The number of treatment units (subjects or groups of subjects) assigned to control and treatment groups, affects an RCT's reliability. If the effect of the treatment is small, the number of treatment units in either group may be insufficient for rejecting the null hypothesis in the respective statistical test . The failure to reject the null hypothesis would imply that the treatment shows no statistically significant effect on the treated in a given test . But as the sample size increases, the same RCT may be able to demonstrate a significant effect of the treatment, even if this effect is small. 
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.