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Vulnerable Subjects

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The Ethics of Research with Human Subjects

Part of the book series: International Library of Ethics, Law, and the New Medicine ((LIME,volume 74))

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Abstract

In previous chapters, we have touched on some ethical issues pertaining to research involving vulnerable subjects, such as risks to children and pregnant women/fetuses. In this chapter, we will focus on dilemmas faced by investigators, institutions, IRBs, and sponsors related to research involving vulnerable subjects. In Chap. 2, we noted that the federal regulations include a general requirement for protecting vulnerable subjects (45 CFR 46.111a3, 45 CFR 46.111b) as well as specific requirements pertaining to pregnant women, fetuses and neonates (Subpart B), prisoners (Subpart C), and children (Subpart D). The Helsinki Declaration also provides guidance on research involving vulnerable subjects:

All vulnerable groups and individuals should receive specifically considered protection. Medical research with a vulnerable group is only justified if the research is responsive to the health needs or priorities of this group and the research cannot be carried out in a non-vulnerable group. In addition, this group should stand to benefit from the knowledge, practices or interventions that result from the research (World Medical Association 2013).

Likewise, CIOMS guidelines requires additional protections for vulnerable subjects:

When vulnerable individuals or groups are considered for recruitment in research, researchers and research ethics committees must ensure that specific protections are in place to safeguard the rights and welfare of these individuals and groups in the conduct of research (Council for the International Organizations of Medicals Sciences 2016:70).

The 2002 and 2016 versions also includes sections which address research involving children, pregnant women, and adults with mental disabilities or diseases that affect decision-making (Council for the International Organizations of Medicals Sciences 2002, 2016). Research regulations an ethical guidance include the following types of additional protections for vulnerable subjects:

  • Justification for including vulnerable subjects in research. The CIOMS guidelines recommend that a justification be provided for including vulnerable subjects. For example, children should not be included in a study if the research objectives can be accomplished by enrolling only adults (Council for the International Organizations of Medicals Sciences 2002, 2016). The federal research regulations require that the selection of research subjects be equitable (45 CFR 46.111a3), which implies that vulnerable subjects should not be unfairly included in research (Mastroianni and Kahn 2001).

  • Limits on research risks. Federal regulations place limits on the risks that fetuses, neonates, children, pregnant women, and prisoners can be exposed to in research that does not offer them direct benefits (45 CFR 46, Subparts B, C, D).

  • Rules for IRB Composition. Federal regulations require that an IRB which reviews research on prisoners include a prisoner or prisoner representative (45 CFR 46.304). Commentators have argued that IRBs which review research on mentally disabled people, children, and other vulnerable subjects also should include members with the appropriate background and experience concerning the study population or that they should consult with outside experts (National Bioethics Advisory Commission 1998; Institute of Medicine 2004).

  • Safeguards for Consent. Federal regulations specify procedures for obtaining consent from the parent(s) and assent from the child in pediatric research (45 CFR 46 Subpart D). The National Bioethics Advisory Commission (1998) recommends that investigators follow procedures for assessing decision-making capacity in mentally disabled or ill adults and identifying surrogate decision-makers for subjects who are incapable providing consent. In some cases, an IRB might require independent monitoring of the consent process to protect vulnerable subjects.

  • Safeguards for privacy /confidentiality. Additional protections for privacy and confidentiality might be appropriate for research involving students or employees to prevent their professors or employers from having access to private information that could be used against them (Bonham and Moreno 2008; Resnik 2016b).

  • Benefit sharing. Some ethical guidelines include procedures for sharing benefits with research subjects or host communities/nations to minimize the potential for exploitation (see discussion in Chap. 8).

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Notes

  1. 1.

    Some commentators use the term “vulnerable population” instead of vulnerable subject. I prefer to use the term “vulnerable subject” because it coincides with phrasing used in the federal regulations and reminds us that we are protecting the rights and welfare of individuals, not groups.

  2. 2.

    Prior to revisions of the federal research regulations pertaining to research with prisoners in 1978, pharmaceutical companies frequently used prisoners in Phase I drug studies. See Hornblum (1999).

  3. 3.

    Although I have identified 15 different types of potentially vulnerable subjects, I will focus on the three types which have generated the most debate, i.e. children, mentally disabled or ill adults, pregnant women/fetuses .

  4. 4.

    As noted in Chap. 2, the EPA has its own regulations pertaining to research involving children. The EPA does not allow funded-investigators to conduct any research that intentionally exposes children to environmental agents. See Resnik (2007c).

  5. 5.

    Some refer to this as “therapeutic” research but this terminology is misleading because it conflates research and therapy (Levine 1988). As noted in Chap. 2, research and therapy are distinct conceptual categories: research aims to develop knowledge, while therapy aims to help patients. I prefer to use the term “beneficial” research to indicate that the research offers the subject the prospect of direct, medical benefits.

  6. 6.

    See Kopelman (1997) for further discussion of the best interests standard in parental decision-making .

  7. 7.

    Although the FDA has its own research regulations it follows Subpart D of the Common Rule for overseeing pediatric research. The study fell under the FDA regulations because the sponsor was seeking approval for the leuprolide test.

  8. 8.

    Parents of teenagers may disagree, of course!

  9. 9.

    When the FDA approves a drug, it approves it to treat specific populations with specific diseases. It also approves a dosage and route of administration for the drug. Once a drug is on the market, physicians are legally permitted to prescribe for un-approved uses, i.e. off-label.

  10. 10.

    DMC is usually not an all or nothing trait and may vary, depending on the individual’s mental status, emotional temperament, medical condition, etc. A high degree of DMC may be required to make complex and risky decisions, whereas a lower degree of DMC may suffice for making simple, low-risk decisions. See Chen et al. (2002).

  11. 11.

    E.g. the woman has not had a hysterectomy and not gone through menopause.

  12. 12.

    See Powers (1998).

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  1. National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

    David B. Resnik

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Resnik, D.B. (2018). Vulnerable Subjects. In: The Ethics of Research with Human Subjects. International Library of Ethics, Law, and the New Medicine, vol 74. Springer, Cham. https://doi.org/10.1007/978-3-319-68756-8_9

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