A dilemma for research ethics

The following dilemma arises with regard to using placebo in research: Is it appropriate to let a group of people receive 'trick medicine', i.e. placebo? We can here identify similarities with deception research, in which the participants are plainly 'tricked'.

The question is whether placebo is the only way to conduct the study. Assessing this is especially important if the study involves testing on patients who suffer from serious diseases for which there are drugs available that have an effect on survival or symptoms of the disease.

The Helsinki Declaration on placebo

The Helsinki Declaration states that placebo or untreated control groups may be used only in cases where no known treatment has a proven effect. In other cases, a new treatment must be assessed against the 'best proven' one.

There are, however, still some diseases for which no accepted best treatment exists, or where the documentation for use of an established treatment is deficient. In such cases, the use of placebo may be useful for assessing the effect of a new drug.

The Helsinki Declaration makes exemptions for such cases. Exemptions are also made for trials of methods pertaining to harmless conditions, where the patients receiving placebo are not at risk of sustaining a serious or irreversible injury.

Alternative designs

Placebo studies can be undertaken with modified research designs that are ethically preferable, for the patient as well as for society. Three such alternative designs are used in particular.

  • Three-pronged study. In addition to (1) the new drug, the trial includes (2) a placebo and (3) a best available treatment. The advantage of such a three-pronged study is that it provides more information than studies using only placebo and a new drug. It is possible to show how the new treatment scores in comparison to the established treatment, while also obtaining an evaluation of how the new and established forms of treatment score in comparison to placebo.
  • Add-on study. In add-on studies, new drugs or placebo is administered, as well as a standard treatment. No patients receive inferior treatment to that which they would have received at the outset.
  • Crossover study. In a crossover study, comparisons are made of various treatments administered to one and the same patient. Commonly, two treatments are provided in sequence, often with an interval between them. The treatment to be given first is decided at random. This provides the advantage that fewer patients need to be included in the study.

Placebo research as a separate field

Placebo research is a field of study in its own right, and is especially relevant for brain research. In this case, the research does not aim to find the best medical treatment; it is rather the placebo phenomenon in itself which is studied.

Two Italian brain researchers, Fabrizio Bendetti and Luana Colloca, have studied the effect of the patient's own awareness of receiving analgesic treatment (Source: Weekendavisen, 6 January 2009). Two groups of patients were each administered a dose of morphine. One group received the dose as an injection while the doctor informed them that they would feel alleviation of their pain fairly quickly. The other group were given the injection as an intravenous drip without any form of communication with the doctor, without knowing what they were receiving. Measurements of brain activity in the two groups revealed a difference in the secretion of endorphins, the body's own analgesic neurotransmitter. Group 1 secreted endorphins, whereas the other did not. The doctors concluded that the patients' own confidence in and information about the effects of the substance provide for a better perception of pain alleviation. In other words, they believe that the treatment ritual, i.e. the psychological mechanisms surrounding the treatment, have a definite effect.

This article has been translated from Norwegian by Erik Hansen, Akasie språktjenester AS.