The FDA and Helsinki

To gain entry to the lucrative American market, newly developed drugs must be licensed by the U.S. Food and Drug Administration. Since 1975, the FDA has required applications for licensure from research studies conducted outside the United States to comply with the Declaration of Helsinki, one of the most influential international codes of research ethics. But last October, the FDA announced that it will now use Good Clinical Practice (GCP) regulations, an international quality standard written by the International Conference on Harmonisation, to ensure that foreign-based studies have been conducted ethically. What is the motivation behind the FDA’s change of regulatory requirements, and what is the larger ethical significance of this move as ever more clinical trials are outsourced to resource-poor, developing countries?

According to the FDA, the decision to adopt the GCP and ditch the Declaration of Helsinki is driven by concerns about coherence and jurisdiction. The Declaration of Helsinki has undergone nine revisions since its introduction in 1964, including four since 2000. When researchers attempt to adhere to a changing document, confusion can arise. Its changes are also beyond FDA control, which means provisions in the declaration could clash with U.S. law. Besides, the FDA implies that departing from the declaration is no great ethical loss: it argues that the GCP provides equal protection to research participants, requires all research to be reviewed by local ethics committees, and—since it is more detailed than the declaration—may provide better practical guidance for the proper conduct of clinical trials.

Critics see the FDA’s move differently. They contend that the GCP is a rather dry set of regulatory procedures, not a substantive and authoritative ethics document. Unlike the declaration, the GCP was created by a small number of regulatory agencies and drug companies from industrialized nations, with little input from developing countries, and it is silent on disclosures of conflict of interest, public disclosure of study design, publication of negative findings, research responsiveness to health needs of local populations, restrictions on placebo controls, and posttrial access to successfully tested drugs. This casts serious doubt on the claim that the GCP and the declaration are equivalent.

The argument that adopting the GCP will lead to less confusion is also dubious: what if some countries adopt the GCP while others stick with the Declaration of Helsinki? How will the FDA’s decision affect already-challenging ethical review of multisite international drug trials? What if some journals agree to publish studies that violate declaration provisions while others do not? Given these questions about the GCP’s adequacy, critics see other motivations: they accuse the FDA of shopping for regulations that better serve drug company interests, allowing (and even encouraging) studies that would not be approved at home to be undertaken in resource-poor countries abroad.

The critics are largely right. The declaration, for all its shortcomings, at least addresses concerns about inequality and social justice when conducting research with poor and vulnerable populations. Its controversial revisions were responses to legitimate worries. Robert Temple, director of the Office of Medical Policy at the FDA’s Center for Drug Evaluation and Research, has been quoted as saying that the declaration has unfortunately “moved from a purely ethical document to a document that is increasingly interested in social justice.” The FDA has apparently adopted the GCP to provide guidance for research in developing countries while steering clear of sticky questions about justice and inequity. But if you remove those issues, what kind of ethics guidance is left? Or rather, whose interests are served?

The FDA decided to adopt the GCP during the Bush administration, in a climate marked by reluctance to engage with any international regulation not suiting U.S. interests. The Obama administration should adopt research ethics regulation that places the interests of research participants and communities, as well as concerns about social justice, back in the center of the picture, where they belong.