Lessons for Comparative Effectiveness Research from the Trial of Oxygen Therapy for Premature Babies By JOHN D. LANTOS AND CHRIS FEuDTNER

January-February 2015 The Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) has been the focal point of many different criticisms regarding the ethics of the study ever since publication of the trial’s findings in 2010 and 2012. These criticisms center on two major concerns. The first concern rests on a belief that, when the SUPPORT study was being designed, the state of medical knowledge was already sufficiently clear about the optimal amount of oxygen to give premature babies and that therefore any study of differing oxygen therapy protocols was unnecessary and unethically exposed infants to a treatment known to be inferior. In this paper, we will not address this point. Instead, we will assume, as did the Office for Human Research Protection, that the study addressed an important area of uncertainty in neonatology, that there was genuine uncertainty in the expert community as to which level of oxygen was the best, and that there was widespread practice variation within the range of oxygen levels that were generally thought to be acceptable. In this article, we focus on the second major concern, namely, that although SUPPORT may have been warranted based on the uncertainty of the best oxygen therapy strategy for premature infants, the technical design and implementation details of the study itself were ethically flawed. While the OHRP focused on the consent form, rather than on the study design and implementation, OHRP’s critiques of the consent form reveal views about the study design and implementation that we believe are fundamentally flawed. These views were more fully articulated by Public Citizen and many others who criticized the study at an open meeting held by the Department of Health and Human Services (HHS) in August 2013. These criticisms about the design and implementation of SUPPORT, if generalized, become relevant concerns about these aspects of The design of SuPPORT has been widely misunderstood. This confusion has driven much of