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Major Issues for Discussion

Most of the regulations regarding the use of human subjects were developed through what is called The Common Rule. The Common Rule, regarding the use of human participants in research, covers all federal agencies and departments that provide funding for such research. The Rule is formally titled, Code of Federal Regulations, Title 45 Public Welfare, Department of Health and Human Services, National Institutes of Health, Office for Protection from Research Risks, Part 46, Protection of Human Subjects. It was most recently revised November 13, 2001. As these regulations set the standard of practice for the industry, all institutions that accept federal funds must conform to the standards. Ethically speaking, human participants in all research should be treated in a manner that is minimally consistent with these regulations regardless of the source of the funding. Research institutions are expected to provide oversight of all research involving human participants. The Institutional Review Board (IRB) ensures ethical treatment for all participants in research conducted by employees or others connected to the institution. The IRB also provides oversight for research that would engage students, faculty, or other employees through their connection with the institution. The expectations included in this section are statements or interpretations of how human participants in research should be treated based on The Common Rule and derivative documents.

Research is defined as a systematic investigation (including development, testing and evaluation) designed to discover or contribute to a body of generalized knowledge.

A human participant in research is a living individual about whom a researcher obtains (1) data through intervention or interaction or (2) identifiable private information.

The human participant is required to provide informed consent if bodily materials are collected for research purposes, if diagnostic specimens are retained for research purposes, or if private information is compiled including medical records, DNA samples, or cell lines. In social and behavioral sciences, any research involving human subjects requires informed consent if (1) identifying information is recorded and (2) disclosure could place the participant at risk for criminal or civil liability or damage to their financial standing, employability or reputation, or if the research involves a vulnerable population. Initial IRB review is required unless the institution has provided alternative procedures for projects that obviously do not require the participants' informed consent. IRB review, in these cases, involves determination by the committee or designated representative that the project is "exempt." Continued oversight is not required.

1). Informed Consent/Privacy/Confidentiality
Respect for autonomy implies that potential human participants in research should have the opportunity to give voluntary, educated consent about whether they wish to participate in the study or not.

Informed consent requires that participants truly understand, from their perspective rather than the researcher's, what will actually happen to them through their inclusion in the study. All risks and any benefits should be known. What follows from a decision not to participate is important, particularly to people who are ill and choosing to participate in an experimental drug study or if participants perceive that their participation is expected or coerced.

It is important that participants know what will happen to any data or information collected from them.

Privacy refers to the right of an individual to control what other people know about them. This right is limited in that no person can completely control what other people know about him or her if that knowledge is based on the individual's public speech, actions, or location. Informed consent is not required for research projects that monitor unidentified subjects' public behavior. However, when information that individuals would normally control is collected, informed consent indicates that the participant has voluntarily chosen to disclose certain information to investigators.

Confidentiality refers to the care researchers exhibit toward data collected from individuals. Confidentiality is ensured by investigators following one or more of these procedures:

1). Maintain a research culture based on respect for human participants and disclosure of information within the research team on a need-to-know basis; all team members should sign confidentiality agreements;
2). Use codes or encryption for identifying information;
3). Separate forms containing identifying information from instruments containing data;
4). Electronic and paper files containing identifying information should be stored in an area away from public access and should be locked.

Confidentiality methods should be explained along with an explanation of how participants can gain access to their own data or how they can gain access to the justification for lack of access to their own data. Participants need to know how to get help if they suffer a research-related injury and who to contact with questions during or after the study. Participants should know that their consent is an on-going process that they may withdraw at any time without penalty.

It is standard that participants sign a consent form indicating their understanding of all of these aspects, but a signature is not the same as informed consent. According to Bioethicists David Wendler and Jonathan E. Rackoff, "Any ethically valid process for enrolling competent subjects in research must satisfy three conditions:

1). Sufficient evidence that subjects who enroll want to enroll;
2). Subjects control over whether they enroll; and
3). Sufficient evidence, accessible to observers independent of the research team, that conditions one and two have been satisfied when subjects enroll."/1

Framing informed consent from an independent observer's perspective provides an easy to apply publicity test: If someone were to ask participants what they are doing and why and what the conditions are regarding their participation, they should be able to answer those questions.

It is also important to note that while a signed consent form provides the usual evidence that an informed consent process has been followed, federal policy does not always require a signed form. Participants who provide highly sensitive information or who are asked to describe illegal activity should not be asked to sign consent forms. The participant's signature on a consent form, in these cases, unnecessarily raises the degree of risk to the participants. Here, investigators must develop alternative procedures to demonstrate that participants have voluntarily and knowingly agreed to share information for use in the study. If a signed consent form is used, it must be written in language suitable to the understanding and comfort level for the potential participants and must include the following:

1). A statement that labels the study as research;
2). An explanation of the reasons for the research, an invitation to participate and explanation of why the participant was selected, and the expected duration of the participant's participation;
3). A description of procedures to be followed and identification of which procedures are investigational and which might be provided as standard care to the participant in another setting. Use of research methods such as randomization and placebo controls should be explained;
4). A description of any foreseeable risks or discomforts to the participant, an estimate of their likelihood, and a description of what steps will be taken to prevent or minimize them; as well as acknowledgment of potentially unforeseeable risks;
5). A description of any benefits to the participant or to others that may reasonably be expected from the research, and an estimate of their likelihood;
6). A disclosure of any appropriate alternative procedures or courses of treatment that might be advantageous to the participant;
7). A statement describing to what extent records will be kept confidential, including examples of who may have access to research records;
8). For research involving more than minimal risk, an explanation and description of any compensation and any medical treatments that are available if participants are injured through participation; where further information can be obtained, and whom to contact in the event of research-related injury;
9). An explanation of whom to contact for answers to questions about the research and the research participant's rights (including the name and phone number of the PI;
10). A statement that research is voluntary and that refusal to participate or a decision to withdraw at any time will involve no penalty or loss of benefits to which the participant is otherwise entitled;
11). A statement indicating that the participant is making a decision whether or not to participate, and that his/her signature indicates that he/she has decided to participate having read and discussed the information presented.

When appropriate, the following elements should also be included:

1). If the participant is or may become pregnant, a statement that the particular treatment or procedure may involve risks, foreseeable or currently unforeseeable, to the participant, or to the embryo or fetus;
2). A description of circumstances in which the participant's participation may be terminated by the investigator without the participant's consent;
3). Any costs to the participant that may result from participation in the research;
4). The possible consequences of a participant's decision to withdraw from the research and procedures for orderly termination of participation;
5). A statement that the PI will notify participants of any significant new findings developed during the course of the study that may affect them and influence their willingness to continue participation;
6). The approximate number of participants involved in the study /2.

Compensation and Coercion
Compensation is payment or the potential of monetary gain for human participants in research. Coercion means to compel participation by real or perceived force, authority or intimidation. Participation is coerced if participants believe that they will suffer if they choose not to participate. While coercion most often occurs because participation is requested or expected by someone who has power over the potential participant, compensation can be coercive if it is likely to encourage a participant to take risks that he or she would not take if it were not for the money. It should be clear to participants whether the level of compensation is dependent on continued participation and any circumstances in which the level of compensation is out of the participant's control (e.g., compensation based on group performance in a collaborative exercise). In situations in which participants are vulnerable to authority, participants should be able to explain to researchers how their voluntary participation is unrelated to potential negative consequences involving student evaluation or job performance.

2). Vulnerable Populations and Justice
Certain groups require special consideration regarding inclusion in research and in the consent process.

Women and racial minority groups, for example, have generally not been included in research protocols because investigators traditionally preferred not to introduce the variable of gender or race into their studies. Treatments have not been tested on women or non-Caucasians, with the result that women or racial minorities may not receive the same degree of benefit from health sciences research as do white men. The NIH Revitalization Act of 1993 legislated that women and minority groups be included in research funded through NIH "unless a clear and compelling rationale and justification establishes ... that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research"./3 A research study on testicular cancer may exclude women just as a study on genetic disease affecting a particular racial population may exclude all others.

Women who are pregnant may be excluded unless the research will meet the health needs of the woman and the fetus. Informed consent from the biological father may also be required for research involving the use of pregnant women unless:

1). The purpose of the research is to meet the health needs of the mother;
2). His identity or whereabouts cannot reasonably be ascertained;
3). He is not reasonably available; or
4). The pregnancy resulted from rape."/4

Children and adults who are cognitively impaired are considered to be vulnerable research subjects because of limited intellectual capacities. However, the 1998 NIH policy guidelines require that children be included in all human research unless there are scientific or ethical reasons for excluding them, just as women and racial minorities are required to be included./5 NIH recognizes the importance of including individuals who are cognitively impaired in studies, particularly those that increase understanding of these individuals and their maladies. Informed consent is required from parents or guardians. To the extent possible, based on age and cognitive ability, the child or cognitively impaired participant is required to give "assent." Assent means that the participant agrees to participate. Failure to object is not equivalent to assent. The elderly are considered a vulnerable population because of possible diminished capacity and because of increased level of risk of research-related injuries. They, too, are required to "assent", even if a competent caregiver or guardian has provided "consent."

Prisoners, students and employees are considered vulnerable populations because of the possibility of coercion. Due to their special circumstances, they may involuntarily consent to participate in research due to pressure, perceived expectations or the promise of compensation that may not affect the decision of a potential participant who is not in that circumstance.

Some of the vulnerability of research populations can be reduced by inclusion of members of those populations or advocates for those populations on the Institutional Review Board.

Just as informed consent in vulnerable populations involves a more complicated process, such as obtaining "assent" from children or less competent participants as well as "consent" from caregivers, research on populations that are vulnerable culturally may require that investigators obtain group as well as individual consent. For example, projects involving indigenous populations should include, prior to seeking individual consent, an opportunity for elder leaders and members to hear a description and justification of the planned project, and for them to ask questions or provide input that might lead to greater project success. Community or elder knowledge, however, does not substitute for the need for individual informed consent.

3). Institutional Review Board
Research institutions are required to have an Institutional Review Board (IRB) to provide oversight for the conduct of research using human participants. The IRB primarily provides a review of potential benefits and risks of the proposed study and analyzes the informed consent procedure proposed.

The IRB must have at least five members. Through the composition of the committee, the IRB must have a diversity, including race, gender, and cultural backgrounds, a broad set of experiences, and sensitivity to such issues as community attitudes. The IRB should also be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. If an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.

The IRB must know reasons for exclusions and stipulated provisions for the inclusion of human participants from vulnerable populations. Children may not be excluded from research without good reason. However, in protocols involving children, the IRB and investigator must determine in which of the following categories the research belongs and document in the minutes the rationale for the category:

1). Category 1 is research that does not involve greater than minimal risk to children;
2). Category 2 is research involving greater than minimal risk, but presenting the prospect of direct benefit to the child participant;
3). Category 3 is research that involves greater than minimal risk with no prospect of benefit for the child participant. The IRB will approve Category 3 research only if all of the following conditions are met:

a). The risk is no more than a minor increase over minimal risk;
b). The intervention or procedure is not unlike what the child participant would encounter in actual or expected medical, dental, psychological, social or educational situations; and
c). The intervention or procedure is likely to yield generalized knowledge about the subject's disorder or condition which is of vital importance for understanding or amelioration of the disorder or condition.

Each IRB shall, except when an expedited review procedure is used, review proposed research at convened meetings at which a majority of the members of the IRB are present, including at least one member whose primary concerns are in non-scientific areas. In order for the research to be approved, it shall receive the approval of a majority of those members present at the meeting. An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities involving human subjects. An IRB decision to disallow research may not be overruled by the institution's administration and IRB approval must be obtained before the start of any research involving human participants. More detailed information regarding IRB procedures at The University of Montana can be found here.

IRB meetings at The University of Montana are open to investigators and other interested parties under state law.

4). Inclusion and Exclusion for IRB Review
Research "means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalized knowledge."

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

Intervention "includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes."

Interaction "includes communication or interpersonal contact between investigator and subject."

Minimal Risk "means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests."

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 which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects."/7

While these definitions seem straightforward, the line between research and non-research is not that clear.

Generally, it is not necessary to submit a protocol to the IRB if investigators are asking others their professional opinions about the need for particular research, even if they will use those opinions in the writing of a grant proposal. However, if investigators are systematically developing data to determine need, that would count as "systematic investigation" and "research development" and would need IRB approval.

"Generalized Knowledge" means that the investigator intends to draw conclusions or make statements, based on the data, that go beyond an individual case. On this basis, journalistic accounts, even though intended for publication, are usually excluded from IRB review. Research intended for publication in an academic journal or marketing research would require an IRB review.

Development of a research protocol, including pilot studies, require IRB review. If the research involves identifiable members who would be placed at risk for criminal or civil liability or could damage them in terms of financial standing, employability, or reputation, or if it involves vulnerable populations is also subject to IRB review.

The most difficult determinations need to be made regarding student work. If the work is being developed for thesis or dissertation research, or with the intention of presentation or publication, IRB must approve the human participation in the study. Dissertations and theses are usually open to public reading and review and, thus, qualify as presentation or publication.

The guideline is less clear if the research is being done with the intention of educating the student in research design, methodology or techniques. Generally, while IRB's do not have a federally-mandated role in these cases, they generally provide advice to department and research course instructors. For example, Stanford University does not require such research to be reviewed by IRB./8 Other institutions require review if the student's work involves vulnerable populations or if it places human participants at more than minimal risk or if the results are likely to leave the classroom./9

The University of Montana has provided a middle ground to ensure supervision of student research and student research practice, without requiring IRB review for each student project. Instructors of courses that require students to carry out research that uses human participants submit an IRB proposal for course review each time the course is offered. The submission requires instructors to delineate their procedure for teaching students about risk and ethical soundness of research. The syllabus must describe how ethical issues in research will be discussed, including the materials to be used. However, student projects that involve vulnerable populations or more than minimal risk must be submitted as separate protocols for IRB review. More information on IRB requirements and research method courses at UM can be found here.

Research that is excluded from review by IRB must be conducted in an ethical manner. The primary ethical principles of respect, beneficence and justice must be applied any time that human participants are approached by investigators or students regardless of level of intervention or risk.

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Case Studies

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Case Study 1: Blood in the Lab.

Case Study 2: A Test of Anxiety.

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Footnotes

1/Wendler, D. and Rackoff, J.E., "Informed Consent and Respecting Autonomy: What's a Signature Got to Do with It?" IRB: Ethics & Human Research 23, no. 3 (2001) p. 2.

2/cme.nci.nih.gov/ic-pop2.htm.

3/ohsr.od.nih.gov/info/kinfo_11.php3.

4/45 CFR 46.207.

5/ohsr.od.nih.gov/info/jinfo_10.php3.

6/Research Involving Children, OHSR Information Sheet #10, ohsr.od.nih.gov/info/jinfo_10.php3.

7/orhp.osophs.dhhs.gov/humansubjects/guidance/45cfr46.htm.

8/www.stanford.edu/dept/DoR/rph/7-3.html.

9/www.indiana.edu/~resrisk/stures.html and grants-svr.admin.iastate.edu/vpr/humansubjects/student_projects.html.

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Additional Resources

Below are links that may help you understand human subject issues a little better:

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Section Assessment and Certificate

Make sure you have reviewed all of the materials within this section, before you attempt the assessment.

When you have successfully completed the assessment, you will be offered an opportunity to print out a certification document for your records. You can then close the window and return to the course.

To begin the assessment, click this link.

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