It is widely held that in order to be ethical, clinical trials must satisfy the requirement known as “clinical equipoise”—that is, a genuine uncertainty and lack of consensus exists within the medical community about whether the investigational treatment evaluated in a clinical trial is as good as or better than standard treatment or placebo, when no effective treatment is available (10–12). Clinical trials that comply with this ethical standard still have features that depart substantially from clinical practice. Treatment alternatives (or placebo) may be randomly assigned to patient–participants, patient–participants and physician–investigators are typically blind to which alternative is received, and protocol-driven limitations may be placed on the types and doses of interventions. In addition, clinical trials may include research procedures that impose discomforts or risks for harm to patient–participants that are not compensated by personal diagnostic or therapeutic benefits; instead, they are justified by the importance of the knowledge from the study (13). For example, participation in some trials may include medication washout periods, biopsies, overnight hospital stays, imaging studies, blood draws, and questionnaires—not because something will be learned that will benefit the patient–participant, but because they are needed to generate data necessary to test study hypotheses. Although patient–participants may benefit from research participation, that is not the primary purpose of research.