Because of its placebo-control design, the study by D Tashkin and colleagues (May 19, p 1571)1
of buproprion for smoking cessation seems to be a violation of the 2000 revision of the Declaration of Helsinki's paragraph 29, which calls for testing “against those of the best current prophylactic, diagnostic or therapeutic method.” Moreover, The Lancet
itself seems to be in violation, since paragraph 27 admonishes against publication of reports not in accordance with the Declaration.
But who is out of step? The buproprion study seems ethical on its face and I seriously doubt you would publish it in the journal if you thought otherwise. In my view, this example is but one for which the Helsinki Declaration has overextended its guidelines, and, if literally implemented, would inhibit research useful to many people.
Granted, placebo-control trials deserve careful ethical review, but they can vary widely. On the one hand, the buproprion study deals with a serious situation—tobacco addiction in the context of chronic obstructive pulmonary disease. However, other characteristics of the study support its ethics. First, exposure was short at 6 weeks. Second, all participants, including those receiving placebo, received counselling and verbal support they might not otherwise have received. Third, the behavioural nature of the outcome (smoking cessation) provides a scientific rationale for a placebo design so as to assess any effect over and above placebo effect. Fourth, access to the alternative pharmacological therapy (therapeutic nicotine) is readily available (even over-the-counter in the USA), although most smokers do not use it. Last, society views smoking and smoking cessation as matters of personal discretion. So surely individual participants can also exercise that discretion in the context of research.
Can there be a fixed formula to decide whether a particular placebo-control trial is ethical? Probably not. The buproprion study is simply one example of the varied and complex circumstances of such research. For many trials, such as for certain severe continuous medical disorders, there might well be general agreement on a case-by-case basis that a placebo study is not ethical. Conversely, other types of placebo trials such as for fairly benign disorders might be judged ethical. Generalisation is virtually impossible. Reasonable people will sometimes disagree. Therefore, human judgment is indispensable. Documents such as Helsinki 2000 are invaluable in advancing general principles, but they err when they are so specific as paragraph 29.
Of the three major ethical considerations—beneficence, equity, and autonomy—medical culture prizes beneficence above all. Extreme beneficence, however, can become paternalism. The 2000 Helsinki Declaration seems to suffer from this extremism. Also troubling, in light of the complexity of these issues is the World Medical Association's hubris in asserting primacy through the Declaration, over all national ethics systems and scientific journals. Fortunately, the Association seems to recognise some of the weaknesses and will revisit them.2