Comparative effectiveness trials: generic misassumptions underlying the SUPPORT controversy.

Abstract

* Abbreviations: CE — : comparative effectiveness OHRP — : Office for Human Research Protection ROP — : retinopathy of prematurity SUPPORT — : Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments As emphasized by the Institute of Medicine,1 the effectiveness of more than half of therapies used in clinical practice is unclear. High priority should be given to promoting comparative effectiveness (CE) trials, trials of alternative therapies performed to facilitate better informed and more evidence-based decisions by clinicians, patients, third-party payers, and policy makers.2,3 In such trials, the effectiveness of different treatment options is assessed under usual clinical circumstances across a broad range of patients treated clinically with these therapies. CE trials provide essential information to improve outcomes in everyday clinical practice that cannot be obtained from trials performed to assess the efficacy of a new experimental therapy. Such trials are conducted in ideal or restricted circumstances; enroll a limited number of carefully selected, and often uncomplicated, patients; and thus generally yield an optimistic view of efficacy. In comparing alternative therapies already used in clinical practice, CE trials have no “experimental” arm and no “control” arm, and the potential risks of one treatment are the potential benefits of the other. Yet CE trials fall under the same regulatory requirements for trials of experimental interventions never previously administered to patients. The appropriate regulation of CE trials was a central issue in a public meeting in August 2013 held by the Office for Human Research Protection (OHRP) in response to heated controversy regarding the SUPPORT (Surfactant, Positive Pressure, and Oxgenation Randomized Trial) published in 2010 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.4 This 20-center CE trial included 1316 infants 24 to 27 weeks’ gestation randomized to oxygen saturation goals of 85% to 89% or 91% to 95%, the upper and lower ends of the goal range (85%–95%) suggested by the American Academy of Pediatrics. Caregivers were blinded to the … Address correspondence to Jon E. Tyson, MD, MPH, University of Texas Health Science Center at Houston, 6431 Fannin St, MSB 2.106, Houston, Texas 77030. E-mail: jon.e.tyson{at}uth.tmc.edu