By Marcia Angell, M.D.
An essential ethical condition for a randomized clinical trial comparing two treatments for a disease is that there be no good reason for thinking one is better than the other.1,2 Usually, investigators hope and even expect that the new treatment will be better, but there should not be solid evidence one way or the other. If there is, not only would the trial be scientifically redundant, but the investigators would be guilty of knowingly giving inferior treatment to some participants in the trial. The necessity for investigators to be in this state of equipoise2 applies to placebo-controlled trials, as well. Only when there is no known effective treatment is it ethical to compare a potential new treatment with a placebo. When effective treatment exists, a placebo may not be used. Instead, subjects in the control group of the study must receive the best known treatment. Investigators are responsible for all subjects enrolled in a trial, not just some of them, and the goals of the research are always secondary to the well-being of the participants. Those requirements are made clear in the Declaration of Helsinki of the World Health Organization (WHO), which is widely regarded as providing the fundamental guiding principles of research involving human subjects.3 It states, “In research on man [sic], the interest of science and society should never take precedence over considerations related to the wellbeing of the subject,” and “In any medical study, every patient — including those of a control group, if any — should be assured of the best proven diagnostic and therapeutic method.”
Read more: NEJM