The American Journal of Bioethics

Miller and Brody (2002) have addressed the important problem of using placebo controls in clinical studies when at least some believe that a safe and effective treatment already exists. While they present an interesting discussion of the potential conflict between "the ethics of clinical research and the ethics of clinical medicine," I propose that a more fundamental problem is generated by insisting that "clinical equipoise" exists before a randomized placebo-controlled trial is deemed to be ethical.

What if this "safe and effective treatment" has never been subjected to significant scientific scrutiny and persists only because of the imprimatur of history and the emotions of medical practitioners? Although the concept of clinical equipoise has considerable utility, it also has an inherent and potential flaw—its validity requires the ability to admit that in some cases we do not know. And often this is just what we are unwilling to do. History amply demonstrates (Cohen 1998) that a treatment can be universally held to be correct despite its being inefficacious or even harmful. A few examples are:

1. administration of high concentrations of oxygen to premature babies (resulting in blindness);

2. use of the Vineberg procedure for coronary insufficiency (with the risk of surgery and no real benefit); and

3. superficial temporal to middle cerebral artery anastomosis for cerebral vascular insufficiency (again with surgical risk and no true benefit).

Each of these "treatments" was perpetuated until scientifically valid investigations demonstrated them to be of no value and, in some cases, significantly harmful.

The Vineberg Procedure is notable; although it never restored an adequate coronary blood flow, it did produce subjective effects—a placebo effect well described by Beecher (1961):

At first when this procedure was tried in man, it was believed to be beneficial. Unfortunately, the early studies were uncontrolled: results were not for the reasons thought . . . [and its] benefit was not due to changes in blood flow produced by the ligations. . . . Benefit was due to what happened in the minds of the patients and the surgeons involved.

Such therapies have persisted because of the belief that it would be unethical to conduct a randomized controlled study of an accepted standard treatment. What is unethical, however, is the failure to undertake a randomized controlled study before the therapy becomes embedded in most clinicians' minds as effective.

Even if there is a minority of one who disputes the "accepted therapy" and who offers a sound rationale for his or her view, a randomized clinical trial is both morally appropriate and scientifically necessary.

I certainly agree that it may be unethical for investigators to use a placebo when a proven treatment already exists. However, it is equally unethical for clinicians to cling to a treatment that at worst is harmful and at best is no better than a placebo simply because they are convinced that this untested therapy is efficacious. I maintain that ethics and patient care are best served by insisting that investigators provide cogent reasons for not using a placebo rather than the opposite.