The Declaration of Helsinki (DoH, ) is a set of ethical principles regarding human experimentation developed originally in 1964 for the medical community by the World Medical Association (WMA). It is widely regarded as the cornerstone document on human research ethics.
It is not a legally binding instrument under international law, but instead draws its authority from the degree to which it has been codified in, or influenced, national or regional legislation and regulations. Its role was described by a Brazilian forum in 2000 in these words: "Even though the Declaration of Helsinki is the responsibility of the World Medical Association, the document should be considered the property of all humanity."
Principles The Declaration is morally binding on physicians, and that obligation overrides any national or local laws or regulations, if the Declaration provides for a higher standard of protection of humans than the latter. Investigators still have to abide by local legislation but will be held to the higher standard.
Basic principles
The fundamental principle is respect for the individual (Article 8), his or her right to self-determination and the right to make informed decisions (Articles 20, 21 and 22) regarding participation in research, both initially and during the course of the research. The investigator's duty is solely to the patient (Articles 2, 3 and 10) or volunteer (Articles 16, 18), and while there is always a need for research (Article 6), the participant's welfare must always take precedence over the interests of science and society (Article 5), and ethical considerations must always take precedence over laws and regulations (Article 9).
The recognition of the increased vulnerability of individuals and groups calls for special vigilance (Article 8). It is recognized that when the research participant is incompetent, physically or mentally incapable of giving consent, or is a minor (Articles 23, 24), then allowance should be considered for surrogate consent by an individual acting in the participant's best interest, although his or her consent should still be obtained if at all possible (Article 25).
Operational principles Research should be based on a thorough knowledge of the scientific background (Article 11), a careful assessment of risks and benefits (Articles 16, 17), have a reasonable likelihood of benefit to the population studied (Article 19) and be conducted by suitably trained investigators (Article 15) using approved protocols, subject to independent ethical review and oversight by a properly convened committee (Article 13). The protocol should address the ethical issues and indicate that it is in compliance with the Declaration (Article 14). Studies should be discontinued if the available information indicates that the original considerations are no longer satisfied (Article 17). Information regarding the study should be publicly available (Article 16). Ethical principles extend to publication of the results and consideration of any potential conflict of interest (Article 27). Experimental investigations should always be compared against the best methods, but under certain circumstances a placebo or no treatment group may be utilized (Article 29). The interests of the participant after the study is completed should be part of the overall ethical assessment, including assuring their access to the best proven care (Article 30). Wherever possible unproven methods should be tested in the context of research where there is reasonable belief of possible benefit (Article 32).
Additional guidelines or regulations Investigators often find themselves in the position of having to follow several different codes or guidelines, and are therefore required to understand the differences between them. One of these is Good Clinical Practice (GCP), an international guide, while each country may also have local regulations such as the Common Rule in the US, in addition to the requirements of the FDA and Office for Human Research Protections (OHRP) in that country. There are a number of available tools which compare these. Other countries have guides with similar roles, such as the Tri-Council Policy Statement in Canada. Additional international guidelines include those of the CIOMS, Nuffield Council and UNESCO.
History The Declaration was originally adopted in June 1964 in Helsinki, Finland, and has since undergone eight revisions (the most recent at the General Assembly in October 2024) and two clarifications, growing considerably in length from 11 paragraphs in 1964 to 37 in the 2024 version. The Declaration is an important document in the history of research ethics as it is the first significant effort of the medical community to regulate research itself, and forms the basis of most subsequent documents.
Prior to the 1947 Nuremberg Code there was no generally accepted code of conduct governing the ethical aspects of human research, although some countries, notably Germany and Russia, had national policies. The Declaration developed the ten principles first stated in the Nuremberg Code, and tied them to the Declaration of Geneva (1948), a statement of physicians' ethical duties. The Declaration more specifically addressed clinical research, reflecting changes in medical practice from the term 'Human Experimentation' used in the Nuremberg Code. A notable change from the Nuremberg Code was a relaxation of the conditions of consent, which was 'absolutely essential' under Nuremberg. Now doctors were asked to obtain consent 'if at all possible' and research was allowed without consent where a proxy consent, such as a legal guardian, was available (Article II.1).
First revision (1975) The 1975 revision was almost twice the length of the original. It clearly stated that "concern for the interests of the subject must always prevail over the interests of science and society."Vanderpool, Harold Y. (1996). The Ethics of Research Involving Human Subjects: Facing the 21st Century. Frederick, Maryland: University Publishing Group, Inc. p. 85. It also introduced the concept of oversight by an 'independent committee' (Article I.2) which became a system of Institutional Review Boards (IRB) in the US, and research ethics committees or ethical review boards in other countries. In the United States regulations governing IRBs came into effect in 1981 and are now encapsulated in the Common Rule. Informed consent was developed further, made more prescriptive and partly moved from 'Medical Research Combined with Professional Care' into the first section (Basic Principles), with the burden of proof for not requiring consent being placed on the investigator to justify to the committee. 'Legal guardian' was replaced with 'responsible relative'. The duty to the individual was given primacy over that to society (Article I.5), and concepts of publication ethics were introduced (Article I.8). Any experimental manoeuvre was to be compared to the best available care as a comparator (Article II.2), and access to such care was assured (Article I.3). The document was also made gender neutral.
Second to fourth revisions (1975–2000) Subsequent revisions between 1975 and 2000 were relatively minor, so the 1975 version was effectively that which governed research over a quarter of a century of relative stability.
Second and third revisions (1983, 1989) The second revision (1983) included seeking the consent of minors where possible. The third revision (1989) dealt further with the function and structure of the independent committee. However, from 1993 onwards, the Declaration was not alone as a universal guide since CIOMS and the World Health Organization (WHO) had also developed their International Ethical Guidelines for Biomedical Research Involving Human Subjects.
Fourth revision (1996)
Background The AIDS Clinical Trials Group (ACTG) Study 076 of 100 Zidovudine in maternal-infant transmission of HIV had been published in 1994. This was a placebo controlled trial which showed a reduction of nearly 70% in the risk of transmission, and Zidovudine became a de facto standard of care. The subsequent initiation of further placebo controlled trials carried out in developing countries and funded by the United States Centers for Disease Control or National Institutes of Health raised considerable concern when it was learned that patients in trials in the US had essentially unrestricted access to the drug, while those in developing countries did not. Justification was provided by a 1994 WHO group in Geneva which concluded "Placebo-controlled trials offer the best option for a rapid and scientifically valid assessment of alternative antiretroviral drug regimens to prevent transmission of HIV". These trials appeared to be in direct conflict with recently published guidelines for international research by CIOMS, which stated "The ethical standards applied should be no less exacting than they would be in the case of research carried out in country", referring to the sponsoring or initiating country. In fact a schism between ethical universalism and ethical pluralism was already apparent before the 1993 revision of the CIOMS guidelines.
Fourth revision In retrospect, this was one of the most significant revisions because it added the phrase "This does not exclude the use of inert placebo in studies where no proven diagnostic or therapeutic method exists" to Article II.3 ("In any medical study, every patient--including those of a control group, if any—should be assured of the best proven diagnostic and therapeutic method."). Critics claimed that the Zidovudine trials in developing countries were in breach of this because Zidovudine was now the best proven treatment and the placebo group should have been given it. This led to the US Food and Drug Administration (FDA) ignoring this and all subsequent revisions.Temple R. Impact of the Declaration of Helsinki on medical research from a regulatory perspective. Address to the Scientific Session, World Medical Association General Assembly, September 2003.
Fifth revision (2000)
Background Following the fourth revision in 1996 pressure began to build almost immediately for a more fundamental approach to revising the declaration. The later revision in 2000 would go on to require monitoring of scientific research on human subjects to assure ethical standards were being met. In 1997 Lurie and Wolfe published their seminal paper on HIV trials, raising awareness of a number of central issues. These included the claims that the continuing trials in developing countries were unethical, and pointing out a fundamental discrepancy in decisions to change the study design in Thailand but not Africa. The issue of the use of placebo in turn raised questions about the standard of care in developing counties and whether, as Marcia Angell wrote "Human subjects in any part of the world should be protected by an irreducible set of ethical standards" (1988). The American Medical Association put forward a proposed revision in November that year,General Assembly WMA Hamburg, Germany 1997 and a proposed revision (17.C/Rev1/99) was circulated the following year, causing considerable debate and resulting in a number of symposia and conferences.