Ethical Concerns in Placebo-Controlled Studies: An Analytical Approach *

Abstract

The fifty-second revision of the Declaration of Helsinki included a statement that proscribed, on an ethical basis, the use of placebo in clinical research when treatment is available. Scientific methods suggest that this determination could affect the validity of research in conditions that show placebo response. Researchers became concerned about the impact that this could have on the quality of drug development. Although the clarification to the Declaration of Helsinki reversed this position, the situation called for revisions to the ethical implications of the use of placebo. Most authors agree that placebo is unacceptable in life-threatening diseases or when there is a risk of irreversible damage, but other instances require evaluation on a case-to-case basis. Institutional review boards (IRBs) have to consider the principles of research ethics when deciding whether to approve or reject placebo-controlled studies. Some algorithms to review placebo-controlled studies on ethical grounds have been published Based on these efforts and the ethical and methodological considerations derived from our own IRB experiences, the authors of this paper have designed a checklist to assist IRBs in the evaluation of placebo-controlled studies. The checklist was tested in IRB meetings and modified to better reflect the needs expressed in the discussions. It has been useful in guiding deliberations and obtaining consistency in the evaluation of placebo-controlled studies.