The American Journal of Bioethics

With his introduction of the concept of clinical equipoise, Benjamin Freedman claimed to have solved what he called the "clinician's dilemma" (Freedman 1987). This is a dilemma for the physician in clinical practice who is called on to enroll patients in a randomized controlled trial (RCT). On the one hand, the physician has a duty to participate in RCTs (the progress of biomedical research depends on physicians' enrolling patients in the trials for which they are eligible); on the other hand, the physician has a duty to provide for each of her patients whatever treatment is, in her judgment, best for that patient (the therapeutic obligation). These two duties seem to conflict, a problem traditionally resolved by showing that they don't so long as the physician enrolls patients in randomized trials only when she is in a state of equipoise with respect to the two arms of the trial; that is, only when she has no preference between the two courses of treatment with respect to their value as treatment for the particular patient concerned. ¹ This cognitive state was, however, not often enough experienced by physicians for there to be subjects enough for otherwise permissible trials to go ahead. This is the problem Freedman hoped to solve by introducing a new concept of equipoise.

Freedman argued that a physician could responsibly enroll a patient in a trial, even when the physician was not herself in a state of equipoise, as long as she determined that the profession as a whole might be said to be in a state of equipoise—evincing no preference for one treatment over the other. Freedman's solution was thought by many to have been a great success, but, in fact, it was a deeply flawed solution to the problem it was meant to solve, precisely because the physician in practice does have a therapeutic obligation to her patient—an obligation that surpasses that of avoiding the exploitation of a potential research subject. ² What Freedman had successfully (if inadvertently) described are the conditions under which a research proposal adequately reflects (at least along one dimension) the rights of potential subjects. When investigators recognize that the profession is in a state of clinical equipoise, they can confidently put out a call for volunteers. This is the use of the concept of clinical equipoise that Miller and Brody (2002) have in mind when they say that it is taken to be a requirement of legitimate research and when they argue that it should not be.

Miller and Brody argue that investigators have no obligation to ensure a state of clinical equipoise between the proposed arms of an RCT, on the grounds that they have no therapeutic obligation to potential subjects. It is true enough that the investigators have no therapeutic obligation to the potential subjects of a proposed trial, but then the therapeutic obligation physicians have to their patients is not behind the requirement of clinical equipoise as it applies to questions of the legitimacy of research proposals. The only obvious connection between them is that Freedman hoped to solve a problem involving the physician's therapeutic obligation and succeeded in describing a duty for investigators. Behind the requirement that investigators recognize a state of clinical equipoise in the profession before initiating a trial is their duty to avoid exploiting potential subjects. It would be exploitative for investigators to initiate a trial in which they expect that half of those participating will receive substandard (or no) care. This seems most obvious in examples in which the proposal would involve a serious illness for which there exists significantly effective treatment. Miller and Brody suggest that these intuitions can be explained in terms of the uncontroversial requirement that subjects not be subject [End Page 32] to unreasonable risks of harm. We are asked to consider examples in which the patient would very likely be just fine even if he never sought medical attention. But our intuitions that in these cases placebo trials would be unproblematic despite the availability of effective treatment point in no definite direction. We might wish to say that patients for whom it scarcely matters if they get treatment or placebo—either because the available treatment is of little use or because the condition is trivial—can be treated like patients who have no "condition" at all; that is, like healthy volunteers. In more serious cases (like those on which much related attention has recently been focused), it is ethically problematic to proceed, and it is problematic because the equipoise requirement is not met. We are all familiar with the claim that when a patient would have received no medical attention at all without the conduct of clinical trials in which she is invited to participate, she cannot be said to have been put at risk by the trial's giving her only a chance of receiving what might be an effective treatment—a claim that simply must be true. This claim only becomes worrisome, however, when it is combined with an abandonment of the equipoise requirement. This is not to say that we can never justify placebo trials. It is to say that any worthy justification will show how opting for one is the best way to balance respect for the rights of subjects against other values (e.g., the need to make progress against diseases that are currently taking more lives than we can stomach and destroying the communities in which those lives might have thrived). It will not rest on the misguided thought that the quality of the care received by subjects in a trial need not con- cern those responsible for determining what that "care" will be.