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, although references to its use go back to 1795 by Dr. Edward Jenner. 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 that it will be completely ineffective. 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. History Shaw and Chalmers argued early on that "If the clinician knows, or has good reason to believe, that a new therapy (A) is better than another therapy (B), he cannot participate in a comparative trial of Therapy A versus Therapy B. Ethically, the clinician is obligated to give Therapy A to each new patient with a need for