Declaration of Helsinki

History and Current Status

Before World War II, no formal international statement of ethical principles to guide research with human participants existed, leaving researchers to rely on organizational, regional, or national policies or their own personal ethical guidelines. After atrocities were found to have been committed by Nazi medical researchers using involuntary, unprotected participants drawn from concentration camps, the 1947 Nuremberg Code was established. This was followed in 1948 by the WMA's Declaration of Geneva, a statement of ethical duties for physicians. Both documents influenced the development of the Declaration of Helsinki, adopted in 1964 by the WMA. The initial Declaration, 11 paragraphs in length, focused on clinical research trials. Notably, it relaxed conditions for consent for participation, changing the Nuremberg requirement that consent is “absolutely essential” to instead urge consent “if at all possible” but to allow for proxy consent, such as from a legal guardian, in some instances.

The Declaration has been revised six times. The first revision, conducted in 1975, expanded the Declaration considerably, nearly doubling its length, increasing its depth, updating its terminology, and adding concepts such as oversight by an independent committee. The second (1983) and third (1989) revisions were comparatively minor, primarily involving clarifications and updates in terminology. The fourth (1996) revision also was minor in scope but notably added a phrase that effectively precluded the use of inert placebos when a particular standard of care exists.

The fifth (2000) revision was extensive and controversial. In the years leading up to the revision, concerns were raised about the apparent use of relaxed ethical standards for clinical trials in developing countries, including the use of placebos in HIV trials conducted in sub-Saharan Africa. Debate ensued about revisions to the Declaration, with some arguing for stronger language and commentary addressing clinical trials and others proposing to limit the document to basic guiding principles. Although consensus was not reached, the WMA approved a revision that restructured the document and expanded its scope. Among the more controversial aspects of the revision was the implication that standards of medical care in developed countries should apply to any research with humans, including that conducted in developing countries. The opposing view held that when risk of harm is low and there are no local standards of care (as is often the case in developing countries), placebo-controlled trials are ethically acceptable, especially given their potential benefits for future patients. Debate has continued on these issues, and cross-national divisions have emerged. The [Page 339]U.S. Food and Drug Administration rejected the fifth revision because of its restrictions on the use of placebo conditions and has eliminated all references to the Declaration, replacing it with the Good Clinical Practice guidelines, an alternative internationally sanctioned ethics guide. The National Institutes of Health training in research with human participants no longer refers to the Declaration, and the European Commission refers only to the fourth revision.

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