The University of Mississippi
Research and Sponsored Programs
Currently, researchers from all disciplines strive to protect research participants from harm or discomfort. This is due in part to moral obligation and in part to institutional and federal regulation. The last fifty years have seen the formulation of inter-institutional and multi-national guidelines for the protection of human subjects. Prior to the 1940's researchers were solely responsible for the protection of participants. Unfortunately, history holds many accounts of unethical treatment of human subjects. Research that placed participants at undue risk resulted in a range of harm to the participants from questionable psychological distress (Milgram obedience studies) to chronic illness and death (Tuskegee syphilis studies, radiation experiments; for example, see Maloney, 1984, or Rothman, 1991). Despite many clear violations it took the atrocities of war to bring attention to this area of human rights.
An initial step in the evolution of formal ethical regulation was the creation of the Nuremberg Code (Appendix B). This doctrine was established by the prosecution at the Nuremberg trials to serve as basic ethical principles universally applicable to human research. The ten principles found in the Nuremberg Code were used in the war crimes trials of 23 Nazi physicians. The establishment of the Nuremberg Code marked the beginning of a series of concerns regarding research involving human participants.
The next major step in the evolution of ethical guidelines was the Declaration of Helsinki (1974), (Appendix B). The Declaration extended the Nuremberg Code by allowing surrogate consent when the actual participant was unable to give consent. In addition, it included a distinction between therapeutic clinical research and non-therapeutic clinical research. Subsequent revisions of the Helsinki Declaration (1975, 1983, 1989) continued to emphasize the need for informed voluntary consent in human research (World Medical Association, 1991; Perly et al., 1992).
Other documents continue to foster ethical responsibility in research. These include the Federal regulations regarding Institutional Review Boards and the American Psychological Association Code for Social and Behavioral Research. Based on these documents, the "Belmont Report" (1978) was published by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report sets forth basic ethical principles for researchers to follow in designing responsible research. These principles include respect for persons, beneficence, and justice. These principles can be realized by designing research that respects the individual's right to self determination through voluntary participation. Researchers also have the responsibility to maximize benefits to individual participants or to society while making concerted efforts to minimize possible risks from participation. Moreover, researchers carry the burden of making equitable participant selection in order to represent the population adequately, while not manipulating compromised classes of subjects into consent. It is the responsibility of all researchers to observe and maintain these ethical principles in all of their work.
These documents were developed to aid investigators in designing research that would assure that human subjects were treated in an ethical manner. Despite the considerable effort placed in the creation of these documents, no formal monitoring mechanism was established. Again, the responsibility of assuring ethical treatment of participants fell on the researcher. However, the guidelines alone did not prevent unethical treatment of human subjects. The Tuskegee study continued unabated throughout the evolution of these various guidelines for over 40 years. While many informal research evaluation committees were formed across the country, there was a growing need for a formal review process. In 1974 the federal government mandated the establishment of IRBs at all institutions that receive funding from the Department of Health and Human Services (DHHS).
IRB administration is overseen by the Office for Human Research Protections (HRP), a division of the National Institutes of Health (NIH). The IRB was designed to be a local review committee representing the needs of the local community. It is believed that this local review can far better protect human subjects than a national review process. An IRB is made up of various people in the community representing a number of areas of expertise. An IRB is guided by CFR 45 part 46 and CFR 21 parts 50 and 56, which mandate the minimum requirements for the protection of human subjects and allow considerable latitude on the local level for decisions regarding research.
The Institutional Review Board for the Protection of Human Subjects (IRB) at The University of Mississippi is appointed by the Vice Chancellor for Research and Sponsored Programs and is commissioned to review all proposals for research which involve human subjects, according to the University's Federalwide Assurance (FWA00008602) with the Department of Health and Human Services. The task of the IRB is to ensure that the research is in compliance with ethical standards, University policy, and federal regulations. All human research conducted at, by, or under the auspices of this institution, whether funded or not and whether conducted by administrators, faculty, staff, or students, must be reviewed and approved before the research begins.
The IRB has the authority to approve, require modifications in, or disapprove all research activities that fall within its jurisdiction as specified by both the federal regulations and University policy. Research that has been reviewed and approved by the IRB may be subject to review and disapproval by officials of the University. However, those officials may not approve research if it has been disapproved by the IRB.
For the definitions of what constitutes "research" and "human subjects" please see Chapter 3.
The University of Mississippi IRB is located in the Division of Research Integrity and Compliance (DRIC) within the Office of Research and Sponsored Programs. The UM IRB is staffed by Diane W. Lindley (dlindley@olemiss.edu), IRB Coordinator, and Sean King, IRB Assistant. Together with the IRB Chair they handle the day-to-day operations of the IRB. The IRB staff may be reached during regular University hours at 662-915-7482, by fax at 662-915-7577, or by email at irb@research.olemiss.edu. The IRB office is in the Office of Research and Sponsored Programs suite on the first floor of Barr Hall (reception desk in Room 100).
The IRB Application Packet, which contains all forms and instructions for filing a protocol with the IRB, is found in Appendix E of this manual. Forms may also be downloaded from the Compliance Forms page .
The membership of the University of Mississippi IRB is as follows:
Chapter 3 discusses the basic IRB process and is especially relevant to graduate students and their advisors. It concludes with issues of interest to only a few investigators.
University policy specifies that any research involving human subjects must be approved by the Institutional Review Board". Whether this provision applies to you is based on your answers to two questions:
If you answered yes to both questions, then your study is defined as research with human subjects and must be approved by the IRB before you begin recruitment of research participants or data collection. Please note that survey research, all pilot studies, and oral history research do meet this definition and must be approved by the IRB before you send out questionnaires, interview subjects, or otherwise have contact with potential subjects.
Prior IRB approval is mandated by Federal Law and by policy of The University of Mississippi.
Note: Investigators should begin to consider IRB issues during the planning stages of a research project. One should consider issues such as subject selection, the use of deception, and the collection of sensitive data. When possible the investigator should try to eliminate the need for these higher risk procedures. When it is not possible to eliminate these risks the investigator must demonstrate the need for such high risk procedures and take steps to minimize the potential risk to the subject.
Risks to subjects posed by participation in research should be justified by the anticipated benefits to the subjects or society. This requirement is clearly stated in all codes of research ethics, and is central to the federal regulations. (OPRR, 1993, p 3-1)
The federal regulations under which IRBs operate do not clearly call for IRB review of the scientific validity of an investigator's research design. However, the federal regulations do require that IRBs determine whether "risks to subjects are reasonable in relation to...the importance of the knowledge that may reasonably be expected to result" [Federal Policy __.111(a)(2)]. "One of the ethical justifications for research involving human subjects is the social value of advancing scientific understanding and promoting human welfare by improving health care. But if a research study is so methodologically flawed that little or no reliable information will result, it is unethical to put subjects at risk or even to inconvenience them through participation in such a study" (OPRR, 1993: 4-1)
In general, if an investigator is seeking funding from an external agency a study, the IRB leaves thorough scrutiny of the research design to the peer review process. The proposals of investigators who are not submitting to external agencies may be examined more closely for research design flaws, and they may be required to correct these flaws before IRB approval is granted.
Researchers assume certain responsibilities:
Primary
General
During the Application Process
During the Research Process
All investigators working with human subjects have a responsibility to comply with the regulations specified in federal law and University policy designed to protect the rights and welfare of those research subjects. The most common lapses in investigator compliance are related to a misunderstanding of the application and reporting requirements, failure to submit necessary documents to the Institutional Review Board, and forgetting to submit an application to conduct research involving humans before the study commences. Most of these cases can be resolved by the IRB without jeopardizing the welfare of the subjects.
Occasionally, an investigator will either avoid or ignore the IRB. Such cases present a serious challenge to the IRB and to the University. Regardless of investigator intent, unapproved research involving human subjects places those subjects at unacceptable risk, and places the University at risk for federal sanctions.
It is the responsibility of the IRB and its staff to facilitate researcher compliance with regulations and policies governing human subject research. However, failure to cooperate with the IRB in fulfilling application and reporting requirements, and failing to respond to requests for information and documentation constitutes non-compliance. If an investigator fails to supply the IRB with requested information or documents after a third request from the IRB, the Vice Chancellor for Research and Sponsored Programs will be informed of this non-compliance. The Vice Chancellor will notify the investigator's department chair and academic dean of this non-compliance, and instruct the investigator to cease further research involving humans until they comply with all IRB requirements. Depending on the nature of the research and the level of risk to subjects, the Vice Chancellor will have the option of confiscating all data collected prior to approval of the research by the IRB.
Privacy refers to a person's interest in controlling the access of others to himself or herself. Confidentiality, an extension of privacy, refers to the way in which personal information is handled by a second party who controls access to that information by others. Anonymity refers to the separation of personal identifiers from any information about an individual. The procedures for protecting confidentiality and anonymity and the limitations to confidentiality and anonymity must be discussed in the informed consent document.
IRBs must decide to what extent privacy, confidentiality, and anonymity apply to each project to protect participants adequately. These concepts can be thought of as existing independently in the abstract. However, within IRB approval each serves to counterbalance subjects' ultimate protection from risk, relative to the degree of risk involved in a project. An essential concern of the IRB is how any proposed invasion of privacy could harm an individual. IRBs must assess the potential repercussion to an individual that results from private information becoming known to others, such as past criminal activity becoming known to an employer. The investigator can regulate the degree of risk that occurs in a project by varying one of these three variables:
Varying the level of each of these factors in accordance with the level of risk will allow investigators to collect the needed data. It is important to remember that limitations to confidentiality and anonymity must be addressed in the informed consent document. For example, data may be subject to subpoena by court authorities, in which case researchers cannot guarantee confidentiality. However, IRB staff members are available to advise ways to limit the risks to confidentiality, such as means for delinking subject identifiers from data, construction of informed consent forms, and application to the Secretary of Health and Human Services for a certificate of confidentiality when appropriate.
Several principles guide the selection of subjects for research:
◊ The burdens of research should be distributed equally among the persons who will benefit from it; therefore, overinclusion or underinclusion of any class of subjects must be justified (see Application for a Public Health Service Grant, PHS 398, for a discussion of research with women and minorities);
◊ Convenience alone does not justify using a particular class of subjects; the nature of the research should require or justify the use of a particular class of subjects;
◊ As a matter of social justice, there should be an order in the selection of classes of subjects: adults before children, competent individuals before incompetent individuals, and noninstitutionalized persons before institutionalized persons; in brief the least vulnerable classes of subjects should always be selected;
◊ Participation in research is voluntary; therefore, researchers are discouraged from using subjects who may have restricted freedom to refuse to participate (e.g., researchers' students, employees, or patients); and
◊ In order to ensure voluntary participation, subjects should be recruited through general announcements or advertisements rather than through personal solicitation.
(Selection of subjects is also discussed in Chapter 4 of this manual.)
Frequently, subjects receive remuneration for participating in research, e.g., money, free medical care, or course credit. Modest incentives or reimbursements for expenses incurred by subjects are appropriate. However, if incentives are so strong that prospective subjects do not think that they can refuse them, then the incentives become essentially coercive (i.e., "undue". Undue inducements are troublesome because (1) offers that are too attractive may blind prospective subjects to the risks of a study or impair their ability to exercise proper judgment, and (2) they may prompt subjects to lie or conceal information that, if known, would prevent them from enrolling or continuing as participants in research projects. IRB standards for judging whether incentives constitute undue influence must vary according to research procedures and subject populations, but the following questions form the general basis for determining whether incentives are appropriate:
1. Are all research conditions in keeping with standards for voluntary and informed consent?
2. Are the incentives offered reasonable, based on the complexities and inconveniences of the study and the particular subject population?
Informed consent is an integral component of research insuring that participants are aware of and understand fully the consequences of participation. Informed consent is the process by which participants are provided the information necessary to make a decision about participation. Current Federal regulations (45 CFR 46.116) describe eight basic elements of informed consent that are necessary to provide an individual with adequate information for making such a decision:
Each of these elements serves a specific function in the process of informing participants of their involvement in the research project. However, as it has been mentioned by many (Porter, 1995; OPRR, 1993; & Grunder, 1986), informed consent is more than a form, it is an ongoing process. It is crucial to consider the participant's specific involvement in a project and a participant's abilities to assure proper informed consent. Often involvement in a research project may occur over the course of several weeks or months. In these instances it is important to review informed consent issues from time to time in order to reaffirm the participant's understanding. The need for renegotiating informed consent will vary from study to study. As with many aspects of IRB review, this issue must be considered on a case by case basis. The IRB will make a final determination as to the extent to which an investigator will need to reaffirm consent. This could range from reminding the participants of what will be expected at each session to a formal review of the informed consent document. Regardless of the determination by the IRB, the investigator bears the responsibility for assuring that participants have a full understanding of the nature of their involvement in the research throughout the project.
Special Population Issues
A special issue in consent arises when participants are unable to give consent for themselves, as with children or cognitively impaired individuals. In such cases consent is generally given by "proxy". However, this proxy consent is not the same as true consent, and thus raises other ethical questions. In the event proxy consent is obtained, the subject should be given veto power whenever feasible. Such is often the case with children involved in research activities. While they are unable to give legal consent, they may still be able to grasp at least basic aspects of the research project. When this is the case, assent of the subject is necessary. While there is no clear rule regarding the age at which children can adequately give assent to participate, the rule of thumb is that assent should be obtained from children seven years and older. In general, if the participants have the cognitive ability to understand what they will be asked to do in a project, they should be asked if they would like to participate. Again, this issue must be assessed on a case by case basis, and the IRB will make a final determination as to whether both assent from participants and consent from guardians are necessary. (See also Chapter 4.)
Deception
Many research questions cannot be adequately addressed when full informed consent is required. In many cases incomplete disclosure or deception is necessary to obtain essential information. This presents a "Catch 22" in the informed consent process. The first solution should be to attempt to design a study which can answer the research question without any form of deception. The IRB will expect an explanation as to the necessity of deception in any project. When it is not possible to answer the research question without deception, the IRB will assess the risks to participants and make a decision as to what is necessary to protect them. With any research utilizing deception, a thorough debriefing procedure is necessary. The debriefing allows the investigator to explain tactfully what happened and why deception was necessary. At times deception may generate ill feelings among research subjects. It is the responsibility of the investigator to address the ill will and attempt to restore subjects to the pre-testing state of feeling and mind that was disrupted by deceptive methodology. (For a more complete discussion of deception in research, refer to Deception," in this manual.)
Placebo, Randomizing, and Blind Clinical Trials
A related issue is that of placebo, randomized, and blind clinical trials. When these types of designs are utilized it is impossible to inform the participants concerning which treatment they will receive. The informed consent document should define single and double blind procedures in a way participants can understand. They should be informed of all the possibilities which may occur if they agree to participate.
Language Used in Consent Forms
Many special circumstances can arise when developing an adequate informed consent procedure. One of the most important factors to consider is the language of the document. While investigators have complete control over the language contained in the document, they have limited control over the prospective participants' comprehension levels. It is crucial that investigators consider the possible variation in comprehension levels of subjects in their sample and write informed consent documents that reflect the subjects' reading abilities. While this is a difficult task to accomplish, there are several rules of thumb to follow:
Many consent forms contain extensive amounts of technical information and are written at a college/graduate level. Reducing the reading level and complexity of the document does not guarantee comprehension, but it does provide a better opportunity for participants to understand their involvement in the research project.
Although the IRB has a standard consent form format, there are situations when this format may be counterproductive for a given group of subjects. Researchers are encouraged to contact the IRB if they believe an alternate format would be more appropriate. (See Appendix F for sample consent forms.)
By its very nature, deception in research violates the principles of voluntary and informed consent to participate in research. Therefore, deception is an extraordinary measure that is not normally permitted in research. In all cases proposed research involving deception must meet the following criteria:
(Also, see the discussion of deception in INFORMED CONSENT)
Continuing monitoring and observation of research is the responsibility of both the researcher and the IRB. Monitoring of the research by the researcher is important because preliminary data may signal the need to (a) change the research design, (b) change the information presented to the subjects, or even (c) terminate the project before the scheduled date. Concurrent monitoring by the IRB helps ensure the protection of subjects and continued compliance with federal regulations. IRB monitoring is related to the degree of risk posed by the research and the history of compliance demonstrated by researchers. When risk to subjects is minimal, the IRB usually will ask for an annual progress report for a given study. However, when risks are more than minimal or when researchers have a history of serious noncompliance with IRB guidelines, the IRB may ask for detailed progress reports at intervals specified by the IRB. The IRB has the authority to observe all research procedures first hand or to assign monitoring of research to another individual or group of individuals (45 CFR 46.109).
Protocols approved under the Expedited or Full review procedure require a continuing review. The IRB establishes the intervals of review at the time of approval. The intervals between reviews are commensurate with the level of risk involved to participants. However, continuing review must occur at a minimum of every 12 months from the original approval date.
OPRR mandates that all continuing reviews must be substantive and meaningful." Continuing reviews will include the following:
In addition to IRB initiated reviews, investigators are required to submit any changes to the original protocol for IRB approval prior to enacting these changes. Again, it is important to consider the IRB approval as a process rather than an isolated event.
Frequently, faculty and graduate students conduct their research at sites other than the Oxford, DeSoto, or Tupelo campuses of the University of Mississippi. As always, researchers have a primary responsibility to protect human subjects from undue research risks. In research away from the University campuses, researchers incur additional obligations including obtaining the permission of institutions to conduct the research in their locations and with subjects for whom they have some responsibility.
The University of Mississippi IRB requires that researchers provide documentation from the off-campus institution that the researcher has been given permission to conduct research at locations administered by the institution. The type of permission depends on the location and the nature of the research.
IRB approval: When the off-campus institution has an Institutional Review Board, the University of Mississippi IRB expects the researcher to provide an approval letter from the off-campus IRB stating its permission for research to be conducted at that location. Examples of institutions with IRBs include another comprehensive university, a teaching hospital, or a state mental health institution.
A letter of permission: When the off-campus institution does not have an IRB, the University of Mississippi IRB requires a letter of permission from an official of the institution, on institutional letterhead. Examples of institutions without IRBs include public and private elementary schools, small colleges, and health care clinics.
Under certain circumstances, additional paperwork is required when conducting human subject research. If you are using human blood, other fluids, or tissue in your research, you must, in addition to the IRB application, contact the Institutional Biosafety Committee(IBC), Dr. Mike Mossing, Chair, at 915-5339, email: mmossing@olemiss.edu, for review and approval of the research protocol. Final IRB approval is contingent upon IBC approval.
The Transmittal Sheet is the official University form for the documentation of the concurrence of University officials with plans and commitments contained in proposals for externally funded programs. One of its purposes is to document other institutional reviews that may be necessary because of the specific nature of the program, e.g., use of human subjects.
The second page of the Transmittal Sheet contains a check-off for use of human subjects and a space for IRB signature. If your IRB protocol has been approved, enter your protocol number in the space provided. If your IRB protocol has not yet been approved, or if you have not yet submitted a protocol, write "Pending" on the line.
It is important to check with the external agency to whom you are applying to find out if IRB approval is required at the time the proposal is submitted. PHS, for example, requires certification of IRB approval within 60 days after the application receipt date. (See the PHS 398 application kit for more information.) If not, you have a choice of submitting a protocol before or after a funding decision is made by the agency. Note that if you wait, you run the risk of either having to return the funds, or experiencing a delay in being allowed to spend funds, should the proposal be funded and the protocol not be approved by the IRB. However, preparing a protocol for a project which will not be funded may not be the best use of your time. Often, it is wise to consult with IRB staff before submitting a proposal to determine if there may be problems with IRB approval.
In cases where a grant is awarded for the purpose of developing and administering a questionnaire, IRB approval will be granted in two stages. A conditional approval will allow the Principal Investigator to precede only with the instrument development phase of the project. The IRB must review the completed instrument before full approval can be granted and human subject contact initiated. Please be aware that the IRB must be satisfied that the instrument meets IRB regulations or approval will be suspended. In this event, depending on the granting agency and the project, you may be responsible for returning all or part of the original award.
This discussion is taken directly from (OPRR 1993). Investigators, who are interested in research with the special classes of subjects discussed here, should refer to (OPRR) for more information or contact IRB staff.
Certain groups of persons are especially vulnerable research subjects. They include:
In general, when an IRB is considering research with especially vulnerable subjects, the IRB can approve research that is of minimal risk or will benefit subjects directly. If the research involves more than minimal risk and does not benefit the subject directly, the study may be subject to approval by the Secretary of Health and Human Services.
Children and minors are defined as persons who have not attained the legal age for consent to treatment or procedures involved in the research. In the State of Mississippi the age of consent is 18. When children or minors are research subjects, researchers must obtain both the permission of the parents (i.e., parental informed consent) and the assent of the child (i.e., the child's affirmative agreement to participate). Mere failure to object is not assent. The IRB has the authority to waive the requirement of assent. Special DHHS regulations applying to children may be found in 45 CFR 46, Subpart D.
Pregnancy encompasses the period of time from the confirmation of implantation until the expulsion or extraction of the fetus. A fetus is the product of conception from the time of conception until a determination is made, following expulsion or extraction, that it is viable. Viable as it pertains to the fetus means being able, after either spontaneous or induced delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heart beat and respiration. Nonviable refers to a fetus ex utero which is living but not viable. Dead fetus means a fetus ex utero that exhibits neither heart beat, spontaneous respiration, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord. In vitro fertilization means any fertilization of the human ova that occurs outside the body of a human female. Special DHHS regulations applying to pregnant women and fetuses may be found in 45 CFR 46, Subpart B. No research may be conducted with pregnant women or fetuses unless the following conditions have been met:
Prisoners are persons involuntarily confined or detained in a penal institution. The term encompasses individuals sentenced to such institutions under a criminal or civil statute, individuals detained in other facilities by virtue of statutes of commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing. Special DHHS regulations applying to prisoners may be found in 45 CFR 46, Subpart C. No research may be conducted with prisoners unless the following conditions have been met:
Persons with cognitive or emotional impairments are those persons having a psychiatric or developmental disorder that affects cognitive or emotional functions to the extent that the capacity for judgment and reason is significantly diminished. Other persons, including those under the influence of or dependent on alcohol or drugs, those affected by degenerative brain diseases, those who are terminally ill, and those who have severe physically disabling handicaps, may be compromised in their ability to make decisions in their best interests. Persons with cognitive or emotional impairments may not be able to give legally valid informed consent. However, researchers have a responsibility to persons with cognitive impairments (1) to inform subjects with impairments about the procedures, risks, and benefits of the research to the extent that the subject can understand, and (2) to obtain affirmative assent in so far as the subject is able to do so.
Selection of subjects is a particularly important issue as it relates to persons with cognitive or emotional impairments. Research involving persons whose autonomy is compromised by disability or restraints on personal freedom should bear some direct relationship to their condition or circumstances. Persons who are institutionalized should not be chosen as subjects simply because is convenient to the researcher. Nevertheless, persons do not become incompetent the moment they enter a mental institution, and their right and considered judgment to participate in research should be respected.
Economically or educationally disadvantaged persons are those persons placed at special risk by socioeconomic and educational background. Economically disadvantaged persons include those persons who struggle to provide basic necessities for themselves and their families or communities. Therefore, the use of financial incentives for research participation is a special issue with economically disadvantaged persons. Medical care, remedial education, and financial remuneration are common incentives in research. To a person who is economically disadvantaged, seemingly nominal inducements may be powerfully coercive. Incentives cannot be so strong that they take away a person's voluntary choice to participate in research. Educationally disadvantaged persons may have educational deficits, learning disabilities, or cultural backgrounds that limit communication with a researcher. It is the responsibility of the researcher to ensure that a subject is fully informed. This includes presenting material at an appropriate level, in an appropriate language, and via an appropriate medium (e.g., verbal or visual).
Members of racial and ethnic minority groups are vulnerable research subjects in two respects: overrepresentation and underrepresentation. On the one hand, members of minority groups should not be over-included in research out of mere convenience or availability. No group of persons should be asked to bear the risks of research when many groups will share the benefits of that research. On the other hand, members of minority groups should not be excluded from research out of mere convenience or availability. For generalizability of research findings, investigators must include the widest possible range of population groups. Therefore, investigators must provide a "clear compelling rationale for their exclusion or under representation" of minority group members from research.
Elderly subjects are persons over the age of 65. Advancing age may place them at increased physical, cognitive, or financial risks. However, there is no specific age at which persons become high risk subjects and thereby ineligible for research. Researchers have the responsibility to determine the level of risk that research poses on an individual basis and to minimize risks accordingly. The use of age per se to define the ability to consent and therefore to participate in research is not valid , and the inclusion of older persons in the research enterprise is important. When older persons are cognitively impaired or institutionalized, the same protections apply to them that apply to persons with cognitive or emotional impairments and to children. They should not be used as subjects merely because they provide a convenient sample, but research involving elderly institutionalized persons should bear some direct relationship to their condition or circumstances. Furthermore, they should be informed and given the opportunity to assent to research, to the extent they are able, even if a guardian must provide informed consent for them to be subjects.
Persons who are in a subordinate relationship to researchers may experience a loss of autonomy because of that relationship. Students, employees, and patients may fear a loss of grades, work benefits, or maximal health care when they are asked to be research subjects. This means that they are subject to undue coercion, even if researchers do not intend to be coercive. Therefore, proposed research using any subjects who are in direct subordinate relationships to investigators is scrutinized by the IRB. The researcher is obligated to inform the subject clearly that the subject's participation is voluntary, that the subject may withdraw from participation at any time, and that grades, employment, or health care will not be affected by the subject's choice to participate or not to participate.
45 CFR 46, Code of Federal Regulations, Final Regulations for the Protection of Human Research Subjects (revised June 18, 1991, as the Federal Policy for the Protection of Human Subjects; Notices and Rules) (Appendix D)
The Belmont Report--Ethical Considerations and Principles for the Protection of Human Subjects of Research.
The Nuremberg Code. Reprinted in Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, vol. 12:81-82. Washington, DC: US Government Printing Office, 1949. Also printed in Medical Research Council of Canada, Ethics in Human Experimentation, pp. 59-60, 1978.
World Medical Organization. "Declaration of Helsinki".World Medical Journal (September 1974). Revised 1975.
Ethical Principles in the Conduct of Research with Human Participants, adopted by the American Psychological Association, 1973.
National Library of Medicine. Evolving Concern: Protection of Human Subjects. Produced for the U.S. National Institutes of Health and the U.S. Food and Drug Administration. Bethesda, MD: National Institutes of Health, Office for Protection from Research Risks, 1986. (Videotape)
National Library of Medicine. The Belmont Report: Basic Ethical Principles and the Application. Produced and written for the U.S. National Institutes of Health and the U.S. Food and Drug Administration by Michael D. Hamilton. Bethesda, MD: National Institutes of Health, Office for Protection from Research Risks, 1986. (Videotape)
National Library of Medicine. Balancing Society's Mandates: IRB Review Criteria. Produced for the U.S. National Institutes of Health and the U.S. Food and Drug Administration. Bethesda, MD: National Institutes of Health, Office for Protection from Research Risks, 1986. (Videotape)
All of the above are available in the IRB office in the Office of Research and Sponsored Programs during regular University hours; some may be borrowed on a short-term basis. Call 232-7482 for details.
The following references may also be helpful:
Books and Articles:
Annas, George; Glantz, Leonard; and Katz, Barbara. Informed Consent to Human Experimentation: The Subject's Dilemma. Cambridge, MA: Ballinger Publishing Company, 1977.
Appelbaum, Paul S., and Rosenbaum, Alan. "Tarasoff and the Researcher: Does the Duty to Protect Apply in the Research Setting" American Psychologist 44 (No. 6, June 1989): 885-894.
Beauchamp, Tom L.; Faden, Ruth R.; Wallace, R. Jay, Jr.; and Walters, LeRoy, eds. Ethical Issues in Social Science Research. Baltimore, MD: Johns Hopkins University Press, 1982.
Beauchamp, Tom L., and Childress, James F. Principles of Biomedical Ethics, 3d ed. New
York: Oxford University Press, 1989.
Beecher, Henry K. "Ethics and Clinical Research." New England Journal of Medicine 274 (1966):1354-1360.
Beecher, Henry K. Research and the Individual: Human Studies. Boston: Little, Brown and Company, 1970.
Benson, P.R. "The Social Control of Human Biomedical Research: An Overview and Review of the Literature." Social Science and Medicine 29 (No. 1, 1989): 1-12.
Berg, Kare, and Tranoy, Knut Erik, eds. Research Ethics. Progress in Clinical and Biological
Research, Vol. 128. New York: Alan R. Liss, 1983.
Bemard, Claude. An Introduction to the Study of Experimental Medicine, translated by N.C.
Greene. New York: The Macmillan Company, 1927.
Capron, A.M. "Human Experimentation." In Medical Ethics, edited by Robert M. Veatch, pp.
125-172. Boston: Jones and Bartlett, 1989.
Cohen, Carl. "Moral Issues in Medical Experimentation on Humans." Philosophic Exchange 2
(No. 5, Summer 1979): 37-5 1.
Davidson, Richard A. "Source of Funding and Outcome of Clinical Trials." Journal of General Internal Medicine I (No. 3, May-June 1986): 155-158.
Faden, Ruth R. and Beauchamp, Tom L. A History and Theory of Informed Consent. New York: Oxford University Press, 1986.
Freund, Paul A., ed. Experimentation With Human Subjects. New York: George Braziller, 1970.
Greenwald, Robert A.; Ryan, Mary Kay; and Mulvihill, James E., eds. Human Subjects Research: A Handbook for Institutional Review Boards. New York and London: Plenum Press, 1982.
Grunder, T.M. (1980). "On the readability of surgical consent forms." New England Journal of Medicine, 302, 900-902.
Healy, Bernadine, et al. "Conflict-of-Interest Guidelines for a Multicenter Clinical Trial of Treatment after Coronary-Artery Bypass-Graft Surgery." New England Journal of Medicine 320 (No. 14, April 6, 1989): 949-951.
Herman, Samuel S. "A Noninstitutional Review Board Comes of Age." IRB 11 (No. 2, March/April 1989): 1-6.
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JOURNALS
Clinical Research
Evaluation Research
Hastings Center Report
IRB: A Review of Human Subjects Research
Journal of Philosophy and Medicine
Journal of the American Medical Association
Kennedy Institute of Ethics Journal
Law, Medicine and Health Care
New England Journal of Medicine
REPORTS AND RECOMMENDATIONS OF THE NATIONAL COMMISSION
U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Reports and Recommendations:
The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-0012. Reprinted in Federal Register 44 (April 18, 1979): 23192.
Appendix (Volumes I and II) to The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-0013 and (OS) 78-0014.
Proceedings of March 14-15, 1975 Meeting.
Report and Recommendations: Ethical Guidelines for the Delivery of Health Services by DHEW. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-0010.
Appendix to Report and Recommendations: Ethical Guidelines for the Delivery of Health Services by DHEW. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-001 1.
Report and Recommendations: Institutional Review Boards. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-0008.
Appendix to Report and Recommendations: Institutional Review Boards. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 780009.
Report and Recommendations: Psychosurgery. Washington, D.C.: U.S. Government
Printing Office, 1977. DHEW Publication No. (OS) 77-0001.
Appendix to Report and Recommendations: Psychosurgery. Washington, D.C.: U.S.
Government Printing Office, 1977. DHEW Publication No. (OS) 77-0002.
Report and Recommendations: Research Involving Children. Washington, D.C.: U.S.
Government Printing Office, 1977. DHEW Publication No. (OS) 77-0004.
Appendix to Report and Recommendations: Research Involving Children. Washington, D.C.: U.S. Government Printing Office, 1977. DHEW Publication No. (OS) 770005.
Report and Recommendations: Research Involving Prisoners. Washington, D.C.: U.S.
Government Printing Office, 1976. DHEW Publication No. (OS) 76-131.
Appendix to Report and Recommendations: Research Involving Prisoners. Washington,
D.C.: U.S. Government Printing Office, 1976. DHEW Publication No. (OS) 76-132.
Report and Recommendations: Research Involving Those Institutionalized As Mentally Infirm. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-0006.
Appendix to Report and Recommendations: Research Involving Those Institutionalized As Mentally Infirm. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-0007.
Report and Recommendations: Research on the Fetus. Washington, D.C.: U.S. Government Printing Office, 1975. DHEW Publication No. (OS) 76-127.
Appendix: Research on the Fetus. Washington, D.C.: U.S. Government Printing Office, 1976. DHEW Publication No. (OS) 76-128.
Report and Recommendations: Special Study: Implications of Advances in Biomedical and Behavioral Research. Washington, D.C.: U.S. Government Printing Office, 1978. DHEW Publication No. (OS) 78-0015.
REPORTS OF THE PRESIDENT'S COMMISSION
U.S. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research:
Compensating for Research Injuries: The Ethical and Legal Implications for Programs to Redress Injured Subjects. Washington, D.C.: U.S. Government Printing Office, 1982. G.P.O. Stock Number 040-000-00455-6.
Deciding to Forego Life-Sustaining Treatment: A Report on the Ethical, Medical, and Legal Issues in Treatment Decisions. Washington, D.C.: U.S. Government Printing Office, 1983.
Defining Death: A Report on the Medical, Legal and Ethical Issues in the Determination of Death. Washington, D.C.: U.S. Government Printing Office, 1981.
Implementing Human Research Regulations: Second Biennial Report on the Adequacy and Uniformity of Federal Rules and Policies, and of their Implementation, for the Protection of Human Subjects. Washington, D.C.: U.S. Government Printing Office, 1983.
Making Health Care Decisions: A Report on the Ethical and Legal Implications of Informed Consent in the Patient-Practitioner Relationship. Volume One: Report. Washington, D.C.: U.S. Government Printing Office, 1982.
Making Health Care Decisions: A Report on the Ethical and Legal Implications of In-Informed Consent in the Patient-Practitioner Relationship. Volume Two: Appendices, Empirical Studies of Informed Consent. Washington, D.C.: U.S. Government Printing Office, 1982.
Making Health Care Decisions: A Report on the Ethical and Legal Implications of Informed Consent in the Patient-Practitioner Relationship. Volume Three: Appendices Studies on the Foundations of Informed Consent. Washington, D.C.: U.S. Government Printing Office, 1982.
Protecting Human Subjects: The Adequacy and Uniformity of Federal Rules and their Implementation. Washington, D.C.: U.S. Government Printing Office, 1981.
Screening and Counseling for Genetic Conditions: The Ethical, Social, and Legal Implications of Genetic Screening, Counseling, and Education Programs. Washington, D.C.: U.S. Government Printing Office, 1983.
Securing Access to Health Care: A Report on the Ethical Implications of Differences in the Availability of Health Services. Volume One: Report. Washington, D.C.: U.S. Government Printing Office, 1983.
Securing Access to Health Care: The Ethical Implications of Differences in the Availability of Health Services. Volume Two: Appendices, Sociocultural and Philosophical Studies. Washington, D.C.: U.S. Government Printing Office, 1983.
Securing Access to Health Care: The Ethical Implications of Differences in the Availability of Health, Services. Volume Three: Appendices, Empirical, Legal, and Conceptual Studies. Washington, D.C.: U.S. Government Printing Office, 1983.
Splicing Life: A Report on the Social and Ethical Issues of Genetic Engineering with Human Beings. Washington, D.C.: U.S. Government Printing Office, 1982.
Summing Up: Final Report on Studies of the Ethical and Legal Problems in Medicine and Biomedical And Behavioral Research. Washington, D.C.: U.S. Government Printing Office, 1983.
Whistleblowing in Biomedical Research: Policies and Procedures for Responding to Reports of Misconduct. Proceedings of a Workshop September 21-22, 1981. Edited by Judith P. Swazey and Stephen R. Scher. Washington, D.C.: U.S. Government Printing Office, 1981.