Our Clinical Research 101 series takes an in-depth look at key steps and tips for navigating the clinical research process. The fifteenth installment in our Clinical Research 101 series is by CHÉOS Scientist Dr. Anita Ho.
*This post was originally published in 2019 and was updated in 2022 and 2023.
In addition to being a Scientist at CHÉOS, Anita is currently a Clinical Associate Professor in bioethics and health services research at the Centre for Applied Ethics at the University of British Columbia, and an Associate Adjunct Professor in the Bioethics Program at the University of California, San Francisco. She is the former Director of Ethics Services at Providence Health Care. If you would like to inquire about our services, please submit your request here.
Vulnerability in the Research Context
According to the Tri-Council Policy Statement 2 (TCPS2), which guides the ethical conduct of research involving humans and/or human biological materials in Canada, some individuals or groups may face situations or circumstances that make them vulnerable in the context of a research project. For example, some people’s physical, cognitive, or mental health circumstances may render it more challenging for them to provide truly informed and voluntary consent for a particular research project. Young children and adults with diminished decisional capacity may not adequately understand what it means to participate in research, their rights as a research participant, and the implications (e.g., risks and benefits) of enrolling in a research study.
Nonetheless, cognitive and health status does not determine people’s vulnerability level in research in isolation. Cultural, social, and economic circumstances may diminish some (prospective) research participants’ ability to fully safeguard their own interests, regardless of their health status. People may experience vulnerability because they have been subjected to various forms of structural inequalities or historical wrongs, which limit their abilities to exercise their rights, opportunities, and power. Some examples may include people of Indigenous backgrounds who have faced structural racism in social and health care systems; people who are socio-economically disadvantaged and have less access to essential care; and people with stigmatized conditions, such as various mental illnesses, substance use disorders, or infectious diseases, who may have been subjected to additional medical surveillance. These social disadvantages may render people less able to advocate for themselves in the research setting in ways they see fit.
In other words, vulnerability is not an inherent quality of an individual or group — rather, it is generated by circumstantial and structural barriers. As stated by the TCPS2, people should not automatically be considered vulnerable because of assumptions made about the group to which they belong. There is heterogeneity within groups, and members of any group may face different and intersecting circumstances, especially since people may belong to multiple groups. The determination of any individual or group as potentially experiencing vulnerability in the context of a research project is thus dynamic, relative, socio-culturally dependent, and often imperfect. Moreover, research participants may experience different degrees or types of vulnerability and at different times, depending on their particular situations and researchers’ ability to attend to these circumstances. Researchers should therefore be familiar with the varying circumstances of prospective participants, groups, or communities so that they can anticipate their respective needs that may arise in the context of the proposed research project.
In research, vulnerability is most often discussed in relation to the concept of informed consent but is also related to other important research ethics principles and practices. As respect for persons, prevention of harm, promotion of welfare, and fair distribution of research burdens and benefits are widely accepted ethical principles of responsible research, the possibility that some individuals and groups may be susceptible to exploitation or harm due to their circumstances raises important ethical concerns. Some scholars have argued that vulnerability in research can be thought of as an increased likelihood of incurring additional or greater autonomy, welfare, or justice wrongs for some participants if researchers fail to adhere to their ethical duties.
The TCPS2 emphasizes the principle of Respect for Persons. Recognizing researchers’ broad ethical obligation to uphold respect for all persons and to promote fairness and equity, this principle highlights the duty of researchers to determine if their research may require special procedures to ensure that participants are not made (more) vulnerable due to the research, and that they are protected against abuse, exploitation, discrimination, and undue harm. For example, researchers may consider if having additional channels and opportunities for research participants to gather more information regarding the research project, voice their concerns, or withdraw their participation or data sharing consent may help to enhance all prospective participants’ autonomy and interests.
It should be noted that, in the United States, the Code of Federal Regulations 45 CFR 46 (“Common Rule”) highlights that some participants may be particularly “vulnerable to coercion or undue influence, such as children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged persons.” In particular, the Common Rule outlines additional protections for research with 1) pregnant women, neonates, and fetuses, 2) prisoners, and 3) children.
Attention to vulnerability generated by circumstantial and structural barriers is also important from the ethical perspective of fair distribution of benefits and burdens. For example, in global pharmaceutical research, there are often concerns about whether people from economically impoverished regions, who may be heavily recruited by researchers for vaccine or intervention trials, would be able to afford the expensive treatments developed based partly on their contribution. Recruitment of participants who face economic vulnerability and may be denied the benefits of the knowledge generated but are subjected to a larger share of research risks (e.g., side effects of an experimental treatment) may exacerbate their undue burdens and ongoing health inequity.
Protection of people who experience vulnerabilities: A note of caution
Vulnerability is especially important in the context of clinical research because of inherent knowledge and power asymmetry between researchers and participants. Researchers generally set research agendas and how their projects will be carried out. Moreover, unlike clinical care that focuses on the needs and well-being of individual patients, the purpose of clinical research is to generate generalizable knowledge to enhance the care for future patients, such that research participants may not directly benefit from being involved in a study. This power imbalance may be compounded if some prospective participants also face circumstances and structural factors such as colonialism, racism, misogyny, or ableism that can exacerbate their susceptibility to coercion, manipulation, or exploitation. It is thus ethically important to be mindful that we carefully understand prospective participants’ circumstances and how they may affect people’s ability to advocate for their own interests in the research arena. Broad terms such as “vulnerable” may conceal the structural nature of disadvantages and risk implying that biological and/or behavioural mechanisms are (solely) responsible for disadvantages facing various individuals, groups, or communities. Therefore, in research protocols or grant applications, it is important to clearly articulate what it is we mean by vulnerability in each context, including not only who is potentially vulnerable, but why these people are vulnerable, and to what they are vulnerable.
While protection of participants from exploitation and other undue influences is important in promoting respect, research professionals need to ensure that individuals, groups, and communities whose situation or circumstances may render them vulnerable are not unfairly excluded from research opportunities. Over-protectionist attitudes or practices by researchers or Research Ethics Boards (REBs) may ironically deny people access to benefits of research, thereby reinforcing their vulnerable circumstances. The inclusion of people of different demographic and socio-economic backgrounds in research is also scientifically important, as it helps to ensure that treatments frequently given to populations in these situations are effective and safe.
To fully respect the autonomy and well-being of people who may otherwise be in vulnerable circumstances and to promote justice and fairness in research, engagement with relevant populations and community stakeholders to better understand their broader context, concerns, and priorities is vital. Consultation and collaboration with relevant stakeholders can help to determine the most appropriate ethical framework and procedures for research participation and benefit sharing that are fitting for people’s contexts and realities. For example, the TCPS2 recommends that, when a research project is likely to affect the welfare of an Indigenous community or its members, researchers should engage with that community. Such engagement may help to not only inform how research can be conducted in ways that can minimize or mitigate participants’ vulnerabilities, but also to balance power relationships in research.
References and Further Reading
Bassett MT, Graves JD. Uprooting Institutionalized Racism as Public Health Practice. Am J Public Health. 2018 Apr;108(4):457–8.
Benatar SR. Avoiding exploitation in clinical research. Cambridge Q Healthcare Ethics. 2000 Oct;9(4):562-5.
Bracken-Roche D, Bell E, Macdonald ME, et al. The concept of ‘vulnerability’ in research ethics: an in-depth analysis of policies and guidelines. Health Res Policy Syst. 2017 Feb 7;15(1):8.
Denny CC, Grady C. Clinical research with economically disadvantaged populations. J Med Ethics. 2007 Jul;33(7):382–5.
Government of Canada: Panel on Research Ethics. Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans – TCPS 2. www.pre.ethics.gc.ca. Data modified: 2017 Nov 12.
Katz AS, et al. Vagueness, power and public health: use of ‘vulnerable‘ in public health literature. Critical Public Health. 30:5, 601–11.
Luna F. Elucidating the concept of vulnerability: Layers not labels. Int J Feminist Approach Bioethics. 2009;2(1):121–39.
Macklin R. Bioethics, vulnerability, and protection. Bioethics. 2003 Oct;17(5-6):472–86.
Nix, HP, Largent, EA, Taljaard, M, Mitchell, SL, Weijer, C. Ethical analysis of vulnerabilities in cluster randomized trials involving people living with dementia in long-term care homes. J Am Geriatr Soc. 2022; 1–11.
Office for Human Research Protections. 2018 Requirements (2018 Common Rule). US Department of Health and Human Services. 2017 Jan 19.
Rogers W, Ballantyne A. Special populations: Vulnerability and protection. RECIIS. 2008;5(4):11–38.
Stranges, J. Words matter: The use of ‘vulnerable’ in health care and public health. Unity Health Toronto. 2019 Aug 30.