What is Vulnerable Population?
Vulnerable population refers to the individual that does not have the decision-making capacity to provide voluntary Informed Consent. Vulnerable population is considered as a disadvantaged sub-segment of the community requiring utmost care, specific ancillary considerations and augmented protections in research. There are two types of vulnerable groups, namely:
Historically, those who are vulnerable have been subjected to one or more of these four common types of abuses in human research.
|Common Types of Abuses in Human Research
|Types of Abuse
|Subjects who are physically forced to participate in research. This represents a complete lack of voluntariness. When subjects have no choice about whether or not to participate in research and are under the complete physical control of the investigators.
|The use of a credible threat of harm or force to control another person. This also represents a lack of voluntariness.
|The misuse of a position of confidence or power to lead or influence others to make a decision they would not otherwise make.
|The deliberate design and management of conditions or information intended to lead subjects to make a decision they would not otherwise make. Examples include lying about information, withholding information, or exaggerating information.
Sources of Vulnerability: Situational Considerations
Based on the 2011 Health Research and Development Ethics Standard Guidelines (KEPPKN Guidelines), vulnerable groups are defined as human beings, either individually, in households, groups, socially, or in society who are relatively or absolutely unable to protect their own interests or their group. They may lack the freedom, intelligence, education, economy, resources, power, and other necessary things to protect their own interests.
This method of classifying vulnerability does not account for situations in which an individual might be vulnerable (such as, someone who is acutely ill). Additionally, the group-based classification of vulnerability does not adequately address when an individual has multiple sources of vulnerability (such as, pregnant minors, individuals with mental illness who are also homeless, and others).
The NBAC (2001) provided an alternative way of thinking about and analyzing vulnerability. The NBAC looked at characteristics individuals might have that would prevent them from being able to provide voluntary informed consent. The traits may be thought of as falling into six broad areas: cognitive or communicative, institutional, deferential, medical, economic, and social.
Prospective research subjects who are not able to comprehend information, deliberate, and make decisions about participation in a proposed research study have a cognitive or communicative vulnerability. This vulnerability may be thought of in three broad categories. In any of these situations, subjects may not be able to provide the PSP to participate in the research.
Prospective subjects in research who are subject to the formal authority of others may have an institutional vulnerability. These individuals have the cognitive capacity to give Informed Consent but may not be able to make a truly voluntary choice, and may be unduly influenced (or coerced) to participate when they otherwise might not have done so. Institutional vulnerability may arise when subjects are prisoners, enlistees in the military, employees, or college students. For example, college students may be required to be research subjects for course credit or participate to earn a higher grade. In these situations, Informed Consent may be compromised because it is not truly voluntary. Further, those individuals might be exploited because of their subordinate status.
3. Deferential Vulnerability
Deferential vulnerability is similar to institutional vulnerability, but the authority over the prospective subject is due to informal power relationships rather than formal hierarchies. The power relationship may be based on gender, race, or class inequalities, or they can be inequalities in knowledge (such as in the doctor-patient relationship). Like institutional vulnerability, deferential vulnerability increases the risk of harm because PSP would be compromised and not fully voluntary.
4. Medical Vulnerability
Medical vulnerability occurs when prospective subjects have a serious health condition for which there is no standard of treatment. Subjects may not be able to weigh the risks and potential benefits of the study, so PSP may be carried out with insufficient understanding. Further, these subjects are at risk of being exploited because they may overestimate the benefit. When subjects’ views of the role of physicians and research (in cases where the physician treating the patient is also an investigator) are blurred or they fail to distinguish between research and treatment, the misunderstanding exacerbates medical vulnerability.
5. Economic Vulnerability
Economic vulnerability occurs when prospective subjects are disadvantaged in the distribution of social goods and services (income, housing, or healthcare). Participation in research provides the possibility of paying, obtaining health care, or other services and encouraging individuals to participate in research when they may not want to. These inducements to participate undermine the voluntary value of the PSP and increase the risk of exploitation in research.
6. Social Vulnerability
Prospective subjects who belong to undervalued social groups may be subject to social vulnerability. The perception of these groups as less valuable to society could lead to reduced concern (by investigators) for risks and burdens on those groups, and increase the risk of exploitation.
Terms of Research with Vulnerable Groups
This guideline provides a detailed procedure for KEP LPEM FEB UI and investigators in reviewing research involving vulnerable populations.
Research Involving Children as Subjects
Children are individuals who have not attained the legal age for consent to treatments or procedures involved in the research. According to Indonesian Law, children refer to any human being under the age of 18 (Law No. 35/2014 on Child Protection).
The involvement of children in research raises particular ethical concerns due to their lack of autonomy and inability to provide PSP. They are possibly vulnerable to control, coercion, undue influence, and manipulation by others (for example, parents or guardians, investigators, and teachers).
Permitted Research Categories Involving Children as Subject
Protocol 1: If the research is not involving greater than minimal risk
To approve this category of research, KEP LPEM must ensure the following conditionalities:
Protocol 2: If the research involves risks that are greater than minimal risk but have the prospect of direct benefit to the children involved in the study.
This category of research will only be approved by KEP if the board finds that:
Protocol 3: If the research involves greater risk than minimal risk and no prospect of direct benefit to the child involved in the study, but has the potential to yield general knowledge about the subject’s disorder or condition.
This category of research will only be approved by KEP if the board finds that:
Protocol 4: If the research does not meet the permitted conditions, but may be able to understand, prevent, or address issues affecting children’s health or well-being.
The research that falls within this category will only be proceed if the consultation with a panel of experts in pertinent disciplines has determined that:
Investigators must seek a child’s consent, unless the KEP decides that:
Parent or Guardian’s Permission
Guidelines for the 13th KEPPKN 2011 regarding the Inclusion of Children Subjects:
Before starting research involving children, investigators should ensure that:
Research Involving Prisoners as Subjects
Prisoner means any individual involuntarily confined or detained in a penal institution. According to Indonesian Law, a prisoner is suspect or defendant who is detained by investigator (Law No. 8/1981 on Criminal Procedure Code). Prisoners may be subject to coercion because they are under the control of regulators. They may also experience state abuse because they may wish to participate in research to improve their existence or receive parole.
Prisoners are considered under constraints because of their imprisonment which could affect their ability to make a truly voluntary and uncoerced decision regarding their participation as the subject of a research.
Permitted Research Involving Prisoners as Subject:
The KEP can approve research involving prisoners, only if all of the following conditions are met:
The KEP should only approve such research only if it finds that:
Pregnant Women, Human Fetuses and Neonates Involved in Research
Pregnancy encompasses the period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery. Fetus means the product of conception from implantation until delivery.
Some types of studies may include procedures that could potentially harm an unborn child or pregnant woman. For this reason, pregnant women should be included as a group that guarantee special protection.
Pregnant women or fetuses may be involved in research if all of the following conditions are met:
Informed Consent of Research Involves Pregnant Women, Fetuses, and Infants as Subjects
Guidelines for the 15th KEPPKN 2011 regarding the Participation of Pregnant Women Subjects
Before starting the research by including pregnant women as research subjects:
Subject with Limited Ability to Read, See, and Hear
Individuals in this group may be unable to read consent forms or instructional materials or hear answers to questions.
Subjects with Cognitive Disorders
Subjects with cognitive disorder requires special protection because of their limitations in making decisions. This group includes infants and young children, as well as individuals who are mentally impaired, have Alzheimer’s disease, are comatose, etc.
Vulnerability Due to Critical Illness
Vulnerability for the group of critically ill individuals and in the situation of emergency research may be due to intrinsic factors (such as reduced decision-making capacity of subjects and reduced capacity of subjects to provide Informed Consent) and situational factors (such as coercive conditions or abuse of circumstances).
Even if potential subjects can understand and communicate well, their voluntary decision can be influenced by situational factors, as in emergency research. If the treating physician also has a research role, this may result in an abuse of circumstances in the individual’s willingness to participate in a study.
Vulnerability Due to Terminal Illness (Research at the End-of-Life)
Individuals with terminal illness are vulnerable because of cognitive and physical impairment, which may worsen as death approaches.
Threats to voluntariness may occur as a result of an often a desperate desire for relief from pain and suffering, presenting the risk of exploitation. Desire to please caregivers may be particularly prominent. In addition, the risks and benefits that are important to patients near the end-of-life may be much more difficult to define. In other words, an individual’s goals and perceptions of burden and risk may change substantially as he or she nears death.
Vulnerability Due to Decisional Impairment
It is important to recognize that decisional impairment can result from a variety of intrinsic and situational factors and is not limited to individuals with a psychiatric diagnosis. Decisional impairment exists along a spectrum and therefore must be assessed in the context of the information that must be understood and the nature of the decisions to be made.
Decisional impairment can result from many causes including stroke and other central nervous system disorders, trauma, medical treatment, and drug abuse. In some cases, decisional impairment can arise through disability.
Decisional impairment is often compounded by situational factors that limit freedom of choice and the ability to understand the nature and consequences of research participation. Some examples include:
Vulnerability Due to Physical Disabilities or Impairments
Physical disabilities and impairments can result in diminished participation in society because the disability limits a major life activity (Equal Opportunity for Individuals with Disabilities 2009). The diminished participation in society can lead to vulnerability both because of an intrinsic factor (such as, a physical limitation the individual experiences) or a situational factor (such as, a lack of an adequate accommodation for the disability allowing for full participation).
Intrinsic factors such as a limitation in one of the senses (like sight) can lead to a very strong desire to participate in research that may have the prospect of direct benefit to the subject. This may potentially lead to undue influence. Additionally, situational factors in the study design can lead to vulnerability. For example, not providing a large-print or Braille consent form to an individual who has a visual impairment or blind can interfere with the voluntariness of consent.
Vulnerability Due to Economic Disadvantage or Social Marginalization
Economically disadvantaged individuals are those who are under-resourced to provide for themselves or their families, and experience particular hardships due to disparities and inequalities in the society in which they live. These situational factors can affect or limit the subject’s voluntariness to participate in research.
Socially marginalized individuals are those who lack influence in society or standing for a socially constructed reason (such as, race, religion, or disease state). Individuals who are socially marginalized often lack adequate access to social organizations such as the legal system.
The potential for undue influence or manipulation is higher for these subjects. For example, the prospect of getting monetary compensation for participation in research could significantly affect the willingness to participate, influencing the subject to accept greater risks of harm than they would otherwise accept. Economically disadvantaged individuals may also enroll in health research because it could mean access to healthcare where they may not otherwise have access.
Vulnerability Due to Social Hierarchy
Hierarchical social structures are found in situations throughout society. Examples include hospitalized individuals, nursing home residents, students, employees, prisoners, soldiers, other military personnel, or in some cases ethnic groups (such as, indigenous populations).
Hierarchical structures have the potential to create issues centered on power/control, coercion, undue influence, and manipulation. The “higher” hierarchical individual has the ability to exercise power or control over others (subordinates) in some way that is either real or perceived. Examples include:
Vulnerability Due to Minority Sexual Orientation Status
“Sexual and gender minority” is an umbrella phrase that encompasses lesbian, gay, bisexual, and transgender populations as well as those whose sexual orientation, gender identity and expressions, or reproductive development varies from traditional, societal, cultural, or physiological norms (NIH 2017). Members of the community may be vulnerable to discrimination, bullying, violence, and prejudice. Gender differences in societal structures, usually directed towards women, may render one gender vulnerable to these forces as well.
Individuals with minority sexual orientations face social and cultural vulnerability because many have experienced some forms of prejudice and discrimination at home, school, work, and/or other social contexts or organizations due to their sexual orientation. Gender differences may also make some individuals vulnerable, especially in areas of the world where women do not have the basic rights of citizenship (for example, access to an education, the right to divorce, and the right to vote). These vulnerabilities can lead to increased risks of harm to the individuals in their participation in research, and the prospect of undue influence or manipulation.
The principle of beneficence, or “do no harm,” is particularly important in research involving minority sexual orientations. Social and behavioral investigators should be aware of the potential harm to research participants and use safeguards to minimize the potential risk of harm when conducting research involving such groups.
Vulnerability Due to Uncertain Immigration Status and Individuals Involved in Illegal Activities
Individuals or groups of people who are regarded as being involved in illegal activities or are undocumented immigrants may be vulnerable because of the potential consequences that exposure may have to them. This can include risks of retaliation against them by others and legal consequences.
The risks of harm are higher for such individuals and often include group-based harm risks such as violating public trust which may have negative impacts on public health and well-being. For example, if undocumented individuals or those involved in illegal activities fear that they will be exposed when seeking medical care, they may not seek medical care when they need it. This can result in an increased negative health impact on this group of individuals.
Research Ethics Implications
The three pillars often described in research ethics (respect for persons, beneficence, and justice) are important to examine in the context of vulnerable individuals or groups participating in research. A combination of intrinsic factors and situational conditions that lead to vulnerability also open up the individual or group to potential problems that interfere with one of the pillars, requiring attention by the KEP and potentially additional safeguards being put in place in the research.
Autonomous Decision Making (Respect for Persons)
There is the possibility that due to intrinsic factors or situational conditions individuals or groups can be open to coercion or undue influence. The National Commission (1977) asserts that coercion occurs when one person intentionally presents an overt threat of harm in order to obtain compliance. An example is a professor telling students, “participate in my research or you will fail the class”. Physicians who threaten patients who refuse to participate in research are also coercive measures. However, the National Commission’s definition may be too narrow, as coercion is not always explicit. For example, a patient who participates in a study run by her primary care physician, because the patient fears her care is contingent on participation, is reacting to fear of retribution (coercion), whether the physician intends this or not.
Inducements, in contrast, are offers that influence people to make decisions, or do things they would not otherwise do. Inducements and the influence they cause may be acceptable or they may be “undue.” The difference is not always clear or generally accepted. Offering IDR 50,000 may be acceptable for research of one hour duration; offering IDR 500,000, or more, may not be appropriate for the same length of time and research load. In general, inducements constitute an undue influence if they alter a potential subjects decision-making processes such that they do not appropriately consider the research’s risk-benefit relationship.
Misunderstanding of the research is also a problem that can interfere with autonomous decision-making. For individuals or groups who are vulnerable, the prospect of direct benefit, whether real or perceived, can dramatically affect the individual’s voluntariness. This can lead to a person accepting a much higher level of risk of harm than they otherwise would accept or subscribing to the false belief that the research may hold out the prospect for direct benefit to them.
The concept of beneficence in research includes weighing the research’s risks of harm against the benefits. When conducting research involving vulnerable individuals or groups, two issues arise related to risks of harm.
There are three considerations that may arise when assessing justice in research involving vulnerable individuals or groups.
Guidance for KEP and Reviewers
The breadth of the expanded view of vulnerability described here and the complications involved with adhering to the regulations, combined with a common-sense approach to try to protect subjects, result in increased difficulty in the KEP’s review of research. Therefore, a stepwise approach to consideration of the research proposal may be helpful.
Are subjects vulnerable?
Investigators need to fully describe the population to be studied and the situation that will be felt by potential research subjects. This should answer both the question about the intrinsic factors or attributes, as well as the situational forces that may give rise to different types of vulnerability. It will also help the KEP and investigators quickly identify if there are any regulations that must be applied. Investigators generally have a much clearer understanding of the circumstances and potential challenges their research subject’s face. They are in a unique position to share their insight. When KEPs request this information, it facilitates the review of research and in the best circumstances leads to better designed research studies, improved review of research, and better protection of human subjects. Investigators and KEPs should consider:
Is inclusion of vulnerable subjects appropriate?
As discussed above, if some potential subjects are vulnerable, the IRB must then decide if inclusion of this population is indeed appropriate. The IRB must consider the competing ethical imperatives of respect for persons (especially protection of persons who lack self-determination and require protection), beneficence, and justice (offering a fair opportunity to benefit from participation).
According to the 2011 KEPPKN Guidelines in Point 12, the involvement of vulnerable groups in research can be appropriate if:
Is Protection of Vulnerable Subjects Sufficient?
If the inclusion of vulnerable subjects is appropriate, does the research plan (including subject identification, recruitment, and PSP) minimize the possibility of coercion, undue influence, manipulation, and exploitation? Meanwhile, does the research plan maximize the likelihood of valid PSP? At a very minimum, is the process of PSP valid? That is, is information presented in an understandable manner, do subjects comprehend the details of the research and their rights as research subjects, and is the process of PSP conducive to volunteering?
In addition, investigators and KEP should consider:
It is important to remember that the review process described here is an iterative process. Adequate protections may now allow inclusion of a population previously considered too vulnerable, or indeed may make a population not vulnerable at all.
Download this guide: A Guide to Reviewing Research Involving Vulnerable Groups