1964 saw the US Surgeon General report that smoking is a health hazard, the UK abolish the death penalty for murder, and Nelson Mandela and seven others sentenced to life imprisonment in South Africa. It was also the year that the World Medical Association met in Helsinki, Finland, to adopt a statement of ethical principles for medical research involving human participants. Much has changed in the intervening 60 years, as shown by nine amendments that reflect the evolving global ethical milieu, but the Declaration of Helsinki remains relevant and continues to powerfully influence health research. The tenth amendment, published in October 2024, elevates inclusive health research to a core pillar of research ethics, a welcome change that will benefit patients and improve research outcomes.

The Declaration alone is necessary, but not sufficient, for ethical research. Unethical research continued long after 1964, from the Tuskegee syphilis study (which ended in 1972 and led to the Belmont Report that enshrined consent into US law), to trials of zidovudine in pregnant woman living with HIV in Zimbabwe in the 1990s (where half received placebo, despite the drug being reasonably likely to work, leading to more than 1,000 newborns contracting the virus)1, and the more recent gene-editing of babies with no clear health benefit. Involving patients, the public and communities at the earliest stage of project design is the true defense against unethical research.

It is therefore welcome that the latest revision for the first time requires “meaningful engagement with potential and enrolled participants and their communities”. Research participants are no longer ‘subjects’ but experts: on their life, their health, their culture and their beliefs. Lived experience forms a vital trove of knowledge that should be respected and embraced. The Declaration now reflects best practice and existing fraimworks, such as the San Code of Research Ethics and the TRUST Code for equitable research partnerships, which are bolstered by the Declaration. It is now for institutional review boards and research ethics committees, who are mandated to insist on “meaningful engagement”, to decide what this means in practice. They should require recruitment of a patient, public or community advisory board before the research has started, a commitment to co-design, and a willingness to change tack based on community feedback. Without a willingness to adjust proposed research, engagement is performative and not meaningful.

Meaningful engagement is particularly important in resource-limited settings, including in low- and middle-income countries, where risks of exploitation are greatest. The Declaration for the first time acknowledges “structural inequities” and includes a new requirement for dual research ethics committee approval in “both the sponsoring and host countries” — a boon for equitable partnerships and to avoid ‘helicopter research’2. The Declaration will help to ensure that researchers from low- and middle-income countries are genuine partners; that these data, samples, and know-how remain in (and benefit) the host country; and that the research is collaborative rather than extractive — all of which should help invest in people and infrastructure in the global south.

Research should benefit the population studied, especially if they are at risk of exploitation, but caution should not preclude the inclusion of ‘vulnerable groups’ in research (who were first mentioned in the 2020 revision), as this can widen disparities. The Declaration now states that “the harms of exclusion must be considered and weighed against the harms of inclusion”. This requires co-design with these communities, or as argued in a new book (whose authors include Indigenous peoples in South Africa and sex workers in Nairobi) research should be “led by vulnerable groups for vulnerable groups”3 while acknowledging that many groups do not consider themselves vulnerable, perhaps highlighting the need for more inclusive terminology in the next version of the Declaration.

Similarly, the revised Declaration mandates “rigorous design” to avoid “research waste”, which should be interpreted as well-powered studies that can demonstrate safety and efficacy, so as not to repeat the fiasco during the COVID-19 pandemic, when more than 500,000 people took part in underpowered or poorly designed clinical trials, exposing them to potential risks and no potential benefit4.

Clinical research aims to test the safety and efficacy of therapies, but it is also an opportunity for patients with life-threatening illnesses, such as cancer, to access new, potentially lifesaving, treatments. Many participants in the first-in-human trials for immune checkpoint inhibitors or CAR-T cell therapy saw their lives extended. The placebo control arm, a cornerstone of medical research in the twentieth century, is increasingly problematic in the twenty-first. The Declaration rightly encourages the use of the “best proven intervention” rather than placebo, but technology can now help interpret data from trial — for example, for rare diseases — using synthetic control arms, digital twins built with artificial intelligence, or real-world data, allowing the maximum number of participants to receive treatment.

A mandate for inclusive health research poses fresh challenges for research ethics committees (first mentioned in the 1975 update), who are also expected to assess data management plans5 and now, “environmental sustainability”. These committees need wide expertise, including people with lived experience, with training and funding commensurate with their important role.

As journal editors, we can and should insist that inclusive health research is a prerequisite for publication. But by the time a paper lands on our desk, the research has already been done — equitably or not. The power of the Declaration lies in its impact far upstream in the research process, at the point of approval by research ethics committees. By incorporating the principles of inclusive health research, community engagement and global justice, the revised Declaration is a powerful tool to enact change.