Perspectives on the Fifth Revision of the Declaration of Helsinki

The first Declaration of Helsinki adopted by the World Medical Association in 1964 was one of the first attempts to transform reactions to the atrocities committed in the name of biomedical research during the Nazi period into preventive measures with a full global perspective. The second version, released in 1975, was rewritten from an observation point closer to active clinical science. The resulting impact on biomedical science was obvious within a few years. The requirement to establish research ethics committees made research ethics visible, not only among scientists but also in society at large.

At the same time, biomedical research expanded toward society in epidemiology and toward basic life processes in molecular biology. Further extension took place geographically with an increasing globalization of research results and multinational research projects.

Consequently, a thorough revision of the 1975 version has been necessary for some years, not to change its fundamental principles, but to account for the expanded scope of biomedical research. A new version should still serve the original aim: to balance the protection of, and respect for, research patients and healthy volunteers with the necessary freedom of research to facilitate scientific progress as a public good.

The number of new regional and international roles involved in "how to control research ethics" is increasing. The Council of Europe, comprising more than 40 European nations, made a major statement with its Convention on Human Rights and Biomedicine,¹ called "the Bioconvention," that binds the ratifying members to adapt their legislations in accordance with the convention. The Bioconvention deals with both general biomedical ethics and ethics related to research. New important aspects of research are covered, for instance, genetics research (where the subjects are not just individuals but families) and research on archived hospital and outpatient records, pathoanatomic specimens, cell cultures, frozen serum samples, and many other information sources for contemporary research.²

The Council of Europe has further initiated a small number of "protocol" groups (a protocol in this context is an additional statement open to signature for those states that have signed the Bioconvention, and legally binding to the same extent). One of these protocol groups, the Working Party on Biomedical Research, deals further with the same topic as the Declaration of Helsinki, but with inclusion of the new types of biomedical research mentioned above. Despite its European platform, both the Bioconvention and the supplementing protocols are expected to exert a strong influence on research ethics outside Europe.

The World Health Organization (WHO) and United Nations Educational, Scientific, and Cultural Organization (UNESCO) both continue to deal with research ethics in a global perspective. For example, UNESCO's initiative to provide ethical principles for genetics research represents yet another voice reaching active scientists.³

Both the National Institutes of Health in the United States and the Nuffield Foundation in England work with ethical issues regarding biomedical research projects performed in developing countries but funded and directed by developed countries. The problems involved are cultural and political diversity, weak Third-World economies and infrastructures, need for consensus building, and need to prevent exploitation. Evaluated in this context, I believe the fifth revision of the Declaration of Helsinki⁴ (adopted in October 2000 in Edinburgh, Scotland) embodies both advances and problems.

It is important that "other participants in medical research" have entered the introduction as those, in addition to physicians, for whom the Declaration is intended to provide guidance. Yet, it would have been preferable if the term "other scientists" had been chosen instead of "participants." It is also an important step forward that "research on identifiable human material or identifiable data" is included. Again, it would have been an advantage if anonymized information also had been included, because even group data can be an ethical problem due to group stigmatization. That "sources of funding" and "any possible conflicts of interest" are obligatory parts of the participant information is also an advancement.

The term "benefit" should be explained as comprising not only a possible health gain, but also further insight into pathoanatomic/physiologic/genetic processes as the first steps toward a later direct health benefit. Under the section on ethics of publication it is not only a question of "preserving the accuracy of the results," but a much broader problem complex, including such issues as fabrication and plagiarism. Hopefully, this can be indicated in the future with: "The results are collected and presented in truthful ways."

The current version has also preserved the demand from the earlier versions that "The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic or therapeutic methods." In this way accessibility due to economic constraints in developing countries is not mentioned. This does not eliminate the problems that other international ethical bodies deal with regarding the developing countries. Also, the use of placebo in phase 2 or phase 3 studies seems to be acceptable only "in studies where no proven prophylactic, diagnostic or therapeutic method exists," if the current section on use of placebo is taken literally. The final statement of the new version that physicians "must be free to use unproven or new . . . measures" outside of research situations seems still to be a truism that does not belong to a declaration on research ethics.

Probably the main omission is the brief mention of "human material" and "data" without including statements applicable to epidemiological and large-scale genetics research. Such projects are still rapidly increasing in number, meaning that the traditional controlled drug trial is no longer a fully representative paradigm of biomedical research in humans.

What can be expected, or at least hoped for, in the future? I hope that international organizations start to coordinate their declaration writing, which they have not done so far despite previous attempts. This would prevent scientists from struggling to meet a multitude of ethical signals from national laws, the World Medical Association, WHO, UNESCO, the Council of Europe, and many others. I further hope that such coordinated new declarations do not reflect primarily the political views of medical associations, but instead the scientific realities that exist when the trial patient or healthy volunteer meets the researcher.