Vulnerable & Protected Populations

This Module will discuss research with vulnerable and protected populations. We will begin by discussing the issues that all IRBs must consider when reviewing research with vulnerable populations. The Department of Health and Human Services (DHHS) and Food and Drug Administration (FDA) guidelines related to vulnerability will be reviewed. Populations given extra protection in the Code of Federal Regulations will be presented. Traits that may make individuals vulnerable will be discussed. Other groups of individuals who may be vulnerable will be discussed: the cognitively impaired, individuals with disabilities, individuals with mental illness, individuals with substance abuse issues, individuals who are culturally vulnerable, and workers and employees. Finally, we will discuss group harm. The module will conclude with a brief quiz.

Objectives:

  • Define vulnerable and protected populations
  • Understand ethical issues related to vulnerable and protected populations
  • Review DHHS and FDA guidelines related to vulnerability and protected populations
  • Identify traits that can make individuals vulnerable and protected populations.
  • Understand cultural vulnerability and group harm

Vulnerable and Protected Populations

Introduction

(VIDEO ref 87)

This Module will discuss research with vulnerable and protected populations. We will begin by discussing the issues that all IRBs must consider when reviewing research with vulnerable populations. The Department of Health and Human Services (DHHS) and Food and Drug Administration (FDA) guidelines related to vulnerability will be reviewed. Populations given extra protection in the Code of Federal Regulations will be presented. Traits that may make individuals vulnerable will be discussed. Other groups of individuals who may be vulnerable will be discussed: the cognitively impaired, individuals with disabilities, individuals with mental illness, individuals with substance abuse issues, individuals who are culturally vulnerable, and workers and employees. Finally, we will discuss group harm.

Issues Concerning Vulnerable Populations

There are several issues that are common to all vulnerable populations that IRBs must consider when evaluating proposed research. These include consent, level of risk, coercion, and the reason for choosing this particular subject population. The IRB Handbook, Chapter 3 points out that among vulnerable populations . . . “[e]asy availability, compromised position, and susceptibility to manipulation often overlap (ref 53).” This is why IRBs need to carefully consider all research where the potential for vulnerability exists.

First the IRB will examine whether or not the particular population is able to give consent to participate in research. This requires a certain cognitive ability to understand what will happen in the research, what risks may be involved, and that participation is voluntary.

Second, the IRB will look at the level of risk involved in the study and weigh it against the level of reward that will result from the study. Minimal risk studies are more easily approved. If the risk level is above minimal risk, then there must be definite benefits to the study. The IRB will also consider whether or not individual subjects will benefit from the study, or if the study will benefit the group to which study subjects belong. Individual benefits are given greater weight than group benefits.

Third, the possibility of coercion will be examined. Some vulnerable subjects may be easily coerced because they might feel that they must participate in research in order to continue to be taken care of or because a person of authority tells them to participate.

Finally, the researcher’s reason for choosing the particular group of study subjects will be considered. Generally, it is not enough simply for vulnerable subjects to be easily available for research, the research must pertain to the group of study subjects. The IRB will look specifically at the Belmont Principle of Justice when considering the population under study and bearing in mind that protected populations also should not be left out of research simply because they are protected and extra protections may be required to include them in research. “Whenever possible, research should be designed to encourage the participation of all groups while protecting their rights and welfare. To accomplish this, we recommend that rather than focusing primarily on categorizing groups as vulnerable, investigators and IRBs should also recognize and avoid situations that create susceptibility to harm and coercion.” (ref 54)

Classes of Vulnerable Populations

Subject populations given extra protection in the Code of Federal Regulations (45 CFR 46) include: pregnant women, human fetuses and neonates (45 CFR 46, Subpart B), prisoners (Subpart C), and children (Subpart D). There has also been specific guidance given for individuals involved in AIDS/HIV research. But the Code of Federal Regulations does not present us with an exhaustive list of vulnerable populations, but rather vulnerability is based upon: ability to consent, risk and reward in the study, potential for coercion, and choice of subjects. (ref 55)

Traits of Vulnerability

DuBois (ref 56) discusses six traits identified by the National Bioethics Advisory Committee that may make an individual vulnerable: cognitive or communicative vulnerability, institutional vulnerability, deferential vulnerability, medical vulnerability, economic vulnerability, and social vulnerability. In many instances, one individual may possess more than one trait of vulnerability.

Cognitive or communicative vulnerability encompasses several different types of individuals. This group encompasses those who do not have the cognitive capacity to understand all or part of the research. They may lack the ability to understand what consent means or what they are consenting to. Communicative vulnerability encompasses those who are presented a consent form in a language they cannot read or presented with explanations in a language they do not understand. Individuals may also be cognitively or communicatively vulnerable if they are given a consent form when they are in crisis. (ref 56)

Institutional vulnerability pertains to individuals who are under at least partial control of an institution, like students or prisoners. These individuals may be more likely to consent because they may (correctly or incorrectly) believe that consenting will confer upon them some form of benefit, such as a better grade or privileges. A considerable amount of research is still conducted using convenient undergraduates as the sample. (ref 56)

Deferential vulnerability refers to individuals who are informally subordinate to another person. In some cultures, women may defer to their husbands wishes for them to participate. In this case it is not so much that the individual subject is making a decision to participate but the person to whom they are subordinate is making it for them. (ref 56)

Medical vulnerability pertains to individuals who have serious health conditions for which there is no satisfactory treatment. These individuals may be more likely to consent to research because there is no cure for their ailment and it offers them hope. Oftentimes, these individuals lack the capacity to determine what sort of experimental treatment could offer them a reasonable chance of increased lifespan or increased quality of life. (ref 56)

Economic vulnerability may happen when participation is sought from individuals who lack basic necessities like housing, healthcare, and money. If participation in the research is perceived to be offering them these basics of life then they cannot make informed decisions regarding participation. (ref 56)

Finally, social vulnerability pertains to those research subjects who may be seen as less respected or “less-than” because of social position. If researchers see the participants as less valuable members of society, then they may subject them to more risk. (ref 56)

Choosing to Conduct Research with a Vulnerable Population

For any IRB reviewing a study that proposes using a vulnerable population serious consideration must be given as to why that population has been chosen. In some circumstances, a vulnerable population is chosen because there is a social condition or circumstance that occurs only with that population that must be investigated—for example, to investigate the impact of long-term confinement in a correctional facility, the subjects need to be prisoners. Aldridge (2012), however, points out that vulnerable populations should be included in research so that they may have a voice in research—and not just that research which is about their particular set of circumstances. By seeking to protect potential subjects, researchers may be choosing to exclude members of vulnerable populations, which, in turn, robs them of their ability to be active partners in the research discourse. This, of course, relates directly back to The Belmont Report and the principle of justice. We cannot exclude individuals who might benefit from research simply because of their vulnerability.

Research with Prisoners

(VIDEO ref 77)

It may be difficult for some people to see prisoners as a “vulnerable” population—especially in light of the wrongs that these individuals may have committed. In fact, many of the past abuses in human subjects’ research have been committed against prisoners. (Go To Ethical Human Subject Research, History and Principles Course) The vulnerability of prisoners is linked to their position in society and their position within an institution. Prisoners do not have their freedom, they are often confined and frequently what they do is proscribed. Because of this their ability to make a voluntary decision free from coercion is questionable.

The Code of Federal Regulations defines a prisoner as “any individual involuntarily confined or detained in a penal institution. The 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.” (ref 57)

Categories of Research Permitted

Research is permitted with prisoners, but in order to approve research using prisoners as subjects, the IRB must perform additional duties. First, research with prisoners can only be approved if it represents no more than minimal risk and minimal inconvenience to the subjects. Second, the study must examine the possible causes, effects, and processes of incarceration, and of criminal behavior. Research may investigate conditions affecting prisoners as a class. Research may also be conducted on practices which have the intent and probability of improving the health or well-being of the subjects. Finally, in general, biomedical or behavioral research may not involve prisoners as subjects unless that research also falls under the second condition just mentioned. (CFR 45, 46.306) (ref 57)

When IRBs review studies involving prisoners, they will look closely at incentives to ensure the amount or type of incentive does not constitute coercion. The level of risk appropriate for prisoner-subjects can be no greater than the risks that are acceptable for non-prisoner-subjects. Selection procedures must be fair and not subjected to arbitrary intervention from prison authorities or prisoners. The language used in the study must be understandable to the subjects, keeping in mind that prisoners, on average, have a lower reading level than the general population. Prisoner-subjects must know that their participation will not impact parole board decisions in any way. If participation in the research will require any sort of follow up care, the researcher must make sure that such care is provided. (CFR 45, 46.305) (ref 57)

Any IRB that reviews prisoner research must have at least one board member who is a prisoner or prisoner representative. Also, a majority of the IRB members (except for those that are prisoner members) must have no association with the prison involved in the study. (CFR 45, 46.304) (ref 57)

Research with Children

Research with children requires extra protections. These protections are outlined in (CFR 45 part 46, subpart D) and will be discussed more extensively in the Research with Children Module. (Go To Research with Children Course) (ref 27)

Research with children is permitted, but it must be reviewed with extra caution by the IRB because of the inherent vulnerability of the potential child-subject. Children are more vulnerable than the average adult because many children, especially younger children have a diminished capacity to understand what is being done in a research study when compared to the average adult. Children are also more likely to be vulnerable to a variety of types of coercion. They may feel they have to participate in a research study because the researcher is seen as a person in authority. If an incentive is offered to participate, even a small monetary incentive may be coercive to a child who has little money of his or her own.

The following types of research with children may be permitted by IRBs, if the research is ethically sound, the risks and benefits are appropriately balanced, and if assent of the child and permission of the parents has been obtained:

Research that involves no more than minimal risk.

Research involving greater than minimal risk to the child subject but presenting the possibility of direct benefit to the individual subjects.

Research involving greater than minimal risk, without possibility of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject’s disorder or condition.

Research which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children. (ref 27)

Pregnant Women and Neonates

Research with pregnant women and neonates is permissible but only when very specific conditions are met. The Code of Federal Regulations offers the following definition of pregnancy: “Pregnancy encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.” (CFR 45, 46.102 (f)) (ref 58)

Research with pregnant women can only be permitted when appropriate preclinical studies have been conducted to assess potential risks; the risk to the fetus is caused solely by interventions that have the potential of direct benefit for the woman or fetus or the risk to the fetus in minimal and the knowledge from the study cannot be obtained by other means. The risk is as low as possible considering the aims of the study. If the research only involves benefit to the fetus then consent must be obtained from the mother and in some cases also the father. When consent is provided, the individual giving consent must be fully informed regarding the possible impact of the research on the fetus. Inducements cannot be made to terminate a pregnancy. None of the individuals involved in the research can have any part in any decisions about terminating the pregnancy nor may they have any part in determining the viability of the fetus. (CFR 46.204) (ref 58)

If the research holds direct benefit to the woman or to the woman and fetus or there is no direct benefit to the woman and fetus but the risk is minimal and the development of important biomedical knowledge cannot be obtained by other means. The woman’s consent must be obtained in the normal fashion. (CFR 46.204 (d)) (ref 58)

Research involving neonates of uncertain viability and non viable neonates may take place if the following conditions are met: Preclinical and clinical studies have been conducted to determine potential risks. All individuals providing consent must be fully informed about the impact of the research on the neonate. No individual engaged in the research can have part in determining the viability of a neonate. (CFR 46.205) (ref 58)

Neonates of uncertain viability can only be involved in research if the research might increase chances of viability or the research will create important biomedical knowledge that cannot be obtained in any other way. Legally informed consent must be obtained from one or both of the parents or an appropriate legal representative. (CFR 46.205) (ref 58)

Cognitively impaired

Individuals who are cognitively impaired are may be vulnerable due to a lack of ability to understand and give consent; these individuals may also be vulnerable due to institutionalization which also makes them more susceptible to coercion. Research can use cognitively impaired subjects but only under particular circumstances.

The Institutional Review Board Guidebook, Chapter 6 defines cognitively impaired 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. Others, including persons under the influence of or dependent on drugs or alcohol, those 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.” (ref 59)

There is a long history of exploiting institutionalized individuals for research, so their availability for research alone is not enough for an IRB to permit their participation in a research study. Any research study proposing cognitively impaired individuals as subjects should be of minimal risk, should have a direct benefit to the participants or at least to the class of individuals they represent, should study situations or conditions that these individuals as a class are prone to have or be involved in.

Individuals with Disabilities

Individuals with disabilities are not excluded from research; however, the IRB needs to review all studies that propose using subjects with disabilities for issues of vulnerability. It should not be assumed that all individuals with disabilities are vulnerable, but rather research with individuals with certain types of disabilities may require special considerations. For example, if the subjects are hearing impaired, they may need to read all instructions and/or require an interpreter, depending on the type of research. Likewise, if the subjects are visually impaired, instructions may need to be read to them or provided for them in Braille. It should not be assumed that a disability interferes with an individual’s ability to give consent to research; whether or not the disability will impact the ability to consent must be considered based upon the particular disability. Plans will need to be in place to check for understanding in a way that is meaningful to participants.

Any IRB that is reviewing research that proposes involving a disabled population will consider why these individuals been chosen as potential subjects. Choosing a disabled population for a research study because they are readily available or unlikely to refuse is generally not a sufficient reason for approval.

Individuals with Mental Illness

Individuals with mental illness are not excluded from research, like individuals with disabilities, how vulnerable an individual is depends upon the individual’s diagnosis. Some mental illnesses have severe impairment of cognitive function which would interfere with those individuals’ ability to give consent; other mental illnesses may require hospitalization or institutionalization. The ability of an individual suffering from a mental illness to consent may also change over time. A depressed individual who has been on medication long-term and undergone appropriate psychotherapy may be perfectly able to give consent to participate in a research study, whereas a similar individual who is not taking medication, has not had psychotherapy and, in fact, is in the middle of a major depressive episode may not be able to provide informed consent.

Whether or not an IRB will allow research to take place that proposes using a mentally ill population will depend upon a variety of factors, not just related to the vulnerability of the individual subjects but also to whether or not the researcher has special training or background in working with the proposed population.

Other potentially vulnerable populations

Individuals with substance abuse issues are not excluded from research; however, their substance abuse may make them vulnerable. Individuals who are currently abusing substances have a definite impaired ability to give consent and may also be more likely to accept monetary inducements to participate in research. Individuals who have spent considerable time in recovery are much less vulnerable.

Certain medical diagnoses and conditions can also make individuals vulnerable. There are very specific guidelines for conducting research with individuals with AIDS or HIV, not only because of their illness, but because society has attached a stigma to their illness. IRBs will give special attention to how these individuals are recruited and to the protection of their data.

There are no specific guidelines for research with elderly and aged populations and the elderly are not considered to be vulnerable merely because they are elderly and they are not considered to be in need of special protections. It is recognized that the elderly are a very diverse group and their vulnerability is to be determined more by other circumstances, whether they are cognitively impaired or institutionalized. If they belong to either of these groups, then they are entitled to the same protections as any other member of those groups. (ref 59)

Workers and Employees

Workers and employees are considered vulnerable because of the potential for coercion that exists among this population. If an individual is asked to be part of a study by a supervisor, then that individual may rightly or wrongly assume that participation is necessary. Often, these subjects are recruited because they are readily available. This availability is not a sufficient reason for an IRB to approve research. (ref 59)

Students

Students are vulnerable for many of the same reasons that workers and employees are vulnerable. There is a long history of use of college students, first year psychology students in particular in research. Often, this participation was required for class credit. This is considered coercive as a student may not feel that they can refuse to participate in a study because they may perceive that it will negatively impact their grade, or their ability to obtain letters of recommendation at a later date. It has been suggested that any research that utilizes students, care be taken to assure that coercion does not exist—this can take the form of perceived pressure from grades or because monetary inducement is high. Also, when participation in research is required for a course grade, all students should be given the option to complete another activity not related to research for that grade without penalty. (ref 59)

Cultural vulnerability and group harm

Individuals may also be considered culturally vulnerable. Any individual who is not a member of the dominant culture may be vulnerable, as are individuals who are immigrants or individuals who have lower status either in our society or in their society of origin. Any of these individuals may be more prone to consenting because they feel they have no choice. Among the issues that researchers need to keep in mind when proposing to conduct research with a culturally vulnerable population are language barriers and cultural norms (both the potential subject’s home-culture’s norms and the cultural norms of our own society).

When reviewing research studies IRBs will also look at the potential for group harm that exists. There is a long history of research that was conducted to prove certain groups were of inferior status (women, African Americans, Native Americans), or prone to certain illnesses (alcoholism, mental illness). Any time an IRB reviews a study that is examining a group of individuals, especially an out-group that IRB must also look very carefully at the study for the potential for group harm. Could the results of the study be used to deny that group access to education or healthcare or social justice? In these cases, the IRB will not allow the research to move forward. While it is very important for minorities and individuals who are not part of the dominant power-structure of society to be involved in research—that research should never be used to reinforce their position of less-power.

Conclusion

This Module discussed research with a variety of vulnerable and protected populations. First, we presented the issues that all IRBs must consider when reviewing research with vulnerable populations: ability to provide informed consent, level or risk, coercion, and choice of subjects. The Department of Health and Human Services (DHHS) and Food and Drug Administration (FDA) guidelines related to vulnerability were reviewed. Types of vulnerability were presented and the following classes of vulnerable subjects were discussed in detail: prisoners, children, pregnant women, the cognitively impaired, individuals with disabilities, individuals with mental illness, individuals with substance abuse issues, individuals who are culturally vulnerable, and workers and employees. Finally, we discussed group harm. (ref 61) (ref 60) (ref 56)