Clinical equipoise, also known as the principle of
equipoise, provides the ethical basis for medical research that involves
assigning patients to different treatment arms of a clinical trial. The term
was first used by Benjamin Freedman in 1987. In short, clinical equipoise means
that there is genuine uncertainty in the expert medical community over whether
a treatment will be beneficial. This applies also for off-label treatments
performed before or during their required clinical trials.
An ethical dilemma arises in a clinical trial when the investigator(s) begin to believe that the treatment or intervention administered in one arm of the trial is significantly outperforming the other arms. A trial should begin with a null hypothesis, and there should exist no decisive evidence that the intervention or drug being tested will be superior to existing treatments or effective at all. As the trial progresses, the findings may provide sufficient evidence to convince the investigator of the intervention or drug’s efficacy. Once a certain threshold of evidence is passed, there is no longer genuine uncertainty about the most beneficial treatment, so there is an ethical imperative for the investigator to provide the superior intervention to all participants. Ethicists contest the location of this evidentiary threshold, with some suggesting that investigators should only continue the study until they are convinced that one of the treatments is better, and with others arguing that the study should continue until the evidence convinces the entire expert medical community.
The extent to which major research ethics policies endorse clinical equipoise varies. For instance, the Canadian Tri-Council Policy Statement endorses it; whereas, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) does not. With regard to clinical equipoise in practice, there is evidence that industry-funded studies disproportionately favor the industry product, suggesting unfavorable conditions for clinical equipoise. In contrast, a series of studies of national cancer institute funded trials suggests an outcome pattern consistent with clinical equipoise.
An ethical dilemma arises in a clinical trial when the investigator(s) begin to believe that the treatment or intervention administered in one arm of the trial is significantly outperforming the other arms. A trial should begin with a null hypothesis, and there should exist no decisive evidence that the intervention or drug being tested will be superior to existing treatments or effective at all. As the trial progresses, the findings may provide sufficient evidence to convince the investigator of the intervention or drug’s efficacy. Once a certain threshold of evidence is passed, there is no longer genuine uncertainty about the most beneficial treatment, so there is an ethical imperative for the investigator to provide the superior intervention to all participants. Ethicists contest the location of this evidentiary threshold, with some suggesting that investigators should only continue the study until they are convinced that one of the treatments is better, and with others arguing that the study should continue until the evidence convinces the entire expert medical community.
The extent to which major research ethics policies endorse clinical equipoise varies. For instance, the Canadian Tri-Council Policy Statement endorses it; whereas, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) does not. With regard to clinical equipoise in practice, there is evidence that industry-funded studies disproportionately favor the industry product, suggesting unfavorable conditions for clinical equipoise. In contrast, a series of studies of national cancer institute funded trials suggests an outcome pattern consistent with clinical equipoise.
Criticism
Miller and Brody
argue that the notion of clinical equipoise is fundamentally misguided. The
ethics of therapy and the ethics of research are two distinct enterprises that
are governed by different norms. They state, “The doctrine of clinical
equipoise is intended to act as a bridge between therapy and research, allegedly
making it possible to conduct RCTs without sacrificing the therapeutic
obligation of physicians to provide treatment according to a scientifically
validated standard of care. This constitutes therapeutic misconception
concerning the ethics of clinical trials, analogous to the tendency of patient
volunteers to confuse
treatment in the context of RCTs with routine medical care.”
Equipoise, they argue, only makes sense as a normative assumption for clinical
trials if one assumes that researchers have therapeutic obligations to their
research participants. Further criticisms of clinical equipoise have been
leveled by Robert Veatch and by Peter Ubel and Robert Silbergleit.
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