- Ethical Principles
- Human Subjects Research Defined
- Obtaining Consent
- Research Risks and Benefits
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. Also, it is the foundation for University Policy #2060 and must be considered in the design, conduct, and evaluation of any human subjects research effort at the University.
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 incorporates at least two basic ethical tenets: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. The principle of respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy and the requirement 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.
Persons are treated in an ethical manner not only through respecting their decisions and protection 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: first, do no harm and second, 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.
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 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 subjects research includes investigations that use human tissue, human subjects records, or secondary data collected from human subjects (e.g., medical records, service records, etc.).
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 subjects policies, whether or not they are considered research for other purposes.
What It Isn’t. If results are not disseminated (e.g., published, presented, or shared) externally (i.e., outside the Metropolitan State University campus), 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.
If results from these activities are disseminated externally, the activities constitute human subjects research and must receive HSRB approval.
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.
HSRB means a human subjects review board established in accord with and for the purposes expressed in University Policy #2060.
Ethical, professional, federal, and campus guidelines for human subjects 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; should 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 should 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; the method and means by which it is to be conducted; all inconveniences and hazards reasonable to be expected; and the effects upon his health or person which may possibly come from his 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 or what they 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 the economically disadvantaged, the very sick, and the 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, by contrast, 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 subject. A continuum of such influencing factors exists, however, and it is impossible to state precisely where justifiable persuasion ends and undue influence begins. But undue influence would include actions such as manipulating a person's choice through the controlling influence of a close relative and threatening to withdraw health services to which an individual would otherwise be entitled.
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. The inequity was starkly revealed in the Tuskegee Syphilis Study, in which disadvantaged blacks 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., the institutionalized mentally infirm or prisoners) 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. Thus 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. Also, 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 racial minorities, the economically disadvantaged, the very sick, and the 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 socioeconomic 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 minorities and women in study populations. If a proposed project includes a study population in which women and minorities are not appropriately represented, the investigator must provide "a clear and compelling rationale for their exclusion or inadequate representation."
The methods used to obtain consent may vary. They should be designed to fit the nature of the research, the nature and magnitude of the risks involved, the research setting, the nature of the subjects who will participate, and the requirements of applicable policies, laws, and regulations. If appropriate justification is given, an oral or passive consent process may be approved by the HSRB.
In order to obtain informed consent, Federal regulations require that certain information must be provided to each subject:
- a statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental;
- a description of any reasonably foreseeable risks or discomforts to the subject;
- a description of any benefits to the subject or to others which may reasonably be expected from the research;
- a disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the subject;
- a statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained;
- for research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained;
- an explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the event of a research-related injury to the subject; and
- a statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled.
When appropriate, one or more of the following elements of information shall also be provided to each subject:
- a statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or fetus, if the subject is or may become pregnant) which are currently unforeseeable;
- anticipated circumstances under which the subject's participation may be terminated by the investigator without regard to the subject's consent;
- any additional costs to the subject that may result from participation in the research;
- the consequences of a subject's decision to withdraw from the research and procedures for orderly termination of participation by the subject;
- a statement that significant new findings developed during the course of the research which may relate to the subject's willingness to continue participation will be provided to the subject; and
- the approximate number of subjects involved in the study.
The HSRB may approve a consent procedure that does not include, or which alters, some or all of the elements of informed consent set forth in this section, or waive the requirements to obtain informed consent provided the HSRB finds and documents that:
- the research involves no more than minimal risk to the subjects;
- the waiver or alteration will not adversely affect the rights and welfare of the subjects;
- the research could not practicably be carried out without the waiver or alteration; and
- whenever appropriate, the subjects will be provided with additional pertinent information after participation.
"Respect for persons requires that subjects, to the degree that they are capable, be given the opportunity to choose what shall or shall not happen to them. This opportunity is provided when adequate standards for informed consent are satisfied" [Belmont Report]. As stated in University Policy #2060, "no investigator may involve a human being as a subject in research unless the investigator has obtained informed consent of the subject or the subject's legally authorized representative." The manner and context in which information is conveyed is as important as the information itself. For example, presenting information in a disorganized and rapid fashion, allowing too little time for consideration or curtailing opportunities for questioning, all may adversely affect a subject's ability to make an informed choice.
Because the subject's ability to understand is a function of intelligence, rationality, maturity and language, it is necessary to adapt the presentation of the information to the subject's capacities. Investigators are responsible for ascertaining that the subject has comprehended the information. In addition, Title 45 Code of Federal Regulations, Part 46 requires "the information that is given to the subject or their representative shall be in language that is understandable to them."
Children must provide assent to participation when, in the judgment of the HSRB the children are capable of providing assent. Children are defined in the U.S. Department of Health and Human Services regulations as "persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted" 45 CFR §46.402(a). Assent is defined as the voluntary "affirmative agreement to participate in research. Mere failure to object should not, absent affirmative agreement, be construed as assent" 45 CFR §46.402(b). In determining whether children are capable of assenting, the HSRB will take into account the age, maturity, and psychological state(s) of the children, either individually or as a group. Children under age 8 may give assent orally or, in cases involving infants or very young children, by the act of participating. Children who can read (those 8-18 years old) should provide assent by signing a written form unless HSRB approves a different process.
In addition to the assent of the children, regulations require legally effective informed consent from the parent(s) (the child's biological or adoptive parent) or the legally appointed guardian (authorized under applicable State or local law to consent on behalf of a child) of all children who are participants in research. The consent of just one parent is allowed if the research presents no greater than minimal risks or if it holds out the prospect of providing direct benefits to the child. If the research presents greater than minimal risks and no prospect of direct benefit to the individual child, the consent of both parents is required, unless one parent is deceased, unknown, incompetent, not a legal custodian, or not reasonably available.
Fieldwork and ethnographic research typically involve observation of and interaction with groups of subjects in their own environment, often over long periods of time. It may not be possible to specify in an informed consent statement the detailed contents of the research, as it is often an emerging process. In addition, differences in language and culture may preclude the use of a written or formal consent agreement. If appropriate justification is given, the HSRB may waive the requirement for formal, written consent in these cases. The American Sociological Association (www.asanet.org/members/ecoderev.html) and the American Anthropological Association (www.aaanet.org/committees/ethics/ethics.htm) have developed guidelines that address ethical issues in field and ethnographic research, including informed consent. Investigators conducting this type of research may wish to consult their discipline’s professional society or accepted practice for similar guidelines when designing a protocol for research involving human subjects.
Under federal regulations (Title 45 Code of Federal Regulations, Part 46 §46.116), informed consent must be documented by the use of a written form approved by the HSRB and signed by the subject or their legally authorized representative. The consent form may be one of the following; in either case, a copy must be given to the research participant or their representative.
- A written consent document that embodies the elements of informed consent. This form may be read to the subject or the subject's legally authorized representative, but in any event, the investigator should give either the subject or the representative adequate opportunity to read it before it is signed; or
- A short form written consent document stating that the elements of informed consent have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there should be a witness to the oral presentation. Also, the HSRB must approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness should sign both the short form and a copy of the summary, and the person actually obtaining consent should sign a copy of the summary. A copy of the summary should be given to the subject or the representative, in addition to a copy of the short form.
The HSRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:
- That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or
- That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.
In cases in which the documentation requirement is waived, the HSRB may require the investigator to provide subjects with a written statement regarding the research.
In order to help researchers, the HSRB has outlined the specific elements for informed consent to be followed at Metropolitan State University in the Informed Consent Guide (PDF), which can be downloaded and printed for reference and guidance. It cannot be overly stated that the language used in every consent form or script must be understandable to the research participants or their representatives. Commonly, HSRB approval of research is delayed due to inadequate consent forms that have either too much or too little information, are confusing, or are written above the average participant's reading level (the average American adult has an 8th grade reading level). Consent forms should be written for the average participant's level of understanding and avoid technical language or terminology.
Signed consent forms should be retained by the RPI for a period of at least three years after the research is finished. It's possible that consent forms might contain information (e.g., names, phone numbers,locations) that will vary with time or with circumstances of the project. The HSRB Office must be informed in writing of any modifications in consent forms and must approve revisions before new forms are used.
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.
Data Security: What do you do with the data (not with the HSRB application materials) you have collected during your research?
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 whether the benefits clearly outweigh the risks to participants.