Introduction
Vulnerability and concerns around the protection of vulnerable persons are central themes in research ethics. The significance of the concept of vulnerability was first outlined in the seminal Belmont Report of 1979. It has later been widely adopted by international bodies in guidelines and regulations such as in the American Common Rule, the Council for International Organizations of Medical Sciences, and the Declaration of Helsinki. (Racine and Bracken-Roche 2018; Gordon 2020) Over the years, the concept of vulnerability has been repeatedly fleshed out in attempts to better define and instrumentalize it to enable adequate application and protection of research subjects by IRBs, researchers, and other stakeholders.
The first normative justifications of vulnerability centered around issues of justice, later on appeals to the principles of respect for persons, informed consent, autonomy, and harm also entered the discussion (Racine and Bracken-Roche 2018; Emmanuel et. al. 2000; Bracken-Roche et al 2017). Guided by these principles the initial notions of vulnerability tended to label individuals into pre-identified and predetermined groups such as: children, pregnant women, mentally disabled, refugees, etc… These categories expanded over the years to include more and more groups but notably failed to clearly demonstrate what factors made subjects vulnerable, thus ignoring conditions that could be fixed and required attention, as well as overlooking intersectionalities and the complex relation between different grouped categories.
Fortunately, academic literature shifted the perspective on the dimensions of vulnerability from a categorical to an analytical approach that now focuses on analyzing the types and sources of vulnerability. (Racine and Bracken-Roche 2018; Gordon 2020; Kipnis 2001). Notably, unlike the static and rigid categories of labels, like prisoner and refugee, Luna (2008) examines the status of women in research ethics to posit a more sophisticated and nuanced account of vulnerability.
According to Luna’s account the conception of vulnerability is best understood as a metaphor of layers. This notion provides for a more dynamic, flexible, and “softer” interpretation of vulnerability that illustrates the multiplicity and overlap in different vulnerabilities based on roles, status, social, and situational contexts, etc… An advantage of identifying layers of vulnerability is that it enables researchers to potentially address and minimize these layers, or develop multiple approaches to navigate around them.
In another approach Hurst (2008) defines vulnerability in research as a claim to special protection with “identifiably increased likelihood of incurring additional or greater wrong.” According to Hurst, this shifts the normative impetus and focus on special protection away from vulnerability in and of itself, towards pre-identified wrongs. By identifying potential wrongs, researchers can directly mitigate issues stemming from research protocols rather than inherent to the condition or status of research subjects (Levine et al 2004). Moreover, by anticipating potential harms and wrongs, stakeholders are able to proceed to weighing out ethical considerations, minimize wrongs, and provide compensation where it is due.
On the opposite side of the debate other ethicists deny the need for so much conceptual investigation of the dimensions of vulnerability on the grounds that the concept has lost its force and fails to reliably protect participants from harm (Kottow 2003). Alternatively, research ethics could focus on assessing research protocols and require a high ethical standard for all participants of human subject research such as undergoing a strict scrutiny test that applies to all, not merely those deemed vulnerable (Levine et al 204). Nevertheless, the concept remains central to best understand and navigate the legacy of bioethics and its impact on policy and biomedicine (Rogers et al 2012)
**Participants in the seminar series specifically focused on the concept of vulnerability and its use and implications in the special case of pregnant women.**
Assigned Reading
Seminar participants were asked to read the following papers prior to meeting for discussion:
Racine, E. & Bracken-Roche, D. (2019). Enriching the concept of vulnerability in research ethics: An integrative and functional account. Bioethics. 3, 19– 34. https://doi.org/10.1111/bioe.12471
Thesis: Authors propose and demonstrate a comprehensive, functional, and integrative account of vulnerability inspired by pragmatism and enriched by scholarly literature from bioethics. They posit that this account based on four main components can serve as a framework and guide all major stakeholders in research ethics and fill current gaps in ethics governance.
Bracken-Roche, D., Bell, E., Macdonald, M. E., & Racine, E. (2017). The concept of ‘vulnerability’ in research ethics: an in-depth analysis of policies and guidelines. Health research policy and systems, 15(1), 8. https://doi.org/10.1186/s12961-016-0164-6
Thesis: Authors conducted in-depth policy analysis of research ethics literature and guidelines and determined there remained major disagreement amongst scholars and regulatory bodies about the nature and scope of vulnerability. They conclude that the concept of vulnerability needs to be revisited and that engagement with all stakeholders would benefit research ethics.
Discussion Questions
Seminar participants were asked to consider the following questions prior to meeting for discussion:
1. Are pregnant women vulnerable in clinical research? How/to what?
2. Are there particular vulnerabilities during childbirth and how does that work into a framework of inclusion?
3. How should we think about cases of multiple vulnerabilities (e.g., a pregnant woman in prison, a pregnant adolescent) in this context?
The Case of Pregnant Women
The potential for pregnancy has historically deterred and limited the recruitment of women in research studies (ACOG 2015). The alleged vulnerability of pregnant women was primarily derived from concerns over autonomy, informed consent, and coercion, as well as the vulnerability of the fetus itself and situations of maternal fetal conflict (van der Zande 2017; Kaye 2019; Lyerly et al 2008). Concerns over fetal safety, shared by both researchers and mothers, and their inability to provide consent, has also warranted extra layers of protection and of scrutiny as is done in research with children and prisoners (Lyerly et al 2008; Blehar 2013). However, after assessing the literature van der Zande et al (2017) concluded that the main vulnerability faced by pregnant women all boiled down to their higher exposure to risk because of the lack of scientific data. Acknowledging the biological differences between women and men requires being able to study and understand the processes and mechanisms that happen at this important stage of a woman’s life. Moreover, specifically following pregnant women is necessary to avoid generalizations since all the physiological changes that happen during pregnancy often do not enable researchers and physicians to draw valid inferences about health and disease in all women (ACOG 2015; Blehar 2013; van der Graaf 2018).
While IRBs and researchers continue to regard pregnancy as a near automatic cause for exclusion, this reticence and appeal to the precautionary principle also comes with a profound cost (Lyerly et al 2008). As Baylis (2010) puts it “Pregnant women get sick, and sick women get pregnant” therefore, to treat pregnant women we must be able to study pregnant women (Lyerly et al 2008). Research ethics is faced with a dilemma where pregnant women are excluded and deemed vulnerable because of a lack of scientific knowledge. This paucity in the scientific knowledge base is because they were not included in research, thus to overcome this vulnerability requires inclusion and involvement in research (van der Zande et al 2017). Consequently, it is imperative to shift the paradigm and move away from presumed exclusion to presumed inclusion in order to end the vicious cycle and “protect pregnant women through [sic] research, and not just from research” (Blehar et al 2013; Krubiner and Faden 2017).
Efforts towards inclusion have included a change in CIOMS guidelines in 2016 highlighting pregnant women must not be considered vulnerable merely because they are pregnant, and the Common Rule’s elimination of pregnant women from the vulnerability classification, effective since July 2018 (Krubiner and Faden 2017; van der Graaf 2018). Moreover, members of the NIH’s Office of Research on Women’s Health have pushed to reclassify pregnant women from the status of a vulnerable population to that of a “medically complex population necessitating special scientific and ethical consideration” (Blehar et al 2013).
Moving forward, inclusion in research efforts will have to involve more normative analysis on the status of pregnant women as a medically complex population. Research wise, collaborative efforts at the state and federal levels, and between funding bodies, IRBs, researchers, patients, and all other relevant stakeholders will also be needed to promote smooth and equitable inclusion (van der Zande et al 2017; Lyerly et al 2018; Blehar et al 2013).
Ultimately the inclusion of pregnant women in research ethics will serve the needs of this population and underscore the important purpose of biomedical research: to tell us when medication is unsafe but also to reassure us of when drugs are safe (Lyerly et al 2018).
Reflection Points
In discussion, seminar participants reflected on the following points.
- One could argue that it is the fetus, not the pregnant woman, that is in the vulnerable position.
- Fetuses are not children and should not be considered to the detriment of pregnant women as they are not equal patients.
- We should not consider pregnant women and fetuses in conflict as expecting women also want what is best for their fetus. Their interests are tied and pregnant women sometimes opt to do what is best for their fetus and disregard their own wellbeing or health (even if the two are related).
- The pregnant woman and fetus are an intertwined dyad and in the context of research should be viewed as a unit. It is inaccurate and inadequate to assess women and fetuses as two separate organisms.
- Pregnant women could be considered vulnerable in some moments of pregnancy, without necessarily belonging to a vulnerability classification, e.g. emergencies, pain, manipulations during birth. To address and mitigate them the specific moments of vulnerability need to be recognized and considered.
- What does moving from vulnerability to scientific and medically complex population entail? Is the complexity moral complexity?
References and Additional Resources
Levine, C., Faden, R., Grady, C., Hammerschmidt, D., Eckenwiler, L., Sugarman, J., & Consortium to Examine Clinical Research Ethics (2004). The limitations of “vulnerability” as a protection for human research participants. The American journal of bioethics : AJOB, 4(3), 44–49. https://doi.org/10.1080/15265160490497083
Hurst S. A. (2008). Vulnerability in research and health care; describing the elephant in the room?. Bioethics, 22(4), 191–202. https://doi.org/10.1111/j.1467-8519.2008.00631.x
Krubiner, C. B., & Faden, R. R. (2017). Pregnant women should not be categorised as a ‘vulnerable population’ in biomedical research studies: ending a vicious cycle of ‘vulnerability’. Journal of medical ethics, 43(10), 664–665. https://doi.org/10.1136/medethics-2017-104446
van der Zande, I., van der Graaf, R., Oudijk, M. A., & van Delden, J. (2017). Vulnerability of pregnant women in clinical research. Journal of medical ethics, 43(10), 657–663. https://doi.org/10.1136/medethics-2016-103955
Lyerly, A. D., Little, M. O., & Faden, R. (2008). The second wave: Toward responsible inclusion of pregnant women in research. International journal of feminist approaches to bioethics, 1(2), 5–22. https://doi.org/10.1353/ijf.0.0047
Bracken-Roche, D., Bell, E., Macdonald, M. E., & Racine, E. (2017). The concept of ‘vulnerability’ in research ethics: an in-depth analysis of policies and guidelines. Health research policy and systems, 15(1), 8. https://doi.org/10.1186/s12961-016-0164-6
Chervenak, F. A., & McCullough, L. B. (2011). An ethically justified framework for clinical investigation to benefit pregnant and fetal patients. The American journal of bioethics : AJOB, 11(5), 39–49. https://doi.org/10.1080/15265161.2011.562595
Lange, M. M., Rogers, W., & Dodds, S. (2013). Vulnerability in research ethics: a way forward. Bioethics, 27(6), 333–340. https://doi.org/10.1111/bioe.12032
Gordon B. G. (2020). Vulnerability in Research: Basic Ethical Concepts and General Approach to Review. The Ochsner journal, 20(1), 34–38. https://doi.org/10.31486/toj.19.0079
Luna, F. (2009). Elucidating the Concept of Vulnerability: Layers Not Labels. International Journal of Feminist Approaches to Bioethics, 2(1), 121–139. http://www.jstor.org/stable/40339200
Kottow M. H. (2003). The vulnerable and the susceptible. Bioethics, 17(5-6), 460–471. https://doi.org/10.1111/1467-8519.00361
Rogers, W., Mackenzie, C., & Dodds, S. (2012). Why bioethics needs a concept of vulnerability. International Journal of Feminist Approaches to Bioethics, 5(2), 11–38. https://doi.org/10.2979/intjfemappbio.5.2.11
Raciti, C.G. & Enane, L.A. & MacDonald, K.R. et al. (2021). Ethical considerations for research involving pregnant women living with HIV and their young children: a systematic review of the empiric literature and discussion. BMC Med Ethics 22, 38 https://doi.org/10.1186/s12910-021-00601-x
Kaye D. K. (2019). The moral imperative to approve pregnant women’s participation in randomized clinical trials for pregnancy and newborn complications. Philosophy, ethics, and humanities in medicine : PEHM, 14(1), 11. https://doi.org/10.1186/s13010-019-0081-8
van der Graaf, R., van der Zande, I., & van Delden, J. (2019). How the CIOMS guidelines contribute to fair inclusion of pregnant women in research. Bioethics, 33(3), 367–373. https://doi.org/10.1111/bioe.12520
Baylis, F. (2010). Pregnant women deserve better. Nature 465, 689–690. https://doi.org/10.1038/465689a
Blehar, M. C., Spong, C., Grady, C., Goldkind, S. F., Sahin, L., & Clayton, J. A. (2013). Enrolling pregnant women: issues in clinical research. Women’s health issues : official publication of the Jacobs Institute of Women’s Health, 23(1), e39–e45. https://doi.org/10.1016/j.whi.2012.10.003
Kipnis, K. (2001). Vulnerability in research subjects: a bioethical taxonomy. In: National Bioethics Advisory Commission, editor. Ethical and policy issues in research involving human participants. Bethesda: National Bioethics Advisory Commission. G1–G13. http://www.aapcho.org/wp/wp-content/uploads/2012/02/Kipnis-VulnerabilityinResearchSubjects.pdf