Declaration of Helsinki

The Declaration of Helsinki was developed by the World Medical Association^[1] (WMA), as a set of ethical principles for the medical community regarding human experimentation, and is widely regarded as the cornerstone document of human research ethics. (WMA 2000, Bošnjak 2001, Tyebkhan 2003)

It is not a legally binding instrument in 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 (Human and Fluss 2001). 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" (Human and Fluss 2001).

The 1975 revision was almost twice the length of the original, and 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 (Riis 1977). 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 and provisions were made for safeguarding animals. Protocols now had to state explicitly that they adhered to the Declaration (Article I.12).

Fifth revision (2000)

Aftermath

Given the lack of consensus on many issues prior to the fifth revision it is no surprise that the debates continued unabated (Macklin 2001, Williams 2004). The debate over these and related issues also revealed differences in perspectives between developed and developing countries (Loff 2000, Schuklenk 2001; CMAJ 2003). Zion and colleagues (Zion 2000, Loff and Black 2000, Loff 2000) have attempted to frame the debate more carefully, exploring the broader social and ethical issues and the lived realities of potential subjects lives as well as acknowledging the limitations of absolute universality in a diverse world, particularly those framed in a context that might be considered elitist and structured by gender and geographic identity. As Macklin (2001) points out, both sides may be right, since justice "is not an unambiguous concept".

Clarifications of Articles 29, 30 (2002-2004)

Eventually Notes of Clarification (footnotes) to articles 29 and 30 were added in 2002 and 2004 respectively, predominantly under pressure from the US (CMAJ 2003, Blackmer 2005). The 2002 clarification to Article 29 was in response to many concerns about WMA's apparent position on placebos. As WMA states in the note, there appeared to be 'diverse interpretations and possibly confusion'. It then outlined circumstances in which a placebo might be 'ethically acceptable', namely 'compelling...methodological reasons', or 'minor conditions' where the 'risk of serious or irreversible harm' was considered low. Effectively this shifted the WMA position to what has been considered a 'middle ground' (Emmanuel 2001, Huston 2001). Given the previous lack of consensus, this merely shifted the ground of debate, ^[2] which now extended to the use of the 'or' connector. For this reason the footnote indicates that the wording must be interpreted in the light of all the other principles of the Declaration.

Article 30 was debated further at the 2003 meeting, with another proposed clarification (CMAJ 2003) but did not result in any convergence of thought, and so decisions were postponed for another year (De Roy 2004, WMA 2003), 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. ^[3] Later that year the American Medical Association proposed a further note of clarification that was incorporated (Blackmer 2005). 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 (Lie 2004), and even the question of the future of the Declaration became a matter for conjecture (Wolinsky 2006)

Sixth revision (2008)

The sixth revision cycle commenced in May 2007. This consisted of a call for submissions, completed in August 2007. The terms of reference included only a limited revision compared to 2000.^[4]

^[5] was issued for consultation till February 2008, and led to a workshop in Helsinki in March. ^[6] Those comments were then incorporated into a second draft in May. ^{[7] [8]} 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. ^[9] Input was received from a wide number of sources, some of which have been published, such as Feminist Approaches to Bioethics. ^[10] Others include CIOMS and the US Government. ^[11]

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.^{[citation needed]}

Basic principles

The fundamental principle is respect for the individual (Article 8), their 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 subject'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 recognised 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 subject's best interest. In which case their assent 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 publications 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 utilised (Article 29). The interests of the subject 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. ^[12] 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.

Future

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 (Wolinsky 2006), and in 2006 announced it would eliminate all reference to the Declaration. After consultation, which included expressions of concern, ^[13] a final rule was issued on April 28 2008 replacing the Declaration of Helsinki with Good Clinical Practice effective October 2008. ^[14] This has raised a number of concerns regarding the apparent weakening of protections for research subjects outside the United States. ^{[15] [16] [17] [18] [19] [20] [21] [22] [23]} The NIH training in human subject research participant protection no longer refers to the Declaration of Helsinki. The European Commission refers to the fourth (1996) 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 2004). The recent controversies undermine the authority of the document, as does the apparent desertion by major bodies, and any rewording must embrace deeply and widely held values, since continual shifts in the text do not imply authority.

Carlson raises the question as to whether the document's utility should be more formally evaluated, rather than just relying on tradition.

References

External links

Declaration of Helsinki - Current (2008) version