International collaborative trials, placebo controls and The Declaration of Helsinki: need for clarification in paragraph 32.
Inequities in socio-economic and healthcare systems between developed and developing countries have been thrown into sharp relief by globalisation. At the same time, pharmaceutical companies have started conducting clinical trials in developing countries in order to reduce their costs substantially. Together, these two developments create ethical challenges for sponsors and researchers of these trials. One such challenge is that of placebo-controlled trials (PCTs). In this paper we analyse Paragraph 32 of the Declaration of Helsinki referring to PCTs, identifying ambiguities in the wording, and then examine three arguments presented by sponsors of PCTs in developing countries, in defence of such trials. These arguments are: (i) a placebo control provides a definitive answer, and is therefore methodologically superior; (ii) placebo-controlled trials are ethical because they serve the principle of utility, and (iii) interpreting the "best current proven intervention" as the local standard of care allows PCTs to be conducted, if the local standard of care is "no treatment". We argue that PCTs are not methodologically superior; nor are they ethically defensible. Other trial designs conforming to the ethics of research are feasible; the reason for conducting PCTs is expediency. We further propose that, given the global applicability of the Declaration of Helsinki, it is imperative to remove the ambiguities in Paragraph 32. In the context of collaborative trials, when a treatment exists, conducting PCTs is ethically unacceptable, irrespective of the geographic location of the trial. Universal standards ought to be applied universally.
Ethox Centre, Department of Public Health, University of Oxford, Oxford, OX3 7LF United Kingdom. aisha.malik@ethox.ox.ac.uk
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D003906:Developing Countries; D004341:Drug Evaluation / Q000941:ethics*; D006381:Helsinki Declaration; D006801:Humans; D010919:Placebos; D028662:Principle-Based Ethics; D016032:Randomized Controlled Trials as Topic / Q000941:ethics*; D059039:Standard of Care; D057212:Therapeutic Equipoise
D010919:Placebos