Placebo-controlled trials and active-control trials in the evaluation of new treatments - Part 1: Ethical and scientific issues

In recent years, several authors have argued that placebo-controlled trials are invariably unethical when known effective therapy is available for the condition being studied, regardless of the condition or the consequences o f deferring treatment. Some have also disputed the Value of placebo-control led trials in such a setting, asserting that the comparison of new treatmen t with old treatment is sufficient to establish efficacy and is all that sh ould be of interest. This article considers the ethical concerns about use of placebo controls and describes the limited ability of active-control equ ivalence (also known as noninferiority) trials to establish efficacy of new therapies in many medical contexts. The authors conclude that placebo-cont rolled trials are not uniformly unethical when known effective therapies ar e available; rather. their acceptability is determined by whether the patie nt will be harmed by deferral of therapy. If patients are not harmed, such trials can ethically be carried out. Furthermore, active-control trials, al though valuable, informative, and appropriate in many circumstances, often cannot provide reliable evidence of the effectiveness of a new therapy.