Declaration of Helsinki redux

The Declaration of Helsinki was revised last week, apparently not to much fanfare. In fact, I could only find two news articles on the web about it (here and here), and Science published a piece about the lingering controversies surrounding the Declaration and its revisions. But other than that, the revised Declaration seems to have generated little interest, excitement or opposition. For those unfamiliar with this document, or the organization that acts as its custodian, the Declaration of Helsinki is a statement of principles concerning medical research with human participants developed by the World Medical Association (WMA). There is nothing particularly Finnish about the Declaration, only the name -- it happened to be where the WMA General Assembly first adopted it in 1964 -- but the name lends the document a certain austere, Nordic and 'internationalist' feel. This is only fitting for a document that is regarded by some as a cornerstone of research ethics with global reach.

Careful and prolonged attention is bestowed to the precise wording of the Declaration, as though the lives of millions depended on each word. So what is new about the revision? Three main changes seem to stand out:

• Registering clinical trials. Paragraph 19 of the revised Declaration states: "Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject." Apparently representatives of pharmaceutical companies are unhappy with this new paragraph, because it implies that all phases of clinical trials must be registered, even phase 1 trials. They argue that such registration drives up research costs and because it involves disclosure of what research projects are doing, it could violate intellectual property rights. On the other hand, it is predictable that something would be added to the Declaration about registering clinical trials (without being specific about any phase) after the high-profile injuries to humans involved in the Northwick Park TGN1412 Phase I trial. Nevermind: the pharmaceutical industry will probably just ignor this paragraph anyway.

• The use of placebos in clinical trials. When is it ethically acceptable to have a placebo arm in a clinical trial? Paragraph 32 is meant to deal with this sticky issue, and the answer (to paraphrase) is that a new experimental intervention should be tested against the 'best current proven intervention', except when (a) no current proven intervention exists, or (b) where there are really good scientific reasons to use a placebo and where those who receive the placebo will not be subject to any risk of serious or irreverible harm. The paragraph adds: "Extreme care must be taken to avoid abuse of this option." Reports on the revision suggest that this Paragraph is really restrictive of placebo use -- which some find troubling because it could hamper the progress of science, and others find noble because it protects research participants and does not bow down to pharmaceutical industry interests. Nevermind: FDA recently implemented rules allowing applicants for new drug approvals bypass the Declaration ofHelsinki when conducting certain trials overseas.

• Post-trial benefits. The concern that research participants (particularly those in impoverished countries) ought to get something back from their participation has been growing in reserach ethics circles in recent years. There is a feeling that it is unjust for drugs to be tested on the world's poor, while the benefits of the research mostly accrue to the richer nations -- in short, the poor are good enough to be tested on, but not good enough to have access to the finished product. The new Paragraph 33 reads: "At the conclusion of the study, patients entered into the study are entitled to be informed about the outcome of the study and to share any benefits that result from it, for example, access to interventions identified as beneficial in the study or to other appropriate care and benefits." For better or for worse, this leaves the question what counts as an 'appropriate benefit' wide open. A research team could say that there were things in a study that the participants got that non-participants didn't get, and that is 'benefit' enough to fulfill the requirements of the Declaration of Helsinki. Nevermind.