Адамдарға жасалатын медициналық тәжірибелер этикасы: Хельсинки Декларациясы

Document outlining the ethics of human medical experimentation
the human medical experimentation ethics document
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 the 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." 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.

The Declaration was originally adopted in June 1964 in Helsinki, Finland, and has since undergone seven revisions (the most recent at the General Assembly in October 2013) and two clarifications, growing considerably in length from 11 paragraphs in 1964 to 37 in the 2013 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 [3a]. 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).

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." 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.

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.

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.

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. This led to the US Food and Drug Administration (FDA) ignoring this and all subsequent revisions.

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, 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. Recommendations included limiting the document to basic guiding principles. Many editorials and commentaries were published reflecting a variety of views including concerns that the Declaration was being weakened by a shift towards efficiency based and utilitarian standards (Rothman, Michaels and Baum 2000), and an entire issue of the Bulletin of Medical Ethics was devoted to the debate. Others saw it as an example of Angell's 'Ethical Imperialism', an imposition of US needs on the developing world, and resisted any but the most minor changes, or even a partitioned document with firm principles and commentaries, as used by CIOMS. The idea of ethical imperialism was brought into high attention with HIV testing, as it was strongly debated from 1996 to 2000 because of its centrality to the issue of regimens to prevent its vertical transmission.

Given the lack of consensus on many issues prior to the fifth revision it is no surprise that the debates continued unabated. The debate over these and related issues also revealed differences in perspectives between developed and developing countries. Zion and colleagues (Zion 2000) Given the previous lack of consensus, this merely shifted the ground of debate,
but again a commitment was made to protecting the vulnerable. A new working group examined article 30, and recommended not amending it in January 2004. Later that year the American Medical Association proposed a further note of clarification that was incorporated. In this clarification the issue of post trial care now became something to consider, not an absolute assurance. Despite these changes, as Macklin predicted, consensus was no closer and the Declaration was considered by some to be out of touch with contemporary thinking, and even the question of the future of the Declaration became a matter for conjecture. Considerable deliberation has taken place regarding the most effective approach to address the concerns related to paragraph 30. Two distinct working groups have explored this matter and put forth various suggestions, which encompass potential revisions to the paragraph, the inclusion of a preamble, and the introduction of a clarifying note (similar to what was incorporated into paragraph 29). At a gathering of the WMA Council in France in May 2004, the American Medical Association presented the subsequent clarifying statement:

The WMA reaffirms its stance that it is imperative, within the study planning phase, to identify provisions for post trial access by research participants to prophylactic, diagnostic, and therapeutic procedures deemed beneficial in the study or to access to other appropriate healthcare. The specifics of post trial access arrangements or alternative care should be outlined in the study protocol, enabling the ethical review committee to evaluate these provisions during its assessment. In November 2007 a draft revision was issued for consultation until February 2008, and led to a workshop in Helsinki in March. Those comments were then incorporated into a second draft in May. Further workshops were held in Cairo and São Paulo and the comments collated in August 2008. A final text was then developed by the Working Group for consideration by the Ethics Committee and finally the General Assembly, which approved it on October 18. Public debate was relatively slight compared to previous cycles, and in general supportive. Input was received from a wide number of sources, some of which have been published, such as Feminist Approaches to Bioethics. Others include CIOMS and the US Government.

The most recent iteration of Helsinki (2013) was reflective of the controversy regarding the standard of care that arose from the vertical transmission trials. The revised declaration of 2013 also highlights the need to disseminate research results, including negative and inconclusive studies and also includes a requirement for treatment and compensation for injuries related to research. In addition, the updated version is felt to be more relevant to limited resource settings—specifically addressing the need to ensure access to an intervention if it is proven effective.

The controversies and national divisions over the text have continued. The US FDA rejected the 2000 and subsequent revisions, only recognizing the third (1989) revision,
a final rule was issued on April 28, 2008, replacing the Declaration of Helsinki with Good Clinical Practice effective October 2008. This has raised a number of concerns regarding the apparent weakening of protections for research subjects outside the United States. The NIH training in human subject research participant protection no longer refers to the Declaration of Helsinki. The European Union similarly only cites the 1996 version in the EU Clinical Trials Directive published in 2001. The European Commission, however, does refer to the 2000 revision. While the Declaration has been a central document guiding research practice, its future has been called into question. Challenges include the apparent conflict between guides, such as the CIOMS and Nuffield Council documents. Another is whether it should concentrate on basic principles as opposed to being more prescriptive, and hence controversial. It has continually grown and faced more frequent revisions. Carlson raises the question as to whether the document's utility should be more formally evaluated, rather than just relying on tradition.

There appears to be a noticeable trend toward more frequent changes in the Declaration of Helsinki (DoH). However, it's important to note that only two of the revisions, in 1975 and 2000, introduced significant alterations.

2014: This was the 50th anniversary of declaration. To mark this special occasion, the WMA published "The World Medical Association Declaration of Helsinki: 1964 2014 50 Years of Evolution of Medical Research Ethics.". 2016: The Declaration of Taipei on Ethical Considerations regarding Health Databases and Biobanks finally complemented the Declaration of Helsinki.

U. S. National Institutes of Health (NIH) Protecting Human Subject Research Participants

International response to Helsinki VI (2000). WMA 2001