Intended for healthcare professionals


Does the FDA have the authority to trump the Declaration of Helsinki?

BMJ 2009; 338 doi: (Published 21 April 2009) Cite this as: BMJ 2009;338:b1559
  1. Michael D E Goodyear, assistant professor of medicine1,
  2. Trudo Lemmens, associate professor of medicine and law2,
  3. Dominique Sprumont, professor of health law and deputy director3,
  4. Godfrey Tangwa, professor of philosophy4
  1. 1Dalhousie University, Halifax, Nova Scotia, Canada B3H 2Y9
  2. 2University of Toronto, Toronto, Ontario, Canada M5S 2C5
  3. 3Institute of Health Law, University of Neuchâtel, 2000 Neuchâtel, Switzerland
  4. 4University of Yaoundé 1, PO Box 13597, Yaoundé, Cameroon
  1. mgoodyear{at}

    A new rule seems to be more about imperialism than harmonisation

    The Food and Drug Administration (FDA) of the United States has ruled that clinical trials performed outside the US no longer have to conform to the Declaration of Helsinki if used to support applications for registration of products in the US.1 Instead, the International Conference on Harmonisation Good Clinical Practice (GCP) has been designated as the new regulatory standard. This suggestion met considerable opposition from scientists, ethicists, and consumer groups before and during the consultations.1 2 3 The FDA’s justifications included the arguments that it was merely harmonising its regulations with a global standard, and that legal instruments, such as the US Code of Federal Regulations, cannot embed external documents subject to change beyond the agency’s control (dynamic referencing).1 4

    This justification failed to explain why GCP was any different in this respect, or why the declaration and the GCP were considered mutually exclusive.2 Although such dynamic referencing can create legal problems,5 6 because legislatures cannot unreservedly commit to indefinite amendments, the declaration can, and should, be considered a minimum standard that reflects core ethical principles, operationalised through instruments such as the GCP and national regulatory policy. Static referencing of specific versions has not created substantial problems to date, and no reason is given about why this should be a problem now. The concerns remain unresolved,7 but the question of what impact the change will make needs to be answered at both the instrumental (direct) level and the symbolic (indirect) level.

    At first sight, the potential impact seems relatively small. Only a subset of clinical trials performed outside the US are affected, and supporters (mainly from industry) see the differences between the two documents as relatively minor. The real impact cannot be accurately ascertained at present, but it may be much greater than claimed because the US is the world’s largest drug and medical device market.7 In addition, increasing globalisation and movement of clinical trials “off shore” mean that a large proportion of such trials will be used in applications for marketing in the US.8 9

    Some of the differences between the documents, such as those relating to the use of placebo controls in trials, are important and may have motivated the FDA to make this change. The fourth revision of the Declaration of Helsinki (1996) created difficulties for the FDA by restricting the use of placebos where proved interventions had become established. This had major implications for research in resource poor nations, where placebos were being used in such situations.5 Despite heated debate,10 the World Medical Association (WMA) has stood firm on the principle of not withholding effective interventions in its most recent (sixth) revision of 2008.11 The FDA’s decision therefore seems to reinforce its defence of placebo controlled trials.

    Whatever the instrumental impact, in light of this history it is the symbolic aspects of the decision that should concern us most.2 8 The withdrawal of an unproblematic reference has far more significance than simply omitting it. We have grave misgivings about the future of international ethical norms, at least in the US. Despite assurances by the FDA, GCP is not an ethical code, but a procedural regulatory manual based on the regulatory frameworks of the US, Japan, and Europe. Thus, it is a description of existing procedures, not an aspirational document.

    It is not the procedural nuances that are at stake, but rather the moral reasoning that forms the basis of a culture of ethically responsible research.5 11 12 The declaration, along with other international ethical guides,5 remains a signpost for the collaborative development of international ethical principles and practice, the influence of which far exceeds national laws and regulations, and which was extended further in the 2008 revision. The declaration is the primary source and arbiter of research ethics worldwide. It guides legislation and the ethical conduct and oversight of research, particularly in developing countries, which are the site of an increasing share of clinical research.

    This symbolic move away from the declaration contrasts with its growing recognition elsewhere. Although not explicitly part of international or national law, the legal status of codes of ethical principles is recognised. The US Court of Appeals ruled that the declaration (and other conventions) constituted a sufficient customary norm to be considered binding in the Pfizer trovafloxacin case in January 2009.13 The court reversed a dismissal by a lower court of a lawsuit by families of children who had died or were injured in a Nigerian meningitis trial. The children had received this experimental antibiotic, and the court ruled that the declaration established a universal norm prohibiting non-consensual experimentation. At a time of growing concern about the politics and increased globalisation of biomedical research, a more international view of research ethics is needed, rather than primacy of national policies that fall short of accepted principles.9

    The FDA is at best acting as if its standards are distinct from globally accepted norms by pressuring the declaration to agree to its demands. At worst, it is creating an impression that it is more interested in facilitating research than respecting the rights of people who are the subjects of research. This has been variously depicted as entrenching different standards for different parts of the world (ethical pluralism),5 8 establishing the US’s right to unique policies (exceptionalism),2 and one country imposing standards on others (moral imperialism).8 We must hope that the new administration in Washington will review the FDA’s ill advised actions.7

    The declaration and the WMA’s International Code of Ethics contain the crucial statement that a doctor or investigator’s conscience and ethical duty of care must transcend national laws. To be compliant with national laws that respect basic human rights and ethical norms is necessary, but is not in itself a sufficient standard

    How then can we best protect ethical principles in research? Historically, individual conscience, training, and ethical culture were considered sufficient. These have repeatedly fallen short of expectations, however, given the political, social, and fiscal contexts in which research occurs, with its potential for power differentials and conflict of interest. If organisations such as the FDA are unable or unwilling to foster an international culture of ethical research, it must fall to others, such as professional associations, to ensure that ethical reasoning is as central to research as it is to care,10 and that ethical oversight has sufficient powers and resources to be effective. Although transgressions of ethical codes sometimes invite administrative and criminal sanctions, all professional associations have a responsibility to scrutinise the ethical competence, capacity, and practice of their members’ research. Ultimately, ethically responsible research remains a collective responsibility.5


    Cite this as: BMJ 2009;338:b1559


    • Competing interests: None declared.

    • Provenance and peer review: Commissioned; not externally peer reviewed.


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