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|J Med Ethics 2004;30:190-193
On what ethical grounds may a physician offer trial participation to his or her patient? The answer seems to depend greatly on which side of the Atlantic you reside. In the United Kingdom, the uncertainty principle is widely endorsed. 1 2 However, in North America, clinical equipoise reflecting collective uncertainty is the dominant ethical basis.3 Which of these principles offers the preferred moral underpinning for the randomised controlled trial?
It is widely acknowledged that physicians have a primary duty to promote their patients' welfare. When physicians become investigators, however, other ends such as recruiting enough subjects and retaining them in the trial may conflict with this duty.4 How can the physician maintain fidelity to the patient and further the ends of a randomised controlled trial? The uncertainty principle offers an appealing solution to this problem.
Physicians who are convinced that one treatment is better than another for a particular patient cannot ethically choose at random which treatment to give, they must do what they think best for the patient. For this reason, physicians who feel they already know the answer cannot enter their patients into a trial. If they think, whether for a wise or silly reason, that they know the answer before the trial starts, they should not enter any patients.2
On the other hand, if the physician is uncertain about which treatment is best for a patient, offering the patient randomisation to equally preferred treatments is acceptable and does not violate his or her duty. The uncertainty principle has been successfully used as a key eligibility criterion for large, simple trials. 1 5 6
But is the uncertainty principle a solid moral basis for the randomised controlled trial? We think not. Under the uncertainty principle it would be difficult, if not impossible, to conclude that a physician ever errs in enrolling a patient in a trial. So long as the physician claims he or she was uncertain, even if madly or incompetently so, he or she cannot be said to be wrong. Recent articles on the uncertainty principle have added "reasonably" and "substantially" to qualify uncertainty. 1 6 But who decides what counts as reasonable or substantial uncertainty? If it is the individual physician and the uncertainty principle certainly maintains that the proper normative locus for decision making is the individual physician we are left with the same problem.
Clinical equipoise, on the other hand, recognises explicitly that it is not the individual physician but the community of physicians that establishes standards of practice. According to Freedman, the
ethics of medical practice grant no ethical or normative meaning to a treatment preference, however powerful, that is based on a hunch or anything less than evidence publicly presented and convincing to the clinical community. Persons are licensed as physicians after they demonstrate the acquisition of this professionally validated knowledge, not after they reveal a superior capacity for guessing.3
Competent medical practice is defined widely as that which falls within the bounds of standard of care that is, practice endorsed by at least a respectable minority of expert practitioners. The innovation of clinical equipoise is the recognition that study treatments, be they the experimental or control treatments, are potentially consistent with this standard of care. Thus, a physician, consistent with his or her duty to the patient, may offer trial enrolment when there "exists . . . an honest, professional disagreement among expert clinicians about the preferred treatment."3
Clinical equipoise may arise in several ways. Evidence may emerge from early clinical studies that a new treatment offers advantages over standard treatment. Alternatively, there may be a split within the clinical community, with some physicians preferring one treatment and other physicians preferring another. This last scenario is well documented in the published report and calls for a randomised controlled trial to settle which is the better treatment.7 Clinical equipoise does, however, permit these important randomised controlled trials. It would have physicians respect the fact that "their less favoured treatment is preferred by colleagues whom they consider to be responsible and competent."3
The second part of clinical equipoise states: "the trial must be designed in such a way as to make it reasonable to expect that, if it is successfully concluded, clinical equipoise will be disturbed. In other words, the results of a successful trial should be convincing enough to resolve the dispute among clinicians."3 Clinical equipoise, therefore, generally requires a trial design that will "compare two treatments under the conditions in which they would be applied in practice [and] answer the question which of the two treatments should we prefer?"8 In short, clinical equipoise supports a pragmatic approach to the design of randomised controlled trials.
Clinical equipoise . . . recognises explicitly that it is not the individual physician but the community of physicians that establishes standards of practice