May 16, 2025 – University of Alabama at Birmingham

Study Title: Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) in Extremely Low Birth Weight Infants (“SUPPORT”)

Dear Dr. Brown,

The Office for Human Research Protections (OHRP) is closing its investigation related to allegations of noncompliance with the U.S. Department of Health and Human Services (HHS) regulations for the protection of human research subjects against the University of Alabama at Birmingham (UAB)’s Human Research Protections Program (HRPP). All events related to these allegations occurred prior to January 21, 2019, and were subject to the Common Rule as it existed at that time (the “Pre-2018 Requirements”). Therefore, all citations in this letter are to the Pre-2018 Requirements.

Background: The SUPPORT study was a randomized multi-site study conducted at approximately 22 sites and reviewed by at least 23 institutional review boards (IRBs). Approximately 1,300 infants were enrolled in this study from 2004 to 2009. The study was designed, in part, to learn the appropriate levels of oxygen saturation in extremely low birth weight infants by comparing a lower versus a higher range of levels of oxygen saturation in such infants. UAB was the lead site for the portion of the study relating to the second purpose.

Infants were randomized to lower or higher ranges of oxygen levels to test the effects on infants’ survival, neurological development, and likelihood of developing retinopathy of prematurity (ROP), a serious - often blinding - visual disorder.

On March 7, 2013, OHRP issued a determination of noncompliance against UAB, specifically finding that the template informed consent (IC) reviewed and approved by the UAB Institutional Review Board (IRB) in the SUPPORT trial failed to include or did not adequately address the reasonably foreseeable research related risks, in contravention of 45 CFR 46.116(a)(2).¹ Specifically, we determined that the informed consent failed to describe the risks of blindness, neurological damage, and death. In the subsequent months, significant scientific and public discussion occurred about OHRP’s determination and, more broadly, what “reasonably foreseeable” risks or discomforts must be disclosed to participants in research that compares two or more clinically accepted standards of care.

In the wake of extensive scientific and public discussions after OHRP’s determination letter, OHRP become aware of widespread differences in viewpoints about the risks that are required to be disclosed in obtaining informed consent for certain types of clinical trials. In June 2013, OHRP clarified in a follow-up letter to UAB that, based on the information available at the time UAB reviewed and approved the SUPPORT IC, “there is justification for an incomplete understanding of how [45 CFR 46.116(a)(2)]…might apply to this study.” To that end, OHRP paused all SUPPORT-related compliance actions against UAB and indicated that it would not take compliance action in studies involving similar designs until OHRP issued guidance on this topic.²

In October 2013, OHRP held an open public meeting entitled “Matters Related to Protection of Human Subjects and Research Considering Standard of Care Interventions.”³ In October 2014, OHRP issued for public comment Draft Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care.⁴

We regret the amount of time it has taken to close this investigation. We appreciate your institution’s continued commitment to the protection of human research participants. Please feel free to contact me if you have any questions.

Sincerely,

Crystal Kelly, MPH
Compliance Specialist
Division of Compliance Oversight

CC (email only):
Mr. Adam J. McClintock, Human Protections Administrator, UAB
Ms. Winifred Meeker-O’Connell, Director, Office of Clinical Policy, Food and Drug Administration (FDA)
Dr. Michelle Bulls, Director, OPERA, Office of Extramural Research, National Institutes of Health (NIH)
Dr. Pamela Kearney, Director, Division of Human Subjects Research, Office of Extramural Research, NIH
Dr. Adam Berger, Director, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Ms. Lydia Kline, Team Lead, Clinical Research Policy, Division of Clinical and Healthcare Research Policy, Office of Science Policy, NIH
Center for Devices and Radiological Health (CDRH) IRB: BIMO-CDRH@fda.hhs.gov
Center for Biologics Evaluation and Research (CBER): CBERBIMONotification@fda.hhs.gov 
Office of Regulatory Affairs (ORA): orabimoinspectionpoc@fda.hhs.gov
Center for Drug Evaluation and Research (CDER): BIMO-CDEROSI@fda.hhs.gov

References:

¹ UAB SUPPORT Determination Letter (March 2013): https://www.hhs.gov/ohrp/sites/default/files/ohrp/detrm_letrs/YR13/mar13a.pdf.

² Follow-up to OHRP’s March 2013 Determination Letter against UAB (June 2013): https://www.hhs.gov/ohrp/sites/default/files/ohrp/detrm_letrs/YR13/jun13a.pdf

³ OHRP Public Meeting “Matters Related to Protection of Human Subjects and Research Considering Standard of Care Interventions” (August 2013): https://www.hhs.gov/ohrp/regulations-and-policy/requests-for-comments/public-meeting-08-28-2013/index.html

⁴ OHRP Draft Guidance on Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care (October 2014): https://www.hhs.gov/ohrp/regulations-and-policy/requests-for-comments/draft-guidance-disclosing-risk-in-standards-of-care/index.html

June 4, 2013 - University of Alabama at Birmingham

March 7, 2013 - University of Alabama at Birmingham