SUMMARY

The placebo is an inert substance without any specific effect that is administered to please the patient, whom it produces a positive effect derived from his or her own expectations. The term comes from the Middle Ages and its use within the field of modern clinical research is ubiquous. It embraces other phenomena closely related to the so-called placebo effect, as the Hawthorne effect and the regression to the mean, effects that stay under a common consideration in practice. The effect is produced, to a greater or lesser extent, in every pathology, and it is more relevant and constant when the pathology has subjective measuring variables. Its mechanisms of action are badly known; some neuromediators, above all from the endogenous opioid system have been related to it.

In the clinical trial environment, the greatest usefulness of placebos is found to be the fact that they allow both the observer and the observed to keep in hiding and, above all, to add a sensitivity index to the measurements that are carried out. The drug regulatory agencies require, very often, that the trials include a group of patients treated with placebo to this purpose.

Its use, under these circumstances, has been vastly argued among clinical researchers, bioethitists and regulatory agencies. The last reviews of the Declaration of Helsinki, the deontological code related to the most important biomedical research in the world, have had a lot to do with the polemics generated by the use of placebo. In the last review of the Declaration (that of Edinburgh, 2000), an Explanatory Note has been added to the 29th paragraph to satisfy the point of view of the different parties. However, this controversy has not yet been concluded. The methodological and ethical analysis of the clinical trials require an itemized analysis of the use of placebo in each clinical trial. A Decalogue of principles that could act as a guide-list to the above mentioned analysis is introduced.