Federal research-ethics regulators have retreated from their consideration of punitive action over a medical trial at 23 universities in which premature babies faced potentially lethal oxygen levels, saying government rules may have been unclear.
The federal Office for Human Research Protections, in a letter to the University of Alabama at Birmingham, the lead institution in the “Support” study, cited a series of problems with the research project, including the failure to properly notify parents of the risks that infants enrolled in the study might face.
The agency then blamed itself, saying it had an “obligation to provide clear guidance on what the rules are with regard to disclosure of risks in randomized studies whose treatments fall within the range of standard of care.”
The human-research-protections office therefore will “put on hold all compliance actions against UAB relating to the Support case,” Lisa R. Buchanan, a compliance-oversight coordinator at the agency, said in a letter on Tuesday to Richard B. Marchase, vice president for research and economic development at Birmingham.
The study—"Support” is an abbreviation of its full title, the “Surfactant, Positive Pressure, and Oxygenation Randomized Trial"—involved some 1,300 premature infants at two dozen hospitals. It was designed to determine the optimal levels of oxygen to give to the babies in the neonatal unit.
All of the oxygen levels that were used in the study were considered as being within a commonly used range, but previous research and clinical experience had suggested that too little oxygen could increase the risk of death, and too much could lead to blindness.
Ms. Buchanan issued her letter less than two months after the director of the research-protections office, Jerry A. Menikoff, in response to public revelations of the study’s handling, criticized the consent form given to parents. The form “was written in a slanted way,” describing the benefits but not all of the risks, he said.
Implications for Researchers
The agency’s retreat was endorsed on Wednesday both by the National Institutes of Health, which financed the study, and by a group of 46 university experts in medicine and ethics, writing in The New England Journal of Medicine.
The university experts, led by Benjamin S. Wilfond, a professor of bioethics in the pediatrics department at the University of Washington, said the original position of Dr. Menikoff’s agency “was a substantive error and will have adverse implications for future research.”
Writing in the same journal, the NIH’s director, Francis S. Collins, and two other top NIH officials also urged a pullback, saying the controversy had “alarmed some of the parents of infants who were in the study, confused the biomedical-research community, and befuddled IRBs,” the institutional review boards that approve study protocols.
The reversal nevertheless is likely to generate its own pushback among both parents of the infants and university bioethics experts who regard the case as a clear-cut violation of the right of patients to informed consent, said Alice D. Dreger, a professor of clinical medical humanities and bioethics at Northwestern University.
Ms. Buchanan’s letter “did a beautiful job” of reiterating the specific risks faced by babies in the trial and making clear that the parental consent forms did not convey those risks, Ms. Dreger said. In her letter, therefore, “the OHRP has said, ‘You’re guilty, but we’re not going to do anything about it,’” she said.
At least one lawsuit has been filed against the University of Alabama at Birmingham and its institutional review board over the matter. The case, filed in April in a federal court in Alabama, names 11 families as plaintiffs and contends that infants in the research “suffered permanent neurological and vision issues, among other catastrophic injuries.”
Other institutions that were involved in the research, which took place from 2004 to 2009, include Duke, Stanford, and Yale Universities.
The NIH agrees that the federal government needs to do a better job of setting rules in such cases, and it plans a process to accomplish that, including a public hearing, said Kathy L. Hudson, the NIH’s deputy director for science, outreach, and policy.
But the NIH does not accept Ms. Buchanan’s conclusion that there was a reasonably foreseeable increased risk of death from the lower oxygen levels provided to some of the infants in the trial, Ms. Hudson said. “That’s where NIH and OHRP disagree,” she said.
Although the research-protections office took issue with the consent form, Ms. Buchanan emphasized her agency’s belief that the study itself was fundamentally ethical and designed to gain important information.
She was less clear on whether the state of scientific knowledge at the outset of the trial could have reasonably justified a warning to parents of heightened risk.
At one point in her letter, she said investigators did not design the study with the expectation that they would find a difference in mortality rates between the high and low oxygen groups. Yet she also wrote that many researchers and clinicians were worried that low oxygen levels could lead to increased mortality and neurodevelopmental problems. Those concerns, she said, were a prime reason for the study.
