April 10, 2013
Update posted April 11: After we sent out this press release, Dr. Marchase of the University of Alabama tried to defend the study - and the universities that conducted it - by claiming that non-study babies who were eligible to be in the study had even higher mortality rates than those in the study. This comparison is invalid and unscientific, as the non-study babies overall were rated as sicker at the time of birth – hence their slightly higher mortality rates. Please read our April 11 letter to Dr. Marchase for more.
HHS-Funded Experiment Exposed Babies to Risk of Death and Blindness Without Informing Parents
HHS Secretary Should Apologize to Parents of Premature Infants Enrolled in Unethical Trial at 23 U.S. Medical Centers
WASHINGTON, D.C. – Health and Human Services Secretary Kathleen Sebelius should personally apologize to the parents of 1,316 premature infants who were exposed to increased risk of blindness and death as part of a clinical trial funded by the National Institutes of Health and held throughout the U.S. several years ago because they were not informed of the risks to their babies or the true nature and purpose of the research, Public Citizen said today in a letter to the secretary.
The trial, known as the SUPPORT study, was conducted between 2005 and 2009 at 23 prominent research facilities throughout the country, including the Stanford University School of Medicine, Yale University School of Medicine, Brown University, Duke University and University of Alabama at Birmingham (a complete list is at the end of this release).
Premature babies usually require treatment with oxygen. As part of routine care, the amount of oxygen given to such babies is adjusted based on a measure of blood oxygen level called oxygen saturation, which can be continuously checked with a probe placed on the skin.
For the medical centers participating in the SUPPORT study, routine care of premature infants not in the study typically involved giving enough oxygen to maintain oxygen saturation levels between 85 and 95 percent. The exact oxygen target level for a particular infant at any particular time would be based on the baby’s individual medical needs and the wishes of the baby’s parents.
In contrast to usual clinical care, the extremely premature infants enrolled in the SUPPORT study were randomly put in two groups that each received a different experimental target range of oxygen saturation: a low range (85-89 percent) and high range (91-95 percent). The researchers primarily wanted to see whether the babies were more likely to die or suffer retinal damage, which can lead to blindness, if their oxygen levels were targeted to the low or high range. It has long been known that, in general, giving high levels of oxygen to premature infants can lead to retinal damage, blindness and lung injury, while giving too little oxygen can cause brain damage and death.
However, as documented in a March 7, 2013, letter from the Office for Human Research Protections (OHRP) in the Department of Health and Human Services (HHS) to the University of Alabama at Birmingham, one of the lead institutions for the SUPPORT study, the consent forms for the study did not disclose to the babies’ parents any of the risks of the experimental oxygen management interventions, including risks of severe retinal damage, possible blindness, neurologic injury and death. The consent forms also failed to address two other critically important pieces of information:
• That one purpose of the research was to determine whether extremely premature infants were more likely to die if treated with the higher versus lower oxygen target; and
• An explanation of how the infants would be treated if they weren’t in the study compared to how they would be treated by participating in the study.
“The word ‘unethical’ doesn’t even begin to describe the egregious and shocking deficiencies in the informed-consent process for this study,” said Dr. Michael Carome, deputy director of Public Citizen’s Health Research Group. “The failure to disclose such critically important information about the research undoubtedly directly affected parents’ decisions to enroll their extremely premature infants in this study. It is highly likely that had they been appropriately informed about the nature of the research and its risks, many, if not most, parents would not have allowed their babies to be in this study.” (Note: For 10 years prior to joining Public Citizen, Carome was on the OHRP staff, serving most recently as its associate director for regulatory affairs and previously as its director of the Division of Compliance Oversight).
Not surprisingly, the study found differences between the two groups of infants in rates of death and retinal damage. In the lower oxygen group, 41 babies (nine percent of those evaluated) developed severe retinal problems and 130 (20 percent) died. In the higher oxygen group, 91 babies (18 percent of those evaluated) developed retinal problems and 107 (16 percent) died. Because there was no control group that received the usual care with individualized oxygen management, and because the babies were so sick to begin with, it is impossible to determine how these rates of death and retinal damage compare to what otherwise would have occurred had the babies been managed according to usual clinical care based solely on their individual needs. However, a comparison of the two study groups clearly shows more deaths in the lower oxygen group and more cases of severe retinal damage in the higher oxygen group.
OHRP got a complaint about the SUPPORT study approximately two years ago. The other research centers involved were copied on the OHRP’s March 7 letter to the University of Alabama at Birmingham. But the agency did not demand adequate and meaningful corrective actions from that school or any of the other universities and hospitals involved.
“As a result of the informed-consent deficiencies, the investigators of the SUPPORT study failed to obtain the legally effective informed consent from the babies’ parents, and the conduct of the study was highly unethical,” said Carome. “Because this study was funded by NIH, HHS has a moral obligation to formally apologize to the parents of all infants in the study and tell them at last about its purpose, nature and risks.”
In addition to issuing an apology to parents, Public Citizen urges Sebelius to take the following actions:
• Direct OHRP to require each participating institution to submit corrective action for avoiding such serious deficiencies in the consent process for future research;
• Launch an independent investigation into how the HHS system for review and oversight of clinical trials failed so miserably. This should include an assessment of all entities within NIH or other HHS agencies that played a role in the review, approval and funding of the study.
• Determine what system-wide actions are necessary to prevent similar future failures; and
• Identify and suspend any similarly unethical ongoing research involving premature infants that is funded by NIH or any other HHS agency.
The letter can be found here.
The 23 research centers that conducted the trial are:
• Brown University
• Case Western Reserve University
• Duke University
• Emory University School of Medicine
• Indiana University School of Medicine
• Sharp Mary Birch Hospital for Women and Newborns
• Stanford University School of Medicine
• Tufts Medical Center
• University of Alabama at Birmingham
• University of California, San Diego
• University of Cincinnati
• University of Iowa
• University of Miami Miller School of Medicine
• University of New Mexico Health Sciences Center
• University of Rochester School of Medicine and Dentistry
• University of Tennessee
• University of Texas Health Science Center, Houston
• University of Texas Southwestern Medical Center
• University of Utah School of Medicine
• Wake Forest University School of Medicine
• Wayne State University
• Women and Infants Hospital of Rhode Island
• Yale University School of Medicine