Challenge: Vulnerability in Biomedical Research: a Broad Spectrum

Learn here about how biomedical research can interact with existing vulnerabilities or, even, create new ones

Overview

Vulnerability is a concept intended to protect individuals and groups who face an increased likelihood of harm to their rights, interests, dignity, or well-being through participation in biomedical research. The concept has been etched in international guidelines and widely discussed in scientific literature, as well as being practiced in life sciences research.

The term derives from the Latin vulnus (wound or injury), which means wound or injury, i.e., physical, psychological, and by extension also of a right. It refers both to the possibility of being harmed and to the condition of suffering harm.

By this definition, everything that is exposed to the possibility of being hurt, violated, injured, struck, beaten, offended, cut or damaged may be considered vulnerable.

In this way vulnus, seems to refer both to:

• the action of injuring, the cause, the blow inflicted by those who have the power and the possibility to offend, if we think in research terms not to recognize and respect the individual as a participant,
• and to the state of the subject who suffers (the effect, the violation of the body, soul, affections, etc.).

The National Bioethics Advisory Commission (NBAC) in its “Ethical and Policy Issues in Research Involving Human Participants” document has stressed that in the context for research, vulnerability refers to intrinsic or situational conditions that place individuals at greater risk of exploitation, coercion, undue influence, or other forms of harm during the research process. Vulnerability exists on a spectrum and may arise from:

• Limited decision-making capacity;
• Social, economic, institutional, or situational circumstances;
• Increased susceptibility to exploitation or abuse.

Vulnerability is not a fixed state but a potential condition Vulnerability is linked to the aspect of possibility and not of state: vulnerable is who could, potentially, be injured. Consequently, the Barcelona Declaration highlights that:

“The vulnerable are those whose autonomy or dignity or integrity are capable of being threatened. And that vulnerability specifically requires not merely non-interference with the autonomy, dignity or integrity of beings, but also that they (vulnerable) receive assistance to enable them to realise their potential.”

A vulnerable population therefore is a group of people who require greater protection than the others due to the potential risks of participating in research. It requires additional protections to ensure that participation in research is voluntary, informed, and respectful of fundamental rights.

Key Ethical, Legal and Societal Issues

Protection of Autonomy and Informed Consent: Vulnerable individuals may face difficulties in providing free and informed consent due to cognitive limitations, dependency relationships, language barriers, social pressures, or other circumstances. Researchers must ensure that consent procedures are adapted to participants’ specific needs.

Risk of Exploitation and Undue Influence: Individuals in vulnerable situations may be more susceptible to coercion, manipulation, or inducements that compromise voluntary participation. Ethical safeguards are necessary to prevent exploitation.

Respect for Human Dignity and Integrity: Research involving vulnerable populations must uphold participants’ dignity, privacy, physical and psychological integrity, and fundamental rights throughout the research lifecycle.

Fair Inclusion and Access to Benefits: The Declaration of Helsinki emphasizes that research involving vulnerable groups is justified only when it addresses the health needs or priorities of the vulnerable group; otherwise, the research cannot be carried out in a non-vulnerable population. The group stands to benefit from the resulting knowledge, interventions, or practices.

Safeguarding and Prevention of Harm: Researchers have a responsibility to:

• Ensure participants’ safety and welfare;
• Prevent abuse, neglect, discrimination, and stigmatization;
• Implement additional protective measures proportionate to the level of vulnerability.

Role of Research Ethics Committees (RECs): Research Ethics Committees are responsible for assessing whether adequate safeguards are in place to protect vulnerable participants and whether the anticipated benefits justify the risks.

Empowerment and Inclusion: Protection should not result in exclusion from research. Ethical research should empower vulnerable individuals, support their participation where appropriate, and promote equitable access to the benefits of scientific progress.

Relevant EU Legislation

• Charter of Fundamental Rights of the European Union: art. 1 on Human dignity, art. 3 on the Right to the integrity of the person, art. 8 on the protection of personal data, art. 21 on non-discrimination. The Charter provides the overarching framework for protecting vulnerable individuals participating in research.
• Regulation (EU) No 536/2014: it requires special protection for vulnerable subjects participating in clinical trials. It establishes conditions for informed consent and ethical review and includes specific provisions for minors, incapacitated adults, and other vulnerable populations.
• Regulation (EU) 2016/679: it protects personal data processed in research. It requires particular safeguards when processing sensitive personal data and supports principles of fairness, transparency, and accountability.
• Commission Regulation (EU) No 141/2000: it is relevant when research involves rare disease populations, which may experience specific forms of vulnerability.

Resources

• World Medical Association, Declaration of Helsinki: The cornerstone international ethics document for research involving human participants. The 2024 revision contains an updated section on vulnerability, emphasizing fair inclusion, additional protections, and responsiveness to the needs of vulnerable groups

• Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization (WHO), International Ethical Guidelines for Health-related Research Involving Humans: see Guideline 15 about research involving Vulnerable Persons and Groups.

• Partners in the BIOMED II Project, Barcelona Declaration on Policy Proposals to the European Commission on Basic Ethical Principles in Bioethics and Biolaw
• National Bioethics Advisory Commission (NBAC), Ethical and Policy Issues in Research Involving Human Participants
• Council of Europe, Guide for research ethics committee members

Relevant Publications

• Kipnis, K. (2001). Vulnerability in Research Subjects: A Bioethical Taxonomy. Commissioned Paper at the University of Hawaii at Manoa.
  http://www.aapcho.org/wp/wp-content/uploads/2012/02/Kipnis-VulnerabilityinResearchSubjects.pdf
• Bracken-Roche, D., Bell, E., Macdonald, M.E. et al. The concept of ‘vulnerability’ in research ethics: an in-depth analysis of policies and guidelines. Health Res Policy Sys 15, 8 (2017). https://doi.org/10.1186/s12961-016-0164-6
• Levine C, Faden R, Grady C, Hammerschmidt D, Eckenwiler L, Sugarman J; Consortium to Examine Clinical Research Ethics. The limitations of “vulnerability” as a protection for human research participants. Am J Bioeth. 2004 Summer;4(3):44-9. https://doi.org/10.1080/15265160490497083

• Hurst SA. Vulnerability in research and health care; describing the elephant in the room? Bioethics. 2008 May;22(4):191-202. https://doi:10.1111/j.1467-8519.2008.00631.x
• Grigis A, Beretta G, Borry P, Sanchini V. Vulnerability in research ethics: A systematic review of policy guidelines and documents. PLoS One. 2025 Jul 1;20(7):e0327086. https://doi.org/10.1371/journal.pone.0327086
• Lindholm, O., Karjalainen, S. & Launis, V. Chasing ‘vulnerability’ across six decades of the Declaration of Helsinki. Monash Bioeth. Rev. 43, 1–33 (2025). https://doi.org/10.1007/s40592-025-00235-4