Abstract
The Declaration of Helsinki (DoH) serves as an authoritative international guideline for the ethical conduct of biomedical research involving human participants. 1 The DoH was first issued by the World Medical Association in 1964 and has been revised eight times since its creation. The original declaration built on the Nuremberg Code of 1947—developed in response to criminal experimentation under the Nazi regime—and influenced the 1979 Belmont Report, which established respect for persons, beneficence, and justice as tenets of American research ethics. 2 The release of the 2024 declaration presents a valuable opportunity for re-examining fundamental ethical principles in biomedical research and for exploring new developments relevant to thyroidology.
Since 1964, the DoH has consistently begun with the physician’s pledge from the 1948 Declaration of Geneva, the World Medical Association’s reinterpretation of the Hippocratic Oath: “The health and well-being of my patient will be my first consideration.” This framing conceptualizes research ethics as an extension of medical ethics and, therefore, as another case of the doctor–patient relationship. The language of the original declaration makes this quite explicit, stating, “In the purely scientific application of clinical research carried out on a human being, it is the duty of the doctor to remain the protector of the life and health of that person.” 3 In other words, physicians pursuing scientific discovery for the benefit of humanity are, above all, obligated to protect their individual patients from being harmed by potentially exploitative societal interests.
To this end, the original DoH established ethical safeguards that are now so widespread as to seem self-evident: research must be conducted by qualified professionals with the anticipation of actual benefit to society, risks to participants should be minimized, participants or their surrogate decision-makers must give informed consent, and participants are free to withdraw at any time. Notably, the concept of independent ethics review committees—what we now recognize as Institutional Review Boards (IRBs)—was not formally introduced in the Declaration until 1975, and confidentiality protections were not included until 1983. Despite these safeguards, conducting research that poses any degree of risk to individuals remains ethically challenging. Some authors have even criticized the foundational framing of the DoH for being disingenuous in its stated reliance on the Hippocratic principle of primum non nocere (“first, do no harm”). 4
Given these challenges, the declaration continues to be revised in an effort to more thoughtfully and specifically guide the ideal conduct of research. By its seventh revision in 2013, the original 11 principles of 1964 had grown to 37 and come to include more wide-ranging provisions, from the use of placebos in controlled trials to principles upholding environmental sustainability and animal welfare. 5 The 2024 DoH retains and expands upon these 37 principles and, importantly, is written not only for doctors but for any health care provider or non-clinician who is engaged in research. What began as a special case of the doctor–patient relationship is now a broad code of conduct for all clinical researchers. In its revision of this code, the 2024 DoH introduces greater nuance into informed consent, deeper awareness of the impact of structural inequities, and new ideas about the ethics of data stewardship, among other important updates.
Free and Informed Consent
Informed consent is one of the cornerstones of the modern ethical practice of medicine and is grounded in the related philosophical principles of autonomy and respect for persons. These entail an inviolable respect for the value of being human, which includes the capacity to choose for oneself. Although the aim of clinical research is different from clinical medicine, obtaining the informed consent of research participants is just as fundamental to the ethical practice of research. Previous versions of the DoH have emphasized that consent must be informed in order to be truly voluntary, but the 2024 Declaration goes further and defines ideal consent as being both “free and informed.” Informed consent means that an individual who understands the nature, risks, and benefits of a research experiment agrees to participate out of their own willingness. Free and informed consent means that an informed individual not only agrees to participate willingly, but that they also have the ability to refuse without coercion or undue influence. The philosopher John Locke, in his Essay Concerning Human Understanding, provides a useful analogy: a person locked in a room may choose to stay, but they are not truly free unless the door is also unlocked. 6 This distinction recognizes the power imbalances inherent in the researcher-participant relationship, much like the 2024 DoH’s shift from “subject” to “participant,” which reflects a more egalitarian approach to research. Instead of research being conducted on a subject, a participant is ideally seen as an active partner in the process.
Structural Inequities and Inclusion
Building on this concern for potential abuses of power, the 2024 DoH places greater emphasis on the impact of structural inequities on the research process. Historically, racial and ethnic minorities have been both the targets of unethical, often abhorrent experimentation—as in the Tuskegee Syphilis Study—and underrepresented in biomedical research, which can lead to greater disparities in their health outcomes. To address this dual problem of exploitation and marginalization, the 2024 DoH advocates more strongly for the inclusion of underrepresented groups and calls for critical examination of how social structures can distribute benefits, risks, and burdens unfairly among research participants. As an example, the 2024 DoH now mandates equitable community engagement in research design and implementation, including representation of relevant community members on the IRB. The declaration also questions the practice of prima facie excluding traditionally vulnerable people from research participation—populations such as pregnant women, minors, prisoners, or persons with intellectual disabilities. While the original exclusion of these groups may have been intended to protect vulnerable populations, their systematic exclusion from biomedical research can also worsen health disparities by preventing research findings from being applied to these groups and is no longer sanctioned in the DoH.
Data Stewardship and Other Updates
Several more specific amendments to the updated DoH are worth highlighting. In the wake of the coronavirus pandemic, the 2024 DoH addresses the ethics of biomedical research during public health emergencies, cautioning that even when urgent research is needed, the same ethical principles must be upheld. The revision also reframes the imperative to minimize environmental harm into a more active commitment to promoting environmental sustainability, and in so doing criticizes research waste. What constitutes research waste is not defined but may be tied to the declaration’s principle of maintaining scientific integrity and eschewing scientific misconduct.
Perhaps one of the most innovative updates to the 2024 Declaration of Helsinki is the incorporation of principles for data security derived from the World Medical Association’s Declaration of Taipei, a 2016 guideline for the ethical use of large databases and biobanks. According to the 2024 DoH, research participants must provide free and informed consent not only for their initial participation but also for potential secondary uses of their data. This stipulation extends to cases where data may be reused in multiple studies or stored indefinitely for future research. When informed consent cannot be obtained, the onus shifts to independent research ethics committees to determine whether and how data can be used. These updates reflect contemporary ethical concerns surrounding data stewardship in an era of artificial intelligence (AI) and global data sharing. Issues such as data ownership and the possibility of re-identification are increasingly pressing and underscore the importance of governance structures that can balance ethical concerns with the potential for scientific discovery and medical breakthrough.
Implications for Thyroidology
In thyroidology, the 2024 Declaration of Helsinki provides a framework for how we as endocrinologists, surgeons, and clinical researchers can continue to generate ethical evidence for the treatment of thyroid disease. The DoH’s call for scientific integrity and equitable inclusion in research should enhance our standards for research design, peer review, and publication. The declaration’s emphasis on free and informed consent, especially for secondary data use, can guide future research into AI-driven diagnostics and predictive models being trained on thousands of ultrasound images for thyroid nodule risk stratification. The same applies to research with large biobanks in the further development of molecular diagnostics. Perhaps most importantly, the release of the 2024 DoH highlights inevitable tensions in biomedical research between individual well-being and the broader common good—and raises the critical question: whose common good?
While the 2024 DoH upholds the importance of minimizing harm to patients, it remains true that both research participants and researchers must acknowledge that the goals of research do not necessarily align with maximizing the patient’s benefit and that there are limits to how much participant harm is permitted in the service of adding to scientific knowledge. As thyroidology continues to advance, the 2024 Declaration of Helsinki offers researchers principles for navigating these complexities, drawing from a historical tradition in research ethics and contemporary international consensus, and should remind us that scientific discovery must be pursued with a steadfast commitment to the well-being of those who entrust us with their participation.
Footnotes
Authors’ Contributions
J.T., M.A., and P.A. Contributed equally to the conceptualization, writing, and critical revision of this article. All authors approved the final version for submission.
Author Disclosure Statement
No competing financial interests exist.
Funding Information
No funding was received for this article.