The World Medical Association’s just-released draft version of the Declaration of Helsinki contains a number of significant changes, including some that raise important questions about the scope and status of the Declaration.

Over the summer of 2007, the WMA invited comments from member organizations and other stakeholders to identify revisions, amendments, and new topics for inclusion. While the responses received have not been made available to the public, they have been considered by the WMA’s Medical Ethics Committee and Council and by a working group composed of members of medical associations from Brazil, Germany, Japan, South Africa, and Sweden. The revised draft includes a commentary on why particular changes have been made. National medical association members of the WMA are now asked to conduct consultations within their countries and submit combined comments by February 25, 2008, while relevant international organizations do so separately. A final version of the Declaration is expected to be approved by the WMA General Assembly next year.

While the Declaration’s overall structure remains unchanged, some interesting shifts in paragraphs, rewordings, and additions are suggested. But first, to satisfy curiosity about Paragraphs 29 (on standard of care/use of placebos) and 30 (on what happens when the research is over): expect controversies to continue.

The note of clarification on Paragraph 29 has been integrated into the paragraph itself, with no substantial changes except replacing a contentious “or” by an “and.” Paragraph 29 now lists two exceptions from testing a new method against the best current one, namely (1) absence of a proven method and (2) use of placebo when this is supported by compelling and scientifically sound methodological reasons and the placebo will not subject research participants to any additional risk of serious or irreversible harm. The commentary is of course right to observe that by removing the note, “the apparent contradiction between the paragraph and the note … disappears.” However, the tension clearly remains within the paragraph itself. Questions about the limits of placebo use in research and about the best local, as opposed to the best globally available standard of care, when this is absent locally, are hence still far from settled.

With regard to post-trial access to care and access to other appropriate care, the new draft Declaration underscores the importance of both – or so it seems. The note of clarification on Paragraph 30 now appears as part of Paragraph 14 among the basic principles for biomedical research, putting more weight on the requirement to identify arrangements for post-trial access. On the other hand, this requirement is not quite in line with the substantially reworded Paragraph 30. Paragraph 30 now reads that patients are “entitled to be informed about the outcome of the study and to share any benefits that result from it, for example, access to prophylactic, diagnostic, therapeutic or palliative treatments identified by the study.” The draft Declaration seems to both emphasize and deemphasize post-trial access to care.

Setting these notorious controversies aside, the suggested amendments to the Declaration are a rich reflection of recent debates in research ethics. Some of the interesting additions include the following:

• Populations previously underrepresented in research – in particular, children and pregnant women – should be provided equitable access (Paragraph 4).
• Research protocols should contain provisions for treating patients who suffer as a consequence of research interventions (Paragraph 13). 
• The community risks, burdens, and benefits of research should be carefully assessed (Paragraph 16).
• Family and community consent, if supplementary to individual consent, can be appropriate (Paragraph 20).
• Clinical trials should be listed in publicly available registries (Paragraph 16).
• Researchers must inform participants that secondary findings or genetic information can impact on personal or professional lives (Paragraph 22).
• A new Paragraph 22a on nonclinical epidemiological research allows for exceptions from informed consent provided that the research has been approved by an ethical review committee.
• Paragraphs 24 and 26 seek to add extra protection for incompetent research participants by requiring that research risks and benefits be assessed in the best interest of the potential participant. (Paragraph 26 appears to cover emergency research, but this is not made explicit.)
• A new Paragraph 26a requires informed consent for sample collections and renewed consent when samples are used for a different purpose – irrespective, it seems, of whether the samples are in “anonymous” or identifiable form or general consent for future research has been given beforehand.
• A new Paragraph 26b discourages re-exposure of “professional participants.”

While these and other additions and changes clearly merit individual consideration, here we flag two more general points concerning the scope and status of the Declaration.

The new draft considerably broadens the scope of the document. It does so in three important ways. First, the draft Declaration no longer pertains to medical research, but to biomedical research more generally. Second, it is now meant to guide biomedical research with human beings rather than human subjects. And third, it addresses researchers rather than physicians – with the exception of Paragraphs 2 and 3 (setting out WMA’s authority on the matter) and Paragraphs 28, 31 and 32 (covering additional principles for biomedical research combined with medical care).

These changes are not merely terminological. They have important implications for the content, authority, and acceptance of the document. Combine the new terms, and the scope of the Declaration appears to expand well into areas of basic science. Arguably, embryo research involves “human beings“ at a very early stage of their development. But would it be useful if such research was perceived to come under the Declaration? Similar ambiguities in scope have also been raised by UNESCO’s recent Universal Declaration on Bioethics and Human Rights, and it seems prudent to avoid repeating such confusion here (for example, by replacing “human beings” with, where appropriate “human subjects, materials or data”).

Furthermore, the WMA’s authority for issuing guidance for researchers at large is unclear, and it would need to be considered how the Declaration’s provisions concerning researchers at large relate to those included in other relevant documents – for example, the UNESCO Declaration or perhaps Rigour, Respect and Responsibility: A Universal Ethical Code for Scientists (2006) developed initially by the UK’s Chief Scientific Advisor and the Council for Science and Technology.

Related questions concern the status of the Declaration. Should it be viewed as a set of binding ethical rules that defines what is ethical and what is not? The use of “must” in paragraphs 13, 15, 20, 21, 22, 24-26, and 31 suggests there is no scope for deviating from the provisions. Also, several of these paragraphs apply to precisely defined medical or research practices, with little room for interpretation. At the same time, the use of the softer “should” in paragraphs 9, 13-18, 21-24, 26-27, 29, and 31 appears to give more scope for specifications. Physicians or researchers might argue that their research is ethical even if it does not comply fully with the norms of the Declaration. Alternatively, then, perhaps the Declaration should be viewed primarily as an enunciation of aspirational ideals?

In the review of Paragraph 30 in 2004, the WMA’s working group made a proposal to add a preamble to this effect, which would have clarified that the Declarations’ “ethical principles provide the basis of moral reflection on the means and goals of research involving human subjects, distinct from national legal and regulatory requirements.” If Paragraph 9, addressing related matters, had been revised accordingly, such clarification would have been helpful. First, it would have underscored that the Declaration itself is not a regulatory device. Second, it would have emphasized that deciding what is ethical in a given circumstance is not simply a case of applying the Declaration. Ethical principles are not computational devices. Instead, the proposed preamble would have clarified that the Declaration’s role is to function as a framework specifying the areas in which explicit justification is required.

The point is not just a philosophical one. It is not uncommon for the Declaration, in particular in the absence of national regulations, to be annexed to both public and commercial trial protocols. The expectation often is that litigation issues will be settled as long as there is compliance with the Declaration. But many of the Declaration’s provisions are simply too general or too ambiguous, and using the document in a legalistic way is misunderstanding its proper purpose.

One way of treating the Declaration as the basis of moral reflection on research with human subjects could look like this. Instead of just annexing the document, research protocols could include a statement that clarifies how the respective provisions have been interpreted and addressed and justifies possible departures from the provisions. Admittedly, this might seem to demote the status of the Declaration to a mere check-list, but this would be a wrong interpretation. As a document expressing ethical ideals agreed by the world’s leading representative body of physicians, it would still carry substantial weight.

In practical terms, the usefulness of such a document should also not be underestimated. First, it could help in making progress in the debate about how to “do” research ethics. Second, putting the emphasis on providing explicit, case-sensitive justification rather than on declaring an oath to comply with a set of necessarily abstract rules can have the effect that sponsors, physicians, researchers, and others actively involved in research realize their roles and reflect on their responsibilities. It is to be hoped that debates in the coming months will focus not only on the necessity and appropriateness of the suggested amendments to the new draft Declaration, but also on its overall scope and status.

Harald Schmidt is assistant director of the Nuffield Council on Bioethics, based in London, United Kingdom. The views expressed here are his own and may not be attributed to the Council. Annette Schulz-Baldes is a post-doctoral fellow at the NIH Department of Bioethics, Bethesda, with support by the Swiss National Science Foundation. The opinions expressed here are the author’s and do not reflect the policies and positions of the National Institutes of Health, the U.S. Public Health Service, or the U.S. Department of Health and Human Services.

The authors are grateful for Dave Wendler’s suggestions on the manuscript.