Protections for Vulnerable Populations
Vulnerable populations include individuals who may be vulnerable to coercion or undue influence to participate in research projects, or who may be at greater risk when participating in research. They may also include research populations, or be associated with populations, that are simply unable or have limited capacity to provide consent. Thus, federal regulations require additional protections for special participant populations, such as: (1) children, (2) prisoners, (3) pregnant women, (4) activities involving fetuses and human in vitro fertilization, (5) persons with cognitive impairment, (6) economically or educationally disadvantaged persons, and (7) other potentially vulnerable groups.
It is important to note that, in some cases, state and local laws will also be relevant in these considerations.
According to 45 CFR 46.303(c), a prisoner is defined as any individual involuntarily confined or detained in a penal institution. This term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing. It is important to note that this category of special protections also includes situations where a research participant may become a prisoner after the research has commenced.
Only certain types of research may be conducted utilizing prisoners as participants: (1) study of the possible causes, effects, and processes of incarceration, and of criminal behavior, provided that the study presents no more than minimal risk and no more than inconvenience to the participants; (2) study of prisons as institutional structures or of prisoners as incarcerated persons, provided that the study presents no more than minimal risk and no more than inconvenience to the participants; (3) research on conditions particularly affecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is much more prevalent in prisons than elsewhere, or research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults); and (4) research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well-being of the participant.
Coercion is the IRB’s main concern when reviewing studies involving prisoners. Many factors will be taken into account regarding this issue before a study may be approved. When prisoner research is reviewed by the IRB, IRB membership in attendance at that meeting will include a prisoner representative with appropriate background and experience to serve in that capacity.
(3) Pregnant Women
Research involving women who are or may become pregnant receives special attention from IRBs because of women’s additional health concerns during pregnancy and because of the need to avoid unnecessary risk to the fetus. Pregnancy is defined as the period from confirmation of implantation of a fertilized egg within the uterus until the fetus has entirely left the uterus (i.e., has been delivered). In studies involving pregnant women, IRBs must also determine when the informed consent of the father is necessary. Additionally, because of the involvement of the fetus (who cannot give consent), the IRB must consider the need to prevent harm or injury to future members of society. At the same time, IRBs must also recognize that the inclusion of women in research study populations is important so that research findings can be generalizable and of benefit to all persons at risk of a disease, disorder, or condition under study. Therefore, pregnant women may be involved in several kinds of research which present differing IRB duties for each kind of research.
The three basic types of research are:
- Studies in which pregnancy is coincidental to participant selection. Any study where women of childbearing potential are possible participants could inadvertently include pregnant women. Depending on the research procedures, these participants may need to be notified that a particular treatment or procedure "may involve risks to the participant (or to the embryo or fetus if the participant is or becomes pregnant) that are currently unforeseeable." Non-pregnant participants may need to be advised to avoid pregnancy or nursing while involved in or for a period of time following the research.
- Studies directed primarily toward the mother’s health. As women’s health can be positively or negatively affected by pregnancy, some research may be undertaken to explore these issues. As such, a woman’s needs generally take precedence over those of the fetus. The IRB will, however, attempt to ensure that the risks to the fetus are minimized.
- Studies directed toward pregnancy. Many studies are directed to examine the normal and abnormal processes of pregnancy, labor, and delivery. In these cases, the IRB must determine that the risk to the fetus is "minimal." "Minimal" is defined as where the risk to the fetus is no more than that from established procedures routinely used in an uncomplicated pregnancy or in a pregnancy with complications comparable to those being studied. If the IRB cannot conclude that the risk is minimal, it can consult with experts for advice. Basically, it must then be determined that the risks are far outweighed by the benefits to the participant and the importance of the knowledge to be gained.
A fetus is defined as the product of conception from the time of implantation until delivery. Once the fetus is delivered or expelled and is viable (likely to survive to the point of sustaining life independently, given the benefit of available medical therapy), it is designated as an infant and is thus subject to federal regulations governing research with children. The fetus should be treated respectfully and with dignity and its genetic heritage and vulnerability should be recognized, regardless of its life prospects. Because the fetus shares a unique relationship with its mother and cannot consent to be a research participant, special federal regulations are in place to guide fetal research.
In research, risks to the fetus may not be more than minimal, unless they are justified by the anticipated benefit for the health of the mother or the particular fetus. It can be problematic, however, to determine what exactly is minimal risk for a fetus as compared to a child or adult, and the IRB will work closely with investigators to make this determination. However, if risk to the fetus is more than minimal and without anticipated medical benefit to the mother or fetus, special provisions apply, and the IRB must determine that data gained from such a study is not obtainable in any other research design or format.
Basic types of research involving fetuses include:
- Research directed toward the fetus in utero. The IRB can approve this kind of research if the purpose of the research is to meet the health needs of the fetus and will be conducted in such a way to minimize risk or if the research presents no more than minimal risk to the fetus and the purpose of this activity is the development of new knowledge that is unobtainable by any other method. As always, risks should be justified by a consideration of potential benefits.
- Research involving the fetus ex utero. If the fetus is judged viable outside of the uterus, then it is considered an infant and is thus governed by research regulations involving children. If a fetus is nonviable (unable to survive to the point of sustaining life independently), then research is forbidden.
- Research with dead fetuses, fetal material, and placenta. Research with dead fetuses, fetal material, or cells, tissues, or organs removed from a dead fetus are governed by state laws and regulations. Ethical considerations commonly held about respect for the dead should be observed if proposing such research.
(5) Persons with Cognitive Impairment
A cognitively impaired person is defined as having either a psychiatric disorder (e.g., psychosis, neurosis, personality or behavior disorders), an organic impairment (e.g., dementia), or a developmental disorder (e.g., mental retardation) that affects cognitive or emotional functions to the extent that capacity for judgment and reasoning is significantly diminished. In addition, persons under the influence of or dependent on drugs or alcohol, persons suffering from degenerative diseases affecting the brain, terminally ill patients, and persons with severely disabling physical handicaps, may also be compromised in their ability to make decisions in their best interests.
Thus, the major ethical concern in research involving individuals with psychiatric, cognitive, or developmental disorders, or those who are substance abusers, is that their disorders may affect their capacity to understand the information presented and their ability to make a reasoned decision about participation. Also, many individuals with such disabilities may be residents of institutions responsible for their total care and treatment and this factor may have an impact on or further compromise these individuals’ ability to exercise free choice (voluntariness) in participating in research. (For example, these individuals may agree too readily to requests for their "cooperation" or may be vulnerable to perceived or actual pressures for fear of being denied services.) It is for these reasons that special protections must be considered by the IRB when reviewing research involving cognitively impaired persons. The IRB's questions may include:
Do such individuals comprise the only appropriate participant population? In other words, do the research questions focus on issues unrelated to their disorders or institutionalization?
Are there sufficient protections for privacy and confidentiality of information gathered?
How are issues of consent and competence addressed?
As a general rule, there should be specific evidence of individuals’ incapacity to understand and to make a choice before they are deemed unable to consent. If cognitive impairment cannot be judged a priori, then mental status testing should be included in the research design. If a person is capable of understanding the nature of the project, consent should be obtained from both the participant and a parent, guardian, or advocate as appropriate. In instances where the person is not competent to consent, parental or guardian consent alone is sufficient. When individuals are deemed unable to consent, investigators and IRBs must consider state and local laws governing the selection of an appropriate representative to consent on behalf of these individuals. The IRB will consider the possibility of obtaining "assent" (see the discussion on involving children in research) from potential research participants when they are cognitively impaired.
(6) Economically or Educationally Disadvantaged Persons - see Compensation of Participants
(7) Other Potentially Vulnerable Groups
It is the investigator's responsibility to be alert to any other potential vulnerabilities that may affect the ability of their proposed study population to give voluntary informed consent, and to bring those vulnerabilities to the IRB's attention during the review process.