Thursday, March 20, 2014

Test TubeOn the 50th anniversary of the Declaration of Helsinki,1 the World Medical Association (WMA) revised this important document that set the bioethical principles and standards for the basic rights of individuals involved in medical research.

The original Declaration of Helsinki (1964), along with the Nuremberg Code (1947),2 was born from a history of abuses, of people used in unethical medical experiments during the Second World War. These groundbreaking documents established the international legal framework of medical research standards for human subjects’ research and were incorporated into national legislations including Title 45 Part 46 (Protection of Human Subjects) of the U.S. Code of Federal Regulations.3 The Declaration is frequently referenced by researchers and research participants, ethics review committees, and funding agencies all over the world to establish the ethical appropriateness of clinical trials.

Helsinki Quote 1The 64th WMA General Assembly at Fortaleza, Brazil, adopted the new, revised version of the Declaration in October 2013. This marks the seventh edition of the guidelines. The substantially revised new version has the following subsections:

  • Preamble
  • General Principles
  • Risks, Burdens, and Benefits
  • Vulnerable Groups and Individuals
  • Scientific Requirements and Research Protocols
  • Research Ethics Committees
  • Privacy and Confidentiality
  • Informed Consent
  • Use of Placebo
  • Post-trial Provisions
  • Research Registration and Publication and Dissemination of Results
  • Unproven Interventions in Clinical Practice

Sections related to the changing landscape of medical research received major updates.4 The growing number of international studies in countries with limited resources presents new ethical challenges. The post-trial access to care, use of placebo and unproven interventions, provision of underrepresented groups’ access to research, and compensation and treatment for intervention-related injuries are all issues increasingly important to developing countries. The acknowledgment of the role of cultural differences in the consenting process and the need to simplify the informed consent forms by using graphics and video presentations are also highlighted in the revised Declaration. The document emphasizes the key role of the ethics committees and institutional review boards in enforcing basic bioethical principles and the importance of disseminating results from medical research, even those that are negative or inconclusive.

The revised Declaration addresses some of the criticism received for earlier versions but remains somewhat controversial.5 The Declaration is an international policy statement that spells out the moral obligations of physicians performing medical research and has no legal authority in any particular country. On the other hand, it declares the primacy of ethical standards over laws and regulations.

Helsinki Quote 2aMany national regulatory agencies, including the U.S. Food and Drug Administration (FDA) adopted the ethical principles of the earlier versions. Subsequent revisions, especially the fifth revision in year 2000, introduced more contentious issues, including social justice, performing research in developing countries, and limiting the use of placebo. The FDA first rejected the 2000 version and then, in a controversial decision, abandoned the Declaration in favor of the less restrictive International Conference on Harmonization’s Guideline for Good Clinical Practice for international drug trials.6,7,8

One of the contentious issues is the compensation for research related injuries. According to the Declaration, “Appropriate compensation and treatment for subjects who are harmed as a result of participating in research must be ensured.” In the United States, coverage for research-related injuries varies by institution and is not mandatory. Some developing countries, however, increasingly adopt the Declaration’s recommendation requiring financial compensation and treatment for research related harm. Last year, about 40 National Institutes of Health (NIH)-funded clinical trials were suspended in India when the Indian Ministry of Health and Family Welfare imposed strict new rules for trial related injury or death.9 Liability includes cases where a participant suffers because he or she received a placebo or did not receive the therapeutic benefit promised by the trial drug. Some of the halted trials have restarted as the result of intensive negotiations between the NIH and the Indian Health Authorities, but the excessive new rules caused serious disruption in research.10

As a “living document”, the Declaration of Helsinki remains relevant in spite of these controversies and criticism, especially for countries with limited resources. The regular updates reflect the rapidly evolving new scientific discoveries and the ethical challenges that those bring to the health care professional community.

References

  1. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013 Nov 27;310(20):2191–1194.
  2. U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health. The Nuremberg Code. Available at: http://www.hhs.gov/ohrp/archive/nurcode.html. Accessed March 11, 2014.
  3. U.S. Government Printing Office. Public welfare. Available at: http://www.gpo.gov/fdsys/pkg/CFR-2000-title45-vol1/content-detail.html. Accessed March 12, 2014.
  4. Ndebele P. The Declaration of Helsinki, 50 years later. JAMA. 2013 Nov 27;310(20):2145–2146.
  5. Millum J, Wendler D, Emanuel EJ. The 50th anniversary of the Declaration of Helsinki: Progress but many remaining challenges. JAMA. 2013 Nov 27;310(20):2143–2144.
  6. Human subject protection; foreign clinical studies not conducted under an investigational new drug application. Federal Register. 2008 Apr 28;73(82):22800–22816.
  7. Lurie P, Greco DB. U.S. exceptionalism comes to research ethics. Lancet. 2005 Mar;365(9465):1117–1119.
  8. Kimmelman J, Weijer C, Meslin EM. Helsinki discords: FDA, ethics, and international drug trials. Lancet. 2009 Jan 3;373(9657):13–14.
  9. Bhattacharjee Y. Public health. Clinical trials paused as India adopts new rules. Science. 2013 Jul 26;341(6144):327.
  10. Reardon S. NIH makes wary return to India. Nature. 2014 Feb 13;506(7487):143–144.

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