Guidelines

Ethical principles

The use of human subjects in research is extremely important to the development of new knowledge in many areas. However, careful attention must be given to questions of ethics and human dignity whenever humans are subjects in research. In 1978, the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research developed broad ethical principles to provide a basis on which specific rules could be developed. These principles are discussed in the Belmont Report, which provides the philosophical underpinnings for current Federal laws governing research involving human subjects, contained in Title 45 Code of Federal Regulations, Part 46, Protection of Human Subjects. 45 CFR Part 46 is not a set of rules that can be applied rigidly to make determinations of whether a proposed research activity is ethically "right" or "wrong." Rather, it provides a framework in which investigators and others can ensure that serious efforts have been made to protect the rights and welfare of research subjects. It is likewise the foundation for University Policy 2060 and must be considered in the design, conduct and evaluation of any human subjects research effort at Metropolitan State.

Three basic principles are particularly relevant to the ethics of research involving human subjects: respect for persons, beneficence, and justice. These excerpts are from the Belmont Report:

Respect for persons

Respect for persons incorporates at least two basic ethical tenets:

• Individuals should be treated as autonomous agents and
• Persons with diminished autonomy are entitled to protection

The principle of respect for persons thus divides into two separate moral requirements:

• To acknowledge autonomy and
• To protect those with diminished autonomy

To respect autonomy is to give weight to autonomous persons' considered opinions and choices while refraining from obstructing their actions unless they are clearly detrimental to others. Respect for the immature and the incapacitated may require protecting them as they mature or while they are incapacitated. Except in rare cases, respect for persons demands that subjects enter the research voluntarily and on the basis of adequate information about the research situation and possible consequences.

Beneficence

Persons are treated in an ethical manner not only through respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being. Such treatment falls under the principle of beneficence. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: -Do no harm and -Maximize possible benefits and minimize possible harms Learning what will, in fact, benefit may require exposing persons to risk. The problem posed by these imperatives is how to decide when it is justifiable to seek certain benefits, despite the risks involved, and when the possible benefits should be foregone because of the risks. The obligations of beneficence affect both individual investigators and society at large, because they extend both to particular research projects and to the entire enterprise of research. In the case of particular projects, investigators and members of their institutions are obliged to give forethought to the maximization of benefits and the reduction of risks that might occur from a research investigation. In the case of scientific research in general, members of the larger society are obliged to recognize the longer term benefits and risks that may result from the improvement of knowledge and from the development of novel medical, psychotherapeutic, and social procedures.

Justice

Who ought to receive the benefits of research and bear its burdens? This is a question of justice, in the sense of "fairness in distribution" or "what is deserved." An injustice occurs when some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly. The selection of research subjects needs to be scrutinized in order to determine whether some groups (e.g., welfare patients, racial or ethnic minorities, persons confined to institutions, students, children, pregnant women, fetuses) are being systematically selected simply because of their easy availability, their compromised position, or their manipulability, rather than for reasons directly related to the problem being studied. Especially when research supported by public funds leads to the development of therapeutic devices and procedures, justice demands 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.

Human subjects research definitions

Human subject definition

Human subject means a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual, or obtains individually identifiable private information.

• Intervention includes both physical procedures by which data are gathered and manipulations of the research participant or the participant's environment that are performed for research purposes.
• Interaction includes communication or interpersonal contact between the investigator and research participant.
• Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public.

Thus, human subject research includes investigations that use human tissue, human subject's records, or secondary data collected from human subjects (e.g., medical records, service records, etc.).

Research definition

What it is: Research is any systematic investigation, inquiry, or analysis - such as scholarly or critical study or inquiry or scientific investigation, development, testing or evaluation - designed to develop or contribute generalizable knowledge.

• This includes activities that aim to test a hypothesis, discover or collate facts, principles, or effects, reach new conclusions, or reexamine information by the critical study of a subject or by a course of scientific inquiry.
• It includes both original studies and replications of existing studies. Activities that meet this definition constitute research for purposes of human subject policies, whether or not they are considered research for other purposes.

What it isn't: The term research is not intended to apply to the following:

• Routine course, workshop, or curriculum development activities using accepted educational practices sponsored by Metropolitan State University, including evaluations to determine student or participant satisfaction, attitude change, or knowledge gained during the educational experience; or
• Aid or services provided by professionals to their clients that are consistent with accepted and established practice, and intended only to meet the clients' own personal needs.

Principal investigator/responsible project investigator

Principal investigators are those who are primarily responsible for the design and conduct of the research. In most cases, the PI is also the Responsible Project Investigator (RPI). The RPI must be a qualified, non-visiting member of Metropolitan State University faculty or staff who will serve as the project supervisor or representative at Metropolitan State. The RPI is responsible for supervising and monitoring the conduct of the research and is directly responsible for the HSRB application and approval process. In cases of research conducted by a student, or research conducted by individuals who are not employed by Metropolitan State University, an RPI must be designated. In the case of research conducted by a student, a faculty member will be the RPI, and for individuals not employed by Metropolitan State University, a Metropolitan State faculty or staff member will be the RPI.

Ethical conduct of research expectations

Voluntariness

Ethical, professional, federal and campus guidelines for human subject research all require voluntary participation of subjects. The Nuremberg Code, developed by the International Military Tribunal that tried Nazi physicians for the "experiments" they performed on non-consenting inmates of concentration camps, was the first widely recognized document to deal explicitly with the issue of voluntary and informed consent. The first principle of the code states:

The voluntary consent of the human subject is absolutely essential. This means that the person involved should:

• have legal capacity to give consent;
• be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching or other ulterior form of constraint or coercion; and
• have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision.

This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the:

• nature, duration and purpose of the experiment,
• method and means by which it is to be conducted,
• all inconveniences and hazards reasonable to be expected, and
• effects upon health or person that may possibly come from participation in the experiment.

The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.

Therefore, each subject must give her or his agreement to participate in the research based upon adequate knowledge and understanding of relevant information, under circumstances that minimize the possibilities of coercion or undue influence.

Information about the research and what participants should expect if they participate should not be withheld, especially if withholding it would influence a reasonable person's decision to participate or would damage his or her subsequent self-esteem. Information about risks shall never be withheld for the purpose of eliciting cooperation, and truthful answers should always be given to questions about the research. Certain groups, such as those who are economically disadvantaged, those who are very sick and those who are institutionalized, may have compromised autonomy and should be protected against danger of being involved in research solely for administrative convenience or because they can be relatively easily manipulated. No coercion, explicit or implicit, should be used to obtain or maintain cooperation. Subjects must feel completely free to decline to participate and to withdraw their participation at any time. As established by the National Commission for the Protection of Human Subjects and documented in the Belmont Report:

• An agreement to participate in research constitutes a valid consent only if voluntarily given.
• This element of informed consent requires conditions free of coercion and undue influence.
• Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance.
• Undue influence occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance.
• Also, inducements that would ordinarily be acceptable may become undue influences if the subject is especially vulnerable.

Unjustifiable pressures usually occur when persons in positions of authority or commanding influence -- especially where possible sanctions are involved -- urge a course of action for a prospective participant. A continuum of such influencing factors exists, however, and it is impossible to state precisely where justifiable persuasion ends and undue influence begins. However, undue influence would include actions such as manipulating a person's choice through the controlling influence of a close relative or threatening to withdraw health services to which an individual would otherwise be entitled.

Subject selection

In recruiting or selecting subjects, an important consideration, in addition to requirements based on scientific merit and practicability, is whether or not the selection is fair and equitable [§46.111(a)(3)]. In the 19th and 20th centuries, the burdens of research fell largely upon poor patients in hospital wards, while the benefits flowed primarily to private patients. This inequity was starkly revealed in the Tuskegee Syphilis Study, in which disadvantaged African American men in the rural south were recruited for studies of the untreated course of a disease that was by no means confined to that population. Such unjustified over-utilization of certain segments of the population led the National Commission to recommend that selection of research subjects be scrutinized to determine "whether some classes (e.g., welfare patients, racial and ethnic minorities or persons confined to institutions) are being systematically selected simply because of their easy availability, their compromised position or their manipulability, rather than for reasons directly related to the problem being studied." As documented in the Belmont Report  the principle of justice is relevant to the selection of subjects of research at two levels: the social and the individual.

• Individual justice in the selection of subjects would require that researchers exhibit fairness: thus, they should not offer potentially beneficial research only to some patients who are in their favor or select only "undesirable" persons for risky research.
• Social justice requires that distinction be drawn between classes of subjects that ought, and ought not, to participate in any particular kind of research, based on the ability of members of that class to bear burdens and on the appropriateness of placing further burdens on already burdened persons. Thus, it can be considered a matter of social justice that there is an order of preference in the selection of classes of subjects (e.g., adults before children) and that some classes of potential subjects (e.g., those who are institutionalized, those with cognitive disabilities or those who are incarcerated) may be involved as research subjects, if at all, only on certain conditions.

Injustice may appear in the selection of subjects, even if individual subjects are selected fairly by investigators and treated fairly in the course of research. Injustice arises from social, racial, sexual and cultural biases institutionalized in society. Thus, even if individual researchers are treating their research subjects fairly, and even if IRBs are taking care to assure that subjects are selected fairly within a particular institution, unjust social patterns may nevertheless appear in the overall distribution of the burdens and benefits of research. Although individual institutions or investigators may not be able to resolve a problem that is pervasive in their social setting, they can consider distributive justice in selecting research subjects.

Some populations, especially institutionalized ones, are already burdened in many ways by their infirmities and environments. When research is proposed that involves risks and does not include a therapeutic component, other less burdened classes of persons should be called upon first to accept these risks of research, except where the research is directly related to the specific conditions of the class involved. In addition, even though public funds for research may often flow in the same directions as public funds for health care, 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.

One special instance of injustice results from the involvement of vulnerable subjects. Certain groups, such as those from communities marginalized due to their race or economic means, those who are very sick and those who are institutionalized, may continually be sought as research subjects, owing to their ready availability in settings where research is conducted. Given their dependent status and their frequently compromised capacity for free consent, they should be protected against the danger of being involved in research solely for administrative convenience, or because they are easy to manipulate as a result of their illness or marginalized condition.

Just as the inclusion of disproportionate numbers of certain groups in research studies might overburden these groups without affording them the benefits that may result from the research, so will under-representation of groups ensure that they will not benefit from the research. As such, many research funding agencies, such as the National Institutes of Health (NIH), require that research include those from marginalized racial groups and women in study populations. If a proposed project includes a study population in which women and those from marginalized racial groups are not appropriately represented, the investigator must provide "a clear and compelling rationale for their exclusion or inadequate representation."

Confidentiality

Researchers have a responsibility to maintain the confidentiality of data collected during a study. Confidentiality refers to the researcher's management of private information shared by a subject that must not be shared with others without the authorization of the subject. Confidentiality is a separate consideration from anonymity which exists if the subject's identity cannot be linked, even by the researcher, with his or her individual responses. In most studies, researchers know the identity of their subjects and promise that their identity will not be disclosed to others. The researcher should describe the level of confidentiality of the research data and the measures that will be taken to ensure that confidentiality is maintained. These measures include how records or information will be handled, stored, and accessed.

Research risks and benefits

To address the principle of beneficence, researchers must consider the risks and benefits of the project. A research risk is the possibility of harm or discomfort that may occur as a result of participation in a research study. Potential risks to participants include time, stress, intrusion into personal or sensitive issues, emotional discomfort, physical harm (e.g., injury, fatigue), breach of confidentiality, etc. All research involves some risks, but in many instances, the risk is minimal. Minimal risk is defined as anticipated risks that are not greater than those ordinarily encountered in daily life or during routine physical or psychological tests or procedures. A research benefit is something of a health-related, psychosocial or other value to an individual research subject or something that will contribute to the acquisition of generalizable knowledge. Potential benefits may include a chance to talk with others experiencing a similar health issue, improved services, information that could lead to new grants in the community, etc. The researcher must consider and document whether the benefits clearly outweigh the risks to participants.