Varieties of standard-of-care treatment randomized trials: ethical implications.

Comparative effectiveness research has received considerable attention in recent years and has been accompanied by controversy, especially in response to the 2013 Office for Human Research Protections (OHRP) investigation of the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial (SUPPORT)—a randomized trial of 2 contrasting oxygen saturation settings in mechanical ventilation of premature infants within the established standard of care.1 The OHRP convened a public meeting in August 2013 on “Matters Related to Protection of Human Subjects and Research Considering Standard of Care Interventions” and recently issued draft guidance on “Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care.”2 This guidance has been sharply criticized. The phrase “research evaluating standards of care” suggests that standard-of-care treatment randomized clinical trials (RCTs) comprise a class of studies with ethically relevant characteristics (ie, testing of standard-of-care interventions) that have specific