The Placebo Problem, Part 15: Ethical Considerations

This is the fifteenth and final installment of our look at the increasingly high placebo response that is plaguing clinical trials in analgesia and psychiatry. Read the rest of the posts in the series here.

As our Placebo Problem series draws to a close, we conclude by taking a brief look at three ethical issues that surround the use of placebos in clinical trials. A complete discussion of these issues is well beyond the scope of a single blog post, so we also provide links to articles that can provide a deeper understanding. 

When is it ethical to use placebos in clinical trials?
First, we turn to the most obvious ethical issue surrounding placebo-controlled trials – under what circumstances is the use of placebos morally correct? According to the World Medical Association’s Declaration of Helsinki, which addresses ethical issues surrounding the use of human subjects in research, placebo use is acceptable when there is no proven acceptable treatment for the condition, when “for compelling and scientifically sound methodological reasons” it’s necessary to determine the experimental treatment’s efficacy or safety, and when patients who receive placebo “will not be subject to additional risks of serious or irreversible harm as a result of not receiving the best proven intervention.” However, determining which methodological reasons and risks of harm fall under this description is difficult at best. This article discusses the issue further.

Can open-label placebos sidestep the issue of deception?
Historically, deception has been considered a major component of placebos, and one of the main ethical problems of placebo use. However, perhaps surprisingly, a small body of literature suggests that placebos are still effective even when patients know they are receiving a placebo.

A few such open-label placebo trials have been conducted in the last decade. In the most well-known study, 80 patients with irritable bowel syndrome (IBS) were randomized to receive either no treatment or an open-label placebo, which they were told was a non-active placebo pill that has been shown reduce IBS symptoms. Participants who received the open-label placebo had significantly greater symptom improvement than those who received no treatment.

Although more research is certainly needed, these results raise the possibility that deception is not integral to the placebo effect, and therefore not needed. To learn more about the ethics of open-label placebos, please see this article.

Is truly informed consent the best option?
In clinical trials, participants are informed of the possible side effects that may result from the experimental treatment. But, the mere suggestion that these negative outcomes could occur may lead to a greater incidence of them, a phenomenon known as the nocebo effect. In other words, the side effects become a self-fulfilling prophecy. As we saw in our nocebo post a few weeks ago, the nocebo effect can not only increase symptoms but also leads to patient distress. It can also lead to medication nonadherence, participant dropouts, and the need for additional medications to treat the added symptoms. Traditionally, a full disclosure of potential side effects is considered the most ethical course of action, but, at least in some cases, should we consider only disclosing the most critical information about possible adverse events in order to avoid undue patient distress? For an additional discussion of this issue, check out this article.

We hope you’ve found our Placebo Problem series helpful. Be sure to check out the rest of the series!

Author Details

Scott Millard
Scott Millard, Executive Director, Strategic Development, Analgesia, has worked in the clinical research industry since 1991. Mr. Millard joined Premier Research in 1997. Since joining Premier, he has served in a variety of roles with increasing scope and responsibility inclusive of Senior Clinical Research Associate, Team Lead, Senior Manager, Project Manager, Senior Project Manager, Project Director, Senior Director and Executive Director. Mr. Millard served at a director level managing project managers and sponsor programs for more than 13 years specializing in Analgesia and Rheumatology.
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