The Declaration of Helsinki—a foundational text that outlines international ethical principles for medical research—has undergone one of the most extensive revisions since it was adopted in 1964. For the first time, the document calls for medical research to protect healthy volunteers and consider structural inequities in medicine and society. It also demands compliance not just from physicians, but all researchers involved in medical science.
The revision, published in JAMA on 19 October, is the 10th update to the declaration and “the most dramatic one in a long time,” says Jack Resneck, who chaired the World Medical Association (WMA) working group that rewrote the text, a process that included eight workshops around the world and two rounds of public consultation. Still, some had hoped for more sweeping changes.
WMA created the Declaration of Helsinki in response to gruesome experiments in Nazi concentration camps and later bioethical failures such as the thalidomide scandal, in which a poorly tested drug led to missing or malformed limbs in thousands of newborns. The text laid out broad principles, such as the right for participants to withdraw from research and the need for consent; later updates added crucial clauses such as the role of ethical approval. Although it is not legally binding, some countries refer to the declaration in legislation, and its broad principles are fleshed out in more detailed documents, such as the ethical guidelines published by the Council for International Organizations of Medical Sciences.
One key change in the new version is evident even in the title of the declaration, which now refers to “research involving human participants”—not subjects, as before. That’s “much more than a change in rhetoric—it’s really a shift in perspective, a kind of paradigm change,” says Philippe Amiel, a member of the ethics committee at the French biomedical research agency INSERM. The new wording signals that participants are no longer seen as “potential victims of possible torturers,” but as people with agency who often have a deep desire to participate in research, he says.
The same thinking underlies changes in the language about protecting vulnerable groups, Amiel says. The previous version said especially vulnerable participants—such as pregnant people or members of ethnic and racial minorities—should be protected. As a result, those groups were often excluded from trials altogether, says Paul Ndebele, a bioethicist at George Washington University. The new version says exclusion could exacerbate disparities, and that potential harms from taking part in a study must be weighed against those of exclusion. “We want to ensure that pregnant women are involved in research while ensuring there is safety in their involvement,” Ndebele says.
The new text also responds to a recent scandal: the promotion during the coronavirus pandemic of ineffective COVID-19 therapies, such as hydroxychloroquine and ivermectin, sometimes by researchers invoking the declaration itself. For example, French microbiologist Didier Raoult and his colleagues wrote in a 2023 draft paper that it was permissible to treat 30,202 COVID-19 patients with hydroxychloroquine based on the declaration’s provisions for unproven interventions. (French scientific societies have denounced the study as an “illegal clinical trial.”)
The revised declaration now says ethical principles must be upheld even in public health emergencies. Although doctors can sometimes try to alleviate a patient’s suffering with unproven drugs when nothing else is available, they should always seek advice from experts and informed consent from patients, and researchers should never use this route to “circumvent the protections for research participants set forth in this Declaration.”
The update was unanimously approved by the national medical organizations that make up WMA’s General Assembly. But at less than four pages, the declaration is brief, intended to contain only “high altitude” principles, Resneck says. Some stakeholders see omissions.
François Bompart, secretary of an INSERM project dedicated to concerns about healthy volunteers in medical research, says the call for protection of healthy volunteers as well as patients is “good news.” But specific concerns aren’t addressed, which he calls a “missed opportunity.” Healthy volunteers typically join studies for money, are often confined to study centers for long periods, and may also suffer health problems as a result of participating in drug trials, says Jill Fisher, a social medicine professor at the University of North Carolina at Chapel Hill who has studied healthy volunteers and worked alongside Bompart in the project. Fisher had hoped the updated text would engage with such issues.
Caesar Atuire, an ethicist at the University of Oxford and the University of Ghana, had hoped for a more profound change in thinking. “Ethics is not just about avoiding evil,” he says: “It’s also about promoting good.” The declaration is “quite silent” on potential benefits to participants, he says. Researchers currently have little power to guarantee that communities have access to concrete benefits such as medications, he notes. “If we thought more structurally about the researcher as belonging to a community, then we could actually include the obligations of that community to participants.” That would be a more African, communitarian approach, Atuire argues, and he and other African bioethicists have discussed how to reflect that perspective in the declaration. Without it, the update is “just an incremental change,” Atuire says.
Carla Saenz, a bioethicist at the Pan American Health Organization, thinks the revised declaration overlooks concerns in Latin America and the Caribbean, where some countries lean heavily on the declaration in their own laws and regulations. The new text expands its scope, by saying its principles should be upheld by all individuals and groups involved in medical research, not just physicians. But it still covers only medical research, not other types of human studies such as epidemiological or even behavioral research, Saenz says. For countries such as Paraguay and Peru, which refer directly to the declaration in legislation governing ethical research, the limited scope of the declaration means the laws leave out some human studies.
The new declaration does have other omissions, says Barbara Bierer, a clinician scientist at Harvard Medical School and Brigham and Women’s Hospital. For example, it says nothing about the use of data from sources such as insurance or pharmaceutical companies, gathered from people who might not expect their information to be used for research. “Each revision of the [declaration] has been quite thoughtful about trying to both catch up and be aspirational in terms of where we should be going on these issues,” Bierer says—and it remains a crucial document. But, “It’s very easy to lay out ethical principles—and very, very difficult to apply them.”
More: https://www.science.org/content/article/key-global-bioethics-guidelines-get-dramatic-update
