Employees of LLU and its Affiliates
Terminally Ill Patients
Pregnant Women (or Women or Childbearing Potential)
Research involving children should only be conducted when it is not contrary to the best interests of the child, where consent has been obtained by the child's parents, guardians, or others as required by law. Where appropriate, assent should also be obtained from the child. Social or peer pressure to participate should be minimized . Punishment or other negative actions should not follow a child’s refusal to participate in a research study. Further, all clinical investigators must be familiar with State laws requiring reports of suspected child abuse or neglect.
If the research poses more than minimal risk and no direct benefit to the child, the investigator is required to obtain permission from both parents or the child’s guardian in order for the child to participate in the research. If the research poses more than minimal risk but may directly benefit the child, only one of the child’s parents or guardian need give permission. The investigator is not required to gain permission from both parents, if one of the parents is not reasonably available, deceased, unknown, legally incompetent, or from a parent who does not have legal responsibility for the care and custody of the child . This caveat does not exempt the investigator from obtaining the permission from at least one parent who has legal responsibility for the child. For additional information, please refer to 45 CFR 46 Subpart D.
Employees, such as office staff, lab technicians, and post-doctoral fellows, are similar to students in that they are vulnerable to perceived, even if not intended, pressures to appear cooperative and supportive of their supervisor’s work. Accordingly, many of the same procedures employed to reduce the likelihood of coercion in recruiting student volunteers apply equally to employees. The IRB will not approve recruitment procedures that include employees from the investigator’s own lab or office as research subjects.
Students traditionally have served as subjects for biomedical research and behavioral research. The obvious concern is that their participation may not be truly voluntary because of a desire to appear particularly cooperative or highly motivated, or because participation in research is a course requirement. The IRB suggests several procedures to reduce the possibility of unintended coercion, while still permitting students to participate as subjects in research. These include:
- Design study advertisements so that they recruit subjects from a broad base of students;
- Avoid personal solicitations of students by faculty, graduate assistants, or fellow students;
- Provide a number of research projects from which to chose, if participating as a subject in research can be used as a course requirement;
- Provide alternative and equal methods for meeting course credit (or extra credit) requirements, such as attending a series of research presentations by faculty, writing a brief paper, conducting one’s own research.
Also see Tools for Students and Faculty Mentors.
Federal regulations require the equitable selection of minorities as research subjects (45 CFR 46.111.(a)(3)). The inclusion of minorities in research is important both to ensure that they are eligible for an equal share of the benefits of research, and to ensure that they do not bear a disproportionate burden. Sometimes minorities are subject to different clinical conditions compared to other populations. For example, sickle cell anemia and Tay Sachs disease only affect a few minority groups. Other research focuses on characteristics of diseases or effectiveness of therapies in particular populations (e.g., HIV transmission, treatment for hypertension), and may also concern conditions or disorders that disproportionately affect a certain racial or ethnic group. Exclusion or inappropriate representation of these groups, by design or inadvertence is unjust. Considering that participation in research could potentially offer direct benefits to the subjects (e.g. HIV/AIDS research), under-representation of minorities denies them, in a systematic fashion, the opportunity for direct benefit.
Prisoners are considered vulnerable because they are in a restrictive, institutional environment that affords little opportunity for voluntary choices, earning wages, interaction with the community, and obtaining medical care. Studies have shown that prisoners often volunteer for medical research as a means of access to a competent medical examination, because health care may be woefully inadequate in prison.
Because a prisoner’s autonomy is limited, they may participate only in certain categories of research, and special precautions are needed to assure that their consent to participate in the research is both knowing and voluntary [45 CFR 46.302].
The IRB will only allow research studies involving prisoners when the research involves the following methods and goals:
- Studies of the possible causes, effects, and process of incarceration and criminal behavior, if these studies present no more than minimal risk or inconvenience to the subjects;
- Studies of prisons as institutions, or of prisoners as incarcerated persons, if those studies present no more than minimal risk or inconvenience to the subjects;
- Research on conditions affecting prisoners as a class (e.g., research on hepatitis, drug addiction, sexual assaults, and other conditions more prevalent in a prison population than elsewhere), but only after the Secretary of Health and Human Services has consulted with experts in medicine, ethics, and penology and published a notice approving the proposed research in the Federal Register; and
- Research on practices that are intended, and reasonably likely, to enhance the well-being of the subjects. However, if some of the prisoners will be assigned to control groups which will not benefit from the research, then the study must first be approved by the Secretary of Health and Human Services, after consultation with appropriate experts, as described above.
Additionally, the IRB will review each submitted protocol to verify that:
- Any advantages that prisoners will realize as a result of participating in the research, when compared to the general living conditions within the prison, are not so great as to impair prisoners’ ability to weigh the risks and benefits of participation and freely choose whether or not to participate;
- The risks involved in the research are commensurate with risks that would be accepted by non-prisoner volunteers (usually demonstrated by enrolling non-prisoner subjects from the community, as well);
- Procedures for selecting subjects within the prison are fair, and free from arbitrary manipulation by prison authorities or prisoners;
- Control subjects will be selected randomly from among the group of eligible volunteers, unless the principal investigator justifies a different procedure;
- The information presented during recruitment and consent procedures is in a language, and level of complexity, understandable to the subject population;
- The IRB must be assured that the parole board will not take research participation into account in making decisions about parole, and each prisoner is informed in advance that participation will have no effect on the possibility of parole;
- If medical follow-up is necessary to protect the health and welfare of the subjects, adequate provision is made for such care, taking into account the varying length of prisoners’ sentences.
- The IRB that reviews research involving prisoners is required to have at least one member who is either a prisoner, or a prisoner representative. The majority of the IRB members cannot be in any way associated with the prison(s) involved.
Epidemiological research involves the collection of data relating to the health of populations. It may require the use of identified, coded or de-identified data. The University Research Affairs Committee (URAC) has designated a subcommittee for reviewing and approving research among Seventh-day Adventists. This approval is necessary to protect the members of the cohorts of Seventh-day Adventists (some of whom have been followed for over thirty years by LLU investigators) from excessive utilization and potential confusion. Prior to submission to the IRB, investigators wishing to pursue such research must contact the Office of Sponsored Research to arrange review by the URAC subcommittee.
Terminal patients (generally recognized as those with six months or less to live) are a vulnerable research population. Out of desperation, these patients may be willing to "try anything" that might offer hope of either a cure or a slowing of the disease process. Others, aware that nothing further can be done to cure their disease, might fear abandonment by the medical establishment or their family, and agree to participate in research as a means of maintaining contact with physicians expert in treating their condition or to prevent alienation from their relatives. Knowing this, the classification as “terminally ill” should not necessarily be an exclusion criterion for participating in research. Many terminally ill individuals are willing to submit to considerable discomfort and risk for the possible benefit of future patients suffering from the same condition, and will volunteer for research about their particular condition in hopes of helping other, similarly situated patients in the future.
Investigators should be sensitive to these matters and remind potential research subjects that in general, they will likely not experience any personal medical benefit from their participation in a particular study, rather the benefit is anticipated for future patients as data is generated and analyzed. This is especially important because in some research studies, the dosage subjects will be given is not expected to produce a therapeutic result. At the same time, it is important not to automatically treat terminally ill patients as incompetent or incapable of autonomous decision-making. This needs to be assessed on an individual basis, with the help of a psychiatrist, if needed.
The primary aim of clinical trials is to provide scientific evidence leading to a change in health policy or a standard of care, therefore it is imperative to determine if the intervention or therapy being studied affects men and women differently. NIH has concluded that the inclusion of women in research is sufficiently important that the only justifiable reason to exclude non-pregnant women of child-bearing potential from research is compelling evidence that the proposed project would be inappropriate with respect to the health of the subject or the purpose of the research. A discussion of this determination can be found in their guideline: NIH Outreach Notebook of the Inclusion of Women and Minorities in Biomedical and Behavioral Research (1994).
Research on women with childbearing potential is regulated by the following Federal Codes: Federal Register, Vol. 58, No. 139, p 39411, Sections G and H, Thursday, July 22, 1993; Federal Register, Vol. 58, No. 139, p 39409, Section G, Thursday, July 22, 1993.
Prior to the initiation of a trial, investigators should discuss with the participants known or theoretical risks as a result of becoming pregnant during the trial period. The following is suggested language for use in informed consent documentation for a trial of a potentially toxic drug substance in women of childbearing potential:
"If you are a woman who is able to become pregnant, it is expected that you will use a medically accepted method of birth control [outline the recommended forms of birth control] to prevent exposing a fetus to a potentially dangerous agent with unknown risk. If you are pregnant or currently breast feeding, you may not participate in this drug study. If you are pregnant, if you become pregnant, or if you are breast-feeding during this study, you or your child may be exposed to an unknown risk. There are also known risks to you or your unborn baby, including [state specific risks].
"To confirm to the extent medically possible that you are not pregnant, you are required to agree [to have a pregnancy test done before beginning this research study] [to begin the study after the onset of your next menstrual period] [choose one]. You must agree to avoid sexual intercourse or use a birth control method judged to be effective by the investigator and which will not interfere with the proposed investigation. Pregnancy could still result despite the responsible use of a reliable method of birth control while participating in this research study. You agree to notify the investigator as soon as possible of any failure of your birth control method, or if you become pregnant, either of which may result in your being withdrawn from the study."
Per 45 CFR 46.208, no fetus in utero may be involved as a subject in any activity covered by this subpart unless: (1) the purpose of the activity is to meet the health needs of the particular fetus and the fetus will be placed at risk only to the minimum extent necessary to meet such needs, or (2) the risk to the fetus imposed by the research is minimal and the purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means. The research activity may be conducted only if the mother and father are legally competent and have given their informed consent [see full regulations for exceptions regarding the father's informed consent.]
Until it has been ascertained whether or not a fetus ex utero is viable, a fetus ex utero may not be involved as a subject in an activity covered by this subpart unless: (1) There will be no added risk to the fetus resulting from the activity, and the purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means, or (2) The purpose of the activity is to enhance the possibility of survival of the particular fetus to the point of viability.
No nonviable fetus may be involved as a subject in an activity covered by this subpart unless: (1) Vital functions of the fetus will not be artificially maintained, (2) Experimental activities which of themselves would terminate the heartbeat or respiration of the fetus will not be employed, and (3) The purpose of the activity is the development of important biomedical knowledge which cannot be obtained by other means. In the event the fetus ex utero is found to be viable, it may be included as a subject in the activity only to the extent permitted by and in accordance with the requirements of other subparts of this part. The research activity may be conducted only if the mother and father are legally competent and have given their informed consent [see full regulations for exceptions regarding the father's informed consent.]
Activities involving the dead fetus, macerated fetal material, or cells, tissue, or organs excised from a dead fetus shall be conducted only in accordance with any applicable State or local laws regarding such activities.