describe four basic requirements for the conduct of an IRB: (a) a statement of principles, (b) designation of one or more IRBS, (c) appointment of IRB members, and (d) written procedures for the IRB. It is within these parameters that the Daemen College HSRRC operates. THE BELMONT REPORT The Belmont Report was developed by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1979. This commission was created when the National Research Act (PL 93-348) was passed in 1974. The Belmont Report summarizes the general ethical principles identified by the Commission that should underlie the conduct of biomedical and behavioral research involving human subjects. In carrying out its mission, the Commission considered the boundaries between biomedical/behavioral research and the accepted routine practice of medicine, the role of the assessment of the risk and benefit balance in determining whether humans should be used in the research, guidelines for the selection of human subjects, and the nature and definition of informed consent. Since research and practice often occur together, it is necessary to distinguish between these two terms in order to know what activities ought to be reviewed for the protection of human subjects. The term practice is used to mean a commonly accepted intervention or procedure which is designed to enhance the well-being of an individual or client and is considered by the practicing community to have a reasonable expectation of success. Research is used to mean an activity designed to test a hypothesis or answer research questions, so that conclusions may be drawn and contributions to the general knowledge of a field may be made. While research and therapy or research and education may be carried out together, for example, when evaluating the safety and efficacy of a therapy or of an educational strategy, this need not cause confusion regarding whether the activity requires review by the IRB. The general rule is that if there is an element of research in any activity involving human subjects, the activity should be reviewed. The following summary identifies the boundaries between medical/behavioral research and the practice of medicine, and the three basic ethical principles which, when practically applied, lead to informed consent, assessment of risk and benefits, and the selection of subjects. The three principles identified by the Commission as- generally accepted in our cultural tradition are labeled: (a) respect for persons, (b) beneficence, and (c) justice. These principles are stated in a sufficiently general manner to allow scientists, subjects, reviewers, and informed citizens to understand the ethical issues that are an integral part of research using human subjects. In stating these principles, the objective is to provide an analytical framework that will guide the resolution of ethical problems involving research with human subjects. Respect for Persons The first principle, which in its practical application gives rise to the idea of informed consent, is respect for persons. There are two ethical convictions which are the basis of this principle. First, individuals should be treated as autonomous agents. Second, individuals with diminished autonomy are entitled to protection. This principle carries two moral requirements: that we acknowledge the autonomy of individuals and protect those individuals with diminished autonomy. 'Me autonomous person is capable of choice, that is, capable of deliberation about personal goals and acting freely in the pursuit of those goals. To respect that autonomy is to allow the individual the freedom to pursue those goals without interference when there are no compelling reasons not to do so. Although the capacity for self-determination is expected to be part of the normal maturation process, some individuals lose this capacity because of illness or mental disability. So, not every individual is capable of self-determination, and some individuals require extensive protection. The extent of the protection afforded individuals who are considering participation in a research activity depends upon an assessment of the risk of harm and the likelihood of benefit from the research. These individuals must also enter into the research activity voluntarily and with adequate information. In its practical application, this principle requires that autonomous individuals, insofar as they are capable, be given the opportunity to choose what will and what will not happen to them. The possibility of this occurring is maximized when three standards for informed consent are satisfied. The first of these standards is information, generally including the procedure, purpose of the research, possible risks, anticipated benefits, and opportunity to ask questions and withdraw from the study. A simple listing of these items does not convey the full meaning of all of what is meant by the term information. A general rule often used to determine what information to give requires the researcher to provide information that reasonable persons would wish to know in order to make a decision regarding their care. Even then, subjects should clearly understand the range of the probable risks and the voluntary nature of their participation. Information concerning risk should never be withheld for the purpose of eliciting the cooperation of subjects, but care should be taken to avoid disclosures which would invalidate the research. The second standard to insure informed consent is comprehension. This standard is met when the information is conveyed in a manner that the subject can understand. This means that the researcher must adapt the presentation of the information to the subject's capacities for intelligence, rationality, language, and level of maturity. The obligation of the researcher to determine whether or not the subject comprehends the information increases with the seriousness of harm and probability of risks. The third standard for informed consent is voluntariness. Agreement to participate in research is valid only if the consent is voluntary. This means that the consent must be obtained without coercion, undue influence, unjustifiable pressure, or deception. Beneficence The second principle which the Commission established to guide resolution of ethical issues inherent in research was the principle of beneficence. This is the obligation to secure the wellbeing of participants in research by maximizing possible benefits and minimizing possible harms. In practical terms, this involves determining when it is justifiable to seek certain benefits despite the risks and when the benefits should be abandoned because of the risks. The assessment of benefits and risks is concerned with the probabilities and magnitudes of possible harms, such as psychological, physical, legal, social, and economic harm, measured against the possible benefits to the subject and to society. This assessment of risks and benefits requires the researcher's careful consideration of data, including consideration of alternate means of obtaining the same research information, and concern for the subject, subject's family, and society at large. This is accomplished by a systematic, non-arbitrary approach by the reviewing committee which requires those making decisions about the justifiability of the proposed research to be thorough in gathering and assessing information about all aspects of the research. This includes a determination of the presuppositions of the research, clarification of the probability and magnitude of risk, and estimation of compliance with five considerations: (a) brutal and inhumane treatment is never justified; (b) risks are reduced to those necessary to obtain the research goals; (c) if risk involves the possibility of serious impairment, review committees should require a very high level of justification; (d) the use of vulnerable populations must be justified; and (e) relevant risks and benefits must be communicated to the subject in the appropriate language. Justice The third principle is justice, which requires that there be fair procedures and outcomes in the selection of research subjects. The question is: Who ought to receive the benefits of research and who ought to bear its burdens? This principle is applicable at both individual and social levels. At the individual level, research is constrained to offer the benefits of research to all subjects and not to seek vulnerable subjects for research procedures involving higher levels of risks. Social justice requires that a distinction be made with respect to the ability of the social class selected for research to bear the burdens of the research. For example, this moral requirement would require the selection of adults before children, all other factors being reasonably equal. Thus, the selection of research subjects needs to be examined in order to determine whether some classes (racial and ethnic minorities, welfare recipients, children, or prisoners) are being selected simply because of their easy availability, rather than for reasons directly related to the problem under investigation. Except where research is directly related to the specific conditions of the class involved, it seems unfair that populations dependent on public health care constitute a pool of preferred research subjects if more advantaged populations are likely to be the recipients of the benefits of the research. Justice demands that benefits coming out of publicly funded research be available to all individuals and not just to those who can afford the benefits, and that publicly funded research not be confirmed to groups of individuals who are unlikely to be among the recipients of the benefits. This principle is more often than not overlooked. Therefore, the IRB must exercise a heightened degree of vigilance to insure that the principle of justice is fully applied to proposed research. Summary The Belmont Report attempts to summarize the basic ethical principles identified by the Commission in the course of its deliberations. The Commission was charged to consider the boundaries between medical/lbehavioral research and medical practice, the role of risk benefit assessment, the appropriate guidelines for selection of human subjects, and the nature and definition of informed consent. The report is a statement of basic ethical principles and guidelines to assist scientists in resolving the ethical problems surrounding the conduct of research with human subjects.